CLINICAL PRACTICE GUIDELINE

No. 334 (Replaces No. #121, November 2002)

Diabetes in Pregnancy
This Clinical Practice Guideline has been prepared by the
Maternal Fetal Medicine Committee; reviewed by the Family
Physicians Advisory, Aboriginal Health Initiative, and Clinical
Practice e Obstetrics Guideline Committees and the
Canadian Diabetes Association; endorsed by the Canadian
Diabetes Association; and approved by the Board of the
Society of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Howard Berger, MD, Toronto ON
Robert Gagnon, MD, Montreal QC
Mathew Sermer, MD, Toronto ON
MATERNAL FETAL MEDICINE COMMITTEE
Melanie Basso, RN, Vancouver BC
Abstract
Objective: This guideline reviews the evidence relating to the
diagnosis and obstetrical management of diabetes in pregnancy.
Outcomes: The outcomes evaluated were short- and long-term
maternal outcomes, including preeclampsia, Caesarean section,
future diabetes, and other cardiovascular complications, and fetal
outcomes, including congenital anomalies, stillbirth, macrosomia,
birth trauma, hypoglycemia, and long-term effects.
Evidence: Published literature was retrieved through searches of
PubMed and the Cochrane Library using appropriate controlled
vocabulary (MeSH terms “diabetes” and “pregnancy”). Where
appropriate, results were restricted to systematic reviews,
randomized control trials/controlled clinical trials, and observational
studies. There were no date limits, but results were limited to
English or French language materials.

Hayley Bos, MD, Victoria BC Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Richard N. Brown, MD, Beaconsfield QC
Care (Table 1).
Emmanuel Bujold, MD, Quebec QC
Summary Statements
Stephanie L. Cooper, MD, Calgary AB
1. The adverse outcomes associated with diabetes in pregnancy are
Robert Gagnon, MD, Montreal QC substantially associated with hyperglycemia and the coexisting
Katy Gouin, MD, Quebec QC metabolic environment. Women with preexisting diabetes should
receive preconception care to optimize blood sugar control and
N. Lynne McLeod, MD, Halifax NS other comorbidities. Outcomes for the fetus/neonate and the mother
Savas M. Menticoglou, MD, Winnipeg MB in both pre-gestational diabetes mellitus and gestational diabetes
mellitus pregnancies are improved by multidisciplinary management
William R. Mundle, MD, Windsor ON in which the goal is achieving optimal blood sugar control and
Anne Roggensack, MD, Calgary AB appropriate fetal surveillance. (II-2)
Frank L. Sanderson, MD, Saint John NL 2. Retrospective studies indicate that women with pre-gestational
diabetes mellitus have an increased risk of stillbirth before 40
Jennifer D. Walsh, MD, Rothesay NB
weeks’ gestation compared with the general obstetrical population.
Disclosure statements have been received from all members of Similarly, large recent cohort and simulation studies of women with
the committee(s). gestational diabetes mellitus pregnancies also indicate a higher risk
of stillbirth between 36 to 39 weeks’ gestation. (II-2)
3. Women with gestational diabetes mellitus have a higher risk of
Key Words: Diabetes, pregnancy, stillbirth preeclampsia, shoulder dystocia, Caesarean section, and large for
http://dx.doi.org/10.1016/j.jogc.2016.04.002 gestational age infants. (II-2)
4. Treatment of women with gestational diabetes mellitus and optimi-
zation of glycemic control reduce the risk of preeclampsia, shoulder
J Obstet Gynaecol Can 2016;-(-):1e13 dystocia, and large for gestational age infants. (I)
Copyright ª 2016 by the The Society of Obstetricians and 5. The occurrence of gestational diabetes mellitus increases the risk of
Gynaecologists of Canada/La Société des obstétriciens developing type 2 diabetes in the future for the mother. (II-2)
et gynécologues du Canada

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be
construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions.
They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written
permission of the SOGC.

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CLINICAL PRACTICE GUIDELINE

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventative Health Care
Quality of evidence assessment* Classification of recommendations†
I Evidence obtained from at least one properly randomized A. There is good evidence to recommend the clinical preventive
controlled trial action
II-1 Evidence from well-designed controlled trials without B. There is fair evidence to recommend the clinical preventive
randomization action
II-2 Evidence from well-designed cohort (prospective or C. The existing evidence is conflicting and does not allow to make a
retrospective) or case-control studies, preferably from more recommendation for or against use of the clinical preventive
than one centre or research group action; however, other factors may influence decision-making
II-3 Evidence obtained from comparisons between times or places D. There is fair evidence to recommend against the clinical pre-
with or without the intervention. Dramatic results in uncontrolled ventive action
experiments (such as the results of treatment with penicillin in E. There is good evidence to recommend against the clinical pre-
the 1940s) could also be included in the category ventive action
III Opinions of respected authorities, based on clinical experience, F. There is insufficient evidence (in quantity or quality) to make a
descriptive studies, or reports of expert committees recommendation; however, other factors may influence decision-
making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive
Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in The Canadian Task Force on
Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the Canadian Task
Force on Preventive Health Care. CMAJ 2003;169:207e8.

Recommendations Gestational diabetes mellitus is diagnosed if 1 value is met or

exceeded:
1. The “preferred screening and diagnostic 2-step” approach for
gestational diabetes mellitus of the Canadian Diabetes Association i. Fasting plasma glucose
5.3 mmol/L
2013 guidelines is endorsed. All pregnant women should be offered ii. 1-hour plasma glucose
10.6 mmol/L
screening between 24 to 28 weeks using a standardized non-fasting
iii. 2-hour plasma glucose
9.0 mmol/L
50-g glucose challenge screening test with plasma glucose
measured 1 hour later. (III-B) 1.3. If the value of the glucose challenge screening test is
11.1
mmol/L, gestational diabetes mellitus is diagnosed.
1.1. If the value is < 7.8 mmol/L, no further testing is required.
2. The “alternative 1-step diagnostic” approach of the Canadian Dia-
1.2. If the value of the glucose challenge screening test is 7.8 to
betes Association 2013 guidelines is acceptable. In this strategy
11.0, a 2-hour 75-g oral glucose tolerance test with fasting
pregnant women should be offered testing between 24 to 28 weeks
plasma glucose, 1-hour plasma glucose, and 2-hour plasma
using a standardized 2-hour 75-g oral glucose tolerance test with
glucose should be performed.
fasting plasma glucose, 1-hour plasma glucose, and 2-hour plasma
glucose. (III-B)

ABBREVIATIONS Gestational diabetes mellitus is diagnosed if 1 value is met or

exceeded:
ACOG American College of Obstetricians and Gynecologists
BMI body mass index i. Fasting plasma glucose
5.1 mmol/L
CDA Canadian Diabetes Association ii. 1-hour plasma glucose
10.0 mmol/L
DM diabetes mellitus iii. 2-hour plasma glucose
8.5 mmol/L It is recognized that
the use of different diagnostic thresholds for the “preferred”
FPG fasting plasma glucose
and “alternative” strategies could cause confusion in certain
GCT glucose challenge screening test settings. Despite this, the committee has identified the
GDM gestational diabetes mellitus importance of remaining aligned with the current Canadian
Diabetes Association 2013 guidelines as being a priority. It
HAPO Hyperglycemia and Adverse Pregnancy Outcome is thus recommended that each care centre strategically
IADPSG International Association of Diabetes and Pregnancy Study align with 1 of the 2 strategies and implement protocols to
Groups ensure consistent and uniform reporting of test results.
LGA large for gestational age 3. If there is a high risk of gestational diabetes mellitus based on
multiple risk factors, screening or testing should be offered dur-
NST non-stress test
ing the first half of the pregnancy and repeated at 24 to 28 weeks’
OGTT oral glucose tolerance test gestation if initially normal. If for any reason it was missed or if
PG plasma glucose there is a clinical suspicion of later onset of gestational diabetes,
a screening or diagnostic test should be performed. (II-2B)
PGDM pre-gestational diabetes mellitus
4. Women with preexisting or gestational diabetes mellitus should be
RR relative risk provided with care by a multidisciplinary team aimed at attaining
SMBG self-monitored blood glucose and then maintaining euglycemia. (II-2B)

2 l - JOGC - 2016

5. For patients with pre-gestational diabetes mellitus or gestational
diabetes mellitus, starting at 28 weeks as a baseline, with subse-
quent serial assessment of fetal growth, every 3 to 4 weeks is
suggested to assess the effect of maternal glycemic control on fetal
growth rate and amniotic fluid volume. (II-2B)
6. Initiation of weekly assessment of fetal well-being at 36 weeks is
recommended in pre-gestational diabetes mellitus and gestational
diabetes mellitus. It is also reasonable to consider weekly fetal
assessment for women with diet controlled gestational diabetes
mellitus beginning at 36 weeks. Acceptable methods of assess-
ment of fetal well-being near term can include the non-stress test,
non-stress test þ amniotic fluid index, biophysical profile, or a
combination of these. (III-A)
7. If comorbid factors are present, such as obesity, evidence
of suboptimal glycemic control, large for gestational age
(> 90%), previous stillbirth, hypertension, or small for gesta-
tional age (< 10%), earlier onset and/or more frequent fetal
health surveillance is recommended. In specific cases in which
fetal growth restriction is suspected, the addition of umbilical
artery and fetal middle cerebral artery Doppler assessment may
be helpful. (II-2A)
8. Pregnant women with gestational diabetes mellitus or pre-
gestational diabetes mellitus should be offered induction between
38 to 40 weeks’ gestation depending on their glycemic control and
other comorbidity factors. (II-2B)
9. The administration of betamethasone to pregnant women with
gestational diabetes mellitus should be restricted to the routine
obstetric indications related to the risk of preterm and late preterm
delivery between 24 to 36 weeks’ gestation, when clinically
Diabetes in Pregnancy
indicated. When administered, close maternal glycemic surveil-
lance is recommended. (I-A)
10. If not previously done, in women with threatened preterm labour
requiring betamethasone, a screening for gestational diabetes
mellitus should be performed either before or at least 7 days after
the administration of betamethasone. (III-B)
11. Women with gestational diabetes mellitus should be offered testing
with a 75-g oral glucose tolerance test between 6 weeks and 6
months postpartum to detect prediabetes and diabetes.1 (II-2A)
11.1. Normal
i. Fasting plasma glucose < 6.1 mmol/L
ii. 2-hour plasma glucose < 7.8 mmol/L
iii. Glycated hemoglobin < 6.0%
11.2. Pre-diabetic
i. Fasting plasma glucose 6.1 to 6.9 mmol/L or
ii. 2-hour plasma glucose 7.8 to 11.0 mmol/L or
iii. Glycated hemoglobin 6.0% to 6.4%
11.3. Type 2 diabetes mellitus
i. FPG
7.0 mmol/L
ii. Random plasma glucose or 2-hour plasma glucose

11.1 mmol/L
iii. Glycated hemoglobin
6.5%
12. Breastfeeding is strongly recommended after delivery for all
women with pre-gestational diabetes mellitus or gestational dia-
betes mellitus. (II-2A)
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CLINICAL PRACTICE GUIDELINE
INTRODUCTION
A large population-based study in Ontario demon-
strated that between 1996 and 2010 the incidence of
both GDM and PGDM, which includes both type 1 and
type 2 DM, doubled from 2.7% to 5.6% for GDM and
from 0.7% to 1.5% for PGDM.2 When compared with
non-diabetic pregnant women, the risk of both congenital
anomalies (OR 1.86, 95% CI 1.49 to 2.33) and perinatal
mortality (OR 2.33 [1.59 to 3.43]) remained higher in
PGDM pregnant women.2 Similarly, in a Swedish
population-based cohort of over 1.2 million pregnancies
with singleton gestations, women with GDM had a higher
risk of adverse maternal outcomes (OR 1.81 [1.64 to 2.00];
for shoulder dystocia of (OR 2.74 [2.04 to 3.68]); and for
Caesarean section (OR 1.46 [1.38 to 1.54]).3 In addition,
with GDM, a higher risk of adverse neonatal outcomes has
been reported, including LGA (OR 3.43 [3.21 to 3.67]),
Erb’s palsy (OR 2.56 [1.96 to 3.32]), prematurity (OR 1.71
[1.58 to 1.86]), and major malformations (OR 1.19 [1.02 to
1.39]).3 It is of interest that no statistically significant
improvement in maternal and neonatal outcome was seen
over time in either study, with the exception of a decline in
the rate of congenital anomalies by 23%.2,3
Even though the benefits of specialized management of
pregnancies complicated by PGDM is well-known, we now
have data from RCTs that document a reduction in certain
perinatal morbidities after diagnosis and management of
GDM.4,5 The primary goal of this management is to attain
and then maintain euglycemia. This is best done by a
multidisciplinary team with attention to diet and exercise;
glucose monitoring; and, as appropriate, medical manage-
ment with insulin and/or oral hypoglycemic agents.
The purpose of these guidelines is to review the diagnostic
criteria and issues related to the obstetrical management of
GDM and PGDM. Specific recommendations regarding
glycemic control are beyond the scope of this document
Table 2. Risk of Stillbirth (GDM vs. No GDM)
Gestational
Author age cutoff Population (n)
Hutcheon et al.6
20 weeks 2 001 749
Peticca et al.7
20 weeks 120 604
Karmon et al.8
20 weeks 184 256
Ohana et al. 9

20 weeks 228 293
Fadl et al.3 > 28 weeks 1 260 297
Hutcheon et al.6 > 28 weeks 1 988 320
Rosenstein et al. 10

36 weeks 4 190 953
4 l - JOGC - 2016
but can be found in the 2013 CDA Clinical Practice
Guidelines, available at: http://guidelines.diabetes.ca/
browse/chapter36.
IMPACT OF DIABETES MELLITUS ON PERINATAL
MORTALITY
Table 2 summarizes the RR or OR for stillbirth in preg-
nancies with GDM in different populations studied
compared with non-GDM pregnancies. A wide range of
absolute stillbirth rate (per 1000 pregnancies) has been re-
ported, from as low as 0.32 to 4.2 per 1000 pregnancies,
depending on the population studied and the gestational age
cutoff used to define stillbirth (see Table 2). Some studies11
have confirmed that GDM may be diagnosed before 24
weeks’ gestation approximately 22% to 27% of the time.
Almost one third (or 8% of the total diagnosed with GDM)
of these patients will have type 2 diabetes when tested
postpartum.12 This is particularly true in the presence of the
following risk factors: maternal age > 35 years; obesity (BMI
> 30); ethnicity (Aboriginal, African, Asian, Hispanic, South
Asian); family history of diabetes; polycystic ovary syn-
drome; acanthosis nigricans; corticosteroid use; previous
pregnancy complicated with GDM; or previous macrosomic
infant.1 Hutcheon et al.6 have suggested that only stillbirths
greater than 28 weeks’ gestation should be included to
determine the risk of stillbirth associated with GDM.
Including women with an earlier diagnosis may not represent
the risk associated with GDM but rather a mix of GDM and
other causes of stillbirths, leading to the introduction of a
bias by including a period of follow-up during which, by
design, death or the study outcome cannot occur. Because
GDM is usually diagnosed after 24 to 28 weeks’ gestation, it
would be more appropriate to include only late stillbirth
occurring after 28 weeks. Table 2 illustrates this phenome-
non. When defining stillbirth occurring at > 20 weeks, the
risk of stillbirth attributable to GDM is reduced or insig-
nificant.6e9 This is because more than 30% of stillbirths
Absolute stillbirth
rate in GDM (per 1000
pregnancies) RR or OR (95% CI) Policy management
4.2 0.88 (0.79 to 0.99) Not available
2.0 0.31 (0.11 to 0.67) Induction rate: 38% vs 24%
4.0 0.5 (0.4 to 0.7) Routine induction at 40 weeks
0.32 0.7 (0.5 to 0.8) Not available
4.0 1.18 (0.87 to 1.60) Not available
3.5 1.25 (1.11 to 1.41) Not available
1.71 1.34 (1.2 to 1.5) At > 39 weeks risk higher if
expectant management

occur at 20 to 23 weeks, before GDM is usually diagnosed.13
When including only stillbirths occurring after 28 weeks,
many studies to date have shown a trend or a statistically
significant increased risk of stillbirth attributable to
GDM.3,6,10 The specific excess risk of stillbirth in relation to
week of gestation has recently been shown in a cohort10 and
simulation study derived from this cohort.14 This retro-
spective analysis14 of population-based data from California
showed that the overall risk of stillbirth from 36 to 42 weeks’
gestation was higher in women with GDM compared with
women without GDM (17.1 vs. 12.7/10 000 deliveries; RR
1.34; 95% CI 1.2 to 1.5). Stillbirth rates were also examined at
each gestational age, and from 36 to 39 weeks, women with
GDM had a statistically significant elevated RR of stillbirth
compared with women without GDM, ranging from RR
1.45 (95% CI 1.1 to 1.9) at 36 weeks to RR 1.84 (95% CI 1.5
to 2.3) at 37 weeks.14 This increased risk of stillbirth
remained statistically significant at 39 weeks with a RR of
1.56 (95% CI 1.2 to 2.0) but not at 40 and 41 weeks’ gesta-
tion. The loss of significance at 40 to 41 weeks’ gestation was
either due to the increase in stillbirths in non-GDM preg-
nancies15 or due to the relatively low number of patients after
39 weeks’ gestation in GDM pregnancies compared with
non-GDM pregnancies. In addition, the risk of expectant
management in women with GDM carried a higher risk of
perinatal mortality than the risk of delivery at 39 and 40
weeks’ gestation.10,14 The number of women with GDM
needed to be delivered at 39 and 40 weeks to prevent 1
excess death was 1518 and 1311, respectively.13 This is
comparable with the number needed to be delivered of 1299
at 40 weeks for women without GDM and
40 years at the
time of delivery.15 The retrospective nature of this study and
the inability to control for glycemic control and insulin
treatment presented limitations. A retrospective cohort
study from a center with a policy of induction by 40 weeks’
gestation for all pregnant women with diet-controlled GDM
suggested that it is protective against stillbirth compared with
the general obstetrical population (OR 0.5 [0.4 to 0.7]).8 The
impact of this policy of induction on Caesarean section rates
and neonatal morbidity is controversial. However, a small
RCT in mainly non-diabetic women by Nicholson et al.16
demonstrated a lower neonatal intensive care unit admis-
sion rate, a higher uncomplicated vaginal birth rate, and a
lower mean adverse outcome index score (better pregnancy
outcomes) among women who were actively managed using
elective labour induction based on a unique management of
risk scoring system.
There is good evidence that PGDM is associated with a
3- to 5-fold increased risk in stillbirths compared with
non-diabetic pregnant women.17 Further prospective
research is needed on the optimization of timing of
Diabetes in Pregnancy
delivery in both GDM and PGDM pregnancies with
specific attention to stratification by adequacy of glycemic
control; the impact on maternal, fetal and neonatal out-
comes; and economic analysis of different management
strategies.
Summary Statements
1. The adverse outcomes associated with diabetes in
pregnancy are substantially associated with
hyperglycemia and the coexisting metabolic
environment. Women with preexisting diabetes
should receive preconception care to optimize blood
sugar control and other comorbidities. Outcomes for
the fetus/neonate and the mother in both pre-
gestational diabetes mellitus and gestational diabetes
mellitus pregnancies are improved by multidisci-
plinary management in which the goal is achieving
optimal blood sugar control and appropriate fetal
surveillance. (II-2)
2. Retrospective studies indicate that women with pre-
gestational diabetes mellitus have an increased risk of
stillbirth before 40 weeks’ gestation compared with the
general obstetrical population. Similarly, large recent
cohort and simulation studies of women with gesta-
tional diabetes mellitus pregnancies also indicate a
higher risk of stillbirth between 36 to 39 weeks’
gestation. (II-2)
Screening for GDM (Appendix A)
Despite not meeting many of the criteria for a program of
population-based screening,18 screening for GDM has
been accepted widely and is almost universally practiced
among health care professionals in North America.19,20
Methods for screening for GDM include the following:
1. Screening with a 1-hour 50-g glucose load (or
alternative)
2. Risk factor based screening
3. One-step testing with a diagnostic 2-hour 75-g OGTT
(this does not in fact constitute a screening test but
rather universal testing)
4. Screening with alternative biochemical tests: FPG, gly-
cated hemoglobin, random plasma glucose
There have been no RCTs comparing screening for GDM
with no screening,20 thus the decision to perform screening
is based on the recent RCTs that have shown certain health
benefits for treatment of GDM.4,5 Because GDM is an
asymptomatic condition, logic dictates that some form of
screening would need to be performed to diagnose cases
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CLINICAL PRACTICE GUIDELINE

that might benefit from treatment and management. The
Toronto Tri Hospital study established that adverse out-
comes associated with GDM increase along a continuum
of increasing glucose thresholds.21 More recently, the Hy-
perglycemia and Adverse Pregnancy Outcome study22
confirmed these findings in a large, prospective, observa-
tional study but was unable to define outcome-based
thresholds for the diagnosis of GDM. Despite this, the
International Association of Diabetes and Pregnancy Study
Group published recommendations for new thresholds for
the diagnosis of GDM based on statistical re-analysis of the
HAPO data.23 The thresholds for the 2-hour 75-g OGTT
used were calculated by defining glucose concentrations at
which the OR of the 4 HAPO primary outcomes (birth-
weight > 90%, primary Caesarean section rate, neonatal
hypoglycemia, and cord C-peptide levels > 90%) reached
1.75. These thresholds, when applied to the HAPO cohort,
led to an average GDM incidence of 17% across all HAPO
sites. In addition the IADPSG recommended abandoning
the 1-hour 50-g glucose load in favour of a 1-step testing
strategy. Table 3 provides a summary of the glucose
thresholds, screening, and diagnostic strategies used
worldwide. In North America, either a 2-step or a 1-step
approach is believed to be acceptable because there is no
demonstrated difference in outcome using either
strategy.1,24,25
The CDA guidelines, in which SOGC was represented in
an attempt to achieve consensus between obstetricians and
endocrinologists, were updated in 2013.1 Guiding the de-
cisions of the committee were the realization that: (1)
women with 1 abnormal value on the OGTT (previously
classified as intolerance to glucose of pregnancy) have
similar outcomes of women with 2 abnormal values and
are routinely managed in the same manner12,29e33; (2) the
HAPO trial22 provided data that could be used to help
formulate outcome-based diagnostic thresholds for GDM;
and (3) there is a need to achieve some degree of unifor-
mity with regard to screening methodology and diagnostic
criteria in Canada. The CDA 2013 guidelines recommend a
universal screening for GDM for all pregnant women be-
tween 24 and 28 weeks’ gestation followed by a 2-hour
75-g OGTT if the 1-hour PG after a 50-g glucose load
value is
7.8 mmol.1 This is referred to as the “preferred
2-step” approach, with diagnostic criteria thresholds cor-
responding to an OR of 2.0 for the 4 main HAPO out-
comes.22 An “alternative 1-step” approach with diagnostic
criteria thresholds with an OR of 1.7522 for adverse peri-
natal outcome is also acceptable.1 The 2014 American
Diabetes Association guidelines25 endorsed an approach
similar to those of the CDA 2013 guidelines, although the
second step differs with the diagnostic test remaining the
100-g OGTT.25 These guidelines are also more in line with

Table 3. Universal Screening and Diagnostic Criteria for GDM (mmol/L)

ACOG 201324 CDA 20131 “alternative
ADA 201425 ACOG 2013 24
CDA 2013 1
approach,” IADPSG
Carpenter ADA 201425 National “preferred 2010,26 ADIPS 2014,27
and Coustan Diabetes Data Group approach” ADA 201425 WHO 201328
Gestational age at 24 to 28 weeks 24 to 28 weeks 24 to 28 weeks 24 to 28 weeks Any time
screening*
Steps 2-step 2-step 2-step 1-step 1-step
Step 1 Screening Step 2 if value
7.8 Step 2 if value GDM if
11.1
1-hour 50-g No diagnostic cutoff for
7.8 Step 2 if value
glucose GDM No diagnostic cutoff 7.8 to 11.0
challenge for GDM
Step 2
Loading dose 100 g 100 g 75 g 75 g 75 g
Fasting
5.3
5.8
5.3‡
5.1†
5.1†
1 hour
10.0
10.6
10.6‡
10.0†
10.0†
2 hours
8.6
9.2
9.0‡
8.5†
8.5†
3 hours
7.8
8.0 Not needed Not needed Not needed
GDM if
2 abnormal
2 abnormal
1 abnormal
1 abnormal
1 abnormal
values values value value value
Prevalence of GDM 4.8 3.2 7.0 16.1 16.1
(%)
ADA: American Diabetes Association; ADIPS, Australasian Diabetes in Pregnancy Society.
*Screening offered at any stage in the pregnancy if multiple risk factors.
†OR 1.75 for adverse perinatal outcome based on HAPO study.
‡OR of 2.00 for adverse perinatal outcome based on HAPO study.

6 l - JOGC - 2016

the ACOG 2013 guidelines.25 It is of note that the Aus-
tralasian Diabetes in Pregnancy Society and the World
Health Organization have both adopted the IADPSG
criteria in their 2013 guidelines.27,28 The incidence of
GDM varies between 3.2% and 16.1%, depending of the
thresholds used and the composition of the screened
population. Table 3 summarizes the different screening and
diagnostic criteria used for GDM.
THE 1-HOUR 50-G GCT
It is recognized that there is controversy regarding the use
of a 1-hour 50-g non-fasting GCT as a screening test for
GDM. Criticism is focused on the following issues: (1) the
inability to identify women with isolated elevated FPG, (2)
limited reproducibility, (3) incomplete uptake of the diag-
nostic test in those whose screening result is positive, (4)
delay in diagnosis of GDM, and (5) test sensitivity of only
76.6%.34 In contrast, this test is widely practiced in North
America and has high acceptance in both patients and
caregivers. Until data emerge that support significant su-
perior outcomes with a 1-step diagnostic test, the SOGC
has decided to recommend the continued use of the 50-g
OGTT as the primary screening tool in women without
high-risk characteristics.
There are no established criteria for the diagnosis of GDM
based on the 1-hour 50-g post-load value, but it is recog-
nized that there are results of this test that indicate a very
high chance of diagnosing GDM on the confirmatory test.
Cheng et al.,35 in a cohort of 14 771 pregnancies with
GDM, showed that there is an increase in Caesarean sec-
tion (OR 4.18 [1.15 to 15.2]) and an increase in shoulder
dystocia (OR 15.14 [1.64 to 140]) in women who had a
screening 1-hour 50-g glucose post-load value above 11.1
mmol/L. When the outcome 1-hour 50-g glucose
post-load is defined by an abnormal OGTT only, the
cutoff value that can reliably diagnose GDM is probably
> 12.2 mmol/L.35,36
For these reasons, the joint CDA-SOGC 2013 committee
on diabetes in pregnancy decided that if a value of
11.1
mmol/L after a 1-hour 50-g glucose post-load is obtained,
a 2-hour 75-g OGTT is unnecessary.
When the a priori risk of diagnosing GDM or overt DM is
high based on clinical, demographic, or historical risk
factors, it will be prudent to offer either screening or
testing earlier in gestation. This is mainly to facilitate the
diagnosis of unrecognized type 2 DM that will benefit from
earlier interventions to ensure adequate glycemic control.
In the presence of the following risk factorsdmaternal age
> 35 years; obesity (pre-pregnancy BMI > 30); ethnicity
Diabetes in Pregnancy
(Aboriginal, African, Asian, Hispanic, South Asian); family
history of diabetes; polycystic ovary syndrome; acanthosis
nigricans; corticosteroid use; previous pregnancy compli-
cated with GDM; or previous macrosomic infantdeither a
1-hour 50-g GCT or a diagnostic 75-g OGTT can be
offered in the first half of the pregnancy and repeated at 24
to 28 weeks’ gestation if the result is negative.1 Until there
is evidence to support alternative thresholds for the early
50-g GCT or 75-g OGTT, we suggest using the same
criteria that is used for the standard 24 to 28 weeks’
gestation test.
Pregnancy after bariatric surgery is becoming more com-
mon. GDM diagnostic testing, when applied to women
who have undergone Roux-en-Y gastric bypass, increases
the GDM diagnosis without changing pregnancy
outcome.37 In addition, a high incidence of 58% of reactive
hypoglycemia is encountered during OGTT. Therefore,
studies are needed to provide alternative screening and
diagnostic criteria for GDM in women who have under-
gone bariatric surgery. Due to a lack of evidence sup-
porting different thresholds for screening for GDM, it is
not possible to define alternative thresholds. Until then, it
is reasonable to order fasting and 1-hour postprandial
blood glucose in addition to the glycated hemoglobin level
in these women to rule out abnormalities in carbohydrate
metabolism (see Appendix A).
Recommendations
1. The “preferred screening and diagnostic 2-step”
approach for gestational diabetes mellitus of the Ca-
nadian Diabetes Association 2013 guidelines is
endorsed. All pregnant women should be offered
screening between 24 to 28 weeks using a standardized
non-fasting 50-g glucose challenge screening test with
plasma glucose measured 1 hour later. (III-B)
1.1. If the value is < 7.8 mmol/L, no further testing
is required.
1.2. If the value of the glucose challenge screening
test is 7.8 to 11.0, a 2-hour 75-g oral glucose
tolerance test with fasting plasma glucose,
1-hour plasma glucose, and 2-hour plasma
glucose should be performed.
Gestational diabetes mellitus is diagnosed if 1 value is
met or exceeded:
i. Fasting plasma glucose
5.3 mmol/L
ii. 1-hour plasma glucose
10.6 mmol/L
iii. 2-hour plasma glucose
9.0 mmol/L
1.3. If the value of the glucose challenge screening
test is
11.1 mmol/L, gestational diabetes
mellitus is diagnosed.
- JOGC - 2016 l 7
CLINICAL PRACTICE GUIDELINE
2. The “alternative 1-step diagnostic” approach of the
Canadian Diabetes Association 2013 guidelines is
acceptable. In this strategy pregnant women should be
offered testing between 24 to 28 weeks using a stan-
dardized 2-hour 75-g oral glucose tolerance test with
fasting plasma glucose, 1-hour plasma glucose, and 2-
hour plasma glucose. (III-B)
Gestational diabetes mellitus is diagnosed if 1 value is
met or exceeded:
i. Fasting plasma glucose
5.1 mmol/L
ii. 1-hour plasma glucose
10.0 mmol/L
iii. 2-hour plasma glucose
8.5 mmol/L
It is recognized that the use of different diagnostic
thresholds for the “preferred” and “alternative” strate-
gies could cause confusion in certain settings. Despite
this, the committee has identified the importance of
remaining aligned with the current Canadian Diabetes
Association 2013 guidelines as being a priority. It is thus
recommended that each care centre strategically align
with 1 of the 2 strategies and implement protocols to
ensure consistent and uniform reporting of test results.
3. If there is a high risk of gestational diabetes mellitus
based on multiple risk factors, screening or testing
should be offered during the first half of the pregnancy
and repeated at 24 to 28 weeks’ gestation if initially
normal. If for any reason it was missed or if there is a
clinical suspicion of later onset of gestational diabetes,
a screening or diagnostic test should be performed.
(II-2B)
ANTEPARTUM MANAGEMENT OF GDM
The benefits of treating GDM are now generally
accepted.4,5 There is also an association between the
presence of GDM and hypertensive disorders of preg-
nancy.22,38 The goals of treatment are: (1) optimizing
fetal growth and preventing macrosomia, (2) reducing the
risk of intrauterine fetal death, (3) reducing the risk of
preeclampsia,39 (4) reducing the risk of Caesarean section,
and (5) reducing the risk of neonatal complications,
including shoulder dystocia, birth trauma, and neonatal
hypoglycemia.
Summary Statements
3. Women with gestational diabetes mellitus have a
higher risk of preeclampsia, shoulder dystocia,
Caesarean section, and large for gestational age
infants. (II-2)
8 l - JOGC - 2016
4. Treatment of women with gestational diabetes
mellitus and optimization of glycemic control reduce
the risk of preeclampsia, shoulder dystocia, and large-
for-gestational-age infants. (I)
5. The occurrence of gestational diabetes mellitus
increases the risk of developing type 2 diabetes in the
future for the mother. (II-2)
Optimizing Fetal Growth and Preventing
Macrosomia
Fetal macrosomia may occur without gestational diabetes.
However, the incidence of macrosomia in pregnancies
complicated with maternal hyperglycemia is a function of
maternal glycemic control.22,32,33,38,40e42 There is an
association between excessive fetal weight and certain
perinatal complications, including shoulder dystocia and
birth trauma,43,44 perinatal mortality,45 and Caesarean
delivery.21,46e49 Landon et al.5 have shown that the treat-
ment of mild gestational diabetes results in a significant
reduction compared with usual care in several prespecified
secondary outcomes, including mean birth weight (3302 vs.
3408 g), neonatal fat mass (427 vs. 464 g), the frequency of
LGA infants (7.1% vs. 14.5%), birth weight greater than
4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs.
4.0%), and Caesarean delivery (26.9% vs. 33.8%). In a
secondary analysis the Maternal Fetal Medicine Network
RCT for the treatment of mild GDM demonstrated that
induction of labour between 37 to 40 weeks’ gestation in
women did not increase the rate of Caesarean delivery.50
Treatment of GDM compared with usual care was also
associated with reduced rates of preeclampsia and gesta-
tional hypertension (combined rates for the 2 conditions,
8.6% vs. 13.6%; P ¼ 0.01).
Current CDA 2013 guidelines for maternal glycemic con-
trol suggest striving for the following targets on self-
monitored blood glucose: fasting SMBG < 5.3 mmol/L;
1-hour postprandial < 7.8 mmol/L; or 2 hours post-
prandial < 6.7 mmol/L. This often can be achieved with
nutritional counselling and modification of physical activity
level. When treatment with non-medical interventions is
unsuccessful after 1 to 2 weeks, medical therapy should be
initiated.1 Optimizing maternal glycemic control in women
with GDM decreases the risk of preeclampsia, fetal mac-
rosomia, shoulder dystocia, and Caesarean section.5
An SGA fetus can also be a complication of overtreatment
of GDM or a complication of associated risk factors.50 An
RCT comparing insulin therapy based on “tight” maternal
glycemic control (keeping fasting SMBG < 5.0 mmol/L
and 2-hour postprandial at < 6.7 mmol/L) alone versus

ultrasound-based measurement of fetal abdominal
circumference percentile and more “relaxed” maternal
glycemic control (fasting SMBG < 6.6 mmol/L and 2-
hour postprandial < 11.1 mmol/L) demonstrated that
both methods resulted in an equivalent perinatal
outcome.51 The addition of measuring the abdominal
circumference every 3 to 4 weeks helped guide the decision
to treat some pregnant women more aggressively with
tighter glycemic control to prevent macrosomia but using a
more “relaxed” control if the abdominal circumference was
low to prevent the development of an SGA fetus.51e53 If a
SGA fetus is suspected, umbilical artery and middle cere-
bral artery Doppler (if available) should be performed as
part of the assessment of placental function and fetal
well-being. In the presence of fetal macrosomia or poor
glycemic control, polyhydramnios may also develop.
Therefore, the measurement of the amniotic fluid volume
can be another tool used to assess maternal glycemic
control in the context of GDM.54
Reducing the Risk of Intrauterine Fetal Death
The most important factor to minimize fetal death is
optimizing maternal glycemic control to optimize fetal
growth. The 2007 SOGC guidelines on antenatal fetal
surveillance55 lists pre-pregnancy diabetes and insulin-
requiring GDM as conditions associated with increased
perinatal morbidity/mortality and conditions in which
antenatal fetal surveillance may be beneficial. In the light of
more recent evidence that diet-controlled GDM might also
be associated with an increase in perinatal mortality,6,10,14
particularly after 38 weeks’ gestation, these patients
should not be excluded from a protocol for antenatal fetal
surveillance applicable to high-risk pregnancies. Landon
and Vickers56 previously questioned whether patients with
diet-controlled GDM should have any fetal health sur-
veillance prior to 40 weeks’ gestation because the risk of
fetal death is low. In contrast, they advocated twice per
week fetal health surveillance starting at 32 weeks for all
insulin-treated GDM patients. Most published protocols
for antenatal fetal surveillance for diet-controlled GDM
include ultrasound for fetal growth every 3 to 4 weeks
starting at 28 weeks’ gestation and delivery no later than 40
weeks’ gestation.8,51,53,57 The ACOG 2013 guidelines24
state that for women with GDM and poor glycemic con-
trol, fetal surveillance may be beneficial. A retrospective
study of 2134 women with pregnancies complicated by
diabetes reported that an antepartum fetal surveillance
program using a twice-weekly non-stress test and fluid
index assessment was successful in preventing stillbirth.58
The role of the biophysical profile in antenatal surveil-
lance of diabetic pregnancies has not been studied in a
large population, but one can logically extrapolate from the
Diabetes in Pregnancy
known value of the biophysical profile in non-diabetic
pregnancies59,60 to a diabetic pregnancy surveillance
protocol.
The use of pre-delivery weight estimation to detect the
presence of fetal macrosomia is problematic due to the
poor performance of all methods of pre-delivery fetal
weight estimation.61e63 Previous evidence has suggested
that in the context of suspected fetal macrosomia there is
no proven benefit of induction of labour compared with
expectant management.64 However, more recently, Boul-
vain et al.65 demonstrated in a large randomized clinical
trial that induction of labour for suspected large-for-date
fetuses is associated with a reduced risk of shoulder
dystocia and associated morbidity compared with expec-
tant management. Induction of labour did not increase the
risk of Caesarean delivery and improved the likelihood of
spontaneous vaginal delivery. There is only 1 randomized
clinical trial comparing elective induction with expectant
management in GDM pregnancies.66 In a mixed group of
women with uncomplicated insulin-requiring GDM or
PGDM, expectant management of pregnancy after 38
weeks’ gestation did not reduce or increase the incidence of
Caesarean delivery. However, there was an increased
prevalence of LGA infants (23% vs. 10%) and shoulder
dystocia (3% vs. 0% [not significant]) in the expectant
group.
Recommendations
4. Women with preexisting or gestational diabetes
mellitus should be provided with care by a
multidisciplinary team aimed at attaining and then
maintaining euglycemia. (II-2B)
5. For patients with pre-gestational diabetes mellitus or
gestational diabetes mellitus, starting at 28 weeks as a
baseline, with subsequent serial assessment of fetal
growth, every 3 to 4 weeks is suggested to assess the
effect of maternal glycemic control on fetal growth
rate and amniotic fluid volume. (II-2B)
6. Initiation of weekly assessment of fetal well-being at
36 weeks is recommended in pre-gestational diabetes
mellitus and gestational diabetes mellitus. It is also
reasonable to consider weekly fetal assessment for
women with diet controlled gestational diabetes mel-
litus beginning at 36 weeks. Acceptable methods of
assessment of fetal well-being near term can include
the non-stress test, non-stress test þ amniotic fluid
index, biophysical profile, or a combination of these.
(III-A)
7. If comorbid factors are present, such as obesity,
evidence of suboptimal glycemic control, large for
- JOGC - 2016 l 9
CLINICAL PRACTICE GUIDELINE
gestational age (> 90%), previous stillbirth,
hypertension, or small for gestational age (< 10%),
earlier onset and/or more frequent fetal health
surveillance is recommended. In specific cases in
which fetal growth restriction is suspected, the
addition of umbilical artery and fetal middle cerebral
artery Doppler assessment may be helpful. (II-2A)
TIMING OF DELIVERY
A recent systematic review demonstrated a reduction in the
rate of fetal macrosomia with active rather than expectant
management.67 Due to the significant heterogeneity in the
studies analyzed, the authors were limited in their ability to
draw conclusions and provide recommendations for man-
agement. Due to the small number of patients, these studies
were not powered to address the impact of induction or
expectant management on perinatal mortality. In the view
that the risk of intrauterine fetal death appears to outweigh
the risk of infant death after 39 weeks’ gestation,10 induction
of labour at 39 weeks could be considered in insulin-treated
GDM patients. Because retrospective studies suggest that a
policy of induction by no later than 40 weeks is associated
with a decreased rate of stillbirth in women with diet-
controlled GDM compared with the general obstetrical
population (OR 0.5 [0.4 to 0.7]),8 induction by 40 weeks
maybe beneficial in this population. It is also reassuring that a
recent study including all randomized clinical trials
comparing induction of labour at term or post-term with
expectant management for high- and low-risk pregnancies
showed a reduced risk of fetal death (RR 0.50 [0.25 to 0.99])
and neonatal intensive care unit admission (RR 0.86 [0.79 to
0.94]) and no increase in the Caesarean section rate with
labour induction,68 findings that have been replicated in
other studies.69,70
Recommendation
8. Pregnant women with gestational diabetes mellitus or
pre-gestational diabetes mellitus should be offered
induction between 38 to 40 weeks’ gestation
depending on their glycemic control and other co-
morbidity factors. (II-2B)
SPECIAL CONSIDERATIONS
GDM and the Use of Betamethasone
The widespread use of corticosteroids in patients at risk of
preterm delivery, often administered at the same gesta-
tional age for which screening and diagnosis of GDM is
usually performed, can make interpretation of screening
10 l - JOGC - 2016
for GDM difficult. Fisher et al.71 have demonstrated that
abnormal screening tests can be present for more than 1
week after the administration of betamethasone in 48% of
patients. For this reason, they suggested that a 1-step
diagnostic procedure is more appropriate. The overall
incidence of GDM was 14% in women who received
betamethasone compared with 4% in control patients using
a 3-hour 100-g OGTT using the National Diabetes Data
Group criteria (see Table 3).71 Therefore, a 2-hour OGTT
should be performed no less than 7 days post-
administration of the last dose of betamethasone.
Because ketoacidosis in the pregnant diabetic individual is a
potential cause of fetal demise,72e74 it is also recom-
mended to closely monitor maternal glycaemia after beta-
methasone administration in women with poorly controlled
diabetes, particularly during the first 12 hours after
administration. Administration of betamethasone in the
late preterm period at 34 to 36 weeks’ gestation is asso-
ciated with a significant reduction in major respiratory
morbidity.75 Although pre-gestational diabetic women were
excluded from this recent trial, GDM was not. Until such
benefit is proven in women with PGDM, the administra-
tion of betamethasone in the late preterm period should be
limited to women with GDM only.
Randomized and quasi-randomized controlled trials
comparing prophylactic antenatal corticosteroid adminis-
tration with placebo or with no treatment given before
elective Caesarean section at or after 37 weeks’ gestation
resulted in a significant reduction in the risk of admission
to the neonatal intensive care unit for respiratory morbidity
(OR 0.15 [0.03 to 0.64]).76 However, no significant
reduction in respiratory distress syndrome, transient
tachypnea of the newborn, need for mechanical ventilation,
or length of stay in the neonatal intensive care unit was
found.76 The only randomized trial identified77 included
only 6 diabetic pregnant women and therefore could not
assess its safety in diabetic pregnant women. It also sys-
tematically excluded women with severe hypertension, se-
vere fetal rhesus sensitization, and evidence of intrauterine
infection. Long-term follow-up of the infants did not show
any adverse outcomes or reduction in asthma.78 In light of
the marginal short-term benefits for the newborn and the
potential side effects of betamethasone on glycemic con-
trol, its use in pregnancies with diabetes at 37 to 39 weeks’
gestation scheduled for elective Caesarean section is not
recommended.
Recommendations
9. The administration of betamethasone to pregnant
women with gestational diabetes mellitus should be

restricted to the routine obstetric indications related
to the risk of preterm and late preterm delivery
between 24 to 36 weeks’ gestation, when clinically
indicated. When administered, close maternal
glycemic surveillance is recommended. (I-A)
10. If not previously done, in women with threatened
preterm labour requiring betamethasone, a screening
for gestational diabetes mellitus should be performed
either before or at least 7 days after the administration
of betamethasone. (III-B)
Counseling Postpartum (Appendix B)
Women should be encouraged to breastfeed immediately
after delivery to avoid neonatal hypoglycemia and to
continue for at least 6 months postpartum to reduce the
risk of childhood obesity and maternal hyper-
glycemia.79e82 Up to one third of affected women will
have diabetes or impaired glucose tolerance at post-
partum screening. It has also been estimated that 15% to
50% will develop type 2 diabetes later in life.24,25,83e87
Recent data from a prospective observational study
have shown that after a pregnancy complicated by GDM,
higher lactation intensity and longer duration are inde-
pendently associated with lower 2-year incidences of type
2 diabetes.43,88
Recommendations
11. Women with gestational diabetes mellitus should be
offered testing with a 75-g oral glucose tolerance test
between 6 weeks and 6 months postpartum to detect
prediabetes and diabetes.1 (II-2A)
11.1. Normal
i. Fasting plasma glucose < 6.1 mmol/L
ii. 2-hour plasma glucose < 7.8 mmol/L
iii. Glycated hemoglobin < 6.0%
11.2. Pre-diabetic
i. Fasting plasma glucose 6.1 to 6.9 mmol/L or
ii. 2-hour plasma glucose 7.8 to 11.0 mmol/L or
iii. Glycated hemoglobin 6.0% to 6.4%
11.3. Type 2 diabetes mellitus
i. FPG > 7.0 mmol/L
ii. Random plasma glucose or 2-hour plasma
glucose > 11.1 mmol/L
iii. Glycated hemoglobin
6.5%
12. Breastfeeding is strongly recommended after
delivery for all women with pre-gestational diabetes
mellitus or gestational diabetes mellitus. (II-2A)
Diabetes in Pregnancy
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in non-diabetic pregnancies with abnormal screening test. J Matern Fetal
Neonatal Med 2010;23:1193e9.
55. Liston R, Sawchuck D, Young D. Society of Obstetrics and Gynaecologists
of Canada; British Columbia Perinatal Health Program. Fetal health
surveillance: antepartum and intrapartum consensus guideline. J Obstet
Gynaecol Can 2007;29:S3e56.
56. Landon MB, Vickers S. Fetal surveillance in pregnancy complicated by
diabetes mellitus: is it necessary? J Matern Fetal Neonatal Med
2002;12:413e6.
57. Graves CR. Antepartum fetal surveillance and timing of delivery in the
pregnancy complicated by diabetes mellitus. Clin Obstet Gynecol
2007;50:1007e13.
58. Johnson JM, Lange IR, Harman CR, Torchia MG, Manning FA. Biophysical
profile scoring in the management of the diabetic pregnancy. Obstet
Gynecol 1988;72:841e6.
59. Manning FA, Bondagji N, Harman CR, Casiro O, Menticoglou S,
Morrison I. Fetal assessment based on the fetal biophysical profile score:

relationship of last BPS result to subsequent cerebral palsy. J Gynecol
Obstet Biol Reprod (Paris) 1997;26:720e9.
60. Manning FA, Bondaji N, Harman CR, Casiro O, Menticoglou S, Morrison I,
et al. Fetal assessment based on fetal biophysical profile scoring. VIII. The
incidence of cerebral palsy in tested and untested perinates. Am J Obstet
Gynecol 1998;178:696e706.
61. Melamed N, Yogev Y, Meizner I, Mashiach R, Bardin R, Ben-Haroush A.
Sonographic fetal weight estimation: which model should be used?
J Ultrasound Med 2009;28:617e29.
62. Melamed N, Yogev Y, Meizner I, Mashiach R, Ben-Haroush A.
Sonographic prediction of fetal macrosomia: the consequences of false
diagnosis. J Ultrasound Med 2010;29:225e30.
63. Melamed N, Yogev Y, Meizner I, Mashiach R, Pardo J, Ben-Haroush A.
Prediction of fetal macrosomia: effect of sonographic fetal weight-
estimation model and threshold used. Ultrasound Obstet Gynecol
2011;38:74e81.
64. Vendittelli F, Riviere O, Neveu B, Lemery D, Audipog Sentinel N. Does
induction of labor for constitutionally large-for-gestational-age fetuses
identified in utero reduce maternal morbidity? BMC Pregnancy Childbirth
2014;14:156.
65. Boulvain M, Senat MV, Perrotin F, Winer N, Beucher G, Subtil D, et al.
Induction of labour versus expectant management for large-for-date
fetuses: a randomised controlled trial. Lancet 2015;385:2600e5.
66. Kjos SL, Henry OA, Montoro M, Buchanan TA, Mestman JH. Insulin-
requiring diabetes in pregnancy: a randomized trial of active induction of
labor and expectant management. Am J Obstet Gynecol 1993;169:611e5.
67. Witkop CT, Neale D, Wilson LM, Bass EB, Nicholson WK. Active
compared with expectant delivery management in women with gestational
diabetes: a systematic review. Obstet Gynecol 2009;113:206e17.
68. Mishanina E, Rogozinska E, Thatthi T, Uddin-Khan R, Khan KS, Meads C.
Use of labour induction and risk of cesarean delivery: a systematic review
and meta-analysis. CMAJ 2014;186:665e73.
69. Gulmezoglu AM, Crowther CA, Middleton P, Heatley E. Induction of
labour for improving birth outcomes for women at or beyond term.
Cochrane Database Syst Rev 2012;6:CD004945.
70. Melamed N, Ray JG, Geary M, Bedard D, Yang C, Sprague A, et al.
Induction of labor before 40 weeks is associated with lower rate of
cesarean delivery in women with gestational diabetes mellitus. Am J Obstet
Gynecol 2016;214:364.e1e8.
71. Fisher JE, Smith RS, Lagrandeur R, Lorenz RP. Gestational diabetes
mellitus in women receiving beta-adrenergics and corticosteroids for
threatened preterm delivery. Obstet Gynecol 1997;90:880e3.
72. Bhagwanjee S, Muckart DJ, Hodgson RE, Naidoo J. Fatal foetal outcome
from diabetic ketoacidosis in pregnancy. Anaesth Intensive Care
1995;23:234e7.
73. Montoro MN, Myers VP, Mestman JH, Xu Y, Anderson BG, Golde SH.
Outcome of pregnancy in diabetic ketoacidosis. Am J Perinatol
1993;10:17e20.
Diabetes in Pregnancy
74. Sinha N, Venkatram S, Diaz-Fuentes G. Starvation ketoacidosis: a cause of
severe anion gap metabolic acidosis in pregnancy. Case Rep Crit Care
2014;2014:906283.
75. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM,
Saade GR, et al. Antenatal betamethasone for women at risk for late
preterm delivery. N Engl J Med 2016;374:1311e20.
76. Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JP. Corticosteroids
for preventing neonatal respiratory morbidity after elective caesarean
section at term. Cochrane Database Syst Rev 2009:CD006614.
77. Stutchfield P, Whitaker R, Russell I. Antenatal Steroids for Term Elective
Caesarean Section Research Team. Antenatal betamethasone and
incidence of neonatal respiratory distress after elective caesarean section:
pragmatic randomised trial. BMJ 2005;331:662.
78. Stutchfield PR, Whitaker R, Gliddon AE, Hobson L, Kotecha S, Doull IJ.
Behavioural, educational and respiratory outcomes of antenatal
betamethasone for term caesarean section (ASTECS trial). Arch Dis Child
Fetal Neonatal Ed 2013;98:F195e200.
79. Chertok IR, Raz I, Shoham I, Haddad H, Wiznitzer A. Effects of early
breastfeeding on neonatal glucose levels of term infants born to women
with gestational diabetes. J Hum Nutr Diet 2009;22:166e9.
80. Critch JN. Canadian Paediatric Society and Nutrition and Gastroenterology
Committee. Nutrition for healthy term infants, birth to six months: An
overview. Paediatr Child Health 2013;18:206e9.
81. Gunderson EP, Hedderson MM, Chiang V, Crites Y, Walton D,
Azevedo RA, et al. Lactation intensity and postpartum maternal glucose
tolerance and insulin resistance in women with recent GDM: the SWIFT
cohort. Diabetes Care 2012;35:50e6.
82. Schaefer-Graf UM, Hartmann R, Pawliczak J, Passow D, Abou-Dakn M,
Vetter K, et al. Association of breast-feeding and early childhood
overweight in children from mothers with gestational diabetes mellitus.
Diabetes Care 2006;29:1105e7.
83. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest
2005;115:485e91.
84. Chodick G, Elchalal U, Sella T, Heymann AD, Porath A, Kokia E, et al. The
risk of overt diabetes mellitus among women with gestational diabetes: a
population-based study. Diabet Med 2010;27:779e85.
85. Kaaja RJ, Greer IA. Manifestations of chronic disease during pregnancy.
JAMA 2005;294:2751e7.
86. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of
type 2 diabetes: a systematic review. Diabetes Care 2002;25:1862e8.
87. Russell MA, Phipps MG, Olson CL, Welch HG, Carpenter MW. Rates of
postpartum glucose testing after gestational diabetes mellitus. Obstet
Gynecol 2006;108:1456e62.
88. Gunderson EP, Hurston SR, Ning X, Lo JC, Crites Y, Walton D, et al.
Lactation and progression to type 2 diabetes mellitus after gestational
diabetes mellitus: a prospective cohort study. Ann Intern Med
2015;163:889e98.
- JOGC - 2016 l 13
CLINICAL PRACTICE GUIDELINE

APPENDIX A: GESTATIONAL DIABETES MELLITUS

APPENDIX B: GESTATIONAL DIABETES MELLITUS

13.e1 l - JOGC - 2016

 SOGC CLINICAL PRACTICE GUIDELINE

No. 337, October 2016 (replaces no. 161, June 2005)

Ultrasound Evaluation of First Trimester

Complications of Pregnancy

This Clinical Practice Guideline has been prepared by the Abstract

Diagnostic Imaging committee, reviewed by Clinical Practice-
Obstetrics and approved by the Board of the Society of
Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Lucie Morin, MD, Outremont QC
Yvonne M. Cargill, MD, Ottawa ON
Objective:
1. To identify sonographic features suggestive of early pregnancy loss,
2. To identify sonographic features of ectopic pregnancy, and
3. To provide a diagnostic algorithm leading to improve clinical safety
of management decision.

Phyllis Glanc, MD, Toronto ON Outcomes:

DIAGNOSTIC IMAGING COMMITTEE 1. Accuracy and improved safety in the diagnosis of early pregnancy
Kimberly Butt, MD, Fredericton NB loss, and

Yvonne M. Cargill, MD, Ottawa ON
Nanette Denis, RDMS, Saskatoon SK
Johanne Dubé, MD, Mont-Royal QC
Phyllis Glanc, MD, Toronto ON
Kenneth I. Lim (Co-chair), MD, Vancouver BC
Lucie Morin (Co-chair), MD, Outremont QC
Kentia Naud, MD, Edmonton AB
Mila Smithies, MD, Halifax ON
Disclosure statements have been received from all members of
the committee.
Key Words: Missed abortion, anembryonic pregnancy, ectopic
pregnancy, ultrasound, threatened abortion
http://dx.doi.org/10.1016/j.jogc.2016.06.001
J Obstet Gynaecol Can 2016;38(10):982e988
Copyright ª 2016 The Society of Obstetricians and Gynaecologists of
Canada/La Société des obstétriciens et gynécologues du Canada.
Published by Elsevier Inc. All rights reserved.
2. Accuracy and improved safety in the diagnosis of ectopic
pregnancy.
Evidence: A MEDLINE search and review of bibliographies identified
articles was conducted.
Values: The evidence collected was reviewed by the Diagnostic
Imaging Committee of the Society of Obstetricians and
Gynaecologists of Canada. The recommendations were made
according to the guidelines developed by The Canadian Task Force
on Preventive Health Care (Table 1).
Benefits, Harms, and Costs: Women presenting with first trimester
bleeding may be incorrectly diagnosed with a missed abortion, may
have an ectopic pregnancy overlooked, or may be inappropriately
reassured about viability. Improvement in the identification of the
sonographic landmarks of normal embryonic development and
awareness of the sonographic risk factors of pregnancy failure may
lead to more case-specific management strategies. Diagnosis of
suspected ectopic pregnancy often involves an assessment of both
hormonal markers and sonographic features. Maternal morbidity
and mortality can be reduced with an early diagnosis of ectopic
pregnancy.
Recommendations
1. Embryonic demise can be diagnosed when ultrasound imag-
ing documents the following features: intrauterine gestational
sac, embryonic crown-rump length
7 mm, no cardiac activity.
(II-2A)
2. Anembryonic pregnancy can be diagnosed when ultrasound imag-
ing documents the following features: no embryo and mean sac
diameter
25 mm. (II-2A)

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information should not be
construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions.
They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written
permission of the publisher.

982 l OCTOBER JOGC OCTOBRE 2016

 Ultrasound Evaluation of First Trimester Complications of Pregnancy

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventative Health Care
Quality of evidence assessment* Classification of recommendations†
I: Evidence obtained from at least one properly randomized A. There is good evidence to recommend the clinical preventive action
controlled trial B. There is fair evidence to recommend the clinical preventive action
II-1: Evidence from well-designed controlled trials without C. The existing evidence is conflicting and does not allow to make a
randomization recommendation for or against use of the clinical preventive action;
II-2: Evidence from well-designed cohort (prospective or however, other factors may influence decision-making
retrospective) or case-control studies, preferably from more than D. There is fair evidence to recommend against the clinical preventive
one centre or research group action
II-3: Evidence obtained from comparisons between times or places E. There is good evidence to recommend against the clinical preven-
with or without the intervention. Dramatic results in uncontrolled tive action
experiments (such as the results of treatment with penicillin in the L. There is insufficient evidence (in quantity or quality) to make a
1940s) could also be included in the category recommendation; however, other factors may influence
III: Opinions of respected authorities, based on clinical experience, decision-making
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive
Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of recommendations criteria described in The Canadian Task Force on
Preventive Health Care.

3. In clinically stable or asymptomatic patients, when a suspicion of
early pregnancy loss is being considered, a follow-up ultrasound
scan should be booked after an additional 7e10 days. (III-A)
4. Failure to detect an intrauterine gestational sac, by transvaginal
ultrasound, when the b-hCG value exceeds a discriminatory level of
2000e3000 mIU/mL indicates an increased risk for ectopic preg-
nancy. With a complex adnexal mass, a tubal ring, or complex fluid in
the pelvis the probability of tubal ectopic pregnancy is high, while a
live extrauterine embryo is diagnostic of an ectopic pregnancy. (II-2A)
5. b-hCG values in a viable pregnancy rise at least 55% over 48 hours.
Deviation from this before 7 weeks is indicative of a nonviable
pregnancy, intrauterine or ectopic. (II-2A)

ABBREVIATIONS
b-hCG beta human chorionic gonadotropin
CRL crown-rump length
CS Caesarean section

OCTOBER JOGC OCTOBRE 2016 l 983

SOGC CLINICAL PRACTICE GUIDELINE
INTRODUCTION
R ecently published clinical evidence demonstrates that
caution must be emphasized when diagnosing early
pregnancy complications to avoid misdiagnosis.1 As such,
this clinical practice guideline is an update and replaces
guidelines No. 161 published in 2005.2 The criteria for
establishing definitive pregnancy loss have been further
clarified; erroneous diagnosis of miscarriage/intrauterine
pregnancy loss can lead to interventions that will disrupt a
normal intrauterine pregnancy.
Studies published in the early 1990s, which included the
introductory use of vaginal ultrasound, allowed for
acceptance of new biometry parameters used to define
early pregnancy loss. The 2005 SOGC guidelines re-
flected that knowledge and, as such, a CRL of 5 mm
without cardiac activity or an empty gestational sac
measuring 16 mm (mean gestational sac diameter) were
reported diagnostic criteria to confirm early pregnancy
loss.2
More recently, in 2011, two large prospective studies
have challenged these previous cut-offs. In a prospective
series of 1060 women with pregnancies of uncertain
viability, which were followed up to 11e14 weeks
gestation, 55.4% received a diagnosis of nonviable
gestation during the observation period. In that study, a
CRL cut-off of 5 mm was associated with an 8.3% false-
positive rate for early pregnancy loss. A CRL cut-off
of 5.3 mm was required to achieve a false-positive rate
of 0%.3
In addition, the authors reported a 4.4% false-positive
rate for early pregnancy loss when using a mean gesta-
tional sac diameter cut-off of 16 mm. A mean gestational
sac diameter of 21 mm without an embryo and with or
without a yolk sac on the first ultrasound examination was
required to achieve 100% specificity for early pregnancy
loss.3
In the second study using 359 women from the first study
group, the authors concluded that growth rates for the
gestational sac and the embryo could not predict viability
accurately. They demonstrated that the absence of a visible
yolk sac or embryo on second scan performed 7 days or
more after the first scan was always associated with preg-
nancy loss.4
Based on these studies, the Multispecialty Panel on Early
First Trimester Diagnosis of Miscarriage and Exclusion
of a Viable Intrauterine Pregnancy from the Society of
Radiologists in Ultrasound published guidelines that were
984 l OCTOBER JOGC OCTOBRE 2016
more conservative than previous recommendations
resulting in less possibility of error than the previous
studies.1,3,4
The American College of Obstetricians and Gynecologists
has recently published clinical management guidelines for
early pregnancy loss that uses the Society of Radiologist in
Ultrasound’s diagnostic criteria.5
Embryonic Period and b-hCG Levels
b-hCG is a very sensitive and specific test for pregnancy. It
becomes positive as implantation begins day 21 or 22 after
last menstrual period or 8 days post-ovulation. A single b-
hCG value does not differentiate a viable from a nonviable
pregnancy. In a normal, early pregnancy, the b-hCG
doubling time is 1.4e2.1 days.6 The slowest rise in a viable
pregnancy over 48 hours observed was 55%.7 If a preg-
nancy is not visible in the uterus or adnexa on ultrasound
and the b-hCG is falling or plateaus, the pregnancy is not
viable.
Embryonic Period: Sonographic Landmarks
The embryonic period is defined as 8 weeks after
conception or 10 weeks after the last menstrual period.
The first ultrasound evidence of an intrauterine pregnancy
is the gestational sac within the thickened deciduas.8 This
sac, which represents the chorionic cavity, is a small
anechoic fluid collection surrounded by an echogenic ring
that represents trophoblasts and decidual reaction.9 It is
possible to identify the sac by 4 weeks and 3 days gestation
when the mean diameter is 2e3 mm.8,10
The yolk sac is the first structure seen within the gesta-
tional sac and, when seen, confirms an intrauterine preg-
nancy.9 The yolk sac can be identified when the mean
gestational sac diameter is as small as 5e6 mm and is
generally visualized when the mean gestational sac diam-
eter is greater than or equal to 8 mm.10
Table 2. Typical embryonic chronological landmarks in
the development of the embryo, as seen on transvaginal
ultrasound examination (conception to 8 weeks
development)
5 þ 0 weeks Empty gestational sac (mean diameter 10 mm)
5 þ 4 weeks Gestational sac with yolk sac visible
6 þ 0 weeks Gestational sac (mean diameter 16 mm) and yolk
sac with adjacent heart beat but small embryo
(3mm)
8 þ 0 weeks Embryo with CRL of 16 mm with separate amniotic
sac and celomic cavity with yolk sac
Embryo body movements visible, heart rate 175 bpm
 Ultrasound Evaluation of First Trimester Complications of Pregnancy
Table 3. Diagnosis of asymptomatic tubal ectopic
pregnancy
Possible ectopic Serum b-hCG level > 2000 mIU/mL
pregnancy Absence of intrauterine pregnancy on
transvaginal ultrasound
Probable ectopic Serum b-hCG level > 2000 mIU/mL
pregnancy Absence of intrauterine pregnancy on
transvaginal ultrasound
Adnexal mass on transvaginal ultrasound
Diagnosis of Gestational sac inside fallopian tube on
ectopic pregnancy transvaginal ultrasound
The amnion is a thin, rounded membrane surrounding the
embryo and is completely enveloped by the thick echogenic
chorion. The yolk sac is situated between the amnion and
the chorion. The amnion is thin, difficult to visualize, and
best seen when the amnion membrane is perpendicular to
the ultrasound beam. The amnion grows rapidly during
pregnancy and fuses with the chorion between 12 and 16
weeks of gestation.8,10
The embryo can be visualized when as small as 1e2 mm in
CRL length. Cardiac activity immediately adjacent to the
yolk sac indicates a live embryo but may not be seen until
the embryo CRL measures 7 mm. From 5.5e6.5 weeks,
an embryonic heart rate of less than 100 beats per minute
is normal. During the following 3 weeks, there is a
rapid increase up to 180 beats per minute.11,12 Table 2
summarizes the sonographic features of normal early
pregnancy.
Other Ultrasound Features of Early Pregnancy Loss
Certain ultrasound features are associated with early
pregnancy loss including bradycardia (heart rate less than
85 beats per minute) at greater than 7 weeks of
gestation,12e15 a small sac size relative to the embryo
(difference of less than 5 mm between gestational sac and
CRL),16 enlarged (greater than or equal to 5e6 mm),17 or
abnormally shaped (crenelated) yolk sac and subchorionic
hematoma.18,19
Early Pregnancy Loss
Early pregnancy loss may have occurred with findings of
vaginal bleeding and/or abdominal pain. A pregnancy
of unknown viability may incidentally be found at the time
of a dating or prenatal screening ultrasound. It is important
in clinical diagnosis to rule out ectopic pregnancy, gesta-
tional trophoblastic disease, and spontaneous abortion.
When assessing intrauterine pregnancy, the differential
diagnosis would include a developing pregnancy, a missed
abortion, or an ectopic pregnancy.
If the viability and location of a pregnancy needs to be
decided at a single point in time, such as an emergency visit
by a pregnant woman with symptoms of bleeding and pain,
the most useful single test to differentiate a viable from a
nonviable pregnancy is a progesterone level. Progesterone
less than 20 nmol/L have a sensitivity of 75% and speci-
ficity of 98% in predicting nonviable pregnancy.20 The
most useful single test to differentiate an intrauterine from
an ectopic pregnancy is an ultrasound.
An ultrasound diagnosis of an embryonic demise can be
made when there is no cardiac activity in an embryo with a
CRL greater than or equal to 7 mm.1 Ultrasound diagnosis
of an anembryonic pregnancy can be made when the mean
gestational sac diameter is greater than or equal to 25 mm
but without a yolk sac or an embryo. Transvaginal ultra-
sound is the method of choice for early first trimester
pregnancy complications although transabdominal or
transvaginal ultrasound may be used for patients with first
trimester bleeding.
In the absence of cardiac activity, if the gestational sac or
the embryo is smaller than expected by menstrual dating,
the possibility of incorrect dates should always be consid-
ered, especially when there is no pain or bleeding. Under
these circumstances, a repeat ultrasound scan should be
arranged after an additional 7e10 days.1,5 Single or serial
b-hCG values may be used to add support to a diagnosis
of a nonviable pregnancy. b-hCG values that are falling or
not rising appropriately would confirm a nonviable
pregnancy.
Figure 1. First trimester pregnancy ultrasound: intrauterine
pregnancy identified
Intrauterine
No cardiac ac vity Cardiac ac vity present
Normal intrauterine
CRL > 7 mm CRL < 7 mm
Repeat ultrasound in 7-10
days and/or Serial β-hCG.
If β-hCG not rising
appropriately or absent FHR
Non-viable intrauterine pregnancy
OCTOBER JOGC OCTOBRE 2016 l 985
SOGC CLINICAL PRACTICE GUIDELINE
Figure 2. First trimester pregnancy ultrasound
No intrauterine pregnancy
and β-hCG available
Ultrasound signs of an
ectopic?
Yes
β-hCG greater than 2000-3000
If β-hCG greater than 2000-3000 or
not rising appropriately
Yes
Likely, an ectopic pregnancy
(Consider a complete
abor on if β-hCG falling)
Ectopic Pregnancy
The initial diagnostic test in women with suspected ectopic
pregnancy is measurement of the serum b-hCG. A nega-
tive test rules out pregnancy, including ectopic pregnancy.
An ultrasound that demonstrates an intrauterine preg-
nancy is reassuring because a heterotopic pregnancy oc-
curs in only 1:7000e1:30 000 of spontaneously conceived
pregnancies.21 The suspicion of a possible heterotopic
pregnancy should be higher with the use of assisted
reproduction techniques because of the incidence in this
circumstance is up to 1%.22,23 The diagnosis of an in-
trauterine pregnancy involves visualizing a gestational sac,
within the endometrial cavity, and showing an embryo or
yolk sac.24 Although an intrauterine fluid collection
without these characteristics may be a pseudogestational
sac, the likelihood is much higher that this represents an
intrauterine pregnancy. Doubilet et al. have demonstrated
that any intrauterine fluid collection is associated with a
99.5% chance that the pregnancy is intrauterine.25 The
appearance of an ectopic pregnancy is varied. The first
ultrasound in ectopic pregnancies is reported as normal
i.e., empty uterus, no adnexal mass, and no free fluid in
15% to 25% of cases.26,27 The most common ectopic
pregnancy is tubal, thus the findings may include an empty
uterus, simple adnexal cyst, complex adnexal mass, solid
adnexal mass, tubal ring, free fluid in the adnexa-cul de
sac area, or complex fluid in the pelvis. Other ectopic
pregnancy locations would include cornual, cervical,
986 l OCTOBER JOGC OCTOBRE 2016
(1) empty uterus, (2) simple adnexal cyst, (3) complex adnexal mass, (4)
solid adnexal mass, (5) tubal ring,( 6) free fluid in the adnexa-cul de sac
area, or (7) complex fluid in the pelvis .
No
No
Repeat β-hCG every 48 hours
If β-hCG rises not
appropriately, β-hCG reaches
2000-3000, or symptoms
increase
Repeat ultrasound
within the cesarean section scar, intraovarian or an intra-
abdominal ectopic pregnancy.26,28
With the clinical suspicion of an ectopic pregnancy, a
normal scan (no signs of an intrauterine or extrauterine
pregnancy), or the presence of a simple adnexal cyst
carries a low probability of ectopic pregnancy (5%),
whereas the probability is above 90% with a solid or
complex adnexal mass separate from the ovary or a tubal
ring.28 A live pregnancy that is not implanted within the
endometrial cavity is diagnostic of an ectopic pregnancy.
Isolated free fluid in the pelvis is rarely the only sono-
graphic finding.28
Colour Doppler waveforms from the peri-trophoblast have
been shown to demonstrate low impedance flow. Colour
Doppler may demonstrate an ectopic pregnancy as a ring-
like structure. Colour Doppler may add useful information
when other ultrasound findings lead to a diagnostic
dilemma or uncertainty. For example, with a complex
adnexal mass, the finding of low impedance colour
Doppler waveform or a ring of colour Doppler may more
strongly suggest an ectopic pregnancy.29 Nonetheless, it is
important to recognize that the corpus luteum, including
an exophytic corpus luteum, may present with similar
colour Doppler findings.
Quantitative level of maternal serum b-hCG and high-
resolution ultrasound imaging are complementary. The
 Ultrasound Evaluation of First Trimester Complications of Pregnancy
b-hCG level of an ectopic pregnancy can be above or
below the discriminatory zone. Rupture of ectopic preg-
nancy can occur at any b-hCG level. Failure to detect an
intrauterine gestational sac when the b-hCG values exceed
a discriminatory level indicates a high risk of ectopic
pregnancy.30 Although intrauterine pregnancy can be
documented on transvaginal ultrasound when b-hCG
level is as low as 1500 UI/L, current literature review
supports the use of a discriminatory level of b-hCG from
2000 UI/L up to 3000 UI/L especially when measured
before 7 weeks of gestation.1 In the absence of an intra-
uterine pregnancy a b-hCG level greater than 2500 has an
11% sensitivity and a 95% specificity for an ectopic
pregnancy.31 As such, in asymptomatic patient and in the
absence of ultrasound features suggestive of ectopic
pregnancy, expectant management when serum b-hCG
level is less than that cut-off at less than 7 weeks gestation
is not associated increased morbidity. A b-hCG not rising
appropriately over 48 hours is diagnostic of a nonviable
pregnancy intrauterine or ectopic. A single b-hCG level
cannot be used to diagnose an ectopic pregnancy without
considering the patient’s clinical presentation, physical
examination, and ultrasound findings. A complete spon-
taneous abortion can take place at a b-hCG level above or
below 3000. Table 3 simplifies the diagnosis of non-
ruptured ectopic pregnancy.
Figures 1 and 2 propose decision trees for the diagnostic
evaluation of first trimester pregnancy complications.
Recommendations:
1. Embryonic demise can be diagnosed when ultrasound
imaging documents the following features:
intrauterine gestational sac, embryonic crown-rump
length
7 mm, no cardiac activity. (II-2A)
2. Anembryonic pregnancy can be diagnosed when
ultrasound imaging documents the following features:
no embryo and mean gestational sac diameter
25
mm. (II-2A)
3. In clinically stable or asymptomatic patients, and when
a suspicion of early pregnancy loss is being considered,
a follow-up ultrasound scan should be booked after an
additional 7e10 days. (III-A)
4. Failure to detect an intrauterine gestational sac, by
transvaginal ultrasound, when the b-hCG value
exceeds a discriminatory level of 2000e3000 mIU/mL
indicates an increased risk for ectopic pregnancy. With
a complex adnexal mass or a tubal ring, the probability
of tubal ectopic pregnancy is high, while identification
of a live extrauterine embryo is diagnostic of an ectopic
pregnancy. (II-2A)
5. b-hCG values in a viable pregnancy rise at least 55%
over 48 hours. Deviation from this before 7 weeks is
indicative of a nonviable pregnancy, intrauterine or
ectopic. (II-2A)
REFERENCES
1. Doubilet PM, Benson CB, Bourne T, Blaivas M, Barnhart KT,
Benacerraf BR, et al. Diagnostic criteria for nonviable pregnancy early in
the first trimester. Society of Radiologists in Ultrasound Multispecialty Panel
on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable
Intrauterine Pregnancy. N Engl J Med 2013;369:1442e51.
2. Morin L, Van den Hof M, Bly S, Farquharson D, Lewthaite B, et al.
Ultrasound evaluation of first trimester pregnancy complications. J Obstet
Gynaecol Can 2005;27(6):581e5.
3. Abdallah Y, Daemen A, Kirk E, Pexsters A, Naji O, Stalder C, et al.
Limitations of current definitions of miscarriage using mean gestational
sac diameter and crown-rump length measurements: a multicenter
observational study. Ultrasound Obstet Gynecol 2011;38:497e502.
4. Abdallah Y, Daemen A, Guha S, Syed S, Naji O, Pexsters A, et al.
Gestational sac and embryonic growth are not useful as criteria to define
miscarriage: a multicenter observational study. Ultrasound Obstet Gynecol
2011;38:503e9.
5. Prager S, Dalton VK, Allen RH. ACOG. Practice Bulletin No 150: Early
pregnancy loss. Obstet Gynecol 2015;125:1258e67.
6. Daya S. Human chorionic gonadotropin increase in normal early pregnancy.
Am J Obstet Gynecol 1987;156:286e90.
7. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W.
Symptomatic patients with an early viable intrauterine pregnancy: hCG
curves redefined. Obstet Gynecol 2004;104:50e5.
8. Goldstein S. Early detection of pathologic pregnancy by transvaginal
sonography. J Clin Ultrasound 1990;18:262e73.
9. Sauerbrei E, Coooperberg PL, Poland JB. Ultrasound demonstration of the
normal fetal yolk sac. J Clin Ultrasound 1980;8:217.
10. Timor-Tritsch IE, Farine D, Rosen MG. A close look at early embryonic
development with the high-frequency transvaginal transducer. Am J
Obstet Gynecol 1988;159:166e81.
11. Merchiers EH, Dhont M, De Sutter PA, Beghin CJ, Vandekerchove DA.
Predictive value of early embryonic cardiac activity for pregnancy
outcome. Am J Obstet Gynecol 1991;165:11e4.
12. Achiron R, Tadmor O, Mashiach S. Heart rate as a predictor of first
trimester spontaneous abortion after ultrasound-proven viability. Obstet
Gynecol 1991;78:330e4.
13. Laboda LA, Estroff JA, Benacerraf BR. First trimester bradycardia a sign of
impending fetal loss. J Ultrasound Med 1989;8:561e3.
14. Howe RS, Isaacson KJ, Albert JL, Coutifaris CB. Embryonic heart rate in
human pregnancy. J Ultrasound Med 1991;19:367e71.
15. Falco P, Milano V, Pilu C, Grisolia DG, Rizzo N, Bovicelli L. Sonography of
pregnancies with first-trimester bleeding and a viable embryo: a study of
prognostic indicators by logistic regression analysis. Ultrasound Obstet
Gynecol 1996;7:165e9.
16. Bromley B, Harlow BL, Laboda LA, Benacerraf BR. Small sac size in the
first trimester: a predictor of poor fetal outcome. Radiology
1991;178:375e7.
17. Hurwitz SR. Yolk sac sign: sonographic appearance of the fetal yolk sac in
missed abortion. J Ultrasound Med 1986;5:435e8.
OCTOBER JOGC OCTOBRE 2016 l 987
SOGC CLINICAL PRACTICE GUIDELINE
18. Ferrazzi E, Brambati B, Lanzani A, Oldrini A, Stripparo L, Guerneri S, et al.
The yolk sac in early pregnancy failure. Am J Obstet Gynecol
1988;158:137e42.
19. Mantoni M, Pedersen JF. Intrauterine haematoma an ultrasonic study of
threatened abortion. British J Obstet Gynecol 1981;88:47e51.
20. Verhaegen J, Gallos ID, van Mello NM, Abdel-Aziz M, Takwoingi Y, et al.
Accuracy of single progesterone test to predict early pregnancy outcome in
women with pain or bleeding: meta-analysis of cohort studies. BMJ
2012;345:e6077.
21. DeVoe RW, Pratt JH. Simultaneous intra- and extrauterine pregnancy. Am J
Obstet Gynecol 1948;56:1119.
22. Dimitry ES, Subak-Sharpe R, Mills M, Maragara R, Winston R. Nine cases
of heterotopic pregnancies in 4 years of in vitro fertilization. Fertil Steril
1990;53:107e10.
23. Gamberdella FR, Marrs RP. Heterotopic pregnancy associated with assisted
reproductive technology. Am J Obstet Gynecol 1989;160:1520e4.
24. Nyberg DA, Laing FC, Filly RA, Uri-Simmons M, Jeffrey RB.
Ultrasonographic differentiation of the gestational sac of early intrauterine
pregnancy from the pseudogestational sac of ectopic pregnancy. Radiology
1983;146:755e9.
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25. Doubilet PM, Benson CB. First, do no harm.to early. J Ultrasound Med
2010;29:685e9.
26. Fleischer AC, Pennell RG, McKee MS, Worrell JA, Keefe B, Herbert CM,
et al. Ectopic pregnancy: features transvaginal sonography. Radiology
1990;174:375e8.
27. Richardson A, Gallos I, Dobson S, Campbell BK, Coomarasam A, Raine-
Fenning N. Accuracy of first trimester ultrasound diagnosis of tubal
pregnancy in the absence of an obvious extrauterine embryo: systematic
review and meta analysis. Ultrasound Obstet Gynecol 2016;477:28e37.
28. De Crespigny LC. Demonstration of ectopic pregnancy by transvaginal
ultrasound. British J Obstet Gynaecol 1988;95:1253e6.
29. Jurkovic D, Bourne TH, Jauniaux E. Transvaginal colour Doppler study of
blood flows in ectopic pregnancies. Fertil Steril 1992;57:68e72.
30. Kadar N, DeVore G, Romero R. Discriminatory hCG zone: its use in the
sonographic evaluation for ectopic pregnancy. Obstet Gynecol
1981;58:156e61.
31. Condous G, Kirk E, Lu C, Van Huffel S, Gevaert O, de Moor B, et al.
Diagnostic accuracy of varying discriminatory zones for the prediction of
ectopic pregnancy in women with a pregnancy of unknown location.
Ultrasound Obstet Gynecol 2005;26:770e5.
 SOGC CLINICAL PRACTICE GUIDELINE
Adolescent Pregnancy Guidelines
This Clinical Practice Guideline has been prepared by the
Canadian Paediatric and Adolescent Gynaecology and
Obstetricians (CANPAGO) committee, reviewed by the
Family Physician Advisory, Aboriginal Health Initiative,
Maternal Fetal Medicine, and the Clinical Practice—
Obstetrics Committees, and approved by the Executive and
Board of the Society of Obstetricians and Gynaecologists
of Canada.
PRINCIPAL AUTHORS
Nathalie Fleming, MD, Ottawa ON
Teresa O’Driscoll, MD, Sioux Lookout ON
Gisela Becker, RM, Calgary AB
Rachel F. Spitzer, MD, Toronto ON
CANPAGO COMMITTEE
Lisa Allen, MD (Co-chair), Toronto ON
Debra Millar, MD (Co-chair), Vancouver BC
Philippa Brain, MD, Calgary AB
Nancy Dalziel, RN, Ottawa ON
Elise Dubuc, MD, Montreal QC
Julie Hakim, MD, Ottawa ON
Deanna Murphy, MD, St. John’s NL
Rachel Spitzer, MD, Toronto ON
Disclosure statements have been received from all contributors.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
Key Words: Pregnancy, adolescent, teen, teenager, youth
J Obstet Gynaecol Can 2015;37(8):740–756
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
740 l AUGUST JOGC AOÛT 2015
No. 327, August 2015
Abstract
Objective: To describe the needs and evidence-based practice
specific to care of the pregnant adolescent in Canada, including
special populations.
Outcomes: Healthy pregnancies for adolescent women in Canada,
with culturally sensitive and age-appropriate care to ensure the
best possible outcomes for these young women and their infants
and young families, and to reduce repeat pregnancy rates.
Evidence: Published literature was retrieved through searches
of PubMed and The Cochrane Library on May 23, 2012
using appropriate controlled vocabulary (e.g., Pregnancy in
Adolescence) and key words (e.g., pregnancy, teen, youth).
Results were restricted to systematic reviews, randomized control
trials/controlled clinical trials, and observational studies. Results
were limited to English or French language materials published
in or after 1990. Searches were updated on a regular basis and
incorporated in the guideline to July 6, 2013. Grey (unpublished)
literature was identified through searching the websites of health
technology assessment and health technology-related agencies,
national and international medical specialty societies, and clinical
practice guideline collections.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Benefits/Harms/Costs: These guidelines are designed to help
practitioners caring for adolescent women during pregnancy
in Canada and allow them to take the best care of these
young women in a manner appropriate for their age, cultural
backgrounds, and risk profiles.
Recommendations
  1. Health care providers should adapt their prenatal care for
adolescents and offer multidisciplinary care that is easily
accessible to the adolescent early in the pregnancy, recognizing
that adolescents often present to care later than their adult
counterparts. A model that provides an opportunity to address all
of these needs at one site may be the preferred model of care for
pregnant adolescents. (II-1A)
  2. Health care providers should be sensitive to the unique
developmental needs of adolescents through all stages of
pregnancy and during intrapartum and postpartum care. (III-B)
  3. Adolescents have high-risk pregnancies and should be managed
accordingly within programs that have the capacity to manage their
care. The unique physical risks of adolescent pregnancy should be
recognized and the care provided must address these. (II-1A)

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.119
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.119
  4. Fathers and partners should be included as much as possible in
pregnancy care and prenatal/infant care education. (III-B)
  5. A first-trimester ultrasound is recommended not only for the usual
reasons for properly dating the pregnancy, but also for assessing
the increased risks of preterm birth. (I-A)
  6. Counselling about all available pregnancy outcome options
(abortion, adoption, and parenting) should be provided to any
adolescent with a confirmed intrauterine gestation. (III-A)
  7. Testing for sexually transmitted infections (STI) (II-2A) and
bacterial vaginosis (III-B) should be performed routinely upon
presentation for pregnancy care and again in the third trimester;
STI testing should also be performed postpartum and when
needed symptomatically.
a. Because pregnant adolescents are inherently at increased
risk for preterm labour, preterm birth, and preterm pre-labour
rupture of membranes, screening and management of
bacterial vaginosis is recommended. (III-B)
b. After treatment for a positive test, a test of cure is needed 3
to 4 weeks after completion of treatment. Refer partner for
screening and treatment. Take the opportunity to discuss
condom use. (III-A)
  8. Routine and repeated screening for alcohol use, substance
abuse, and violence in pregnancy is recommended because of
their increased rates in this population. (II-2A)
  9. Routine and repeated screening for and treatment of mood
disorders in pregnancy is recommended because of their
increased rates in this population. The Edinburgh Postnatal
Depression Scale administered in each trimester and postpartum,
and more frequently if deemed necessary, is one option for such
screening. (II-2A)
10. Pregnant adolescents should have a nutritional assessment,
vitamins and food supplementation if needed, and access to a
strategy to reduce anemia and low birth weight and to optimize
weight gain in pregnancy. (II-2A)
11. Conflicting evidence supports and refutes differences in
gestational hypertension in the adolescent population; therefore,
Adolescent Pregnancy Guidelines
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
the care usual for adult populations is supported for pregnant
adolescents at this time. (II-2A)
12. Practitioners should consult gestational diabetes mellitus (GDM)
guidelines. In theory, testing all patients is appropriate, although
rates of GDM are generally lower in adolescent populations.
Practitioners should be aware, however, that certain ethnic groups
including Aboriginal populations are at high risk of GDM. (II-2A)
13. An ultrasound anatomical assessment at 16 to 20 weeks
is recommended because of increased rates of congenital
anomalies in this population. (II-2A)
14. As in other populations at risk of intrauterine growth restriction
(IUGR) and low birth weight, an ultrasound to assess fetal well-
being and estimated fetal weight at 32 to 34 weeks gestational
age is suggested to screen for IUGR. (III-A)
15. Visits in the second or third trimester should be more frequent to
address the increased risk of preterm labour and preterm birth
and to assess fetal well-being. All caregivers should be aware of
the signs and symptoms of preterm labour and should educate
their patients to recognize them. (III-A)
16. It should be recognized that adolescents have improved vaginal
delivery rates and a concomitantly lower Caesarean section
rate than their adult counterparts. (II-2A) As with antenatal care,
peripartum care in hospital should be multidisciplinary, involving
social care, support for breastfeeding and lactation, and the
involvement of children’s aid services when warranted. (III-B)
17. Postpartum care should include a focus on contraceptive
methods, especially long-acting reversible contraception
methods, as a means to decrease the high rates of repeat
pregnancy in this population; discussion of contraception should
begin before delivery. (III-A)
18. Breastfeeding should be recommended and sufficient support
given to this population at high risk for discontinuation. (II-2A)
19. Postpartum care programs should be available to support
adolescent parents and their children, to improve the mothers’
knowledge of parenting, to increase breastfeeding rates, to screen
for and manage postpartum depression, to increase birth intervals,
and to decrease repeated unintended pregnancy rates. (III-B)
AUGUST JOGC AOÛT 2015 l 741
SOGC clinical practice guideline
20. Adolescent women in rural, remote, northern, and Aboriginal
communities should be supported to give birth as close to home
as possible. (II-2A)
21. Adolescent pregnant women who need to be evacuated from
a remote community should be able to have a family member
or other person accompany them to provide support and
encouragement. (II-2A)
22. Culturally safe prenatal care including emotional, educational,
and clinical support to assist adolescent parents in leading
healthier lives should be available, especially in northern and
Aboriginal communities. (II-3A)
23. Cultural beliefs around miscarriage and pregnancy issues, and
special considerations in the handling of fetal remains, placental
tissue, and the umbilical cord, must be respected. (III)
INTRODUCTION
A dolescence is a distinct and unique physical and
developmental stage in a woman’s life. Consequently,
the diagnosis and management of pregnancy during this
time, before the age of 20, deserves acknowledgement of
its distinctive inherent risks and an understanding of the
relevant elements of care required for successful outcomes
for the mother, the infant, and their surrounding social
circle. The SOGC represents a wide variety of practitioners
and disciplines involved in maternity care and is therefore
well placed to present guidelines on the care of the pregnant
adolescent, of which multidisciplinary care is a key feature.
Adolescent pregnancy is a subject relevant to practices in
Canada and around the world, and it bears mentioning that
not all adolescent pregnancies are unplanned or unwanted.
Annually, 14 million 14- to 19-year-olds deliver babies
globally. Births to adolescent mothers represent 10% of
ABBREVIATIONS
aRR adjusted relative risk
BV bacterial vaginosis
CS Caesarean section
DMPA depot medroxyprogesterone acetate
GA gestational age
GDM gestational diabetes mellitus
IPV intimate partner violence
IUD intrauterine device
IUGR intrauterine growth restriction
LARC long-acting reversible contraception
LBW low birth weight
NICU neonatal intensive care unit
PPROM preterm pre-labour rupture of membranes
PTB preterm birth
PTL preterm labour
SGA small for gestational age
STI sexually transmitted infection
SVD spontaneous vaginal delivery
742 l AUGUST JOGC AOÛT 2015
births worldwide, but 23% of maternal morbidity and
mortality.1 Adolescent pregnancy is the leading cause of
mortality in girls aged 15 to 19 worldwide; 90% of these
deaths occur in resource-poor countries and most of them
are preventable.1,2 Adolescent pregnancy is also a cause
for concern worldwide because of high rates of unsafe
abortion and poor knowledge-seeking behaviours, prenatal
care, and support.1
In Canada, the fertility rate for adolescents aged 15 to 19 in
2009 was 14.2 births per 1000 women; 15 638 babies were
born to women under 20 that year, up slightly from the all-
time low reached in 2005 (13.4), though still significantly
lower than the rates seen in the 1980s.3 Across the country,
adolescent pregnancy rates are highest in Nunavut and the
Northwest Territories and lowest in Prince Edward Island
and Ontario. Between 1996 and 2006, adolescent birth
rates in Canada decreased in a continuous downward trend
from 22.1/1000 to 13.7/1000 and abortion rates decreased
from 22.1/1000 to 14.2/1000. The birth rate is higher in
older adolescents (23.3, age 18–19) than in younger (6.5,
age 15–17). In Canada, younger adolescents are more likely
to have an induced abortion than to give birth, whereas
the majority of pregnancies among older adolescents end
in a live birth. In 2010, abortion was the most common
outcome of adolescent pregnancies in Canada.4
Worldwide, poverty and lower educational attainment are
risk factors for adolescent pregnancy.1 Once pregnant, an
adolescent becomes more likely than her non-pregnant
peers to have lower educational attainment, to drop out of
school, and to have lower socioeconomic status and lower
social capital. Children of an adolescent parent are similarly
more likely than their peers to have lower educational
achievement, grow up in a single-mother household, be
involved in alcohol and drugs, and to become a single
adolescent parent themselves.5–7
Adolescent pregnancies worldwide are noted to have
higher maternal, obstetrical, and neonatal risks, with
those in women aged ≤ 15 having risks noted to be even
higher than those in adolescents aged ≥ 16. Adolescent
pregnancies should therefore be managed as high risk in
programs that can accommodate their unique risks and
concerns.8–10
Consent and Confidentiality in Caring
for Adolescent Patients in Canada
In caring for pregnant adolescents, their ability to consent
within their relationship should be considered, as should the
possible need to report the relationship to child protection
authorities if it violates or violated the law. In Canada, by
law, the general age of consent for sexual activity is 16, with

age-related exceptions for adolescents aged 12 to 16 with
partners ranging from up to 2 years older to 5 years older
depending on their own age. For exploitive sexual activity,
the age of consent is 18. See Appendix A for a detailed
outline of consent for different ages and the definition of
exploitive sex.11
Respecting the autonomy and confidentiality of the
adolescent patient may at times be complicated by the
care setting and the surrounding environment. Issues of
confidentiality are likely to arise with care of very young
adolescents, care in a small community, and care of other
family members in the clinic and potentially even within
team care. Child protection agencies, although not actively
involved and part of the circle of care until after the birth
of the baby in cases of newborn apprehension, may be
able to provide support for counselling, parenting, and
financial assistance.
When considering options for pregnant adolescents in
our country, it is important to remember that there is no
specific age of consent for medical treatment in Canada.
As long as individuals are deemed to have the capacity
to provide consent (i.e. to understand the nature of the
procedure as well as its risks and alternatives), they do not
need to have reached a particular age in order to provide
consent. (By law in Quebec, however, parents have the
right to access the medical records of children under the
age of 14).12
ANTEPARTUM CARE
Prenatal Care and Multidisciplinary Care Programs
Unfortunately, adolescents have a significantly lower
attendance of prenatal classes (aRR 0.87, 95% CI 0.85 to
0.91) and first-trimester antenatal visits (aRR 0.53, 95% CI
0.51 to 0.55) than adult women.6,13,14 Reasons for delay in
seeking care are multifactorial: lack of knowledge about
the importance of prenatal care and lack of understanding
of the consequences of its absence; history as a victim
of violence, desire to hide pregnancy, fear of potential
apprehension of the baby, contemplation of abortion
services; concerns about lack of privacy or judgemental
attitudes from health care providers or adults; and financial
barriers.14 Lack of, or delayed, adolescent prenatal care is
associated with adverse maternal, obstetrical, and neonatal
outcomes.9,13,15–17
Standard prenatal care improves outcomes in adolescent
pregnancy18–21; adequate prenatal care has been shown
to be protective against fetal and infant mortality in this
population.9 However, studies suggest that standard care
misses psychosocial vulnerabilities, STI screening,22 and
Adolescent Pregnancy Guidelines
postpartum issues such as breastfeeding, contraception,
and school return.23
Multidisciplinary adolescent-focused prenatal care
leads to better outcomes than standard prenatal care in
adolescents,8,10,24 including reductions in PTB,8,10 LBW,10,25
and NICU admissions,26 increased SVD,10,26 and reduction
in operative delivery.8,10 Major cost savings related to infant
and paediatric health could be realized by preventing
preterm births.
Adolescent-centred multidisciplinary comprehensive care
with a goal to improving outcomes for mothers and their
infants is considered the gold standard for management
of the myriad problems that present in an adolescent
pregnancy (Appendix B).8 Elements of care are aimed at
reducing adverse maternal and neonatal outcomes. Teaching
strategies and topics are important considerations when
providing health information for pregnant adolescents.
The adolescent should have easy access to care based on a
philosophy of providing care in a welcoming environment
with multidisciplinary teams to meet the many health care
needs of the adolescent. It is also important to encourage
early enrollment into prenatal care and participation in
community support programs.8
Two cohort studies demonstrated a significant reduction
in PTB and LBW when adolescents attended specialized
multidisciplinary antenatal care. An Australian cohort
showed that screening for and treating STIs resulted
in a significant reduction in PTB in a general antenatal
clinic (OR 0.4; 95% CI 0.25 to 0.62),27 and the Canadian
cohort demonstrated that dedicated multidisciplinary
care provided in an adolescent-friendly community
outreach program led to a 53% reduction in PTB (OR
0.47, 95% CI 0.22 to 1.00).10 This Canadian study
observed a 59% reduction in LBW babies (95% CI
0.18 to 0.95).10 It is important to address nutritional
requirements and maternal weight gain when caring for
pregnant adolescents; useful strategies may include dietary
assessments, a comprehensive prenatal nutrition program,
and a community food donation program in addition to
access to prenatal care.10 Multidisciplinary adolescent-
focused antenatal care therefore has tremendous potential
to reduce the significant health care costs associated with
PTB and LBW infants.
A number of models of multidisciplinary care have been
described that achieve the aforementioned desired objectives.
Successful models have been implemented in hospitals,
schools, clinics, and community facilities.10 Multidisciplinary
care is usually provided in one place at one time,10 and
further study should continue to evaluate this mode of
AUGUST JOGC AOÛT 2015 l 743
SOGC clinical practice guideline
care. Where possible “one-stop shopping” and easy visits
work best for the adolescent.10 Home visiting programs by
health care professionals and trained lay visitors have also
been assessed; though this model may impact a particular
outcome, it does not appear to contribute to the overall
desired outcomes.28–31 Helping the pregnant adolescent to
navigate the system is an important function for all team
members to be aware of and participate in, including being
aware of the roles of other team members, the services
available, and in particular client-centred issues, to assist
patients to access needed services.32
Antenatal opportunities to develop parenting skills that
continue in the postpartum period are likely to improve
birth outcomes, increase maternal school attendance, and
reduce rapid repeat pregnancy.33 Assistance with varied
parenting structures to reduce parenting stress and child
dysfunction can also be helpful. The family system and the
intergenerational dynamics within a multigenerational care-
giving structure are critical to the health and well-being
of both mothers and their children.34 Decisions about
including families of origin and fathers when appropriate in
the parenting process are often complex and require special
consideration of their risks and benefits. Many fathers
struggle to stay involved in the lives of their children, and
prenatal and young family support programs seek to find
opportunities to engage young fathers in the programs
and ultimately in their children’s lives.35 Adolescents who
participate in such support and education in adolescent-
centred care models are more likely to continue their
education during the pregnancy and the postpartum year
than peers who do not participate in such programs.
Recommendations
1. Health care professionals should adapt
their prenatal care for adolescents and offer
multidisciplinary care that is easily accessible to
the adolescent early in the pregnancy, recognizing
that adolescents often present to care later than
their adult counterparts. A model that provides an
opportunity to address all of these needs at one site
may be the preferred model of care for pregnant
adolescents. (II-1A)
2. Health care providers should be sensitive to
the unique developmental needs of adolescents
through all stages of pregnancy and during
intrapartum and postpartum care. (III-B)
3. Adolescents are high-risk pregnancies and should
be managed accordingly within programs that
have the capacity to manage their care. The unique
physical risks of adolescent pregnancy should be
recognized and the care provided must address
these. (II-1A)
744 l AUGUST JOGC AOÛT 2015
4. Fathers and partners should be included as much as
possible in pregnancy care and prenatal/infant care
education. (III-B)
5. A first-trimester ultrasound is recommended not
only for the usual reasons for properly dating the
pregnancy, but also for assessing the increased risks
of preterm birth. (III-A)
Choice in Pregnancy
Upon diagnosis of intrauterine pregnancy, adolescents can
and should be counselled, without specific consideration
of their age, about their options for continuation with the
intent to parent, adoption, or termination. They should
be offered support with the participation of the support
person(s) of their choice. Canada has no abortion law, and
thus abortion remains an option for the patient so long as
access permits. Access to abortion, however, varies greatly
in different jurisdictions and provinces across the country.36
Recommendation
6. Counselling about all available pregnancy outcome
options (abortion, adoption, and parenting) should
be provided to any adolescent with a confirmed
intrauterine gestation. (III-A)
Sexually Transmitted Infections
Adolescents are at greater risk for STIs because they
frequently have multiple partners, have unprotected
intercourse, are biologically more vulnerable to sexually
acquired infections and face multiple obstacles to
utilization of health care.37 Pregnant adolescents may be
at further risk because they are less likely to use condoms
with intercourse during their pregnancy than non-pregnant
adolescents.21,38 In pregnancy, STIs have been associated
with preterm delivery, chorioamnionitis, and postpartum
infections.39 Adolescents with an STI have a higher risk
of PPROM leading to PTB.10,27,40 Vertical transmission
of chlamydia during vaginal delivery ranges from 30%
to 50% and may result in pneumonia and ophthalmia
neonatorum.39 Screening and treatment is associated with
a significant decrease in the incidence of newborn febrile
morbidity (10% vs. 25%, P = 0.02).41 These infections can
also increase the risk of HIV acquisition and transmission.41
Adolescent women are at heightened risk because of the
physiologic immaturity of their cervix and the consequent
susceptibility of the tissues to infection.42
Prevalence of chlamydia in adolescent pregnancy is high.
At initial prenatal visit, infection rates range from 11.8%
to 31%.41,43–47
The recurrence rate throughout the pregnancy is also high
among adolescents. A Canadian retrospective study reported

an infection rate of 22.1% in routine third trimester screening.44
A prospective cohort of 125 adolescents with chlamydia or
gonorrhoea in pregnancy who were retested in third trimester
reported a reinfection rate of 11%; 7% had a new infection,
while 3% had recurrent gonorrhoea.45 Repeated testing
between 3 and 4 weeks later to ensure treatment success and
lack of reinfection is recommended in this population.48
BV in pregnancy has also been associated with adverse
outcomes including PPROM, PTL, PTB, and postpartum
endometritis. There is evidence to support screening
and treatment at 12 to 16 weeks in high-risk (those
with previous PTL, PTB, or PPROM) or symptomatic
pregnancies, although it is not recommended in low-risk
or asymptomatic pregnancies.48 Because of their inherently
increased risks of PPROM, PTL, and PTB, adolescent
pregnancies are all considered to be high-risk.
Recommendation
7. Testing for sexually transmitted infection (II-2A)
and bacterial vaginosis (III-B) should be performed
routinely upon presentation for pregnancy care
and again in the third trimester; testing for sexually
transmitted infection should also be performed
postpartum and when needed symptomatically.
a. Because pregnant adolescents are inherently at
increased risk for preterm labour, preterm birth,
and preterm pre-labour rupture of membranes,
they are a high-risk group and therefore
screening and management of bacterial
vaginosis is recommended. (III-B)
b. After treatment for a positive test, a test of
cure is needed 3 to 4 weeks after completion
of treatment. Refer partner for screening and
treatment. Take the opportunity to discuss
condom use. (III-A)
Smoking, Substance Abuse, and Alcohol Abuse
Adolescents who are pregnant have higher rates of
smoking (38.8% vs. 11.9%, P < 0.001) and substance
abuse (11.7% vs. 5.1%, P < 0.0001) than their adult
counterparts.13 An Australian retrospective study revealed
20.3% of adolescents used marijuana during pregnancy, of
which 33.5% were multidrug users. Of adolescents who
were non-users, 50% were previous users who ceased drug
use immediately before or early during pregnancy. Illegal
drug use was associated with concomitant cigarette and
alcohol use.49 However, pregnancy is a powerful incentive
for many adolescents to reduce tobacco, alcohol, and drug
use; previous studies have shown cessation rates of up to
60% to 75%.49 A critical component of the care of this
pregnant population should therefore be aimed at reducing
the effects of smoking and substance abuse, including
Adolescent Pregnancy Guidelines
alcohol. For general recommendations concerning alcohol
and substance use in pregnancy, see the SOGC Alcohol
Use and Pregnancy Consensus Clinical Guidelines50 and
Substance Use in Pregnancy.51
Violence and Coercion
Violence in adolescent pregnancy is unfortunately quite
common, with an odds ratio of 1.8 in one study.52 Violence
in pregnancy is associated with late engagement in prenatal
care and an increased risk of adverse perinatal outcomes
such as LBW, PTB, and fetal death,53 and postpartum
depression.54,55 Rates of IPV in pregnant adolescents, at
26% to 31%, are higher than in their adult counterparts.
Violence often begins in the first trimester and is usually
committed by the partner. A history of abuse within
the last year is predictive of violence in pregnancy.56 In
addition, 26% of pregnant adolescents known to be
victims of IPV also reported sexual coercion from their
partner.57 A history of past physical abuse at any point is
strongly associated with adolescent pregnancy.58 See the
SOGC Intimate Partner Violence Consensus Statement59
for recommendations concerning IPV in pregnancy and
Appendix C60 for a short screening tool for IPV.
Exploring pregnancy intentions and the behaviours of
partners of sexually active adolescents may help to identify
youth experiencing IPV57; questions about all types of
abuse should routinely be asked of adolescent patients.59
Recommendation
8. Routine and repeated screening for alcohol use,
substance abuse, and violence in pregnancy is
recommended because of their increased rates in
this population. (II-2A)
Mood Disorders
Depression is diagnosed in 4% to 8% of adolescents.
In pregnancy, the rate varies from 16% to 44%, almost
twice as high as among adult pregnant women and non-
pregnant adolescents. Depressive symptoms among
pregnant adolescents become more severe between the
second and third trimesters,61 and half of adolescent
mothers experience symptoms of depression in the early
postpartum period.62 Adolescent mothers are twice as
likely to experience depression than adult mothers.16
Factors significantly associated with depressive symptoms
in pregnancy include antenatal depressive symptoms and
IPV.55,63
Untreated maternal depression is associated with adverse
maternal, neonatal, and childhood outcomes, as well as
with postpartum depression16,61 and increased frequency
of subsequent pregnancies. Untreated maternal depression
AUGUST JOGC AOÛT 2015 l 745
SOGC clinical practice guideline
is also associated with preterm delivery and SGA
infants. Finally, untreated depression is associated with
unresponsive mothering and behavioural and cognitive
problems in children.64
The risk of postpartum depression is significant in
adolescent mothers. Indeed, 47% of adolescent mothers
had significant symptoms of depression at 4 to 6 weeks
postpartum, and the depressive symptoms continued at 12
months postpartum.62 Of particular concern, by 12 months
postpartum, none of the adolescent mothers in this study
with symptoms of depression had pursued referrals for
mental health evaluation and treatment.62
It is therefore crucial to promote improved maternal
mental health in the adolescent population including early
recognition and management of psychiatric disorders
and treatment of depression and suicidal ideation and
intent.61,62,64 The Edinburgh Postnatal Depression Scale is
one option for routine screening.65
Recommendation
9. Routine and repeated screening for and treatment
of mood disorders in pregnancy is recommended
because of their increased rates in this population.
The Edinburgh Postnatal Depression Scale
administered in each trimester and postpartum, and
more frequently if deemed necessary, is one option
for such screening. (II-2A)
Anemia and Nutritional Care
Anemia (hemoglobin < 105 g/L) is a very common
complication in pregnant adolescents, with a reported
prevalence of from 50% to 66%27,66 and an increased
relative risk of 1.27 (95% CI 1.15 to 1.4),67 usually
attributed to inadequate replacement or nutrition. In
addition, a prospective study demonstrated that low
body iron stores and low ferritin were significantly more
common in pregnant adolescents than in pregnant adults.68
Smoking status was an important risk factor for LBW and
anemia.69 Care for the pregnant adolescent should therefore
incorporate nutritional care to both optimize weight gain
and manage potential nutritional deficiencies.
Recommendation
10. Pregnant adolescents should have a nutritional
assessment, vitamin and food supplementation if
needed, and access to a strategy to reduce anemia
and low birth weight and to optimize weight gain in
pregnancy. (II-2A)
Hypertensive Disorders of Pregnancy
There is conflicting evidence regarding the risk of
preeclampsia and gestational hypertension in adolescents.
746 l AUGUST JOGC AOÛT 2015
Some studies demonstrate a higher rate of hypertensive
disorders in adolescent pregnancies than in adults.70,71
Other studies, however, do not demonstrate a difference
in gestational hypertension between adolescents and adults
of the same parity.6,13 While the methodologies of the
studies differ, it is also important to control for potential
confounders such as parity, smoking, and substance use.
When adjusted for these factors, a decreased risk of
gestational hypertension was seen in a Canadian cohort
(aRR 0.73, 95% CI 0.68 to 0.79).13
Recommendation
11. Conflicting evidence supports and refutes
differences in gestational hypertension in the
adolescent population; therefore, the care usual
for adult populations is supported for pregnant
adolescents at this time. (II-2A)
Gestational Diabetes
In Canada, the prevalence of GDM in all pregnancies is
higher than previously thought, varying from 3.7% in the
non-Aboriginal population to 8% to 18% in Aboriginal
populations.72 However, recent retrospective studies
indicate that non-Aboriginal adolescents have lower rates
of GDM (OR 0.04; 95% CI 0.01 to 0.29),73 (aRR 0.34;
95% CI 0.30 to 0.39)13 than adult women. However, at this
time, screening of pregnant adolescents should follow the
same guidelines and management for GDM as for adult
women.71
Recommendation
12. Practitioners should consult gestational diabetes
mellitus (GDM) guidelines. In theory, testing all
patients is appropriate, although rates of GDM
are generally lower in adolescent populations.
Practitioners should be aware, however, that certain
ethnic groups including Aboriginal populations are
at high risk of GDM. (II-2A)
Prevention of Adverse Maternal and Neonatal
Outcomes: PTB, LBW, and IUGR
Adolescent pregnancies have a higher risk of adverse
outcomes such as PTB (< 37 weeks),9,15,18,66,74,75 very PTB,
(< 32 weeks),9,13,18,74,75 and extremely PTB (< 28 weeks),9,76
LBW (< 2500 g),9,15,66,74,75 very LBW (< 1500 g),9,74 IUGR
(< 3rd centile for GA) and stillbirths,9,67,70,76 and NICU
admissions and neonatal deaths.9,13,17,74–77 In addition,
congenital anomalies are more common in adolescent
pregnancies. These include central nervous system
anomalies (anencephaly, spina bifida, hydrocephaly,
microcephaly), gastrointestinal anomalies (gastroschisis,
omphalocele), and musculoskeletal anomalies (cleft lip,
cleft palate, polydactaly, syndactaly).74,75,78

Since a significant proportion of pregnant adolescents
have a low socioeconomic status, it has been assumed that
the high risk nature of these pregnancies is due to their
environment.79,80 However, 2 large retrospective cohort
studies challenge this assumption.
The first is a retrospective cohort study of almost 2 million
adolescent births in the United States adjusted for potential
confounders such as state, race, marital status, smoking,
alcohol use, and prenatal care.74 In this cohort, even after
adjusting for those confounders, adolescent pregnancy
was independently associated with increased risk of PTB
(RR = 1.2), very PTB (RR = 1.26), LBW (RR = 1.14), very
LBW (RR = 1.11), SGA (RR = 1.07), and neonatal mortality
(RR = 1.15). The effect of adolescent pregnancy on neonatal
mortality disappeared after adjustment of birth weight and
gestational age; this suggests that neonatal mortality may
be explained by the higher rate of PTB and LBW infants
in adolescent mothers.74 Other studies have found similar
results, proposing that increased NICU admission rates are
likely a result of increased preterm deliveries.9,17,75
The second study is a recent retrospective cohort study
with data adjusted for race, twins, and number of prior
births in 37 million births in the United States, of which
over 300 000 were to adolescent mothers ≤ 15 years of age.
These young adolescents were at significantly increased risk
of PTB (OR = 1.76), very PTB (OR = 2.4), extremely PTB
(OR = 2.48), LBW (OR = 1.37), very LBW (OR = 1.47),
SGA (OR = 1.14), IUGR (OR = 1.21), stillbirth (OR = 1.31),
and infant death (OR = 1.87). Adequate prenatal care was
protective against fetal and infant mortality.9
When reviewing the fetal and infant outcomes of Canadian
adolescent pregnancies, similar adverse outcomes are seen.
A recent retrospective study comparing almost 24 000
adolescents with adults in Ontario revealed that neonates
born to adolescent mothers have a significantly higher
risk of admission to NICU (aRR = 1.08) and very PTB
(aRR = 1.16). The risk of having a large for gestational
age infant was significantly lower in the adolescent group
(aRR = 0.92). There were no significant differences in
SGA (aRR = 1.00), LBW (aRR = 1.05), PTB (aRR = 1.04),
and fetal death (aRR = 1.02).13 In another study, Canadian
adolescents had a 3-fold increase in the risk of delivery
before 34 weeks, with a subsequent increase in NICU
admissions.75 This is a concerning finding, because preterm
birth is an important indicator of neonatal well-being that
has been associated with severe morbidity and mortality.80–83
Recommendation
13. An ultrasound anatomical assessment at 16 to 20
weeks is recommended because of increased rates
of congenital anomalies in this population. (II-2A)
Adolescent Pregnancy Guidelines
14. As in other populations at risk of intrauterine
growth restriction (IUGR) and low birth weight, an
ultrasound to assess fetal well-being and estimated
fetal weight at 32 to 34 weeks’ gestational age is
suggested to screen for IUGR. (III-A)
15. Visits in the second or third trimester should be
more frequent to address the increased risks of
preterm labour and preterm birth and to assess fetal
well-being. All caregivers should be aware of the
signs and symptoms of preterm labour and should
educate their patients to recognize them. (III-A)
INTRAPARTUM CARE
Many retrospective studies in high income countries
have demonstrated a higher rate of vaginal deliveries in
adolescents than in adults, along with a shorter active phase
of labour, similar length of second stage, and a lower rate
of assisted vaginal delivery and CS varying from 2% to
14%.6,10,18,67,74,84,85
Two large retrospective studies found a higher rate of
vaginal deliveries in adolescents than in adult women (aRR
1.76; 95% CI 1.70 to 1.82),13 while their rates of assisted
vaginal deliveries (aRR = 0.62 to 0.76) and CS (aRR 0.57 to
0.79) were lower.13,18,84 The adolescent group also had lower
epidural use.13,86 However, when adolescents required a CS,
unlike adult women, it was most often in an emergency.13,84
The most common indications for emergency CS in the
adolescent group in one study were non-reassuring fetal
status and labour dystocia.13
Recommendation
16. It should be recognized that adolescents
have improved vaginal delivery rates and a
concomitantly lower Caesarean section rate than
their adult counterparts. (II-2A). As with antenatal
care, peripartum care in hospital should be
multidisciplinary, involving social care, support for
breastfeeding and lactation, and the involvement of
children’s aid services when warranted. (III-B)
POSTPARTUM CARE
Contraception
Adolescent mothers are at significant risk for repeat
pregnancy, with 25% becoming pregnant again within
2 years of delivery.87 However, not all adolescent pregnancies
are undesired, and a significant number of them are in fact
planned. A prospective cohort study of adolescents in a
multidisciplinary care setting demonstrated that over 50% of
adolescents idealized pregnancy as the “single most exciting
and positive event to have occurred.”30 In a Canadian
AUGUST JOGC AOÛT 2015 l 747
SOGC clinical practice guideline
retrospective study, one third desired their pregnancy.
Efforts to promote awareness and the availability of
contraception would not have prevented these pregnancies.88
Protective factors against repeat pregnancy include use of
LARC, school attendance, and living alone or with a parent
as opposed to with a partner.89 Postpartum care and the
provision of options for contraception are therefore crucial
elements of pregnancy care for the adolescent. Evidence in
the postpartum adolescent population specifically suggests
that LARCs such as DMPA and IUDs are far better at
preventing repeat pregnancies than are shorter-term methods
such as oral contraception, contraceptive patch, or barrier
methods.90 In one study, 14.2% of adolescents on DMPA
were pregnant again one year later compared with 29.7%
and 31.8% of oral contraception and patch users.91 LARCs
are specifically endorsed for adolescents by the American
Congress of Obstetricians and Gynecologists.92 Educational
encounters with health care providers and education +
contraception programs have shown protective outcomes,93
while behavioural interventions alone have not shown
consistent results.94 Provision of emergency contraception
in addition to the usual contraceptive methods has been
associated with a higher likelihood of its use, although these
adolescents may also be more likely to engage in unprotected
intercourse.95 Immediate postpartum contraception, with
initiation of DMPA postpartum, placement of IUD at the
time of delivery, or placement of contraceptive implant
before hospital discharge have also shown significantly
decreased repeat pregnancy rates.96 However, expulsion
rates of IUDs are noted to be higher with immediate
postpartum placement.97 Other novel techniques to decrease
repeat pregnancy rates include peer-led educational models,
varied educational modalities, and the use of cell phones
and social media to promote participation and follow-up.
More investigation of such options is required. Pregnancy
prevention and contraception counselling in this population
require extra time and energy to improve knowledge,33,98,99
uptake, and management of sociodemographic risk factors.
Recommendation
17. Postpartum care should include a focus on
contraceptive methods, especially long-acting
reversible contraception methods, as a means to
decrease the high rates of repeat pregnancy in this
population; discussion of contraception should
begin before delivery.
Breastfeeding and Postpartum Support
The joint WHO/UNICEF global recommendations for
optimal infant feeding is exclusive breastfeeding during the
first 6 months.100 In Canada, a joint statement by Health
Canada, the Canadian Paediatric Society, Dieticians of
748 l AUGUST JOGC AOÛT 2015
Canada, and the Breastfeeding Committee for Canada also
states that exclusive breastfeeding for the first 6 months
is important for the nutrition, immunologic protection,
growth, and development of infants and toddlers.101
In Canada, breastfeeding initiation rates have increased
significantly in the last decades. In 1965, fewer than 25%
of mothers breastfed compared with 88.4% in 2011.101
However, in 2011 only 27.8% continued to breastfeed their
infants to 6 months.2,3 Adolescent mothers have an even
lower initiation and continuation rate of breastfeeding
than adult women.102–105 Published data for breastfeeding
rates among adolescent mothers is sparse.102 An American
study indicated that 42.8% of adolescent women initiated
breastfeeding, but only 9.1% continued to breastfeed to 6
months compared with 15% to 34% of mothers from all
other age groups.102
Adolescent mothers and their infants are at greater risk
for many health and socioeconomic issues such as anemia
and depressive disorders in the mother; LBW, PTB,
developmental problems, and learning difficulties in the
infants, and rapid repeat pregnancy. Breastfeeding could
greatly benefit these young mothers and their infants by
ameliorating some of these outcomes.
Studies in the adolescent population have suggested
multiple sociodemographic factors are associated
with lower rates of breastfeeding including age, race,
educational level, marital status, and socioeconomic
status.102,103,105 Other studies have suggested that lack of
knowledge, a negative opinion about pregnancy, and lack
of breastfeeding support from family, friends, and partner
could affect breastfeeding rates.102,103
Programs should be available during pregnancy and
postpartum to support breastfeeding, enhance parenting
skills, reduce rapid repeat pregnancies and improve
continuation of maternal education. These may be
continuations of an adolescent pregnancy program
or specific early-years parenting programs provided
through public health agencies and other locally available
supports. Increased breastfeeding rates can be achieved
and supported by adolescent mothers’ involvement in
antenatal classes and proactive breastfeeding support from
a lactation consultant, physician, midwife, or nurse with
consideration of specific adolescent concerns such as
privacy, body image, and pumping.
Recommendation
18. Breastfeeding should be recommended and
sufficient support given to this population at high
risk for discontinuation. (II-2A)

19. Postpartum care programs should be available to
support adolescent parents and their children, to
improve the mothers’ knowledge of parenting,
to increase breastfeeding rates, to screen for and
manage postpartum depression, to increase birth
intervals, and to decrease repeated unintended
pregnancy rates. (III-B)
SPECIAL CONSIDERATIONS IN ABORIGINAL
ADOLESCENT POPULATIONS
Culturally, adolescent pregnancies have been accepted
in most Aboriginal communities. By tradition, babies
are regarded as a gift from the Creator and children are
welcomed into the families regardless of the mother’s
age. Most of the young mothers keep their babies and are
well supported by their own mothers, extended families,
and communities.106 At the same time it appears that
there is some stigma attached to adolescent childbearing
in Aboriginal communities, especially when the mother is
very young.107
Currently, concerns about adolescent pregnancies in
Aboriginal communities are growing for a number of
reasons. While recent Canadian statistics show a steady
decline in adolescent pregnancy and birth rates since
the 1990s, adolescent pregnancy rates in Aboriginal and
northern communities continue to be up to 4 times higher
than the national average.108 Among women who reported
an Aboriginal background, 24% were adolescent mothers
compared with just 10% of non-Aboriginal women.
The prevalence of current smoking among Aboriginal
youth is more than double that among non-Aboriginal
youth (24.9% vs. 10.4%).109 Aboriginal youth also had a
higher prevalence of regular exposure to second-hand
smoke at home (37.3% vs. 19.7%) and in cars (51.0%
vs. 30.3%). Aboriginal youth were more likely than non-
Aboriginal youth to have tried marijuana and other illicit
drugs and to engage in binge drinking; it is also suggested
that fetal alcohol spectrum disorder rates are higher in
this population than in other populations in Canada.110
Aboriginal youth were less likely than non-Aboriginal
youth to have tried to quit smoking.109 Although alcohol
and substance abuse have been frequently reported
as influencing factors in becoming pregnant, they are
generally not an ongoing lifestyle choice for most
Aboriginal adolescents. The responsibility of motherhood
is a powerful motivator for many of the young women to
stop harmful behaviours and to start planning for their
futures.111 Access to culturally safe maternity care for
adolescents may not always be available in Aboriginal and
Adolescent Pregnancy Guidelines
northern communities. Young mothers and fathers require
emotional, educational, medical, and potentially financial
support to lead healthier lives without drugs and alcohol
and to become positive role models for their children,
younger siblings, and the community.
Management of diabetes, including GDM, in Aboriginal
people should follow the same clinical practice guidelines
as those for the general population with recognition of,
respect for, and sensitivity to the unique language, cultural,
and geographic issues relating to diabetes care and
education in Aboriginal communities across Canada and
the increased rates of diabetes mellitus in this population.72
Aboriginal adolescent mothers in remote northern
communities face additional challenges around birthplace
choices and locations. Local maternity care programs do not
exist in many communities and frequently young mothers
are required to travel weeks in advance to a regional centre
to give birth. This practice leads to separation and isolation
from family members and the home community and has
an even greater impact on adolescent mothers who require
additional support during the labour and birth process.112
The loss of indigenous knowledge and medicine in
Aboriginal cultures has been described by many leaders
and Elders as the root of many contemporary health and
well-being issues faced by Aboriginal peoples today.113
Supporting existing traditional practices (such as the
inclusion of Elders in prenatal care, the use of herbal
medicines, specific diet recommendations, the young
woman’s desire to give birth on traditional territory) and
the use of traditional birthing practices (such as Aboriginal
midwifery, smudging, naming ceremony, and retention
of placental tissue, and umbilical cord remnants) are
important when caring for adolescent pregnant women in
northern and Aboriginal communities.113,114 Recognizing
and acknowledging the importance and the wide variety of
community-specific practices both across the country and
within a region are important, as is the acceptance of those
practices by the pregnant adolescent.115,116
Custom adoption, the cultural practices of Aboriginal
peoples to raise a child by a person who is not the child’s
parent, according to the custom of the First Nations and/
or Aboriginal community of the child, is a common form
of adoption in Aboriginal communities; it is recognized
in the Indian Act of 1985117 and in most Canadian
jurisdictions, for example in the 1990 Aboriginal Custom
Adoption Recognition Act of the Northwest Territories.118
Custom adoption ensures that Aboriginal children maintain
their cultural, linguistic, and spiritual identity.
AUGUST JOGC AOÛT 2015 l 749
SOGC clinical practice guideline
Aboriginal custom adoption takes place usually between 2
families who know each other or have connected with one
another through word of mouth in the community and
often includes a custom adoption ceremony. Statistics on
custom adoptions are difficult to obtain.
Recommendations
20. Adolescent women in rural, remote, northern,
and Aboriginal communities should be supported
to give birth as close to home as possible. (II-2A)
Adolescent women in rural, remote, northern, and
Aboriginal communities should be supported to
give birth as close to home as possible. (II-2A)
21. Adolescent pregnant women who need to be
evacuated from a remote community should be
able to have a family member or other person
accompany them to provide support and
encouragement. (II-2A)
22. Culturally safe prenatal care including emotional,
educational, and clinical support to assist
adolescent parents in leading healthier lives should
be available, especially in northern and Aboriginal
communities. (II-3A)
23. Cultural beliefs around miscarriage and pregnancy
issues, and special considerations in the handling
of fetal remains, placental tissue, and the umbilical
cord, must be respected. (III)
SUMMARY
Adolescence is a unique stage of the life cycle, and
adolescent pregnancy, while perhaps slowly on a decline
in North America, remains a uniquely high-risk pregnancy
situation requiring multidisciplinary care adapted
specifically to meet the physical and emotional needs of
the adolescent. Special populations within the Canadian
population with high rates of adolescent pregnancy, such
as Aboriginal populations, demand culturally appropriate
care. Appropriate contraception and education also needs
to be provided to reduce rapid repeat pregnancy rates in
this high risk population.
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Appendix begins on next page
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SOGC clinical practice guideline

APPENDIX A

What is Canada’s age of consent?

The age of consent for sexual activity is 16 years. It was raised from 14 years on May 1, 2008 by the Tackling
Violent Crime Act.
However, the age of consent is 18 years where the sexual activity “exploits” the young person—when it
involves prostitution, pornography, or occurs in a relationship of authority, trust, or dependency (e.g., with a
teacher, coach, or babysitter). Sexual activity can also be considered exploitative based on the nature and
circumstances of the relationship, e.g., the young person’s age, the age difference between the young person
and their partner, how the relationship developed (quickly, secretly, or over the Internet) and how the partner
may have controlled or influenced the young person.

Are there any exceptions to this?

The Criminal Code provides “close-in-age” or “peer group” exceptions.
For example, a 14- or 15-year-old can consent to sexual activity with a partner as long as the partner is less
than five years older and there is no relationship of trust, authority or dependency or any other exploitation
of the young person. This means that if the partner is 5 years or older than the 14- or 15-year-old, any
sexual activity will be considered a criminal offence unless it occurs after they are married to each other
(in accordance with the “solemnization” of marriage requirements that are established in each province
and territory, governing how and when a marriage can be performed, including the minimum age at which
someone may marry).
There is also a “close-in-age” exception for 12- and 13-year-olds: a 12- or 13-year-old can consent to sexual
activity with another young person who is less than two years older and with whom there is no relationship of
trust, authority or dependency or other exploitation of the young person.

Are 16 and 17 year olds also protected against sexual exploitation?

The Criminal Code protects 16- and 17-year-olds against sexual exploitation, where the sexual activity
occurs within a relationship of trust, authority, dependency, or where there is other exploitation. Whether
a relationship is considered to be exploiting the 16- or 17-year-old will depend upon the nature and
circumstances of the relationship, e.g., the age of the young person, the age difference between the young
person and their partner, how the relationship developed and how the partner may have controlled or
influenced the young person. As well, 16- and 17-year-olds cannot consent to sexual activity that involves
prostitution or pornography.

Department of Justice, Canada11

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 Adolescent Pregnancy Guidelines

APPENDIX B

Risks Interventions/solutions
Socioeconomic
Financial/housing Consult social work
Smoking Smoking cessation program: Kick Butt for 2; harm reduction strategies
Substance use/alcohol Addiction counselling
Violence Screen for violence (see validated questionnaire)
Mood Screen for depression, ± referral to psychiatry
Compliance with appointment Adolescent-focused multidisciplinary care
Provide assistance with transportation
School curriculum, prenatal class
Maternal
Anemia Dietician, food donation, vitamins
Inadequate nutrition Prenatal nutrition program, Buns in the Oven
STI Screen/treat STI initial visit; each trimester, if symptomatic
Neonatal
Prematurity Accurate dating scan
Screen/treat STI initial visit; each trimester, if symptomatic
Frequent visits in 2nd and 3rd trimester
Screen for substance use and violence in pregnancy
LBW, very LBW, IUGR, stillbirth Frequent visits in 2nd and 3rd trimester
32 week ultrasound for growth
Assessment of fetal well-being
Nutritional assessment/support
Postnatal
Repeat pregnancy Assess desire
Contraception counselling during pregnancy
Follow-up at 1 to 2 weeks and 6 weeks postpartum and beyond
Provide free contraception (CCAP)
Breastfeeding Lactation consultant (pre- and post pregnancy)
Breastfeeding class
Postpartum depression Assess risk in pregnancy, refer to psychiatry if necessary
Follow-up at 2 and 6 weeks postpartum
CCAP: Compassionate Contraceptive Assistance Program (available through Society of Obstetricians and Gynaecologists of Canada)

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SOGC clinical practice guideline

APPENDIX C
Screening questions relating to domestic violence

1. Do you feel safe in your relationship with your partner or family?

Code: Yes
No
Unsure/declined to answer

2. Are there situations in the past 6 months when you have felt afraid of
your partner or a family member?
Code: Yes by partner by family member
No
Unsure/declined to answer

3. In the past 6 months, have you ever been a victim of domestic violence
from your partner or a family member?
Code: Yes If yes, by Family member Yes/No
Partner, current Yes/No
Partner, previous Yes/No
Other Yes/No
No
Unsure/declined to answer

4. In the past 6 months, have you ever been hit, kicked, punched,
or physically hurt by a partner or family member?
Code: Yes If yes, by Family member Yes/No
Partner, current Yes/No
Partner, previous Yes/No
Other Yes/No
No
Unsure/declined to answer

5. In the past 6 months, have you ever been forced to have sex or
do sexual things that you did not want to do by a partner or family
member?
Code: Yes If yes, by Family member Yes/No
Partner, current Yes/No
Partner, previous Yes/No
Other Yes/No
No
Unsecure/declined to answer
Note: “Fig. 1. Screening questions on domestic violence and the coding of answers.” Journal
of Pediatric and Adolescent Gynecology.60 Reproduced with permission of Elsevier Inc.

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 SOGC CLINICAL PRACTICE GUIDELINE

No. 322, April 2015

Endometrial Ablation in the Management

of Abnormal Uterine Bleeding
Abstract
This clinical practice guideline has been reviewed by the
Clinical Practice–Gynaecology Committee and approved by Background: Abnormal uterine bleeding (AUB) is the direct cause
the Executive and Board of the Society of Obstetricians and of a significant health care burden for women, their families,
Gynaecologists of Canada. and society as a whole. Up to 30% of women will seek medical
assistance for the problem during their reproductive years.
PRINCIPAL AUTHORS
Objective: To provide current evidence-based guidelines on the
Philippe Laberge, MD, Quebec QC techniques and technologies used in endometrial ablation (EA),
a minimally invasive technique for the management of AUB of
Nicholas Leyland, MD, Ancaster ON
benign origin.
Ally Murji, MD, Toronto ON
Methods: Members of the guideline committee were selected on the
Claude Fortin, MD, Montreal QC basis of individual expertise to represent a range of practical and
Paul Martyn, MD, Sydney, Australia academic experience in terms of both location in Canada and
type of practice, as well as subspecialty expertise and general
George Vilos, MD, London ON background in gynaecology. The committee reviewed all available
evidence in the English medical literature, including published
CLINICAL PRACTICE–GYNAECOLOGY COMMITTEE guidelines, and evaluated surgical and patient outcomes for the
Nicholas Leyland, MD (Co-chair), Hamilton ON various EA techniques. Recommendations were established by
consensus.
Wendy Wolfman, MD (Co-chair), Toronto ON
Evidence: Published literature was retrieved through searches of
Catherine Allaire, MD, Vancouver BC MEDLINE and The Cochrane Library in 2013 and 2014 using
Alaa Awadalla, MD, Winnipeg MB appropriate controlled vocabulary and key words (endometrial
ablation, hysteroscopy, menorrhagia, heavy menstrual bleeding,
Sheila Dunn, MD, Toronto ON
AUB, hysterectomy). Results were restricted to systematic
Mark Heywood, MD, Vancouver BC reviews, randomized control trials/controlled clinical trials, and
observational studies written in English from January 2000 to
Madeleine Lemyre, MD, Quebec QC
November 2014. Searches were updated on a regular basis and
Violaine Marcoux, MD, Montreal QC incorporated in the guideline to December 2014.
Frank Potestio, MD, Thunder Bay ON Grey (unpublished) literature was identifies through searching the
David Rittenberg, MD, Halifax NS websites of health technology assessment and health technology-
related agencies, clinical practice guideline collections, clinical
Sukhbir Singh, MD, Ottawa ON trial registries, and national and international medical specialty
Grace Yeung, MD, London ON societies.

Disclosure statements have been received from all contributors.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
Keywords: Endometrial ablation, hysteroscopy, menorrhagia,
heavy menstrual bleeding, abnormal uterine bleeding,
hysterectomy.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Results: This document reviews the evidence regarding the
available techniques and technologies for EA, preoperative and
postoperative care, operative set-up, anaesthesia, and practical
considerations for practice.
J Obstet Gynaecol Can 2015;37(4):362–376

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

362 l APRIL JOGC AVRIL 2015

 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.51
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.51
Benefits, harms, and costs: Implementation of the guideline
recommendations will improve the provision of EA as an effective
treatment of AUB. Following these recommendations would allow
the surgical procedure to be performed safely and maximize
success for patients.
Conclusions: EA is a safe and effective minimally invasive option for
the treatment of AUB of benign etiology.
Summary Statements
1. Endometrial ablation is a safe and effective minimally invasive
surgical procedure that has become a well-established alternative
to medical treatment or hysterectomy to treat abnormal uterine
bleeding in select cases. (I)
2. Endometrial preparation can be used to facilitate resectoscopic
endometrial ablation (EA) and can be considered for some non-
resectoscopic techniques. For resectoscopic EA, preoperative
endometrial thinning results in higher short-term amenorrhea
rates, decreased irrigant fluid absorption, and shorter operative
time than no treatment. (I)
3. Non-resectoscopic techniques are technically easier to perform
than resectoscopic techniques, have shorter operative times, and
ABBREVIATIONS
AUB abnormal uterine bleeding
CS Caesarean section
D&C dilatation and curettage
EA endometrial ablation
FDA United States Food and Drug Administration
GnRH gonadotropin releasing hormone
HSG hysterosalpingogram
LNG-IUS levonorgestrel intrauterine system
NSAIDS non-steroidal anti-inflammatories
RCT randomized control trial
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
allow the use of local rather than general anaesthesia. However,
both techniques have comparable patient satisfaction and
reduction of heavy menstrual bleeding. (I)
4. Both resectoscopic and non-resectoscopic endometrial ablation
(EA) have low complication rates. Uterine perforation, fluid
overload, hematometra, and cervical lacerations are more
common with resectoscopic EA; perioperative nausea/vomiting,
uterine cramping, and pain are more common with non-
resectoscopic EA. (I)
5. All non-resectoscopic endometrial ablation devices available in
Canada have demonstrated effectiveness in decreasing menstrual
flow and result in high patient satisfaction. The choice of which
device to use depends primarily on surgical judgement and the
availability of resources. (I)
6. The use of local anaesthetic and blocks, oral analgesia, and
conscious sedation allows for the provision of non-resectoscopic
EA in lower resource-intense environments including regulated
non-hospital settings. (II-2)
7. Low-risk patients with satisfactory pain tolerance are good
candidates to undergo endometrial ablation in settings outside the
operating room or in free-standing surgical centres. (II-2)
8. Both resectoscopic and non-resectoscopic endometrial ablation
are relatively safe procedures with low complication rates. The
complications perforation with potential injury to contiguous
structures, hemorrhage, and infection. (II-2)
9. Combined hysteroscopic sterilization and endometrial ablation
can be safe and efficacious while favouring a minimally invasive
approach. (II-2)
Recommendations
1. Preoperative assessment should be comprehensive to rule out
any contraindication to endometrial ablation. (II-2A)
2. Patients should be counselled about the need for permanent
contraception following endometrial ablation. (II-2B)
3. Recommended evaluations for abnormal uterine bleeding,
including but not limited to endometrial sampling and an
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SOGC clinical practice guideline
assessment of the uterine cavity, are necessary components of
the preoperative assessment. (II-2B)
4. Clinicians should be vigilant for complications unique to
resectoscopic endometrial ablation such as those related to fluid
distention media and electrosurgical injuries. (III-A)
5. For resectoscopic endometrial ablation, a strict protocol should be
followed for fluid monitoring and management to minimize the risk
of complications of distension medium overload. (III-A)
6. If uterine perforation is suspected to have occurred during cervical
dilatation or with the resectoscope (without electrosurgery),
the procedure should be abandoned and the patient should be
closely monitored for signs of intraperitoneal hemorrhage or
visceral injury. If the perforation occurs with electrosurgery or if the
mechanism of perforation is uncertain, abdominal exploration is
warranted to obtain hemostasis and rule out visceral injury. (III-B)
7. With resectoscopic endometrial ablation, if uterine perforation
has been ruled out acute hemorrhage may be managed by using
intrauterine Foley balloon tamponade, injecting intracervical
vasopressors, or administering rectal misoprostol. (III-B)
8. If repeat endometrial ablation (EA) is considered following non-
resectoscopic or resectoscopic EA, it should be performed by
a hysteroscopic surgeon with direct visualization of the cavity.
Patients should be counselled about the increased risk of
complications with repeat EA. (II-2A)
9. If significant intracavitary pathology is present, resectoscopic
endometrial ablation combined with hysteroscopic myomectomy
or polypectomy should be considered in a non-fertility sparing
setting. (II-3A)
INTRODUCTION
E ndometrial ablation refers to a number of minimally
invasive surgical procedures designed to treat AUB,
which is defined as changes in frequency of menses,
duration of flow, or amount of blood loss. EA consists of
targeted destruction or removal of the endothelial surface
of the uterine cavity in selected women who have no desire
for future fertility. The procedure was designed to treat
heavy menstrual bleeding refractory to medical therapy
and not caused by structural uterine pathology. It is a less
invasive alternative to hysterectomy.
Although endometrial destruction through the endocervical
canal dates back to 1937, this technique became more
widely adopted in 1981 with laser EA, followed by rollerball
and loop resection in the late 1980s. In the last 20 years,
non-resectoscopic ablation techniques have become
available. They use different energy sources to achieve
endometrial destruction of the endometrium, including
heated liquid (either free circulating or confined within
a balloon), radiofrequency electricity, and tissue freezing.
Currently, 6 of these systems are available in Canada. The
use of microwave energy has been discontinued in Canada.
According to the Association of Obstetricians and
Gynecologists of Quebec, 3646 cases of EA were
performed in Quebec in 2012, more than twice those
364 l APRIL JOGC AVRIL 2015
performed in 2000. EA is now more prevalent than vaginal
hysterectomy in Quebec. However, the impact of EA on
hysterectomy rates remains uncertain. American statistics
from 6 states show EA being used as an “additive medical
technology rather than a substitute” for hysterectomy.1 In
the United Kingdom, there has been a significant reduction
in hysterectomy rates over the past 20 years, explained in
part by both improved medical treatment and increased
use of EA techniques.2,3 EA improves treatment access for
those women who have AUB and provides an alternative
to major procedures such as hysterectomy.
In the past 10 years alone there have been more than 600
publications on the subject of EA. This guideline reviews
the indications and contraindications for performing
EA (Table 2) and compares resectoscopic and non-
resectoscopic techniques. The document also includes
discussions of operative set-up, anaesthesia, preoperative
and postoperative care, and some special considerations
in clinical practice. A patient information sheet has been
included to help patients better understand the benefits
and limitations of this procedure (Appendix).
COMPARISON OF EA TO OTHER THERAPIES
EA Versus LNG-IUS
The LNG-IUS is a simple treatment option for women with
AUB and is more cost-effective than any surgical technique,
including EA. In one meta-analysis of 6 randomized trials,
LNG-IUS and EA had similar patient efficacy up to 2 years
after treatment.4 A Cochrane review concluded that EA
and LNG-IUS had similar patient satisfaction, although
EA was associated with a greater reduction in menstrual
bleeding.5 During the first 6 months of use, the LNG-
IUS may be associated with a number of progestogenic
side effects including but not limited to irregular bleeding,
breast tenderness, and headache.
CLINICAL TIP
This option (LNG-IUS) should be discussed prior to any surgical
option for women with AUB and a normal cavity.
EA Versus Hysterectomy
In a review of 9 prospective randomized clinical trials,
hysterectomy was associated with improved control of pain
and bleeding.6 In another study at 4 years’ follow-up 98%
of women in the hysterectomy group versus 85% in the EA
group were satisfied.7 However, hysterectomy was associated
with a higher risk of adverse events, severe complications,
and longer hospital stay. In a large retrospective study with
11 years’ follow-up, risk of surgery for subsequent pelvic
floor repair and stress urinary incontinence associated with
EA was lower than with hysterectomy.8 Although the direct
 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
costs of EA are about half that of hysterectomy, it seems
that the costs of the 2 procedures become equivalent at 4
years because some women with EA will need additional
treatment. Age < 40 years, prior tubal ligation, and
preoperative dysmenorrhea are independent predictors of
EA failure and subsequent re-intervention.9,10
Summary Statement
1. Endometrial ablation is a safe and effective
minimally invasive surgical procedure that has
become a well-established alternative to medical
treatment or hysterectomy to treat abnormal uterine
bleeding in select cases. (I)
Recommendation
1. Preoperative assessment should be comprehensive
to rule out any contraindication to endometrial
ablation. (II-2A)
PREOPERATIVE AND POSTOPERATIVE CARE
Preoperative Care
The work-up of patients with AUB and the algorithm for
decision-making have been previously described.11
Patients must not desire future fertility as serious maternal–
fetal complications have been reported in pregnancies
following EA (uterine rupture causing maternal death,
limb defects, premature labour).12 Therefore, women must
be counselled that EA is not considered a sterilization
method. Women must also be appropriately counselled
about realistic expectations of ablation outcomes. The
goal of EA is to reduce bleeding symptoms; amenorrhea,
although possible, cannot be guaranteed.
Endometrial preparation can be considered preoperatively
as a thin endometrium can improve visualization for the
resectoscopic techniques and improve patient outcomes.
A thin endometrium can be achieved by scheduling
the procedure in the immediate post-menstrual phase,
performing curettage prior to the procedure or administering
of preoperative hormonal therapy. A systematic review
suggested that preoperative endometrial thinning with GnRH
agonists and danazol resulted in higher rates of amenorrhea
at 12 and 24 months than placebo/no treatment.13 Whether
or not this difference is maintained beyond 24 months is
uncertain. GnRH agonists and danazol also had a beneficial
effect on the intrauterine operating environment with
respect to shorter operating time and reduced absorption of
distention media. The disadvantages of these agents include
the costs and side effects. Randomized data assessing the
value of progestins in preoperative endometrial thinning
prior to EA are scarce. In a study of resectoscopic EA,
Table 2. Indications and contraindications to EA
Indications
• AUB of benign origin
• EA may be considered as a primary intervention in
circumstances such as intolerance to or failure of medical
therapy, or patient preference
• EA may be considered for patients who refuse or are poor
surgical candidates for hysterectomy
Absolute contraindications
• Pregnancy
• Desire to preserve fertility
• Known or suspected endometrial hyperplasia or cancer
• Cervical cancer
• Active pelvic infection
• Specific contraindications related to non-resectoscopic
techniques*
*See “Special Considerations”
amenorrhea rates at 12-month follow-up were 39% for
endometrial preparation with GnRH agonists compared
with 34% for danazol, 26% for medroxyprogesterone
acetate, and 18% for D&C.14
The use of endometrial preparation prior to non-resectoscopic
EA will depend on the product monograph for each individual
device. Meta-analysis of a few randomized trials on second-
generation devices (radiofrequency ablation and balloon
devices) suggest that preoperative endometrial thinning does
not improve postoperative rates of amenorrhea.13
No RCTs have yet supported or refuted the role of
antibiotic prophylaxis before EA by any technique.15
Postoperative Care
Patients can usually be discharged within 1 to 3 hours
of EA depending on the type of anaesthesia used. They
can resume their normal activities progressively, but are
advised to abstain from sexual intercourse for one week.
Pain can be managed with NSAIDS or opiates, and will
usually resolve within 24 hours. Light vaginal bleeding or
pinkish discharge is usual and can last up to several weeks
following the procedure. Patients are counselled to seek
medical care if they have fever, intense pain, or profuse
vaginal bleeding.
Summary Statement
2. Endometrial preparation can be used to facilitate
resectoscopic endometrial ablation (EA) and can be
considered for some non-resectoscopic techniques.
For resectoscopic EA, preoperative endometrial
thinning results in higher short-term amenorrhea
rates, decreased irrigant fluid absorption, and
shorter operative time than no treatment. (I)
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SOGC clinical practice guideline
Recommendations
2. Patients should be counselled about the need for
permanent contraception following endometrial
ablation. (II-2B)
3. Recommended evaluations for abnormal uterine
bleeding, including but not limited to endometrial
sampling and an assessment of the uterine cavity,
are necessary components of the preoperative
assessment. (II-2B)
CLINICAL TIP
Required investigations prior to EA include:
• pregnancy test,
• Papanicolaou test within 2 years,
• cervical cultures if clinically appropriate,
• endometrial sampling, and
• assessment of uterine cavity for Müllerian anomalies or
intracavitary pathology using transvaginal ultrasound,
contrast infusion sonography, or diagnostic hysteroscopy.
(See also SOGC Clinical Practice Guideline No. 292, Abnormal
Uterine Bleeding in Pre-Menopausal Women.11)
Because it is often difficult to interpret residual menstrual discharge
post procedure, the efficacy of the EA should be assessed no
earlier than 6 to 12 weeks postoperatively.
COMPARISON OF RESECTOSCOPIC AND
NON-RESECTOSCOPIC EA TECHNIQUES
The first-generation techniques introduced in the 1980s
consisted of targeted endometrial destruction under direct
hysteroscopic visualization. These techniques included
laser ablation and electrosurgical endometrial resection
or ablation. Despite their efficacy, the first-generation
methods had certain disadvantages. They required a skilled
hysteroscopic surgeon and an operating room environment.
Their uncommon but serious complications of fluid
overload and uterine perforation led to the advent of
simpler, less user-dependant alternatives.
These second-generation techniques, also known as non-
resectoscopic ablation, use a variety of energy sources to
non-selectively destroy the endometrial lining. The advantage
of these newer technologies is that they require shorter
surgical time and less specialized training, and they can be
performed in the outpatient setting. They also help to avert
complications associated with the use of fluid distention
media while achieving similar clinical outcomes.16 For
these reasons non-resectoscopic procedures have become
increasing popular.17
Resectoscopic EA
Resectoscopic endometrial resection/ablation is an
attempt to destroy the basal endometrial layer to prevent
366 l APRIL JOGC AVRIL 2015
further endometrial proliferation. Operative hysteroscopy,
first described by Neuwirth in 1976, involved resection
of submucosal myomas using a modified urological
resectoscope.18 Laser ablation was described by Goldrath
in 1981,19 but lost favour due to its expense and
unreliability. Loop electrode and rollerball ablation using
bipolar or monopolar radiofrequency electrosurgery were
subsequently described by DeCherney and Polan in 1983
and Lin et al. in 1988, as reported in a previous summary
of ablation techniques.20
Patients are placed in supported lithotomy position
and the cervix dilated to at least 10 mm. Most operative
hysteroscopic systems employ a 9 mm (27 French)
scope. Hysteroscopes are usually rigid, with operative
hysteroscopy using 12, 15, or 30 degrees of angulation.
After uterine distension is achieved, the cavity is inspected
and endometrial lesions or abnormalities are mapped.
Importantly, intrauterine landmarks (tubal ostia, internal
cervical os, and/or the characteristic appearance of the
endometrium) are identified to confirm that the cavity has
been entered and ensure that the operator has not created a
false passage. Focal lesions are biopsied, resected, and sent
separately to the pathology laboratory.
The rollerball is used at the fundus and ostial regions with
a touch technique applying no pressure. The treatment
endpoint is a visual change in the endometrium to a yellow-
brown honeycomb appearance indicating myometrial
tissue has been reached. Tissue destruction to a depth of
4 to 6 mm will usually destroy the basal endometrial layer.
The uterine walls can be ablated with the ball electrode
or resected using the loop electrode, which also provides
a specimen for histology. The electrode should always
be visible, in contact with tissue, and moving toward
the surgeon when activated. Prolonged activation of the
electrode should be avoided to prevent capacitive coupling
and other causes of electrosurgical injuries. The surgeon
should avoid ablating beyond the cervico-uterine junction
to avoid cervical stenosis.
Endometrial polyps and small submucosal fibroids
can be resected using the resectoscope, but larger
(> 3 cm) myoma resection requires advanced operative
hysteroscopy skills. Endometrial resection may result in
more fluid absorption, which is associated with longer
operating times.16
Use of a fluid management system is recommended.
Bipolar resectoscopic systems require the use of normal
saline as a distention medium, thereby eliminating concerns
about hyponatremia; however, large quantities of normal
saline can still result in fluid overload complications.
 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
Efficacy of Resectoscopic EA
Early studies reported high rates of improvement in heavy
menstrual bleeding and high rates of patient satisfaction.
O’Connor and Magos reported a 20% repeat surgery rate
including a 9% hysterectomy rate over 5 years follow-up in a
group of 525 patients undergoing endometrial resection.21
Martyn and Allan reported similar results with a repeat
surgery rate of 19.2% including an 11.6% hysterectomy
rate at 5 years of follow-up.22 The presence of fibroids and
dysmenorrhea did not increase the risk of failure.
A meta-analysis of 21 randomized trials comparing
different resectoscopic techniques of endometrial
destruction showed no difference in rates of amenorrhea
and subsequent hysterectomy.16 First-generation techniques
showed improvement in bleeding in 72.5% to 79.5% at
1-year follow-up and high patient satisfaction rates.
Advantages and Disadvantages of Resectoscopic EA
Compared with the non-resectoscopic techniques, the
resectoscopic EA offers certain advantages. It allows for
accurate assessment of uterine pathology with directed
biopsies, documentation with photography, and concurrent
treatment of intracavitary pathology. It can also be used
in patients who have had previous EA or transmyometrial
surgery. However, resectoscopic EA is a skill-dependent
procedure that requires an operative room environment
and has a higher complication rate than non-resectoscopic
methods.
Distending Media for Resectoscopic EA
Distending media provide uterine distension and irrigate
blood and tissue fragments from the surgical field. A non-
electrolyte solution is required for monopolar resectoscopic
surgery, but normal saline can be used with bipolar systems.
The following are common distending media:
Conductive solutions (electrolytic/crystalloids)
•• Normal saline (290 mOsm/L): isotonic/isonatremic
Non-conductive (non-ionic, non-electolytic)
•• mannitol (275 mOsm/L): isotonic/hyponatremic,
induces diuresis
•• glycine 1.5% (200 mOsm/L): hypotonic/hyponatremic;
acidic with a pH of 6.1
•• sorbitol 3.3% (165 mOsm/L): hypotonic/
hyponatremic
•• cystosol (mannitol 0.54% and sorbitol 2.7%):
isotonic/hyponatremic
Osmotically active particles must be added to hypotonic
solutions to prevent complications from fluid absorption.
Although absorption of isotonic fluids may also lower
serum sodium, it is less likely to cause cerebral edema than
the absorption of hypotonic media.
Fluid absorption increases significantly when intrauterine
pressure exceeds mean arterial pressure. For every 100 mL
of non-electrolyte solution absorbed, serum sodium falls
by 1 meq. Electronic fluid management systems provide an
accurate measurement of fluid deficits and can safeguard
against complications of excess absorption. Excess absorption
of isotonic solutions may be less dangerous than absorption
of hypotonic solutions because there is a smaller chance of
cerebral edema. Excessive fluid absorption may be prevented
by pre-treatment of the endometrium,14 intracervical
injection of pressor agents (vasopressin, epinephrine) and the
use of distension pressure less than that of the patient’s mean
arterial pressure. Electronic fluid monitoring systems, which
allow regulation of the flow rate, infusion pressure, outflow
suction, and fluid deficit may be more accurate in calculating
fluid deficits than traditional gravity infusion systems and
manual estimation of fluid deficit.
Non-resectoscopic EA
Currently various energy sources are used in 6 non-
resectoscopic EA devices approved by Health Canada:
bipolar radiofrequency ablation(NovaSure), cryotherapy
(Her Option),23 heated fluid freely circulated in the uterine
cavity (Hydro ThermAblator), and fluid contained in a
balloon (Thermachoice, Thermablate EAS, and Cavaterm).
Specifications of each of these devices are compared in
Table 3. Future technologies such as the Aurora ablation
system (radiofrequency energy and heated Argon gas
forming plasma energy) have promising preliminary results.24
In the absence of large differences in effectiveness and
with low complication rates for each of the devices, the
choice of which to use depends primarily on the following
practical issues and patient factors:
•• availability of scientific evidence
•• cost effectiveness
•• surgeon preference
•• ease of use in outpatient/clinic setting
•• requirement of endometrial preparation
•• uterine cavity characteristics (size, cavitary pathology)
CLINICAL TIP
• For safety and appropriate intracavitary device placement,
pre- and post -procedural diagnostic hysteroscopy or
intraprocedural ultrasound guidance may be considered.
• The balloon technologies involve coagulation of the
endometrium that eventually leads to fibrosis. The maximum
effect of this process is seen at 6 months post procedure rather
than the 2 to 4 weeks seen with other technologies.
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SOGC clinical practice guideline

Table 3. Comparison of non-resectoscopic endometrial ablation devices
Mechanism Device Treatment
of action size (mm) time (min) Advantages Disadvantages Procedural points
Novasure Bipolar 7.2 1 to 2 Rapid treatment time Cavity limitations After cervical dilatation to Hegar 8 (25 fr), the device
radiofrequency (mostly suitable for is inserted against the fundus then slightly retracted.
No endometrial preparation
normal cavities) It is deployed after proper seating. Pending a CO2
required
perforation detection check, negative pressure is
Cost of disposable
High amenorrhea and applied and power is delivered until 50 Ohms of
equipment
satisfactioes tissue impedance is reached. Blood/steam from the
Seating the device cavity is removed during the procedure.
requires practice
Her Option Cryo-ablation 5.5 10 to 18 Minimal anaesthesia Long treatment time After cervical dilatation to Hegar 5–5½ (15 fr), a
at −90°C disposable 4.5mm cryoprobe is used to form an
Minimal or no cervical Variability of outcome
elliptical freezing zone starting at both cornua.
dilatation data23
Concurrent trans-abdominal ultrasound allows
Able to treat larger cavities Requires ultrasound visualization of the freezing process. Frequently
guidance and hormonal additional applications are necessary to treat the
endometrial preparation lower uterine body.
Hydro- Saline at 90°C 7.8 3 to heat Direct visualization of Requires hormonal After cervical dilatation, a disposable sheath that
Therm- circulated freely fluid, 10 treatment effect endometrial preparation adapts to a 2.7–3.0 mm hysteroscope is inserted.
Ablator to treat The fluid is heated to target temperature for 3 min
Able to treat irregular Safety: fluid leaks may
followed by a 10 min treatment time under direct
cavities (fibroids) cause burns
visualization. Loss of more than 10 mL of fluid
Short learning curve Long treatment time (through the cervix or the Fallopian tubes) will shut
the system off automatically.
Hot liquid-filled silicone balloon devices
Therma- 5% dextrose 5.5 8 Short learning curve Cramping from balloon The cervix is dilated, the cavity is measured, and the
choice III at 87°C distention pear-shaped balloon catheter is inserted. Automated
Long-term safety and
treatment maintains a pressure of 180 to 185
effectiveness data Long treatment time
mmHg. Safety features monitor and prevent excess
temperature and pressure. Endometrial preparation
(hormonal/mechanical) is optional.
Thermablate Glycerine 6 2.2 Short learning curve RCT results not yet Fluid takes 8 min to heat prior to catheter insertion.
EAS at 173°C available During the treatment, the balloon undergoes serial of
Rapid treatment time
pressurizations (200 mmHg) and depressurizations.
Fluid pressure is monitored by transducers that
react to contractions or relaxations of the uterus.
Endometrial preparation (hormonal/mechanical)
is optional.
Cavaterm 1.5% Glycine 8 10 Simple to use Cramping During the treatment, the fluid is maintained at
at 75°C to 80°C approximately 200 mmHg. A safety mechanism
Adjustable balloon length Long treatment time
will stop the procedure if it exceeds 250 mmHg.
Endometrial preparation (hormonal/mechanical)
is optional.
 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
Comparing the Efficacy of Non-resectoscopic Devices
Patient satisfaction and re-intervention rates may be
more clinically meaningful than absolute amenorrhea
rates in comparing outcomes of procedures using non-
resectoscopic devices. All of these devices work well and
lead to high levels of patient satisfaction, as demonstrated
by the FDA’s pivotal trials that showed satisfaction rates of
86% to 99% at 1 year.25
Direct comparisons of non-resectoscopic devices are
scarce, and differences between trials with respect to
outcome measures, preoperative endometrial preparation,
practice settings, and follow-up times make it challenging
to compare outcomes accurately. NovaSure radiofrequency
ablation has been the most studied in randomized trials
comparing it with Hydro ThermAblator and the hot liquid
balloons Thermachoice and Cavaterm.
NovaSure versus Hydro ThermAblator
At 12 months’ follow-up, NovaSure had significantly higher
rates of patient satisfaction (87% vs. 68%) and amenorrhea
(47% vs 24%) than Hydro ThermAblator.26 This benefit
persisted at 5 years, with NovaSure having significantly
higher satisfaction rates (81% vs. 48%), higher amenorrhea
rates (55% vs. 37%), and fewer surgical re-interventions
(15% vs. 35%).27
NovaSure versus Thermachoice
At the 5-year follow-up, both groups had similar
improvements in health-related quality of life measures
and no significant differences in amenorrhea rates (48%
vs. 32%) and surgical re-interventions (10% vs. 13%).28
NovaSure versus Cavaterm
In a small randomized trial of 57 patients at 1-year
follow-up, there was no difference in patient satisfaction
(92% vs. 83%) or re-intervention rates between groups.
Amenorrhea rates, however, were significantly higher with
NovaSure (42% vs. 12%).29
A network meta-analysis reported that bipolar radio
frequency EA resulted in higher rates of amenorrhea
than thermal balloon at 12 months.30 This has also been
confirmed by other systematic reviews.31 However, there
was no difference between techniques in patient satisfaction
or number of women still experiencing heavy bleeding.
EFFECTIVENESS OF RESECTOSCOPIC
VERSUS NON-RESECTOSCOPIC TECHNIQUES
Primary outcome measures when evaluating EA procedures
include rates of amenorrhea, patient satisfaction, and
surgical re-intervention. A Cochrane Database review
compared resectoscopic and non-resectoscopic techniques
and reported similar amenorrhea rates at 1 year (37% vs.
28%) and at 2 to 5 years (53% vs. 48%).16 Because women
who suffer from menorraghia are likely to be satisfied with
either hypomenorrhea or normal menses, satisfaction rates
for both types of ablations are high.32 In the Cochrane
meta-analysis, satisfaction rates were also comparable at 1
year (91% vs. 88%) and at 2 to 5 years (93% vs. 87%).16 In
an updated analysis of 25 RCTs with over 4000 patients,
the rates of amenorrhea and patient satisfaction were not
significantly different, even up to 10 years after surgery.33
The surgical re-intervention rate (repeat ablation and/or
hysterectomy) for AUB has been reported to be similar
between techniques (21% vs. 25% at 2 to 5 years).16
However, analysis of studies with longer follow-up shows
that non-resectoscopic EA has a lower re-intervention rate
(RR 0.6, 95% CI 0.38 to 0.96) than resectoscopic EA.33
Although clinical outcomes between techniques were
comparable, non-resectoscopic procedures required
shorter surgical time, were more likely to be performed
under local anaesthesia, and resulted in patients’ quicker
return to normal activity.32,33 The overall perioperative
complication rate was low with both techniques (< 2.5%
each), but the non-resectoscopic procedures had a
lower incidence of uterine perforation, fluid overload,
hematometra and cervical laceration.32,33 These advantages
were offset by increased nausea/vomiting and uterine
cramping in the perioperative period.33 A higher incidence
of equipment failure of second-generation devices was
reported in earlier trials, but this is becoming less of a
concern with updated models.
Summary Statements
3. Non-resectoscopic techniques are technically easier
to perform than resectoscopic techniques, have
shorter operative times, and allow the use of local
rather than general anaesthesia. However, both
techniques have comparable patient satisfaction and
reduction of heavy menstrual bleeding. (I)
4. Both resectoscopic and non-resectoscopic
endometrial ablation (EA) have low complication
rates. Uterine perforation, fluid overload,
hematometra, and cervical lacerations are more
common with resectoscopic EA; perioperative
nausea/vomiting, uterine cramping, and pain are
more common with non-resectoscopic EA. (I)
5. All non-resectoscopic endometrial ablation devices
available in Canada have demonstrated effectiveness
in decreasing menstrual flow and result in high
patient satisfaction. The choice of which device to
use depends primarily on surgical judgement and
the availability of resources. (I)
APRIL JOGC AVRIL 2015 l 369
SOGC clinical practice guideline
ANAESTHESIA AND OPERATIVE SET-UP
Resectoscopic ablation is frequently performed under
general or regional anaesthesia in the operating room.
However, in the appropriate setting, it can also be safely and
effectively performed using a local paracervical block with
intravenous sedation.
Local, regional, or general anaesthesia can be used for non-
resectoscopic EA. A main advantage of non-resectoscopic
proce­dures is that they may be conducted under local
anaesthesia in a lower resource-intense environment than the
operating room. Performing such procedures in the operating
room rather than through a hysteroscopic procedure in
another setting adds significant instrumentation costs but no
value to the patient.
In addition to local anaesthesia by paracervical block, oral
or intravenous conscious sedation may be used depending
on patient pain tolerance and surgeon preference. NSAIDS
can be administered preoperatively and are moderately
effective in diminishing uterine contractions during and
after the procedure.34
Procedure Room Versus Operating Room Setting
In the United States non-resectoscopic EA is frequently an
office-based procedure, and provider payment processes
promote these less resource-intense environments.35
Currently no mechanisms in the Canadian health care system
compensate providers for non-resectoscopic EA in such a
setting. EA performed in a hospital-based procedure room or
a free-standing surgical centre rather than an operating room
offers the advantages of a patient-centred environment,
easier scheduling, and reduced costs per case. Appropriate
low-risk patient selection and a satisfactory pain management
strategy are critical in this environment. Procedure rooms
must have appropriate emergency equipment available and
all personnel must be trained in appropriate adverse event
protocols. A systematic review comparing non-resectoscopic
EA performed in the outpatient setting to resectoscopic EA
in the operating room, showed varying amounts of cost-
savings.31 In the Canadian setting, an estimated savings of
$562 per patient receiving EA has been attributed to the
introduction of balloon devices in the outpatient setting.31
Summary Statements
6. The use of local anaesthetic and blocks, oral
analgesia, and conscious sedation allows for the
provision of non-resectoscopic EA in lower
resource-intense environments including regulated
non-hospital settings. (II-2)
7. Low-risk patients with satisfactory pain tolerance
are good candidates to undergo endometrial
ablation in settings outside the operating room or
free-standing surgical centres. (II-2)
370 l APRIL JOGC AVRIL 2015
COMPLICATIONS OF ENDOMETRIAL ABLATION
The most common adverse events following EA are
pelvic pain, cramping, and nausea/vomiting. These will
generally resolve within 12 to 24 hours of the procedure.
Other problems that can develop post-procedure are
hematometrium, pyometrium, or endometritis. More
severe complications are rare with both techniques of
EA, but can include injury to contiguous pelvic structures
such as pelvic blood vessels, the bowel, and urinary tract
anatomic components. Procedural complications such as
severe pain, bleeding, uterine perforation, and infection
may require emergent surgical management.16
The FDA has a reporting system for non-resectoscopic
ablation complications, and bowel injury is the most
common complication reported to its Manufacturer and
User Facility Device (MAUDE) database.36 Other major
complications reported more infrequently are urinary
tract injuries, immediate hysterectomy, gas embolism,
necrotizing fasciitis, and death. The incidence of such
complications is unavailable from such databases as
the denominator (total number of cases) is not known.
However, the majority of these adverse events were
associated with non-compliance with the manufacturers’
instructions for use. To mitigate the risk of injury with
non-resectoscopic procedures, surgeons may consider
post-dilatation hysteroscopy or concurrent ultrasound
surveillance during the procedure.
Serious Complications of EA
Uterine perforation has been reported in 0.3% of non-
resectoscopic EA procedures and 1.3% of resectoscopic
ablations or resections.16 If uterine perforation is suspected
to have occurred during cervical dilatation or with the
resectoscope (without electrosurgery), the procedure should
be abandoned and the patient should be closely monitored
for signs of intraperitoneal hemorrhage or visceral injury.
If the perforation occurs while using electrosurgery or if
the mechanism of perforation is uncertain, abdominal
exploration is warranted to obtain hemostasis and rule out
visceral injury.
Perioperative hemorrhage has been reported in 1.2% of women
undergoing non-resectoscopic ablation and 3.0% of those
undergoing resectoscopic ablation.16
Hematometra have been reported in 0.9% of women
undergoing non-resectoscopic ablation and in 2.4 of
those undergoing in resectoscopic ablation.16 Although
intrauterine scarring is an expected result of EA,
hematometra will occur when areas of the endometrium
are adherent and there is endometrial bleeding behind
the occlusion. Hematometra and cervical stenosis may be
 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
managed by cervical dilation, hysteroscopic adhesiolysis
and drainage, or hormonal endometrial suppression.
For persistent pain despite minimally invasive treatment,
hysterectomy may be indicated.
Postablation tubal sterilization syndrome has been reported to
occur at a rate as high as 10%.37 Some women who have
undergone tubal ligation prior to EA experience cyclic or
intermittent pelvic pain. The proposed etiology is bleeding
from active endometrium trapped in the uterine cornua.
This can be managed laparoscopically by excision of the
tubal stumps or hysterectomy.
Pelvic infections and fever occur in the immediate postoperative
period in approximately 1% of women who have
undergone EA.16 In a meta-analysis, the incidence of
infectious complications included endometritis (1.4 to
2.0%), myometritis (0 to 0.9%), pelvic inflammatory
disease (1.1%), and pelvic abscess (0 to 1.1%).16
Long-term recurrent AUB after EA may be caused by
endometrial proliferation, adenomyosis, or (rarely)
pre-malignant or malignant condition of the uterus.
Investigation should include an endometrial biopsy if
more than 1 year has passed since the procedure. Because
dense intrauterine synechiae sometimes follow EA,
endometrial biopsy, even D&C, may often be impossible.38
Transvaginal ultrasound can also be used to exclude
abnormal proliferation of the endometrium. When
adequate sampling of the endometrium cannot be obtained
and AUB persists, with ultrasonic evidence of a thickened
endometrium, hysterectomy is generally indicated for both
curative and diagnostic purposes.38
CLINICAL TIP
• For resectoscopic EA, if uterine perforation has been ruled out,
acute hemorrhage may be managed with intrauterine Foley
balloon tamponade, intracervical vasopressors injection, or
rectal misoprostol administration.
• Hematometra should be suspected in a patient with a history
of an EA who presents with amenorrhea and cyclic pain,
even remote from the procedure.39 This can be diagnosed by
transvaginal ultrasound and prevented by ensuring complete
ablation of the uterine fundus, cornua, and tubal ostia while
avoiding ablation of the cervix or cervico-uterine junction.
• Tips for administering paracervical block :
40
–– Infiltration of the cervix carries the risks of intravascular
injection and toxicity of the local anaesthetic. These
risks can be minimized by infiltrating slowly, using lower
concentrations of local anaesthetic, frequently aspirating,
and monitoring for symptoms of intravasation (tinnitus,
blurring of vision, peri-oral/facial numbness). If the local
anaesthetic contains epinephrine, patients may experience
palpitations, tachycardia, or feelings of anxiety. Basic
resuscitative equipment should be available.
–– Allow the block to take effect by waiting 10 to 15 minutes
prior to proceeding with cervical dilatation.
Complications Specific to Resectoscopic EA
Resectoscopic EA has potential complications specific to
this surgical modality. Careful fluid management is critical
to the safe use of hysteroscopic EA. In addition, surgeons
must possess a comprehensive understanding of potential
electrosurgical injuries during hysteroscopic EA.
Safe hysteroscopic surgery requires careful fluid
management to avoid excessive intravasation of
hysteroscopic distension media. Adherence to a strict
protocol of fluid monitoring and management criteria
will minimize the risk of complications of distension
medium overload such as cardiovascular compromise
and pulmonary edema, electrolyte abnormalities, and
encephalopathy. Table 4 provides an approach to prudent
management of hysteroscopic distention fluid issues.
Electrosurgical injuries with monopolar operative
hysteroscopy can occur due to capacitive coupling and
defective insulation and result in cervical, vaginal, or
perineal burns. There is an increased risk of this occurring
when the tip of the resectoscope is in the cervical
canal, when the cervix is over-dilated, or when there are
electrode insulation defects. There is a greater degree of
capacitive coupling injury with higher voltage outputs,
which may occur with use of coagulation mode, long
uninterrupted periods of electrode activation, and non-
contact with tissue.41 Risks of capacitive coupling can
be reduced by preventing cervical over-dilatation, using
the lower voltage “cut” current, avoiding prolonged and
uninterrupted activation, checking for insulation defects,
ensuring contact with tissue during activation, and using a
weighted speculum during the procedure to disperse any
stray currents.
Summary Statement
8. Both resectoscopic and non-resectoscopic endometrial
ablation are relatively safe procedures with low
complication rates. The complications perforation
with potential injury to contiguous structures,
hemorrhage, and infection. (II-2)
Recommendations
4. Clinicians should be vigilant for complications
unique to resectoscopic endometrial ablation such
as those related to fluid distention media and
electrosurgical injuries. (III-A)
5. For resectoscopic endometrial ablation, a strict
protocol should be followed for fluid monitoring and
management to minimize the risk of complications
of distension medium overload. (III-A)
6. If uterine perforation is suspected to have occurred
during cervical dilatation or with the resectoscope
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SOGC clinical practice guideline

Table 4. Management of hysteroscopic distention fluid losses

Measurement of Intake and Output (I&O) During Hysteroscopy
a. I&O should be measured accurately, ideally by an electronic fluid management system, for all operative hysteroscopy procedures.
b. I&O values for all distention media should be monitored and fluid deficits reported to the surgeon and anaesthesiologist.
c. The circulating nurse should seek assistance, and additional staff if required, to monitor fluid I&O.
d. Final I&O values or fluid deficit should be recorded on the operative record.
e. Final I&O values should be reported to the surgeon and anaesthesiologist at the end of the procedure.
Excess Fluid Deficit for Non-conductive Solutions
At a fluid deficit of 500 cc:
• Ensure anaesthesiologist and surgeon are aware of the deficit in return of uterine distension fluid.
At a fluid deficit of 1000 cc:
• The procedure should be completed as expeditiously as possible.
• Consider placing Foley catheter in bladder for accurate monitoring of urine output.
• Consider fluid restriction and IV to keep vein open.
• Consider IV diuretic ( e.g. furosemide) administration.
At a fluid deficit of 1500 cc:
• The procedure should be discontinued immediately.
• Serum electrolyte values should be obtained and abnormalities managed appropriately.
• Observe patient for signs of fluid overload and encephalopathym, changes in level of consciousness, seizure activity, pulmonary edema,
and tachypnea.
• Admit patient for observation and management of complications.
• If normal saline is used as the distending medium, consider completing and terminating the procedure at volumes of 2000 cc and
2500 cc, respectively.

(without electrosurgery), the procedure should If repeat EA is considered, a hysteroscopic approach

be abandoned and the patient should be closely
monitored for signs of intraperitoneal hemorrhage
or visceral injury. If the perforation occurs with
electrosurgery or if the mechanism of perforation
is uncertain, abdominal exploration is warranted to
obtain hemostasis and rule out visceral injury. (III-B)
7. With resectoscopic endometrial ablation, if uterine
perforation has been ruled out acute hemorrhage
may be managed by using intrauterine Foley balloon
tamponade, injecting intracervical vasopressors, or
administering rectal misoprostol. (III-B)
SPECIAL CONSIDERATIONS
Repeat Ablation
Irrespective of technique, EA has a success rate of 73%
to 85%. Therefore, EA failures raise the issue of repeat
ablation or hysterectomy. The decision for repeat ablation
versus another approach will depend on the surgeon’s skill
and the patient’s consent, appropriately informed about
possible complications. If the initial EA was deemed a
failure because it did not reduce menstrual flow and if the
symptoms are highly suggestive of adenomyosis, definitive
management should be considered.
using the resectoscope is recommended. With the
possible exception of the HydroThermAblator,40 a non-
resectoscopic blind procedure is generally contraindicated
in this clinical scenario, as is a global EA technique under
hysteroscopic visualization. Complication rates of repeat
EA are statistically higher than primary procedures. The
risks of perforation, higher fluid absorption, and bleeding
have been reported to be in the order of 9.3% to 11%
compared with 2.05% for primary ablation.42 Repeat
ablation should therefore be performed by skilled surgeons
with experience in hysteroscopic surgery. When repeat
procedures are performed in patients with the appropriate
indications, success rates of avoiding hysterectomy have
been reported to be about 55% to 60%.43
Concomitant Hysteroscopic (Essure)
Tubal Sterilization
Hysteroscopic sterilization has rapidly replaced laparoscopic
sterilization in the United States but has not yet been widely
accepted in Canada. Essure is highly successful, with a
reported 5-year effectiveness of 99.8% and most failures
related to deviations from protocol.44 Over the last few
years there have been multiple reports on the concomitant
use of Essure and different ablation techniques, most

372 l APRIL JOGC AVRIL 2015

 Endometrial Ablation in the Management of Abnormal Uterine Bleeding
often non-resectoscopic procedures such as NovaSure,
Thermachoice, Thermablate, HydroThermAblator.45
In most cases, both procedures were reported to be
successful for the ablation and placement of the implants
at rate of 83% to 89%. The NovaSure requires placement
of implants after the procedure, while balloon thermal
transfer and circulating saline could be performed before
or after hysteroscopic tubal sterilization.
Problems with combined Essure placement arise from the
FDA’s mandatory requirement of confirming postoperative
tubal occlusion by HSG at 3 months. Obliteration of the
uterine cavity following EA may make confirmation of tubal
occlusions by HSG difficult. However, in other countries
including Canada, HSG is not mandatory following
hysteroscopic sterilization and many articles advocate
using three-dimensional US and X-ray to confirm bilateral
placement and the non-migration of the tubal inserts.46
Previous Caesarean Section
The literature regarding EA in patients with previous CS
consists primarily of small retrospective cohorts studies.
For resectoscopic EA, there are generally no restrictions
following previous CS. However, caution should be
exercised over the CS scar as myometrial thinning may
predispose it to perforation or thermal injury. For a patient
with previous transmural myomectomy, obtaining adequate
visualization of the cavity using a pressure pump should
allow for safe treatment.
For the available non-resectoscopic technologies, no
restriction on the minimum myometrial thickness has
been mentioned. However, caution is recommended with
patients who have had more than 2 CS. Non-resectoscopic
EA is contraindicated in patients with previous classical
Caesarean section or transmural myomectomies. Five-
year data on satisfaction, treatment failure, and operative
complications of non-resectoscopic EA in patients with
previous CS are similar to those in patients without
previous CS.47
Intracavitary Pathology and Non-Resectoscopic EA
Intracavitary fibroids and polyps were excluded from
the original randomized controlled trials evaluating
non-resectoscopic EA techniques. These procedures
were originally designed to treat normal uterine cavities.
Subsequently, various attempts have been made to examine
the utility of these technologies in distorted cavities with
submucosal fibroids. The HydroThermAblator, which relies
on freely circulating heated fluid under direct visualization,
may be suited to treat distorted cavities as it does not rely
on the fixed shape of a mesh or balloon. A prospective
study of patients with type 0 or type 1 submucosal fibroids
< 4 cm reported an amenorrhea rate of 39% with the
HydroThermAblator treatment. However, amenorrhea rates
were significantly higher for patients with normal cavities
(62% at 30 months’ follow-up).48 Rates of re-intervention
were also significantly higher in patients with distorted
cavities.48 Women with types 1 and 2 submucosal fibroids
< 3 cm who were followed prospectively following treatment
with NovaSure had amenorrhea rates of 69% at 1 year.49
Thermachoice also demonstrated a decrease in menstrual
flow in 4 women with submucosal myomas < 3 cm.50
Despite encouraging results showing that non-
resectoscopic EA may be beneficial in treating AUB in
women with small (< 3 cm) submucosal fibroids, further
research is still required. Where possible, hysteroscopic
myomectomy/polypectomy combined with resectoscopic
EA should be used to treat women with symptomatic
intracavitary pathology.
Summary Statement
9. Combined hysteroscopic sterilization and
endometrial ablation can be safe and efficacious
while favouring a minimally invasive approach. (II-2)
Recommendations
8. If repeat endometrial ablation (EA) is considered
following non-resectoscopic or resectoscopic EA,
it should be performed by a hysteroscopic surgeon
with direct visualization of the cavity. Patients
should be counselled about the increased risk of
complications with repeat EA. (II-2A)
9. If significant intracavitary pathology is present,
resectoscopic endometrial ablation combined with
hysteroscopic myomectomy or polypectomy should
be considered in a non-fertility sparing setting. (II-3A)
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Obstet Invest 2001;51:128–33.
51. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.
Appendix begins on next page
APRIL JOGC AVRIL 2015 l 375
SOGC clinical practice guideline

APPENDIX
ENDOMETRIAL ABLATION PATIENT INFORMATION SHEET

Endometrial ablation is an alternative surgical procedure for heavy menstrual bleeding. It attempts to destroy or remove the
endometrium—the lining of your uterus. This can replace hysterectomy in many cases.
This is a day surgery procedure. The technique varies depending on the method used to destroy the endometrium.
Most EA procedures can be done in an outpatient surgical centre while others must be performed in an operating room. Factors such
as the size of your uterus, presence of fibroid tumours, and experience of the surgeon will help determine which endometrial ablation
method is best for you.
While medications are typically recommended as first line treatment for heavy menstrual bleeding, endometrial ablation may be an
option if medications don’t help or you decline to try them.
Endometrial ablation is not recommended for women who: Endometrial ablation risks may include:
• wish to become pregnant in the future, • perforation of the uterine wall,
• have cancer of the uterus, • damage to nearby organs, and/or
• have large fibroid tumours in the uterus, and/or • pain, bleeding, or infection.
• have had recent pelvic infection.

Future pregnancy
Many women stop having periods after endometrial ablation, but pregnancy is still possible in some women. Most of these pregnancies
will have an abnormal outcome. Women who wish to become pregnant in the future should not consider endometrial ablation.
Some women may choose to undergo a sterilization procedure at the time of endometrial ablation or consider other forms of reliable
contraception to prevent pregnancy. Concomitant laparoscopic tubal ligation would usually require general anaesthetic.

Preparation for surgery

• Check for abnormal endometrial cells. Your doctor may take a small sample of the lining of your uterus using a small
endometrial biopsy instrument. This is done in the office before surgery.
• Thin your endometrium. Endometrial ablation is often performed more successfully when the uterine lining is thin. This can be
accomplished with preoperative medications or by undergoing a D and C (dilation and curettage) on the day of surgery.
• Discuss method of anaesthesia. Most procedures can be performed with conscious sedation and local anaesthetic block.
In some instances general anaesthesia is required.

The procedure
Endometrial ablation can be performed in your doctor’s office, but some types of endometrial ablation are performed in a hospital
operating room, especially if you will need general anaesthesia.
The cervix is dilated to allow for the passage of the instruments used in endometrial ablation. Endometrial ablation procedures vary by
the method used to destroy your endometrium.
• Electrosurgery. This method uses a small hysteroscope to view the uterine cavity during the procedure. An electrode is used to
resect or destroy the lining of the uterus.
• Free-flowing hot fluid. Saline fluid heated to 80°C to 90°C is circulated within the uterus for about 10 minutes.
• Heated balloon. A balloon device is inserted through your cervix and then inflated with fluid heated to 87°C for about 2 to
10 minutes.
• Bipolar radiofrequency. This uses a bipolar wire mesh electrode that contacts the uterine cavity. The instrument transmits high
frequency electrical energy that vaporizes the endometrial tissue in about 90 seconds.

After the procedure

After endometrial ablation, you may experience:
• Cramps. You may have menstrual-like cramps for a few days.
• Vaginal discharge. A watery discharge, mixed with blood, may occur for a few weeks. The discharge is typically heaviest for the
first few days after the procedure.
• Frequent urination. You may need to pass urine more often during the first 24 hours after endometrial ablation.
Avoid intercourse for one week after surgery.
All endometrial ablation techniques show similar improvement in bleeding pattern. It may take a few months to see the final results of
surgery, but endometrial ablation causes marked reduction in menstrual blood loss in over 80% of patients. Most women will have lighter
periods or spotting, and some will stop having periods entirely.
You should continue to use contraception.

376 l APRIL JOGC AVRIL 2015

 SOGC CLINICAL PRACTICE GUIDELINE

No. 296, September 2013 (Reviewed March 2015)

Induction of Labour: Review

This clinical practice guideline review has been prepared
by Clinical Practice Obstetrics Committee and approved by
the Executive and Board of the Society of Obstetricians and
T he issue of induction of labour and risk of Caesarean
section has been a topic of recent discussion, catalyzed
by the publication of a new review paper in the Canadian
Gynaecologists of Canada. Medical Association Journal.1 In response to an influx of queries
regarding the CMAJ paper and its potential effect on SOG
PRINCIPAL AUTHORS
guidelines, the Clinical Practice Obstetrics Committee has
Dean Leduc, MD, Ottawa ON
reviewed the SOGC Induction of Labour guidelines published
Anne Biringer, MD, Toronto ON in 20132 and concluded that no update or revision to the
Lily Lee, RN, MSN, Vancouver BC SOGC is required at this time. The committee emphasized
Jessica Dy, MD, Ottawa ON that the CMAJ meta-analysis included no new information or
studies that were not used in the 2013 SOGC guideline.
CLINICAL PRACTICE OBSTETRICS COMMITTEE
Hussam Azzam (Chair), MD, Thompson MB It is also important to note that results from the CMAJ
Jon Barrett, MD, Toronto ON
review paper report on an induction group encompassing all
indications for induction of labour, with term labour defined
Anne Biringer, MD, Toronto ON
as 37 to 42 weeks’ gestation and measured outcomes limited
Kim Campbell, RM, Vancouver BC to Caesarean section. The SOGC guideline recommends
Louise Duperron, MD, Montreal QC requiring an obstetrical or medical indication (e.g. premature
Jessica Dy, MD, Ottawa ON rupture of membranes, hypertension, intrauterine growth
Ellen Giesbrecht, MD, Vancouver BC restriction) for induction of labour before 41 weeks. This is
consistent with guidelines published by the Royal College of
Lisa Graves, MD, Hamilton ON
Obstetricians and Gynaecologists and the American Congress
Michael Helewa, MD, Winnipeg MB
of Obstetricians and Gynecologists.
Ian Lange, MD, Calgary AB
Lily Lee, RN, MSN, Vancouver BC
The data does confirm that induction of labour for specific
indications is not associated with higher risk of Caesarean
Suzanne Muise, MD, Camana Bay, Grand Cayman
section and in some indications, such as post-term induction,
Barbara Parish, MD, Halifax NS it lowers the risk of Caesarean section. It is important to note
Disclosure statements have been received from all contributors. that these study findings should not be generalized to any
and all inductions of labour, especially when no indications
exist; SOGC stands by its recommendation that induction of
labour should be carried out only after careful discussion with
women who have specific indications.
The SOGC is aware of two clinical trials underway that
are examining induction of labour versus expectant
J Obstet Gynaecol Can 2015;37(4):380–381 management.3,4 The outcomes of these studies will be

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

380 l APRIL JOGC AVRIL 2015


monitored by the Clinical Practice Obstetrics Committee
for potential change of practice implications.
It is to be noted that, to ensure the best quality of care, the
SOGC is currently developing a standard of practice under
which evidence will be reviewed on a regular basis to decide
whether all or part of a guideline should be updated based
on new robust (Canadian Task Force on Preventive Health
Care5 level I) evidence.
REFERENCES
1. Mishanina E, Rogozinska E, Thatthi T, Uddin-Khan R, Khan KS,
et al. Use of labour induction and risk of cesarean delivery: a systematic
review and meta-analysis. CMAJ 2014;186:665–73.
Induction of Labour: Review
2. Leduc D, Biringer A, Lee L, Dy J; Clinical Practice Obstetrics
Committee, Society of Obsetricians and Gynaecologists of
Canada. Induction of labour. SOGC Clinical Practice Guideline
No. 296, September 2013. J Obstet Gynaecol Can 2013;36:248–52.
3. Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD). A Randomized Trial of Induction
Versus Expectant Management (ARRIVE). Bethesda, MD: US National
Institute of Health; 2014. Available at: http://clinicaltrials.gov/ct2/show/
NCT01990612?term=ARRIVE&rank=2. Accessed on December 10, 2014.
4. Nottingham Clinical Trials Unit. Induction of labour versus
expectant management for women over 35 years of age. Nothingham, GB:
NCTU; 2013. Available at: http://www.35-39trial.org.
Accessed on December 10, 2014.
5. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W;
Canadian Task Force on Preventive Health Care. New grades for
recommendations from the Canadian Task Force on Preventive
Health Care. CMAJ 2003;169:207–8.
APRIL JOGC AVRIL 2015 l 381
 SOGC CLINICAL PRACTICE GUIDELINE
The Management of Uterine Fibroids in Women
With Otherwise Unexplained Infertility
This clinical practice guideline was prepared by the
Reproductive Endocrinology and Infertility Committee,
reviewed by Family Physician Advisory and Clinical
Practice Gynaecology Committees, and approved by the
Executive and Board of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Belina Carranza-Mamane, MD, Sherbrooke QC
Jon Havelock, MD, Vancouver BC
Robert Hemmings, MD, Montreal QC
REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY
COMMITTEE
Anthony Cheung (Co-chair), MD, Vancouver BC
Sony Sierra (Co-chair), MD, Toronto ON
Belina Carranza-Mamane, MD, Sherbrooke QC
Allison Case, MD, Saskatoon SK
Cathie Dwyer, RN, Toronto ON
James Graham, MD, Calgary AB
Jon Havelock, MD, Vancouver BC
Robert Hemmings, MD, Montreal QC
Kimberly Liu, MD, Toronto ON
Ward Murdock, MD, Fredericton NB
Tannys Vause, MD, Ottawa ON
Benjamin Wong, MD, Calgary AB
SPECIAL CONTRIBUTOR
Margaret Burnett, MD, Winnipeg MB
Disclosure statements have been received from all contributors.
Keywords: Female infertility, unexplained infertility, fibroid,
leiomyoma, myomectomy, uterine artery embolization,
in vitro fertilization, ovarian reserve, ulipristal acetate,
magnetic resonance-guided focused ultrasound surgery.
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 321, March 2015
Abstract
Objective: To provide recommendations regarding the best
management of fibroids in couples who present with infertility.
Usual and novel treatment options for fibroids will be reviewed
with emphasis on their applicability in women who wish to
conceive.
Options: Management of fibroids in women wishing to conceive
first involves documentation of the presence of the fibroid and
determination of likelihood of the fibroid impacting on the ability
to conceive. Treatment of fibroids in this instance is primarily
surgical, but must be weighed against the evidence of surgical
management improving clinical outcomes, and risks specific to
surgical management and approach.
Outcomes: The outcomes of primary concern are the improvement
in pregnancy rates and outcomes with management of fibroids in
women with infertility.
Evidence: Published literature was retrieved through searches of
PubMed, MEDLINE, the Cochrane Library in November 2013
using appropriate controlled vocabulary (e.g., leiomyoma,
infertility, uterine artery embolization, fertilization in vitro) and key
words (e.g., fibroid, myomectomy). Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies published in English and French.
There were no date restrictions. Searches were updated on a
regular basis and incorporated in the guideline to November 2013.
Grey (unpublished literature) was identified through searching the
websites of health technology assessment and health technology-
related agencies, clinical practice guideline collections, clinical
trial registries, and national and international medical specialty
societies.
Values: The quality of evidence in this document was rated using
the criteria described by the Canadian Task Force on Preventive
Health Care (Table).
Benefits, harms, and costs: These recommendations are expected
to allow adequate management of women with fibroids and
infertility, maximizing their chances of pregnancy by minimizing
risks introduced by unnecessary myomectomies. Reducing
complications and eliminating unnecessary interventions are also
expected to decrease costs to the health care system.
J Obstet Gynaecol Can 2015;37(3):277–285
MARCH JOGC MARS 2015 l 277
SOGC clinical practice guideline
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.52
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.52
Summary Statements
  1. Subserosal fibroids do not appear to have an impact on fertility;
the effect of intramural fibroids remains unclear. If intramural
fibroids do have an impact on fertility, it appears to be small
and to be even less significant when the endometrium is not
involved. (II-3)
  2. Because current medical therapy for fibroids is associated with
suppression of ovulation, reduction of estrogen production, or
disruption of the target action of estrogen or progesterone at the
receptor level, and it has the potential to interfere in endometrial
development and implantation, there is no role for medical
therapy as a stand-alone treatment for fibroids in the infertile
population. (III)
  3. Preoperative assessment of submucosal fibroids is essential to
the decision on the best approach for treatment. (III)
  4. There is little evidence on the use of Foley catheters, estrogen, or
intrauterine devices for the prevention of intrauterine adhesions
following hysteroscopic myomectomy. (II-3)
ABBREVIATIONS
CPR clinical pregnancy rates
FSH follicle-stimulating hormone
IR implantation rates
IVF in vitro fertilization
LBR live birth rates
MR miscarriage rates
MRGfUS magnetic resonance-guided focused ultrasound surgery
MRI magnetic resonance imaging
OBR ongoing pregnancy rates
RCT randomized control trial
UAE uterine artery emolization
278 l MARCH JOGC MARS 2015
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
  5. In the infertile population, cumulative pregnancy rates by the
laparoscopic and the minilaparotomy approaches are similar, but
the laparoscopic approach is associated with a quicker recovery,
less postoperative pain, and less febrile morbidity. (II-2)
  6. There are lower pregnancy rates, higher miscarriage rates, and
more adverse pregnancy outcomes following uterine artery
embolization than after myomectomy. (II-3) Studies also suggest
that uterine artery embolization is associated with loss of ovarian
reserve, especially in older patients. (III)
Recommendations
  1. In women with infertility, an effort should be made to adequately
evaluate and classify fibroids, particularly those impinging on the
endometrial cavity, using transvaginal ultrasound, hysteroscopy,
hysterosonography, or magnetic resonance imaging. (III-A)
  2. Preoperative assessment of submucosal fibroids should include,
in addition to an assessment of fibroid size and location within the
uterine cavity, evaluation of the degree of invasion of the cavity and
thickness of residual myometrium to the serosa. A combination of
hysteroscopy and transvaginal ultrasound or hysterosonography
are the modalities of choice. (III-B)
  3. Submucosal fibroids are managed hysteroscopically. The fibroid
size should be < 5 cm, although larger fibroids have been
managed hysteroscopically, but repeat procedures are often
necessary. (III-B)
  4. A hysterosalpingogram is not an appropriate exam to evaluate and
classify fibroids. (III-D)
  5. In women with otherwise unexplained infertility, submucosal
fibroids should be removed in order to improve conception and
pregnancy rates. (II-2A)
  6. Removal of subserosal fibroids is not recommended. (III-D)
  7. There is fair evidence to recommend against myomectomy in
women with intramural fibroids (hysteroscopically confirmed intact
endometrium) and otherwise unexplained infertility, regardless of
their size. (II-2D) If the patient has no other options, the benefits
of myomectomy should be weighed against the risks, and
management of intramural fibroids should be individualized. (III-C)
 The Management of Uterine Fibroids in Women With Otherwise Unexplained Infertility
  8. If fibroids are removed abdominally, efforts should be made
to use an anterior uterine incision to minimize the formation of
postoperative adhesions. (II-2A)
  9. Widespread use of the laparoscopic approach to myomectomy
may be limited by the technical difficulty of this procedure. Patient
selection should be individualized based on the number, size, and
location of uterine fibroids and the skill of the surgeon. (III-A)
10. Women, fertile or infertile, seeking future pregnancy should not
generally be offered uterine artery embolization as a treatment
option for uterine fibroids. (II-3E)
INTRODUCTION
U
terine fibroids, myomas, or leiomyomata are smooth
muscle cell tumours and are the most common benign
gynaecologic tumour in women of reproductive age.1 They are
often found as part of the investigation of a couple presenting
with infertility, and their origin is monoclonal.2 They are rarely
found before menarche and usually regress after menopause.3
They are hormonally responsive, and estrogens appear to
promote their growth.4,5 Local estrogen concentrations have
been shown to be higher in myomas than in the surrounding
myometrium, possibly because of a higher concentration of
aromatase.6 Hormonal responsiveness appears to be greater
in submucosal than subserosal myomas.7
EVALUATION AND CLASSIFICATION OF FIBROIDS
Submucosal fibroids have a negative impact on rates of
implantation, clinical pregnancy, ongoing pregnancy,
miscarriage, and live birth. An important feature of fibroid
classification systems is the evaluation of the uterine cavity
in order to define a fibroid as submucosal. Many studies
have not included proper evaluation of the cavity, and
therefore potential biases can be expected in their results.
Imaging is now recognized as a necessary tool in the
preoperative evaluation of myomas, especially for uterus-
sparing procedures.8
Ultrasound has been shown to be an adequate, rapid, safe,
and cost-effective means of evaluating the size, number, and
location of fibroids.9 Transvaginal ultrasound may identify
fibroids of up to 4 to 5 mm in diameter.10 Ultrasound
may, however, be suboptimal for multiple fibroids, because
of acoustic shadowing, and for the proper evaluation of
endometrial impingement. Interobserver variation has also
been found to be greater with this technique than with MRI.11
MRI has been well studied in the evaluation of fibroid
uteruses, especially for fibroid mapping and submucosal
penetration. It was shown to be the most reliable
method of evaluation when compared with vaginal
ultrasound, hysterosonography, and hysteroscopy, with
100% sensitivity and 91% specificity (gold standard was
pathological examination).9 The main drawbacks of MRI
evaluation are lack of accessibility and high cost.8
Hysterosalpingography is often performed to assess
tubal patency in women with infertility and to exclude
intrauterine pathology. However, the sensitivity and
positive predictive value of this test for the identification
of intrauterine lesions can be as low as 50% and 28.6%
respectively.12 Hysterosalpingography cannot therefore
be considered reliable to exclude endometrial distortion
secondary to submucosal myomas.
Hysterosonography, which has the advantages of
pelvic ultrasound, has been advocated as superior to
transvaginal ultrasound alone13 and equal to hysteroscopy
in the evaluation of endometrial impingement.14 It has
been shown to be highly sensitive and specific in the
identification of submucosal myomas. Its main drawbacks
are the risk of infection (approximately 1%) and the
discomfort associated with the injection of sterile saline.13
No studies to date have evaluated the optimal mode of
evaluating uterine myoma in women presenting with
infertility. It is also unclear whether all women with
infertility should have the integrity of their endometrial
cavity evaluated. However, it seems clear that part of the
heterogeneity in the results of studies attempting to clarify
the relationships between fibroids and infertility and the
impact of treatment on conception is due to inadequate
classification of fibroids, and in particular their impact on
the endometrial cavity.
Recommendations
1. In women with infertility, an effort should be
made to adequately evaluate and classify fibroids,
particularly those impinging on the endometrial
cavity, using transvaginal ultrasound, hysteroscopy,
hysterosonography, or magnetic resonance
imaging. (III-A)
2. Preoperative assessment of submucosal fibroids
should include, in addition to an assessment of
fibroid size and location within the uterine cavity,
evaluation of the degree of invasion of the cavity
and thickness of residual myometrium to the serosa.
A combination of hysteroscopy and transvaginal
ultrasound or hysterosonography are the modalities
of choice. (III-B)
3. Submucosal fibroids are managed hysteroscopically.
The fibroid size should be < 5 cm, although larger
fibroids have been managed hysteroscopically, but
repeat procedures are often necessary. (III-B)
4. A hysterosalpingogram is not an appropriate exam to
evaluate and classify fibroids. (III-D)
MARCH JOGC MARS 2015 l 279
SOGC clinical practice guideline
IMPACT OF FIBROIDS ON
REPRODUCTIVE FUNCTION
The prevalence of fibroids in the infertile population
of women is controversial. According to Donnez,15
approximately 5% to 10% of women presenting with
infertility are found to have one or multiple fibroids.
However, when all other causes of infertility are excluded,
fibroids are found in only 1% to 2% of the remaining
women.16 Both infertility and age have been associated
with the presence of myomas and may therefore confound
results of studies attempting to clarify the relationship
between fibroids and infertility.17 There have been no
appropriately designed studies to demonstrate a direct
causal relationship between the presence of fibroids and
infertility.
Many hypotheses have been generated to explain how
fibroids might cause infertility. Perfusion studies have
shown that blood flow to uterine fibroids is less than that
to the adjacent myometrium.18–20 Blood flow to the uterine
arteries is also different in fibroid uteruses than non-fibroid
uteruses.21 This and the fact that there may be endometrial
inflammation and an altered local hormonal environment
may impede embryo implantation. Myomas also seem to
alter uterine contractility possibly interfering with sperm
and ovum interaction or embryo migration.4,15 This may
especially be true in uteruses with multiple large fibroids
with important cavity distortion.
Six systematic reviews or meta-analyses published between
2001 and 201015,22–26 assessed whether fibroids have an
impact on fertility. On the whole, it appears that women
with fibroids have decreased fertility. The presence of
fibroids, regardless of location, significantly decreases
both implantation and clinical pregnancy rates (RR 0.821;
95% CI 0.722 to 0.932, P = 0.002 and RR 0.849; 95% CI
0.734 to 0.982, P < 0.03 respectively).25 The impact of
fibroid number and size on fertility has not been clearly
elucidated.17 Reproductive success does, however, seem to
be related to fibroid location.
Subserosal fibroids do not appear to have an impact on
fertility; all systematic reviews and meta-analyses agreed on
this point. Submucosal fibroids (fibroids with endometrial
impingement), however, have been shown uniformly
to have a negative impact on rates of implantation,
clinical pregnancy, miscarriage, and live birth/ongoing
pregnancy, although available studies are few and small
(IR: RR 0.283; 95% CI 0.123 to 0.649, P = 0.003; CPR:
RR 0.363; 95% CI 0.179 to 0.737, P = 0.005; MR:
RR 1.678; 95% CI 1.373 to 2.051, P = 0.022; LBR/OPR:
RR 0.318; 95% CI 0.119 to 0.850, P < 0.001).25
280 l MARCH JOGC MARS 2015
The greatest debate remains on the impact and treatment of
intramural fibroids. Part of the disagreement between studies
may result from inappropriate evaluation of the endometrial
cavity causing the erroneous inclusion of submucosal fibroids
in the group of intramural fibroids. Considering only the
most recent good quality meta-analysis, intramural fibroids do
seem to have an impact on both IR and CPR (RR 0.684; 95%
CI 0.587 to 0.796, P < 0.001 and RR 0.810; 0.696 to 0.941,
P = 0.006, respectively) but less than that of submucosal
fibroids. Although the number of studies reporting this
outcome was small, there was no impact found on LBR/
OPR.25 This finding remained significant regardless of study
design and when looking exclusively at studies on IVF, except
that Sunkara et al.27 found a reduction in LBR in women
undergoing IVF in the presence of intramural fibroids (RR
0.79; 95% CI 0.70 to 0.88, P < 0.001). This discrepancy in
IVF studies could be explained by the authors’ not controlling
for age and number of IVF cycles. Considering only studies
that included an adequate hysteroscopic evaluation of the
uterine cavity, implantation remains the only rate significantly
affected by the presence of intramural fibroids.25 Fibroid size
did not seem to have an impact on these results, although
large intramural fibroids would presumably have been
treated surgically and hence not included in such studies.
Most studies included intramural fibroids < 5 cm. No
studies have examined the distance between fibroid edge
and endometrium. Only one retrospective study evaluated
the impact of a single intramural fibroid on IVF outcomes
for severe male factor. Endometrial cavity was assessed using
hysteroscopy in all patients. Fibroid sizes ranged from 5 to
43 mm. IR and CPR were similar between cases (n = 61)
and controls (n = 444).28 Miscarriage rates were found to be
increased in women with intramural fibroids (RR 1.747; 95%
CI 1.22 to 2.489, P = 0.002), but this effect was lost when
only studies with adequate cavity involvement evaluation
were included.25
Another way of assessing whether a uterine pathology
has an impact on conception rates is to evaluate whether
pregnancy rates increase more after removal than after
expectant management. It is equally important to ensure
that treatment does not have an intrinsically negative
impact on fertility, particularly in surgical treatments that
can result in the formation of scar tissue and adhesions
known to have deleterious effects on conception rates.
Studies on treatment for leiomyomas in women with
infertility have been few and small. Two types of control
groups have been used: women with fibroids left in situ
and women with unexplained infertility without fibroids.
No large trials have evaluated the impact of myomectomy
in women with submucosal fibroids. A meta-analysis of
 The Management of Uterine Fibroids in Women With Otherwise Unexplained Infertility
the small studies available found an apparent benefit of
hysteroscopic myomectomy over fibroids left in situ
on CPR (RR 2.034, 95% CI 1.081 to 3.826, P = 0.028).
Pregnancy rates after myomectomy become statistically
similar to those in women with infertility without fibroids.25
In the matter of the surgical removal of intramural fibroids
to improve fertility, data fail to show a clear benefit of
myomectomy over myomas left in situ.
Summary Statement
1. Subserosal fibroids do not appear to have an impact
on fertility; the effect of intramural fibroids remains
unclear. If intramural fibroids do have an impact on
fertility, it appears to be small and to be even less signifi-
cant when the endometrium is not involved. (II-3)
MEDICAL MANAGEMENT
Contemporary medical management of uterine fibroids
exploits the estrogen- and progesterone-responsiveness
of uterine fibroids; however, no pharmacological agent is
curative of fibroids. As a result, medical therapy is essentially
a treatment option for the control of symptoms. Several
agents exist for the management of uterine fibroids through
symptom control, reduction in fibroid volume, and reduction
in menstrual blood loss. Most commonly used agents have
been GnRH analogues. Newer, novel therapies including
aromatase inhibitors, mifepristone, selective estrogen
receptor modulators, and selective progesterone receptor
modulators have shown promise in symptom improvement
and fibroid regression without the hypoestrogenic symptoms
associated with GnRH analogues.
Summary Statement
2. Because current medical therapy for fibroids is
associated with suppression of ovulation, reduction
of estrogen production, or disruption of target
action of estrogen or progesterone at the receptor
level, and it has the potential to interfere in
endometrial development and implantation, there is
no role for medical therapy as stand-alone treatment
for fibroids in the infertile population. (III)
SURGICAL MANAGEMENT
Well-designed surgical intervention trials for myomectomy
and infertility are sparse, with a single RCT published
to date.28 This study demonstrated an improvement in
spontaneous conception rates after the surgical removal
of submucosal fibroids, but pregnancy rates following
the removal of intramural or subserosal fibroids were no
more improved than in the expectant management group
of women with intramural-subserosal fibroids in situ.
A recent meta-analysis demonstrated similar findings, with
an improvement in pregnancy rates in infertile patients
undergoing surgical removal of submucosal fibroids, but
not in those undergoing surgical removal of intramural
fibroids.25
Surgical treatment of fibroids can be associated with
morbidity. It has been associated with both pelvic and
intrauterine adhesions, so any potential benefit from the
removal of the fibroids may be negated by the detrimental
effect of the surgery on uterine integrity. In addition, the
consequences of myomectomy on pregnancy outcomes
are not negligible. It is therefore imperative that surgical
management of fibroids for infertility be undertaken
only when there is evidence to support improvement
in pregnancy outcomes through surgical intervention.
There may, however, be instances when surgical removal
of fibroids in an infertile patient may be undertaken for
reasons other than fertility enhancement, such as relief of
pressure symptoms or surgical management of menstrual
disturbances secondary to fibroids.
Recommendations
5. In women with otherwise unexplained infertility,
submucosal fibroids should be removed in order to
improve conception and pregnancy rates. (II-2)
6. Removal of subserosal fibroids is not
recommended. (III-D)
7. There is fair evidence to recommend against
myomectomy in women with intramural fibroids
(hysteroscopically confirmed intact endometrium)
and otherwise unexplained infertility, regardless of
the size of the fibroids. (II-2D) If the patient has no
other options, the benefits of myomectomy should
be weighed against the risks, and management of
intramural fibroids should be individualized. (III-C)
Surgical approach to fibroids can be either vaginal or
abdominal. The abdominal approach may be either by
laparotomy or laparoscopy. The specific approach will
depend on fibroid size and location and on skill of the
practitioner. The decision to proceed with myomectomy
for improvement in fertility outcomes, especially when
laparotomy is recommended, should be weighed against
the patient’s clinical fertility history, subsequent plans for
fertility treatment, and estimated fecundability with or
without myomectomy.
Hysteroscopic Myomectomy
Hysteroscopic myomectomy is the least invasive surgical
approach to fibroid removal. It is most effective for
patients with submucosal fibroids completely within the
uterine cavity (Type 0) or with at least 50% of the fibroid
MARCH JOGC MARS 2015 l 281
SOGC clinical practice guideline
volume within the uterine cavity (Type I). Fibroids with
less than 50% of the fibroid volume in the cavity (Type II)
are much more difficult to resect completely and are more
often associated with the need for repeated procedures.29,30
Additionally, it has generally been recommended that
hysteroscopic myomectomy be undertaken with fibroids
under 5 cm; however fibroids greater than 5 cm and
Type II fibroids have been resected hysteroscopically.31
Summary Statement
3. Preoperative assessment of submucosal fibroids is
essential to the decision on the best approach for
treatment. (III)
Of late, complications that may further impair fertility
after hysteroscopic myomectomy, intrauterine adhesions
are the most concerning. The incidence of intrauterine
adhesions after hysteroscopic myomectomy was shown
in one study to be 7.5%.32 Postoperative adjuvant therapy,
including estrogen therapy for 4 to 8 weeks or insertion
of an intrauterine device, pediatric Foley catheter, or other
balloon for 1 week postoperatively, have all been used to
prevent further adhesion development. However, there is
scant evidence to support the use of these postoperative
therapies.33,34
Summary Statement
4. There is little evidence on the use of Foley catheters,
estrogen, or intrauterine devices for the prevention
of intrauterine adhesions following hysteroscopic
myomectomy. (II-3)
Abdominal Myomectomy
Abdominal myomectomy is an effective surgical procedure
for women wishing to preserve their fertility and who have
pressure symptoms due to the mass effect of large fibroids.
It may also be performed in women wishing to preserve
their fertility with symptomatic menorrhagia that is neither
controlled by medical management nor effectively managed
by hysteroscopic myomectomy. With improvements
in hysteroscopic myomectomy techniques, the use of
abdominal myomectomy to improve fecundity has narrowed
to a small subgroup of infertile patients with fibroids. The
current indication for abdominal myomectomy is for infertile
patients with large (> 5 cm) Type II submucosal fibroids or
Type II fibroids with < 1 cm between the external surface of
the fibroid and the uterine serosa. The goal, similar to that
of hysteroscopic myomectomy for infertility, is to remove
the fibroid in its entirety and to restore normal uterine cavity
size and architecture. Abdominal myomectomy may be
conducted through a subumbilical vertical incision for large
fibroids, as a mini-laparotomy through a Pfannenstiel incision
for smaller fibroids (typically < 10 cm), or laparoscopically.
282 l MARCH JOGC MARS 2015
Postoperative formation of adhesions after myomectomy is
extremely high: in one study it was 94% with uterine incisions
on the posterior wall and 55% when the incision occurred
on the anterior uterine wall. Obviously these adhesions may
have a negative impact on fertility in women where this is
already a concern. These adhesions were lysed at second-
look laparoscopy 6 weeks post myomectomy, with a 67%
cumulative pregnancy rate 12 months post myomectomy.35
Recommendation
8. If fibroids are removed abdominally, efforts should be
made to use an anterior uterine incision to minimize
the formation of postoperative adhesions. (II-2A)
Best practice for adhesion prevention in gynaecologic
surgery has been thoroughly described elsewhere.36
Two RCTs with a combined 267 patients compared
reproductive outcomes of laparoscopic myomectomy
and myomectomy by laparotomy. In the first study of
patients undergoing myomectomy for infertility and
at least 1 fibroid > 5 cm, pregnancy rates were similar
following in the laparoscopy and laparotomy groups
(53.6% vs. 55.9%).37 There was lower febrile morbidity in
the laparoscopy group (26.2% vs. 12.1%), shorter hospital
stay, and a lower postoperative drop in hemoglobin. In
the second study, 12 months postoperatively, cumulative
pregnancy rates were similar in the laparoscopy and
laparotomy groups (52.9% vs. 38.2%).38 Miscarriage rates
and preterm delivery rates were also similar between
groups and similar to expected rates in the general
population. Interestingly, in the subgroup of patients
undergoing myomectomy for non-fertility indications the
cumulative pregnancy rate was greater in the laparoscopy
subgroup (73.7% vs. 50%). In this study, it appears
myomectomy was not considered a contraindication to
vaginal delivery, and 31% of all patients who delivered
underwent a successful vaginal delivery.
Summary Statement
5. In the infertile population, cumulative pregnancy
rates by the laparoscopic and minilaparotomy
approaches are similar, but the laparoscopic
approach is associated with a quicker recovery, less
postoperative pain, and less febrile morbidity. (II-2)
Recommendation
9. Widespread use of the laparoscopic approach
to myomectomy may be limited by the technical
difficulty of this procedure. Patient selection should
be individualized based on the number, size, and
location of uterine fibroids and the skill of the
surgeon. (III-A)
 The Management of Uterine Fibroids in Women With Otherwise Unexplained Infertility
NEW METHODS OF TREATMENT OF
FIBROIDS AND INFERTILITY
The last decade has seen increasing demand for safe and
effective uterus- and “reproductive potential”-sparing
treatment options for symptomatic uterine fibroids. The goal
of this section is to review the important new techniques for
uterus-sparing treatment of uterine fibroids and particularly
their use in women with fibroids and infertility.
Newer uterus-sparing treatments include laser ablation,
laparoscopic and vaginal occlusion of uterine arteries,
MRGfUS, and UAE. However, many of these techniques
have not been used on a large scale, and data on their
reproductive outcomes in patients trying to conceive are
insufficient to make recommendations. Here we review
2 techniques other than myomectomy, namely UAE and
MRgFUS, that are currently being evaluated for patients
who desire to keep their fertility.
Uterine Artery Embolization:
Technique and Indications
UAE was first introduced in 1995 for treatment of uterine
fibroids.39 Uterine embolization has been well studied as
an alternative to myomectomy and hysterectomy, mainly
in women who no longer desire children, and it has
progressively become one of the most widely used non-
invasive conservative methods of treatment of uterine
fibroids after myomectomy.
Current contraindications to UAE include pregnancy,
infertility (or desire for future pregnancy), clinical findings
and imaging suggestive of gynaecological malignancy,
anaphylactic reaction to contrast material, renal failure, and
coagulopathy.40
MRI studies during the hours following embolization
have shown a transient ischemia of the uterine corpus and
fundus affecting the endometrium and inner and middle
myometrial layers, which subsides 48 to 72 hours later, but
the fibroids undergo irreversible infarction.41 Although
intra-abdominal adhesions have been described to develop
following this process, they are much less common than
adhesions following myomectomy.42,43 These findings
imply, however, possible irreversible damage to the
endometrium and formation of adhesion, which may be
deleterious to women who already suffer from infertility.
Fertility in patients following UAE
Spontaneous pregnancy may be possible following UAE,
but this conservative method of treatment is currently
contraindicated in women seeking future pregnancy.
In general, data on UAE in women with fibroids and
infertility remains difficult to interpret because of patient
heterogeneity (studies include women undergoing UAE
for symptomatic fibroids, but also women with postpartum
hemorrhage) and the almost exclusive inclusion of women
who no longer desired pregnancy. The best comparative
evidence available is in an RCT by Mara et al.44 121 patients
wishing to become pregnant and having intramural
fibroids > 4 cm were randomized to either UAE (n = 58)
or abdominal (open or laparoscopic according to surgeon
preference) myomectomy (n = 63). Of patients who
attempted to conceive, 50% of the UAE group versus 78%
of the myomectomy group were able to do so. The RR for
UAE patients of not getting pregnant was 2.22 (95% CI
1.11 to 4.44), and of miscarriage was 2.79 (95% CI 1.25 to
6.22). Therefore, myomectomy was associated with more
pregnancies and deliveries than UAE and a lower rate of
miscarriage up to 2 years post therapy.
Another finding that raises concerns about the use of
UAE in women with infertility is the fact that significantly
more women in the UAE group presented with an
FSH > 10 IU/L 6 months after the procedure (13.8% vs.
3.2%; P < 0.05), although the numbers were small. Other
studies have found loss of ovarian reserve and an increase
in ovarian failure in women undergoing UAE, particularly in
women in later reproductive years. Transient or permanent
amenorrhea associated with a decrease in ovarian reserve
has been reported, with an incidence of 1% to 2% in
women under 45.45 A prospective study by Hovsepian et al.
found that in patients between the ages of 35 and 40 there
was a transient increase in FSH 3 months after UAE, but
that after 6 months, FSH levels were similar to those of
patients having undergone myomectomy or hysterectomy.46
Another study found a loss of ovarian reserve in patients
around 45 years of age expressed by increased FSH and
decreased anti-Müllerian hormone lasting for at least 24
months following UAE and hysterectomy.47
It is important to mention that FSH is a poor marker of
ovarian reserve and a poor predictor of ovarian response
to IVF. It is also a later marker than antral follicle count or
anti-Müllerian hormone, which have been shown to have
much higher sensitivities and specificities for response to
IVF. As IVF is usually required in women with unexplained
infertility, ovarian reserve should be an important concern
in treatment of fibroids. Unfortunately, no data using
adequate markers were found regarding the impact of
UAE on ovarian reserve in women of reproductive age.
The incidences of Caesarean section and postpartum
hemorrhage were also both found to be higher following
UAE (66% vs. 48.5% and 13.9% vs. 2.5%, respectively)
than in control pregnancies matched for age and fibroid
location.48
MARCH JOGC MARS 2015 l 283
SOGC clinical practice guideline
Concerns also remain about the formation of synechia
from smaller particles lodging in the endometrial
vasculature and about the obstetrical outcomes of women
who undergo UAE and then conceive. UAE has been
associated with increased risks of spontaneous miscarriage,
preterm delivery, abnormal placentation, and postpartum
hemorrhage.49
Summary Statement
6. There are lower pregnancy rates, higher
miscarriage rates, and more adverse pregnancy
outcomes following uterine artery embolization
than after myomectomy. (II-3) Studies also suggest
that uterine artery embolization is associated
with loss of ovarian reserve, especially in older
patients. (III)
Recommendation
10. Women, fertile or infertile, seeking future
pregnancy should not generally be offered uterine
artery embolization as a treatment option for
uterine fibroids. (II-3E)
Magnetic Resonance-guided Focused
Ultrasound Surgery
In 2004, the United States Federal Drug Administration
approved the use of MRgFUS for treatment of uterine
fibroids. This technique involves the destruction of uterine
fibroid tissue by coagulative necrosis through heating tissue
to over 70°C by focusing many high frequency ultrasound
beams on the target tissue. For maximum accuracy, the
ultrasound beams are guided with MRI, which has the best
resolution and sensitivity to detect uterine fibroids.50
International experience of 54 pregnancies in 51 women
following MRgFUS was recently reported from 13 sites.51
These women had previously declared that they were not
interested in future pregnancy and their mean age was 37.2
years. The miscarriage rate was 26%; 42% of the women
had delivered at the time of publication, while 20% of the
pregnancies were ongoing. 64% of women had a vaginal
delivery and the mean weight at birth was 3.3 kg. There
were 2 placenta praevia in this group of patients. Only 1
patient had a serious complication after a myomectomy
done at the time of a Caesarean section. Her second
pregnancy was uneventful.
There are currently no data comparing MRgFUS with
myomectomy and no studies of its use in women with
fibroids and infertility as their main complaints. Further
studies are needed before offering this treatment to women
with fibroids and otherwise unexplained infertility.
284 l MARCH JOGC MARS 2015
SUMMARY
Women presenting with both fibroids and a history of
otherwise unexplained infertility represent a challenge.
These women may or may not be symptomatic from these
fibroids. They may have one or more fibroids that are only
detectable through ultrasound examination or the fibroids
may be easily palpable on abdominal examination. With
such a heterogeneous disorder, studies are difficult to
perform and adequate conclusions difficult to draw.
The effect of fibroids on reproduction remains in question.
Submucosal fibroids seem to have an impact, whereas
subserosal do not. Intramural fibroids might have an
impact, but randomized studies with adequate evaluation of
intracavitary involvement are necessary to adequately evaluate
whether the benefits of treatment will outweigh the serious
surgical and obstetrical risks that follow myomectomy.
Treatment of fibroids should be individualized, and
symptomatology may be a decisive factor in whether or
not a fibroid is removed. Myomectomy remains the gold
standard for treatment.
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MARCH JOGC MARS 2015 l 285
 SOGC CLINICAL PRACTICE GUIDELINE
The Management of Uterine Leiomyomas
This clinical practice guideline has been prepared by the
Uterine Leiomyomas Working Group, reviewed by the
Clinical Practice Gynaecology, Reproductive Endocrinology
& Infertility, and Family Physician Advisory Committees,
and approved by the Executive and Board of the Society of
Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
George A. Vilos, MD, London ON
Catherine Allaire, MD, Vancouver BC
Philippe-Yves Laberge, MD, Quebec QC
Nicholas Leyland, MD, MHCM, Hamilton ON
SPECIAL CONTRIBUTORS
Angelos G. Vilos, MD, London, ON
Ally Murji, MD, MPH, Toronto, ON
Innie Chen, MD, Ottawa, ON
Disclosure statements have been received from all contributors.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical Reserch
Analyst, Society of Obstetricians and Gynaecologists of Canada.
Abstract
Objectives: The aim of this guideline is to provide clinicians with an
understanding of the pathophysiology, prevalence, and clinical
significance of myomata and the best evidence available on
treatment modalities.
Options: The areas of clinical practice considered in formulating this
guideline were assessment, medical treatments, conservative
treatments of myolysis, selective uterine artery occlusion, and
surgical alternatives including myomectomy and hysterectomy.
The risk-to-benefit ratio must be examined individually by the
woman and her health care provider.
Key Words: Myoma, leiomyoma, fibroid, myomectomy, uterine
artery embolization, hysterectomy, heavy menstrual bleeding,
menorrhagia
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 318, February 2015 (Replaces, No. 128, May 2003)
Outcomes: Implementation of this guideline should optimize
the decision-making process of women and their health care
providers in proceeding with further investigation or therapy for
uterine leiomyomas, having considered the disease process
and available treatment options, and reviewed the risks and
anticipated benefits.
Evidence: Published literature was retrieved through searches
of PubMed, CINAHL, and Cochrane Systematic Reviews in
February 2013, using appropriate controlled vocabulary (uterine
fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy
menstrual bleeding, and menorrhagia) and key words (myoma,
leiomyoma, fibroid, myomectomy, uterine artery embolization,
hysterectomy, heavy menstrual bleeding, menorrhagia). The
reference lists of articles identified were also searched for other
relevant publications. Results were restricted to systematic
reviews, randomized control trials/controlled clinical trials, and
observational studies. There were no date limits but results were
limited to English or French language materials. Searches were
updated on a regular basis and incorporated in the guideline
to January 2014. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology–related agencies, clinical practice
guideline collections, and national and international medical
specialty societies.
Benefits, Harms, and Costs: The majority of fibroids are
asymptomatic and require no intervention or further
investigations. For symptomatic fibroids such as those causing
menstrual abnormalities (e.g. heavy, irregular, and prolonged
uterine bleeding), iron defficiency anemia, or bulk symptoms
(e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy
is a definitive solution. However, it is not the preferred solution
for women who wish to preserve fertility and/or their uterus. The
selected treatment should be directed towards an improvement
in symptomatology and quality of life. The cost of the therapy
to the health care system and to women with fibroids must
be interpreted in the context of the cost of untreated disease
conditions and the cost of ongoing or repeat investigative or
treatment modalities.
Values: The quality of evidence in this document was rated using
the criteria described in the Report of the Caadian Task Force on
Preventive Health Care (Table 1).
J Obstet Gynaecol Can 2015;37(2):157–178
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SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.204
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.204
Summary Statements
  1. Uterine fibroids are common, appearing in 70% of women by
age 50; the 20% to 50% that are symptomatic have considerable
social and economic impact in Canada. (II-3)
  2. The presence of uterine fibroids can lead to a variety of clinical
challenges. (III)
  3. Concern about possible complications related to fibroids in
pregnancy is not an indication for myomectomy except in women
who have had a previous pregnancy with complications related
to these fibroids. (III)
  4. Women who have fibroids detected in pregnancy may require
additional maternal and fetal surveillance. (II-2)
  5. Effective medical treatments for women with abnormal uterine
bleeding associated with uterine fibroids include the levonorgestrel
intrauterine system, (I) gonadotropin-releasing hormone
analogues, (I) selective progesterone receptor modulators, (I) oral
contraceptives, (II-2) progestins, (II-2) and danazol. (II-2)
  6. Effective medical treatments for women with bulk symptoms
associated with fibroids include selective progesterone receptor
modulators and gonadotropin-releasing hormone analogues. (I)
  7. Hysterectomy is the most effective treatment for symptomatic
uterine fibroids. (III)
  8. Myomectomy is an option for women who wish to preserve their
uterus or enhance fertility, but carries the potential for further
intervention. (II-2)
  9. Of the conservative interventional treatments currently available,
uterine artery embolization has the longest track record and has
been shown to be effective in properly selected patients. (II-3)
10. Newer focused energy delivery methods are promising but lack
long-term data. (III)
Recommendations
  1. Women with asymptomatic fibroids should be reassured that
there is no evidence to substantiate major concern about
malignancy and that hysterectomy is not indicated. (III-D)
158 l FEBRUARY JOGC FÉVRIER 2015
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
  2. Treatment of women with uterine leiomyomas must be
individualized based on symptomatology, size and location of
fibroids, age, need and desire of the patient to preserve fertility
or the uterus, the availability of therapy, and the experience of
the therapist. (III-B)
  3. In women who do not wish to preserve fertility and/or their uterus
and who have been counselled regarding the alternatives and
risks, hysterectomy by the least invasive approach possible may
be offered as the definitive treatment for symptomatic uterine
fibroids and is associated with a high level of satisfaction. (II-2A)
  4. Hysteroscopic myomectomy should be considered first-
line conservative surgical therapy for the management of
symptomatic intracavitary fibroids. (II-3A)
  5. Surgical planning for myomectomy should be based on mapping
the location, size, and number of fibroids with the help of
appropriate imaging. (III-A)
  6. When morcellation is necessary to remove the specimen,
the patient should be informed about possible risks and
complications, including the fact that in rare cases fibroid(s) may
contain unexpected malignancy and that laparoscopic power
morcellation may spread the cancer, potentially worsening their
prognosis. (III-B)
  7. Anemia should be corrected prior to proceeding with elective
surgery. (II-2A) Selective progesterone receptor modulators
and gonadotropin-releasing hormone analogues are effective at
correcting anemia and should be considered preoperatively in
anemic patients. (I-A)
  8. Use of vasopressin, bupivacaine and epinephrine, misoprostol,
peri-cervical tourniquet, or gelatin-thrombin matrix reduce blood
loss at myomectomy and should be considered. (I-A)
  9. Uterine artery occlusion by embolization or surgical methods
may be offered to selected women with symptomatic uterine
fibroids who wish to preserve their uterus. Women choosing
uterine artery occlusion for the treatment of fibroids should be
counselled regarding possible risks, including the likelihood that
fecundity and pregnancy may be impacted. (II-3A)

10. In women who present with acute uterine bleeding associated
with uterine fibroids, conservative management with estrogens,
selective progesterone receptor modulators, antifibrinolytics,
Foley catheter tamponade, and/or operative hysteroscopic
intervention may be considered, but hysterectomy may
become necessary in some cases. In centres where
available, intervention by uterine artery embolization may
be considered. (III-B)
INTRODUCTION
Clinical Importance of Uterine Fibroids
T he terms fibroid, myoma, and leiomyoma are
synonymous and are the commonest gynaecological
tumours, with a prevalence of 70% to 80% in women who
have reached the age of 50.1 In 95 061 US nurses, aged 25
to 44 years, the incidence was 8.9/1000 for white women
and 30.9/1000 for black women.2 The prevalence increases
with age, peaking in women in their 40s. A hysterectomy
study has found leiomyomas in 77% of uterine specimens.3
In many women, myomas may be asymptomatic and are
diagnosed incidentally on clinical examination or imaging.
However, myomas can cause significant morbidity including
menstrual abnormalities (e.g. heavy, irregular, and prolonged
uterine bleeding), iron defficiency anemia, bulk symptoms
(e.g. pelvic pressure/pain, obstructive symptoms), and
fertility issues. Symptomatic fibroids have a considerable
ABBREVIATIONS
AAGL American Association of Gynecologic Laparoscopists
AUB abnormal uterine bleeding
EA endometrial ablation
ER α estrogen receptor alpha
FDA United States Food and Drug Administration
FIGO International Federation of Gynecology and Obstetrics
GnRH gonadotropin-releasing hormone
HRT hormone replacement therapy
LNG-IUS levonorgestrel intrauterine system
MRg-FUS magnetic resonance-guided focused ultrasound
MRI magnetic resonance imaging
NETA norethindrone acetate
PR progesterone receptor
QoL quality of life
RF radio frequency
RFVTA radio frequency volumetric thermal ablation
SERM selective estrogen receptor modulator
SPRM selective progesterone receptor modulator
UAE uterine artery embolization
UAO uterine artery occlusion
UPA ulipristal acetate
The Management of Uterine Leiomyomas
impact on women’s quality of life as well as their productivity:
in one survey of more than 21 000 women from 8 different
countries, including 2500 from Canada, these symptoms had
a negative impact on sexual life (43%), performance at work
(28%), and relationship, and family (27%).4–6
Of 11 880 screened Canadian women, aged 20 to 49 years,
12.0% indicated they had been diagnosed with uterine
fibroids, including 3.2% reporting current fibroids. Those
with moderate to severe fibroid symptoms experienced a
significantly heavier burden of illness, with lost productivity
and reduced QoL.7
Uterine fibroids are currently the most common indication
for hysterectomy worldwide, and in Canada they account
for 30% of all hysterectomies, the second most common
surgery for women after Caesarean section.8 Hysterectomy
is associated with significant morbidity, mortality, and
economic burden on the health care system,9–10 and 1 in
4 Canadian women over age 45 have had a hysterectomy.8
The social and economic impact of uterine fibroids is
therefore considerable.
Summary Statement
1. Uterine fibroids are common, appearing in 70%
of women by age 50; the 20% to 50% that are
symptomatic have considerable social and economic
impact in Canada. (II-3)
Pathophysiology of Myomas
Uterine fibroids are monoclonal tumours that arise from
the uterine smooth muscle tissue (i.e. the myometrium).
They are benign neoplasms composed of disordered
“myofibroblasts” buried in abundant quantities of
extracellular matrix that accounts for a substantial portion
of tumour volume. The initiating events for fibroid genesis
remain speculative.
The cells proliferate at a modest rate and their growth
is dependant on the ovarian steroids estrogen and
progesterone and therefore most fibroids shrink after
menopause. The biologically potent estrogen estradiol
induces the production of PR by means of ER-α.
PR is essential for the response of fibroid tissue to
progesterone secreted by the ovaries. Progesterone and
PR are indispensable to tumour growth, increasing cell
proliferation and survival and enhancing extracellular
matrix formation. In the absence of progesterone and PR,
estrogen and ER-α are not sufficient for fibroid growth.11
Myomas can be single or multiple and can vary in size,
location, and perfusion. Myomas are commonly classified
into 3 subgroups based on their location: subserosal
(projecting outside the uterus), intramural (within the
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SOGC Clinical Practice Guideline
Figure 1. The FIGO leiomyoma subclassification system12
S – Submusosal
Leiomyoma
Subclassification System O – Other
Hybrid
leiomyomas
(impact both
endometrium
and serosa)
myometrium), and or submucosal (projecting into the cavity
of the uterus). A newer, more detailed classification system
has been devised and advocated by FIGO (Figure 1).12
Recognized risk factors for development of uterine fibroids
include nulliparity, early menarche, increased frequency of
menses, history of dysmenorrhea, family history of uterine
fibroids, African descent, obesity, and age (peak incidence
at 40 to 50). Clinical conditions that seem to increase risk
of fibroids include hypertension and diabetes.13
Clinical Presentation
The presence of uterine fibroids can lead to various clinical
challenges. The need for and choice of intervention must
be individualized to the clinical situation.
The most common symptom of uterine leiomyoma is
AUB. In a published series of myomectomies, 30% of
women suffered from heavy menstrual bleeding.14–15 The
mechanism of leiomyoma-associated AUB is unknown.
Increased endometrial surface area, vascular dysregulation,
and interference with endometrial hemostasis have been
offered as possible explanations.16 Clinicians with patients
presenting with AUB should refer to the SOGC clinical
practice guideline on the management of AUB.17
Pelvic pain is rare with fibroids and usually signifies
degeneration, torsion, or possibly associated adenomyosis
and/or endometriosis. Pelvic pressure, bowel dysfunction,
and bladder symptoms such as urinary frequency and
urgency may be present with larger fibroids. Urinary
symptoms should be investigated prior to surgical
160 l FEBRUARY JOGC FÉVRIER 2015
0 Pedunculated intracavitary
1 < 50% intramural
2 ≥ 50% intramural
3 Contacts endometrium; 100% intramural
4 Intramural
5 Subserosal ≥ 50% intramural
6 Subserosal < 50% intramural
7 Subserosal pedunculated
8 Other (specify e.g. cervical, parasitic)
Two numbers are listed separated by a hyphen. By convention,
the first refers to the relationship with the endometrium while
the second refers to the relationship to the serosa.
One example is below
2-5 Submusocal and subserosal, each with less
than half the diameter in the endometrial
and peritoneal cavities, respectively.
management of fibroids to exclude other possible causes.15
In the postmenopausal woman presenting with new
onset of pain and/or bleeding in new or existing fibroids,
leiomyosarcoma should be considered.18
Fibroids and Fertility
A new SOGC guideline on the management of uterine
fibroids in women with otherwise unexplained infertility
will be published in the spring of 2015.19
Fibroids in Pregnancy
Estimates of the prevalence of fibroids in pregnancy vary
depending on the quality of the ultrasound study and
the race and age of the women being studied. A recent
ultrasound study found the prevalence to be 18% in
African-American women, 8% in white women, and 10%
in Hispanic women.20
Most ultrasound studies found that fibroids remain the
same size or become smaller during pregnancy.21–23 In a
2011 report, 171 pregnant women with fibroids were
followed by serial ultrasound. Postpartum, 36% of women
had no identifiable fibroid and 79% of remaining fibroids
had decreased in size.24 One study reported an increase in
myoma size during pregnancy.25
Several large retrospective studies of ultrasounds and
medical records of pregnant women have reported on
the impact of fibroids on pregnancy outcomes.26–30 A
2008 meta-analysis found an overall increased risk of
malpresentation (OR 2.9; 95% CI 2.6 to 3.2), Caesarean
delivery (OR 3.7; 95% CI 3.5 to 3.9), and preterm delivery

(OR 1.5; 95% CI 1.3 to 1.7).31
 In 2010, a study including
72 000 pregnancies reported significant differences in odds
ratios for placenta previa, abruption, premature rupture of
membranes, preterm birth < 34 weeks, and intrauterine
fetal death, but the differences were all < 2%, which would
not be considered clinically relevant.32 It would seem that
women with fibroids, especially large ones, merit close
obstetrical follow-up but are likely to have a good outcome.
Traditional teaching has been that myomectomy, other
than for symptomatic pedunculated fibroids, should not be
performed in pregnant women because of the increased risk
of uncontrolled bleeding. However, a number of case series
report good outcomes after myomectomy performed during
pregnancy or at the time of Caesarian section, therefore it
can be considered as an option if clinically necessary.33–36
Concerns about Malignancy
Leiomyosarcomas
In clinical practice, the mere finding of pelvic tumours in
symptomatic or asymptomatic women may raise the concern
of malignancy in both patients and health care providers.
In a review of 6815 patients who underwent myomectomy
between 1950 and 1993, only 18 patients (0.26%) had
leiomyosarcomas. In the subpopulation of women whose
masses had grown rapidly, the prevalence was the same at
0.27%.37 Based on this evidence, rapid growth of a fibroid
does not seem to be a predictor of leiomyosarcoma.
However postmenopausal growth or onset of symptoms
should carry a higher index of suspicion for malignancy.
Other case series have estimated the incidence of
leiomyosarcoma at 0.22% to 0.49%, although in women
in their 6th decade it may rise to 1% of hysterectomy
specimens.37,38 Most recent reviews are consistent with
older studies and estimate that in women undergoing
surgery for fibroids approximately 1 in 400 (0.25%) is at
risk of having a leiomyosarcoma.39
Although incidental uterine leiomyosarcomas have been
encountered during routine resectoscopic myomectomy,40
their incidence appears to be lower than that reported
following hysterectomy (0.13%).41 Whether leiomyosarcomas
develop from leiomyomas or arise independently is not
known. The challenge lies in the fact that leiomyomas and
leiomyosarcomas cannot reliably be distinguished clinically
or by any imaging technique.
Smooth muscle tumours of uncertain
malignant potential
Morphologically, there exists a spectrum of uterine
smooth muscle tumours with conventionally well-defined
histologic criteria and predictable clinical outcomes at
The Management of Uterine Leiomyomas
the 2 extremes, leiomyomas and leiomyosarcomas. The
spectrum includes several variants with unusual features
showing various combinations and permutations of 3
histologic criteria including nuclear atypia, mitotic index,
and zonal necrosis that may indicate malignancy.
Frequently, these variants pose diagnostic challenges because
they exhibit some features of malignancy but do not meet
full criteria and therefore cannot be clearly interpreted and
classified as either benign or malignant. Furthermore, the
behavioural and clinical outcomes associated with some of
these variants have not yet been elucidated. This uncertainty
frequently leads to therapeutic dilemmas, especially when
the diagnosis is made in myomectomy specimens from
women who wish to maintain or enhance their fertility.
In 2003, the World Health Organization labelled these
tumours “smooth muscle tumours of uncertain malignant
potential” (STUMP).42,43
Other malignancies
Other uterine malignancies such as cervical cancer and
endometrial cancer may be present and contribute to AUB;
these should be ruled out by appropriate evaluation and
screening.
Summary Statements
2. The presence of uterine fibroids can lead to a variety
of clinical challenges. (III)
3. Concern about possible complications related
to fibroids in pregnancy is not an indication for
myomectomy except in women who have had a
previous pregnancy with complications related to
these fibroids. (III)
4. Women who have fibroids detected in pregnancy
may require additional maternal and fetal
surveillance. (II-2)
Recommendation
1. Women with asymptomatic fibroids should be
reassured that there is no evidence to substantiate
major concern about malignancy and that
hysterectomy is not indicated. (III-D)
Evaluation
On physical examination, an enlarged, mobile uterus
(correlating to a weight of approximately 300 g or 12
weeks of pregnancy) with irregular contour is consistent
with fibroids.
Ultrasonography (transabdominal, transvaginal, contrast
sonohysterorography) is the most widely used modality
because of its availability, ease of use, and cost-effectiveness.
It is particularly helpful to assess myoma growth and the
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SOGC Clinical Practice Guideline
adnexae if these cannot be palpated separately with
confidence.44 Contrast infusion saline or gel sonography and
2D and 3D sonohysterography are very accurate diagnostic
procedures to detect submucosal lesions, all with sensitivity
and specificity of 98% to 100%.45,46 In women with large
fibroids, diagnostic imaging occasionally demonstrates
hydronephrosis, the clinical significance of which is
unknown. Complete ureteric obstruction is extremely rare.47
CT is of limited value in delineating the location of myomas
relative to the endometrium or myometrium.48 MRI is the
most accurate modality in assessing the adnexae49 and
the uterus because it provides information on the size,
location, number, and perfusion of leiomyomas as well
as the presence of other uterine pathology including
adenomyosis and/or adenomyoma.50–52
Treatment
The majority of uterine leiomyomas are asymptomatic and
will not require therapy. However, 20% to 50% are clinically
symptomatic, causing AUB, iron deficiency anemia, bulk
effects, and/or reproductive issues,53 and may require
treatment. Treatment of women with uterine leiomyomas
must be individualized, based on symptomatology, the
size and location of fibroids, age, the needs and desires of
the patient for preservation of fertility or the uterus, the
availability of therapy, and the experience of the therapist.
Symptomatic uterine fibroids may be treated medically,
surgically, or with a combination of both (Figure 2).
Expectant Management
Prospective imaging studies indicate that 3% to 7% of
untreated fibroids in premenopausal women regress over
6 months to 3 years.54,55 Most women experience shrinkage
of fibroids and relief of symptoms at menopause;
therefore, depending on the severity of their symptoms,
women who are approaching menopause may choose
to wait for the onset of menopause before deciding on
treatment. Postmenopausal hormone replacement therapy
is not contraindicated in the presence of fibroids and does
not lead to the development of new fibroids, although it
may be associated with some myoma growth, which may in
turn lead to clinical symptoms.56,57
MEDICAL MANAGEMENT
Until recently, medical management options for uterine
leiomyomas have been of limited value because of their
moderate efficacy and/or associated adverse effects. Novel
therapies at the receptor and gene levels have emerged
or are undergoing investigation and may eventually offer
better long-term management options.58
162 l FEBRUARY JOGC FÉVRIER 2015
Because estrogen upregulation of both ERs and PRs
during the follicular phase is followed by progesterone-
induced mitogenesis during the luteal phase, all hormonal
therapies to control uterine bleeding aim to regulate the
effect of these 2 gonadal steroids.
Oral Contraceptives
There is no evidence that low-dose oral contraceptives
cause benign fibroids to grow, thus uterine fibroids are
not a contraindication to their use. Oral contraceptives are
effective in reducing menstrual bleeding in the short-term
and may prevent the development of uterine fibroids.59
Progestins/Levonorgestrel Intrauterine System
Progestogens are natural or synthetic progestational
hormones which may potentially have dual actions on
fibroid growth. While the natural hormone progesterone
augments epidermal growth factor, which stimulates fibroid
growth, it also inhibits insulin-like growth factor-1, which
may inhibit growth.60 Progestogens also down-regulate both
estrogen and progesterone receptors in fibroids, which may
act as another mechanism in modulating fibroid biology and
growth.61 Both natural progesterone and synthetic progestins
cause endometrial atrophy, which has the potential to
decrease menstrual blood loss in women with fibroids.
One study concluded that the LNG-IUS significantly
reduces menstrual blood loss and uterine volume in
women with menorrhagia, with and without fibroids,
while it does not significantly reduce fibroid volume.62
Another RCT found that although the rate of treatment
failure was similar in both groups, the LNG-IUS was more
effective in reducing menstrual blood loss than combined
oral contraceptives in women with fibroid-related
menorrhagia.59
A systematic review reported on both oral progestogens
and the LNG-IUS for the treatment of leiomyomas. The
authors found that the oral progestogen lynestrenol was
not as effective as leuprolin in reducing uterine fibroid
size at 16 weeks,63 and they concluded that evidence was
lacking to support the use of progestogens for treating
premenopausal women with uterine fibroids.64
Gonadotropin-Releasing Hormone Agonists
GnRH agonists are available in nasal spray, subcutaneous
injections, and slow-release injections. In general, fibroids
may be expected to shrink by up to 50% of their initial
volume within 3 months of therapy. However, GnRH
agonist treatment is restricted to a 3- to 6-month interval,
following which regrowth of fibroids usually occurs within
12 weeks. Prolonged use of GnRH agonists with estrogen
add-back therapy requires investigation. However, there is
 The Management of Uterine Leiomyomas

Figure 2. Algorithm for the management of uterine myomas

Uterine myomas

Asymptomatic Symptomatic

Clinical surveillance Pre-menopause Post-menopause

Enhance fertility Retain fertility Retain uterus Other Investigations:

f - Endometrial biopsy
- Imaging
- Hysteroscopy

See SOGC AUB Bulk effects Bulk effects Hysterectomy ± Hysteroscopic

Guideline19 ± AUB ± AUB BSO myomectomy
Medical therapy:
- SPRM (Ulipristal) Medical therapy: Interventional
- OC - SPRM (Ulipristal) therapy:
- Danazol - GnRH-agonist ± - UAE
- LNG-IUS add-back - MRg-FUS
- Tranexamic acid - Myolysis
- GnRH agonist ±
add-back

Surgical therapy: Surgical therapy Surgical therapy:

Myomectomy Myomectomy Myomectomy ± EA
- Hysteroscopic - Hysteroscopic - Hysteroscopic
- Laparoscopic - Laparoscopic - Laparoscopic
- Laparotomic - Laparotomic - Laparotomic

BSO: bilateral salpingo-oophorectomy; MRg-FUS: Magnetic resonance-guided focused ultrasound; OC: oral contraceptives

evidence that progestin add-back negatively impacts the
effectiveness of GnRH agonists on fibroid size.65,66
GnRH agonists are useful preoperatively to shrink fibroids
and to reduce anemia related to uterine bleeding.47,67
Gonadotropin-Releasing Hormone Antagonists
While GnRH agonists work by down-regulation and
desensitization of the GnRH receptors, GnRH antagonists
work via the classical competitive blockage mechanism.
The main advantage of using GnRH antagonists is their
lack of the initial “flare” effect seen with GnRH agonist
stimulation and supraphysiological amounts of follicle
stimulating hormone, luteinizing hormone, and estradiol,
and hence have a much shorter onset of action and
treatment period.68,69
The use of GnRH antagonists as a treatment for fibroids
requires further evaluation.
Androgens (Danazol)
Danazol is chemically related to 17-α ethinyl testosterone.
It competes with natural androgens, progesterone, and
glucocorticoids in receptor binding and acts at different
levels of the hypothalamic-pituitary-ovarian-uterine
axis. Aside from its androgenic effects, it also lowers
estrogen levels by suppressing gonadotropin secretion
at the levels of the hypothalamus and inhibits ovarian
steroidogenesis.70
Danazol has been associated with a reduction in volume
of fibroids in the order of 20% to 25%.71 Although the
use of danazol for the shrinkage of uterine fibroids has
been described in cohort studies, a systematic review did
not find any randomized trials comparing its efficacy with
placebo or other treatments.72
Although the long-term response to danazol is modest,
it may offer an advantage in reducing myoma associated
heavy menstrual bleeding.71
Aromatase Inhibitors (Letrozole)
Myometrial cultured cells overexpress aromatase P450
and synthesize sufficient estradiol to accelerate their own
cell growth. Aromatase inhibitors may serve to block the
aromatase activity and growth of leiomyomata.73

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SOGC Clinical Practice Guideline
Letrozole, an aromatase inhibitor, inhibits the conversion
of androgen into estrogen. In a systematic review, only one
trial involving 70 participants was included. Significantly
fewer women reported hot flushes in the letrozole
group than in the GnRH agonist group (0/33 vs. 26/27,
P < 0.05). Use of letrozole reduced fibroid volume by
46% and use of a GnRH agonist by 32% after 12 weeks
of treatment, although these results were not statistically
significant. The authors concluded that the evidence is
currently insufficient to support the use of aromatase
inhibitor drugs in the treatment of women with uterine
fibroids.74
Estrogen Receptor Antagonists (Fulvestrant)
The estrogen receptor antagonist fulvestrant promotes
degradation and down-regulation of estrogen receptors.75
However, fulvestrant was not as effective as the GnRH
agonist goserelin in reducing fibroid and uterine volume
and in inducing amenorrhea.76
Selective Estrogen Receptor Modulators
SERMs are nonsteroidal drugs that bind to estrogen
receptors and may act as agonists or antagonists to
produce tissue-specific effects. They are generally used for
treating and preventing recurrence of estrogen receptor
positive breast cancers. Tamoxifen has agonist properties
on the uterus, but raloxifene is the most studied SERM
for treatment of leiomyomata.77,78 Given the conflicted
and limited data regarding the use of raloxifene alone, it
is difficult to ascertain its true effect on uterine fibroids,
though it may be a useful adjunct to a GnRH agonist in
inducing fibroid shrinkage.
Selective Progesterone Receptor Modulators
Compared with the myometrium, fibroids overexpress
estrogen and progesterone receptors,79 and there is “cross-
talk” between ER and PR.80 It has been shown that
fibroids grow primarily during the secretory phase of the
menstrual cycle,81,82 and exogenous progesterone increases
mitotic activity and cellularity in fibroids.83
In a randomized trial of a GnRH analogue plus add-
back therapy with progestin alone versus progestin plus
estrogen, the authors reported that, in most instances,
the add-back progestin alone (but not the progestin plus
estrogen) negated the effects of the GnRH analogue on
fibroid volume reduction.84 Progesterone is therefore
essential for fibroid growth, and these observations have
stimulated research for the development of progesterone
antagonist and/or SPRM drugs. SPRMs are progesterone
receptor ligands that have agonist, antagonist, partial, or
mixed effects on progesterone target tissues.85
164 l FEBRUARY JOGC FÉVRIER 2015
While mifepristone is thought to have almost pure antagonistic
properties, other SPRMs such as ulipristal acetate exhibit
mixed agonist and antagonist properties. Though the exact
mechanisms of this new class of medications are still being
studied, several studies have evaluated their effectiveness in
the shrinkage of fibroids and control of menstrual bleeding
symptoms. While several other SPRMs are currently under
investigation, here we present the evidence for SPRMs that
have been studied in randomized controlled trials.
Mifepristone
Mifepristone (RU-486) is a progesterone receptor modulator
that has almost pure antagonistic properties and may directly
decrease the PR in the myometrium and leiomyoma. Though
the exact mechanism for myoma size reduction is unclear, a
2013 meta-analysis of 11 RCTs involving 780 premenopausal
women with symptomatic leiomyomas concluded that
mifepristone significantly reduced uterine and leiomyoma
volume and alleviated leioma-related symptoms. The authors
recommended 2.5 mg daily for 3 to 6 months as the optimum
treatment. There is insufficient evidence that mifepristone
treatment led to atypical endometrial hyperplasia.86
Ulipristal acetate
UPA is an SPRM that also exhibits antiproliferative effects
on leiomyoma cells and the endometrium.87 One RCT that
investigated the effects of UPA versus placebo before
surgical treatment of symptomatic fibroids showed a
reduction in myoma volume with 13 weeks of 5 mg and
10 mg of UPA of 21.2% and 12.3%, respectively, while
the placebo group had a median 3% growth of myoma
volume (P < 0.01).88 Patients also experienced significant
decreased uterine bleeding symptoms with treatment.
In a parallel RCT, UPA appeared to be no less effective than
leuprolide acetate in controlling heavy menstrual bleeding:
90% of the 5 mg group and 98% of the 10 mg group
experienced controlled bleeding symptoms versus 89% of
the leuprolide acetate group. Median time to amenorrhea
was 7 days, 5 days, and 21 days for the 5 mg, 10 mg, and
leuprolide acetate groups, respectively (P < 0.001 for
10 mg vs. leuprolide acetate). However, in terms of uterine
volumes, the 47% reduction in the leuprolide acetate group
was significantly greater than the reductions of 20% in the
5 mg group and 22% in the 10 mg group. No differences
were seen in hemoglobin at the end of the treatment
period. Vasomotor symptoms were experienced in 11% of
the 5 mg and 10% of the 10 mg groups versus 40% of the
leuprolide acetate group (P < 0.001).89
Novel PRM-associated endometrial changes have been
noticed with the SPRM class of drugs and appear to
be benign and fully reversible.89 These changes may be

confused with endometrial hyperplasia by a pathologist
who is not informed that the patient received UPA
treatment or who has not been updated on the potential
effect of UPA on the endometrium. It is important that
the pathologist be aware of the use and effects of UPA.
A recent study investigated the efficacy and safety of UPA
for long-term treatment of symptomatic uterine fibroids
by repeated intermittent 3-month open-label UPA courses
(10 mg daily), each followed by randomized double-
blind 10-day courses of NETA 10 mg daily or placebo.
The study concluded that NETA did not affect fibroid
volume or endometrial histology, and repeated 3-month
UPA courses effectively and safely controlled bleeding and
shrunk fibroids in patients with symptomatic fibroids.90
Fibroid volume reduction in patients receiving UPA also
appears to be maintained in the majority of patients for 6
months after the end of treatment.88
Summary Statements
5. Effective medical treatments for women with
abnormal uterine bleeding associated with uterine
fibroids include the levonorgestrel intrauterine
system, (I) gonadotropin-releasing hormone
analogues, (I) selective progesterone receptor
modulators, (I) oral contraceptives, (II-2)
progestins, (II-2) and danazol. (II-2)
6. Effective medical treatments for women with
bulk symptoms associated with fibroids include
selective progesterone receptor modulators and
gonadotropin-releasing hormone analogues. (I)
Recommendation
2. Treatment of women with uterine leiomyomas must
be individualized based on symptomatology, size and
location of fibroids, age, need and desire of the patient
to preserve fertility or the uterus, the availability of
therapy, and the experience of the therapist. (III-B)
SURGICAL THERAPIES
Hysterectomy
In women who have completed childbearing, hysterectomy
is indicated as a permanent solution for symptomatic
leiomyomas. The only indications for hysterectomy in
a woman with completely asymptomatic fibroids are
enlarging fibroids after menopause without HRT, which
raises concerns of leiomyosarcoma, even though it remains
very rare. 91,92 Women with asymptomatic fibroids should be
reassured that there is no evidence to substantiate concern
about malignancy, and that hysterectomy is not indicated.
Hysterectomy need not be recommended as a prophylaxis
The Management of Uterine Leiomyomas
against increased operative morbidity associated with
future growth.93
Type of hysterectomy
The choice and type of hysterectomy, whether it is
performed by abdominal, laparoscopic, or vaginal route,
should be based on surgeon’s training, experience, and
comfort and on clinical practice guidelines.93 The least
invasive approach feasible should be used.
The advantages of abdominal supracervical or total
hysterectomy are questionable, as randomized trials have
demonstrated no differences in sexual and urinary function
outcomes in women treated with the 2 procedures.
However, there may be less blood loss and complications
associated with supracervical hysterectomy.94–96
Summary Statement
7. Hysterectomy is the most effective treatment for
symptomatic uterine fibroids. (III)
Myomectomy
Myomectomy is an alternative to hysterectomy for women
who wish to retain their uterus, regardless of their fertility
desire. Removal of fibroids should be considered if they
are thought to be associated with heavy mentrual bleeding,
pelvic pain and/or pressure symptoms, and in some cases
reproductive issues.19
Although myomectomy allows preservation of the uterus,
there is a higher risk of blood loss and greater operative time
with myomectomy than with hysterectomy, athough the risk
of ureteric injury may be decreased with myomectomy.
Fibroids have a 15% recurrence rate and 10% of women
undergoing a myomectomy will eventually require
hysterectomy within 5 to 10 years.97 Risk of recurrence is
associated with age, preoperative number of fibroids, uterine
size, associated disease, and childbirth after myomectomy.98
Five years following laparoscopic myomectomy, the
cumulative probability of recurrence (new or unremoved
fibroids) in women who subsequently gave birth was 42%.
In those who did not give birth, it was 55%.99
Women should be counselled about the risks of requiring
a hysterectomy at the time of a planned myomectomy.
This would depend on the intraoperative findings and the
course of the surgery. Hysterectomy remains the treatment
of choice for the vast majority of women who require a
surgical solution.93
Surgical planning
Myomectomy can be performed according to the number,
size, and location of fibroids by laparotomy, mini-
laparotomy, laparoscopy, hysteroscopy, or a combination of
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these.100 Surgical planning should be based on an accurate
mapping of the location, size, and number of fibroids with
preoperative imaging. It is particularly important to identify
the presence and size of the submucosal component to
myomas as this may affect the approach taken.
Summary Statement
8. Myomectomy is an option for women who wish to
preserve their uterus or enhance fertility, but carries
the risk of requiring further intervention. (II-2)
Hysteroscopic myomectomy
An AAGL practice guideline for the diagnosis and manage­
ment of submucous leiomyomas was published in 2012.101
Hysteroscopic myomectomy has been shown to be effective
for treatment of AUB in 5 series involving 1422 women.
Failure rates ranged from 14.5% to 30% at 3 to 4 years’
follow-up.102 It should be considered as first-line conservative
surgical therapy for the management of symptomatic
intracavitary fibroids. In general, submucous myomas (types
0, I, and II) up to 4 to 5 cm in diameter can be removed
hysteroscopically by experienced surgeons. Type II myomas
are more likely to require a 2-staged procedure than types 0
and I because of the risk of excessive fluid absorption and
uterine perforation, and caution should be used particularly
with those with less than 5 mm thickness between the
fibroid and the uterine serosa.103,104
Myomectomy plus endometrial ablation
When the main symptom is heavy menstrual bleeding,
consideration should be given to concomittant EA at
the time of transcervical resection of myoma when
preservation of fertility is not desired. A cohort study
showed a higher success rate in controlling bleeding when
ablation was added to myomectomy.105
In selecting patients for transcervical resection of myoma,
it is important to consider other factors that increase the
risk of needing subsequent surgery. Women in whom
myomectomy results in a normal uterus without residual
myomas are at a low risk of requiring further treatment.
Predictors of an increased risk for additional treatment
include the presence of multiple myomas, large intramural
or subserous myomas, adenomyosis, and young age at the
time of treatment.106–108
Perforation of the uterus can occur with uterine sounding,
dilation, or use of the resectoscope. The preoperative use
of laminaria or misoprostol decreases the force needed
for cervical dilation and reduces the risk of perforation.
If perforation occurs with mechanical instruments and
no visceral injury is suspected the patient can be observed
expectantly. Laparoscopy should be considered if there is
166 l FEBRUARY JOGC FÉVRIER 2015
a large defect or heavy bleeding. If perforation occurs with
an activated electrode, until proven otherwise a visceral
or vascular injury should be assumed, and laparoscopy or
laparotomy is recommended.109,110
Excessive fluid absorption is another potential risk.
An AAGL practice guideline for the management of
hysteroscopic distending media was published in 2013.111
The use of the lowest distention pressure necessary for
good visualization and the careful selection of the safest
distending medium will lower the risks and sequelae of
excessive fluid absorption.110
Burns to the vulva, vagina, and cervix from stray electrical
current during resectoscopic procedures have been
documented.112–114
Laparoscopic myomectomy
The benefits of the laparoscopic approach are well
known and have been found superior to laparotomic
myomectomy in terms of less blood loss, diminished
postoperative pain, fewer overall complications, faster
recovery, and significant cosmetic advantage.115–118
However, laparoscopic myomectomy usually takes
longer to accomplish and requires extra training, surgical
expertise, and specialized equipment. The size or the
number of fibroids that can be removed by laparoscopy
seem to be limited only by the surgeon’s experience and
technique.119 Multilayer suturing may be challenging, as
may the identification and excision of smaller fibroids.
Laparoscopic removal of larger fibroids in more difficult
locations such as in the lower segment or at the cervical
junction may present more risk of complications such as
profuse bleeding; in those cases an open approach may
be preferable. Consideration should also be given to the
prolonged operative time required with the laparoscopic
approach when faced with cases of very large (> 10 cm)
or multiple leiomyomas; in these cases a myomectomy by
laparotomy may be more appropriate.
Injuries can occur with laparoscopic entry, and their
occurrence should be minimized by following good
surgical principles and the recommendations in the SOGC
clinical practice guideline on laparoscopic entry.120 A
prospective study reported that the short-term morbidity
of laparoscopic myomectomy was similar to that of
laparoscopic hysterectomy.121
Uterine scar integrity and rupture following laparoscopic
myomectomy have not been fully evaluated. Uterine
rupture during subsequent pregnancy seems to be a
rare event and its possibility should not systematically
preclude a trial of vaginal delivery.122–124 However,

because of the relatively poor quality of available
evidence, close follow-up should be exercised in all cases.
Uterine rupture during pregnancy after myomectomy has
been reported to possibly be linked to the absence of
multilayer closure in cases of deep intramural leiomyoma
or to the excessive use of electrosurgical energy.125,126
Some indirect evidence based on MRI assessment of
myometrial repair after Caesarian section suggests that
a waiting period of 6 months between myomectomy and
subsequent pregnancy would allow for optimal tissue
repair of the myometrium.127
A meta-analysis of 6 randomized controlled trials from
1996 to 2007 concluded that rates of major complications,
pregnancy rates and outcomes, and myoma recurrence
in laparoscopic and laparotomic myomectomy were
comparable.115 Two RCTs on laparoscopic versus
laparotomic myomectomy reported pregnancy rates of
54% and 57%, respectively.128,129
Mini-laparotomy
Mini-laparotomy, used as an alternative to laparoscopy,
has the proposed advantage of easier suturing of the
myometrium while providing a less invasive approach
than conventional laparotomy. A randomized study of
laparoscopic versus mini-laparotomic myomectomy
reported lower decline in hemoglobin, reduced
postoperative ileus and pain, and shorter hospitalization in
the laparoscopy group.117
Mini-laparotomy can also be used in laparoscopically
assisted mini-laparotomy. In one study, 51 women were
randomized to open myomectomy, mini-laparotomy, or
laparoscopically-assisted mini-laparotomy. The latter 2
approaches were associated with decreased postoperative
pain and less blood loss than myomectomy by laparotomy.100
In another prospective study of 116 patients, a shorter
uterine incision was found in the laparoscopically assisted
myomectomy, but the estimated blood loss was greater.
Complications and postoperative return to normal
activities were comparable between the groups.130
Robotic assisted laparoscopy
Robotic assisted gynaecological surgery has increased
exponentially in popularity in the last decade. Up to 9.5%
of hysterectomies were done with the assistance of the
robot in a retrospective U.S. cohort of 264 758 cases.131
However, robotic assisted myomectomy was associated
in one study with greater blood loss than standard
laparoscopic myomectomy.132 This, along with other
well-designed studies that consistently show a longer
operative time,133 prompted the AAGL to state that at
this time robotic surgery offers no significant advantage
The Management of Uterine Leiomyomas
in benign gynaecological surgery and is more costly than
conventional laparoscopic surgery.134
Specimen morcellation
Because laparoscopic hysterectomy and myomectomy often
requires morcellation of the specimen, complications related
to this step may occur, including vascular or visceral trauma
with the use of a mechanical rotating blade.135 Furthermore,
morcellation can lead to dissemination of leiomyoma
chips leading to parasitic leiomyomas (leiomyomatosis) or
dissemination of incidental leiomyosarcoma.136–144
The currently available evidence indicates that one in 400
women undergoing surgery for fibroids is at risk of having
a leimomyosarcoma.39 According to the American Cancer
Society’s surveillance, epidemiology, and end results data,
5-year survival for leiomyosarcoma is 60% for stage I, 35%
for stage II, 22% for stage III, and 15% for stage IV.145
An increased rate of recurrence and lower rate of survival
following morcellation of a uterine sarcoma has been
reported in several studies, implying that morcellation
results in the upstaging of the disease. In cases of
myomectomy, the initial steps of the procedure, including
uterine incision and myoma manipulation and enucleation,
are likely to spread and upstage the disease prior to myoma
extraction by any method of morcellation.
These findings reinforce the need for careful preoperative
assessment of patients and consideration of using enclosed
morcellation techniques if feasible. For laparoscopic
morcellation, spillage may be minimized by placing the
specimen in a bag and using the mechanical morcellator
inside the bag. However use of a bag may limit visualization
and has not been well studied. For larger specimens, a mini-
laparotomy with or without use of self-retaining retractor
can be performed and the specimen be morcellated
mechanically or with a scalpel blade within a bag. If the
specimen is delivered vaginally and requires morcellation,
again a bag can be used to enclose it to mimimize spillage.
In light of concerns over morcellation of unsuspected
leiomyosarcomas, the FDA issued a warning about
laparoscopic power morcellation in April 2014. This
prompted Health Canada (May 2014) to make the following
recommendations to health-care professionals treating
women with uterine fibroids146:
•• Recognize the prevalence of unsuspected uterine
sarcoma in patients under consideration for
hysterectomy or myomectomy for the treatment of
uterine fibroids.
•• Consider the treatment alternatives for women with
symptomatic uterine fibroids and review these options
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Table 2. Summary of recommendations regarding uterine morcellation

Society of Gynecologic Oncology (December 2013)147
The use of power morcellator is generally contraindicated in the presence of documented or highly suspected malignancy,
and it may be inadvisable in premalignant conditions or risk-reducing surgery.
No reliable method is currently available to differentiate benign from malignant leiomyomas (leiomyosarcomas or
endometrial stromal sarcomas) before they are removed. Furthermore, these diseases offer an extremely poor prognosis
even when specimens are removed intact.
Patients and doctors should communicate about the risks, benefits, and alternatives of all procedures so that a patient is
able to make an informed and voluntary decision about accepting or declining medical care.

American Association of Gynecologic Laparoscopists (April 2014)148

Most women with uterine cancer can be diagnosed prior to surgical intervention.
Between 1 in 400 and 1 in 1000 women who undergo hysterectomy for presumed benign uterine myomas will be
diagnosed with uterine leiomyosarcoma.
The prognosis of patients with uterine leiomyosarcoma is universally poor and may be worsened in the setting of power
morcellation.

American College of Obstetricians and Gynecologists (May 2014)149

Recommend comprehensive patient counselling and including the following points in consent:
There is a risk of inadvertent uterine leiomyosarcoma diagnosis when a myomectomy/hysterectomy is being performed for
a benign leiomyoma (2:1000)
Morcellation will increase peritoneal dissemination if uterine leiomyosarcoma is diagnosed and may worsen patients’
prognosis.
Minimally invasive surgical approach does decrease perioperative risks to the patient.

U.S. Food and Drug Administration (April 2014)150

1 in 350 women undergoing hysterectomy or myomectomy for the treatment of fibroids is found to have an unsuspected
uterine cancer.
Laparoscopic power morcellation poses a risk of spreading unsuspected cancerous tissue, notably uterine sarcomas,
beyond the uterus.
The FDA discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids

with each prospective surgical patient. Apart from a
laparoscopic approach, alternative surgical procedures
exist that do not require electric morcellation and
potential tissue spread to the peritoneal cavity. Also,
some surgeons and centres may recommend closed
morcellation in a bag as a way to reduce the risk of
inadvertent spread of uterine tissue.
•• Be aware and inform patients that laparoscopic electric
morcellation of unsuspected uterine sarcoma during
hysterectomy or myomectomy may disseminate the
disease and negatively impact prognosis.
Numerous societies have responded to the FDA warning
with very thorough reviews and discussion of the issue
(Table 2).147–150
Recommendations
3. In women who do not wish to preserve fertility and/
or their uterus and who have been counselled
regarding the alternatives and risks, hysterectomy
by the least invasive approach possible may be
offered as the definitive treatment for symptomatic
uterine fibroids and is associated with a high level of
satisfaction. (II-2A)
4. Hysteroscopic myomectomy should be considered first-
line conservative surgical therapy for the management
of symptomatic intracavitary fibroids. (II-3A)
5. Surgical planning for myomectomy should be based
on mapping the location, size, and number of
fibroids with the help of appropriate imaging. (III-A)
6. When morcellation is necessary to remove the
specimen, the patient should be informed about
possible risks and complications, including the fact
that in rare cases fibroid(s) may contain unexpected
malignancy and that laparoscopic power morcellation
may spread the cancer, potentially worsening their
prognosis. (III-B)

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Pre-operative Evaluation and Adjuncts
Prior to proceeding with surgery for fibroids, appropriate
evaluation and patient preparation, including correction
of anemia and shrinkage of fibroid and uterine volume,
are of paramount importance since preoperative anemia
and uterine size can have a significant bearing on surgical
outcomes. A recent large study reported that preoperative
anemia, even to a mild degree, is independently associated
with an increased risk of 30-day morbidity and mortality in
patients undergoing major non-cardiac surgery.151
For preoperative treatment, a variety of pharmacological
agents have been shown to be safe and effective. Iron
should be provided in the presence of anemia together
with preoperatve adjuncts to correct the anemia.
GnRH agonists
A Cochrane review showed significant improvement with
GnRH agonist over placebo or no treatment in preoperative
hemoglobin and hematocrit and in reduction of uterine
and myoma volumes.152 Compared with no treatment prior
to hysterectomy, GnRH agonists reduce intraoperative
bleeding and operative time, increase postoperative
hemoglobin and haematocrit values, and decrease
postoperative complications and length of hospital stay.
They also increase the proportion of hysterectomies
performed vaginally rather than abdominally and decrease
the proportion of vertical incisions compared with no
treatment.152
In a 2001 systematic review and meta-analysis, when GnRH
agonists were used prior to myomectomy, intraoperative
bleeding and rates of vertical incisions were also reduced,
while postoperative hemoglobin was slightly increased.
However, patients treated with GnRH agonists were more
likely to have recurrence of fibroids at 6 months after
myomectomy compared to no treatment. No differences
were seen in rates of postoperative complications. No
differences were seen in rates of blood transfusion for
either type of surgery.153 A 2011 systematic review of
GnRH-a showed no reduction in operative time but did
show decreased introperative blood loss.154 However there
is controversy over the ability to dissect myomas from
myometrium after exposure to GnRH agonist.155
A double-blind, placebo-controlled trial of GnRH agonist
prior to hysteroscopic myomectomy found no differences
in the number of complete fibroid resections, operative
times, or amounts of fluid absorbed.156
Ulipristal acetate
The 2 RCTs mentioned previously have shown the
effectiveness of 3 months’ treatment to correct anemia
and reduce uterine fibroid size.89,90 There were no surgical
The Management of Uterine Leiomyomas
parameters reported in these studies and surgical experience
is variable.
Intraoperative Adjuncts
A number of intraoperative adjuncts have been used in an
effort to reduce blood loss and improve surgical outcomes
in leiomyoma surgery.
Misoprostol
Misoprostol is a prostaglandin E1 analogue which
reduces uterine blood flow, increases myometrial
contractions, and has potential to reduce blood loss
during uterine surgery.156 The evidence for misoprostol
as an adjunct for hysterectomy is limited and conflicting.
In one randomized trial, no benefit was observed in the
use of misoprostol alone for abdominal hysterectomy,
but misoprostol 400 μg by rectum combined with
intravenous oxytocin (10 U/hour) in women undergoing
laparoscopically assisted vaginal hysterectomy was found
to significantly improve operative outcomes compared
with placebo.156
Placebo-controlled randomized studies have shown that
a single dose of misoprostol 400 μg given vaginally 1
hour prior 157 or rectally 30 minutes prior158 to abdominal
myomectomy resulted in a statistically significant reduction
in operative time,157 operative blood loss, postoperative
hemoglobin drop, and need for postoperative blood
transfusion.157,158 No differences were observed in length
of hospital stay.157
The role of misoprostol for cervical priming before
operative hysteroscopy has also been reported, though not
all patients in this study had fibroids as the indication for
surgery. The authors found that the misoprostol group
had significantly smaller initial dilation estimated by Hegar
dilator, less need for surgical dilation, shorter time for
cervical dilation to Hegar 9, shorter operative time, and
fewer occurrences of cervical lacerations than the placebo
group. Though not statistically significant, there were
also fewer instances of false passages (1.4% vs 6.3%) and
perforations (0% vs. 2.5%) observed.159
Oxytocin
While recent evidence suggests the presence of oxytocin
receptors in uterine myomas,160 the evidence for its use as
an intraoperative adjunct is somewhat conflicting.
One study of women undergoing laparoscopically assisted
vaginal hysterectomy indicated reduced blood loss and
transfusion rates with intraoperative 20 U of oxytocin
in 1000 mL of saline solution running at 40 mu/min
compared to saline placebo. No differences were seen in
postoperative complications and length of stay.161
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SOGC Clinical Practice Guideline
For myomectomy, a systematic review of 2 randomized
trials that compared intraoperative oxytocin against
placebo for operative outcomes at myomectomy did not
suggest a benefit for operative bleeding, although the
pooled numbers may be difficult to interpret due to the
significant heterogeneity between the 2 trials.162
Vasopressin
Vasopressin is a naturally occurring hormone that can
cause vascular spasm and uterine muscle contraction, and
hence has the potential to prevent bleeding during uterine
surgery. As there have been several reports of cardiovascular
collapse following intra-myometrial injection of vasopressin,
caution should be taken to ensure proper dilution and clean
communication with the anaesthesiologist.163
One randomized trial of women undergoing abdominal
hysterectomy for uterine fibroids found that injection of 5 mL
of 10 U in 10 mL of normal saline 1 cm medial to the uterine
vessels bilaterally decreased total blood loss by approximately
40%. No differences were seen in postoperative hemoglobin,
need for transfusion, or operative time.164
In a systematic review of interventions to reduce hemorrhage
during myomectomy,162 2 trials comparing vasopressin to
placebo showed a pooled mean difference of 298.7 mL in
blood loss.165,166 No statistical differences were seen in need
for blood transfusion, duration of surgery, duration of
hospital stay, postoperative adhesions, or pregnancy rates at
1 year after myomectomy.
Two trials compared vasopressin to tourniquets in
myomectomy. In one trial, dilute vasopressin (20 units in
20 mL saline injected prior to uterine incision) had effects
comparable to mechanical vascular occlusion (Penrose drain
tourniquet and vascular clamps at the infundibulopelvic
ligament) with respect to blood loss, postoperative
morbidity, and transfusion requirements.166 In contrast,
another study reported less blood loss in the vasopressin
(20 U in 20 mL) group than in the tourniquet group
(512.7 ± 400 mL) (P = 0.036). However, no statistically
significant differences were seen in the hemoglobin drop,
number of transfusions, intraoperative blood pressure, or
highest postoperative pulse and temperature.166
A recent study compared intraoperative bleeding during
laparoscopic myomectomy using dilute vasopressin (6 U in
20 mL) with Roeder knot loop ligation at the base of the
fibroid with use of vasopressin alone and with placebo.
Blood loss in the placebo (mean ± SD, 363.7 ± 147.8 mL)
and vasopressin only (224.4 ± 131.2 mL) groups was
significantly reduced by the addition of loop ligation at the
base of the myoma (58.7 ± 27.5 mL).167
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Bupivacaine and epinephrine
In one study on laparoscopic myomectomy, the use of
bupivacaine (50 mL of 0.25%) and epinephrine (0.5 mL
of 1 mg/mL) was significantly more effective than placebo
in reducing intraoperative bleeding, total operative time,
myoma enucleation time, and subjective surgical difficulty
as measured on a 1 to 10 visual analogue scale. Analgesic
requirement was also reduced in the bupivacaine group
(P < 0.05 for all comparisons). No differences in blood
pressure or heart rate were observed.168
Antifibrinolytics
Tranexamic acid is a synthetic derivative of lysine with
antifibrinolytic activity that has been used to reduce blood
loss and need for blood transfusion in surgical procedures.169
However, only 1 trial has studied its effect during abdominal
myomectomy using intravenous tranexamic acid (10 mg/kg
patient body weight to a maximum of 1 g) given 15
minutes before skin incision versus placebo. The trial did
show average reduced blood loss of 243 mL, but did not
reach the authors’ level of clinical significance (250 mL).170
Gelatin-thrombin matrix
Gelatin-thrombin matrix is a hemostatic sealant with bovine
derived gelatin and thrombin components. In contrast to
fibrin glue, gelatin-thrombin matrix is hydrophilic and
adheres well to wet tissue. When applied to tissue, the large
concentration of thrombin and gelatin can result in rapid
hemostasis, which may be useful in gynaecologic surgery.162
In one randomized study, application of the gelatin-
thrombin matrix to the site of uterine bleeding resulted
in less intraoperative and postoperative blood loss than
no application during abdominal myomectomy.162 Five of
25 (20%) patients in the control group required a blood
transfusion, while none in the treatment group were
transfused (P < 0.001).
Intraoperative Uterine Artery Occlusion
Another option is to perform UAO by laparoscopy at
the time of myomectomy, although the benefit seems
controversial. In one study comparing laparoscopic
myomectomy with or without UAO, blood loss did not
differ significantly and operating time was slightly longer
when UAO was performed.171 In another study, the mean
operative time was significantly longer (107 minutes vs. 93
minutes; P = 0.03), but there was less intraoperative blood
loss (84 mL vs. 137 mL; P < 0.001) in the UAO group,
with no blood transfusions.172
Peri-cervical tourniquet
In 2 trials, occlusion of the uterine artery with or without
occlusion of the ovarian arteries significantly reduced

blood loss during myomectomy and the need for blood
transfusion.173,174
Anti-adhesion barriers
After the completion of myomectomy, application of anti-
adhesion barriers has been proposed and there is evidence
of significant reduction in adhesion formation with some
of them.175–177 However, none of these adjuncts has
demonstrated an improvement in fertility and pregnancy
outcomes.
Recommendations
7. Anemia should be corrected prior to proceeding
with elective surgery. (II-2A). Selective progesterone
receptor modulators and gonadotropin-releasing
hormone analogues are effective at correcting
anemia and should be considered preoperatively in
anemic patients. (I-A)
8. Use of vasopressin, bupivacaine and epinephrine,
misoprostol, peri-cervical tourniquet, or gelatin-
thrombin matrix reduce blood loss at myomectomy
and should be considered. (I-A)
OTHER CONSERVATIVE TREATMENTS
Uterine Artery Embolization
An SOGC clinical practice guideline on UAE has
been published,178 and an up-to-date-review of UAE
to treat uterine fibroids is included in the upcoming
SOGC guideline.19 UAE is a procedure carried out by
interventional radiologists and consists of injecting an
occluding agent into one or both uterine arteries. First
described in 1995, it has become one of the most common
alternative conservative therapies offered to women with
sympotomatic uterine fibroids. The procedure is minimally
invasive and performed with the patient awake, but it is
associated with significant immediate post-procedure
discomfort, although recovery and return to function are
rapid. Very large uteri (over 20 weeks) may not have a
clinically significant response. Single submucosal fibroids
or subserosal fibroids may respond better to surgery than
UAE.
Though successful pregnancies have been reported
following UAE,179 an RCT comparing UAE to myomectomy
showed that pregnancy rates were lower and miscarriage
rates higher following UAE.180 This option is still best
reserved for women who do not desire future pregnancy.
A 2013 review and meta-analysis reported on
complications and re-intervention of UAE for
symptomatic uterine fibroids. Common complications
were vaginal discharge and fever (4.0%), bilateral UAE
The Management of Uterine Leiomyomas
failure (4.0%), and postembolization syndrome (2.9%).
The study concluded that overall, UAE has a significantly
lower rate of major complications relative to surgery, but
it comes at the cost of increased risk of re-intervention
in the future.181
Educating patients about the rate and types of
complications of UAE versus surgery, as well as the
potential for reintervention, should help the patient and
clinician come to a reasoned decision.
Recommendation
9. Uterine artery occlusion by embolization or
surgical methods may be offered to selected
women with symptomatic uterine fibroids who
wish to preserve their uterus. Women choosing
uterine artery occlusion for the treatment of
fibroids should be counselled regarding possible
risks, including the likelihood that fecundity and
pregnancy outcomes. (II-3A)
Focused Energy Delivery Systems
A number of focused energy delivery systems have been
tested in the past decade including those based upon
radiofrequency electricity, supercooled cryoprobes, and
most recently, MRg-FUS or high frequency ultrasound
guided transcutaneous focused ultrasound ablation.182–185
A major disadvantage of all systems and techniques used
to desiccate or ablate fibroids may be that they treat one
fibroid at a time and they target the centre of fibroids,
while fibroids have been shown to grow mostly from their
periphery.186
These technologies are relatively new and although many
are promising, they often lack long-term data, which
interferes with our ability to present all risks and benefits
with assurance. Ongoing research and data collection are
required to assess the relative merit of newer options as
the technology continues to expand.
MR-guided focused ultrasound
The ExAblate 2000 (InSightec Inc., Haifa, Israel) was the
first clinical MRg-FUS system approved by the FDA for
treating uterine fibroids. Case series for MRg-FUS ranging
from 51 to 359 patients have been published and short-
term efficacy is adequate, but complications such as skin
burns have occurred in up to 7% of patients and at least
one bowel perforation was reported.182,187,188 Disadvantages
of the MRg-FUS system include high exclusion rate,
requirement of an MR machine, prolonged time (minutes
to several hours), treatment of 1 fibroid at a time, and
ablation of fibroids centrally, while fibroids seem to grow
peripherally.
FEBRUARY JOGC FÉVRIER 2015 l 171
SOGC Clinical Practice Guideline
Radiofrequency myolysis
A new development in laparoscopic myolysis involves
delivering of RF energy to myomas under ultrasonic
guidance in an attempt to dessicate them directly. The
Acessa RFVTA system by Halt Medical has been approved
for fibroid treatment in Canada. Mapping of myomas is
performed by laparoscopic and ultrasound visualization.
When a myoma is targeted for ablation, the RF probe
is inserted percutaneously under laparoscopic guidance
through a 2-mm skin incision. A recent multicentre trial
concluded that RFVTA of myomas is well tolerated
and results in rapid recovery, high patient satisfaction,
improved quality of life, and effective symptom relief.189
Total mean fibroid volume was reduced by 45.1% and
mean blood loss by 38.3% at 12 months post-procedure.
Disadvantages of the Halt System include the requirement
of laparoscopy and concomitant use of ultrasound,
additional percutaneous skin incision(s), its treatment of
1 fibroid at a time (< 8 cm diameter), and its ablation of
fibroids centrally while fibroids grow peripherally.
Summary Statements
  9. Of the conservative interventional treatments
currently available, uterine artery embolization has
the longest track record and has been shown to be
effective in properly selected patients. (II-3)
10. Newer focused energy delivery methods are
promising but lack long-term data. (III)
SPECIAL CONSIDERATIONS
Acute Uterine Bleeding
Acute uterine bleeding unrelated to pregnancy has been
defined as that which is sufficient in volume, in the opinion
of the treating clinician, to require urgent or emergent
intervention.190 Women with fibroids may present with
acute intraperitoneal or vaginal hemorrhage, which can
become life-threatening on rare occasions. Since acute
uterine bleeding may or may not be associated with
leiomyomas, the approach to investigation and treatment
should be the same.45
Endometrial biopsy and sonographic and hysteroscopic
evaluation of the uterine cavity may be limited because of
patient instability, excessive bleeding, and/or blood clots.
Although the evidence is very limited, after resuscitation
is initiated and other causes of bleeding are ruled out by
history, physical examination, and preliminary imaging, the
usual approach used for acute uterine bleeding should be
for uterine hemorrhage associated with fibroids.17,191,192
Only a few treatments used for acute bleeding have been
studied in the context of uterine fibroids.
172 l FEBRUARY JOGC FÉVRIER 2015
Tranexamic acid, 1 g intravenously over 10 minutes
or orally, 3 times daily for 5 to 7 days, has also been
shown to be relatively effective when used to treat heavy
menstrual bleeding in patients with fibroids.193–195 There is
no evidence that tranexamic acid increases the incidence
of thromboembolic disease, even when used in women
at high risk. The risk of thromboembolism is less than
1%.196,197
Of all the hormonal options available for women with
fibroids, ulipristal acetate has the most rapid documented
onset of action and control of bleeding, with 80% of
women achieving a pictorial blood assessment chart score
< 75 within 7 days. However in the published studies, the
treatment was initiated at onset of regular menses, and the
results may not be applicable to intermenstrual bleeding or
acute hemorrhage.198
Placement of an intrauterine Foley catheter has been
described as a method to temporize bleeding until
hormonal/medical therapies can take effect. The Foley
balloon is left inflated for 1 to 48 hours depending on a
number of factors, including the suspected cause of the
bleeding.199,200
Occasionally, fibroids are found prolapsing through the
cervix and their removal (myoma extraction) will usually
stop the bleeding. Submucous fibroids may bleed heavily
and some may prolapse through the cervix after initiation
of GnRH agonist therapy or treatment by uterine fibroid
embolization.201
There are case reports of emergency EA to control acute
uterine bleeding. 202,203 EA and hysteroscopic myomectomy
of submucous fibroids associated with bleeding is an option,
but may be technically difficult due to poor visualization.
If the woman does not respond to conservative measures,
UAE can be performed if it is readily available. In cases
where the bleeding is severe and not responsive to any of
these measures, an emergency hysterectomy may need to
be performed.
Recommendation
10. In women who present with acute uterine
bleeding associated with uterine fibroids,
conservative management with estrogens,
selective progesterone receptor modulators,
antifibrinolytics, Foley catheter tamponade,
and/or operative hysteroscopic intervention
may be considered, but hysterectomy may
become necessary in some cases. In centres
where available, intervention by uterine artery
embolization may be considered. (III-B)

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 SOGC CLINICAL PRACTICE GUIDELINE

No. 330, December 2015

Obstetrical Anal Sphincter Injuries (OASIS):

Prevention, Recognition, and Repair
Abstract
This clinical practice guideline has been prepared by the
Urogynaecology Committee, reviewed by the Clinical Objective: To review the evidence relating to obstetrical anal
Practice–Obstetrics and the Family Physician Advisory sphincter injuries (OASIS) with respect to diagnosis, repair
committees, and approved by the Executive and Board of techniques and outcomes. To formulate recommendations as to
the Society of Obstetricians and Gynaecologists of Canada patient counselling regarding route of delivery for subsequent
pregnancy after OASIS.
PRINCIPAL AUTHORS
Options: Obstetrical care providers caring for women with OASIS
Marie-Andrée Harvey, MD, MSc, Kingston ON have the option of repairing the anal sphincter using end-to-
end or overlapping techniques. They may also be involved in
Marianne Pierce, MD, Halifax NS
counselling women with prior OASIS regarding the route of
delivery for future pregnancies.
UROGYNAECOLOGY COMMITTEE
Outcomes: The outcome measured is anal continence following
Jens-Erik Walter, MD (Chair), Montreal QC
primary OASIS repair and after subsequent childbirth.
Queena Chou, MD, London ON
Evidence: Published literature was retrieved through searches
Phaedra Diamond, MD, Toronto ON of Medline, EMBASE, and The Cochrane Library in May
Annette Epp, MD, Saskatoon SK 2011 using appropriate controlled vocabulary (e.g., anal
canal, obstetrics, obstetric labour complication, pregnancy
Roxana Geoffrion, MD, Vancouver BC complication, treatment outcome, surgery, quality of life) and
Marie-Andrée Harvey, MD, Kingston ON key words (obstetrical anal sphincter injur*, anus sphincter,
anus injury, delivery, obstetrical care, surgery, suturing method,
Annick Larochelle, MD, Montreal QC overlap, end-to-end, feces incontinence). Results were
Kenny Maslow, MD, Winnipeg MB restricted to systematic reviews, randomized control trials/
controlled clinical trials, and observational. There were no
Grace Neustaedter, RN, Calgary AB date or language restrictions. Searches were updated on a
Dante Pascali, MD, Ottawa ON regular basis and incorporated in the guideline to September
2014. Grey (unpublished) literature was identified through
Marianne Pierce, MD, Halifax NS
searching the websites of health technology assessment and
Jane Schulz, MD, Edmonton AB health technology-related agencies, clinical practice guideline
David Wilkie, MD, Vancouver BC collections, clinical trial registries, and national and international
medical specialty societies.
SPECIAL CONTRIBUTORS Values: The quality of evidence in this document was rated using the
Abdul Sultan, MB ChB, MD, FRCOG criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Ranee Thakar, MBBS, MD, MRCOG
Benefits, harms, and costs: Benefits from implementation of
Disclosure statements have been received from all contributors. these guidelines include: improved diagnosis of OASIS, optimal
functional outcomes following repair, and evidence-based
counselling of women for future childbirth.

Key words: Anal sphincter injury, anal incontinence, obstetrical

complications, sphincteroplasty, perineal laceration, overlap repair,
end-to-end repair, pregnancy.
J Obstet Gynaecol Can 2015;37(12):1131–1148

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

DECEMBER JOGC DÉCEMBRE 2015 l 1131

SOGC clinical practice guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.125
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.125
Summary Statements
  1. Obstetrical anal sphincter injuries may lead to significant
comorbidities, including anal incontinence, rectovaginal fistula,
and pain. (II-2)
  2. Obstetrical anal sphincter injuries are more commonly associated
with forceps deliveries than with vacuum-assisted vaginal
deliveries. (II-2)
  3. Obstetrical anal sphincter injuries (OASIS) repair:
a. Suture-related morbidity is similar at 6 weeks following the
use of either polyglactin 2-0 or polydioxanone 3-0 for OASIS
repairs. (I)
b. Repair of the internal anal sphincter is recommended as
women who demonstrate an internal anal sphincter defect on
postpartum ultrasound have more anal incontinence. (III)
c. Repair of the external anal sphincter should include the
fascial sheath. An overlapping technique often requires more
dissection and mobilization of the sphincter ends and is only
possible with full thickness 3b sphincter tears or greater. (III)
d. A persistent defect of the external anal sphincter remote
from delivery may increase the risk of worsening symptoms
following subsequent vaginal deliveries. (II-2)
  4. Obstetrical anal sphincter injuries are associated with an
increased risk of postpartum urinary retention. (II-2)
  5. After a successful repair of obstetrical anal sphincter injuries, most
women can safely deliver vaginally in a future pregnancy. (III)
  6. Counselling women about future delivery plans:
a. The risk of recurrence of an obstetrical anal sphincter injury at
a subsequent delivery is 4% to 8%. (II-2)
b. It was calculated that 2.3 Caesarean sections at the cost of
increased maternal risk would be required to prevent one
case of anal incontinence in a woman with prior obstetrical
anal sphincter injury. (II-2)
1132 l DECEMBER JOGC DÉCEMBRE 2015
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
Recommendations
  1. All women should be carefully examined for perineal or vaginal
tears; those with a tear that is more than superficial in depth
should have a systematic rectal examination for obstetrical anal
sphincter injury prior to repair. (II-2B)
  2. The World Health Organization classification should be used to
classify obstetrical anal sphincter injury. This distinguishes the
degree of external sphincter tear (3a: < 50% or 3b: ≥ 50%) and the
presence of internal sphincter defects (3c). A button -hole injury is
distinct and should be classified separately as such. (III-B)
  3. In women having a spontaneous vaginal delivery, the rate of
obstetrical anal sphincter injury is decreased when the obstetrical
care provider slows the fetal head at crowning. (II-2A)
  4. Episiotomy:
a. At the time of either a spontaneous vaginal or instrumental
delivery, the obstetrical care provider should follow a policy
of “restricted” episiotomy (i.e., only if indicated), rather than
“liberal” use (i.e. routine), for the prevention of obstetrical anal
sphincter injuries. (I-A)
b. If an episiotomy is deemed indicated, preference for a
mediolateral over a midline should be considered. (II-2B) The
optimal cutting angle appears to be no less than 45 degrees,
ideally around 60 degrees. (II-2B)
  5. Repair can be delayed for 8 to 12 hours with no detrimental
effect. Delay may be required so a more experienced care
provider is available for the repair. (I-A)
  6. Prophylactic single dose intravenous antibiotics (2nd generation
cephalosporin, e.g. cefotetan or cefoxitin) should be administered
for the reduction of perineal wound complications following the
repair of obstetrical anal sphincter injury. (I-A)
  7. Laxatives (e.g., lactulose) should be prescribed following the
primary repair of obstetrical anal sphincter injury as they are
associated with earlier and less painful first bowel motions and
earlier discharge from hospital. Constipating agents and bulking
agents are not recommended. (I-A)
 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair
  8. Non-steroidal anti-inflammatories and acetaminophen are the
first-line analgesics. Opioids should only be used with caution.
Constipation should be avoided by using a laxative or stool
softener. (I-A)
  9. Following obstetrical anal sphincter injury, providers should disclose
to women the degree of injury and arrange follow-up. Detailed
documentation of the injury and its repair is required. (III-L)
10. Women with anal incontinence following obstetrical anal sphincter
injury should be referred for pelvic floor physiotherapy. (I-A)
INTRODUCTION
W hile maternal mortality related to childbirth is now
rare in the developed world, there continues to be
significant maternal morbidity—including that related to
the pelvic floor function. A group of women who are at
risk of pelvic floor dysfunction following delivery include
those in whom the anal sphincter is disrupted during
childbirth.
Definitions
Perineal trauma occurs either spontaneously with vaginal
delivery or secondarily as an extension to an episiotomy.
Severe perineal trauma can involve damage to the anal
sphincters and anal mucosa. Obstetric anal sphincter
injuries include third and fourth degree perineal tears. Third
degree tears involve a partial or complete disruption of the
anal sphincter complex which includes the external anal
sphincter and the internal anal sphincter. Fourth degree
tears involve disruption of the anal mucosa in addition to
division of the anal sphincter complex.
Clinical Impact
OASIS can have a significant impact on women by
impairing their quality of life in both the short and long
term. One of the most distressing immediate complications
of perineal injury is perineal pain. Short-term perineal pain
is associated with edema and bruising, which can be the
result of tight sutures, infection, or wound breakdown.
Perineal pain can lead to urinary retention and defecation
problems in the immediate postpartum period. In the long
term, women with perineal pain may have dyspareunia
and altered sexual function. Additionally, complications
ABBREVIATIONS
AI anal incontinence
EAS external anal sphincter
IAS internal anal sphincter
NSAID non-steroidal anti-inflammatory
OASIS obstetric anal sphincter injuries
RTC randomized control trial
SVD spontaneous vaginal delivery
WHO World Health Organization
of severe perineal tears include abscess formation, wound
breakdown, and rectovaginal fistulae.
Injury to the anal sphincter is recognized as the most
common cause of anal incontinence and anorectal symptoms
in otherwise healthy women. Obstetrical sphincter injuries
have a variety of long-term complications of which anal
incontinence is the most distressing and disabling. Anal
incontinence incorporates a range of symptoms including:
flatal incontinence, passive soiling, or incontinence of liquid or
solid stool.1 Fecal urgency can also be a symptom experienced
by many women. Any of these symptoms can potentially
be a hygienic, social, and psychological problem for women.
Women are not always forthcoming with symptoms of anal
incontinence either due to embarrassment or they feel that the
symptoms are a normal result of vaginal delivery.
The true prevalence of AI related to OASIS may be
underestimated. The reported rates of AI following the
primary repair of OASIS range between 15% and 61%,
with a mean of 39%.2 This high prevalence highlights the
need to ensure our surgical techniques and postoperative
management are optimal.
Sustaining an OASIS can have a significant impact on a women’s
physical and emotional health. There are personal costs to the
patient with pad use and missed time from work, and costs to
women and the health care system including appointments
and treatments. It may also make women apprehensive about
future childbirth and adversely affect the remainder of their
reproductive lives. Missed tears or inadequate repair may also
present a potential source for litigation.
Obstetrical trauma that can lead to AI includes structural
damage to the anal sphincter complex, pudendal
neuropathy (by direct compression or stretching), or both.
Despite sphincter repairs, some women may have residual
defects and AI symptoms. The onset of symptoms of AI
may occur immediately or several years after delivery; anal
incontinence may only appear in old age, when the aging
process adds to the delivery insult.
Summary Statement
1. Obstetrical anal sphincter injuries lead to significant
comorbidities, including anal incontinence,
rectovaginal fistula, and pain. (II-2)
DIAGNOSIS OF OASIS
Careful examination of the perineum, including a rectal
examination for those with a tear that is more than
superficial in depth, should be performed in all women
prior to suturing.3 Formal training in the recognition
of OASIS improves the detection of such injuries,4 as
DECEMBER JOGC DÉCEMBRE 2015 l 1133
SOGC clinical practice guideline
Figure 1. Urogenital musculature
incident rises from 11% to 24.5% when the obstetrical care
provider’s examination was repeated by a trained fellow.5
The inspection should be done with adequate lighting and
analgesia and include:
•• inspection of perineum with labial parting,
•• inspection of the distal (caudal) posterior vagina, and
•• inspection for a third degree tear behind an “intact
perineum.”
Palpation is best done3 with the examiner’s dominant index
inserted in the anus, and the ipsilateral thumb in the vagina.
The 2 fingers then palpate with a “pill-rolling” motion to
assess thickness.
When the external sphincter tears, the ends retract and a cavity
is often palpated along the course of the sphincter muscle.
This may be less evident in the presence of an epidural.
Special attention should then be given to the IAS. The
IAS is a continuation of the circular smooth muscle of
the rectum. This muscle appears pale (like raw white fish),
is not very thick, and can be found 6 to 8 mm above
(cephalad to) the anal margin (Figure 1; for a more detailed
illustration, see online eFigure 1). Examination of the IAS
will also permit detection of a button-hole injury.
Recommendation
1. All women should be carefully examined for
perineal or vaginal tears; those with a tear that
is more than superficial in depth should have a
systematic rectal examination for obstetrical anal
sphincter injury prior to repair. (II-2B)
1134 l DECEMBER JOGC DÉCEMBRE 2015
Table 2. Classification of OASIS
First degree Injury to perineal skin only
Second degree Injury to perineum involving perineal muscles
but not involving the anal sphincter
Third degree Injury to perineum involving the anal sphincter
complex:
3a Less than 50% of EAS thickness torn
3b More than 50% of EAS thickness torn
3c Both EAS and IAS torn
Fourth degree Injury to perineum involving the anal sphincter
complex (EAS and IAS) and anal epithelium
GRADING OF SEVERITY
Traditionally, the severity of perineal tear was limited to 4
grades: grade 1 (superficial vaginal and/or perineal skin),
grade 2 (vaginal muscles), grade 3 (in or through external
anal sphincter muscle), and grade 4 (external and internal
anal sphincters and anorectal lumen).6
As there was a lack of consistency in the classification
of a partial anal sphincter, with up to 33% of consultant
obstetricians classifying a complete or partial tear of the
EAS as a second degree tear,7 Sultan8 devised a more
specific classification, later adopted by the WHO9 and
the International Consultation on Incontinence.10 In this
classification, grade 3 is further refined as involving the anal
sphincter complex and is divided into 3a, 3b, 3c (Table 2).
The type of third degree tear seems to have an impact on
symptoms, with OASIS grade 3a and 3b having a better
prognosis than 3c. In fact, those with a 3c OASIS had
symptoms similar in severity to those with a fourth degree
laceration.11
A button-hole injury, where only the vaginal and rectal mucosa
are involved, should not be reported as a third or fourth degree
tear if found in isolation. Documentation of the presence or
absence of a tear, as evidenced on rectal examination, should
be disclosed to the patient and incorporated into the delivery
note, and repair should be done to avoid fistulization.
Such a grading system takes into account the degree of tearing
experienced by the external sphincter separately from that of
the internal sphincter. Such distinction is meant to improve
reporting, guide repair, and facilitate outcome research.
 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair

Recommendation Table 3. Risks factors for OASIS

2. The World Health Organization classification Maternal risks factors OR*
should be used to classify obstetrical anal sphincter Primiparity 19–24
3.5 to 9.8
injury. This distinguishes the degree of external Age (> 35)24 1.1
sphincter tear (3a: < 50% or 3b: ≥ 50%) and Age (> 27) 23
1.9
the presence of internal sphincter defects (3c). Race19,23 1.4 to 2.5
A button-hole injury is distinct and should be Maternal diabetes19,23 1.2 to 1.4
classified separately as such. (III-B) Infibulation 25
1.8 to 2.7
Delivery risks factors OR
EPIDEMIOLOGY OF OASIS Operative vaginal delivery†
Vacuum19,21,24,26 1.5 to 3.5
The incidence of OASIS may vary according to many
Forceps 19,21,24,26,27
2.3 to 5.6
variables including use of any type of episiotomy (lateral,
Vacuum + forceps24,28 8.1
mediolateral, or midline), type of delivery (spontaneous or
Episiotomy
assisted vaginal), and type of instrument used (vacuum or
Midline26 2.3 to 5.5
forceps); parity, type of obstetrical care provider, and race.
Mediolateral 26,29
0.21
Overall, studies looking at the incidence of OASIS based on Mediolat episiotomy + instrumental29
the WHO’s International Classification of Diseases12 report Vacuum 0.11
an incidence of 4% to 6.6% of all vaginal birth,13–16 with Forceps 0.08
higher rates in assisted deliveries (6%) than in SVD (5.7%).17 Midline episiotomy + instrumental (nulliparous)30
Vacuum 4.5
An OASIS is often misdiagnosed at the time of delivery
Forceps 8.6
by obstetrical care providers. One study reported that the
overall rate of missed OASIS ranged from 26% to 87%.5 In Unspecified episiotomy + instrumental 31

that study of primiparous women, all women were examined Vacuum 2.9

by a trained fellow after the examination and grading of tear Forceps 3.9
by the obstetrical care provider and confirmed by endoanal Epidural23 1.1 to 2.2
ultrasound prior to repair (considered the gold standard). Second stage >1 h‡ 1.5
When examined systematically as described above, all but Shoulder dystocia 2.7 to 3.3
1.6% (3/182) of women were correctly diagnosed on VBAC21,32 1.4 to 5.5
exam; the other 3 had occult OASIS representing the false- Water birth27 1.46
negative rate of examination, 2 of which only affected the Oxytocin augmentation‡33 1.2
internal sphincter, and would have thus been undetectable Infant risks factors OR
on physical examination. Birth weight > 4000 gm20 2.2 to 3.0
Malpresentation23 2.0
When the diagnosis of OASIS is obtained from endoanal
ultrasound evaluation within 2 months of delivery, Postmaturity20,24 1.1 to 2.5

the incidence of any degree of anal sphincter defect in Fetal distress 1.3

primiparous women is reported to be as high as 27% to OP§

35%, and between 4% and 8.5% of multiparous women SVD23 2.0
have a new sphincter defect.15,18 Instrumental34,35 4.7
*All OR 95% confidence intervals are significant, i.e. do not cross 1
Risk Factors for OASIS †Presence of episiotomy not dissociated from instrumental
Risk factors commonly associated with obstetric anal ‡In primiparous
sphincter tears include maternal, delivery, and infant §Occiput posterior
characteristics. Table 3 shows a summary of OR for various VBAC: Vaginal birth after Caesarean
risks factors from studies reporting this information.19–35

Maternal Risk Factors

Maternal risk factors are presented in the first section of
Table 3. Obesity is protective, in a dose–response manner
(BMI 25 to < 30: 0.89 [95% CI 0.85 to 0.95]; 30 to < 35:

DECEMBER JOGC DÉCEMBRE 2015 l 1135

SOGC clinical practice guideline

0.84 [95% CI 0.76 to 0.92]; and BMI > 35: 0.70 [95%

confidence limit CI 0.59 to 0.82]).36
95% upper

for OR

124.4
191.8

239.5
Delivery Risk Factors
23.2
12.6
10.1

62.6
86.5

75.6
30.8
43.2
8.6
7.6
6.2

—
Risks factors occurring at the time of delivery
that may be independently associated with OASIS
are included in the second section of Table 3. The
impact of midline episiotomy and forceps, together
or in isolation, are presented in Table 4.37
confidence limit
95% lower

for OR

10.2

13.5
Infant Risk Factors
7.9
3.8
4.0
3.6
3.8
1.6

6.9

8.6
6.2
3.0
5.8
4.8
—
Specific infant characteristics appearing to
independently increase the risk of OASIS are
presented in the third section of Table 3.

INTERVENTIONS TO PREVENT OASIS

for factor being
Estimated OR

related to tear

13.6

25.3
24.4
41.0
40.6
21.6

15.9
33.8
1.0

7.0
6.3
5.6
5.3
3.2

9.7

Risk factors for OASIS often become apparent late

— in labour, and the degree to which these factors can
potentially be modified during labour is yet to be
determined. However, some methods of performing
the delivery may show evidence of protection.38
Table 4. Risk of OASIS after instrumental delivery, with or without episiotomy (90% midline)

factor in vaginal
control group
Number with

Head Control
Slowing down the delivery of the head and instructing
235

103
336
25
21
38
66

6
3
4
2
3
4
5
1
0

women to not push at the delivery of the head, using

thus only the uterine expulsive efforts, decreases the
incidence of OASIS by 50% to 70%, as shown by
multicentre studies in Norway.39,40
factor in sphincter

Perineal Support
Number with

tear group

The protective role of perineal support (whereby

122

101
138
220
366
91

52

63
32
61
32
26
15
33
18
17

the delivery care provider holds the perineum with

a sponge, applying medial pressure) in isolation is
unclear. A Cochrane review including RCTs on the
topic41 failed to show a benefit; however, the results
were heavily influenced by a large RCT of hands-
Prolonged second stage + epidural + forceps + episiotomy

poised versus hands-on techniques, which included

No vacuum, forceps, episiotomy or OP (reference group)

both slowing the head and supporting the perineum.

In the study, midwives assigned to poised hands were
Prolonged second stage + forceps + episiotomy

also allowed to slow the head (by applying pressure

on the head itself to control its speed of expulsion) if
delivering too fast, which effectively biased the results.
OP + episiotomy + epidural + forceps

A 2011 Cochrane review showed that the application

OR: odds ratio; OP: occiput posterior
Epidural + forceps + episiotomy

of warm compresses to the perineum (OR 0.5) as

OP + episiotomy + forceps

well as intra-partum perineal massage (OR 0.5) both

Prolonged second stage

decrease the risk of OASIS.41,42 Perineal massage is

Forceps + episiotomy

done with lubricant,

Fetal position OP

OP + episiotomy
Characteristic

OP + vacuum
OP + forceps

using a gentle, slow massage, with 2 fingers

Episiotomy

of the [obstetrical care provider’s] gloved

Epidural
Forceps

Vacuum

hand moving from side to side just inside the

patient’s vagina. Mild, downward pressure

1136 l DECEMBER JOGC DÉCEMBRE 2015

 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair
(towards the rectum) is applied with steady, lateral
strokes, which last 1 second in each direction.43
Delivery Position
While kneeling versus sitting has no impact on rate of
OASIS, a standing position (upright position without
buttocks support: upright standing, squatting, kneeling)
versus a sitting position (upright position but with
support of the ischial tuberosities, with or without sacral
support) might increase the risk of OASIS, as shown in
a retrospective analysis of 814 women (650 standing, 264
sitting, any parity) in which women standing for their
delivery had a nearly 7-fold increase in OASIS (2.5% vs.
0.38%).44 A 2012 RCT comparing traditional method of
delivery (no passive second stage, and active second stage
in the dorsal lithotomy) versus “alternate” method of
delivery (passive second stage lasting up to strong urge or
120 min, and active second stage in the lateral “Gasquet”
position – with upper hip flexed, foot on stirrup higher
than knee) showed no difference in rate of OASIS.45
Episiotomy
There is no doubt that restricted use of episiotomy, of any
type, is preferable in women having a spontaneous vaginal
delivery.46 The results of a pilot RCT of routine versus
restrictive mediolateral episiotomy in nulliparous women,
undergoing instrumental delivery did not reach statistical
significance due to a small sample size.47
Most studies identify midline episiotomy as a risk factor,48
but some do not.19 This might be related to poor coding
in those studies that assess the outcome based on database
information.49 However, while the published rate of OASIS
following mediolateral episiotomy varies between 0.5% to
7%, it may reach as high as 17% to 19% following a midline
episiotomy.26–50 In those having an operative vaginal delivery,
a retrospective large Dutch database study suggested that a
mediolateral or lateral episiotomy lead to less anal sphincter
injuries than no episiotomy or a midline episiotomy.29
The impact of mediolateral episiotomy is somewhat
controversial in instrumental deliveries in primiparous
women. Some authors report an independent increased
risk of OASIS if a mediolateral episiotomy is performed
during instrumented birth (OR 4.04);51 however, once
adjusted for instrumental delivery, the type of episiotomy
no longer remained a risk factor. Others report a lower
rates of OASIS 52–54 and severe perineal trauma (high
vaginal sulcus and OASIS combined)46 with mediolateral
episiotomy than with no episiotomy (OR 0.2 to 0.8).
The balance of the evidence suggests that a mediolateral
episiotomy likely does not increase the risk of OASIS
at the time of instrumental delivery of a primiparous
Figure 2. Episiotomy sites
woman, and in fact, may decrease the incidence of OASIS
compared with no episiotomy.
There is only one published RCT (published in 1980)
comparing rates of OASIS between midline and mediolateral
episiotomy in nulliparas.55 In that study, 12% of women who
had a midline episiotomy sustained an OASIS, versus 2%
of those who had a mediolateral. This study had significant
limitations including a number of protocol violations. For
example, if an obstetrical care provider was opposed to
midline incisions, a mediolateral episiotomy was performed
instead and the patient excluded from the analysis. In a
prospective cohort study of 1302 women who delivered
vaginally, and who all received an episiotomy, 426 received
midline and 876 mediolateral episiotomy, according to the
practitioner’s preferences.56 Deep perineal tears (which
included but were not limited to OASIS) were present in
14.8% of those who had a midline episiotomy versus 7% of
those who had a mediolateral episiotomy.
The terminology used in the literature is at times unclear
between midline, mediolateral, and lateral episiotomies. A
standardization has been proposed57 (as shown in Figure 2;
for a more detailed illustration, see online eFigure 2).
A midline episiotomy (line #1) should indicate those
starting in the midline and continuing at a 0° angle from
the vertical; mediolateral (line #4) episiotomies should
represent those done starting in the midline but at an angle
greater than 0° from the vertical line; while a lateral (#5)
episiotomy starts off the midline and is carried at an angle
greater than 0° from the vertical. Other incisions shown
include: modified median (inverted “T” incision, #2),
“J”-shaped episiotomy (#3), and the seldom used radical
lateral (Schuchardt incision, #6).58
DECEMBER JOGC DÉCEMBRE 2015 l 1137
SOGC clinical practice guideline
The angle of the episiotomy affects the occurrence of
OASIS. A more acute (vertical) angle appears to increase
the risk of OASIS; in an RCT comparing mediolateral
episiotomies made at 60° and 40° angles from the vertical,
the risk of OASIS was 2.4% versus 5.5%, respectively
(did not reach statistical significance); however, 60º
episiotomies carried higher short-term pain.59 This likely
reflects how far away from the anal sphincter complex
the incision is.
The impact of the starting point of the episiotomy
(mediolateral vs. lateral) appears less important. In a large
RCT, published only in abstract form in 2014, comparing
mediolateral to lateral episiotomies.60 In this trial of 790
women, the incidence of OASIS did not differ between
a mediolateral (60° off the midline) and a lateral incision
(1 to 2 cm laterally from the midline, angled towards the
ischial tuberosity): 1.5% versus 1.3%, respectively. There
also seem to have no impact on postpartum pain or
sexually between mediolateral and lateral.61
Looking at healed episiotomy scars, the risk of sustaining
an OASIS is decreased when58:
•• the tip of the episiotomy is further away from a
vertical line drawn from the vagina to anus: OR 0.30
for each 5.5 mm increase in the distance between the
midline vertical line and the tip of the episiotomy,
•• a lateral incision is done: OR 0.44 for each 4.5 mm
distance increase off the midline for the incision start
(i.e. less OASIS when the incision started off the
6 o’clock location on the introitus, e.g. 4 o’clock),
•• a longer episiotomy was done: OR 0.25 for each
increase of 5.5 mm in episiotomy length, and/or
•• the healed angle is between 15° and 60°.
In another study, primigravidas who had mediolateral
episiotomies and OASIS had, when examined 3 months
postpartum, a mean healed angle of 30°, compared with
38° in those without OASIS.62 However, it was shown
that there is a 20° difference between the incision angle
of an episiotomy (typically performed when the head is
crowning) and the sutured angle once healed: whereas the
incision angle was 40° from midline, the angle measured
once healed and scarred was 20°.63 In other words, to
obtain a healed angle of 30°, one must incise at a 50° angle.
Instrumental Delivery
If instrumental delivery is indicated, vacuum extraction
carries less risk to the anal sphincter than forceps.64,65
Most data support the use of mediolateral episiotomy
to protect against OASIS in primiparous women having
instrumental delivery over no episiotomy.29,53,66,67 When
1138 l DECEMBER JOGC DÉCEMBRE 2015
a midline episiotomy is performed concurrently with an
operative vaginal delivery, it acts synergistically in increasing
OASIS.30,68 It is possible that early removal of forceps
(after delivery is assured, but before the largest diameter of
the head is expelled) may also assist in limiting OASIS in
forceps and vacuum deliveries, when combined with other
practices such as rotating an occiput posterior baby to an
occiput anterior position, selecting a vacuum instead of a
forceps, performing a mediolateral episiotomy rather than
a midline (only if an episiotomy is deemed necessary), and
using minimal necessary maternal expulsive efforts at time
of expulsion.64 Some have raised the point of informed
consent at the time of instrumental delivery, arguing that
disclosure of the OASIS risk should be included, as well as
the risks and benefits of any alternative such as Caesarean
section.69
Clearly, performing a Caesarean would prevent OASIS, but
performing it late in labour may not fully protect the anal
canal, as nerve injury can still occur.70,71
Other
Studies evaluating antepartum perineal massage,72 pushing
position (kneeling vs. sitting),73 open versus closed glottis
pushing,74 Ritgen’s manoeuvre,75 water birth,76 and delayed
pushing (in women with epidural)77 failed to show evidence
of a protective effect on the anal canal.
Summary Statement
2. Obstetrical anal sphincter injuries are
more commonly associated with forceps
deliveries than with vacuum-assisted vaginal
deliveries. (II-2)
Recommendations
3. In women having a spontaneous vaginal delivery,
the rate of obstetrical anal sphincter injury is
decreased when the obstetrical care provider slows
the fetal head at crowning. (II-2A)
4. Episiotomy:
a. At the time of either a spontaneous
vaginal or instrumental delivery, the
obstetrical care provider should follow a
policy of “restricted” episiotomy (i.e. only
if indicated), rather than “liberal” use (i.e.
routine), for the prevention of obstetrical anal
sphincter injury. (I-A)
b. If an episiotomy is deemed indicated,
preference for a mediolateral over a midline
should be considered. (II-2B) The optimal
cutting angle appears to be no less than 45
degrees, ideally around 60 degrees. (II-2B)
 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair
PRINCIPLES AND TYPES OF REPAIRS
Obstetric anal sphincter injuries should be repaired by
appropriately trained clinicians comfortable with such
repairs. Repairs are typically carried out in the delivery
room or the operating room. The operating room offers
the benefits of access to optimal lighting, appropriate
equipment, and aseptic conditions.3 Additional equipment
may be required for anal sphincter repairs including self-
retaining retractors and Allis clamps. There have been no
studies that have evaluated anaesthetics used in the repair
of obstetric anal sphincter injuries. Although commonly
repaired under local anaesthetic, general or regional
anaesthesia maybe optimal as they provide both analgesia
and muscle relaxation.3 The EAS has inherent tone and
when torn does retract within its capsular sheath. With
muscle relaxation, the extent of the tear can be thoroughly
evaluated and the sphincter ends can be identified,
grasped, and repaired by either the end-to-end or the
overlap technique. Local anaesthetic may be sufficient
when only the superficial fibres of the EAS are disrupted,78
although without good analgesia, it may be difficult
to make a proper diagnosis. In the United Kingdom,
experts recommend completing the repair under general
or epidural anaesthesia.79 The SOGC Urogynaecology
Committee does not feel this is always necessary, as long as
adequate analgesia is provided, either using local infiltration
or pudendal nerve block.
Suture Material
Although the type of suture material used in the repair of
obstetric anal sphincter tears may be important, there has
been very little research carried out comparing different
suture types used for sphincter repairs. Both absorbable and
delayed absorbable sutures are commonly used. Although
some colorectal surgeons use non-absorbable sutures for
secondary repairs of anal sphincters, there is concern that
such sutures may result in stitch abscesses or suture ends
may cause discomfort requiring their removal.80 The suture
ends should be cut short and the knots covered by the
overlying superficial perineal muscles in order to minimize
any discomfort from suture ends and knots. Monofilament
sutures maybe beneficial as they are less likely to harbour
organisms and predispose to infection.78
A randomized trial by Williams et al.81 (n = 112), compared
OASIS repairs with polyglactin (Vicryl) and polydioxanone
(PDS). At 6 weeks, there was no significant difference in
suture-related morbidity. There may be benefit to delayed
absorbable suture with respect to longer term functional
outcomes but this has yet to be evaluated in clinical trials.
Many of the more recently published studies have used
delayed absorbable sutures but have not been undertaken
to compare suture material. Randomized trials with longer
term outcomes including anal incontinence are required to
compare suture materials.
Repair of the Anal Mucosa
Following a fourth degree perineal tear, the anal mucosa
can be approximated by a number of techniques.78 The
mucosal repair can be carried out with an interrupted
3-0 Vicryl suture with the knots tied in the anal lumen or
external to the anal canal. Alternatively the anal mucosa can
be approximated with a 3-0 PDS suture with a submucosal
continuous suture. There are currently no studies that
suggest a benefit from any of these repair techniques
for the anal mucosa with respect to outcomes including
anovaginal and rectovaginal fistulas. However figure-of-
eight sutures should not be used as they can cause ischemia
and poor healing of the anorectal mucosa.
Separate Repair of the IAS
The literature related to the techniques of repairing the anal
sphincter following obstetric trauma has primarily focused
on the repair of the external anal sphincter. However, the
muscles involved in maintaining anal continence include
not only the EAS but also the internal anal sphincter.
The internal sphincter is a 3 to 5 mm thick continuation of
the rectal smooth muscle and is under autonomic control.
The IAS is responsible for maintaining continence at rest,
by contributing to 70% to 85% of the resting anal pressure,
and, to a lesser degree, of the anal pressure in response
to sudden and constant rectal distension (40% and 65%,
respectively).10
In response to rectal distension by feces, liquids, or gases,
the pressures in the IAS drop to allow “sampling” (whereby
the rectal content transiently enters in contact with
sensory nerve ending of the anal canal to determine the
bowel content (liquid, gas, or solid) and allow processing
and decision about appropriateness of evacuation),
associated with a reflex recto-anal contractile reflex if time
is inconvenient.82 Damage to the IAS muscle may lead to
a poor seal and an impaired sampling reflex,10 leading to
passive incontinence.
Sultan and Thakar78 described identifying and
approximating the IAS with interrupted sutures in addition
to the overlap repair of the EAS. It can be difficult to
identify the IAS which lies between the EAS and the
anal mucosa. In comparison to the striated muscle of the
EAS, the IAS is thin with a pale pink appearance in close
proximity to the anal mucosa. It may appear similar to a
“fascial” layer. A small prospective study, with historical
controls, published by Lindqvist and Jernetz in 2010,83
DECEMBER JOGC DÉCEMBRE 2015 l 1139
SOGC clinical practice guideline
suggested that identifying and separately suturing the IAS
may improve anal continence at 1 year. Both previously
mentioned studies approximated the IAS in an “end-
to-end” fashion using delayed absorbable sutures. In a
randomized trial of obstetric sphincter repairs,84 9 women
had sphincter tears that included the IAS and were
independently approximated. In all 9 women the IAS was
intact on follow-up endoanal ultrasound.
Studies looking at functional results following OASIS
repair report that more women with an IAS defect on
endoanal ultrasound 6 months postpartum have anal
incontinence, and those with incontinence report worse
degree of symptoms than those without IAS.22,65,85,86
EAS Repair Techniques
When repairing a torn anal sphincter following vaginal
delivery the external anal sphincter can be approximated
by 1 of 2 repair techniques; end-to-end repair or overlap
repair. The torn ends of the EAS, normally under tonic
contraction, tend to retract within their sheaths and can be
found latero-posteriorly to the tear, often by palpation of a
depression downward rather than lateral. The muscle ends
must be identified and grasped with Allis clamps.
With an end-to-end repair (for a detailed illustration, see
online eFigure 3), the EAS ends may need to be mobilized
using Metzenbaum scissors for the dissection. The muscle
ends are then approximated end-to-end with 2 or 3
mattress sutures. In theory, mattress sutures may cause less
tissue necrosis although there is no evidence to support
one technique over the other. Sutures should include the
fascial sheath.3
With an overlap repair (for a detailed illustration, see online
eFigure 3), the torn EAS muscle ends often needs much
more dissection and mobilization.3 The dissection is carried
out using the ischioanal fat laterally as a landmark. The
full lengths of the torn ends of the EAS (including fascial
sheath) are overlapped in a double-breasted fashion.80 This
type of repair is only possible with 3b or greater OASIS.50
Following the anal sphincter repair, which approximates
the disrupted anal sphincter complex, the perineal body is
reconstructed by suturing the perineal muscles. This takes
tension off and provides support for the underlying muscle
repair. The vaginal mucosa and perineal skin are repaired in
the usual fashion. A rectovaginal exam at the completion of
the repair is carried out to confirm the adequacy of the repair.
If an obstetrical care provider is insufficiently experienced
in the repair of third and fourth degree tear and an
experienced obstetrical care provider is not available
immediately or locally, repair can be delayed for 8 to 12
1140 l DECEMBER JOGC DÉCEMBRE 2015
hours with no impact on anal incontinence and pelvic floor
symptoms.87
Summary Statement
3. Obstetrical anal sphincter injuries (OASIS) repair:
a. Suture-related morbidity is similar at 6 weeks
following the use of either polyglactin 2-0 or
polydioxanone 3-0 following repair. (I)
b. Repair of the internal anal sphincter is
recommended as women who demonstrate an
internal anal sphincter defect on postpartum
ultrasound have more anal incontinence. (III)
c. Repair of the external anal sphincter should
include the fascial sheath. An overlapping
technique often requires more dissection and
mobilization of the sphincter ends and is only
possible with full thickness 3b sphincter tears
or greater. (III)
d. A persistent defect of the external anal
sphincter remote from delivery may increase
the risk of worsening symptoms following
subsequent vaginal deliveries. (II-2)
Recommendation
5. Repair can be delayed for 8 to 12 hours with
no detrimental effect. Delay may be required so a
more experienced care provider is available for the
repair. (I-A)
Comparison of Repair Techniques
Historically, the most popular technique for the primary
repair of obstetrical anal sphincter injuries has been the
end-to-end approximation of the external anal sphincter
with interrupted or figure-of-eight sutures. In contrast, the
technique commonly used by colorectal surgeons to repair
anal sphincter tears remote from delivery or unrelated to
delivery is the overlap technique. The overlap technique,
described by Parks and McPartlin88 for the secondary
repair of anal sphincters, was first evaluated for the
primary repair of obstetric anal sphincter tears by Sultan
et al. in his 1999 seminal study.89 The small study (n = 27)
showed that in comparison to matched historical controls
with end-to-end repairs, overlap repairs resulted in less anal
incontinence (8% vs. 41%).90 Following this study several
randomized trials have been published comparing end-to-
end approximation and overlap repair of the EAS.
A 2013 Cochrane review compared the effectiveness of
these 2 immediate primary repair techniques in reducing
subsequent anal incontinence, perineal pain, dyspareunia
and improving quality of life.50 The authors included 6 trials
involving 588 women.81,84,91 Three trials followed women
for 12 months.91 The only outcomes showing a difference
 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair
was for fecal urgency and fecal incontinence score, in favour
of the overlapping repair from one trial with 52 women
followed up at 12 months.91 An overlap repair resulted in
fewer with deterioration of incontinence from 6 weeks to
12 months later (n = 41).91 Another trial showed that at 36
months, these differences were no longer present.92
However, the data are limited given the heterogeneity in
the outcome measures, time points, and reported results.
These studies included primiparous and parous women
and partial and complete third degree tears. Furthermore,
their surgical experience is not evaluated in the included
studies. Consequently, the current literature does not
support recommending one obstetric anal sphincter repair
technique over the other
POSTOPERATIVE MANAGEMENT
Prophylactic Antibiotics
Only one randomized trial compared the effect of a single
IV dose of a second generation cephalosporin (cefotetan
or cefoxitin) on postpartum perineal wound complications
(purulent discharge, or abscess and breakdown of repair) 2
weeks following third and fourth degree tears.80 Prophylactic
antibiotics given at the time of obstetrical anal sphincter
repair decreases maternal morbidity related to perineal wound
complications: 8.2% of women who received antibiotics and
24.1% of women who received placebo suffered a wound
complication (P < 0.05), with a relative risk of 0.34 (95%
CI 0.12 to 0.96).93,94 This Cochrane review reported that the
study was limited by a high (27.2%) proportion of lack of
follow-up. There are currently no studies that have evaluated
the value of additional doses of antibiotics following repair
of third and fourth degree perineal tears.
Recommendation
6. Prophylactic single dose intravenous antibiotics
(2nd generation cephalosporin, e.g., cefotetan or
cefoxitin) should be administered for the reduction
of perineal wound complications following the
repair of obstetrical anal sphincter injury. (I-A)
Postoperative Bowel Regimen
Postoperative bowel regimens following the primary repair of
OASIS vary. Some regimens consist of laxatives and bulking
agents to avoid constipation and any potential disruption of
the repair from the passage of hard stool. Other regimens
consist of bowel confinement techniques with the concern
that bowel motions in the immediate postoperative period
may threaten the integrity of the repair.
Mahony et al.95 performed a randomized trial to compare
a laxative regiment (lactulose) with a constipating regiment
(codeine phosphate) in the 3 days following repair of
primary OASIS in 105 women. Laxative use was associated
with a significantly earlier and less painful first bowel motion
and an earlier hospital discharge postpartum. Troublesome
constipation was noted in 19% of women receiving the
constipating regimen compared to 5% receiving the laxative
regimen. Two patients that received the constipating regimen
required hospital admission for fecal impaction. Overall
there were no significant differences in continence scores
or anal manometry and endoanal scan findings between the
groups at 3 months postpartum.
In 2007 Eogan et al.96 randomized (n = 147) women to
receive laxatives alone (lactulose) or laxatives and a bulking
agent (lactulose and ispaghula husk, Fybogel) for 10 days
after the repair of OASIS. Incontinence in the immediate
postnatal period was more frequent in women taking the
2 preparations than in those taking lactulose alone (33%
vs. 18%). There were no significant differences between
the groups with respect to time to first bowel motion,
length of hospital stay, or overall satisfaction related to
bowel habits, and no significant difference in functional
outcomes at 3 months.
Recommendation
7. Laxatives (e.g., lactulose) should be prescribed
following the primary repair of obstetrical anal
sphincter injury as they are associated with earlier
and less painful first bowel motions and earlier
discharge from hospital. Constipating agents and
bulking agents are not recommended (I-A).
Postoperative Analgesia
While there are no data regarding the use of analgesics
following repair of OASIS, a Cochrane review published
in 200397 found that rectal analgesia including diclofenac
reduces perineal trauma related pain during the first 24
hours following birth and results in women using less
additional analgesia during the first 48 hours. Because
of the constipating effect of opioids, an NSAID in
conjunction with acetaminophen is likely preferable as
first-line management of perineal pain. Although rectal
administration of NSAID may be better, it should be
avoided in cases of fourth degree laceration, because it
theoretically could impair.98 However, opioids should not
be withheld, but rather used along with a stool softener.
Recommendation
8. Non-steroidal anti-inflammatories and
acetaminophen are the first-line analgesics. Opioids
should only be used with caution. Constipation
should be avoided by using a laxative or stool
softener. (1-A)
DECEMBER JOGC DÉCEMBRE 2015 l 1141
SOGC clinical practice guideline
Bladder Catheterization
Studies have demonstrated a relationship between
significant perineal trauma and postpartum urinary
retention.99–102 Glavind and Bjork looked specifically
at sphincter injuries and found sphincter rupture was
observed in 33% of women with postpartum urinary
retention compared with 1% of the total population of
women giving birth during the study period.101
The pathophysiology of postpartum urinary retention
related to perineal injury is unclear but maybe related to
perineal discomfort, urethral and perineal edema, and
neurologic damage.
Summary Statement
4. Obstetrical anal sphincter injuries are associated
with an increased risk of postpartum urinary
retention. (II-2)
RISK MANAGEMENT/DOCUMENTATION
Operative delivery, while often indicated, is a risk factor for
sphincter tear, and obstetrical care providers should consider
discussing the possibility of operative delivery and any potential
sequelae prior to labour. The decision for instrumental delivery
should take into consideration the potential for anal sphincter
injury. In addition, prolonged labour may be associated with
sphincter tears and practitioners may consider discussing this
with patients in situations when labour progression is slow.
When faced with an OASIS, the obstetrical care giver
should document (ideally as a formal operative note) the
delivery course, including indication for operative vaginal
delivery, consent obtained, description of procedure,
type and extent of perineal injury, repair method and
suture used, and antibiotics administered. Furthermore,
the patient should be informed of the injury sustained,
and upon discharge a follow-up plan should be made.
Recommendation
9. Following obstetrical anal sphincter injury, providers
should disclose to women the degree of injury and
arrange follow-up. Detailed documentation of the
injury and its repair is required. (III-L)
OUTCOMES FOLLOWING REPAIR
The outcomes following the primary repair of obstetric
anal sphincter injuries are difficult to establish as there
is significant heterogeneity between studies. Studies vary
greatly with respect to repair techniques, outcome measures,
and follow-up intervals. A summary of outcomes following
primary OASIS repair is presented in Table 5.3,103–105
1142 l DECEMBER JOGC DÉCEMBRE 2015
The outcomes following OASIS repair appear to be
related to the extent of the initial sphincter tear, with 3c or
fourthth degree OASIS showing worse results than other
types (see Table 6).11,25,94
Remote from delivery (median follow-up 14 years), the
extent of sphincter damage was found to be independent
of the development of fecal incontinence.106
Following OASIS, the incidence of anal incontinence
may increase with time: from 3–6 months to 3–8 years
following delivery, the rate went from 31% to 54%.107
Women’s continence over time may be affected by aging,
subsequent deliveries, and lifestyle factors.
Overall, the outcomes following the primary repair
of OASIS are not encouraging, with studies reporting
that many women suffer from various degrees of anal
incontinence. Fortunately, the management of anal
incontinence, including that following repaired OASIS, can
be successful with pelvic floor physiotherapy. 108,109
Recommendation
10. Women with anal incontinence following obstetrical
anal sphincter injury should be referred for pelvic
floor physiotherapy. (I-A)
SUBSEQUENT PREGNANCY
Many factors may be taken into account in counselling
women following an OASIS: the functional status (i.e.
symptoms experienced shortly and remotely from the
index delivery), the extent of residual anatomical and/or
functional defects as shown on anal ultrasound and/or
anal manometry, and the patient’s wishes.
A woman who had an OASIS after her first delivery has 3.8-
to 5.9-fold greater odds of a repeat OASIS at her next delivery
than a woman without prior OASIS (Table 7).103–105,110–114
Although higher than in women without a prior OASIS,
the risk of having a recurrent OASIS is the same for a
woman with previous OASIS as the baseline risk at first
delivery; both around 5.3% in Ontario.33 The vast majority
of women with a previous OASIS will not have a recurrent
OASIS during a subsequent vaginal delivery. In fact, 64%
to 90% of all OASIS occurring at a second delivery are in
women without a previous OASIS.112,113
Overall, the rate of anal incontinence in women with
OASIS and a subsequent vaginal delivery worsens in 19% to
56% of women,115–118 particularly if a women had transient
anal incontinence after the index OASIS.116 On the basis
of these studies, the Royal College of Obstetrics and
 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair

Table 5. Summary of outcomes from primary OASIS repair

Repair Follow-up Outcome Prevalence
Reference technique/injury Interval(s) measure(s) mean (range)
Sultan and Thakar 20093 End-to-end repair 1–30 months Anal incontinence 39% (15 to 61%)
(35 studies) (flatal and/or fecal incontinence) (35 studies)
Liquid or solid fecal incontinence 14% (2 to 29%)
(25 studies)
Fecal urgency 6% to 28%
Sonographic anal sphincter defects 34% to 91%
Anal incontinence with coitus (flatal 17%
and/or fecal incontinence)
Bagade and Mackenzie 2010 End-to-end or overlap, 6 months Anal incontinence 11%
n = 79 Fecal incontinence 7.5%
Tjandra et al. 2008 End-to-end, n = 114 18.8 months Fecal incontinence (Wexner ≥ 1) 20.7%
Samarasekera et al. 2008 Unspecified, n = 53 ≥ 10 years Overall anal incontinence (Wexner ≥ 1) 53%
Flatal incontinence 51%
Incontinence to liquid 32%
Incontinence to solid 26%

Table 6. Outcomes following OASIS repairs according to the extent of the initial sphincter tear.
Degree of Type of Follow-up
Reference injury repair Interval(s) Outcome measure(s) Prevalence
Nichols et al. 2005 4th, n = 17 unspecified 6 to 8 weeks Anal incontinence and/or fecal 3rd: 28%
3rd, n = 39 urgency 4th: 59%
Roos et al. 201011 3a or 3b: n = 439 End-to-end 8 to 12 weeks Bothersome fecal incontinence 3c and 4th had worse scores
3b or 4: n = 92 or overlap or fecal urgency on symptoms questionnaires
Any incontinence to liquid stool than 3a and 3b

Fenner et al 200326 3rd and 4th, unspecified 6 months Worsening bowel control after 4th: 30.8%
n = 165 pregnancy 3rd: 3.6%

Table 7. Risks of OASIS at next delivery, based on presence of OASIS at 1st delivery
OASIS at 1st delivery No OASIS at 1st delivery
OASIS at subsequent delivery 3.7% to 7.5% 104,105,110–114
0.6% to 3.2%104,105,112,113

Gynaecologistsis recommend that “All women who have
sustained an obstetric anal sphincter injury in a previous
pregnancy and who are symptomatic or have abnormal
endoanal ultrasonography and/or manometry should have
the option of elective Caesarean birth.”79
A 2003 study using a decision analysis modeling explored
universal Caesarean section in continent women with
previous OASIS.119 Based on the literature, they used the
following assumptions: 5.1% risk of repeat OASIS, anal
incontinence rate of 44% after 2nd OASIS. To prevent
one case of anal incontinence (flatus, liquid, or stool) in
women with prior OASIS who were presumed continent
2.3 elective Caesarean sections would need to be done, at
the cost of increased maternal risks, including an increased
morbidity rate from 4.2% following vaginal delivery to
11.3% after Caesarean section. Furthermore, there would
be one maternal death for 1880 cases of anal incontinence
averted. The balance of risks and benefits should be
discussed when counselling women on the route of future
deliveries after OASIS in a previous pregnancy.
Outcome of Subsequent Vaginal Delivery
Depending on Symptoms Following OASIS
at Index Delivery
Only one published study assessed anal symptoms
in women with a subsequent delivery based on their
symptoms after the index OASIS.116 Women who

DECEMBER JOGC DÉCEMBRE 2015 l 1143

SOGC clinical practice guideline
sustained a fourth degree tear in a previous delivery
associated with transient anal incontinence had a greater
rate of developing subsequent anal incontinence after
a subsequent vaginal delivery (39%, 9/23; 4 of these
women became permanently incontinent compared with
7% [2/29] of asymptomatic women after their OASIS).
In a recent preliminary report, low baseline symptom
scores may predict good outcomes after a vaginal delivery
in women with prior OASIS.120
Outcome of Subsequent Vaginal Delivery
Depending on Finding on Endoanal
Ultrasound Following OASIS at Index Delivery
The literature is limited in number and size of studies, but
the presence of a persistent defect appears to increase the
risk of worsening symptoms. In women who had ultrasound
evidence of anal sphincter injury 3 months following a first
vaginal delivery (any degree of tear), a subsequent vaginal
delivery may increase the rate of abnormal anorectal
symptoms (38%), compared with women who did not
have another child (16%; not statistically significant).
Women without ultrasound evidence of OASIS 3 months
postpartum had a rate of anal incontinence of 3% in the
absence of a subsequent pregnancy versus 10% if they
delivered again (not statistically significant).118
In women who have a second vaginal delivery, the
presence of anal injury on antenatal ultrasound between
deliveries increases the rate of worsening anorectal
symptoms: from 7% of women following a subsequent
vaginal delivery without evidence of persistent defect,
to 37% if ultrasound showed a pre-existing injury (no
significant difference).121
Outcome of Subsequent Vaginal Delivery
Depending on Combined Finding on Endoanal
Ultrasound and Anal Manometry Following
OASIS at Index Delivery
Sultan reported his results following antenatal counselling
for the route of delivery in subsequent pregnancy for
women with previous OASIS,114 with updated results
presented in 2013.122 In his study, substantial anal
compromised was defined as either:
•• external sphincter defect on ultrasound > 30° and a
maximum squeeze pressure increment of < 20 mmHg
on anal manometry;
OR
•• defect <30° and a maximum squeeze pressure
increment of < 20 mmHg;
OR
•• no defect and a maximum squeeze pressure increment
of < 20 mmHg.
1144 l DECEMBER JOGC DÉCEMBRE 2015
Women who had substantial anal compromise were
counselled on having a Caesarean section. All others
were counselled on vaginal delivery. In those women who
delivered as counselled (75% of the study group), results
on anal manometry did not significantly change and
anorectal symptoms did not worsen following delivery.
Similar results have been presented as abstracts.123
Summary Statements
5. After a successful repair of obstetrical anal sphincter
injuries, most women can safely deliver vaginally in
a future pregnancy. (III)
6. Counselling women about future delivery plans:
a. The risk of recurrence of an obstetrical anal
sphincter injuries at a subsequent delivery is 4%
to 8%. (II-2)
b. It was calculated that 2.3 Caesarean sections at
the cost of increased maternal risk would be
required to prevent one case of anal incontinence
in a woman with prior obstetrical anal sphincter
injuries. (II-2)
LEARNING MODEL
For the past decade, Sultan and his group has devised a
hands-on workshop on OASIS repair. The hands-on
part uses both an artificial model and a repair of fresh
anuses originating from male pig.4 It has been shown that
a surgical skill laboratory improves learners’ acquisition
of the skills necessary to repair OASIS as evidenced on
the Objective Structured Assessment of Technical Skills
and written examination administered before and after an
OASIS repair workshop.124
SUMMARY
Obstetrical anal sphincter injuries represent a significant
morbidity encountered after vaginal delivery. Some
intrapartum measures can be taken to diminish the risk
of occurrence. Careful examination after every delivery
is of paramount importance to avoid missing an OASIS.
Systematic repair of the entire anal sphincter complex
should be done by a trained caregiver; full disclosure and
close follow-up should be offered. Most women following
OASIS are good candidates to have a subsequent vaginal
delivery; antenatal evaluation of symptoms and anal function
testing can help guide the choice of future mode of delivery.
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et al. An International Urogynecological Association (IUGA)/
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 Obstetrical Anal Sphincter Injuries (OASIS): Prevention, Recognition, and Repair
2. Sultan AH, Kettle C. Diagnosis of perineal trauma. In: Sultan AH,
Thakar R, Fenner DE, eds. Perineal and anal sphincter trauma. 1st ed.
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 324, May 2015 (Replaces #201, December 2007)

Pre-conception Folic Acid and Multivitamin

Supplementation for the Primary and Secondary
Prevention of Neural Tube Defects and Other
Folic Acid-Sensitive Congenital Anomalies

This Clinical Practice Guideline was prepared by the Aideen Moore, MD, Toronto ON
Genetics Committee, reviewed by the Family Physician
William Mundle, MD, Windsor ON
Advisory Committee, and approved by the Executive and
Board of the Society of Obstetricians and Gynaecologists Deborah O’Connor, PhD RD, Toronto ON
of Canada. Joel Ray, MD, Toronto ON

PRINCIPAL AUTHOR Michiel Van den Hof, MD, Halifax NS

R. Douglas Wilson, MD, Calgary AB Disclosure statements have been received from all contributors.

GENETICS COMMITTEE
R. Douglas Wilson (Chair), MD, Calgary AB
Abstract
François Audibert, MD, Montreal QC Objective: To provide updated information on the pre- and post-
conception use of oral folic acid with or without a multivitamin/
Jo-Ann Brock, MD, Halifax NS
micronutrient supplement for the prevention of neural tube
June Carroll, MD, Toronto ON defects and other congenital anomalies. This will help physicians,
Lola Cartier, MSc, Montreal QC midwives, nurses, and other health care workers to assist in the
education of women about the proper use and dosage of folic
Alain Gagnon, MD, Vancouver BC acid/multivitamin supplementation before and during pregnancy.
Jo-Ann Johnson, MD, Calgary AB Evidence: Published literature was retrieved through searches of
Sylvie Langlois, MD, Vancouver BC PubMed, Medline, CINAHL, and the Cochrane Library in January
2011 using appropriate controlled vocabulary and key words (e.g.,
Lynn Murphy-Kaulbeck, MD, Moncton NB folic acid, prenatal multivitamins, folate sensitive birth defects,
Nanette Okun, MD, Toronto ON congenital anomaly risk reduction, pre-conception counselling).
Results were restricted to systematic reviews, randomized control
Melanie Pastuck, RN, Calgary AB
trials/controlled clinical trials, and observational studies published
in English from 1985 and June 2014. Searches were updated on
SPECIAL CONTRIBUTORS
a regular basis and incorporated in the guideline to June 2014
Paromita Deb-Rinker, PhD, Ottawa ON Grey (unpublished) literature was identified through searching the
Linda Dodds, MD, Halifax NS
Juan Andres Leon, MD, Ottawa ON J Obstet Gynaecol Can 2015;37(6):534–549
Hélène Lowell, RD DtP, Ottawa ON
Key Words: Folic acid, folate, prenatal multivitamins,
Wei Luo, MB MSc, Ottawa ON micronutrients, neural tube defect, spina bifida, myelomeningocele,
Amanda MacFarlane, PhD, Ottawa ON congenital anomalies, fetal anomalies, folate sensitive birth
defects, congenital anomaly risk reduction, preconception
Rachel McMillan, BSc, Ottawa ON
counseling, birth defects, pregnancy, prevention

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

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 Pre-conception Folic Acid/Multivitamin Supplementation for the Prevention of Neural Tube Defects and Other Congenital Anomalies
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.193
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.193
websites of health technology assessment and health technology-
related agencies, clinical practice guideline collections, clinical trial
registries, and national and international medical specialty societies.
Costs, risks, and benefits: The financial costs are those of daily
vitamin supplementation and eating a healthy folate-enriched
diet. The risks are of a reported association of dietary folic acid
supplementation with fetal epigenetic modifications and with an
increased likelihood of a twin pregnancy. These associations may
require consideration before initiating folic acid supplementation.
The benefit of folic acid oral supplementation or dietary folate
intake combined with a multivitamin/micronutrient supplement is
an associated decrease in neural tube defects and perhaps in
other specific birth defects and obstetrical complications.
Values: The quality of evidence in the document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventative Health Care (Table 1).
Summary Statement
In Canada multivitamin tablets with folic acid are usually available in 3
formats: regular over-the-counter multivitamins with 0.4 to 0.6 mg folic
acid, prenatal over-the-counter multivitamins with 1.0 mg folic acid,
and prescription multivitamins with 5.0 mg folic acid. (III)
Recommendations
1. Women should be advised to maintain a healthy folate-rich diet;
however, folic acid/multivitamin supplementation is needed to
achieve the red blood cell folate levels associated with maximal
protection against neural tube defect. (III-A)
2. All women in the reproductive age group (12–45 years of age)
who have preserved fertility (a pregnancy is possible) should
be advised about the benefits of folic acid in a multivitamin
supplementation during medical wellness visits (birth control
renewal, Pap testing, yearly gynaecological examination)
whether or not a pregnancy is contemplated. Because so many
pregnancies are unplanned, this applies to all women who may
become pregnant. (III-A)
3. Folic acid supplementation is unlikely to mask vitamin B12
deficiency (pernicious anemia). Investigations (examination
or laboratory) are not required prior to initiating folic acid
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
supplementation for women with a risk for primary or recurrent
neural tube or other folic acid-sensitive congenital anomalies who
are considering a pregnancy. It is recommended that folic acid
be taken in a multivitamin including 2.6 ug/day of vitamin B12 to
mitigate even theoretical concerns. (II-2A)
4. Women at HIGH RISK, for whom a folic acid dose greater than 1
mg is indicated, taking a multivitamin tablet containing folic acid,
should be advised to follow the product label and not to take more
than 1 daily dose of the multivitamin supplement. Additional tablets
containing only folic acid should be taken to achieve the desired
dose. (II-2A)
5. Women with a LOW RISK for a neural tube defect or other folic
acid-sensitive congenital anomaly and a male partner with low
risk require a diet of folate-rich foods and a daily oral multivitamin
supplement containing 0.4 mg folic acid for at least 2 to 3 months
before conception, throughout the pregnancy, and for 4 to 6 weeks
postpartum or as long as breast-feeding continues. (II-2A)
6. Women with a MODERATE RISK for a neural tube defect or
other folic acid-sensitive congenital anomaly or a male partner
with moderate risk require a diet of folate-rich foods and daily oral
supplementation with a multivitamin containing 1.0 mg folic acid,
beginning at least 3 months before conception. Women should
continue this regime until 12 weeks’ gestational age. (1-A) From
12 weeks’ gestational age, continuing through the pregnancy,
and for 4 to 6 weeks postpartum or as long as breast-feeding
continues, continued daily supplementation should consist of a
multivitamin with 0.4 to 1.0 mg folic acid. (II-2A)
7. Women with an increased or HIGH RISK for a neural tube defect,
a male partner with a personal history of neural tube defect, or
history of a previous neural tube defect pregnancy in either partner
require a diet of folate-rich foods and a daily oral supplement
with 4.0 mg folic acid for at least 3 months before conception
and until 12 weeks’ gestational age. From 12 weeks’ gestational
age, continuing throughout the pregnancy, and for 4 to 6 weeks
postpartum or as long as breast-feeding continues, continued daily
supplementation should consist of a multivitamin with 0.4 to 1.0
mg folic acid. (I-A). The same dietary and supplementation regime
should be followed if either partner has had a previous pregnancy
with a neural tube defect. (II-2A)
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SOGC clinical practice guideline
INTRODUCTION
I t has been estimated that 4% to 5% of babies are born
with a serious congenital anomaly1; 2% to 3% will have
congenital anomalies (malformations, deformations or
disruptions) that can be recognized prenatally by non-
invasive ultrasound screening or anticipated through
invasive diagnostic testing and 2% will have developmental
or functional anomalies and minor congenital anomalies
recognized at birth or during the first year of life.1 Folic
acid, taken orally prior to conception and during the early
stages of pregnancy, plays a role in preventing neural
tube defects2–25 and has been associated with preventing
other folic acid-sensitive congenital anomalies such as
heart defects,15,26–30 urinary tract anomalies,15,28,31 oral facial
clefts,15,32–40 and limb defects.15
FOLIC ACID SUPPLEMENTATION AND
THE PREVENTION OF BIRTH DEFECTS
The initial NTD translational research study investigated
folic acid supplementation for recurrence prevention of
NTDs in a randomized double-blind clinical trial involving
1195 completed high risk pregnancies in women from
33 centres.2 The NTD recurrence rate decreased from
3.5% in a non-supplemented group to 1% for women
randomized to the group receiving an oral 4 mg folic acid
supplementation daily prior to pregnancy and throughout
the first 6 weeks of pregnancy.
The second NTD translational research study was a
randomized controlled trial for the primary prevention
of NTD occurrence.3 The frequency of NTDs was zero
in 2471 women receiving 0.8 mg per day of folic acid
compared with 6 cases in 2391 women not receiving folic
acid. This RCT study supported previous case–control
studies that had provided evidence that pregnant women
using multivitamins containing folic acid or dietary folic
acid had a lower risk of occurrence NTDs than women
not taking supplements.10–14
ABBREVIATIONS
aOR adjusted odds ratio
BMI body mass index
CI confidence interval
GI gastrointestinal
MTHFR 5,10-methylenetetrahydrofolate reductase
NTD neural tube defect
OR odds ratio
RBC red blood cell
RCT randomized controlled trial
536 l JUNE JOGC JUIN 2015
These 2 landmark RCT studies have provided the folic
acid supplementation dosing evidence (from initial
experimental expert opinion) for NTD primary prevention
and recurrence, but they were completed in female
populations without the additional exposure or benefit of
folic acid food fortification that is at present in the North
American food environment. These RCT folic acid dose
results may need to be adjusted due to the present food
environment “with folic acid fortified white flour products
but more research is required for optimization of oral
supplementation dose (maximum benefit; minimum or
no risk) with non-pregnant pre-conception exposure to
fortified food products.16
ORAL FOLIC ACID SUPPLEMENTATION
PREGNANCY CARE
Oral pre-conception folic acid dietary intake or
supplementation is required as it is the primary source
for the trans-placental transfer of folate/folic acid to the
embryo/fetus. No specific studies have been published
looking at the embryonic cell folate availability in
humans during this embryonic target period of 0 to 8
weeks (conception to 10 gestational weeks). Canadian
researchers have made strong contributions in this area
of prevention.41–76
Women should be advised to maintain a nutritionally healthy
diet, as recommended in Eating Well with Canada’s Food
Guide.42 Good or excellent sources of natural folate include
broccoli, spinach, peas, Brussels sprouts, corn, lentils, and
oranges.
Counselling should emphasize that the recurrence risk
for a fetus with an NTD is shared by both mother’s and
father’s personal reproductive history, but only the mother
is treated with the supplemental dose of pre-conception/
first trimester folic acid.
Folic Acid Food Fortification and
Oral Supplementation
In Canada, since 1998, in an effort to reduce the rate of
NTDs, there has been mandatory folic acid fortification
of white flour, enriched pasta, and cornmeal. Food
fortification coincided with an observed decrease in
NTDs in live-born infants,1,6,16 but a proportion of the
documented NTD decrease may also be related to an
increased use of prenatal tests and subsequent pregnancy
termination (secondary prevention) rather than to
fortification alone.45,46 It is possible that certain prevalence
data populations may not have included termination of
pregnancy prior to the 20 weeks’ gestation information
in their reported rate.
 Pre-conception Folic Acid/Multivitamin Supplementation for the Prevention of Neural Tube Defects and Other Congenital Anomalies
Sherwood et al. assessed the dietary folate intake of
pregnant and lactating women at the presently mandated
and predicted folic acid fortification levels to determine
the prevalence of inadequate and excessive intakes. The
conclusion was, at the present mandated levels of food
fortification, many pregnant and lactating women are still
unlikely to meet their appropriate folate requirements
from dietary sources alone, however the actual level of
inadequacy cannot be determined until the level of folic
acid in the food supply is known with greater precision.50
RBC folate testing/screening for the prevention of birth
defects in certain co-existing maternal health conditions
requires more investigation to determine the actual
effectiveness and use of this testing.
Factors that may affect the ability to achieve
adequate maternal folic acid tissue levels
Optimization of oral maternal folic acid supplementation
is difficult because it relies on folic acid dose, type of
folate supplement, bio-availability of the folate from
foods, timing of supplementation initiation, maternal
metabolism/genetic factors, and many other factors.71–76
Recommendations
1. Women should be advised to maintain a healthy
folate-rich diet; however, folic acid/multivitamin
supplementation is needed to achieve the red blood
cell folate levels associated with maximal protection
against neural tube defect. (III-A)
2. All women in the reproductive age group
(12–45 years of age) who have preserved fertility
(a pregnancy is possible) should be advised
about the benefits of folic acid in a multivitamin
supplementation during medical wellness
visits (birth control renewal, Pap testing, yearly
gynaecological examination) whether or not a
pregnancy is contemplated. Because so many
pregnancies are unplanned this applies to all women
who may become pregnant. (III-A)
FOLIC ACID FOR CONGENITAL ANOMALIES
PREVENTION AND EVALUATION
Background for NTD Prevention
Neural tube defects are severe congenital anomalies that
occur due to a lack of neural tube closure at either the
upper, middle, or lower portion of the spine in the third
to fourth week after conception (day 26 to day 28 post-
conception).77
In Canada, the prevalence of NTDs in newborns has
declined since 1998 due to food fortification and increased
vitamin supplementation,78–80 as well as to an increase of
prenatal diagnosis/termination.45,46
Recurrence risks may reflect the genetic contribution in
different regional or population incidence and folic acid
NTD sensitivity (Table 2), as there is still an estimated
1% recurrence rate even with the 4 to 5 mg folic acid
prophylaxis supplementation approach.1,6,7,81–91
Table 2 summarizes the increasing NTD clinical risk groups,
based on the family relationship of the affected individual
to the “at-risk” fetus and the specific NTD population
background risk (based on ethnic/genetic population
demographics). The Canadian population risk varies across
the country, with the highest NTD risk in Newfoundland
and the lowest NTD risk in British Columbia.77
Table 3 summarizes the evidence-based risk factors for low
maternal RBC or serum folate status that are associated
specifically with neural tube defects.15,19-22,41,77–79,81,82,92–106
Table 4 summarizes the commonly used medications/
drugs prescribed for certain medical therapies that have
been shown to have interactions with folate metabolism
and may alter RBC folate levels with a resulting increased
risk for congenital anomaly outcomes.100–103
Table 5 summarizes the studies with case–control, cohort, or
RCT comparisons (odds ratio) and decreased, increased, or
no effects on specific congenital anomalies.15,30,37,38,40,53 Folic
acid in combination with multivitamin supplements has been
shown to reduce certain other congenital anomalies such as
heart defects,15,26–30 urinary tract anomalies,15,28,31 oral facial
clefts,15,32–40 and limb defects.15At present, multifactorial
inheritance (genetic and environmental factors)79,107,108 is
the most commonly reported etiology for NTDs, but
monogenic, chromosomal, and teratogenic etiologies have
specific effects and have not been well studied in their
association with folic acid deprivation or supplementation.109
The risk categories for fetal NTD outcome should consider
the 2 major effect pathways:
1. Genetic factors including gene polymorphisms that
affect the efficiency of folate metabolism, gene
mutations, affects related to DNA methylation/
epigenetics, and associated chromosomal anomalies, and
2. Environmental factors such as dietary folate intake
(food fortification and/or dietary supplementation),
gastrointestinal absorption efficiency, teratogenic
medication exposure (epilepsy or folate antagonist
medications), glucose metabolism (obesity, diabetes
type I and II), drugs, smoking, alcohol, and
“proposed” folate receptor auto-antibodies.
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SOGC clinical practice guideline

Table 2. Anencephaly and spina bifida approximate recurrence risk with no food
folic acid fortification or folate supplementation
Recurrence risk, % based on population NTD incidence
Population Population Population
Relationship of NTD affected incidence incidence incidence
individual to the at-risk fetus 5 per 1000 2 per 1000 1 per 1000
One sibling 5 2 2
Two siblings 12 10 10
One parent 4 4 4
One second-degree relative 2 1 1
One third degree relative 1 0.75 0.5
Adapted from Firth HV, Hurst JA, Hall JG. Oxford desk reference. Clinical genetics. Oxford: Oxford University
Press; 2006.77
NTD: neural tube defect

Table 3. Identified increased risk factors for fetal NTD or low maternal RBC
folate status
Personal/family history
or ethnic risk1–5,19–22
Medical/surgical
condition41,77–79,100–103
Maternal
co-morbidities81,92–97
Maternal lifestyle
factors82,98,99,190–192
NTD: neural tube defect; RBC: red blood cell; MTHFR: methylenete trahydrofolate reductase; GI: gastrointestinal
NTD: maternal or paternal affected, previous affected fetus for
either parent, child, sibling, or second /third degree relative
MTHFR genotype 677TT carrier homozygous
677CST carrier heterozygous
GI: malabsorption/inflammatory bowel, Crohn’s, active Celiac
disease, gastric bypass surgery, advanced liver disease
Renal: kidney dialysis
Pre-gestational diabetes (type I or II)
Anti-epilepsy or folate-inhibiting medications (see Table 4)
Maternal obesity: BMI > 30 kg/m2 or 80 kg
(pre-pregnancy weight)
Smoking
Alcohol overuse
Non-prescription drug use/abuse
Low socio-economic status
Poor/restricted diet

Table 4. Interactions between drugs or medications and folic acid

1. Biology reduced folic acid Interference with Chloramphenicol
activity erythrocyte maturation Methotrexate
Other Metformin
2. Reduced folic acid levels Impaired absorption Sulfasalazine
Increased metabolism Phenobarbital
Phenytoin
3. Other interactions Not reported Primidone
Triamterene
Barbiturates

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 Pre-conception Folic Acid/Multivitamin Supplementation for the Prevention of Neural Tube Defects and Other Congenital Anomalies

Table 5. Summary of congenital anomalies (decreased or increased or no effect) following

folic acid food fortification
Case–Control Cohort/RCT
Study reference Anomaly (95% CI) (95% CI)
Meta-analysis
Goh et al. (2006)15 Neural tube defect 0.67 (0.58–0.77) 0.52 (0.39–0.69)
Oral facial cleft 0.63 (0.54–0.73) 0.58 (0.28–1.19)
Cardiovascular defects 0.78 (0.67–0.92) 0.61 (0.40–0.92)
Limb reduction defects 0.48 (0.30–0.76) 0.57 (0.38–0.85)
Cleft palate 0.76 (0.62–0.93) 0.42 (0.06–2.84)
Urinary tract defects 0.48 (0.30–0.76) 0.68 (0.35–1.31)
Congenital hydrocephalus 0.37 (0.24–0.56) 1.54 (0.53–4.50)
Johnson and Little (2008)38 Cleft lip and palate 0.75 (0.65–0.88)
Cleft palate only 0.88 (0.76–1.01)
Single Population
Li et al. (2013)30 Heart defects isolated 0.52 (0.34–0.78)
and complex 0.27 (0.14–0.55)
Godwin et al. (2008)40 Spina bifida 0.51 (0.36–0.73)
OS atrial septal defects 0.80 (0.69–0.93)
Ureteric obstruction 1.45 (1.24–1.70)
Abdominal wall defect 1.40 (1.04–1.88)
Pyloric stenosis 1.49 (1.18–1.89)
Canfield et al. (2005)53 Anencephaly 0.84 (0.76–0.94)
Spina bifida 0.66 (0.61–0.71)
TGA 0.88 (0.81–0.96)
Cleft palate only 0.88 (0.82–0.95)
Pyloric stenosis 0.95 (0.90–0.99)
Omphalocele 0.79 (0.66–0.95)
Upper limb reduction 0.89 (0.80–0.99)
O’Neill (2007)37 Cleft lip ± palate 0.61 (0.39–0.96) Folic acid 0.4 mg daily
0.75 (0.50–1.11) Folate diet only
0.36 (0.17–0.77) Supplement + diet
Cleft palate only 1.07 (0.56–2.03)
Goh et al (2006) 15
No effect identified for Trisomy 21
Pyloric stenosis
Undescended testis
Hypospadias
RCT: randomized control trial; OS: ostium secunda; TGA: transposition of the great arteries

Details for the genetic and environmental factors/ from oral folic acid intake due to vitamin supplements
considerations with fetal and pediatric outcomes are and/or fortified foods is low. Folic acid is a water soluble
available in the references.19–22,110–149 vitamin, so any excess intake is anticipated to be excreted
in the urine.
POTENTIAL CAUTION FOR MATERNAL, FETAL,
CHILDHOOD, OR GENERAL POPULATION WITH Folic acid has not been shown to promote or to prevent
FOLIC ACID SUPPLEMENTATION breast cancer.153–155

Benefit Ovarian cancer studies suggest (but not with statistical

Folic acid, in a 0.4 to 1.0 mg daily dose60,150–152 is not known significance) that relatively high dietary folate intake may
to cause demonstrable harm to the developing fetus or to be associated with a reduction in ovarian cancer risk among
the pregnant woman. The risk of maternal or fetal toxicity woman with high alcohol and methionine intake.156

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SOGC clinical practice guideline
Evidence has been reported for a decreased pre-
valence of preeclampsia with maternal folic acid
supplementation.143,157–160
An Australian study found that high serum folate did
not mask the macrocytosis of cobalamin (vitamin B12)
deficiency of pernicious anemia.161
A Cochrane Review found no conclusive evidence of benefit
of folic acid supplementation on pregnancy outcomes
(preterm birth, stillbirths, neonatal deaths, low birth weight
babies, pre-delivery anemia, or low pre-delivery red cell
folate).162
Risks and Cautions
Folic acid dosing above the recommended supplement-
ation amounts (supra-physiologic doses) has not been
shown to have any added fetal/maternal health or
developmental benefits, although recent epigenetic/
methylation studies in animals and humans have
indicated that some caution and research is required.
The folic acid doses of 5 mg have not been reported
to have maternal or fetal risks, but long-term high-dose
5 mg folic acid use has not been well studied in a prenatal
population.3,10–14,35,36, 54,55,163
Recent summary conclusions from colorectal cancer
reviews of the topic are still cautionary.164–177 Two studies
show no association of folic acid with colorectal adenoma
or recurrence.178,179
FETAL AND PEDIATRIC ISSUES
Benefit
Pediatric ongoing health benefits have been identified
following prenatal multivitamin supplementation before and
in early pregnancy.40,128 Maternal use of prenatal multivitamins
is associated with a decreased risk for pediatric brain tumours
(OR 0.73, 95% CI 0.60 to 0.88),40,146,180 neuroblastoma (OR
0.53, 95% CI 0.42 to 0.68),40 leukemia (OR 0.61, 95% CI 0.50
to 0.74),40,147 Wilms’ tumour,142 primitive neuroectodermal
tumours,145 and ependymomas.145 It was stated that it is
not known which constituent(s) among the multivitamins
confers this protective effect.
A study looking at maternal use of folic acid supplementation
and the diagnosis of childhood autism found that folic
acid supplementation around the time of conception was
associated with lower risk of autistic disorder in a Norwegian
cohort. The adjusted OR for autistic disorder in children
of folic acid users was 0.61 (95% CI 0.41 to 0.90). These
findings cannot establish causality but they do support the
use of prenatal folic acid supplementation.148,149
540 l JUNE JOGC JUIN 2015
Risks and Cautions
Folic acid and multivitamin supplementation is possibly
associated with an increased incidence of twins, although
positive and negative twinning findings have been reported
with the possible confounders of in vitro fertilization and
ovarian stimulation or other environmental hormones. A
clear relationship between folic acid supplementation and
twinning has not been confirmed.60,181–183
A slightly increased risk of wheeze and respiratory infection
was found in the offspring whose mothers took folic acid
supplements during pregnancy.184 It was suggested that methyl
donors in the maternal diet during pregnancy may influence
respiratory health in children consistent with epigenetic
mechanisms. Zetstra-van der Woude et al. reported maternal
high-dose folic acid (5 mg) was associated with an increased
rate of asthma medication among children (recurrent asthma
medication IRR [incidence rate ratio] = 1.14, 1.04 to 1.30 and
recurrent inhaled corticosteroids IRR = 1.26, 1.07 to 1.47).
In the cohort of 39 602 pregnancies, 2.9% were exposed
to high-dose folic acid.185 Associations were clustered on
the mother and adjusted for maternal age, maternal asthma
medication, and dispensing of benzodiazepines during
pregnancy.186 Veeranki et al. used a retrospective cohort of
167 333 mother–infant pairs to compare no prenatal folic
acid exposure with first trimester only folic acid exposure and
reported higher relative odds of bronchiolitis diagnosis (aOR
1.17, 1.11 to 1.22) and greater severity (aOR 1.16, 1.11 to
1.22). The effect was not significant in the other 2 exposed
groups of “after the first trimester” or “both first trimester
and after the first trimester”.186
Magdelijns et al.187 and Crider188 et al. did not confirm any
meaningful association between folic acid supplementation
during pregnancy with atopic diseases in the offspring.
More population studies are required to understand
whether there is an exposure and an effect risk for
pediatric outcomes, but for now some caution in favour
of using the lowest effective folic acid supplementation
dose is required.
Recommendations
3. Folic acid supplementation is unlikely to mask
vitamin B12 deficiency (pernicious anemia).
Investigations (examination or laboratory) are not
required prior to initiating folic acid supplementation
for women with a risk for primary or recurrent
neural tube or other folic acid-sensitive congenital
anomalies who are considering a pregnancy. It
is recommended that folic acid be taken in a
multivitamin including 2.6 ug/day of vitamin B12 to
mitigate even theoretical concerns. (II-2A)
 Pre-conception Folic Acid/Multivitamin Supplementation for the Prevention of Neural Tube Defects and Other Congenital Anomalies
4. Women at HIGH RISK, for whom a folic acid dose
greater than 1 mg is indicated, taking a multivitamin
tablet containing folic acid, should be advised to
follow the product label and not to take more
than 1 daily dose of the multivitamin supplement.
Additional tablets containing only folic acid should
be taken to achieve the desired dose. (II-2A)
COUNSELLING AND FOLIC
ACID SUPPLEMENTATION
Canadian data indicates clear socio-demographic differences
among women with respect to their knowledge and use of
folic acid. Although most women understood the benefits
of folic acid supplementation, greater than 33% did not
take folic acid supplements prior to becoming pregnant
and less than 50% supplemented according to national
guidelines. Targeted education and other interventions to
improve folic acid use in younger women and women with
lower socio-economic status is recommended.189
Han et al. reported that certain groups of women (from
the Caribbean, Latin America, North Africa, Middle
East, China, and South Pacific) who are immigrants to
Canada take fewer folic acid supplements than Canadian-
born women. This immigrant group may benefit from
enhanced or directed pre-conception education and
counselling.66
Folic acid supplementation and the NTD risk stratified
for maternal BMI requires more consideration. A recent
Chinese cohort study reported the association between
folic acid supplementation and the reduced NTDs risk was
weaker in overweight/obese mothers (overweight/obese
was defined as BMI ≥ 24.0 kg/m2) than in underweight/
normal mothers (BMI < 24.0 kg/m2).190
Oral supplementation success may be variable because
of compliance issues with daily oral tablet use (nausea,
“forgot,” “don’t like to take pills”) but as a result of food
fortification with folic acid, Canada has almost eliminated
folate deficiency.191 The best predictor of prenatal
multivitamin adherence in pregnant women is related to
the women’s previous experiences with multivitamin use.
The most important factors inhibiting prenatal vitamin
use are fear or the experience of nausea, vomiting, and
gagging. For women who took the supplemental vitamins,
the most important factors were the dosing regimen, health
care provider advice, and the mode of product distribution
(prescription, over-the-counter, covered by insurance).191
The limited RCT data for folic acid supplementation in
certain clinical scenarios requires the use of cohort and
case–control evaluation and expert opinion extrapolation.
Alternate opinions regarding oral supplemental dosing
have been published by Motherisk.192
Other long-term uses for folic acid in the other clinical use
context (alcoholics, anemia, liver disease, kidney disease,
malabsorption, cardiac disease, cancer treatment, regular
multivitamin wellness use) are not considered or discussed
in this guideline.
Summary Statement
In Canada multivitamin tablets with folic acid are
usually available in 3 formats: regular over-the-
counter multivitamins with 0.4 to 0.6 mg folic acid,
prenatal over-the-counter multivitamins with 1.0 mg
folic acid, and prescription multivitamins with 5.0 mg
folic acid. (III)
The 3 clinically at-risk groups that will benefit from folic
acid supplementation are derived from evidence-based
review and expert opinion, and are based on the folic acid-
sensitive risk of teratogenic or genetic congenital anomaly,
or the estimated risk of maternal folic acid deficiency. The
supplemental folic acid requirements for the best benefit-
to-risk outcome have used the published Canadian female
population (post fortification) RBC folate values.
It is important to emphasize that all 3 risk recommendations
for the clinically “at-risk” groups have pregnant women
returning to or continuing the oral low dose 1.0 mg folic
acid multivitamin supplementation at 12 weeks’ gestational
age and continuing to minimize any unknown or potential
risk for folic acid supplementation and the exposed mother
or fetus/newborn.
LOW risk group: Women or their male partners with no
personal or family history of health risks for folic acid-
sensitive birth defects.
MODERATE risk group: Women with the following
personal or co-morbidity scenarios (1 to 5) or their male
partner with a personal scenario (1 and 2):
1. Personal positive or family history of other folate
sensitive congenital anomalies (limited to specific
anomalies for cardiac, limb, cleft palate, urinary tract,
congenital hydrocephaly)
2. Family history of NTD in a first or second-degree
relative
3. Maternal diabetes (type I or II) with secondary fetal
teratogenic risk. Measurement of red blood cell
folate levels could be part of the pre-conception
evaluation to determine the multivitamin and folic acid
supplementation dose strategy (1.0 mg with RBC folate
JUNE JOGC JUIN 2015 l 541
SOGC clinical practice guideline
< 906 and 0.4 to 0.6 mg with RBC folate > 906) with a
multivitamin)
4. Teratogenic medications with secondary fetal
teratogenic effects by folate inhibition via
anticonvulsant medications (carbamazepine, valproic
acid, phenytoin, primidone, phenobarbital), metformin,
methotrexate, sulfasalazine, triamterene, trimethoprim
(as in cotrimoxazole), and cholestyramine
5. Maternal GI malabsorption conditions secondary to
co-existing medical or surgical conditions that have
been shown to result in decreased RBC folate levels
(Crohn’s or active Celiac disease, gastric bypass surgery,
advanced liver disease, kidney dialysis, alcohol overuse)
INCREASED/HIGH risk group: Women or their male
partners with a personal NTD history or a previous neural
tube defect pregnancy
Recommendations
5. Women with a LOW RISK for a neural tube
defect or other folic acid-sensitive congenital
anomaly and a male partner with low risk require
a diet of folate-rich foods and a daily oral
multivitamin supplement containing 0.4 mg
folic acid for at least 2 to 3 months before
conception, throughout the pregnancy, and for 4
to 6 weeks postpartum or as long as breast-feeding
continues. (II-2A)
6. Women with a MODERATE RISK for a neural
tube defect or other folic acid-sensitive congenital
anomaly or a male partner with moderate risk
require a diet of folate-rich foods and daily oral
supplementation with a multivitamin containing
1.0 mg folic acid, beginning at least 3 months
before conception. Women should continue this
regime until 12 weeks’ gestational age. (1-A) From
12 weeks’ gestational age, continuing through the
pregnancy, and for 4 to 6 weeks postpartum or as
long as breast-feeding continues, continued daily
supplementation should consist of a multivitamin
with 0.4 to 1.0 mg folic acid. (II-2A)
7. Women with an increased or HIGH RISK for a
neural tube defect, a male partner with a personal
history of neural tube defect, or history of a
previous neural tube defect pregnancy in either
partner require a diet of folate-rich foods and a daily
oral supplement with 4.0 mg folic acid for at least
3 months before conception and until 12 weeks’
gestational age. From 12 weeks’ gestational age,
continuing throughout the pregnancy, and for 4 to
6 weeks postpartum or as long as breast-feeding
continues, continued daily supplementation should
542 l JUNE JOGC JUIN 2015
consist of a multivitamin with 0.4 to 1.0 mg folic
acid. (I-A). The same dietary and supplementation
regime should be followed if either partner has had a
previous pregnancy with a neural tube defect. (II-2A)
To achieve a dose of 4.0 mg/day folic acid, women should
consume a multivitamin containing 1.0 mg folic acid and
add 3 single 1.0 mg folic acid tablets. (See the appendix for
a summary of the risk statuses, risk groups, and appropriate
folic acid dosing.)
Recognizing the challenge some clinical offices might face
implementing the above recommendations based on the
mode of product distribution (prescription, over-the-
counter, covered by insurance) and compliance issues with
taking daily multiple oral tablets,188 the following simplified
regimen could be considered. However, it is important to
keep in mind that the folic acid intake should be at the
lowest effective and safest dose.
Low or moderate risk group: a diet of folate-rich foods
in addition to pre-conception and first trimester folic acid
supplementation with an over-the-counter daily prenatal
multivitamin containing 1.0 mg of folic acid.
Increased/high risk group: a diet of folate-rich foods in
addition to preconception and first trimester folic acid
supplementation with a prescription daily multivitamin
containing 5.0 mg of folic acid.
See the Figure for a detailed decision tree.
SUMMARY
Folic acid (in the diet and/or as a prenatal oral
supplement) with a multivitamin/micronutrient has
been shown to decrease or minimize specific congenital
anomalies including neural tube defects with associated
hydrocephalus, oral facial clefts with or without cleft palate,
congenital heart disease, urinary tract anomalies, and limb
defects, as well as some pediatric cancers. The 1998 public
health initiative for fortification of flour has been very
beneficial with respect to primary prevention of certain
folic acid-sensitive birth defects. The comprehensive
Canadian analysis of neural tube reduction after folic
acid flour fortification has reported a 46% reduction. The
observed reduction was greater for spina bifida (53%) than
for anencephaly (38%) and encephalocele (31%). Further
reductions in the incidence of other congenital anomalies
sensitive to folic acid and multivitamins should be possible
with the participation of key stakeholders. Public health
surveillance strategies should be implemented to look for
any adverse health outcomes (maternal; pediatric) that
Pre-conception Folic Acid/Multivitamin Supplementation for the Prevention of Neural Tube Defects and Other Congenital Anomalies

Decision tree for folic acid supplementation

Woman who may or plans

to become pregnant

No known NTD risk factor and no prior

pregnancy affected with folate sensitive
NTD risk factor† or prior pregnancy
congenital anomaly
affected with other folate sensitive
 daily multivitamin containing 0 .4 mg/day folic
congenital anomaly (Box 1)‡
acid* 3 months prior to pregnancy and continuing
throughout pregnancy

If pregnancy does not occur after 1 year,

consider referral to fertility services

Other risk factors for NTD

Pre-existing diabetes‖
Antiepileptic or folate inhibiting medication (Box 2)
•1st or 2nd degree relative of woman or her partner
with a history of NTD
Previous pregnancy affected with NTD or •GI malabsorptive conditions, such as Celiac
personal history of NTD disease, inflammatory bowel disease, or gastric
daily multivitamin and a total intake of 4 bypass surgery
mg/day folic acid§ 3 months prior to •Advanced liver disease
pregnancy and through the first trimester, •Kidney dialysis
then a multivitamin containing 0 .4 mg/day •Alcohol over-use
folic acid* for the remainder of pregnancy . OR
OR Prior pregnancy affected with a folate sensitive
5 mg¶ congenital anomaly (Box 1)‡
 daily multivitamin containing 1 mg/day folic
acid* 3 months prior to pregnancy and through the
first trimester, then a multivitamin containing 0 .4
mg/day folic acid* for the remainder of pregnancy

If pregnancy does not occur after 6 to 8 months, change to 0 .4 mg/day* for 6 months; if
pregnancy is not achieved in the following 6 months, consider referral to fertility services
and RBC folate testing to ensure level >900 nmol/L .

BOX 1 BOX 2
Congenital anomalies which may be sensitive Practical list of folate-inhibiting medications:
to folate (see text for anomaly detail):
– Anticonvulsant medications: phenytoin, primidone, phenobarbital,
– Oral facial cleft (and palate) carbamazepine, valproic acid
– Certain cardiac defects – Metformin
– Certain urinary tract anomalies – Methotrexate (a medication that is highly teratogenic to the fetus).
– Limb reduction defects – Sulfasalazine
– Triamterene 
– Trimethoprim (as found in cotrimoxazole)

*Folic acid should be taken in the form of a multivitamin containing vitamin B12. Women should not take more than one
multivitamin supplement each day. In large doses, some substances in multivitamins could be harmful.
†Does NOT include spina bifida occulta as this is not a risk for NTD.
‡There are additional folate sensitive congenital anomalies that would benefit from the folic acid levels described.
§To provide a dose of 4 mg/day folic acid, a multivitamin containing 1 mg folic acid should be consumed, with single folic acid
tablets added to achieve the desired folic acid dose.
‖Peri-conceptional glycemic control is strongly recommended to reduce the risk of a congenital anomaly in the offspring of a
woman with pre-pregnancy diabetes.
¶Folic acid intake should be at the safest and lowest effective dose; however, clinical offices that face challenges implementing
recommendations for 4 mg folic acid daily because of the mode of product distribution or compliance issues with taking daily
multiple oral tablets may consider the simplified regimen of one 5 mg folic acid multivitamin tablet daily.
NTD: neural tube defect; GI: gastrointestinal

JUNE JOGC JUIN 2015 l 543

SOGC clinical practice guideline
could possibly be related to folic acid food fortification and
additional folic acid supplementation recommendations.
ACKNOWLEDGEMENTS
Expert opinion and guideline review were obtained from
the Public Health Agency of Canada and Motherisk.
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APPENDIX
FOLIC ACID SUPPLEMENTATION

Risk Folic acid dosing:

status Female partner Male partner A healthy folate-rich diet AND:
Low No personal or family risk for NTD No personal or family risk for NTD Multivitamin with 0.4 to 1.0 mg folic acid for
or folic acid-sensitive birth defects or folic acid-sensitive birth defects 2 to 3 months before conception, throughout
pregnancy and for 6 weeks postpartum or to
completion of lactation
Moderate Personal history positive for folate Personal history positive for folate Multivitamin including 1. 0 mg folic acid for at
sensitive anomalies. sensitive anomalies least 3 months before conception to 12 weeks
Family history for NTD in first- or Family history for NTD in first- or and then for remainder of pregnancy and 6
second-degree relative. second-degree relative weeks postpartum or to completion of lactation

Diabetes type I or II
Teratogenic medications by folate
inhibition
GI malabsorption that decreases
RBC folate
High Personal NTD history. Personal NTD history. Multivitamin including 1.0 mg folic acid plus
Previous NTD pregnancy Previous NTD pregnancy 3 × 1.0 mg folic acid (for total of 4.0 mg) OR
prescription multivitamin including 5.0 mg folic
acid* at least 3 months before conception
until 12 weeks’ gestation, then a multivitamin
including 0.4 to 1.0 mg folic acid for remainder
of pregnancy and 6 weeks postpartum or to
completion of lactation
*It is important to keep in mind that folic acid intake should be at the safest and lowest effective dose (4 mg/daily). However, clinical offices that face a challenge
in implementing the recommended dose because of the mode of product distribution (prescription vs. over-the-counter, covered by insurance or not) and
compliance issues with taking multiple oral tablets daily could consider the simplified regimen of the 5.0 mg folic acid prescription multivitamin.
NTD: neural tube defect; GI: gastrointestinal; RBC: red blood cell

JUNE JOGC JUIN 2015 l 549

 SOGC CLINICAL PRACTICE GUIDELINE
Umbilical Cord Blood:
Counselling, Collection, and Banking
This clinical practice guideline has been prepared by the
Cord Blood Banking Working Group, reviewed by the
Clinical Practice – Obstetrics, Maternal Fetal Medicine,
Family Physician Advisory, and Aboriginal Health Initiative
Committees, and approved by the Executive and Board of
the Society of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
B. Anthony Armson, MD, Halifax NS
David S. Allan, MD, Toronto ON
Robert F. Casper, MD, Toronto ON
Disclosure statements have been received from all contributors.
Abstract
Objective: To review current evidence regarding umbilical cord blood
counselling, collection, and banking and to provide guidelines for
Canadian health care professionals regarding patient education,
informed consent, procedural aspects, and options for cord blood
banking in Canada.
Options: Selective or routine collection and banking of umbilical cord
blood for future stem cell transplantation for autologous (self) or
allogeneic (related or unrelated) treatment of malignant and non-
malignant disorders in children and adults. Cord blood can be
collected using in utero or ex utero techniques.
Outcomes: Umbilical cord blood counselling, collection, and
banking, education of health care professionals, indications for
cord blood collection, short- and long-term risk and benefits,
maternal and perinatal morbidity, parental satisfaction, and
health care costs.
Key Words: pregnancy, umbilical cord blood, informed consent,
counselling, collection, storage, banking, stem cell transplantation,
ethics, public, private, Canada.
J Obstet Gynaecol Can 2015;37(9):832–844
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
832 l SEPTEMBER JOGC SEPTEMBRE 2015
No. 328, September 2015 (Replaces #156, March 2005)
Evidence: Published literature was retrieved through searches
of Medline and PubMed beginning in September 2013 using
appropriate controlled MeSH vocabulary (fetal blood, pregnancy,
transplantation, ethics) and key words (umbilical cord blood,
banking, collection, pregnancy, transplantation, ethics, public,
private). Results were restricted to systematic reviews, randomized
control trials/controlled clinical trials, and observational studies.
There were no date limits, but results were limited to English or
French language materials. Searches were updated on a regular
basis and incorporated in the guideline to September 2014. Grey
(unpublished) literature was identified through searching the
websites of health technology assessment and health technology-
related agencies, clinical practice guideline collections, and
national and international medical specialty societies.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Benefits, Harms, and Costs: Umbilical cord blood is a readily
available source of hematopoetic stem cells used with increasing
frequency as an alternative to bone marrow or peripheral stem cell
transplantation to treat malignant and non-malignant conditions
in children and adults. There is minimal harm to the mother or
newborn provided that priority is given to maternal/newborn
safety during childbirth management. Recipients of umbilical cord
stem cells may experience graft-versus-host disease, transfer
of infection or genetic abnormalities, or therapeutic failure. The
financial burden on the health system for public cord blood banking
and on families for private cord blood banking is considerable.
Recommendations
11. Health care professionals should be well-informed about cord
blood collection and storage and about factors that influence the
volume, quality, and ability to collect a cord blood unit. (III-A)
12. Health care professionals caring for women and families who
choose private umbilical cord blood banking must disclose any
financial interests or potential conflicts of interest. (III-A)
13. Pregnant women should be provided with unbiased information
about umbilical cord blood banking options, including the benefits
and limitations of public and private banks. (III-A)
14. Health care professionals should obtain consent from mothers
for the collection of umbilical cord blood prior to the onset of
active labour, ideally during the third trimester, with ample time to
address any questions. (III-A)

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.78
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.78
15. Health care professionals must be trained in standardized proce­
dures (ex utero and in utero techniques) for cord blood collection to
ensure the sterility and quality of the collected unit. (II-2A)
16. Umbilical cord blood should be collected with the goal of
maximizing the content of hematopoietic progenitors through the
volume collected. The decision to bank the unit will depend upon
specific measures of graft potency. (II-2A)
17. Umbilical cord blood collection must not adversely affect the
health of the mother or newborn. Cord blood collection should not
interfere with delayed cord clamping. (III-E)
18. Health care professionals should inform pregnant women and
their partners of the benefits of delayed cord clamping and of its
impact on cord blood collection and banking. (II-2A)
19. Cord blood units collected for public or private banking can be
used for biomedical research, provided consent is obtained,
when units cannot be banked or when consent for banking is
withdrawn. (II-3B)
10. Mothers may be approached to donate cells for biomedical research.
Informed consent for research using cord blood should ideally be
obtained prior to the onset of active labour or elective Caesarean
section following established research ethics guidelines. (II-2A)
INTRODUCTION
S ince the first umbilical cord blood transplant in 1988,
cord blood has been established as an alternative source
of HSC for bone marrow reconstitution.1 Cord blood
has several advantages over bone marrow and mobilized
peripheral blood HSC for transplantation, including its
availability, negligible risk to the donor, less stringent
HLA matching requirements, and less chance of GVHD.
Limitations of UCB include insufficient quantity and
quality of a single CBU to engraft adults, slow engraftment
rates, and the potential for transfer of genetically abnormal
Umbilical Cord Blood: Counselling, Collection, and Banking
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
or premalignant cells. The establishment of cord blood
banks has allowed rapid access to well-characterized CBU
by transplant centres around the world, and to date, cord
blood has been used in over 30 000 transplants.2
Hematopoietic Stem Cell Transplantation
Transplantation of blood-forming stem cells to
regenerate the blood and immune system following
dose-intensive radiation treatment remains a potentially
life-saving procedure for patients with malignant and
non-malignant blood and immune disorders such as
leukemia, lymphoma, aplastic anemia, and inherited
metabolic diseases.3 Blood-forming progenitors can be
harvested from patients (autologous) or from healthy
HLA-compatible (allogeneic) donors who are related
or unrelated. Blood stem cells can be procured from
bone marrow harvests, via apheresis of peripheral blood
following cytokine stimulation or from umbilical cord
blood.4–6 Health care professionals should understand
that UCB contains blood-forming stem cells that can
be used in HSC transplantation and also contains other
progenitor cells that are involved in tissue repair and in
the modulation of immune responses.
Immune compatibility is determined by the HLA genes
and is a dominant factor in the selection of an allogeneic
donor or CBU. HLA-matched sibling donors are typically
preferred but are available for only a minority of patients.
With declining fertility rates in Canada over the past 50
years, patients will have diminishing odds of having an
HLA-matched sibling donor7 and transplant recipients will
rely more heavily on unrelated donors and umbilical cord
SEPTEMBER JOGC SEPTEMBRE 2015 l 833
SOGC clinical practice guideline
blood donors. More than 23 million volunteer donors on
73 worldwide registries from 53 countries may be searched
on a website facilitated by BMDW2 in accordance with
standards established by the WMDA,8 which permits the
identification of potential unrelated donors who are willing
to donate bone marrow or peripheral blood stem cells,
including donors listed in the Canadian Blood Services One
Match Marrow and Stem Cell Network9 and the Stem Cell
Donor Registry at Héma-Québec.10 The BMDW-affiliated
registries include banked umbilical cord blood from more
than 611 000 donors from 48 public cord blood banks
in 33 countries, which expands the options even further,
especially for patients with more unusual HLA haplotypes.2
Role of Umbilical Cord Blood
Umbilical cord blood is highly enriched for blood-forming
stem cells and offers some advantages in the setting of
allogeneic transplantation. Cord blood inventories can
be searched rapidly using sophisticated and coordinated
global computerized search algorithms in accordance with
guidelines established by the WMDA and units are readily
available from a network of accredited banks worldwide.8
Another advantage of using cord blood is its greater
flexibility in HLA matching. Although fully matched
CBUs are associated with optimal outcomes in cord blood
transplantation,11,12 disparities in HLA between donor and
recipient are better tolerated than with unrelated donor
transplantation because HLA matching requirements are
less stringent and the risks of GVHD and graft failure are
lower.13 Unrelated donor workups require confirmatory
HLA typing and other testing for transmissible diseases
and the general health status of the donor, and there
may be logistical challenges that delay the collection of
cells from unrelated donors; however, unrelated donors
offer the prospect of future donor leukocyte infusions or
additional cells for boosting the graft function, which is
not possible with CBUs.
ABBREVIATIONS
AABB American Association of Blood Banks
BMDW Bone Marrow Donors Worldwide
CBU cord blood unit
CIBMTR Center for International Blood and Marrow Transplant
Research
FACT Foundation for the Accreditation of Cellular Therapy
GVHD graft-versus-host disease
HLA human leukocyte antigen
HSC hematopoietic stem cell
UCB umbilical cord blood
WMDA World Marrow Donor Association
834 l SEPTEMBER JOGC SEPTEMBRE 2015
The major disadvantage of cord blood transplantation
is the limited dose of stem cells available in CBUs. UCB
volume limits the utility of cord blood transplantation
for larger recipients, including most adults, but it remains
an issue even in pediatric transplantation. Despite being
highly enriched for HSCs, the limited volume that can be
collected (100 to 200 mL) means the total dose of stem
cells may contribute to delayed engraftment following
transplantation and increased risk of bleeding or infection
in recipients.14,15 Several strategies to augment the speed
of engraftment following UCB transplantation have
been investigated, including methods to expand to HSCs
ex vivo before transplantation, co-transplantation of
mesenchymal stromal cells to accelerate homing and
engraftment, and double cord blood transplantation16,17
These strategies, however, will likely introduce significant
additional costs, and their role in transplantation remains
under development.
The cost of CBUs poses another significant barrier to
more widespread use of cord blood as an alternative source
of stem cells, especially with the high cost of obtaining
CBUs from international public banks. It may be possible
to acquire domestic CBUs at lower prices than typical
international fees of US$25 000 to $40 000 per cord.18
During an era of cost containment, banks and transplant
centres will need to address economic factors for banking
establishments to remain viable and to allow transplant
centres to embrace greater utilization of cord blood.19,20
Indications for Use of Cord Blood from a
Family Member
A recent analysis of data from the CIBMTR reviewed the
use of related allogeneic transplantation using umbilical
cord blood stored in private family banks or through
a directed donation program with a public bank. This
approach may be useful when bone marrow or peripheral
blood stem cells cannot be collected readily from a
sibling, such as when siblings are infants. A total of 244
patients from 73 centres were reported to the CIBMTR
between 2000 and 2012. Transplants were performed most
commonly for acute leukemia (37%), thalassemia or sickle
cell disease (29%), Fanconi anemia (7%), and inherited red
cell, immune, or metabolic disorders (18%). The Eurocord
registry has identified more than 500 patients transplanted
with related cord blood from 1988 to 2010.21 Most recipients
were children, and all but 29 were HLA-matched. Patients
and their families who travel abroad to undergo related
cord blood transplantation may be exposed to increased
risks of complications that may jeopardize their safety
and also be associated with significant personal expense.22
The regulatory oversight concerning transplantation is

dramatically different from Canada in some jurisdictions
and for the safety of patients this form of medical tourism
is highly discouraged.
Recommendation
1. Health care professionals should be well-informed
about cord blood collection and storage and about
factors that influence volume, quality, and ability to
collect a cord blood unit. (III-A)
PUBLIC CORD BLOOD BANKING
Public cord blood banks are sponsored and funded nationally
or locally to process and store donated umbilical CBUs. The
donated CBUs are HLA-typed and entered into a national
or international registry that allows them to be searched, in
a manner similar to bone marrow registries, by transplant
centres around the world in need of a donor. A CBU stored
in a public bank is made available to any patient in need of a
transplant for which it is a suitable match and is not reserved
for the donating family. With public banks, there is no
guarantee that donors or their family members will necessarily
have access to their specific donor unit in the future.
Public banks do not directly charge the family for the
processing and storage of the donated CBU, but a CBU
obtained from a public bank outside of Canada can be
extremely costly.18 The high cost of obtaining international
CBUs has been the subject of much discussion, and prices
for these units are beginning to decline. The cost of
establishing and running a national public bank, however,
is formidable and is borne by the general public. It may
be possible to recover some costs of the public banking
efforts through fees to international transplant centres,
but reciprocity in reducing costs would allow transplant
centres greater access to CBUs.
Considerations Regarding Public Banking
Both public and family cord blood banking establishments in
Canada must meet Health Canada regulatory requirements
for cells, tissues, and organs.23 These regulations include
all aspects of recruitment, collection, transportation,
storage, testing, and documentation, and ultimately, the
release of the units to transplant centres. Moreover, public
banks should seek accreditation from international bodies
such as AABB24 and FACT25 to remain relevant on the
international stage. This is essential to their economic
viability and the assurance of optimal quality and safety
of the products. Public cord blood banking is ideally
suited to addressing the needs of patients from ethnic
minorities and patients with uncommon HLA haplotypes
who remain underrepresented on worldwide registries
of unrelated donors. The selection of partner hospitals,
Umbilical Cord Blood: Counselling, Collection, and Banking
therefore, should include a careful assessment of how
well the bank can address issues such as ethnic diversity
within the population of expectant mothers and issues that
may impact access to mothers and the collection of large
volume CBUs.
The goal of public cord blood banks is to create an
inventory of assessable CBUs suitable for hematopoietic
stem cell transplantation. Public banks set very strict
criteria for collection volume and total nucleated cell
doses to create an inventory of high quality units that
will be associated with more rapid engraftment and with
acceptable rates of transplant-related complications. As a
consequence, a significant number of CBUs donated to
public banks are discarded or donated to research.
Public cord blood banks are designed to serve the needs
of patients and cannot reasonably accommodate every
mother’s desire to donate cells. The practices of banking
establishments and partner hospitals must adhere to the
regulations outlined by Health Canada,23 and this imposes a
level of standardization and reliance on protocols for health
care professionals that often exceeds normal health care
practices. Managing the impact of public cord blood banking
on the perinatal routines and practices of the health care
team and mothers is an important consideration. Mothers
need to learn about public cord blood banking options well
before delivery and should ideally provide permission to
collect before the onset of active labour or early in labour
while consent can reasonably be given. Working closely with
health care professionals in the community, many public
banking establishments obtain consent to collect first and
then determine whether the unit is bankable based on
the volume and total nucleated cell count at the time of
collection. These parameters are meant to identify units with
the greatest utility in the setting of transplantation. More
than 80% of units selected for transplantation from the
inventory of cord blood banks contain more than 1.2 × 109
nucleated cells,18 and more established banks replenish their
inventories exclusively with units of more than 1.5 × 109
cells. If a collected unit meets initial screening criteria for
eligibility, a more complete acquisition of maternal history,
clinical findings, and lab testing for transmissible infectious
diseases is performed. This 2-stage approach focuses time
and resources on the units with the greatest likelihood of
being requested by transplant centres. The extensive time
and resources required to administer the maternal health
questionnaire and arrange for the testing of infectious
disease markers necessitates the involvement of personnel
dedicated to the banking effort. These personnel need to
work cooperatively with health care professionals to ensure
that banking efforts are fruitful and that the needs of the
SEPTEMBER JOGC SEPTEMBRE 2015 l 835
SOGC clinical practice guideline
mothers and babies are not compromised. When units are
collected but do not meet the threshold for volume or total
nucleated cell count needed for the unit to be banked, the
cord blood can be made available for biomedical research
through programs such as the Cord Blood for Research
Program at Canadian Blood Services. Public cord blood
banking is resource-intensive and banking facilities need
to partner with birth units to meet the demands and
expectations of transplant centres and their patients. Public
banks and collecting hospitals should work collaboratively
to identify compatible donors from underrepresented ethic
groups, particularly First Nations, Inuit, and Metis.
PRIVATE CORD BLOOD BANKING
Private (also known as family) cord blood banks store
processed umbilical CBUs for the private use of the family.
The family of the newborn child pays a fee to process and
store the CBU and the mother is typically named the legal
custodian of the banked CBU. Thus the banked CBU is
accessible only to the family who banked it and will be
available to them if and when required. Some Canadian
private UCB banks also fund “medical needs” programs
whereby the cost to process and store the UCB is waived
for families whose expected child has a sibling in need of a
bone marrow transplant.
Private banks charge the family for processing and storing
the CBU for their exclusive use by the family The average
cost in Canada is about $1200 for processing and first
year of cryopreservation. Subsequent yearly storage fees
generally run between $100 and $130. Alternative payment
plans are often offered, including an 18-year single-cost
plan in some cases. Eighteen years is a logical term for
such a plan, since the child from which the cord blood
was collected will have reached the age of majority at the
end of the term and can then decide whether or not to
continue to bank the CBU.
Considerations Regarding Private Banking
Because of the inheritance of HLA, the chance of any
sibling being a full HLA match to another sibling is
essentially 25%, and this chance increases with the number
of siblings. The use of HLA-matched related CBUs may
reduce the risk of GVHD and improve transplant outcomes
over the use of unrelated cord blood transplantation if the
number of cells in the stored unit is sufficient and if tests
for transmissible disease are satisfactory.
Although GVHD occurs less commonly following HLA-
matched marrow and peripheral blood stem cell transplant
in an era of high resolution HLA typing, studies of cord
blood transplants show a significant reduction in GVHD.
836 l SEPTEMBER JOGC SEPTEMBRE 2015
Indeed, early Eurocord studies in patients with leukemia
suggest that rates of GVHD following related cord blood
transplants26 may be less than rates following unrelated cord
blood transplantation.27 Similarly, in non-malignant diseases
treated by related or unrelated cord blood transplants,
Bizzetto found that the risk of acute GVHD was lower with
related cord blood transplants compared to unrelated cord
blood and the 3-year survival rate was better.28
Since CBUs are already paid for and stored in private
banks, there is no cost to the medical system when the
units are used except for specific hospital costs. The cost
of obtaining public units, however, can be prohibitive,
although they may be discounted or waived for domestic
use and continue to decrease as worldwide inventories
increase.
The goal of private cord blood banks is to cryopreserve
quality CBUs that may be used for hematopoietic stem cell
transplantation or future regenerative medicine therapies.
Thus private banks typically do not use the same banking
criteria as public banks in terms of collection volume and
total nucleated cell doses. Private banks appeal to families
whose intended recipient for a hematopoietic stem cell
transplant may be much smaller than the 60 kg recipient
targeted by public banks. Several new technologies in
development are intended to either expand the number
of HSCs in a given CBU or improve the homing of the
HSCs to the bone marrow with the aim of improving the
speed of engraftment. These developing technologies
are not routinely available at this time. Success in these
technologies, however, would allow “small” units banked
today to be useful for larger recipients in the future.
Regenerative medicine refers to the process of replacing
or repairing human cells, tissues or organs to return or
establish normal functioning. Cord blood stem cells are
presently being examined for use in regenerative medicine
or for treating non-blood diseases including type 1 diabetes,
cardiovascular repair, traumatic brain injury, cerebral palsy,
autism, and hearing loss. Some of these trials are restricted
to patients having access to their own (autologous) cord
blood, whereas many of these research protocols have
reported the use of allogeneic CBUs.29 Therapeutic cell
doses have yet to be established. Private cord blood banks
set their own acceptance criteria for banking CBUs, which
results in a much higher percentage of their collected units
being banked than those of public banks.
A banked CBU from a person with no family history
of disease treatable by bone marrow transplantation
arguably has a very low chance of being used. The chance
that a person will contract a disease treatable by their

stored cord blood by age 21 has been estimated to be
approximately 0.005% to 0.04%.17 A more recent analysis
of the likelihood of requiring a bone marrow transplant
has taken into account treatable diseases up to the age of
70 years, the upper limit for bone marrow or peripheral
blood stem cell transplants at some centres. This is a model
more representative of the concept of family banking,
although it remains unclear how long autologous units can
be stored with current cryopreservation methods. In that
calculation, the probability of the need for hematopoietic
transplantation for a family member is about 1/400 and
may be as high as 1/200.30
With future advances in medical technology such as gene
therapy, tissue therapeutics for treatment of non-blood
diseases, and ex vivo cell expansion, the probability of a
banked CBU, especially an autologous CBU, may increase,
and this provides a compelling rationale for some families
to privately bank their children’s cord blood. On the other
hand, improvement in medical treatment of serious disease
may make the need for stem cell transplantation less
necessary in the future and result in a reduced probability
of using a banked CBU. As a result, it is now impossible
to predict the future value of family UCB banking. Private
cord blood banks must provide accurate and transparent
information regarding fees, likelihood of using the CBU,
methods of opting out and other costs to patients and
families.
Recommendation
2. Health care professionals caring for women and
families who choose private umbilical cord blood
banking must disclose any financial interests or
potential conflicts of interest. (III-B)
COORDINATION OF PRIVATE AND PUBLIC BANKS
CBUs that are stored in private banks cannot be searched
by transplant centres for unrelated patients but may be
used for autologous hematopoietic transplantation or
allogeneic transplantation for another family member.
Although uncommon at present, the use of autologous or
related UCB transplantation may change in the future in
response to ongoing studies of novel applications in areas
such as regenerative therapy. Guidelines and transparency
with respect to fees, chances of using the unit, methods of
opting out and other costs should be available to patients
and families. Transferring banked units from private banks
to public banks is challenging and guiding principles have
been established by the WMDA that highlight issues such
as the requirement for donor consent for public banking
at the time of collection, the need to meet regulatory and
Umbilical Cord Blood: Counselling, Collection, and Banking
accreditation standards applicable for publicly banked
units, and the requirement for separate storage away from
units that do not meet public banking criteria.8 In addition,
the safety of infusing autologous banked units has been
demonstrated in numerous settings although significant
differences in indicators of CBU quality were reported
in a recent study compared with publicly banked units.31
Increased collaboration between private and public banks
may help to improve the quality of all CBUs collected.
EDUCATION OF PARENTS AND
HEALTH CARE PROFESSIONALS
Despite growing evidence of the therapeutic benefits
of umbilical cord derived stem cells and promotion of
umbilical cord blood collection for allogeneic, family-
directed, or autologous use in the media, surveys reveal
that the majority of pregnant women (70 to 80%) lack
knowledge about stem cells and cord blood banking and
want more information.32–36 While most women (80%
to 90%) would prefer to receive information about cord
blood banking from their health care professionals,
prenatal education and counselling is only provided to a
minority (15 to 30%).33,36,37 Consequently, many pregnant
women receive information through printed material, the
internet, or the media.36,37 Surveys from Canada, Europe,
and the United States suggest that once informed, the
majority of women would consider donating cord blood
for therapeutic use.32,36,37 Overall, women appear to be more
inclined to donate to public banks than to private or mixed
banks.32,36,37 Approximately 80% of practicing obstetricians
in the United States feel confident in discussing cord blood
options with their patients, but less than 50% indicate that
they have sufficient knowledge of cord blood donation to
effectively answer patients’ questions about donation.38
Not surprisingly, women are often misinformed and
confused about the risks and benefits of umbilical cord
blood donation and the advantages and limitations of
cord blood banking options. In evaluating their choices,
women may be motivated to donate their baby’s umbilical
cord blood to a public cord blood bank as an altruistic
act of civic responsibility or to a private bank for the
potential future benefit of their child or immediate
family.39 Physicians and other health care professionals
are recognized as the primary source of information
and guidance for pregnant women and should be well-
informed about the practical implications of umbilical
cord blood collection and storage and the benefits and
limitations of public and private cord banks. Health care
professionals in perinatal facilities should become actively
involved in the provision of education about cord blood
SEPTEMBER JOGC SEPTEMBRE 2015 l 837
SOGC clinical practice guideline
banking and policies regarding cord blood collection and
in the development of collection protocols to improve
cord blood volume and quality.33,40,41 Though storage of
cord blood for autologous use remains controversial,
therapeutic indications for umbilical cord blood stem cells
and the use of autologous and family-directed CBUs for
transplantation is growing.42–46 Information about cord
blood collection and banking provided by health care
professionals must be balanced and accurate about its
advantages and disadvantages.47 Prospective parents should
understand that infants with an underlying genetic disease
are very unlikely to be transplanted with autologous cord
blood that generally harbours the same gene abnormality
and that many diseases may not be amenable to therapy
until new treatments are developed.42 Parents also should
be informed about maternal infectious disease and genetic
testing and the process for disclosure of abnormal findings.
Physicians and health care professionals should provide
unbiased information about both public and private cord
blood banking and should encourage directed donation
for immediate family members with specific treatable
diseases.48 Health care professionals are discouraged from
endorsing specific cord blood banks and are obliged to
disclose any financial or other conflicts of interest.42
Obstetricians should be knowledgeable enough about the
present uses of umbilical cord blood to be able to have a
discussion with patients and answer most questions. It is
important to be able to discuss the differences between
public and family banking and to know which options are
available.
Recommendation
3. Pregnant women should be provided with unbiased
information about umbilical cord blood banking
options, including the benefits and limitations of
public and private banks. (III-A)
INFORMED CONSENT
Because newborn infants are unable to consent to the
collection, testing, donation, and storage of their cord blood,
informed consent must be obtained and documented from
the mother or father. Cord blood collected for therapeutic
use or research is not considered waste material and it is
generally agreed that informed consent for collection is
required.49 Prenatal, pre-labour, and post-collection consent
policies have been developed by cord blood banks and
professional organizations to address the procedural and
financial priorities of public and private blood banks,43,44
and so could be obtained at presentation in early labour. It
is generally agreed that consent should be obtained prior
838 l SEPTEMBER JOGC SEPTEMBRE 2015
to the onset of active labour and ideally during the third
trimester of the prenatal period.50 A phased consent policy
for cord blood donation has been proposed and endorsed
by the American Academy of Pediatrics.51 In phase one,
information about cord blood banking including risks,
benefits, advantages, and limitations is provided to parents
as part of prenatal care. Donor registration with the cord
blood bank and perinatal institution is also recommended.
The second phase of the consent policy occurs when a
woman is admitted to the birth unit for labour and delivery.
Eligibility criteria for cord blood collection include the
absence of active labour, intact membranes, term singleton
pregnancy, no history of viral, congenital, or genetic diseases
and the ability of the mother to understand the implications
of cord blood collection.
The procedure for obtaining consent is limited to an
explanation of the need to collect blood immediately
following delivery, a description of the collection
technique, and information about the possible risks of
the procedure. The post-collection consent procedure
addresses maternal infectious and genetic disease testing,
access to health record information and newborn screening
tests, maternal medical history, cord blood processing and
storage, and the potential use of cord blood for therapeutic
and research purposes. The mother’s right to refuse
collection, processing, or storage of the cord blood at any
time without prejudice must be inherent in the consent
process. It is also important for parents to be assured that
information related to the infant donor and the donor’s
family will remain confidential and maintained by the cord
blood bank so that parents or physicians can be notified of
infectious or genetic diseases.49
Consent policies and procedures vary widely across
regional and national jurisdictions, public and private cord
blood banks, and perinatal care facilities. Standardization
of informed consent for umbilical cord blood
donation following AABB24 and FACT25 guidelines is
recommended. Institutional review and approval of cord
blood donation consent policies are also encouraged.49 If
cord blood does not meet criteria for clinical use or when
donors decide to terminate storage of a CBU, cord blood
banks are encouraged to offer donors the opportunity
to donate the cord blood to research, subject to donor
consent.52
Recommendation
4. Health care professionals should obtain consent
from mothers for the collection of umbilical cord
blood prior to the onset of active labour, ideally
during the third trimester, with ample time to
address any questions. (III-A)

UMBILICAL CORD BLOOD COLLECTION
Umbilical cord blood is collected from the umbilical
vein either before the placenta is delivered (in utero) or
following placental delivery (ex utero). Both methods
have advantages and disadvantages.53 Both techniques are
in use at Canadian public cord blood banks, although the
in utero technique is preferred by most public banks in
the United States and many European countries because it
can be performed in the delivery room by birth unit staff,
is easy to learn, and does not usually require additional
personnel or resources.53,54 All private banks use in
utero collection methods. Evidence from comparative
studies suggest that the in utero technique yields slightly
higher volumes of cord blood and higher yields of total
nucleated cells compared to the ex utero technique.55–57
The standard in utero method for cord blood collection
uses a closed collection system to reduce the risk of
infection and maternal fetal fluid contamination. The
umbilical cord is double-clamped approximately 3 to
5 cm from the umbilicus and transected between the
clamps. After the infant has been removed from the field,
the cord is prepared for venipuncture using a povidone
iodine applicator. The needle of the cord collection kit
is then inserted into the umbilical vein and the CBU is
collected by gravity. The time required to perform the
cord collection procedure is approximately 5 to 10 minutes
and additional personnel are not required.54,58,59 Factors
known to reduce cord blood volume include maternal
hypertension, smoking, multiple gestation, preterm
delivery, intrauterine growth restriction, abnormal
placentation, emergency CS, precipitous delivery, and
maternal transfer.17,59 Factors associated with higher cord
blood volumes and greater yield of nucleated cells include
birth weight, placental weight, gestational age, induction
of labour, prolonged labour, CS, early cord clamping,
first born infants, Caucasian ethnicity, and female infant
gender.60 Umbilical cord blood obtained after CS for
acute fetal distress also appears to significantly increase
total nucleated cells, CD34+ cells, and white blood
cells without compromising cord volumes and should
not preclude cord blood collection unless maternal and
newborn safety may be compromised.61,62
A number of manoeuvres have been proposed to optimize
cord blood volume. Using large syringes (50 to 60 cc)
and a syringe withdrawal-saline flush-syringe withdrawal
technique as part of the closed collection system have
yielded significantly higher mean volume collected (150
to 175 mL), compared with standard in utero collection
by gravity (75 to 100 mL). Clamping the umbilical cord
within 30 seconds of delivery and placing the newborn
Umbilical Cord Blood: Counselling, Collection, and Banking
infant on the maternal abdomen after delivery have also
been reported to improve recovery volume and CD34+
cell content;63,64 however, this early clamping defeats the
benefits of delayed clamping.
Ex utero cord blood collection is performed by
dedicated, trained personnel in a separate room and
standard collection bag as soon as possible after delivery
of the placenta. The cord blood is collected by gravity
with the placenta suspended on a specifically designed
stand.54,65 Although this method allows birth unit staff
to focus on maternal and infant health, the procedure
requires additional trained personnel, resources, and
cost but reduces the frequency of non-conformances
associated with collection of units from staff that are not
affiliated with the bank. Disadvantages of this method
are the possibility of lower cord blood volume and total
nucleated cell counts. As with in utero collection, factors
associated with increased collected volume using the ex
utero technique include: singleton pregnancy, post-term
pregnancy, induced labour, prolonged labour, CS, cord
length greater than 30 cm, birth weight ≥ 3500 g, and
placental weight > 700 g.48,54,66
Umbilical cord collection poses a number of logistical
issues that may increase the burden for busy birth units.
The consent procedure and associated paperwork adds
time and inconvenience to the work of health care
professionals. Collection procedures performed during
the third stage of labour at a time when both mother
and baby require attentive care and risk of postpartum
hemorrhage must not jeopardize maternal newborn
health. Birth unit personnel feel under pressure to obtain
adequate volume of cord blood and to avoid bacterial
contamination. Attention to the cord blood collection
may also impact on the care of other mothers and infants.
Consequently, umbilical cord blood collection should
not interfere with the normal management of the third
stage or compromise the safety of mother and baby.59,67
Contraindications to cord blood collection include
preterm birth, serious maternal medical or obstetric
complications, such as cardiac arrest, stroke, eclampsia or
massive hemorrhage, and perinatal asphyxia.
Regulatory Issues and Practice Standards for
Collecting and Processing Umbilical Cord Blood
Cord blood banks must adhere to strict regulatory
requirements and focus on additional factors to ensure that
UCB units stored in the bank are of the highest quality
and thus remain beneficial to transplant centres and their
patients. Accreditation and compliance with nationally and
internationally recognized regulatory bodies ensure that
all aspects of recruitment, donor screening, collection
SEPTEMBER JOGC SEPTEMBRE 2015 l 839
SOGC clinical practice guideline
and transport, processing, testing, freezing, storage, and
distribution are standardized and meet international
thresholds of quality. The use of current measures of
graft potency is also critical so transplant centres and
patients have confidence regarding the assurance of timely
engraftment following transplantation. The collection and
storage of UCB must adhere to Health Canada regulations
under the cells, tissues, and organs guidelines23 to ensure
the quality of CBUs in terms of HSC content, absence of
infectious agents, and risk of transmitting genetic disease.
In addition, international guidelines are provided by FACT
and AABB. These shape operational issues related to cord
blood banking in Canada and around the world through
the International NetCord Foundation).
Recommendations
5. Health care professionals must be trained in
standardized proce­dures (ex utero and in utero
techniques) for cord blood collection to ensure the
sterility and quality of the collected unit. (II-2A)
6. Umbilical cord blood should be collected with the
goal of maximizing the content of hematopoietic
progenitors through the volume collected. The
decision to bank the unit will depend upon specific
measures of graft potency. (II-2A)
7. Umbilical cord blood collection must not adversely
affect the health of the mother or newborn. Cord
blood collection should not interfere with delayed
cord clamping. (III-A)
8. Health care professionals should inform pregnant
women and their partners of the benefits of
delayed cord clamping and of its impact on cord
blood collection and banking. (II-2A)
Timing of Umbilical Cord Clamping
There is growing evidence of the benefit of delayed cord
clamping for 1 to 3 minutes in preterm infants (< 37
weeks).68–71 Systematic reviews have demonstrated that
delayed cord clamping in preterm infants results in reduced
need for transfusions, better circulatory stability, improved
blood pressure and decreased risk of intraventricular
hemorrhage and necrotizing colitis.68,71 Recent evidence
suggests that delayed cord clamping in very preterm and
very low birth infants protects against motor disability
at 7 months of age.70 In light of the this evidence,
several professional organizations have recommended
implementation of delayed cord clamping for preterm
infants despite health care professionals’ concerns about the
need for immediate resuscitation and risk of hypothermia.72
Since umbilical cord banking is generally contraindicated in
preterm infants, delayed cord clamping in this population
should have no impact on cord blood banking.
840 l SEPTEMBER JOGC SEPTEMBRE 2015
Delayed cord clamping in term infants has been consistently
shown to enhance placental transfusion at birth and increase
hemoglobin, hematocrit, ferritin levels, and iron stored
up to 6 months of age.70,73,74 Though prevailing evidence
also suggests that delayed cord clamping promotes higher
iron stores in the longer term,70 delayed cord clamping
did not affect iron status or neurodevelopment at age 12
months in a recent randomized controlled trial of healthy
term-born infants in Sweden.75 Concerns have been raised
regarding the increased risk of phototherapy for postnatal
jaundice and polycythemia associated with delayed cord
clamping.74 WHO recommends a 1 to 3 minute delayed
cord clamping in term infants, particularly in populations
where iron deficiency anemia is endemic and provided
there is provision for screening and treatment of neonatal
jaundice.76 SOGC recommends weighing the risk of
neonatal jaundice against the physiological benefit of
increased hemoglobin and iron levels,71 whereas ACOG
concludes that there is insufficient evidence to support or
refute delayed cord clamping in term infants.72 Based on the
available evidence, delayed cord clamping in health term
infants appears to be beneficial provided that treatment for
jaundice requiring phototherapy is available.70
Umbilical cord collection in preterm infants (< 37
weeks gestation) is generally contraindicated. Early cord
clamping within 30 seconds of delivery is associated
with optimal volume and progenitor cells for cord
blood collection while delayed cord clamping for 1 to 3
minutes decreases the volume of cord blood available for
collection. While cord blood collection following delayed
cord clamping is not contraindicated, parents should
be aware that the practice may preclude collection of
sufficient cord blood for banking.
RESEARCH AND POTENTIAL FUTURE
USE OF UMBILICAL CORD BLOOD
There is increasing interest in the use of cord blood for
novel indications in regenerative therapy or as a means
of immune modulation. A recent systematic review
identified a small number of published studies involving
approximately 300 patients.29 The most common
emerging area described in these studies addressed the
repair of neurological conditions, including cerebral
palsy. A large study using umbilical cord blood in the
treatment of cerebral palsy is ongoing.77 Other diseases
that may be amenable to cord blood transplantation
include type I diabetes and liver disease. Some studies
have investigated the use of mesenchymal stromal cells
expanded from umbilical cord blood. It is not yet clear
how effective cord blood-derived cells are in these novel

indications as most studies are uncontrolled and involve
few subjects and are proof-of-principle in nature only.
Moreover, strategies to culture cells from cord blood may
complicate banking efforts and introduce new regulatory
challenges. It remains to be seen whether public banks
will develop methods to screen for umbilical CBUs that
are better suited to applications in regenerative therapy
or immune modulation or whether increasing numbers
of public banks will develop methods to store HSCs
or other cell types expanded from cord blood. UCB
represents a rich source of progenitor cells with a broad
range of biological functions and tremendous potential
for the development of novel cell-based therapies.
Recommendations
  9. Cord blood units collected for public or private
banking can be used for biomedical research, provided
consent is obtained, when units cannot be banked or
when consent for banking is withdrawn. (II-3B)
10. Mothers may be approached to donate cells for
biomedical research. Informed consent for research
using cord blood should ideally be obtained prior
to the onset of active labour or elective Caesarean
section following established research ethics
guidelines. (II-2A)
CORD BLOOD BANKING IN CANADA
Current banking efforts reflect state of the art practices
which will make the Canadian contribution important.
Public banking activity has occurred in some regions of
the country for several years (Alberta Cord Blood Bank,
Héma-Québec Cord Blood Bank, and the Victoria Angel
Registry of Hope), and the launch of the National Public
Cord Blood Bank at Canadian Blood Services began in
2013. The establishment of a public bank with the capacity
to store many high quality HLA-typed CBUs from a diverse
cross-section of ethnicities should benefit both Canadian
and international patients. Such a bank would increase the
odds of finding a suitably matched CBU for patients in
need of a hematopoietic cell transplant who do not have a
matched sibling or unrelated donor. Recently, some public
banks such as Héma-Québec have instituted a medical
needs program to store, for up to 2 years, a CBU from
a sibling of a child requiring a bone marrow transplant
for the express use of that family member in need of the
transplant. Private banks existed in Canada prior to public
banking efforts and offer the possibility of a related cord
blood transplant for patients and the option of possible
autologous transplantation. Indications for autologous
use, however, remain under debate and are not performed
routinely.
Umbilical Cord Blood: Counselling, Collection, and Banking
Public Cord Blood Collection in Canada as of 2015
The National Public Cord Blood Bank at Canadian
Blood Services has been collecting and storing units since
September 30, 2013, building on the recognized need for
a national effort in public cord blood banking in Canada.
The initial collection and manufacturing site is in Ottawa. A
second manufacturing site and collection site in Edmonton
became operational in July 2014, and additional collection
sites in Vancouver and Brampton began contributing to the
bank in January 2015. The bank intends to store more than
10 000 high quality units by 2018 and the units will have
high cell content and engraftment potency, be searchable
internationally through the BMDW, and reflect the ethnic
diversity of Canada, including First Nations, Inuit, and
Metis who have low UCB representation. Héma-Québec
has a public cord blood bank that is FACT-accredited and
has more than 9000 units stored since they first started
collecting in 2004. The units are searchable through the
BMDW and they have supplied cord blood for more than
100 Canadian and international patients. The collection
hospitals are in Montreal and Laval. The Victoria Angel of
Hope Registry is a third Canadian public cord blood bank
affiliated with the Cells for Life family bank in Toronto
that continues to recruit expectant mothers. It has recently
registered with BMDW and offers international searching
of its inventory of several hundred CBUs.
SUMMARY
The National Public Cord Blood Bank was established
by the Canadian Blood Services in 2013 and public cord
blood banking will be available in selected Canadian sites
focussed on the storage of a diverse ethnic cross-section
of HLA-typed CBUs. Public cord blood banking at
HémaQuebec and the Victoria Angel of Hope Registry
continues to grow. Private cord blood banking facilities are
located in major urban centres in Canada and provide the
opportunity for family cord blood collection and storage
from coast to coast.
Health care professionals should be aware of current
recommendations for education, counselling, obtaining
informed consent, collection, and storage of umbilical
cord blood. Information regarding cord blood banking
options in Canada should be presented in a comprehensive
and unbiased manner.
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U.S. National Library of Medicine; 2015. Available at:
http://www.clinicaltrials.gov. Accessed on May 27, 2015.
78. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W.
Canadian Task Force on Preventive Health Care. New grades for
recommendations from the Canad ian Task Force on Preventive
Health Care. CMAJ 2003;169:207–8.
 SOGC CLINICAL PRACTICE GUIDELINE
Vulvovaginitis: Screening for and Management
of Trichomoniasis, Vulvovaginal Candidiasis,
and Bacterial Vaginosis
This clinical practice guideline has been prepared by the
Infectious Diseases Committee, reviewed by the CANPAGO
and Family Physician Advisory Committees, and approved
by the Executive and Board of the Society of Obstetricians
and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Julie van Schalkwyk, MD, Vancouver BC
Mark H. Yudin, MD, Toronto ON
INFECTIOUS DISEASE COMMITTEE
Mark H. Yudin, MD (Chair), Toronto ON
Victoria Allen, MD, Halifax NS
Celine Bouchard, MD, Quebec QC
Marc Boucher, MD, Montreal QC
Isabelle Boucoiran, MD, Vancouver BC
Sheila Caddy, MD, Calgary AB
Eliana Castillo, MD, Calgary AB
V. Logan Kennedy, RN, Toronto ON
Deborah M. Money, MD, Vancouver BC
Kellie Murphy, MD, Toronto ON
Gina Ogilvie, MD, Vancouver BC
Caroline Paquet, RM, Trois-Rivieres QC
Julie van Schalkwyk, MD, Vancouver BC
Disclosure statements have been received from all contributors.
Key words: bacterial vaginosis, yeast, candidiasis, trichomonas
vaginalis, trichomoniasis, vaginitis, treatment
J Obstet Gynaecol Can 2015;37(3):266–274
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
266 l MARCH JOGC MARS 2015
No. 320, March 2015 (Replaces No. 211, August 2008)
Abstract
Objective: To review the evidence and provide recommendations
on screening for and management of vulvovaginal candidiasis,
trichomoniasis, and bacterial vaginosis.
Outcomes: Outcomes evaluated include the efficacy of antibiotic
treatment, cure rates for simple and complicated infections, and
the implications of these conditions in pregnancy.
Evidence: Published literature was retrieved through searches
of MEDLINE, EMBASE, CINAHL, and The Cochrane Library
in June 2013 using appropriate controlled vocabulary (e.g.,
vaginitis, trichomoniasis, vaginal candidiasis) and key words
(bacterial vaginosis, yeast, candidiasis, trichomonas vaginalis,
trichomoniasis, vaginitis, treatment). Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. There were no date limits, but
results were limited to English or French language materials.
Searches were updated on a regular basis and incorporated in the
guideline to May 2014. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology-related agencies, clinical practice guideline
collections, and national and international medical specialty
societies.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Summary Statements
1. Vulvovaginal candidiasis affects 75% of women at least once. Topical
and oral antifungal azole medications are equally effective. (I)
2. Recurrent vulvovaginal candidiasis is defined as 4 or more
episodes per year. (II-2)
3. Trichomonas vaginalis is a common non-viral sexually transmitted
infection that is best detected by antigen testing using vaginal
swabs collected and evaluated by immunoassay or nucleic acid
amplification test. (II-2)
4. Cure rates are equal at up to 88% for trichomoniasis treated
with oral metronidazole 2 g once or 500 mg twice daily for
7 days. Partner treatment, even without screening, enhances
cure rates. (I-A)
 Vulvovaginitis: Screening for and Management of Trichomoniasis, Vulvovaginal Candidiasis, and Bacterial Vaginosis
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.76
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.76
5. Current evidence of the efficacy of alternative therapies for
bacterial vaginosis (probiotics, vitamin C) is limited. (I)
Recommendations
1. Following initial therapy, treatment success of recurrent
vulvovaginal candidiasis is enhanced by maintenance of weekly
oral fluconazole for up to 6 months. (II-2A)
2. Symptomatic vulvovaginal candidiasis treated with topical azoles
may require longer courses of therapy to be resolved. (1-A)
3. Test of cure following treatment of trichomoniasis with oral
metronidazole is not recommended. (I-D)
4. Higher-dose therapy may be needed for treatment-resistant cases
of trichomoniasis. (I-A)
5. In pregnancy, treatment of symptomatic Trichomonas vaginalis
with oral metronidazole is warranted for the prevention of preterm
birth. (I-A)
6. Bacterial vaginosis should be diagnosed using either clinical
(Amsel’s) or laboratory (Gram stain with objective scoring system)
criteria. (II-2A)
7. Symptomatic bacterial vaginosis should be treated with oral
metronidazole 500 mg twice daily for 7 days. Alternatives
include vaginal metronidazole gel and oral or vaginal clindamycin
cream. (I-A)
8. Longer courses of therapy for bacterial vaginosis are
recommended for women with documented multiple
recurrences. (I-A)
ABBREVIATIONS
HIV human immunodeficiency virus
NAAT nucleic acid amplification test
PHAC Public Health Agency of Canada
STI sexually transmitted infection
VVC vulvovaginal candidiasis
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
VULVOVAGINAL CANDIDIASIS
V ulvovaginal candidiasis is a very common condition
that affects up to 75% of women at least once in their
lifetime.1 Risk factors for VVC include sexual activity, recent
antibiotic use, pregnancy, and immunosuppression from such
conditions as poorly controlled HIV infection or diabetes.2,3
The Organisms
VVC is most often caused by Candida albicans4; however,
other species of Candida such as glabrata, parapsilosis, and
tropicalis are emerging.5
The main reservoir for Candida is thought to be the
rectum, but vaginal colonization is also common. The
factors associated with evolution from colonization
to symptomatic infection are multiple and involve a
combination of host susceptibility, host inflammatory
responses, and Candidal virulence factors. Symptoms are
thought to be caused by an overabundance of yeast and its
penetration of vulvovaginal epithelial cells.6
The Disease
The signs and symptoms of uncomplicated VVC include a
thick cottage-cheese–like discharge associated with vaginal
and vulvar pruritus, pain, burning, erythema, and/or
edema. External dysuria and dyspareunia may also occur.
Complicated VVC may be defined as that which is recurrent
(4 or more episodes in a 12 month period), associated with
severe symptoms, the result of a non-albicans species, or
present in a compromised host.7 This condition is more
MARCH JOGC MARS 2015 l 267
SOGC clinical practice guideline
common in those with immunosuppression, diabetes, or
both.8 Additional testing for HIV9 and diabetes may be
warranted in these situations.
Diagnosis
The diagnosis of VVC requires pelvic examination. The
combination of thick white discharge and vulvar pruritis
is neither sensitive nor specific on its own for diagnosis.
Erythema and edema of vulvar and vaginal tissues, in
conjunction with thick, white clumped vaginal discharge,
are supportive of the diagnosis. The vaginal secretions of
VVC have a pH <  4.5, and budding yeast and pseudohyphae
may be seen on wet mount. Whiff test is negative and
gram stain may reveal polymorphonuclear cells, budding
yeast, and pseudohyphae.
When there is evidence of complicated VVC, collection
of vaginal fluid for culture and yeast speciation may help
direct therapy because there is an increased likelihood of
non-albicans strains in such cases.10
Treatment
Treatment for VVC is necessary only in conjunction with
symptoms. Identification of yeast on wet mount, gram
stain/culture, or Pap screening in the absence of associated
symptoms does not warrant therapy. Over 20% of women
may have yeast as part of their natural vaginal microbiome
and the majority will be asymptomatic.11 Treatment and
dosage options for uncomplicated, recurrent, and non-
albicans VVC are summarized in Table 2.12–17
Pregnancy
In pregnancy, VVC can be prolonged and associated with
more severe symptoms, and resolution of symptoms
typically requires longer courses of therapy. Only topical
azoles are recommended in pregnancy. Treatment using
external imidazole creams and intravaginal ovules for up
to 14 days may be required. Repeat treatments may also be
needed. Oral fluconazole should be avoided in pregnancy
as it may increase the risk of tetralogy of Fallot.18 The
safety of oral fluconazole in the second and third trimesters
has not been investigated. Intravaginal boric acid has been
associated with a greater than 2-fold increased risk of birth
defects when used during the first 4 months of pregnancy,19
and should thus be avoided during this time.
Summary Statements
1. Vulvovaginal candidiasis affects 75% of women
at least once. Topical and oral antifungal azole
medications are equally effective. (I)
2. Recurrent vulvovaginal candidiasis is defined as 4 or
more episodes per year. (II-2)
268 l MARCH JOGC MARS 2015
Recommendations
1. Following initial therapy, treatment success of
recurrent vulvovaginal candidiasis is enhanced by
maintenance of weekly oral fluconazole for up to
6 months. (II-2A)
2. Symptomatic vulvovaginal candidiasis treated with
topical azoles may require longer courses of therapy
to be resolved. (1-A)
TRICHOMONAS VAGINALIS
The Organism
T. vaginalis is an anaerobic parasitic protozoan flagellated
organism that adheres to epithelial cells of the urogenital
tract. For the most part, infection is limited to the
genitourinary tract. With infection, the condition is
referred to as Trichomoniasis.
The Disease
The prevalence of T. vaginalis in the United States is reported
as 3.1% among women of reproductive age (14–49).20
Globally, it is considered the most common non-viral STI,
with an estimated 170 million cases reported annually.21 It
is not a reportable disease in Canada, so precise data on
Canadian prevalence is unavailable.
The symptoms associated with infection can be variable:
64% to 90% of infected people may have no symptoms,22,23
and infection, especially in those who are asymptomatic,
may persist for months or years. Men tend to have
fewer symptoms than women and can therefore serve
as asymptomatic vectors for infection.24 Men who are
symptomatic may experience symptoms of urethritis:
dysuria and a clear or mucopurulent discharge.25 In women,
the organism can be found in the vagina, cervix, bladder,
or Bartholin, Skene, or periurethral glands.26 Symptomatic
women typically have a greatly increased volume of vaginal
discharge; it may be malodorous, green or yellow in color,
and frothy in appearance.27 In addition, significant pruritus
with vulvitis and vaginitis, dysuria, and dyspareunia may
occur. Some may exhibit hemorrhagic spots (petechiae)
on the genital mucosa, referred to as Colpitis macularis
(strawberry cervix).24
Diagnosis
Wet mount for microscopic visualization of the motile
parasite has a sensitivity of up to 65%, and samples should
be visualized within 10 minutes of collection to improve
the likelihood of observing motility.28
Culture of T. vaginalis has high specificity (almost 100%)
but a lower sensitivity (as low as 75%) for diagnosis. Rapid
transport to the laboratory is ideal to insure the viability of
 Vulvovaginitis: Screening for and Management of Trichomoniasis, Vulvovaginal Candidiasis, and Bacterial Vaginosis

Table 2. Treatment options for vulvovaginal candidiasis

Uncomplicated VVC* Therapy Medication Dose
Imidazole antifungals Clotrimazole 1%: once daily × 7 days, or
(over the counter) cream/ointment 2%: once daily × 3 days, or
10%: once only
Insert/ovule/suppository 200 mg: once daily × 3 days or
500 mg: once only
Miconazole 2%: once daily × 7 days, or
cream/ointment 4%: once daily × 3 days
Insert/ovule/suppository 100 mg: once daily × 7 days, or
400 mg: once daily × 3 days, or
1200 mg: once only
Triazole antifungals Fluconazole (oral) (over the counter) 150 mg: once only
Terconazole cream (prescription only) 0.4%: once daily × 7 days
Recurrent VVC†
Induction Imidazole cream 10 to 14 days, as for uncomplicated
VVC above12
Fluconazole (oral) 150 mg: 3 doses, 72 hours apart11
Boric acid insert 300 to 600 mg daily × 14 days13
Clotrimazole insert 500 mg: once monthly × 6 months15
Maintenance‡ Fluconazole (oral) 150 mg: once weekly11
Boric acid insert 300 mg daily × 5 days at the beginning
of each menstrual cycle13
Ketoconazole (oral)§ 100 mg once daily14
Non-albicans VVC
Boric acid insert‖ 300 to 600 mg nightly × 14
Flucytosine cream‖ 5 g once daily × 14 days
Amphotericin B suppository‖ 50 mg once daily × 14 days
Nystatin suppository 100 000 units once daily for 3 to 6 months1
*These types of antifungal regimens are equally effective, with resolution of symptoms occurring in up to 90%.10
†Treatment for recurrent VVC requires induction therapy followed immediately by maintenance treatment.
‡Maintenance therapy should continue for 6 months. In cases of recurrence after completed therapy, induction and maintenance treatment should be
repeated. Recurrence rates on maintenance treatment are low but can be as high as 50% in women off all therapy.
§Monitoring is recommended for rare hepatotoxicity with long-term use and drug interactions.
‖Boric acid insert, flucytosine cream, and amphotericin B may be used in combination

the organism.29 Although the organism may be detected on
Papanicolaou screening tests, this is not considered diagnostic
because of the test’s low sensitivity for T. vaginalis.30
Antigen testing
Immunoassay dipstick testing is available as a rapid antigen
test with results available in 10 minutes. Sensitivity (82–95%)
and specificity (97–100%) are both high.29 NAATs are the
most sensitive tests currently available for use with vaginal
swabs. Urine and cervical swabs can also be used. Sensitivity
and specificity for NAATs are both 95% to 100%.31
Because T. vaginalis is an STI, its diagnosis affords the
opportunity to screen for other STIs.
Treatment
Treatment for T. vaginalis consists of oral metronidazole
either 2 g once or 500 mg twice daily for 7 days. Cure rates
with either of these regimens are as high as 88%, and
are even higher when sexual partners are simultaneously
treated.32 Approximately 5% of T. vaginalis strains will
be resistant to metronidazole. High dose and/or longer
metronidazole therapy tends to be effective in these
situations.33 An alternate therapy for metronidazole-
treatment–resistant cases is Tinidazole 2 g orally once.34,35
This is only available through Health Canada’s Special
Access to Drugs and Health Products Program.36
Partner Treatment
The PHAC 2010 guidelines on STI do not recommend
partner screening but do recommend treatment for all
partners.7 Many men will be asymptomatic. Both patients
and partners should be given the same type of treatment
regimen. The 2010 Centres for Disease Control STI
Guidelines suggest abstaining from intercourse until both

MARCH JOGC MARS 2015 l 269

SOGC clinical practice guideline
patients are treated and asymptomatic.37 Test of cure is not
recommended, but re-evaluation is suggested with symptom
recurrence. There is an increased risk of HIV acquisition
for both men and women with concomitant T. vaginalis
infection, so it would be particularly important to screen and
treat for this disease in HIV discordant couples.38
Pregnancy
T. vaginalis infection in pregnancy has been associated
with preterm delivery. If the patient is symptomatic and
testing reveals infection, treatment is warranted. Screening
and treatment for asymptomatic infection in women with
a history of preterm birth or preterm premature rupture
of membranes is controversial. Some studies have shown
benefit and others have shown higher rates of preterm
birth in the treated group.39 The use of metronidazole
in pregnancy is considered safe; numerous meta-analyses
show no increased risk of teratogenic effects with
metronidazole.40 The recommended dose of metronidazole
in pregnancy is the same as for non-pregnant women.
Side effects
Side effects of metronidazole may include nausea, vomiting,
headache, insomnia, dizziness, drowsiness, rash, dry
mouth, and metallic taste. A disulfiram reaction can occur
if combined with alcohol. Avoidance of alcohol for at least
one day after completing the treatment is recommended in
the drug manufacturer’s product monograph.
Summary Statements
3. Trichomonas vaginalis is a common non-viral sexually
transmitted infection that is best detected by antigen
testing using vaginal swabs collected and evaluated by
immunoassay or nucleic acid amplification test. (II-2)
4. Cure rates are equal at up to 88% for trichomoniasis
treated with oral metronidazole 2 g once or 500 mg
twice daily for 7 days. Partner treatment, even
without screening, enhances cure rates. (I-A)
Recommendations
3. Test of cure following treatment of trichomoniasis
with oral metronidazole is not recommended. (I-D)
4. Higher-dose therapy may be needed for treatment-
resistant cases of trichomoniasis. (I-A)
5. In pregnancy, treatment of symptomatic
Trichomonas vaginalis with oral metronidazole is
warranted for the prevention of preterm birth. (I-A)
BACTERIAL VAGINOSIS
The Organism
Normal vaginal flora consists of both aerobic and anaerobic
bacteria, with Lactobacillus species being the predominant
270 l MARCH JOGC MARS 2015
microorganisms and accounting for greater than 95% of
all bacteria present.41,42 Lactobacilli are believed to provide
defense against infection in part by maintaining an acidic
pH in the vagina and ensuring hydrogen peroxide is present
in the environment. In contrast, bacterial vaginosis is a
polymicrobial syndrome resulting in a decreased concentration
of lactobacilli and an increase in pathogenic bacteria. There
is no single organism whose presence confirms the diagnosis
of bacterial vaginosis, but rather many different bacteria may
be present, including Gardnerella vaginalis, Mobiluncus species,
Bacteroides and Prevotella species, and Mycoplasma species.43,44
The Disease
Bacterial vaginosis is the most common lower genital
tract disorder among women of reproductive age, the
most common cause of vaginitis in both pregnant and
non-pregnant women, and the most prevalent cause of
vaginal discharge and odour.45,46 Prevalence rates are
similar in pregnant and non-pregnant women. It has
been linked to many different obstetric and gynaecologic
complications such as preterm labour and delivery,
preterm premature rupture of membranes, spontaneous
abortion, chorioamnionitis, postpartum endometritis,
post-Caesarean delivery wound infections, postsurgical
infections, and subclinical pelvic inflammatory disease.47–55
Several risk factors have been identified that increase the
risk of acquisition of bacterial vaginosis. It is more common
in black women,56 women who smoke,57 and women who
use vaginal douches or intravaginal products. 58,59 Although
not currently considered an STI, bacterial vaginosis has
been consistently associated with sexual activity. It is more
common among women who are sexually active, and the
risk seems to increase with both number of sexual partners
and frequency of intercourse.60,61
Diagnosis
Bacterial vaginosis can be diagnosed clinically and/or
microbiologically. The clinical diagnostic criteria published
in 1983 by Amsel et al., still in use today, recommend
diagnosis of bacterial vaginosis if 3 of the 4 following
signs are present62: adherent and homogenous vaginal
discharge; vaginal pH greater than 4.5; detection on saline
wet mount of clue cells (vaginal epithelial cells with such
a heavy coating of bacteria that the peripheral borders
are obscured); and/or amine odour after the addition of
potassium hydroxide (positive whiff test).
Gram stain of vaginal fluid is the most widely used and
evaluated microbiologic method for the diagnosis of
bacterial vaginosis. Most laboratories use an objective
diagnostic scheme that quantifies the number of Lactobacillus
morphotypes and pathogenic bacteria, resulting in a score
 Vulvovaginitis: Screening for and Management of Trichomoniasis, Vulvovaginal Candidiasis, and Bacterial Vaginosis

Table 3. Scoring system (0–10) for gram-stained vaginal smears

Gardnerella and Curved
Lactobacillus Bacteroides spp. gram-variable
Score morphotypes morphotypes rods
0 4+ 0 0
1 3+ 1+ 1+ or 2+
2 2+ 2+ 3+ or 4+
3 1+ 3+
4 0 4+

Table 4. Recommended treatment regimens for bacterial vaginosis

Recommended
Metronidazole 500 mg orally twice daily for 7 days
Metronidazole gel 0.75%, one applicator (5 g) intravaginally once daily for 5 days
Clindamycin cream 2%, one applicator (5 g) intravaginally once daily for 7 days
Alternatives
Metronidazole 2 g orally in a single dose
Clindamycin 300 mg orally twice daily for 7 days

that is used to determine whether the infection is present.
The most commonly used system was developed by
Nugent and colleagues and is known as the Nugent score
(Table 3).63 Bacterial vaginosis is diagnosed by a score of 7
or higher. A score of 4 to 6 is considered intermediate and
a score of 0 to 3 is considered normal.
Treatment
Although bacterial vaginosis has been associated with
adverse gynaecologic outcomes, there is no compelling
evidence that treatment decreases the likelihood of these
complications. Therefore, treatment is usually reserved for
women with bothersome symptoms.
The treatments for bacterial vaginosis recommended in
Canada in the PHAC’s guidelines on STI are presented in
Table 4.7 The first line therapy is oral metronidazole 500 mg
twice daily for 1 week. Reported cure rates following
therapy have ranged from 75% to 85% and do not differ
between oral and vaginal metrondiazole.64–66 Oral tinidazole
has been studied as an alternative to metronidazole in trials
in Europe and the United States. The evidence to date
reveals similar cure rates with the possibility of a reduction
in the number of doses required and in gastrointestinal
side effects with tinidazole.67,68 This drug is not currently
readily available in Canada.
Recurrent Bacterial Vaginosis
Unfortunately, recurrence rates following treatment
for bacterial vaginosis have been high in many studies,
with up to one third of treated women recurring within
3 months,69 and with more women recurring the longer
the length of follow-up.70,71 Before embarking on multiple
courses of therapy, it is recommended to reconfirm the
diagnosis. In women with documented recurrences,
extending the course of therapy to continually suppress
the growth of abnormal bacteria has been shown to be
an effective strategy to decrease the likelihood of further
recurrences. The first option is to use oral metronidazole
500 mg twice daily for 10 to 14 days. If this is not effective,
the recommended therapy is metronidazole vaginal gel
0.75% one applicator (5 g) daily for 10 days, then 2 times
per week for 3 to 6 months.7,72 This regimen results in a
significant decrease in the likelihood of recurrences while
on treatment and thereafter compared to placebo.72 There
is also some evidence that condom use may decrease the
likelihood of recurrence among sexually active women.49
Recently there has been increasing interest in exploring the
use of probiotics and other agents for the treatment of
incident and recurrent bacterial vaginosis. Unfortunately
very little literature exists to guide clinicians in the use of
these products. There is one published study from China
in which women with recurrent bacterial vaginosis were
randomized to either daily vaginal probiotic use or placebo.
Women in the probiotic group had lower recurrence
rates than those in the placebo group.73 Another study
investigated the use of vaginal vitamin C tablets compared
to placebo for the treatment of bacterial vaginosis. More
women in the placebo group still had bacterial vaginosis
at the end of the study period.74 Unfortunately, in both

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SOGC clinical practice guideline
studies diagnosis was based on clinical (Amsel’s) criteria
rather than Nugent score or Gram stain, and the total
length of follow-up in the vitamin C study was only
20 days. Until there is more published data from well-
designed trials in this area, it is premature to make a
judgement on the efficacy of these alternative therapies.
Pregnancy
Vaginal discharge is common in pregnancy and may be
physiologic. In women with persistent discharge, screening
for lower genital tract infections (vaginal and cervical) is
recommended. If bacterial vaginosis is diagnosed in a
symptomatic pregnant woman, treatment is indicated. The
PHAC guidelines on STI recommend using metronidazole
500 mg orally twice daily for 7 days or clindamycin 300 mg
orally twice daily for 7 days.7 Topical agents are not
recommended. Treatment has relatively moderate rates of
success with high rates of recurrence in some women.
For a detailed discussion of the implications of bacterial
vaginosis in pregnancy and links to adverse pregnancy
outcomes, including screening and treatment strategies in
pregnant women, please see the SOGC Clinical Practice
Guideline on the screening and management of bacterial
vaginosis in pregnancy.75
Summary Statements
5. Current evidence of the efficacy of alternative
therapies for bacterial vaginosis (probiotics,
vitamin C) is limited. (I)
Recommendations
6. Bacterial vaginosis should be diagnosed using either
clinical (Amsel’s) or laboratory (Gram stain with
objective scoring system) criteria. (II-2A)
7. Symptomatic bacterial vaginosis should be treated
with oral metronidazole 500 mg twice daily for 7
days. Alternatives include vaginal metronidazole gel
and oral or vaginal clindamycin cream. (I-A)
8. Longer courses of therapy for bacterial vaginosis are
recommended for women with documented multiple
recurrences. (I-A)
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62. Amsel R, Totten PA, Spiegel CA, Chen KCS, Eschenbach D, Holmes KK.
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intravaginal 0.75% metronidazole gel for treatment of bacterial vaginosis.
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67. Livengood CH, Ferris DG, Wiesenfeld HC, Hillier SL, Soper DE,
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 310, August 2014

Guidelines for the Care of Pregnant Women

Living With HIV and Interventions to Reduce
Perinatal Transmission
Abstract
This clinical practice guideline has been prepared by the
Infectious Diseases Committee, reviewed by Family Physician Objective: This guideline reviews the evidence relating to the
Advisory Committee and the Aboriginal Health Initiative care of pregnant women living with HIV and the prevention
Committee, and approved by Executive and Council of the of perinatal HIV transmission. Prenatal care of pregnancies
Society of Obstetricians and Gynaecologists of Canada. complicated by HIV infection should include monitoring by a
multidisciplinary team with experts in this area.
PRINCIPAL AUTHORS
Outcomes: Outcomes evaluated include the impact of HIV
Deborah Money, MD, Vancouver BC on pregnancy outcome and the efficacy and safety of
antiretroviral therapy and other measures to decrease the risk
Karen Tulloch, BScPharm, Vancouver BC
of vertical transmission.
Isabelle Boucoiran, MD, Montreal QC
Evidence: Published literature was retrieved through
Sheila Caddy, MD, Edmonton AB searches of PubMed and The Cochrane Library in 2012
and 2013 using appropriate controlled vocabulary (HIV,
INFECTIOUS DISEASES COMMITTEE anti-retroviral agents, pregnancy, delivery) and key words
Mark H. Yudin, MD (Chair), Toronto ON (HIV, pregnancy, antiretroviral agents, vertical transmission,
perinatal transmission). Results were restricted to systematic
Victoria Allen, MD, Halifax NS reviews, randomized control trials/controlled clinical trials,
Celine Bouchard, MD, Quebec QC and observational studies published in English or French.
There were no date restrictions. Searches were updated on
Marc Boucher, MD, Montreal QC a regular basis and incorporated in the guideline to June
Isabelle Boucoiran, MD, Montreal QC 2013. Grey (unpublished) literature was identified through
searching the websites of health technology assessment
Sheila Caddy, MD, Calgary AB
and health technology-related agencies, clinical practice
Eliana Castillo, MD, Calgary AB guideline collections, clinical trial registries, and national and
international medical specialty societies.
Heather Gottlieb, MD, Calgary AB
Values: The quality of evidence in this document was rated using
V. Logan Kennedy, RN, Toronto ON
the criteria described in the Report of the Canadian Task
Deborah Money, MD, Vancouver BC Force on Preventive Health Care (Table 1).
Kellie Murphy, MD, Toronto ON
Gina Ogilvie, MD, Vancouver BC
Caroline Paquet, RM, Trois-Rivieres QC
Julie van Schalkwyk, MD, Vancouver BC

SPECIAL CONTRIBUTORS Key Words: HIV, pregnancy, antiretroviral agents, vertical

transmission, perinatal transmission
Ariane Alimenti, MD, Vancouver BC
Neora Pick, MD, Vancouver BC
Disclosure statements have been received from all contributors.
J Obstet Gynaecol Can 2014;36(8 eSuppl A):S1–S46

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

AUGUST JOGC AOÛT 2014 l S1

SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.154
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.154
Recommendations
01. All women living with HIV who are planning a pregnancy or
who become pregnant should have their individual situations
discussed with experts in the area, with referral to both HIV
treatment programs and obstetrical care providers, and an overall
plan should be made for their pregnancy care. (II-2A)
02. All pregnant women should be offered HIV testing, with
appropriate pre- and post-test counselling, as part of their routine
prenatal care in each pregnancy. This testing should be repeated
in each trimester in women who are recognized to be at high and
ongoing risk for HIV infection. (II-2A)
03. Pregnant women living with HIV should be made aware that
with the consistent use of combination antiretroviral therapy and
abstinence from breastfeeding, the risk of perinatal transmission
is < 1%. (I-A)
04. All pregnant women living with HIV should be treated with
combination antiretroviral therapy regardless of baseline CD4 and
viral load. (II-2A)
05. Antiretroviral therapy should not be discontinued during the
first trimester for obstetrical reasons, but if the woman is not on
therapy and there is no urgent medical indication for combination
antiretroviral therapy, it can be delayed until after 14 weeks’
gestation. (III-B)
06. All women living with HIV (both those who still have a detectable
viral load after exposure to antiretroviral therapy and those who
are antiretroviral-naive) should have their virus genotyped and, if
possible, tested for phenotypic resistance to assist in optimizing
antiretroviral therapy. It is advisable to discuss the interpretation
of the genotype testing and any changes to the antiretroviral
therapy with experienced clinicians. Testing for HLA-B*5701, if
not done previously, is recommended in case abacavir might be
required. (II-2B)
07. A combination antiretroviral therapy regimen including a dual
nucleoside reverse transcriptase inhibitor (NRTI) backbone
that includes one or more NRTIs and a boosted protease
inhibitor should be favoured because there is higher confidence
S2 l AUGUST JOGC AOÛT 2014
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
in its safety and efficacy in pregnancy. Whenever possible,
antiretrovirals known to cross the placenta to the fetal
compartment should be used. (II-2B)
08. Whenever possible, drugs with no safety data should be
avoided during the period of organogenesis. Efavirenz should
not be prescribed in the first trimester of pregnancy because of
its possible teratogenicity; however, if exposure has occurred
and the neural tube has closed, efavirenz can be continued.
Nevirapine should not be started in pregnancy, unless indicated
by the woman’s resistance patterns, because it is associated
with a high rate of serious adverse outcomes in this situation;
however ongoing, pre-pregnancy treatment with nevirapine can
be continued through pregnancy if tolerance and efficacy are
established. (II-3D)
09. If antiretroviral therapy is discontinued for any reason during
pregnancy, all drugs should be discontinued at once (unless the
woman is on non-nucleoside reverse transcriptase inhibitors; in
that case a tail of 2 nucleoside reverse transcriptase inhibitors
is recommended for 1 week), and all drugs should be resumed
simultaneously to minimize the risk of viral resistance developing
during therapy. Antiretroviral therapy should be resumed as
quickly as possible after discontinuance to minimize the risk of
rebound viremia and the potentially increased risk of vertical
transmission. (II-1A)
10. If a pregnant woman has significant nausea of pregnancy, do
not begin antiretroviral therapy until her nausea is adequately
controlled. Most antinauseants used in pregnancy can be co-
administered with antiretrovirals. If the woman is already on
antiretrovirals and has hyperemesis of pregnancy, discontinue
all antiretrovirals at once, and then reinstate all at once, when
nausea and vomiting are controlled (unless the woman is on
non-nucleoside reverse transcriptase inhibitors [NNRTIs],
in which case a tail of 2 nucleoside reverse transcriptase
inhibitors is recommended for 1 week to prevent future NNRTI
resistance). (II-2D)
11. Therapy should be individualized to maximize adherence to the
prescribed antiretroviral regimen. (III-A)
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
12. Routine dose adjustment of the combination antiretroviral
therapy is not recommended in pregnancy. (III-D)
13. The woman’s clinical, virological, and immunological
statuses should be assessed every 4 to 8 weeks during
pregnancy, and again 6 weeks postpartum. Routine criteria
should be used to assess the woman’s response to, and
the possible failure of, antiretroviral therapy. The toxicity of
the antiretrovirals should also be monitored at these times.
Specific testing should be individualized for the known
toxicities of the woman’s antiretroviral therapy regimen. (III-B)
14. As for all pregnant women, all those living with HIV,
regardless of age, should be offered, through an informed
consent process, dating ultrasound and non-invasive prenatal
genetic screening for the most common clinically significant
fetal aneuploidies. (III-A)
15. A detailed obstetrical ultrasound at 19 to 20 weeks’ gestation
is recommended. Additional ultrasounds, for fetal growth
and amniotic fluid volume, are recommended at least each
trimester, or as guided by obstetrical indications. (II-3B)
ABBREVIATIONS
ALT alanine aminotransferase
AST aspartate aminotransferase
cART combination antiretroviral therapy
CBC complete blood count
CD4-cell CD4+ T-lymphocyte cell
CDC Centre for Disease Control
CMV cytomegalovirus
CPHSP Canadian Perinatal HIV Surveillance Program
DDI didanosine
DMPA medroxyprogesterone acetate
EIA enzyme immunoassay
FDA (United States) Food and Drug Administration
FPV fosamprenavir
HBV hepatitis B virus
HCV hepatitis C virus
HIV human immunodeficiency virus
IDV indinavir
IV intravenous
LDH lactate dehydrogenase
MAC mycobacterium avium complex
NIH (United States) National Institutes of Health
NNRTI non-nucleoside/nucleotide analogue reverse transcriptase
inhibitor
NRTI nucleoside/nucleotide analogue reverse transcriptase
inhibitor
NVF nelfinavir
PCP pneumocystis jiroveci pneumonia
PCR polymerase chain reaction
PI protease inhibitor
PO per os
RNA ribonucleic acid
RR relative risk
ZDV zidovudine
16. As for all pregnant women, those living with HIV should be
screened periodically for substance use, and drug addiction
should be addressed as needed in conjunction with HIV
management. (III-A)
17. Mode of delivery should be discussed in detail with all
women:
a. Women on optimal antiretroviral therapy with
acceptable plasma viral load suppression (less than
1000 c/mL) over the last 4 weeks prior to delivery
are recommended to have a vaginal delivery in the
absence of other obstetrical indications for Caesarean
section. If Caesarean section is recommended for
obstetrical indications, it can be conducted at 39 weeks,
as usual for those indications. (I-A)
b. Women not on optimal antiretroviral therapy (i.e., no
antiretroviral therapy, monotherapy only, or with an
incompletely suppressed viral load) should be offered a
scheduled pre-labour Caesarean section at approximately
38 weeks’ gestation. (II-2A)
18. Intravenous zidovudine should be initiated as soon as labour
onset until delivery, in combination with an oral combination
antiretroviral regimen, regardless of mode of delivery, current
antiretroviral regimen, or viral load. (III-B)
19. Intrapartum, a single dose of oral nevirapine (200 mg)
remains an option in the unusual circumstance of a woman
living with HIV who has not received antenatal antiretroviral
therapy in pregnancy. (II-2B)
20. Plans for ongoing HIV care should be established prenatally,
and unless otherwise indicated, maternal antiretroviral
therapy should be continued after delivery and reassessed for
ongoing therapy by providers of adult HIV care. (II-1A)
21. HIV-exposed newborns should receive antiretroviral therapy
for 6 weeks to prevent vertical transmission of HIV. (I-A)
22. Health care practitioners who care for HIV-exposed newborns
should provide timely diagnostic HIV testing: HIV polymerase
chain reaction at birth, 1 month, and 3 to 4 months and HIV
serology at 18 months (II-A), and they should monitor both
short- and long-term outcomes, including screening for
adverse effects of antiretroviral therapy and for developmental
delay. (III-A)
23. Breast-feeding is not recommended regardless of plasma HIV
viral load and use of antiretroviral therapy. (I-E)
24. The pregnancy should be registered with surveillance
programs to allow the collection of provincial and national
data to guide future pregnancy policies. Women undergoing
antiretroviral therapy in pregnancy should also be offered
inclusion in appropriate studies. (III-B)
This document’s Executive Summary
was previously published in:
J Obstet Gynaecol Can 2014;36(8):721–734
AUGUST JOGC AOÛT 2014 l S3
SOGC CLINICAL PRACTICE GUIDELINE
INTRODUCTION
S upportive non-directive counselling regarding
reproductive choices, high-risk prenatal care, modified
management of labour and delivery, and postpartum
and infant care are all important components in the
comprehensive care of the woman living with HIV and
her infant. The provision of pregnancy and reproductive
health care to women living with HIV should involve
collaboration with individuals experienced in the
management of high-risk pregnancy and HIV care of
women and infants.
In Canada, several clinics provide multidisciplinary care and
guidance for this population of adults and children living
with or exposed to HIV, in coordination with provincial
authorities. Longitudinal surveillance on pregnancy
outcomes in women living with HIV is tracked by the
CPHSP through information provided by clinicians who
care for pregnant women living with HIV and their infants.
This is vital for the continuous quality improvement of
antiretroviral prescribing in pregnancy.
BACKGROUND
Scope
This guideline primarily addresses the management of
HIV during pregnancy and does not comprehensively
address pre-pregnancy planning issues. Canadian HIV
pregnancy planning guidelines are available.1 Similarly, HIV
care of non-pregnant women is addressed in guidelines
available elsewhere2 and is not discussed in this document.
Management of HIV in pregnant women with comorbidities
is addressed in brief; readers are referred to available
guidelines for detailed discussion of this3 and other aspects
of caring for people living with HIV (Table 2).
Epidemiology of Perinatal HIV
In 2011, the Joint United Nations Programme on HIV/AIDS
and the World Health Organization (WHO) estimated that
a total of 34 million people worldwide were living with
HIV, approximately half of whom were women.4 The
number of people living with HIV in Canada continues
to rise, from an estimated 64 000 in 2008 to 71 300 in
2011.5 The estimated prevalence rate in Canada in 2011
was 208.0 per 100 000 population (range: 171.0 to 245.1
per 100 000 population), 23% to 28% of whom were
women.5 According to 2009 statistics, women account
for approximately 26% of the new HIV diagnoses in
Canada.6 Cumulative surveillance data report that two
thirds of positive test results for HIV occurred in women
of reproductive age, with 37.6% in women aged 30 to 39
years and 32.5% in women aged 20 to 29 years.6
S4 l AUGUST JOGC AOÛT 2014
Combination antiretroviral therapy has been demonstrated
to prolong the lives of people living with HIV,7 and has
also significantly reduced the rate of vertical transmission
of HIV from a baseline risk of 25% without intervention
to < 2% in the context of comprehensive pregnancy care
and cART administered antenatally, intrapartum, and to the
infant in the early neonatal period.8,9 As a result of these
factors more women living with HIV are considering their
reproductive options and choosing to become pregnant.1
However, the vertical transmission of HIV remains a great
concern globally, as an estimated 26% of women living
with HIV remain unaware of their HIV status,6 and the
majority of childhood HIV infections are acquired in this
manner.3
The CPHSP identified a total of 2692 women known
by care providers to be living with HIV who delivered
infants between 1990 and 2010.10 Based on rates of
spontaneous and therapeutic abortions in Canada, it is
estimated that an equal number of women have been
pregnant but have not delivered a living infant.10 The
incidence of pregnancies in women living with HIV in
Canada has been gradually increasing at different rates
from province to province.10 With the implementation of
cART for pregnant women in the late 1990s, the CPHSP
documented a substantial reduction in HIV transmission
rates from 20.2% (1990–1996) to 2.9% (1997–2010).
Overall, the HIV perinatal transmission rate in women
who have accessed care is 0.4% in Canada.10 However,
despite the availability of routine HIV testing in
pregnancy and effective interventions to reduce vertical
transmission, there were a total of 93 infants perinatally
infected with HIV in Canada between 2000 and 2010.11
PRE-CONCEPTION PLANNING
Detailed information and recommendations regarding pre-
conception planning for people with HIV is beyond the
scope of this document. These issues are addressed in detail
in the Canadian HIV Pregnancy Planning Guidelines1 and
in the National Institutes of Health Perinatal Guidelines.3
In brief, the following important clinical issues need to
be considered with respect to pregnancy planning and
counselling in individuals living with HIV:
1. use of effective methods of birth control if not
desiring pregnancy;
2. pre-conceptional health including the intake of folic
acid;
3. transmission between partners during conception;
and
4. antiretroviral and other drugs in pregnancy planning.
 Table 2. Guidelines related to the care of people living with HIV
Topic
Antiretroviral treatment of adult HIV infection: 2012
recommendations
Adult HIV infection therapeutic guidelines
Opportunistic infections therapeutic guidelines
Primary care guidelines
Guidelines for the use of antiretroviral agents in HIV-1
infected adults and adolescents.
Guidelines for prevention and treatment of opportunistic
infections in adults and adolescents
Recommendations for the use of antiretroviral drugs in
pregnant HIV-1 infected women for maternal health and
interventions to reduce perinatal HIV transmission in the
United States
Canadian HIV pregnancy planning guidelines
Alcohol use and pregnancy consensus clinical guidelines
Substance use in pregnancy clinical practice guidelines
HIV screening in pregnancy clinical practice guidelines
Management of nausea and vomiting of pregnancy clinical
practice guidelines
Canadian contraception consensus
AUGUST JOGC AOÛT 2014 l S5
Website Issuing agency
https://www.iasusa.org/guidelines International AIDS Society, US Panel
http://www.cfenet.ubc.ca/therapeutic-guidelines/adult BC Centre for Excellence in HIV/AIDS
http://www.cfenet.ubc.ca/therapeutic-guidelines/opportunistic-infection
http://cfenet.ubc.ca/therapeutic-guidelines/primary-care
http://www.aidsinfo.nih.gov/guidelines Centers for Disease Control and Prevention,
National Institutes of Health, HIV Medicine
Association of the Infectious Diseases
Society of America
http://www.sogc.org/guidelines/documents/gui278CPG1206E.pdf Society of Obstetricians and Gynaecologists
of Canada
http://www.sogc.org/guidelines/documents/gui245CPG1008E.pdf
http://www.sogc.org/guidelines/documents/gui256CPG1104E.pdf
http://sogc.org/wp-content/uploads/2013/01/185E-CPG-December2006.pdf
http://sogc.org/wp-content/uploads/2013/01/120E-CPG-October2002.pdf
http://sogc.org/wp-content/uploads/2013/01/143E-CPG1-February2004.pdf
http://sogc.org/wp-content/uploads/2013/01/143E-CPG2-March2004.pdf
http://sogc.org/wp-content/uploads/2013/01/143E-CPG3-April2004.pdf
Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
SOGC CLINICAL PRACTICE GUIDELINE
Recommendation
1. All women living with HIV who are planning a
pregnancy or who become pregnant should have their
individual situations discussed with experts in the area,
with referral to both HIV treatment programs and
obstetrical care providers, and an overall plan should
be made for their pregnancy care. (II-2A)
NEW DIAGNOSIS OF HIV IN A PREGNANT WOMAN
All pregnant women should be offered HIV testing, with
appropriate pre- and post-test counselling as part of their
routine prenatal care in each pregnancy.12 Some provinces
have managed this through opt-in testing and others through
opt-out testing. Women involved in ongoing high-risk
HIV transmission activities (see Appendix 1) who are HIV
negative on initial testing should be retested each trimester,
and if possible again near term. Testing women for the
first time during labour and delivery is not optimal, and
HIV issues should be addressed whenever possible early in
the pregnancy in order to optimize the health outcomes of
both the woman and her infant. Rapid HIV antibody testing
(also known as point-of-care HIV testing) in the labour and
delivery setting is now available in some facilities and should
be used as an important last opportunity to identify women
living with HIV before delivery and to provide emergency
pro­phylaxis to decrease the risk of perinatal transmission.12–14
(see Appendix 1)
A clinician who is familiar with HIV management in
pregnancy should evaluate every pregnant woman who is
newly diagnosed with HIV. Women should be informed about
their HIV diagnosis in person, and support and counselling
should be provided for the woman and her family. Women
should be made aware of the improved natural history of
HIV, specifically that with adherence to care and therapy,
individuals living with HIV now experience an improved
quality of life and prolonged life expectancy.15 Women should
also be made aware that with the use of cART and abstinence
from breastfeeding the risk of vertical transmission is < 1%.10
Immediate assessment of risk transmission to others is
important, and the woman should be counselled regarding
the need for safe sexual practices. All previous children that
may have been exposed in the past and all sexual or drug use
partners should be offered testing. Public health consultation
should be sought to adhere to provincial regulations on
reportable diseases. Disclosure to family and friends not at
risk of HIV is not required and should be considered carefully
in light of the unfortunate persistence of stigmatization.
Non-judgemental counselling regarding continuation of
the pregnancy based on a complete understanding of the
woman’s medical and social circumstances is important.
S6 l AUGUST JOGC AOÛT 2014
Recommendation
2. All pregnant women should be offered HIV testing,
with appropriate pre- and post-test counselling, as
part of their routine prenatal care in each pregnancy.
This testing should be repeated in each trimester
in women who are recognized to be at high and
ongoing risk for HIV infection. (II-2A)
NEW DIAGNOSIS OF PREGNANCY
IN A WOMAN LIVING WITH HIV
A clinician familiar with HIV management should evaluate
each woman living with HIV who becomes pregnant.
Medical care recommendations for the pregnant woman
living with HIV will depend on the woman’s wish to
continue or discontinue the pregnancy, her HIV disease
status, and her cART medication history. Pregnancy dating
should be done through taking a careful history and
conducting a dating ultrasound.
Women should be made aware that with the use of cART
and abstinence from breastfeeding the risk of vertical
transmission is < 1% in Canada.10 In the event that the
woman does not wish to continue the pregnancy, access
to termination of pregnancy services should be facilitated.
Health care providers should use this opportunity to
continue to engage in and optimize HIV care and to provide
reproductive health counselling, including contraception, to
reduce the future occurrence of an unintended pregnancy.
The HIV status of the exposed sexual or drug use partner
should also be queried, and if the partner is not known to
be living with HIV, testing is recommended.
If the woman desires to continue the pregnancy, immediate
review of HIV status including recent CD4-cell count, HIV
viral load, and antiretroviral medication use is warranted.
Specific recommendations regarding antiretroviral drug
therapy management and trimester-specific information are
discussed in more depth below. Overall, it is important to
consider that all pregnant women living with HIV present
high-risk pregnancies. Their medical therapy requires
coordination and communication between HIV specialists
and obstetrical providers. If, for geographic reasons, a woman
is unable to attend for specialist consultations, these can be
provided virtually through effective communications between
care providers in remote settings and urban sub-specialists.
Recommendation
3. Pregnant women living with HIV should be made
aware that with the consistent use of combination
antiretroviral therapy and abstinence from
breastfeeding, the risk of perinatal transmission
is < 1%. (I-A)
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
ANTIRETROVIRAL DRUG THERAPY
DURING PREGNANCY
Background
Antiretroviral drug therapy is indicated for all pregnant
women living with HIV, regardless of their HIV viral load
or CD4-cell count, for the woman’s own health, for the
prevention of HIV transmission to a partner, and for the
prevention of HIV vertical transmission.3,10,11,16 In general,
the recommendations for the use of antiretroviral therapy
for the benefit of maternal health during pregnancy are
similar for all women regardless of pregnancy status.2
However there are a number of important considerations
based on limited experience and/or specific concerns with
some antiretroviral drugs in pregnancy.3 While optimizing
maternal care and health is of prime importance, it is
important whenever possible to limit exposure of the
developing fetus to potentially toxic medications. There
are still minimal data available on the pharmacokinetics
and safety of many antiretroviral drugs, particularly the
newer agents, in pregnancy (see Table 3 and Appendix 2);
therefore all treatment decisions during pregnancy require
full discussion between the patient and her physician with
regard to known and unknown benefits and risks.
Antiretroviral agents administered in pregnancy have
demonstrated a reduction in the risk of vertical transmission of
HIV.3 Both published literature and analysis of Canadian data
inform treatment in pregnancy. Literature from resource-rich
countries provides information on optimizing antiretroviral
therapy for both maternal health and the prevention of vertical
transmission, while literature from resource-poor countries
provides insight on recommendations for the care of pregnant
women living with HIV with absent or delayed prenatal
care. A detailed table describing results of major studies on
antiretroviral prophylaxis to prevent perinatal transmission of
HIV is available in the NIH perinatal guidelines.3
The Pediatric AIDS Clinical Trials Group 076 (PACTG
076) was the first major randomized, placebo-controlled
study to demonstrate that zidovudine administered
PO antepartum (between 14 and 34 weeks’ gestation),
intravenously intrapartum, and PO to the infant for
6 weeks could significantly reduce the risk of perinatal
transmission of HIV (25.5% in the placebo group vs. 8.3%
in the zidovudine treated group, P < 0.01).17 Follow-up
results confirmed these findings with no evidence of any
long-term toxicity, other than transient anemia, in infants
up to 5 years of age.18–20
Subsequent clinical trials and observational studies
have demonstrated that further reductions in vertical
transmission, to rates as low as < 1% can be achieved with
the antenatal administration of cART (with at least 2 or
3 agents) to the pregnant woman.3 In the entire Canadian
cohort, the rate of vertical transmission was as low as 0.4%
(6 out of 1585) when the mother received at least 4 weeks
of cART before delivery.10,11
Antiretroviral agents reduce the risk of vertical transmission
through a number of mechanisms, including:
1. lowering maternal viral load using antenatal cART,
2. providing infant pre-exposure prophylaxis using
intrapartum antiretroviral therapy that rapidly crosses
the placenta in order to achieve adequate systemic drug
levels in the infant, and
3. providing infant post-exposure prophylaxis.3
It is important to note, however, that while lowering maternal
viral load is important, antiretroviral prophylaxis is effective
even in women with low viral loads. Among women with
baseline viral loads less than 1000 copies/mL, those who
received antenatal antiretroviral therapy demonstrated a
lower HIV vertical transmission rate than those who did not
(1.0% vs. 9.8%, P < 0.001).16
Two primary treatment strategies have been evaluated in
resource-poor countries and are relevant in the developed
world for managing women living with HIV with absent or
delayed prenatal care who are not receiving recommended
antenatal cART. The first strategy involves use of shorter
course regimens of either mono or dual antiretroviral
therapy (e.g., zidovudine or zidovudine-lamivudine)21,22 or
intrapartum single-dose nevirapine.23,24 The second strategy
involves administration of cART to infants who are born
in high transmission risk settings.25 Overall, both strategies
have demonstrated benefit in reducing transmission;
however, transmission rates are still significantly higher
than those reported with antenatal cART, intrapartum and
infant prophylaxis.
In a large African randomized trial (HIVNET 012),
pregnant women living with HIV received either:
1. 1 single-dose nevirapine 200 mg in labour and 1 dose
of nevirapine to their infant within 72 hours of birth,
or
2. oral zidovudine while in labour and the same to their
infant for one week after birth.
Nevirapine significantly reduced the risk of vertical HIV
transmission at 14 to 16 weeks of age by approximately
50% (13% vs. 25%, P < 0.001) compared with zidovudine.23
It is important to note that none of the women received
antenatal antiretroviral therapy and almost all women in this
study breastfed their infants. Because single-dose nevirapine
AUGUST JOGC AOÛT 2014 l S7
SOGC CLINICAL PRACTICE GUIDELINE
Table 3. Summary of antiretroviral drugs in pregnancy with dosing recommendations
Nucleoside reverse transcriptase inhibitors (NRTIs)
Recommended for use as part of combination regimens, usually
including 2 NRTIs with either an NNRTI or one or more PIs. Use of
single or dual NRTIs alone is not recommended.
Zidovudine (ZDV)
FDA pregnancy category C
High placental transfer (cord-to-maternal blood ratio 0.80)
Animal data3
Vaginal carcinoma reported in mice and rats at 3 times and 24 times
the usual human dose
Embryotoxic in rats and rabbits at high doses
No evidence of teratogenicity in rats or rabbits unless given at
extremely high doses to rats (e.g., 300 times usual human dose)
Human data
PACTG 076 randomized, placebo-controlled trial in pregnant women
showed no increase in congenital abnormalities19,155; the WITS cohort
study reported 10-fold increase in risk of hypospadias in women
receiving ZDV in the first trimester.156
No evidence of human teratogenicity; APR birth defects with first
trimester exposure 3.3% (124 of 3789 births, 95% CI 2.7%–3.9%)42
Infants exposed in utero have shown no differences in immunology,
neurology, or growth to infants receiving placebo, based on
approximately 6 years of follow-up.
Lamivudine (3TC)
FDA pregnancy category C
High placental transfer (cord-to-maternal blood ratio 0.86)158
Animal data3
No evidence of toxicity or teratogenicity in rabbits or rats at 35 to
130 times usual human dose
Embryotoxic in rabbits at doses similar to human doses, however no
indication of this effect in rats at 35 times usual human dose
Human data
No adequate or well-controlled studies in pregnant women.
No evidence of human teratogenicity: APR birth defects with first
trimester exposure 3.1% (127 of 4088 births, 95% CI 2.6%–3.7%)42
Abacavir (ABC)
FDA pregnancy category C
High placental transfer (cord-to-maternal blood ratio 1.0)160
Animal data3
Developmental toxicity (decreased fetal weight and reduced crown-
rump length) and increased incidence of fetal anasarca and skeletal
malformations in rats, at 35 times usual human dose; toxic effects to
embryo and fetus in rats at 8 times usual human dose
No evidence of developmental toxicity or increase in fetal
malformation observed in rabbits at 8.5 times usual human dose
Carcinogenic in rats at 6 to 32 times usual human dose
Human data
No adequate or well-controlled studies in pregnant women
No evidence of human teratogenicity: APR birth defects with first
trimester exposure 3.0% (25 of 823 births; 95% CI 2.0%–4.5%)42
S8 l AUGUST JOGC AOÛT 2014
NRTI class concerns
Causal relationship between mitochondrial toxicity and NRTI
exposure in utero has not been established (see text for details).
Recommendations for use in pregnancy
ZDV plus 3TC is a recommended dual NRTI backbone for pregnant
women.
Do not combine with stavudine (antagonistic mechanism of action);
discontinue stavudine at time of administration of intrapartum
intravenous ZDV.
Dosing
Retrovir 300 mg twice daily or 200 mg 3 times daily
Combivir (ZDV 300 mg/3TC 150 mg) 1 tablet twice daily
Trizivir (ZDV 300 mg/3TC 150 mg/ABC 300 mg) 1 tablet twice daily
Pharmacokinetics similar in third trimester of pregnancy and
non-pregnant patients; no dose alteration required in pregnancy157
Adverse events/concerns in pregnancy
Overall, well tolerated in pregnancy and infants; higher incidence of
anemia reported in neonates; however, reversible within 6 weeks of
discontinuing ZDV19,155
Recommendations for use in pregnancy
3TC plus ZDV is a recommended dual NRTI backbone for pregnant
women.
A preferred NRTI for dual NRTI backbone (in combination with
TDF) for pregnant women with chronic HBV infection
Dosing
3TC 150 mg twice daily or 300 mg once daily
Combivir (ZDV 300 mg/3TC 150 mg) 1 tablet twice daily
Trizivir (ZDV 300 mg/3TC 150 mg/ABC 300 mg) 1 tablet twice daily
Kivexa (3TC 300 mg/ABC 600 mg) 1 tablet once daily
A phase I study, evaluating both daily and twice-daily dosing,
showed pharmacokinetics were similar in the third trimester of
pregnancy and postpartum159; larger study reports 22% higher drug
clearance in pregnant women; however, level of exposure was
therapeutic.158 No dose alteration is required in pregnancy.
Adverse events/concerns in pregnancy
Overall, well tolerated in pregnancy; also active against HBV
Recommendations for use in pregnancy
Alternative NRTI for dual NRTI backbone of combination regimens
Dosing
Ziagen 300 mg twice daily or 600 mg once daily
Kivexa (3TC 300 mg/ABC 600 mg) 1 tablet once daily
Phase I study showed drug area under the curve concentrations
were similar in pregnant, postpartum, and non-pregnant individuals.
No dose alteration is required in pregnancy.161
Adverse events/concerns in pregnancy
Severe hypersensitivity reaction that may be fatal has been
reported; testing for the HLA-B*5701 allele identifies patients at risk
of reaction; patients with the HLA*B-5701 allele should not be given
ABC.
continued
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
Table 3. Continued
Emtricitabine (FTC)
FDA pregnancy category B
High placental transfer (cord-to-maternal blood ratio 1.2)162,163
Animal data 3
No evidence of carcinogenicity in mice or rats at doses up to 26 times
and 31 times usual human dose, respectively
No evidence of developmental toxicity or teratogenicity in mice
or rabbits at doses 60 times and 120 times usual human dose,
respectively
Human data
No adequate or well-controlled studies in pregnant women
No evidence of human teratogenicity: APR birth defects with first
trimester exposure 2.3% (21 of 899 births; 95% CI 1.4%–3.5%)42
Tenofovir (TDF) (nucleotide analogue reverse transcriptase inhibitor)
FDA pregnancy category B
High placental transfer (cord-to-maternal blood ratio 0.6-1.03)165,166
Animal data3
Carcinogenic in female mice at 16 times usual human dose; however,
there is no indication of this effect in rats at 5 times usual human dose.
No evidence of gross structural abnormalities observed in fetal
monkeys at 25 times usual human dose; however, low birth weights
and reduction in fetal bone porosity were observed.
Chronic administration of TDF at high doses to immature animals of
multiple species has resulted in reversible bone abnormalities (ranging
from decreased bone mineral density and content to severe, pathologic
osteomalacia) and evidence of nephrotoxicity in monkeys at doses 12
to 50 times usual human dose.
Human data
No evidence of human teratogenicity: APR birth defects with first
trimester exposure 2.3% (31 of 1370 births; 95% CI 1.5%–3.2%)42
Currently no evidence of nephrotoxicity or decreased growth and
development in infants exposed in utero
Cross-sectional study in HIV-exposed uninfected infants reported
comparable outcomes (low birth weight and length measurements,
quantitative bone ultrasound, and parameters of bone metabolism)
between infants with and without in utero exposure to TDF.57
A cohort study in HIV-exposed uninfected infants compared outcomes
of low birth weight and small for gestational age, newborn length for
age, and head circumference for age in infants with or without in utero
exposure to TDF. No between-group differences were found at birth;
at age 1 year, infants exposed to TDF had lower length for age and
head circumference for age. The clinical significance of these findings
has not been determined.167
Didanosine (DDI)
FDA pregnancy category B
Moderate placental transfer (cord-to-maternal blood ratio 0.38)160
Animal data3
No evidence of toxicity or teratogenicity in rats or rabbits
Human data
No adequate or well-controlled studies in pregnant women
APR birth defects with first trimester exposure 4.6% (19 of 409 births;
95% CI 2.8%–7.2%). No pattern of defects was discovered.42
Recommendations for use in pregnancy
Alternative NRTI for dual NRTI backbone of combination regimens
One of preferred NRTI for dual NRTI backbone (in combination with
TDF) for women with chronic hepatitis B infection
Dosing
Emtriva (not available in Canada) 200 mg once daily
Truvada (TDF 300 mg/FTC 200 mg) 1 tablet once daily
A phase II pharmacokinetic study showed that FTC concentrations
were lower in the third trimester than postpartum164; however,
current data is insufficient to recommend a dosage adjustment in
pregnancy.
Adverse events/concerns in pregnancy
Overall, well tolerated in pregnancy; also active against HBV
Recommendations for use in pregnancy
Alternative NRTI for dual NRTI backbone of combination regimens
Preferred NRTI in combination with 3TC or FTC in women with
chronic hepatitis B infection
Dosing
Viread 300 mg once daily
Truvada (TDF 300 mg/FTC 200 mg) 1 tablet once daily
Atripla (TDF 300 mg/FTC 200 mg/EFV 600 mg) 1 tablet once daily
at nighttime; not recommended in pregnancy (see Efavirenz below)
A pharmacokinetic study showed that TDF AUC is lower in third
trimester than postpartum; however, trough concentrations
were similar in both groups.165 No dose alteration is required in
pregnancy.
Adverse events/concerns in pregnancy
Overall, well tolerated in pregnancy; clinical studies in humans
(particularly children) show bone demineralization with chronic use;
clinical significance is unknown.
Recommendations for use in pregnancy
Alternative NRTI for dual NRTI backbone of combination regimens
Do not prescribe with stavudine (possible fatal lactic acidosis).
Dosing
Videx EC or Videx oral solution: ≥ 60 kg: 400 mg once daily (with
tenofovir give 250 mg PO daily); < 60 kg: 250 mg once daily (with
tenofovir give 200 mg once daily)
Take 30 minutes before or 2 hours after a meal.
Phase I study showed pharmacokinetics were similar in third
trimester of pregnancy and postpartum.168 No dose alteration is
required in pregnancy.
Adverse events/concerns in pregnancy
Fatal lactic acidosis has been reported in pregnant women who
received the combination of DDI and d4T; physicians should avoid
prescribing this combination.
continued
AUGUST JOGC AOÛT 2014 l S9
SOGC CLINICAL PRACTICE GUIDELINE
Table 3. Continued
Stavudine (d4T)
FDA pregnancy category C
High placental transfer (cord-to-maternal blood ratio 0.5–0.8 in
macaques)169
Animal data3
No evidence of developmental toxicity or teratogenicity in rats at 399
times usual human dose or rabbits at 183 times usual human dose
Human data
No adequate or well-controlled studies in pregnant women
No evidence of human teratogenicity: APR birth defects with first
trimester exposure 2.5% (20 of 801 births; 95% CI 1.5%–3.8%)42
Non-nucleoside reverse transcriptase inhibitors
NNRTIs are recommended for use in combination regimens with 2
NRTI drugs (alternative to using a PI).
Nevirapine (NVP)
FDA pregnancy category B
High placenta transfer (cord-to-maternal blood ratio 0.90)26
Animal data3
Hepatocellular adenoma and carcinoma reported in mice and rats;
relevance to humans not known
No evidence of teratogenicity in rats and rabbits at twice the usual
human dose; however, low birth weights observed
Human data
Limited well-controlled studies of NVP in pregnant women; no
evidence of human teratogenicity; antiretroviral pregnancy registry
2.7% (28 of 1020 births, 95% CI 1.8%–4.0%)42
S10 l AUGUST JOGC AOÛT 2014
Recommendations for use in pregnancy
Alternate NRTI for dual NRTI backbone of combination regimens
Do not combine with ZDV (antagonistic mechanism of action);
discontinue d4T at time of administration of intrapartum IV ZDV.
Do not combine with DDI (risk of fatal lactic acidosis).
Dosing
Zerit ≥ 60 kg: 40 mg twice daily, < 60 kg: 30 mg twice daily
Take without regard to meals.
A phase I/II study showed pharmacokinetics in pregnancy were
similar to those in non-pregnant adults.170 No dose alteration is
required in pregnancy.
Adverse events/concerns in pregnancy
Fatal lactic acidosis has been reported in pregnant women who
received the combination of DDI and d4T. Physicians should avoid
prescribing this combination.
NRTI class concerns
Hypersensitivity reactions, including hepatic toxicity and (more
common in women) rash; it is unclear whether these reactions are
increased in pregnancy.
Recommendations for use in pregnancy
Preferred NNRTI for use in combination with dual NRTI backbone
Do not newly initiate in pregnancy because of risk of fatal rash and
hepatotoxicity.
Women who are tolerating NVP and become pregnant may
continue taking NVP.
Dosing
Viramune 200 mg once daily for 14 days, then 200 mg twice daily;
repeat lead-in period if therapy is discontinued for greater than
7 days.
A pharmacokinetic study has shown that pharmacokinetic
parameters in the second and third trimester are similar to those
postpartum171; however, a second study has shown that NVP
concentrations are lower in women in the third trimester than in
non-pregnant women172; current data is insufficient to recommend a
dose adjustment in pregnancy.
Adverse events/concerns in pregnancy
Severe potentially fatal hepatotoxicity and hypersensitive skin
reactions have been reported; some data have suggested that
women with CD4 counts > 250 cells/mm3 are at greater risk of
reaction3; Canadian data has been reported for toxicity across a
wide range of CD4 counts in women exposed to NVP for the first
time during pregnancy58; these toxicities have not been reported in
women or infants receiving single-dose NVP for the prevention of
vertical transmission.
Emergence of NVP resistance following single-dose NVP has been
shown; administration of postpartum antiretrovirals to the mother
(and infant) may reduce the detection of drug-resistant strains.
continued
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
Table 3. Continued
Efavirenz (EFV)
FDA pregnancy category D
Moderate placenta transfer (cord blood concentrations similar to
maternal plasma concentration in rats, rabbits, primates)3
Animal data3
Hepatocellular carcinoma and adenoma and pulmonary alveolar/
bronchiolar adenomas reported in female mice; however, no indication
of this effect in male mice or in rats
Significant central nervous system malformations (anencephaly,
anopthmalmia, cleft palate) reported in monkeys receiving EFV in first
trimester at doses comparable to human therapeutic exposure
Human data
Limited well-controlled studies in pregnant women; a meta-analysis
of birth defects observed in cohorts of infants with first trimester
exposure (1437 live births) found no increased risk of overall birth
defects than in infants exposed to non-EFV-based regimens
(RR 0.85; 95% CI 0.61–1.20), with one neural tube defect observed43;
a large prospective study of a cohort of antiretroviral-exposed infants
(13 124 live births) found significant association between EFV
exposure in the first trimester and neurological defects (adjusted OR
3.15; 95% CI 1.09–9.09).44
APR 2.7% (18 of 679 births, 95% CI 1.6%–4.2%); 6 retrospective
case reports of central nervous system defects (including 3 cases of
meningomyelocele), 1 prospective case report of neural tube defect,
and 1 prospective case report of bilateral facial clefts and anopthalmia
in humans receiving EFV in first trimester42
Etravirine (ETR)
FDA pregnancy category B
Placental transfer unknown (cord-to-maternal blood ratio from case
report data 0.33)174
Animal data3
Hepatocellular carcinoma and adenoma reported in mice; however,
no indication of this effect in rats
No evidence of embryotoxicity or teratogenicity in rabbits or rats at
doses comparable to human therapeutic exposure
Human data
No adequate or well-controlled studies and few case report data in
pregnant women
Rilpivirine (RPV)
FDA pregnancy category B
Placental transfer unknown
Animal data3
Hepatocellular carcinoma reported in mice; however, no indication of
this effect in rats
No evidence of embryotoxicity or teratogenicity in rats or rabbits at
doses 15 times and 70 times usual human dose, respectively
Human data
No published data for human pregnancy
Recommendations for use in pregnancy
Contraindicated in first trimester of pregnancy
Women receiving EFV should be instructed to avoid pregnancy;
recommend barrier contraception in combination with other
hormonal contraceptives.
Dosing
Sustiva 600 mg once daily at bedtime
Atripla (TDF 300 mg/FTC 200 mg/EFV 600 mg) 1 tablet once daily
at bedtime
May take on an empty stomach to reduce side effects
Limited pharmacokinetic data available; one pharmacokinetic
study has shown that EFV AUC is lower in the third trimester
than postpartum; however, a majority of third trimester levels
were above target exposure.173 No dose alteration is required in
pregnancy.
Adverse events/concerns in pregnancy
Avoid in first trimester of pregnancy as described above.
Recommendations for use in pregnancy
Insufficient safety and pharmacokinetic data to recommend use
during pregnancy
Dosing
Intelence 200 mg twice daily
Take with food to increase total AUC drug concentration.
Single pharmacokinetic study in 4 pregnant women reported
that drug levels and AUC were similar to those in non-pregnant
adults.174 Dose adjustment is not currently required in pregnancy.
Recommendations for use in pregnancy
Insufficient safety and pharmacokinetic data to recommend use
during pregnancy
Dosing
Edurant 25 mg once daily
Complera (TDF 300 mg/FTC 200 mg/RPV 25 mg) 1 tablet once
daily
Take with food (avoid protein-rich nutritional drinks) to increase
total AUC and peak drug concentration.
No pharmacokinetic studies in pregnancy; unknown whether dose
adjustment is required
continued
AUGUST JOGC AOÛT 2014 l S11
SOGC CLINICAL PRACTICE GUIDELINE

Table 3. Continued
Protease inhibitors PI class concerns
PIs are recommended for use in combination regimens with 2 NRTI Hyperglycemia and new onset or exacerbation of existing diabetes
drugs (alternative to using an NNRT). have been reported with PIs; unclear whether pregnancy increases
risk. Data regarding preterm delivery in women receiving PIs are
conflicting (see text for details).
Lopinavir-ritonavir (LPV/r) Recommendations for use in pregnancy
FDA pregnancy category C Preferred PI for use in combination with dual NRTI backbone
Low placental transfer (cord-to-maternal blood ratio LPV 0.20, RTV
Dosing
minimal)
Kaletra (LPV/r 200 mg/50 mg; LPV/r 100 mg/50 mg; oral solution
Animal data3 LPV/r 400 mg/100 mg in each 5 mL) 400 mg LPV twice daily; take
Hepatocellular carcinoma and adenoma reported in mice at doses 2 with food to reduce stomach upset.
times (LPV) and 5 times (RTV) usual human dose Pharmacokinetic studies show AUC is decreased in third
trimester.175,176 Increasing the dose of LPV/r from 400 mg/100 mg
Embryotoxic in rats; no evidence of teratogenicity in rats or rabbits twice a day to 600 mg/150 mg twice a day resulted in AUC similar
to non-pregnant adults taking the standard dose177,178; may consider
Human data increased dose to LPV/r 600 mg/150 mg twice daily in third
There are no adequate or well-controlled studies in pregnant women. trimester, particularly in women who have previously had PI.
No evidence of human teratogenicity; APR 2.4% (21 of 883 births, No data exist evaluating LPV/r drug levels using once-daily dosing
95% CI 1.5%–3.6%)42 in pregnancy; once-daily dosing is not recommended.

Adverse events/concerns in pregnancy

Atazanavir (ATV)
Approved by FDA for use in pregnancy
FDA pregnancy category B
Low placental transfer (cord-to-maternal blood ratio 0.10–0.20)
Animal data3
Benign hepatocellular adenomas reported in female mice at 3 times
usual human dose; no evidence of teratogenicity in rats or rabbits at
similar or 2 times usual dose respectively; weight loss or weight gain
suppression observed at 1.3 times usual human dose
Human data
No adequate or well-controlled studies have been reported in
pregnant women.
No evidence of human teratogenicity; APR 1.9% (13 of 669 births;
95% CI 1.0%–3.3%)42
Well tolerated; short-term safety data in Phase I/II clinical studies
Recommendations for use in pregnancy
Alternative PI for use in combination with dual NRTI backbone
Dosing
Must be combined with low-dose RTV (ATV/r) in pregnancy
Reyataz ATV/r 300/100mg once daily
Take with food to increase absorption and minimize stomach upset.
Three pharmacokinetic studies evaluating ATV/r 300 mg /100 mg
(without any interacting medications) have shown lower plasma
concentrations in the third trimester than in non-pregnant adults;
however, most women achieved an HIV viral load < 50 copies/mL and
did not require dose adjustment.50,52,53
Two pharmacokinetic studies evaluating ATV/r 400 mg/100 mg
(without any interacting medications) in the third trimester have shown
drug ATV AUC similar to non-pregnant controls.52,53
TDF reduces ATV exposure 25% in pregnant women; increasing the
dose to ATV/r 400 mg/100 mg in women receiving TDF has shown
ATV AUC similar to that in non-pregnant control subjects.53
Standard dose ATV/r 300 mg/100 mg can be used in pregnancy;
consider increasing the dose in third trimester to ATV/r 400 mg/100 mg
if combined with either an H2-receptor antagonist or tenofovir.
Data are insufficient to support combined use of ATV + TDF +
H2-receptor antagonist.

Adverse events/concerns in pregnancy

ATV increases indirect (unconjugated) bilirubin; the theoretical concern
that increased bilirubin may exacerbate physiologic hyperbilirubinemia
in infants has not yet been indicated in clinical trials.179
continued

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

Table 3. Continued
Ritonavir (RTV) Recommendations for use in pregnancy
FDA pregnancy category B Use only at low-dose in combination with a second PI to increase
Minimal placental transfer the serum drug levels of the second PI.

Animal data3 Dosing

Hepatocellular carcinoma and adenomas observed in male mice
at high doses; developmental toxicity (decreased body weight,
ossification delays) observed at high doses
Human data
Limited experience at full dose in human pregnancy; when used for
low-dose RTV boosting there is no evidence of human teratogenicity;
APR 2.2% (39 of 1741 births, 95% CI 1.6%–3.0%).42
Darunavir (DRV)
FDA pregnancy category C
Placental transfer unknown (cord-to-maternal blood ratio based on
case reports 0.24)181
Animal data3
Hepatocellular carcinoma and adenomas observed in mice and rats;
no evidence of embryotoxicity or teratogenicity in mice, rats, or rabbits
at doses 50% and 5% that of usual human doses
Human data
No adequate or well-controlled studies in pregnancy
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about risk of birth defects.
Saquinavir (SQV)
FDA pregnancy category B
Minimal placental transfer
Animal data 3
No evidence or carcinogenicity, embryotoxicity, or teratogenicity in
mice, rats, or rabbits at doses 21%–26% of usual human doses
Human data
No adequate or well-conducted clinical studies have been conducted
in pregnant women.
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about the risk of birth defects.
Norvir 100–400 mg PO per day in 1–2 divided doses (depending
on combination with specific PI)
Take with food to minimize stomach upset.
Phase I and II pharmacokinetic studies using therapeutic RTV
dosing and studies of other PIs using RTV as a low-dose booster
have shown lower RTV levels in pregnancy than postpartum53,180;
no dose adjustments are recommended in pregnancy.
Recommendations for use in pregnancy
Insufficient safety and pharmacokinetic data to recommend use
during pregnancy
Dosing
Must be combined with low-dose RTV (DRV/r).
Prezista antiretroviral-naive patients or antiretroviral-experienced
patients without DRV resistance mutations: DRV/r 800 mg/100 mg
once daily; antiretroviral experience patients with resistance
mutations: DRV/r 600 mg/100 mg twice daily
Take with food to minimize stomach upset.
Pharmacokinetic studies evaluating DRV/r as 600 mg/100 mg
twice daily or 800 mg/100 mg once daily have shown 17%–35%
reductions in DRV levels in third trimester of pregnancy compared
to postpartum.180–182 DRV/r 600 mg/100 mg twice daily provides
adequate drug exposure during pregnancy. Until more data are
available, twice-daily DRV is suggested. If once-daily dosing is used,
virological response and DRV concentration if available should be
monitored.
Recommendations for use in pregnancy
Alternative PI for use in combination with dual NRTI backbone
Dosing
Must be combined with low-dose RTV (SQV/r).
Invirase SQV/r 1000 mg/100 mg twice daily
Take with meals or within 2 hours after a meal.
Pharmacokinetic study data is conflicting; one study evaluating
SQV/r 1000 mg/100 mg twice daily has shown comparable drug
levels in second and third trimesters and postpartum183; a second
study using the same dosing has shown a 50% decrease in
third trimester levels without loss of virologic control184; data is
insufficient to recommend a dosage adjustment in pregnancy and
too limited to recommend once-daily dosing.

Adverse events/concerns in pregnancy

Well tolerated, short-term safety demonstrated for mothers and
infants; baseline ECG is recommended before starting because PR
and/or QT interval prolongation have been observed; no evidence
that pregnancy increases risk
continued

AUGUST JOGC AOÛT 2014 l S13

SOGC CLINICAL PRACTICE GUIDELINE

Table 3. Continued
Nelfinavir (NVF) Recommendations for use in pregnancy
FDA pregnancy category B Use in special circumstances when alternative agents are not
Minimal placental transfer tolerated in combination with dual NRTI backbone.

Animal data3 Dosing

Thyroid follicular cell adenoma and carcinoma has been observed in Viracept 1250 mg twice daily (750 mg three times daily not
rats receiving similar to 3 times usual human dose; no evidence of recommended in pregnancy)
embryonic or teratogenicity has been observed in rats or rabbits. Pharmacokinetic study data is conflicting; one Phase I/II
pharmacokinetic study has shown that adequate drug levels are
Human data achieved throughout pregnancy using 1250 mg twice daily185;
No evidence of human teratogenicity; APR 3.9% (47 of 1204 births, two other studies have shown lower NVF concentrations in the
95% CI 2.9%–5.2%)42 third trimester compared to the second trimester and postpartum;
however, viral load was adequately suppressed186,187; data is
Well tolerated; short-term safety has been demonstrated for mothers
insufficient to recommend a dosage adjustment in pregnancy.
and infants.
Adverse events/concerns in pregnancy
Extensive experience in pregnancy; however, clinical trials in non-
pregnant NVF based regimens had lower rate of viral response
compared to LPV/r or EFV based regimens, with similar viral
response rates compared to ATV/r and NVP.
The concern regarding the presence of the impurity EMS, a potential
carcinogen and teratogen in animals, in NVF manufactured before
2008 has been mitigated by establishment of maximum allowed
EMS limits established by the FDA.
Indinavir (IDV) Recommendations for use in pregnancy
FDA pregnancy category C For use in special circumstances when alternative agents cannot
Minimal placental transfer be used in combination with dual NRTI backbone

Animal data3 Dosing

Thyroid adenomas observed in rats at 1.3 times usual human dose;
however, no indication of any tumour types in mice
No evidence of embryotoxicity or teratogenicity in rabbits or
dogs at 3% and 50% of maternal levels; increased incidence
of supernumerary and cervical ribs observed in rats at doses
comparable to human doses
Exacerbation of physiologic neonate hyperbilirubinemia did not occur
in Rhesus monkeys with third trimester in utero exposure.
Human data
No adequate or well-controlled studies in pregnant women have been
reported.
No evidence of human teratogenicity; APR 2.1% (6 of 286 births,
95% CI 0.8%–4.5%)42
Fosamprenavir (FPV)
FDA pregnancy category C
Placental transfer unknown
Must be combined with low-dose RTV (IDV/r) in pregnancy.
Crixivan IDV/r 800 mg/100–200 mg twice daily
Two pharmaco­kinetic studies evaluating IDV without RTV have
shown IDV concentrations are lower in the third trimester than in
postpartum and non-pregnant patients, and 2 pharmacokinetic
studies evaluating IDV 400 mg twice daily combined with low-dose
RTV have shown decreases in IDV levels during pregnancy without
loss of virologic control.3
Optimal dose in pregnancy is not established; HIV levels and
trough IDV concentration should be monitored; must be combined
with low-dose RTV.
Adverse events/concerns in pregnancy
IDV increases indirect (unconjugated) bilirubin; evidence for a
theoretical concern regarding increased bilirubin exacerbating
physiologic hyperbilirubinemia in infants has not been reported;
there is a potential for renal stones; it is unclear if pregnancy
increases risk.
Recommendations for use in pregnancy
Safety and pharmacokinetic data are insufficient to recommend use
during pregnancy.

Animal data3 Dosing

Hepatocellular carcinoma and adenoma have been observed in rats
and mice at doses ranging from 0.3 to 1.4 times usual human dose.
Embryotoxic in rabbits; no evidence of gross structural abnormalities
in rats or rabbits; however, minor skeletal variations (decreased
ossification of femur, humerus, trochlea) and decreased body weights
have been observed.
Human data
No adequate or well-conducted studies have been conducted in
pregnant women.
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about risk of birth defects.
Recommended to be combined with low-dose RTV (FPV/r) in
pregnancy
Lexiva antiretroviral naïve patients: FPV 1400 mg twice daily
or FPV/r 1400 mg/100–200 mg once daily; Telzir antiretroviral
naïve patients: FPV/r 700 mg/100 mg twice daily; PI experienced
patients: FPV 700 mg/100 mg twice daily
Limited pharmacokinetic data are available; one study evaluating
FPV/r 700 mg/100 mg twice daily has shown lower amprenavir (active
moiety) concentrations during pregnancy than in postpartum and
non-pregnant patients; however, levels were considered adequate for
patients without PI resistance mutations188; no data are available for
using FPV in pregnancy without low-dose RTV; preliminary evidence
suggests no dose adjustment is required in pregnancy and data is too
limited to recommend once-daily or unboosted FPV.
continued

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

Table 3. Continued
Tipranavir (TPV) Recommendations for use in pregnancy
FDA pregnancy category C Safety and pharmacokinetic data are insufficient to recommend use
Placental transfer unknown; moderate transfer reported in one case during pregnancy.
report (cord-to-maternal blood ratio 0.41)189
Dosing
Animal data3 Must be combined with low-dose ritonavir (TPV/r).
Hepatocellular carcinoma and adenoma was observed in mice; this Aptivus TPV/r 500 mg/200 mg twice daily
effect was not observed in rats. No pharmacokinetic studies in pregnancy have been reported; it is
No evidence of embryotoxicity or gross structural abnormalities in not known whether dose adjustment is required.
rats or rabbits at doses 0.2 to 1.1 times usual human dose have been
reported; however, growth in inhibition was observed in rats at 0.8 Adverse events/concern in pregnancy
times human doses. Severe potentially fatal clinical hepatitis and intracranial
hemorrhage have been reported in non-pregnant population; no
Human data evidence pregnancy increases risk.
No adequate or well-controlled studies in pregnant women have been
reported.
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about risk of birth defects.
Entry Inhibitors
Enfuviritide (T20) Recommendations for use in pregnancy
FDA pregnancy category B Safety and pharmacokinetic data are insufficient to recommend use
No placental transfer based on single case report189 in pregnancy.
No evidence of teratogenicity in rats or rabbits at 27 or 3 times the Dosing
usual human dose, respectively3
Fuzeon 90 mg (1 mL) subcutaneously twice daily
No adequate or well-documented studies in pregnant women have
No pharmacokinetics studies in pregnancy have been reported; it is
been reported.
not known whether dose adjustment is required.
Maraviroc (MVC) Recommendations for use in pregnancy
FDA pregnancy category B Safety and pharmacokinetic data are insufficient to recommend use
Placental transfer unknown during pregnancy.

Animal Data3 Dosing

No evidence of embryotoxicity, carcinogenicity, or teratogenicity has
been found in rats or rabbits at 20 times and 5 times usual human
dose, respectively.
Human Data
No adequate or well-documented studies in pregnant women have
been reported.
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about the risk of birth defects.
Integrase Inhibitors
Raltegravir (RAL)
FDA pregnancy category C
Placental transfer unknown (cord-to-maternal blood ratio from case
reports 1.0)190
Animal Data3
There has been no evidence shown of embryotoxicity, carcinogenicity,
or teratogenicity in rats or rabbits at 3 to 4 times the usual human
dose; however, an increase in incidence of supernumerary ribs was
reported in rats at 3 times usual human dose.
Celsentri 150 mg twice daily when given with strong CYP3A
inhibitors; 300 mg twice daily when given with drugs that are not
strong CYP3A inducers or inhibitors; 600 mg twice daily when
given with CYP3A inducers
No pharmacokinetic studies in pregnancy have been reported;
it is not known whether dose adjustment is required.
Recommendations for use in pregnancy
Safety and pharmacokinetic data are insufficient to recommend use
during pregnancy.
Dosing
Isentress 400 mg twice daily
A pharmacokinetic study published in abstract form reports no
differences between women in the third trimester and postpartum
and non-pregnant patients191; preliminary evidence suggests no
dose alteration is required in pregnancy.

Human Data
No adequate or well-documented studies in pregnant women have
been reported.
Few pregnancy exposures have been reported to the APR;
no conclusion can be made about the risk of birth defects.
continued

AUGUST JOGC AOÛT 2014 l S15

SOGC CLINICAL PRACTICE GUIDELINE
Table 3. Continued
Elvitegravir (EVG)-Cobicistat (COBI)
FDA pregnancy category B
Placental transfer unknown
Animal Data3,192
EVG: No evidence of teratogenicity or an effect on reproductive
function has been reported in rats or rabbits at doses 23 and 0.2 times
higher, respectively, than the usual human dose.
COBI: No evidence of teratogenicity or effect on reproductive function
has been reported in rats or rabbits at doses 1.8 and 4.3 times higher,
respectively, than the usual human dose.
Human Data
No adequate or well-documented studies have been reported in
pregnant women.
APR: Antiretroviral Pregnancy Registry; IV: intravenous, FTC: emtricitabine; EVF: efavirenz; RR: relative risk; OR: odds ratio; AUC: area under the curve;
RPV: rilpinavir; LPV/r: lopinavir/ritonavir; SQV: saquinavir; ECG: electrocardiogram; CYP: cytochrome P450; EMS: ethyl methane­sulfonate
rapidly crosses the placenta and achieves adequate infant
blood levels,26,27 is easily administered, and is well tolerated
in both women and infants, it has been recommended as a
treatment strategy for women living with HIV who present
in labour and are not receiving antenatal antiretroviral
therapy. Nevirapine possesses a long half-life, however, and
therefore use of even a single dose exposes women to an
extended period of nevirapine monotherapy, potentially
increasing the risk of nevirapine drug-resistant mutations.28
One strategy to limit the emergence of nevirapine resistance
after single-dose nevirapine is to provide the woman with an
antiretroviral tail (e.g., postpartum addition of 2 NRTIs for
a period of 3 to 14 days).29–33
The HPTN 040/PACTG 040 study evaluated the alternative
treatment strategy of administering prophylactic cART
to infants born to women living with HIV who were not
receiving antenatal antiretroviral therapy.25 Forty-one percent
of women in this study received intrapartum intravenous
zidovudine and the majority of infants were formula-fed.
This study demonstrated that the cART (the addition of
either 3 doses of infant nevirapine or 2 weeks of lamivudine/
nelfinavir to 6 weeks of zidovudine) was superior in
reducing the risk of vertical HIV transmission (2.2% and
2.4%, respectively) to 6 weeks of infant zidovudine therapy
alone (4.8%, P = 0.046). The rate of neutropenia was higher
in the 3-drug regimen (27.5% with zidovudine/nelfinavir/
lamivudine) than in the 2-drug (14.9% with zidovudine/
nevirapine) and 1-drug (16.4% with zidovudine) regimens.
Principles behind using combination
antiretroviral therapy in pregnancy
Antiretroviral treatment recommendations for the pregnant
woman living with HIV are based on the principle that
therapies of known benefit to the woman should be offered
S16 l AUGUST JOGC AOÛT 2014
Recommendations for use in pregnancy
Safety and pharmacokinetic data are insufficient to recommend use
during pregnancy.
Dosing
Stribild (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg)
1 tablet once daily with food
No pharmacokinetics studies in pregnancy have been reported;
it is not known whether dose adjustment is required.
and not withheld during pregnancy. The benefits of cART
for the overall health of the woman and for prevention
of vertical transmission are known; however, there is
need for improved understanding of the short- and long-
term effects of antiretroviral drug therapy in pregnancy;
therefore parameters of maternal and fetal well-being need
to be closely monitored. Overall, the benefit of prevention
of vertical transmission of HIV is considered to outweigh
the potential risks associated with antiretroviral medications,
provided these agents are administered per treatment
recommendations and with close monitoring and follow-up
by experts in the area of HIV and obstetrics.
Selection of a specific antiretroviral drug therapy regimen
in a pregnant woman living with HIV must take into
account the inter-related issues of:
1. the stage of pregnancy,
2. the current and co-morbid health status of the woman,
3. her HIV-resistance profile,
4. what is currently known about the use of specific drugs
in pregnancy and the risk of teratogenicity,
5. unique pharmacokinetic considerations, including
altered kinetics in pregnancy and issues of placental
passage of medications,
6. the woman’s social status and intravenous drug use, and
7. the ability of the woman to cope with the antiretroviral
drug therapy pill burden.
Timing of initiation of combination
antiretroviral therapy in pregnancy
The timing of initiation will depend on the woman’s HIV
disease status (e.g., CD4-cell count and HIV viral load), her
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
preparedness to start cART, and her degree of nausea and
vomiting of pregnancy. Adult HIV treatment guidelines are
available elsewhere2 and are not discussed in detail here. In
brief, they recommend initiation of cART for all individuals
regardless of CD4-cell counts. In the obstetrical setting there
are controversies about the timing of cART initiation in
pregnant women who have not already been treated. While
cART may reduce the risk of HIV vertical transmission,34
there may also be risks in exposing the fetus to cART.
Women with CD4-cell counts < 200 cells/mm3 are at
high risk of opportunistic infections35,36; therefore, cART
should be started immediately, regardless of gestational
age, in conjunction with prophylaxis for opportunistic
infections as described below. Women with CD4-cell
counts between 200 to 350 cells/mm3 may be at risk of
experiencing more common infections (e.g., herpes zoster,
bacterial pneumonia), therefore cART should be initiated
as soon as possible—usually after the first trimester is
completed (week 14). In other cases, although 14 weeks is
the general recommendation for cART initiation, delayed
initiation of cART until the detailed anatomy ultrasound
(i.e., week 18) may be considered in women with CD4-cell
counts > 350 cells/mm3 on a case-by-case basis.
Antiretroviral drug resistance testing should be performed
before starting an antiretroviral regimen; however, if it
is determined that cART needs to be started urgently,
decisions to start can be made based on the woman’s
antiretroviral history and adjusted later if necessary. All
women should be counselled about the importance of
adherence to the regimen, and should be recommended to
continue therapy after delivery.
Detailed guidelines regarding management and prophylaxis of
opportunistic infections, including specific recommendations
for pregnant women, are available35 and are not discussed in
detail here. In brief, consideration for antibiotic prophylaxis
against the following opportunistic infections must be
made based on CD4-cell count: < 200 cells/mm3 requires
prophylaxis against PCP; < 100 cells/mm3 requires additional
prophylaxis against Toxoplasmosis gondii (if Toxoplasmosis
immunoglobulin G serology is positive and an agent
other than cotrimoxazole is used as prophylaxis for PCP);
< 50 cells/mm3 requires additional prophylaxis against MAC
after obtaining MAC blood cultures and an ophthalmology
referral to rule out CMV retinitis. Treatment and prophylaxis
of all opportunistic infections must be provided as required
with consideration of potential toxicities in pregnancy. While
this is well discussed in available guidelines,35 agents of note
to avoid, particularly in the first trimester of pregnancy,
include continuous oral fluconazole and clarithromycin.37,38
Cotrimoxazole (a folate antagonist which readily crosses the
placenta) may be safely used throughout pregnancy; however,
consideration should be given to increasing the folic acid
dose to 5 mg per day in the first trimester and monitoring
infants postpartum due to increased risk of neonatal
hyperbilirubinemia.39
Continuation of therapy in women already
receiving combination antiretroviral therapy
prior to pregnancy
In most cases, the current antiretroviral regimen should be
continued if the regimen is effective in suppressing HIV
viral load and is tolerated by the woman. Significant nausea
and vomiting of pregnancy may complicate a woman’s
ability to adhere to medication and needs to be addressed
and aggressively managed.40
There are two main populations of women in whom
switching of antiretroviral medications may be considered.
The first is pregnant women living with HIV who are
receiving efavirenz and present pre-conception or very
early for care in the first trimester. As discussed below and
more thoroughly in Appendix 2, efavirenz is not a desirable
choice in the first trimester due to its association with neural
tube defects in primates and in case reports in humans.41–44
Because most women will present after the 5- to 6-week
gestational age time window for neural tube closure, the
NIH guidelines endorse continuation of efavirenz in all
pregnant woman including those who present for care in
the first trimester.3 However because women may not always
present after neural tube closure, and because there is a risk
of women remaining on a potentially teratogenic medication
postpartum, particularly those who do not receive adequate
contraception, these guidelines still recommend considering
switching the woman from efavirenz to an alternative
antiretroviral agent that has greater safety and efficacy
data in pregnancy. If efavirenz is received during the first
trimester, however, ultrasound evaluation of neural tube
closure is very important.
Changing antiretroviral medications may also be considered
in women who are receiving an antiretroviral agent for
which there is little known safety and efficacy data for use
in pregnancy (see Appendix 2). It is important to consider
the safety and risk of continuing each antiretroviral
medication, and prior to any changes to medication there
should be discussion between the woman, her HIV care
provider, and her obstetrical care provider.
Selection of cART regimen in pregnancy
Antiretroviral drug resistance testing should be performed
as described above before starting cART and test results
used to help determine the optimal regimen. A cART
regimen should usually include a dual NRTI backbone
AUGUST JOGC AOÛT 2014 l S17
SOGC CLINICAL PRACTICE GUIDELINE
that includes one or more NRTIs with high levels of
transplacental passage (e.g., zidovudine, lamivudine,
emtricitabine, tenofovir, abacavir) and an additional
boosted protease inhibitor (see Appendix 2).
Consistent adherence to antiretroviral therapy is critical
to its efficacy and to preventing the development of
resistance. In particular, with complications in pregnancy
such as nausea and vomiting of pregnancy, there may
be circumstances when cART needs to be discontinued.
In this case, regardless of reason, the woman should be
advised to discontinue all drugs at once, and to resume
all drugs simultaneously to minimize the risk of viral
resistance developing during therapy (unless on an NNRTI,
then a tail of 2 NRTIs is recommended for 1 week).
Resume antiretroviral therapy as quickly as possible after
discontinuing, to minimize the risk of rebound viremia
and the potentially increased risk of vertical transmission.
In the antiretroviral naive and in a presumed or proven
pan-sensitive virus the recommended NRTI backbone is
zidovudine-lamivudine 300 mg/150 mg 1 tablet PO twice
daily with lopinavir-ritonavir 200 mg/50 mg 2 tablets PO
twice daily. This regimen requires twice-daily dosing and
monthly hemoglobin monitoring as zidovudine can cause
pure red cell aplasia.45 If women are unable to tolerate or
adhere to a twice-daily dosing regimen an alternative regimen
is abacavir-lamivudine 600 mg/300 mg 1 tablet PO once
daily and boosted atazanavir (atazanavir 300 mg plus ritonavir
100 mg PO once daily). Testing for, and confirmation of the
absence of the inherited HLA*B5701 gene must be done
prior to initiation of any abacavir-containing medication
to reduce the risk of a severe allergic reaction.46 Atazanavir
is associated with increased maternal indirect bilirubin.
Although the clinical significance has not been determined,
bilirubin should be monitored monthly in the mother and the
infant after delivery.47,48 It is important to note that both of the
above listed boosted protease inhibitor regimens may require
increased dosing (e.g., abacavir-lamivudine 3 tablets PO twice
daily, atazanavir 400 mg PO once daily with ritonavir 100 mg
PO once daily) in the third trimester as a result of increased
volume of distribution of pregnancy.47,49–53 These empiric dose
increases should be considered, particularly if the woman’s
HIV viral load becomes detectable, cART adherence has been
verified and HIV resistance has been ruled out. If available,
therapeutic drug level monitoring may also be considered in
the third trimester to guide the need for protease inhibitor
dose adjustment.54
In pregnant women with HIV and HBV co-infection, the
dual NRTI backbone should include 2 NRTI agents that
are also active against HBV (e.g., lamivudine, emtricitabine,
tenofovir)2,3,55,56; therefore, the recommended first-line
S18 l AUGUST JOGC AOÛT 2014
regimen in these women is tenofovir-emtricitabine and
boosted atazanavir/ritonavir as described above. HBV DNA
levels should be monitored and should become undetectable
on this regimen. Because chronic administration of tenofovir
to pregnant monkeys has resulted in a slight reduction in
fetal bone porosity (a finding which has conflicting results
in human studies) and is associated with nephrotoxic
effects, tenofovir is not recommended as a first-line agent in
pregnancy except with an HBV co-infection, drug resistance,
and/or medication adherence issues.3,56,57
If women are unable to tolerate or are resistant to the PIs
lopinavir and/or atazanavir, alternative cART regimens may
need to be considered including (a) boosted darunavir/
ritonavir (darunavir 800 mg PO daily with ritonavir 100 mg
PO daily or darunavir 600 mg PO twice daily with ritonavir
100 mg PO twice daily), or (b) efavirenz 600 mg PO at
nighttime, if the virus is sensitive and after the early first
trimester of pregnancy, ideally after a detailed ultrasound
and screening have confirmed the absence of a neural
tube defect. Nevirapine initiation in pregnancy has been
associated with 10% life-threatening toxicity (fatal rash
and hepatotoxicity) and its initiation in pregnancy is not
recommended if there is a suitable alternative.2,3 Although
some data have suggested that nevirapine may be safe if a
woman’s CD4 cell count is > 250 cells/mm3, Canadian data
have suggested that toxicity has occurred at a wide range
of CD4-cell counts in women exposed to nevirapine for
the first time during pregnancy.58 Women who have been
receiving and tolerating nevirapine prior to becoming
pregnant (regardless of CD4-cell count) can continue to
receive this agent.2,3 All other antiretroviral agents used in
adult HIV care must be individually assessed on a case-by-
case basis, depending on the woman’s clinical and personal
circumstances, co-infections, HLA*B5701 results, genotype
of virus, and available options. Detailed information on each
antiretroviral agent is provided in Appendix 2; however, it is
recommended that consultation be made with experts in the
areas of HIV and obstetric care.
Because antiretroviral medications are used as a part
of combination regimens it is difficult to ascertain the
contribution that an individual agent has on potential
maternal and/or fetal toxicity. Studies that have evaluated
the results of cART have shown variable results. Some
early studies have reported serious maternal toxicities
including hepatotoxicity,59–61 higher rates of neonatal
malformations,62,63 increased risk of prematurity and low
birth weight,64–70 or serious neonatal complications including
mitochondrial toxicity.69–75 Other studies, however, suggest
that there are generally few serious effects for the mother or
infant associated with cART.17,76–82
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
The concerns surrounding the use of efavirenz
(teratogen), nevirapine (rash and hepatotoxicity), tenofovir
(bone abnormalities, nephrotoxicity), and atazanavir
(hyperbilirubinemia) in pregnancy have been discussed.
Women living with HIV who are on antiretroviral
therapy are also at a higher risk of preterm delivery than
those who are not (18% vs. 9% in Canada).83,84 There
is conflicting evidence about whether cART further
increases this risk.67,85–92 Data to suggest an association
between antiretroviral drug therapy (including protease
inhibitor use) and premature delivery or low birth weight
infants are mixed; however, a causal relationship has not
been established88,93–95 and PIs should not be withheld
during pregnancy. There is also conflicting evidence
as to whether women taking regimens that include PIs
are at increased risk for impaired glucose tolerance or
gestational diabetes in pregnancy.64,96–98 Standard glucose
screening at 24 to 28 weeks is recommended in pregnant
women living with HIV; if a woman is receiving a PI-
based regimen, the clinician may choose to perform this
screening test earlier.3,99
Recommendations
  4. All pregnant women living with HIV should be
treated with combination antiretroviral therapy
regardless of baseline CD4 and viral load. (II-2A)
  5. Antiretroviral therapy should not be discontinued
during the first trimester for obstetrical reasons,
but if the woman is not on therapy and there is
no urgent medical indication for combination
antiretroviral therapy, it can be delayed until after 14
weeks’ gestation. (III-B)
  6. All women living with HIV (both those who still have
a detectable viral load after exposure to antiretroviral
therapy and those who are antiretroviral-naive) should
have their virus genotyped and, if possible, tested
for phenotypic resistance to assist in optimizing
antiretroviral therapy. It is advisable to discuss the
interpretation of the genotype testing and any
changes to the antiretroviral therapy with experienced
clinicians. Testing for HLA-B*5701, if not done
previously, is recommended in case abacavir might be
required. (II-2B)
  7. A combination antiretroviral therapy regimen
including a dual nucleoside reverse transcriptase
inhibitor (NRTI) backbone that includes one or
more NRTIs and a boosted protease inhibitor
should be favoured because there is higher
confidence in its safety and efficacy in pregnancy.
Whenever possible, antiretrovirals known to cross
the placenta to the fetal compartment should be
used. (II-2B)
  8. Whenever possible, drugs with no safety data should
be avoided during the period of organogenesis.
Efavirenz should not be prescribed in the first
trimester of pregnancy because of its possible
teratogenicity; however, if exposure has occurred
and the neural tube has closed, efavirenz can be
continued. Nevirapine should not be started in
pregnancy, unless indicated by the woman’s resistance
patterns, because it is associated with a high rate of
serious adverse outcomes in this situation; however
ongoing, pre-pregnancy treatment with nevirapine
can be continued through pregnancy if tolerance and
efficacy are established. (II-3D)
  9. If antiretroviral therapy is discontinued for any
reason during pregnancy, all drugs should be
discontinued at once (unless the woman is on non-
nucleoside reverse transcriptase inhibitors; in that
case a tail of 2 nucleoside reverse transcriptase
inhibitors is recommended for 1 week), and
all drugs should be resumed simultaneously to
minimize the risk of viral resistance developing
during therapy. Antiretroviral therapy should
be resumed as quickly as possible after
discontinuance to minimize the risk of rebound
viremia and the potentially increased risk of
vertical transmission. (II-1A)
10. If a pregnant woman has significant nausea of
pregnancy, do not begin antiretroviral therapy
until her nausea is adequately controlled. Most
antinauseants used in pregnancy can be co-
administered with antiretrovirals. If the woman is
already on antiretrovirals and has hyperemesis of
pregnancy, discontinue all antiretrovirals at once,
and then reinstate all at once, when nausea and
vomiting are controlled (unless the woman is on
non-nucleoside reverse transcriptase inhibitors
[NNRTIs], in which case a tail of 2 nucleoside
reverse transcriptase inhibitors is recommended for
1 week to prevent future NNRTI resistance). (II-2D)
11. Therapy should be individualized to maximize
adherence to the prescribed antiretroviral
regimen. (III-A)
12. Routine dose adjustment of the combination
antiretroviral therapy is not recommended in
pregnancy. (III-D)
ANTEPARTUM MANAGEMENT
General Considerations
It is important to consider the broad context of a
woman’s life when managing her HIV and prenatal care.
Considerations include:
AUGUST JOGC AOÛT 2014 l S19
SOGC CLINICAL PRACTICE GUIDELINE
•• Providing empathetic, non-judgemental care to women
living with HIV and their children, in the spirit of
professionalism.100
•• Addressing early and systematically the woman’s need
for social support, with at least one interview with
a social worker. Pregnant women living with HIV
in Canada commonly experience challenging social
and economic environments, with 25% of infections
linked to drug use.10,11 The aim of the comprehensive
assessment by a social worker is to determine the
woman’s needs and to propose culturally relevant
support and follow-up if required.
•• Maintaining confidentiality, including with relatives.100
•• Encouraging the testing of partners and previous
children if their HIV status is unknown.101 The medical
and psychological needs of the fathers should be
addressed, and the men referred to other health care
providers if necessary.102
•• Advising on the use of, and facilitating access to,
condoms for the purpose of preventing transmission
of HIV and other sexually transmitted infections.103
If both members of the couple are living with HIV,
they should be informed of the possible risk of
superinfection associated with unprotected sex.104
•• Respecting the wishes of a mother who refuses
antenatal cART after being fully informed and
counselled. A plan for the care of the newborn should
be prepared prior to delivery.100
Inclusion of de-identified data of the mother and infant
pairs in provincial and national surveillance programs is
highly recommended. The CPHSP, an initiative of the
Canadian Pediatric AIDS Research Group (CPARG)
collects important public health data, which inform
allocation of resources and management of future
pregnancies.10,11
First Trimester (Weeks 0 to 13)
Early pregnancy offers the opportunity for complete HIV
and obstetrical assessments and permits planning for prenatal
genetic screening. In addition to the standard antenatal
assessments for all pregnant women, assessment should
include the following: documentation of history of prior
HIV-related illnesses and past CD4-cell counts and plasma
HIV viral loads; assessment for symptoms of opportunistic
infections; complete physical examination including a pelvic
examination and cervical Pap smear; screening for sexually
transmitted infections (including chlamydia, gonorrhea,
syphilis); screening for HBV (using HBsAg, anti-HBs, and
anti-HBc), HCV (HCV antibody and HCV PCR status if
antibody positive) and tuberculosis (induration of > 5 mm
S20 l AUGUST JOGC AOÛT 2014
using purified protein derivative); and evaluation of
immunization status. In addition to standard prenatal blood
work, the following blood work should also be obtained:
CD4-cell count (absolute count and fraction), HIV viral
load, baseline CBC and differential, and liver (AST, ALT,
LDH) and renal (urea, serum creatinine) function testing
(see Table 4 and Table 5).
All pregnant women who are living with HIV, regardless
of age, should be offered, through an informed
consent process, dating ultrasound and prenatal genetic
screening for the most common clinically significant fetal
aneuploidies. Timely referral is critical to ensure women
are able to undergo the type of screening test they have
chosen. Ideally, first trimester biochemical screening and
nuchal translucency measurements (at 11 to 14 weeks)
should be obtained to integrate with second trimester
biochemical screening, and these results should be used
to inform the need for invasive testing.105 If integrated
prenatal screening is not accessible, then pregnant women
living with HIV should be offered the non-invasive
screening for aneuploidy based on gestational age that is
available in the area. As maternal serum testing of fetal
aneuploidy becomes more available, this method of testing
will be preferred over amniocentesis, particularly in this
population.
Nausea and vomiting can be a significant issue for all
pregnant women, and in women living with HIV, it may
affect their ability to adhere to the prescribed antiretroviral
regimen. Evaluation of nausea and vomiting of pregnancy
should be conducted and aggressive management of this
condition, starting with a prescription for doxylamine-
pyridoxine as needed,40 is necessary to facilitate the initiation
and/or continuation of antiretroviral medications.
Important considerations when evaluating nausea and
vomiting of pregnancy in a woman living with HIV should
include antiretroviral-related lactic acidosis or pancreatitis,
as well as opportunistic infections including intestinal
protozoa if the woman is at risk (e.g., CD4-cell count
< 200 cells/mm3) and symptoms are accompanied by
diarrhea. In particular, in women with very advanced HIV
disease, alternative causes for nausea should be considered
(e.g., gastric lymphoma, central nervous system lesions, or
infections causing increased intracranial pressure).35
As outlined above, the timing of initiation of antiretroviral
therapy will depend on current CD4-cell count and maternal
conditions including nausea and vomiting. Antiretroviral
therapy and prophylaxis or treatment of opportunistic
infections should be started immediately if CD4-cell count
is < 200 cells/mm3 and/or there are AIDS-defining illnesses
requiring therapy. In other cases, it is advisable to ensure
 Table 4. Recommended laboratory tests and investigations for pregnant women living with HIV by visit and gestational age
Initial 10–13+6 15–17 19–20 24–26 28–30 32–36 Delivery 4–6
visit* weeks weeks weeks weeks weeks weeks weeks
Immunologic assessment CD4 √ √ opt √ opt √ √ opt √ √ √ √
HIV plasma viral load HIV viral load √ √ opt √ opt √ √ opt √ √ √ √
Drug resistance & abacavir HIV genotypic drug resistance† √
hypersensitivity testing
HLA-B*5701‡ √
Hematologic assessment CBC with differential √ √ opt √ opt √ √ opt √ √ √ √
Liver function tests AST, ALT, LDH, bilirubin √ √ opt √ opt √ √ opt √ √ √ √
Renal function Creatinine, BUN √ √ opt √ opt √ √ opt √ √ √ √
Phosphatemia§ √ √ opt √ opt √ √ opt √ √ √ √
Urinalysis & urine culture √ √ opt √ opt
Blood glucose Fasting glucose √
Gestational diabetes screen‖ √
Blood type Blood type √
Serology CMV IgG √
Rubella IgG √
Toxoplasma IgG √
Syphilis (RPR) √ √ 154
Varicella IgG √
HAV IgG √
HBsAg, anti-HBs, anti-HBc √
HCV IgG¶ √
Ultrasound & prenatal screening Ultrasound √ dating √ 11–13+6 √ detailed √ opt √ growth √ opt
NT growth growth
PAPP-A √
uE3, hCG, AFP, inhibin A √ 15–20+6
Sexually transmitted & other Cervix chlamydia & gonorrhea √
infections NAAT
Pap smear √ √
HSV history# √
GBS screen anorectal swab** √
opt: optional; BUN: blood urea nitrogen; HAV: hepatitis A virus; NT: nuchal translucency; PAPP-A: pregnancy associated plasma protein A; uE3: unconjugated estriol; hCG: human chorionic gonadotropin; AFP: alpha-
fetoprotein; NAAT: nucleic acid amplification test; HSV: Herpes simplex virus; GBS: group B streptococcus.
*Integrate initial visit laboratory tests and/investigations (as indicated) with all others if the visit occurs after 10 weeks’ gestation.
†HIV genotypic drug testing is recommended at time of first HIV plasma viral load, at time of initiation of antiretrovirals, and if and when treatment fails or viral load suppression is incomplete (> 250 HIV copies/mL).
‡HLA-B*5701 testing is recommended at baseline or if not previously done before initiating therapy with abacavir.
§Phosphatemia should be monitored in women receiving tenofovir-based regimens because it is a potential cause of tubular toxicity.3,56,57
‖Screen for gestational diabetes using 50 g glucose challenge test (1 h plasma glucose [PG]) or 75 g oral glucose tolerance test (fasting PG, 1 h PG, 2 h PG).99 If a woman is receiving a PI-based regimen, particularly
if initiated before pregnancy, consideration can be given to performing this screening test earlier.
¶Confirm positive result of HCV antibodies with HCV PCR.
#If there is a positive genital herpes history, recommend starting prophylactic treatment (e.g., valacyclovir 500 mg orally twice daily) at 34 to 36 weeks to prevent recurrent herpes simplex virus at delivery.

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Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

**Group B streptococcus anorectal swab is recommended at 35 to 37 weeks, or sooner if delivery is anticipated within 5 weeks.
SOGC CLINICAL PRACTICE GUIDELINE

Table 5. United States Food and Drug Administration pharmaceutical pregnancy categories213
A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and
there is no evidence of risk during later trimesters).
B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled
studies in pregnant women
OR
Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to
demonstrate a risk to the fetus in any trimester.
C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies
in humans, but potential benefits may warrant use of the drug in pregnant woman despite potential risks.
D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experiences
or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk
based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in
pregnant women clearly outweigh potential benefits.

nausea and vomiting is controlled prior to initiating
antiretroviral therapy. Women who are receiving antiretroviral
therapy prior to pregnancy should not discontinue their
medication regimen during the first trimester. All drug
therapy should be reviewed for safety in pregnancy,
particularly in the first trimester period of embryogenesis.
Women should be counselled on all relevant aspects of
ensuring a healthy pregnancy including maintaining a
healthy diet and lifestyle. Women should start or ideally
continue taking folic acid 1 mg daily for at least the first 3
months of their pregnancy. If necessary, in cases of food
insecurity, resources should be offered to improve nutrition.
Notably, malnutrition and micronutrient deficiencies have
been linked to vertical transmission risk.106 Live vaccines
(varicella zoster and measles, mumps and rubella) are
contraindicated in pregnancy.107 Women with negative
serologies for these infections should be considered for
immunization postpartum, depending on their CD4 count,
and the schedule of recommended immunization for
adults living with HIV should be followed.33 In particular,
HBV, pneumococcus, and influenza vaccines can be safely
administered in pregnancy. Within a harm reduction
model, women should be encouraged to stop smoking,
drinking alcohol, and using recreational drugs and should
be referred for appropriate counselling support and/or
treatment.1,108,109 Other harm reduction strategies that can
be offered if appropriate include nicotine replacement
treatment and opiate harm reduction measures such as
methadone and/or buprenorphine programs.
Second Trimester (Weeks 14 to 27)
Assessment of the status of the woman’s HIV, review
of laboratory investigations from the first trimester, and
re-evaluation of antiretroviral drug therapy should be
completed during the second trimester. The women’s
clinical, virological, and immunologic status including
CD4-cell count, HIV viral load, CBC, AST, ALT, LDH,
bilirubin, blood urea nitrogen, creatinine, as well as any
other blood work as indicated by clinical history and
specific cART regimen, should be assessed every 4 to
8 weeks throughout pregnancy (see Table 4). Because
comorbidities affect many women living with HIV, more
frequent evaluations may be appropriate. Consideration
for repeat urine cultures in second and third trimester
should be made given the higher rates of hospitalization
for urinary tract infections in women living with HIV.110
All women should be screened for gestational diabetes
between 24 and 28 weeks as recommended in most recent
guidelines.99 As discussed above, there is conflicting
evidence on whether cART regimens containing PIs
increase the risk of hyperglycemia or new-onset or
exacerbated diabetes in pregnancy (see also Appendix 2).
If a woman is receiving a PI-based regimen, particularly
one initiated before pregnancy, consideration can be given
to earlier screening for gestational diabetes.
The second part of the integrated prenatal screening
tests (i.e., second trimester biochemical screening) should
be performed at 15 to 19 weeks.105 A detailed ultrasound
at 18 to 20 weeks is recommended to assess growth and
fetal anatomy.105 If aneuploidy or any other fetal infection
or syndrome that has prenatal diagnostics is a concern,
invasive testing should be considered. Invasive testing
should only occur if statistical risk of the condition is higher
than the risk of the procedure, taking into consideration
the biochemical, serologic, and ultrasound results.105 When
amniocentesis is performed, the woman should ideally be on
cART, but the timing may not permit full suppression of her
HIV viral load prior to the procedure. In the pre-cART era,
the risk of vertical transmission in women who underwent

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
amniocentesis was twice as high as those who did not (30%
vs. 16%, RR = 1.85; 95% CI 0.69–4.98.111 Since the initiation
of cART and the recommendation to treat all pregnant
women, there have been no documented transmissions.112–115
However, it is impossible to rule out a residual small increase
in risk of transmission with amniocentesis in women
on cART with a fully suppressed plasma viral load. Non-
invasive molecular prenatal testing should be considered as
an option to avoid invasive testing.116
General obstetrical management with referral of the
woman to support services as needed is appropriate at
this time. A review of the care providers involved and
the delivery plan, including location of delivery, can be
initiated at this time (at the 19- to 20-week and 23- to
24-week visits).
Third Trimester (Weeks 28 to 40)
The efficacy and toxicity of the particular cART regimen
for each woman should be determined by CD4-cell count,
HIV viral load, and hematologic, liver, and renal parameters
in the third trimester, approximately every 4 to 8 weeks (see
Table 4). Given the risk of placental dysfunction associated
with increased rates of intrauterine growth restriction and
oligohydramnios in the pregnancies of women living with
HIV,117 follow-up growth ultrasound should preferably be
done monthly, but if this is not possible, a third trimester
scan can assist in determining whether there has been
placental or fetal compromise. Considering the higher
rate of preterm birth in this population,67,83,86,92 close
clinical follow-up is recommended and the schedule of
some obstetrical assessments (e.g., group B streptococcus
screening) and prophylaxis (e.g., genital herpes prophylaxis)
may need to be adjusted.
Adherence to cART regimens should be emphasized at
each visit throughout pregnancy; however, this is critical
in the third trimester because virologic suppression (HIV
viral load < 50 copies/mL) should be achieved at this
time. If the woman’s viral load has not been suppressed
or has appeared to rebound, a number of factors must be
considered. Health care providers should reassess overall
adherence, clarify any reasons for non-adherence, and
attempt to implement strategies or provide tools to assist
the woman in taking her medication. Inpatient directly
observed therapy may be considered.118 Clinicians should
also reassess dosing adequacy and consider the need for
increased dosing of antiretroviral medications in the third
trimester. Therapeutic drug level monitoring may also be
considered to guide the need for dose adjustment.54 In
all cases viral genotype history should be reassessed and
current HIV viral load sample sent for repeat genotyping
if applicable.
Between 30 to 35 weeks it is important that a plan for location
and mode of delivery is established and a formula-feeding
plan has been arranged for the infant. Women living with
HIV are recommended to formula feed their infants; to
avoid the 9.3% (3.8 to 14.8%) increased risk of post-natal
transmission of HIV through breast milk, breastfeeding is
not recommended.119–121 The risk of disclosure that may arise
when a women does not breastfeed may compromise her
confidentiality. Health care providers should assist with a plan
before delivery that can help women feel more comfortable
when discussing feeding with family and friends.
Plans for ongoing HIV care should also be established at
this time (see Postpartum Management).
Delivery Plans and Mode of Delivery
Planning the hospital location for delivery should take
into consideration the woman’s gestational history, home
location and transportability, facilities at her regional
hospital, and the comfort and experience of the local care
providers. If delivery is being considered outside a regional
tertiary care facility, information on pregnancy history and
management plans should be provided to the facility prior
to the woman’s estimated date of delivery, communication
with local care providers should be established, and
arrangements should be made to ensure that required
intrapartum and postpartum antiretroviral drugs are
available at the designated facility.
Mode of delivery has been reviewed extensively with
both cohort studies and a randomized controlled trial
of intended mode of delivery. The burden of evidence
supports a vaginal delivery if obstetrically appropriate and
if virologic suppression has been achieved.8,16,122–124 The
initial studies that identified elective Caesarean section as
a method to reduce vertical transmission were conducted
in women who were not receiving any antiretroviral drug
therapy or who received monotherapy with zidovudine
only. Evidence to support elective Caesarean section in the
current cART era, when all women (even with viral loads
< 1000 copies/mL) are recommended to initiate cART
in pregnancy,16 is absent. European surveillance data124,125
did not show a significant benefit of elective Caesarean
delivery in the cohort of women with undetectable viral
loads while on cART. Therefore, the evidence supports
elective Caesarean section at 38 weeks to minimize the
risk of presentation in spontaneous labour only in women
who have an unknown viral load, who have a viral load
> 1000 copies/mL, or who are not on cART regardless
of viral load. The booking time of 38 weeks for Caesarean
section, rather than the usual 39 weeks, is proposed
because avoidance of labour in this setting is paramount.
Considering the potential complications of operative
AUGUST JOGC AOÛT 2014 l S23
SOGC CLINICAL PRACTICE GUIDELINE
delivery, however, women who receive antepartum cART,
are adherent to therapy, and have an HIV viral load
< 1000 copies/mL near term (i.e., obtained within 4 weeks
of delivery) can be delivered vaginally, reserving Caesarean
sections for obstetrical indications only. It is also important
to note that the benefit of Caesarean section shown in
early studies appears to have been found exclusively in pre-
labour elective Caesarean sections; no benefit was shown
for emergency Caesarean sections.8,123
Recommendations
13. The woman’s clinical, virological, and
immunological statuses should be assessed every
4 to 8 weeks during pregnancy, and again 6 weeks
postpartum. Routine criteria should be used to
assess the woman’s response to, and the possible
failure of, antiretroviral therapy. The toxicity of the
antiretrovirals should also be monitored at these
times. Specific testing should be individualized for
the known toxicities of the woman’s antiretroviral
therapy regimen. (III-B)
14. As for all pregnant women, all those living with
HIV, regardless of age, should be offered, through
an informed consent process, dating ultrasound
and non-invasive prenatal genetic screening for
the most common clinically significant fetal
aneuploidies. (III-A)
15. A detailed obstetrical ultrasound at 19 to 20 weeks’
gestation is recommended. Additional ultrasounds,
for fetal growth and amniotic fluid volume, are
recommended at least each trimester, or as guided
by obstetrical indications. (II-3B)
16. As for all pregnant women, those living with HIV
should be screened periodically for substance use,
and drug addiction should be addressed as needed
in conjunction with HIV management. (III-A)
17. Mode of delivery should be discussed in detail with
all women:
a. Women on optimal antiretroviral therapy with
acceptable plasma viral load suppression (less
than 1000 c/mL) over the last 4 weeks prior
to delivery are recommended to have a vaginal
delivery in the absence of other obstetrical
indications for Caesarean section. If Caesarean
section is recommended for obstetrical
indications, it can be conducted at 39 weeks, as
usual for those indications. (I-A)
b. Women not on optimal antiretroviral therapy
(i.e., no antiretroviral therapy, monotherapy
only, or with an incompletely suppressed viral
load) should be offered a scheduled pre-labour
Caesarean section at approximately 38 weeks’
gestation. (II-2A)
S24 l AUGUST JOGC AOÛT 2014
INTRAPARTUM MANAGEMENT
Intrapartum management for
women known to be living with HIV
All women known to be living with HIV should be instructed
to attend the labour and delivery department immediately
upon rupture of membranes or regular contractions so that
measures can be taken to decrease the risk of vertical HIV
transmission. All oral antenatal antiretroviral medications,
with the exception of stavudine, should be continued for
as long as possible during labour. Stavudine should not be
administered concomitantly with IV zidovudine because of
an antagonistic drug interaction.46 There are no randomized
controlled trial data on the additional benefit of intrapartum
IV zidovudine in women who have been receiving antenatal
cART. A large cohort study of > 5000 pregnant women
living with HIV, who received intrapartum IV zidovudine in
addition to various (mono, dual, triple) antenatal antiretroviral
therapy regimens, reported a significant benefit of IV
zidovudine in reducing vertical transmission among those
women with HIV viral loads > 10 000 copies/mL (5.3% vs.
22.7%, P = 0.009) at delivery.126,127 However, there was no
additional benefit of IV zidovudine reported among women
with HIV viral loads < 400 copies/mL at delivery (0.6% vs.
0%, P > 0.99), and data were not provided for women with
viral loads from 400 to 9999 copies/mL. Based on this cohort
data, the most recent perinatal guidelines published by the
NIH in the United States endorse intrapartum IV zidovudine
for women living with HIV who are receiving antenatal cART
and have an HIV viral load > 400 copies/mL (or unknown
viral load) near delivery; however, they do not recommend
its administration for those women on cART with an HIV
viral load ≤ 400 copies/mL.3 Canadian data, however, show
that 8.7% of women with previously suppressed viral load
have unpredictably elevated viral loads at time of delivery.128
On the basis of this evidence, intrapartum IV zidovudine
(2 mg/kg IV load over 1 hour followed by 1 mg/kg/hour
until delivery) continues to remain the standard of care in
Canada and is recommended for all women, regardless of
mode of delivery, current antiretroviral regimen, or viral
load. Intravenous zidovudine should be administered as
soon as it is determined the woman is in active labour and/
or has ruptured membranes, or at least 2 to 3 hours prior
to Caesarean section. If in the future rapid HIV viral load
measurements become available on day of delivery, decisions
regarding the need for IV zidovudine could be modified.
Women who did not receive any antiretroviral therapy
during pregnancy should also receive a single dose of oral
nevirapine (200 mg) as soon as possible at the onset of
labour or at least 2 to 3 hours prior to Caesarean section.
This recommendation also differs somewhat from that
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
in the NIH perinatal guidelines,3 where intrapartum IV
zidovudine (but not single-dose oral nevirapine) and
combination infant antiretroviral with zidovudine plus
3 doses of nevirapine is recommended for women who
were not receiving antepartum antiretroviral therapy (or
those with incomplete viral load suppression). However,
in our experience a number of practicalities must be
considered when women present in labour, including the
frequent difficulty of obtaining IV access, which makes the
administration of IV zidovudine difficult or impossible.
Because single-dose oral nevirapine has been demonstrated
to reduce vertical transmission of HIV,23 it continues to be
recommended for intrapartum administration to women
living with HIV who have not received antenatal therapy,
in addition to administration of cART to their infants. The
addition of 7 days of lamivudine-zidovudine postpartum
for the mother is recommended in order to mitigate the
risk of nevirapine resistance.31
Mode of delivery has been described in detail above. Elective
Caesarean section at 38 weeks of gestation to reduce the
risk of vertical transmission of HIV is recommended for
women with a viral load > 1000 copies/mL at delivery or
those with an unknown viral load (e.g., have not accessed
care and/or are not taking antiretroviral drug therapy) near
the time of delivery. Importantly, there are limited data to
support the benefit of emergency Caesarean section for the
purpose of reducing the risk of vertical HIV transmission.
Women on optimal antiretroviral therapy with acceptable
plasma viral load suppression (less than 1000 c/mL) over
the last 4 weeks prior to delivery are recommended to
have a vaginal delivery (in the absence of other obstetrical
indications for Caesarean section). If Caesarean section
is recommended for obstetrical indications, this can be
conducted at 39 weeks usual for those indications.
Data from the pre-cART era indicate that obstetrical
interventions that increase the exposure of the infant
to maternal blood, such as invasive monitoring or
episiotomies, may increase the risk of transmission.129–132
Extrapolating these data into the present era of cART, it is
recommended that interventions that potentially increase
fetal exposure, including scalp electrodes, intrauterine
catheters,133 prolonged rupture of membranes, operative
vaginal deliveries, and episiotomies, should be avoided
if possible. However, some Canadian data have been
reassuring about the risk of HIV transmission in
HIV-suppressed women with prolonged membrane
rupture.133 Additional important considerations during
the intrapartum period include, among others: epidural
anaesthesia is not contraindicated; if a woman is group
B streptococcus positive, continue to initiate antibiotic
prophylaxis according to protocol; and, if a woman
has ruptured membranes and is not in labour, initiate
oxytocin induction of labour in addition to intravenous
zidovudine (the medications are compatible).
Intrapartum management for woman of
unknown HIV status and/or ongoing HIV risk
Many women who are at risk for HIV infection do not
receive antenatal care and present late in their pregnancy
or in early labour with unknown HIV status. Women at
particular risk of HIV infection include those who use
injection drugs and have shared needles; have had a recent
illness suggestive of seroconversion; have had regular
unprotected sex with a partner known to be living with
HIV or at significant risk for HIV infection; or have had
a diagnosis of a sexually transmitted infection during the
pregnancy. Women who have been recently incarcerated or
who have emigrated from areas with endemic HIV are also
at increased risk if they have not been recently screened.
Women with unknown HIV status or at continued risk of HIV
infection since their last negative HIV serology result should
be offered (if available in the institution) rapid HIV antibody
testing in the labour and delivery setting with appropriate
pre- and post-test counselling. If the test result is positive, the
woman should be informed of the result, and confirmatory
HIV PCR and antibody tests should be performed.12,13
Maternal intrapartum antiretroviral drug therapy (intravenous
zidovudine and single-dose oral nevirapine) plus postpartum
zidovudine-lamivudine (Combivir, 1 tablet orally twice daily for
7 days; see Postpartum Management) and infant prophylactic
cART (see Infant Management) should be initiated pending
results of the confirmatory test. If the confirmatory test
is negative, maternal and infant antiretroviral drugs may be
discontinued.
It is recommended that all women who have not been
tested in pregnancy, particularly those who are recognized
to be at high and ongoing risk for HIV infection, be
offered HIV testing as soon as possible, with appropriate
pre- and post-test counselling. Women involved in
ongoing high-risk HIV transmission activities who are
HIV negative on initial testing should be retested each
trimester,12 and if possible again near term. HIV testing
should also occur with the woman’s knowledge and verbal
consent, and appropriate pre- and post-test counselling
should accompany each test.
If rapid HIV antibody testing is not available within
the institution and/or delivery is imminent and HIV
seropositivity is a possibility, HIV PCR and HIV antibody
tests should be performed. Intrapartum and postpartum
(IV zidovudine, single-dose oral nevirapine, Combivir)
AUGUST JOGC AOÛT 2014 l S25
SOGC CLINICAL PRACTICE GUIDELINE
antiretroviral drugs therapy should be offered to the woman,
and all infants should receive prophylactic antiretroviral
therapy pending results (see Infant Management). If the
HIV antibody test is negative and the woman is out of the
seroconversion period (e.i., has not engaged in high-risk
activities within the previous 4 weeks) and/or HIV PCR
is negative, infant antiretroviral prophylactic therapy and
maternal zidovudine-lamivudine may be discontinued. If
the woman at risk is found to be living with HIV, a full
6-week course of infant antiretroviral prophylactic therapy
should be completed and the woman should receive a
complete 7-day course of oral zidovudine-lamivudine to
prevent the emergence of nevirapine-resistant virus. A
referral should be made for ongoing HIV assessment and
care for both the mother and the infant for all women
who are determined to be living with HIV during labour
or delivery. Appendix 3 summarizes intrapartum and
postpartum recommendations and includes a management
algorithm for women known to be living with HIV or in
whom HIV infection has not been ruled out.
Recommendations
18. Intravenous zidovudine should be initiated as
soon as labour onset until delivery, in combination
with an oral combination antiretroviral regimen,
regardless of mode of delivery, current
antiretroviral regimen, or viral load. (III-B)
19. Intrapartum, a single dose of oral nevirapine
(200 mg) remains an option in the unusual
circumstance of a woman living with HIV who
has not received antenatal antiretroviral therapy in
pregnancy. (II-2B)
POSTPARTUM MANAGEMENT
Postpartum care involves collaborative efforts between
obstetric care providers, HIV specialists, and other
multidisciplinary health care providers to ensure
coordinated HIV care for both the mother and her infant.
A number of comprehensive issues that must be addressed
include contraception, continuation of and adherence to
antiretroviral drug therapy regimens, infant feeding and
pediatric care, and the woman’s needs for mental health
services, social services, and/or treatment of substance use.
The use of ergotamine should be avoided because of the
risk of exaggerated vasoconstriction in women receiving
protease inhibitor therapy.134 Oxytocin, misoprostol,
and prostaglandin F2 alpha are recommended agents for
managing postpartum hemorrhage. A number of studies
have evaluated the risk of infectious morbidity following
delivery in women living with HIV.135–139 Some studies
S26 l AUGUST JOGC AOÛT 2014
report higher rates of endometritis and pneumonia
following Caesarean section in women living with HIV than
in women without,136 but others do not.135 Endometritis
does, however, occur in a higher percentage of all women
following Caesarean section, and routine preoperative
prophylactic antibiotics have been demonstrated to
decrease postoperative infection.140 Preoperative antibiotics
are therefore recommended for all women who undergo
elective or emergent Caesarean section, including women
living with HIV, to decrease infectious postoperative
complications.141 Women who were receiving antenatal
antiretroviral therapy should have their complete regimen
resumed after delivery as soon as oral intake is tolerated.
Women who were not receiving antenatal antiretroviral
therapy but who received single-dose nevirapine during
labour should receive 7 days of zidovudine-lamivudine, 1
tablet orally twice daily, to reduce the risk of developing
nevirapine resistance. Zidovudine-lamivudine therapy
can be discontinued before completion of the 7-day
treatment period if confirmatory HIV testing results show
that the woman is not living with HIV. Plans for ongoing
HIV care should be established prenatally, and unless
otherwise indicated, maternal antiretroviral therapy should
be continued after delivery and reassessed for ongoing
therapy by providers of adult HIV care. Based on future
pregnancy planning and adult HIV status, antiretroviral
treatment modifications may be appropriate. Adherence in
the postpartum period can be challenging142,143 and support
is important.
There is a risk of HIV transmission through breast
milk119,121; therefore breastfeeding is contraindicated
regardless of maternal antiretroviral therapy or viral load.
Management of the effects of not breastfeeding should
include measures such as acetaminophen, ibuprofen, and
cold compresses to minimize pain from engorgement.
Bromocriptine and cabergoline, the classical therapies
used for lactation suppression, are ergot derivates, whose
co-administration with PIs is contraindicated. Women
who test positive on rapid HIV antibody testing or who
are believed to be at high risk of HIV (when rapid HIV
antibody testing is not available) are advised to pump their
breast milk, but they should not feed it to the infant unless
a confirmatory HIV test is negative.
An early return to fertility can be expected as a result
of not breastfeeding. It is critical to discuss safer sex
practices and effective contraception methods with the
women. Condom use is recommended to reduce the
risk of transmission between partners; however, the
contraception failure rate with condoms is reported to be
as high as 14% as commonly used.144 Oral contraceptives
may also be used by women living with HIV, particularly
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
with the use of condoms as part of a dual-protection
strategy. Drug interactions between antiretroviral drugs
and oral contraceptives have been documented; therefore
it is important to assess for potential interactions between
specific antiretroviral agents and oral contraceptives.
This information is available in the NIH Perinatal HIV
Guidelines3 and on the Motherisk website.145 Non-
oral contraceptive methods including DMPA (Depo-
Provera), contraceptive patch or vaginal ring, and
levonorgestrel IUD are also options; however, data for
them in combination with antiretroviral medications is
not available. The side effect profile of DMPA has been
shown to be the same in women living with and without
HIV146; however, consideration should be given to the
bone loss seen in women using DMPA, since bone loss
in women living with HIV is already faster than in their
uninfected counterparts. Data on copper or levonorgestrel
IUD use in women living with HIV are limited, but given
the value of this method for successful contraception
and low general rates of infection, use in women with
CD4-cell counts > 200 cells/mm3 is appropriate.144
Linkage to care is important for all women living with
HIV, particularly those who are newly diagnosed with
HIV during labour and delivery. All women should
have arrangements for follow-up care with providers
experienced in the management of HIV.
Recommendation
20. Plans for ongoing HIV care should be established
prenatally, and unless otherwise indicated, maternal
antiretroviral therapy should be continued after
delivery and reassessed for ongoing therapy by
providers of adult HIV care. (II-1A)
INFANT MANAGEMENT
Mothers should be offered antiretroviral prophylaxis for
their infants regardless of maternal antenatal or intrapartum
antiretroviral therapy, viral load, or mode of delivery. The
recommended regimen will depend on the presumed level
of risk. Infants born to a mother known to be living with
HIV and a viral load < 1000 copies/mL should be offered
prophylactic therapy with oral zidovudine for 6 weeks.
Intravenous zidovudine may be used if the infant is unable
to tolerate oral intake. The dose of zidovudine is determined
based on gestational age, with a twice-daily dosing regimen
now recommended for all infants (see Appendix 4). The
infant zidovudine prophylaxis should be started as soon as
possible, no later than 6 to 12 hours after birth.
Infants born to a mother known to be living with HIV and
who has a known or projected viral load > 1000 copies/mL
or to a mother known to be living with HIV and who
did not receive any antepartum antiretroviral therapy
(this includes a mother who is presumed to be living with
HIV based on a positive rapid HIV antibody test result)
should receive prophylactic cART with a 3-drug regimen
including zidovudine for 6 weeks combined with 3 doses
of nevirapine in the first week of life (at birth, day 2,
and day 6 of life) and twice-daily oral lamivudine for 2
weeks. This recommendation is made on the basis of the
HPTN040/PACTG 1043 trial which enrolled women living
with HIV who were not receiving antenatal antiretrovirals
and demonstrated that combination regimens had better
efficacy (2.2%) in reducing vertical transmission to infants
intrapartum than zidovudine alone (4.8%).25 While this
trial does not address whether prophylactic cART provides
additional protection against transmission in infants born to
mothers who have suboptimal viral suppression near delivery
(i.e., > 1000 copies/mL), extrapolation of those results
suggests that prophylactic cART should be recommended,
particularly in situations involving vaginal delivery. Although
the HTPN040/PACTG 1043 trial evaluated a 2-drug
zidovudine and nevirapine combination regimen, the
addition of a third agent, lamivudine, is recommended in
order to prevent the emergence of nevirapine resistance
should the infant be infected with HIV. The rationale for this
recommendation is to provide a highly active antiretroviral
regimen throughout the first 2 weeks of life when nevirapine
is expected to be circulating at decreasing but significant
levels, due to its very long half-life (median 30 hours, range
18 to 50 hours in newborns).27 In settings where rapid HIV
antibody testing is not yet available, the optimal management
strategy for infants born to women with unknown HIV
status and considered at high risk of HIV infection has
not been established in a randomized clinical trial. In this
clinical scenario, the potential benefit of preventing vertical
transmission of HIV is believed to outweigh the potential
risks of the infant’s unnecessary exposure to antiretrovirals;
therefore combination infant prophylaxis (with zidovudine,
3-dose nevirapine, and lamivudine) is recommended until
confirmatory HIV test results are available. Surveillance
and poll-result data reported out of the United Kingdom,
Ireland, and United States indicate increasing use of
prophylactic cART for infants in high-risk situations.147,148
Until HIV-negative status can be confirmed, pumping breast
milk, but not feeding it to the infant is recommended.
Dosing recommendations and commercial names for
the prophylactic antiretroviral agents are specified in
Appendix 1. Of note, hepatic clearance is slower in preterm
infants, but pharmacokinetic data informing dosing are
limited, particularly in infants with a birth weight below
1.5 kg.149,150
AUGUST JOGC AOÛT 2014 l S27
SOGC CLINICAL PRACTICE GUIDELINE
Breastfeeding remains contraindicated for mothers living
with HIV regardless of maternal viral load, antepartum
cART regimen, and continuation of postpartum
antiretroviral therapy. In Malawi, peripartum HIV
transmission through breastfeeding was found to be as high
as 4% at 48 weeks when mothers were prescribed cART
or infants received daily nevirapine prophylaxis versus
7% in the absence of maternal or infant antiretrovirals.118
Canadian surveillance data and a meta-analysis also show
high rates of postpartum virologic rebound due to non-
adherence among women who are prescribed ongoing
cART.142,143
It is important to discuss feeding practices with the mother
during antenatal visits, using a sensitive approach and
acknowledging the mother’s cultural beliefs about infant
feeding. Because premastication by caregivers living with
HIV has been implicated as a potential route of HIV
transmission to young infants, health care practitioners
should also inquire specifically about premastication and
advise caregivers living with HIV to avoid this practice.
Infants exposed to HIV should be tested for HIV infection
by a virological test at birth, 4 weeks, and 3 to 4 months
of age to determine HIV status. Additional testing for
infants at high risk of vertical transmission should be
discussed with a pediatric HIV specialist. HIV RNA PCR
(or nucleid acid amplification test) is the virological test
currently used for diagnostic purposes. HIV infection
can be excluded when two HIV virological tests are non-
reactive, one collected after 4 weeks of age and the other at
least 4 weeks after the end of prophylactic antiretrovirals.
Serological EIA tests are not indicative of infant status due
to the presence of detectable maternal HIV antibodies up
to 18 to 24 months of age. A confirmatory HIV EIA test
is recommended to document seroconversion after 18
months of age.
If an HIV PCR is reactive, a confirmatory RNA PCR test
should be requested immediately. When an infant is found
to be infected with HIV, antiretroviral prophylaxis should
be discontinued, and an urgent referral to an HIV specialist
should be made for HIV therapy and comprehensive care.
Early initiation of cART has been shown to improve long-
term outcomes151 and may prevent the establishment of
viral reservoirs in infected infants.152
Infants should also be monitored with a CBC and
differential at baseline and at 4 weeks of age. Zidovudine
prophylaxis is generally well tolerated, but low grade
anemia or neutropenia with elevated platelet count are
not uncommon after receipt of 4 weeks of zidovudine
prophylaxis.18,19,93,153 If hemoglobin levels are below 100 g/L
S28 l AUGUST JOGC AOÛT 2014
and expected to be further decreased with continued
zidovudine exposure, early discontinuation of zidovudine
prophylaxis at 4 weeks may be considered. Hematologic
toxicity may be more common with exposure to cART;
however, data are limited.3 In high-risk newborns receiving
cART prophylaxis for the first 2 weeks of life, clinicians
should consider obtaining an earlier CBC to monitor for
toxicity. There is no evidence for nevirapine associated
rash or hepatic toxicity in infants receiving either single-
dose or extended-dose nevirapine. Infants rarely present
symptoms of mitochondrial toxicity; however, if an infant
presents with unexplained neurologic or gastrointestinal
symptoms, hepatic function (ALT, AST) and serum lactate
should be measured.71,73
All infants born to women living with HIV should be
referred for ongoing assessment and care to a pediatrician
with expertise in this area. Developmental follow-up is
crucial for HIV-exposed uninfected children. Factors such
as poverty, food insecurity, low literacy, inexperience in
parenting, and parental substance or alcohol use put infants
at higher risk for failure-to-thrive, developmental delay, and
behavioural disorders. Family physicians and pediatricians
play an essential role in identifying and addressing such
issues in uninfected HIV-exposed infants and children,
and they should facilitate referrals to specialists and
developmental resources.
Long-term follow-up of children who were perinatally
exposed to HIV and antiretrovirals is recommended into
adulthood, due to unknown and theoretical concerns
regarding the potential for carcinogenicity of nucleoside
analogue antiretroviral drugs or other long-term effects of
antiretroviral medications. 3
Including all HIV-exposed mother-infant pairs in the
national surveillance program (CPHSP) is essential to
keep generating important epidemiological data and
to support continued access to resources for these
vulnerable families.
Recommendations
21. HIV-exposed newborns should receive
antiretroviral therapy for 6 weeks to prevent vertical
transmission of HIV. (I-A)
22. Health care practitioners who care for HIV-exposed
newborns should provide timely diagnostic HIV
testing: HIV polymerase chain reaction at birth,
1 month, and 3 to 4 months and HIV serology at
18 months (II-A), and they should monitor both
short- and long-term outcomes, including screening
for adverse effects of antiretroviral therapy and for
developmental delay. (III-A)
 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission
23. Breast-feeding is not recommended regardless of
plasma HIV viral load and use of antiretroviral
therapy. (I-E)
24. The pregnancy should be registered with
surveillance programs to allow the collection
of provincial and national data to guide
future pregnancy policies. Women undergoing
antiretroviral therapy in pregnancy should also be
offered inclusion in appropriate studies. (III-B)
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184. Martinez-Rebollar M, Lonca M, Perez I, Soy D, Brunet M, Martin R,
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185. Bryson Y, Mirochnick M, Stek A, Mofenson LM, Connor J, Capparelli E,
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Appendix begins on next page
AUGUST JOGC AOÛT 2014 l S35
SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 1. RECOMMENDATIONS AND MANAGEMENT ALGORITHM FOR WOMEN

WITH UNKNOWN HIV STATUS OR ONGOING RISK OF HIV INFECTION

Indications of High-risk for HIV Infection

–  Self-identifies as being at high risk of HIV
–  Sex partner of an HIV-infected person
–  Ongoing use of injection drugs or sex with a person using injection drugs
–  Diagnosis of a sexually transmitted infection during pregnancy
–  Belonging to a population with a high prevalence of HIV (e.g., recent incarceration, recent immigrant, or refugee from an
–  HIV-endemic country)

Recommendations for Testing

In institutions where rapid HIV antibody testing is NOT available:
1. Contact the provincial centre for disease control to access prenatal HIV serology results. If laboratory results are not available
proceed to #2.
2. a. If the woman’s HIV status is not available or if she is at ongoing risk of HIV infection since her last serology test result:
i. draw STAT HIV EIA (antibody) and send blood (4 mL) in a gold top tube to local CDC laboratory;
ii. draw STAT diagnostic HIV PCR test and send blood (4 mL) in an EDTA tube to local CDC laboratory.
b. If the woman is unavailable for testing:
i. draw HIV EIA (antibody) from the infant within 48 hours of age as a first priority and send blood (minimum 2 mL) in a gold top
tube to local CDC laboratory;
ii. draw diagnostic HIV PCR from the infant within 48 hours of age and send blood (minimum 2 mL) in an EDTA tube to local CDC
laboratory.
3. Until HIV test results are known:
a. Initiate maternal and infant treatment for prevention of HIV vertical transmission.
b. If any test is positive in mother or infant, refer to local multidisciplinary HIV clinic.
c. If all HIV EIA and HIV PCR tests drawn are negative in the mother and infant, discontinue all antiretroviral drug therapy.

In institutions where rapid HIV antibody testing is available

1. Contact provincial centre for disease control to access prenatal HIV serology results. If laboratory results are not available
proceed to #2.
2. a. All women should be offered rapid HIV antibody testing. A protocol for rapid HIV testing should be established in each institution.
b. For women considered at high risk of HIV with undocumented prenatal HIV serology or who have ongoing risk of HIV since their
most recent HIV serology result, also draw a confirmatory prenatal diagnostic HIV PCR test and send blood (4 mL in EDTA tube)
and appropriate requisition to local CDC.

Pre-test discussion points

Offer information about:
–  HIV and the nature of the test;
–  the reasons HIV testing is recommended (risk of transmission, long-term health of the woman);
–  the expected benefits of testing (treatment of woman and infant, decreased transmission);
–  the voluntary nature of testing.
Answer any questions.

Post-test discussion points

Inform the woman of the test result.

Non-reactive (negative test): no antibodies to HIV were detected

Discuss any needs for harm reduction or further testing and the possibility of acute infection if there was high-risk behaviour in the last 4
weeks (i.e., the implications of the “window period” of infection when antibodies have not yet been produced).
Inform the woman that confirmatory test results will be available in approximately one week.
Inform the woman of treatment recommendations to prevent HIV vertical transmission.

continued

S36 l AUGUST JOGC AOÛT 2014

 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

APPENDIX 1. Continued

Invalid: test will not work with blood sample provided

Inform the woman:
–  that there may be a possibility of infection if high-risk behaviour at any time during pregnancy;
–  that confirmatory testing results will be available in approximately one week;
–  about treatment recommendations to prevent HIV vertical transmission.

Preliminary reactive (preliminary positive): antibodies to HIV were detected OR indeterminate: unable to interpret result
Discuss with woman:
–  the possibility of HIV infection;
–  the need for a confirmatory blood test (diagnostic HIV PCR results available in approximately one week);
–  immediate treatment recommendations to prevent HIV vertical transmission;
–  steps to prevent transmission;
–  the follow-up care and support available to her.

Post-test documentation
Notify the local health authority of any preliminary positive result.
Document discussions in the woman’s Health Record.
Ensure contact information for the woman is available in the Health Record.

Recommended intervention based on rapid HIV test result

HIGH risk of HIV and undocumented prenatal HIV serology (or ongoing risk of HIV risk since most recent HIV test)
Preliminary reactive or Initiate treatment for prevention of HIV vertical transmission
Indeterminate or
Invalid:
Non-reactive but involved in high-risk HIV transmission activity Initiate treatment for prevention of HIV vertical transmission
in previous 4-weeks (within possible ‘window’ period
of infection):
Non-reactive and no identifiable risk within the past 4 weeks No further intervention.
LOW risk of HIV and undocumented prenatal HIV serology
Preliminary reactive or Initiate treatment for prevention of HIV vertical transmission
Indeterminate
Non-reactive or No further intervention
Invalid

continued

AUGUST JOGC AOÛT 2014 l S37

SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 1. Continued

MANAGEMENT ALGORITHM FOR WOMAN OF UNKNOWN HIV STATUS OR ONGOING HIV RISK
in institutions where rapid HIV antiboby test is AVAILABLE
(ZDV = Zidovudine, 3TC = Lamivudine, NVP = Nevirapine)

Unknown HIV status or ongoing HIV risk since last HIV serology was performed
Contact local health services authority to access serology results if available

High risk: self identifies, ongoing

injection drug use, sex partner of
HIGH HIV person infected with HIV or using LOW HIV
risk injection drugs, diagnosis of a sexually risk
transmitted infection during pregnancy,
from a population with a high
prevalence of HIV (e.g., recent
incarceration of refugee from an HIV
endemic country)
Rapid HIV test and
Rapid HIV test
diagnostic HIV PCR

Preliminary reactive Preliminary reactive Non-reactive OR

OR indeterminate Non-reactive OR indeterminate invalid
OR invalid

Recent high-risk Mother: IV ZDV No

Mother: IV ZDV
activities in previous loading dose and Therapy
loading dose and
4 weeks? infusion during
infusion during
labour
labour
and
and
Yes No Single-dose NVP
Single-dose NVP
and
and
ZDV-3TC
ZDV-3TC
(Combivir®)
(Combivir®) No x 7 days postpartum
x 7 days postpartum Therapy

Infant: ZDV Infant: ZDV

x 6 weeks x 6 weeks

and and

3-doses NVP 3-doses NVP

(day 0, 2, 6) (day 0, 2, 6)

and and

3TC x 2 weeks 3TC x 2 weeks

continued

S38 l AUGUST JOGC AOÛT 2014

 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

APPENDIX 1. Continued

MANAGEMENT ALGORITHM FOR WOMAN OF UNKNOWN HIV STATUS OR ONGOING HIV RISK
in institutions where rapid HIV antiboby test is NOT AVAILABLE
(ZDV = Zidovudine, 3TC = Lamivudine, NVP = Nevirapine)

Unknown HIV status or ongoing HIV risk since last HIV serology was performed
Contact local health services authority to access serology results if available

High risk: self identifies, ongoing injection drug

use, sex partner of person infected with HIV or
using injection drugs, diagnosis of a sexually
HIGH HIV LOW HIV
transmitted infection during pregnancy, from a
risk risk
population with a high prevalence of HIV (e.g.,
recent incarceration of refugee from an HIV
endemic country)

Mother: STAT HIV No

EIA (antibody) and Therapy
diagnostic HIV PCR

Mother: IV ZDV loading dose and infusion

during labour A) If any test is POSITIVE in mother or infant:
Refer to local multidisciplinary HIV clinic
and

Single-dose NVP B) If all HIV EIA and HIV PCR tests drawn are
NEGATIVE in mother and infant:
and
DISCONTINUE ALL antiretroviral drug therapy
ZDV-3TC (Combivir®) x 7 days postpartum

Infant: if mother is unavailable for testing:

HIV EIA (antibody) and diagnostic HIV PCR

within 48 hr of age

Note: if difficult to obtain sample HIV EIA is

priority test

Infant: consider administering combination

prophylactic therapy *:

ZDV x 6 weeks

and

3-doses NVP (day 0, 2, 6)

*Alternative consideration is
and
single agent prophylactic
therapy: ZDV x 6 weeks
3TC x 2 weeks

AUGUST JOGC AOÛT 2014 l S39

SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 2. SUMMARY INFORMATION ON ANTIRETROVIRAL MEDICATIONS IN PREGNANCY

Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs)

Drugs in this class function as a group of competitive substrate inhibitors that are intracellularly phosphorylated to form the active
triphosphate nucleoside moiety and incorporated into HIV DNA, which terminates the action of the reverse transcriptase enzyme and
prevents the conversion of viral RNA into DNA.153 NRTIs are recommended for use as part of combination regimens, which usually
include a backbone of 2 NRTIs with the addition of either a non-NRTI (NNRTI) or one or more PIs. The use of single or dual NRTIs
alone is not recommended for treatment of HIV infection because rapidly developing resistance outpaces their ability to suppress viral
replication for prolonged periods.2,3
Among this class of drugs the first-line agents for use in the dual NRTI backbone in pregnancy are zidovudine (ZDV) and lamivudine (3TC);
alternative agents include abacavir (ABC), emtricitabine (FTC; not available in Canada as a single agent), and tenofovir (TDF). TDF would
be a preferred NRTI, in combination with 3TC or FTC, for pregnant women with chronic hepatitis B infection. DDI and stavudine (d4T) are
reserved for use only in special circumstances because they are more toxic than other available agents.
Various combinations of NRTIs can be employed. Clinical safety and efficacy data in pregnancy have been most reported for the first-line
recommended combination of ZDV and 3TC. This combination is formulated as a fixed-dose combination tablet, Combivir, and is generally
well tolerated in pregnancy. It does, however, require twice-daily dosing, and resistance to either ZDV or 3TC is common in antiretroviral-
experienced women.193
Alternative agents or combinations of agents (ABC, FTC, TDF) may be considered in a number of situations including when there is
resistance to first-line agents; a woman conceives on an effective treatment regimen containing alternative agents; tolerability is a concern;
and regimen simplification is desirable. When selecting combination regimens it is important to consider HIV resistance profiles; the
potential for adverse events related to the additive; any co-morbid medical conditions including HBV; concomitant medications and the
potential for drug-drug interactions; and convenience of dosing. Two notable combinations that should be avoided are d4T in combination
with ZDV, because they have competing intracellular mechanisms of activation,124 or d4T with DDI, because the combination has a higher
reported risk of a potentially fatal lactic acidosis and hepatic steatosis reaction.194
NRTI pharmacokinetics are similar in pregnant and non-pregnant women and dosing adjustments are not required in pregnancy. All NRTIs,
with the exception of DDI, readily cross the placenta and have high cord-to-maternal blood ratios greater than 0.60.3,41
All NRTI agents are categorized as either FDA pregnancy category B (TDF, DDI) or C, and none have been demonstrated to be associated
with any known human teratogenic syndrome in pregnancy. Although not considered to be a teratogen, animal studies have demonstrated
that chronic administration of high doses of TDF to pregnant monkeys has resulted in a slight reduction in fetal bone porosity. Continued
administration of high dose TDF to infant monkeys (and other species) has resulted in reversible bone abnormalities ranging from reduction
in bone mineral density to severe pathologic osteomalacia. Evidence of renal toxicity has also been observed in newborn monkeys
given high doses of TDF.4,41,54 Because of the limited data on use in human pregnancy and concern regarding potential fetal effects and
nephrotoxicity, TDF is recommended as an alternative (vs. first-line) drug for use in pregnancy, unless the woman is co-infected with HBV.3

Additional Considerations in Pregnancy

Bone marrow toxicity is a concern with the NRTIs. In the ACTG 076 study there were no significant toxicities noted in the women who
received ZDV monotherapy,16 and in short and longer term follow-up studies (up to 5 years of age post in utero exposure) transient anemia
in the neonate is the only significant adverse effect reported.17–19 Overall, transient and mild hemoglobin reductions have been observed in
most infants exposed to antiretroviral drugs and these resolve by age 3 to 6 months after discontinuation of antiretroviral prophylaxis3,92,151
In utero exposure to cART appears to be associated with increased severity of anemia. Neutropenia and/or lymphopenia have also been
reported, with resolution at age 8 to 24 months.3,92,151 The clinical significance of this is not established and there is no evidence of an
increase in antibiotic use or an increase in the frequency or severity of infections in these infants.195,196
Mitochondrial toxicity/dysfunction has been reported. NRTIs are able to bind to mitochondrial gamma DNA polymerase in different
organ systems, resulting in mitochondrial toxicity.92,195 The clinical effects in adults can include myopathy, bone marrow suppression,
pancreatitis, peripheral neuropathy and hepatic steatosis. Serum lactate, which accumulates when mitochondrial function is significantly
altered, has been used as an indirect marker of mitochondrial toxicity. Mitochondrial toxicity has been most strongly associated with d4T,
DDI, zalcitabine (no longer marketed in Canada), and ZDV.92 As described above, the combination of d4T and DDI should be avoided
because of a higher incidence of fatal lactic acidosis in people receiving cART; it is unknown whether pregnancy increases the risk
further.197 Data for an association between mitochondrial dysfunction and in utero exposure to NRTI therapy are conflicting. In the French
Pediatric Cohort study, the total incidence of clinical symptoms of mitochondrial dysfunction at 18 months was 0.26% (95% confidence
interval [CI] 0.10 to 0.54) in exposed children compared with 0.01% in the general population, and the mortality rate was 0.07%.198 These
findings have not been duplicated in other studies,81,199,200 and severity of maternal illness has been identified as a potential confounding
factor.201,202 Antiretroviral-exposed infants may have transiently elevated lactic acid levels for up to 6 months; however, the clinical
significance of this has not been determined.70,72 Overall, it appears that severe clinically evident mitochondrial diseases secondary to in
utero antiretroviral exposure are likely to be rare.
Abacavir hypersensitivity—ABC has been associated with a severe, potentially fatal hypersensitivity reaction.45,203 Testing for carriage of
the HLA-B*5701 allele identifies patients at risk of reaction, and patients with the allele should not be given ABC.45 Re-challenge with ABC
in patients who have experienced ABC hypersensitivity is contraindicated. To date, there is no evidence that in utero exposure to ABC
increases the risk of any hypersensitivity reaction in the infant.

continued

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

APPENDIX 2. Continued

Non-Nucleoside Reverse Transcriptase Inhibitors

Drugs in this class function as non-competitive inhibitors of reverse transcriptase by binding and inducing a conformational change in the
enzyme, which alters its active site and prevents its ability to convert viral RNA to DNA.153 NNRTIs are recommended for use in pregnancy in
combination with a dual NRTI backbone.
Initiation of nevirapine (NVP) is not recommended in pregnancy because of the risk of potentially fatal rash and hepatotoxicity. Women who
are tolerating NVP and who become pregnant may continue taking NVP. While a preferred agent in the non-pregnant adult, efavirenz (EFV)
is contraindicated in the first trimester of pregnancy because of its association with neural tube defects in primates and in case reports in
humans.40 However, if given inadvertently during this period, the overall risk posed by EFV is low; ultrasound evaluation of neural tube closure
should be done to guide counselling on fetal status. The use of EFV in later trimesters should be reserved for when other agents cannot be
used or are not tolerated. Currently available safety and pharmacokinetic data are insufficient to support the use of etravirine (ETR) or rilpivirine
(RPV) in pregnancy.
NNRTI pharmacokinetics are similar in pregnant and non-pregnant women, and dose adjustments are not required in pregnancy. The extent
of placental transfer varies within the class, ranging from high with NVP (which also rapidly crosses the placenta) to moderate with EFV. The
extent of placental transfer with the newer NNRTIs, ETR, and RPV, is currently unknown.
Teratogenicity data for NNRTIs is more limited and variable than for NRTIs. There is no evidence of animal or human teratogenicity with NVP
(FDA pregnancy category B), and no evidence of teratogenicity in animals with ETR or RPV (FDA pregnancy category B); however, there is
very limited information on these agents in human pregnancy.3,41 Efavirenz, however, is classified as FDA pregnancy category D, and should
not be used in the first trimester of pregnancy. Non-pregnant women who are receiving EFV should be counselled to avoid pregnancy. Central
nervous system malformations including anencephaly, cleft palate, and anophthalmia were reported in 3 of 20 (15%) of monkeys exposed to
efavirenz plasma concentrations similar to human therapeutic concentrations in the first trimester.3 While the Antiretroviral Pregnancy Registry
has reported a birth defect incidence of only 2.7% (comparable to the baseline population risk),41 there have been a total of 7 (1 prospective,
6 retrospective) reported cases of central nervous system defects, including 3 cases of meningomyelocele, in humans following first trimester
EFV exposure.4,41 Meta-analysis of cohort studies reporting first trimester EFV exposure in 1437 women did not detect an increased risk of
birth defects.42 However, a report from a large French perinatal cohort did find a significant association between exposure to EFV in the first
trimester and neurological defects.43

Additional Considerations in Pregnancy

Nevirapine (NVP) has been reported to cause severe, life threatening and in some cases fatal hepatotoxicity and hypersensitivity skin
reactions.203,204 The risk of toxicity is higher in women than men; however, it does not appear that pregnancy increases the risk.3,195,204 There
are data to suggest that the greatest risk of toxicity occurs during the first 6 to 18 weeks of therapy and increases approximately 10-fold when
NVP is initiated at baseline CD4-cell counts greater than 250 cells/mm3.3,195,204 However, a Canadian study found that toxicity occurred at a
wide range of CD4-cell counts in women exposed to NVP for the first time in pregnancy.57 Neither rash nor hepatoxicity have been reported in
women or infants receiving intrapartum single-dose or extended-dose NVP therapy for prevention of vertical transmission.22,205 As described
above, NVP should not be initiated in pregnancy regardless of CD4-cell count; however, women who become pregnant while receiving and
tolerating NVP may continue without interruption.

Protease Inhibitors
Drugs in this class function as competitive inhibitors that bind to the HIV protease enzyme and prevent the conversion of HIV viral particles into
mature infectious forms.153 PIs are recommended in pregnancy in combination with a dual NRTI backbone. Individual PIs are most commonly
administered together with low-dose ritonavir (r), which functions as a pharmacokinetic booster to increase serum drug levels of the first PI.
Short-term studies have demonstrated the safety and tolerance of the co-formulated combination of lopinavir/ritonavir (LPV/r), and as a result
of this and clinical experience with its use, LPV/r is considered the first-line agent for use in pregnancy. Alternative agents for use include
boosted atazanavir (ATV/r), which has growing short-term safety and efficacy data in pregnancy; boosted darunavir (DRV/r), and boosted
saquinavir (SQV/r), which has also been shown to be well tolerated and safe in short-term studies, but requires a baseline electrocardiogram
prior to the start of therapy. Because of associated adverse effect profiles and/or pharmacokinetic limitations in pregnancy, boosted indinavir
(IDV/r) and nelfinavir (NVF) should be reserved for use in special circumstances when other agents cannot be used. Current data in pregnancy
are insufficient to recommend use of the newer agents including boosted fosamprenavir (FPV/r) or tipranavir (TPV/r).
The pharmacokinetics of PIs are variable in pregnancy, particularly in the second and third trimester. Current data suggest that exposure
to LPV/r, ATV, and NVF is decreased during the second and third trimesters. However, the clinical significance of reduced exposure to
antiretroviral drugs during pregnancy is not clear. The need for a dose increase in pregnancy will depend on the treatment experience of the
specific woman, the use of concomitant interacting medications (e.g., TDF or histamine receptor antagonists with ATV), and virologic response
to the prescribed dose throughout pregnancy. HIV viral load must be followed closely, particularly in the second and third trimesters, to ensure
virology failures due to increased plasma volumes, and subsequent reduced PI concentrations, do not occur. Consideration should be given
to a PI dose increase in this situation. There is currently no standard recommendation for monitoring drug levels in pregnancy; however, if
available, therapeutic drug monitoring may also be considered to guide the need for PI dose adjustment.53 All PIs have minimal to low placental
transfer to the fetus, with cord-to-maternal blood ratios < 0.3. All PIs are classified as FDA pregnancy category B or C. None of the PIs have
been demonstrated to cause gross structural abnormalities in animals; however, minor skeletal variations (e.g., increase in supernumerary ribs,
ossification delays) and growth inhibition has been reported with high dose ritonavir (RTV), IDV, TPV/r , and FPV. The majority of PIs have not
been demonstrated to be teratogenic in human studies; however, data with the use of DRV, FPV or TPR/r in human pregnancy are limited.3,41

continued

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SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 2. Continued

Additional Considerations in Pregnancy

Preterm delivery could be a greater risk with combination antiretroviral therapy (vs. none, mono or dual NRTI therapy), but evidence to
date is conflicting. Some studies have suggested an approximate 2-fold increase risk of preterm delivery (< 37 weeks) with combination
antiretroviral therapy than with no treatment, particularly when therapy is initiated prior to pregnancy versus in the third trimester.87,92 A
2007 meta-analysis of 14 published clinical studies suggested that combination regimens that include a PI (vs. no PI) may be at highest
risk of preterm delivery,85,93 and data from the Antiretroviral Pregnancy Registry has suggested an increase in low birth weight infants
since the introduction of combination therapy, with PI-containing regimens identified as a significant risk factor.41 Other studies, however,
have not detected an association between antepartum antiretroviral therapy or PI use and preterm delivery or low birth weight infants.82,93
Overall, data to suggest an association between in utero antiretroviral therapy (including PI use) and premature delivery or low birth
weight infants are mixed. However, a causal relationship has not been established, and PIs should not be withheld because of the
possibility of an increased risk of preterm delivery.
Glucose intolerance/diabetes could be a greater risk with combination antiretroviral regimens containing PIs in pregnancy, but evidence
is conflicting. The risk of glucose intolerance was reported to be increased by PIs in one retrospective study,63 but was not observed in
others.95–97 Secondary analysis of data from 2 prospective cohorts found an increased risk of gestational diabetes only when PIs were
initiated prior to pregnancy or during the first trimester.206 Overall, it is recommended that women living with HIV and taking antiretroviral
drugs during pregnancy should receive standard glucose screening (i.e., 1 h 50 g glucose loading test at 24–28 weeks’ gestation); if a
women is receiving a PI-based regimen, particularly if initiated before pregnancy, the clinician may choose to perform this screening test
earlier.
Hyperbilirubinemia commonly occurs in patients, including pregnant women, who receive the PIs ATV and IDV.46,207 These agents
increase indirect (unconjugated) bilirubin from directly inhibiting uridine diphosphate-glucuronosyl transferase (UGT), the enzyme
responsible for the conversion of indirect to direct (conjugated) bilirubin. There is a theoretical concern that in utero exposure to IDV or
ATV may exacerbate physiologic hyperbilirubinemia in neonates as a result of the transfer of indirect bilirubin from the mother and/or
a direct transplacental drug effect on bilirubin metabolism in the fetus. Hyperbilirubinemia has been observed in neonates following in
utero exposure to atazanavir; however, there is no evidence of severe hyperbilirubinemia elevations or clinical signs of acute or chronic
bilirubin encephalopathy.46,47 Exacerbation of physiologic neonatal hyperbilirubin has not been reported with in utero exposure to IDV.
It is recommended that all infants exposed to ATV (and IDV) should be monitored for development of hyperbilirubinemia in the first few
days of life.46
Postpartum hemorrhage should not be managed with ergot derivatives (e.g., ergonavine maleate), because the combined use of
this drug class with PIs may result in serious and potentially life threatening vasoconstriction reactions characterized by peripheral
vasospasm and ischemia of the extremities and other tissues.48 Other alternatives including oxytocin and/or prostaglandins may be used
if required.3,208

Entry (fusion) Inhibitors

This class of drugs includes 2 agents, enfuviride and maraviroc, that act extracellularly to prevent HIV from attaching to the target cell
surface and entering the host target cell. Enfuviritide binds to glycoproteins (gp41) on the viral surface to inhibit virus–cell membrane fusion.
Maraviroc prevents virus binding to the CCR5 co-receptor on host cells to prevent the entry of virus into the cell. Because HIV can use
other co-receptors, such as CXCR4, an HIV tropism test must be performed to determine whether maraviroc will be effective.
Current data is insufficient to recommend the use of fusion inhibitors in pregnancy. Data regarding their pharmacokinetics in pregnancy
are minimal, and it is not known whether dose adjustments are required. Placental transfer to the fetus is also unknown. Both agents are
classified as FDA pregnancy category D because animal studies have not demonstrated any evidence of teratogenicity; however, there is
no (maraviroc) or very limited (enfuviritide) experience of their use in human pregnancy.

Integrase Inhibitors
This class of drugs includes 2 agents, raltegravir and elvitegravir (EVG), that function as competitive inhibitors of the HIV integrase enzyme,
preventing the insertion or integration of HIV genetic DNA into the host cell DNA (i.e., strand transfer inhibition). Elvitegravir is currently
only available as part of a fixed-dose combination tablet with the pharmacokinetic enhancer cobicistat (COBI) and the NRTIs tenofovir and
emtricitabine (TDF 300 mg/FTC 300 mg/EVG 150 mg/COBI 150 mg).
Current data are insufficient to recommend the use of integrase inhibitors in pregnancy. No pharmacokinetic data or placental transfer
information is available for elvitegravir-cobicistat. Limited pharmacokinetic data suggest that although raltegravir shows extensive variability
in the third trimester, postpartum and historical data show consistent exposure, and standard dosing appears appropriate in pregnancy.
Case report data suggest a high placental transfer rate to the fetus, with a reported cord-to-maternal blood ratio of approximately 1.0.41,209
Raltegavir is classified as FDA pregnancy category C; animal studies have not found evidence of gross developmental abnormalities;
however, increases in the incidence of supernumerary ribs have been observed in rats receiving raltegravir doses 3 times the
recommended human dose. There is only limited experience with raltegravir in human pregnancy; case report data show the addition of
raltegravir in the third trimester to rapidly decrease viral load at the time of delivery.190,210,211
Elvitegravir and colbicistat (as components of the combination antiretroviral Stribil) are classified as FDA pregnancy category B; animal
studies have not shown evidence of teratogenicity or gross structural abnormalities. There are no reported data in human pregnancies.212

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

APPENDIX 3. SUMMARY OF RECOMMENDATIONS AND MANAGEMENT ALGORITHM FOR WOMEN

WITH KNOWN HIV INFECTION OR WOMEN IN WHOM HIV INFECTION HAS NOT BEEN RULED OUT

This Appendix applies to women with known HIV infection, to women with potential HIV infection based on rapid HIV antibody test results,
and (when rapid HIV antibody testing is not available) to women considered at high risk of HIV infection, but whose HIV status is unknown.

1. Maximal confidentiality of the woman’s HIV status should be maintained.

2. Standard universal precautions should be undertaken for protection from blood and bodily fluids (use gown, mask, eye protection, and
gloves during delivery) according to details available in an infection control manual. No additional precautions are required.

3. Laboratory tests:
a. On admission, tests should be performed for
• CBC, differential, creatinine, urea, AST, ALT, bilirubin, and glucose;
• HIV viral load; and
• CD4-cell count.
b. Performance of prenatal blood tests, including HBV and HCV serology, RPR, rubella, and varicella IgG, should be verified.
c. The placenta should be sent to pathology for examination after delivery.
d. Appropriate blood test results should be obtained for any study in which the woman has previously consented to participate.

4. General management of labour and delivery:

a. Epidurals are not contraindicated.
b. Artificial rupture of membranes should be avoided unless necessary for obstetrical management.
c. Prolonged rupture of membranes should be avoided if possible.
d. Oxytocin should be administered as per protocol if there is rupture of membranes and the woman is not in labour.
e. The use of scalp electrodes, fetal scalp sampling, or intrauterine pressure catheters should be avoided unless absolutely necessary.
f. Intermittent auscultation or external fetal monitoring should be used based on usual obstetrical guidelines for fetal surveillance.
g. Group B streptococcus prophylaxis should be offered as per standard guidelines.
h. Because of the risk of exaggerated vasoconstriction in women receiving PIs, ergonovine maleate should be avoided in the
management of postpartum hemorrhage.

5. Mode of delivery should be discussed in detail with women known to be living with HIV.
a. Women on optimal antenatal antiretroviral therapy with a recent (within last 4 weeks) HIV viral load ≤ 1000 copies/mL are
recommended to have a vaginal delivery if obstetrically appropriate and the woman was adherent to antenatal antiretroviral therapy.
b. Women not on optimal antiretroviral therapy (e.g., no antenatal antiretroviral therapy or with a recent [within last 4 weeks] HIV viral
load or projected viral load > 1000 copies/mL) should be offered a pre-labour Caesarean section at approximately 38 weeks of
completed gestation. If the woman is in labour or there has been rupture of membranes, Caesarean section has not been shown to
reduce transmission.

6. Antenatally prescribed antiretroviral therapy should usually be continued for as long as possible during labour; however, oral stavudine
(d4T or Zerit) should be discontinued because of its antagonistic interaction with intravenous zidovudine.

7. Intrapartum antiretroviral therapy should be initiated

• with rupture of membranes at any time;
• with onset of labour—spontaneous or induced, even if preterm;
• at induction of labour if rapid progression is anticipated;
• at least 2 hours prior to planned Caesarean section; and
• in any situation when delivery is anticipated.
a. All women throughout labour and delivery, regardless of their antepartum antiretroviral regimen and mode of delivery, should be
given
• zidovudine 2 mg/kg IV loading dose over 1 hour, followed by
• zidovudine 1 mg/kg/hr IV infusion until delivery.
If the labour stops and the infusion is discontinued for greater than 6 hours, the loading dose should be re-administered and
continuous infusion resumed when labour recommences.
b. Women who did not receive any antenatal antiretroviral therapy during pregnancy should also be given one single-dose of
nevirapine 200 mg orally as soon as possible at onset of labour or presentation to labour/delivery suite.

continued

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SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 3. Continued

  8. Postpartum antiretroviral therapy

a. Women who have been receiving antenatal antiretroviral therapy should have their complete regimen resumed after delivery as
soon as oral intake is tolerated, unless otherwise indicated.
b. Women who have not been receiving antenatal antiretroviral therapy but have received single-dose nevirapine during labour should
receive 7 days of Combivir (zidovudine-lamivudine), 1 tablet orally twice daily, to reduce the risk of the development of nevirapine
resistance. An adult HIV care provider should be consulted to determine the need to continue the therapy or begin an alternate
antiretroviral regimen.

  9. Prophylaxis against opportunistic infections should be offered to women who are immunocompromised.

10. Assessment and discussion of contraception, mental health, need for social services, or treatment of substance use indicated should
be undertaken prior to discharge.

11. Breastfeeding is contraindicated in women with known HIV infection regardless of maternal antiretroviral therapy and viral load. In
women in whom HIV infection has not been ruled out, breast milk pumping and avoidance of breast milk infant feeding is recommended
until HIV negative status is confirmed,

MANAGEMENT ALGORITHM FOR HIV INFECTED WOMAN AND HER INFANT

(VL = viral load, ART = antiretroviral therapy, ZDV = Zidovudine, 3TC = Lamivudine, NVP = Nevirapine)

Received antenatal ART but

Received antenatal ART and Did not receive ART in
VL > 1000 copies/mL
VL  1000 copies/mL pregnancy
(known or projected)
Mother

IV ZDV loading dose and

Continue combination antenatal infusion during labour
Continued combination ART and
antenatal ART Single-dose NVP
IV ZDV loading dose and and
IV ZDV loading dose and infusion during labour ZDV-3TC (Combivir®) x 7 days
infusion during labour postpartum
Caesarean section if not in Caesarean section if not in
active labour active labour

Combination ART:
Infant

ZDV x 6 weeks*
ZDV x 6 weeks and 3-doses NVP (day 0, 2, 6) and 2-weeks 3TC

* Use of combination ART for prophylaxis may be warranted in circumstances when infant is born to a mother with poor adherence to antenatal ART
and/or with non-suppressed VL (i.e., VL 40-999 copies/mL) particularly when delivered vaginally. Consult with pediatrician with expertise in HIV.

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 Guidelines for the Care of Pregnant Women Living With HIV and Interventions to Reduce Perinatal Transmission

APPENDIX 4. SUMMARY OF RECOMMENDATIONS FOR INFANTS BORN TO MOTHERS

WITH KNOWN HIV INFECTION OR IN WHOM HIV INFECTION HAS NOT BEEN RULED OUT

This Appendix applies to infants born to mothers with known HIV infection, mothers with potential HIV infection based on rapid HIV antibody
test result, and mothers considered at high risk of HIV infection but with unknown HIV status when rapid HIV antibody test is not available.

1. Maximal confidentiality of the woman’s HIV status should be maintained.

2. Standard universal precautions should be undertaken for protection from blood and bodily fluids (use gown, mask, eye protection, and
gloves during delivery) according to details available in an infection control manual. No additional precautions are required.

3. Wash injection site prior to intramuscular injections or blood sampling.

4. Breastfeeding is contraindicated in women with known HIV infection regardless of maternal antiretroviral therapy and viral load. In
women in whom HIV infection has not been ruled out, breast milk pumping and avoidance of breast milk infant feeding is recommended
until HIV negative status is confirmed.

5. Prophylaxis should be offered to prevent HIV vertical transmission to the infant, whether or not the mother received antiretroviral
therapy at delivery.
a. All infants should be given oral or intravenous zidovudine beginning immediately after birth. Oral therapy is preferred, but if the
infant is unable to tolerate oral feeds, intravenous therapy may be used.

Zidovudine (ZDV, AZT, Retrovir) Dosage

Alternate (three times daily dosing for

Gestational age
Term (≥ 35 weeks’
gestation)
30–34 weeks’ gestation
< 29 weeks’ gestation
*Use IV formulation only when the infant is unable to tolerate oral feeds.
Recommended (twice daily dosing for all infants) preterm infants)
ZDV 4 mg/kg/dose PO every 12 hours for 6 weeks
or
ZDV 3 mg/kg/dose IV* every 12 hours
ZDV 2 mg/kg/dose PO every 12 hours for 2 weeks, ZDV 2 mg/kg/dose PO (or 1.5mg/kg/dose IV*)
then 3 mg/kg/dose PO every 12 hours until 6 weeks every 12 hours for 2 weeks, then every 8 hours
or until 6 weeks.
ZDV 1.5 mg/kg/dose IV* every 12 hours for 2 weeks,
then 2.3 mg/kg/dose IV* every 12 hours until 6 weeks
ZDV 2 mg/kg/dose PO every 12 hours for 4 weeks, ZDV 2 mg/kg/dose PO (1.5 mg/kg/dose IV*)
then 3 mg/kg/dose PO every 12 hours until 6 weeks every 12 hours for 4 weeks, then every 8 hours
or until 6 weeks.
ZDV 1.5 mg/kg/dose IV* every 12 hours for 4 weeks,
then 2.3 mg/kg/dose IV every 12 hours until 6 weeks

b. Combination antiretroviral therapy with nevirapine and lamivudine (in addition to zidovudine) is given to infants born to mothers
who were not on optimal antiretroviral therapy (e.g., received no antenatal antiretroviral therapy) or with a recent HIV viral load
(measured within last 4 weeks) or projected HIV viral load greater than 1000 copies/mL.
Note: For infants born to mothers considered at high risk of HIV infection, but with unknown HIV status, when the rapid HIV antibody
test is not available prophylaxis with only single agent zidovudine may still be considered.
Nevirapine dosage (there is no IV formulation available):
• Infant > 2 kg: 12 mg PO for a total of 3 doses. First dose given immediately after birth (day 0), second dose given at 2 days
of age, third dose given at 6 days of age.
• Infant 1.5–2 kg: 8 mg PO for a total of 3 doses. First dose given immediately after birth (day 0), second dose given at 2 days
of age, third dose given at 6 days of age.
Lamivudine (3TC) dosage (there is no IV formulation available):
• Infant > 2 kg: 6 mg PO every 12 hours for 2 weeks.
• Infant 1.5–2 kg: 4 mg PO every 12 hours for 2 weeks.
6. Laboratory tests to be ordered within 48 hours after birth:
• CBC, differential, creatinine, urea, AST, ALT, bilirubin
• For infants born to mothers with known HIV infection or potential HIV infection based on rapid HIV antibody testing, infant
diagnostic HIV PCR should be performed with blood (minimum 2 mL in EDTA tube) and appropriate requisition sent to the local
CDC.

continued

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SOGC CLINICAL PRACTICE GUIDELINE

APPENDIX 4. Continued

• For infants born to mothers with unknown HIV status (where rapid HIV antibody testing is not available), HIV EIA (antibody) is
the priority test over HIV PCR if a blood sample from the infant is difficult to obtain. Blood (minimum 2 mL in gold top tube) and
appropriate requisition should be sent to the local CDC. Infant diagnostic HIV PCR should be conducted within 48 hours, with
blood (minimum 2 mL in EDTA tube) and appropriate requisition sent to the local CDC.

7. Check maternal hepatitis B status. If the mother tests positive for hepatitis B surface antigen or has unknown status, administer first
dose of hepatitis B vaccine and hepatitis B immune globulin to the infant within 12 hours after birth.

8. The remainder of the zidovudine bottle should be supplied to the parent/guardian on discharge to treat the infant for the entire 6-week
course. If nevirapine and lamivudine (3TC) are required for the infant, adequate medication should be provided to the parent/guardian
on discharge from hospital to complete the treatment course.

9. Infants born to mothers considered at high risk of HIV infection, but with unknown HIV status (when the rapid HIV antibody test is not
available) should be referred to the local multidisciplinary HIV clinic if any HIV test (HIV EIA or HIV PCR) drawn is positive in mother
or infant. If all HIV tests (HIV EIA and HIV PCR) drawn are negative in both mother and infant all antiretroviral drug therapy may be
discontinued.

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 SOGC CLINICAL PRACTICE GUIDELINES

No. 303, February 2014

Determination of Gestational Age

by Ultrasound
Evidence: Published literature was retrieved through searches
This clinical practice guideline has been prepared by the of PubMed or MEDLINE and The Cochrane Library in 2013
Diagnostic Imaging Committee, reviewed by the Family using appropriate controlled vocabulary and key words
Physician Advisory Committee, and approved by the (gestational age, ultrasound biometry, ultrasound dating).
Executive and Council of the Society of Obstetricians and Results were restricted to systematic reviews, randomized
Gynaecologists of Canada. control trials/controlled clinical trials, and observational studies
written in English. There were no date restrictions. Searches
PRINCIPAL AUTHORS were updated on a regular basis and incorporated in the
guideline to July 31, 2013. Grey (unpublished) literature was
Kimberly Butt, MD, Fredericton NB
identified through searching the websites of health technology
Ken Lim, MD, Vancouver BC assessment and health technology-related agencies, clinical
practice guideline collections, clinical trial registries, and
DIAGNOSTIC IMAGING COMMITTEE national and international medical specialty societies.
Ken Lim, MD (Chair), Vancouver BC Values: The quality of evidence in this document was rated using
Stephen Bly, MD, Ottawa ON the criteria described in the Report of the Canadian Task Force
on Preventive Health Care (Table 1).
Kimberly Butt, MD, Fredericton NB
Benefits, harms, and costs: Accurate assignment of gestational
Yvonne Cargill, MD, Ottawa ON age may reduce post-dates labour induction and may improve
Greg Davies, MD, Kingston ON obstetric care through allowing the optimal timing of necessary
interventions and the avoidance of unnecessary ones. More
Nanette Denis, RDMS, Saskatoon SK accurate dating allows for optimal performance of prenatal
Gail Hazlitt, RN, RDMS, Winnipeg MB screening tests for aneuploidy. A national algorithm for the
assignment of gestational age may reduce practice variations
Lucie Morin, MD, Montreal QC across Canada for clinicians and researchers. Potential
Annie Ouellet, MD, Sherbrooke QC harms include the possible reassignment of dates when
significant fetal pathology (such as fetal growth restriction
Shia Salem, MD, Toronto, ON
or macrosomia) result in a discrepancy between ultrasound
Disclosure statements have been received from all contributors. biometric and clinical gestational age. Such reassignment may
lead to the omission of appropriate—or the performance of
inappropriate—fetal interventions.
Abstract
Summary Statements
Objective: To assist clinicians in assigning gestational age based on 1. When performed with quality and precision, ultrasound alone is
ultrasound biometry. more accurate than a “certain” menstrual date for determining
gestational age in the first and second trimesters (≤ 23 weeks)
Outcomes: To determine whether ultrasound dating provides more
in spontaneous conceptions, and it is the best method for
accurate gestational age assessment than menstrual dating with
estimating the delivery date. (II)
or without the use of ultrasound. To provide maternity health care
providers and researchers with evidence-based guidelines for the 2. In the absence of better assessment of gestational age, routine
assignment of gestational age. To determine which ultrasound ultrasound in the first or second trimester reduces inductions
biometric parameters are superior when gestational age is for post-term pregnancies. (I)
uncertain. To determine whether ultrasound gestational age
assessment is cost effective.

Keywords: ultrasound, gestational age, dating

J Obstet Gynaecol Can 2014;36(2):171–181

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

FEBRUARY JOGC FÉVRIER 2014 l 171

SOGC Clinical Practice Guidelines

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.118
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.118

3. Ideally, every pregnant woman should be offered a first-trimester INTRODUCTION

dating ultrasound; however, if the availability of obstetrical

ultrasound is limited, it is reasonable to use a second-trimester
scan to assess gestational age. (I)
4. Notwithstanding Summary Statements 1, 2, and 3, women vary
greatly in their awareness of their internal functions, including
ovulation, and this self-knowledge can sometimes be very
accurate. (III)
Recommendations
1. First-trimester crown-rump length is the best parameter for
determining gestational age and should be used whenever
appropriate. (I-A)
2. If there is more than one first-trimester scan with a mean sac
diameter or crown-rump length measurement, the earliest
ultrasound with a crown-rump length equivalent to at least 7
weeks (or 10 mm) should be used to determine the gestational
age. (III-B)
3. Between the 12th and 14th weeks, crown-rump length and
biparietal diameter are similar in accuracy. It is recommended
that crown-rump length be used up to 84 mm, and the biparietal
diameter be used for measurements > 84 mm. (II-1A)
4. Although transvaginal ultrasound may better visualize
early embryonic structures than a transabdominal approach,
it is not more accurate in determining gestational age.
Crown-rump length measurement from either transabdominal
or transvaginal ultrasound may be used to determine
gestational age. (II-1C)
5. If a second- or third-trimester scan is used to determine
gestational age, a combination of multiple biometric parameters
(biparietal diameter, head circumference, abdominal
circumference, and femur length) should be used to determine
gestational age, rather than a single parameter. (II-1A)
6. When the assignment of gestational age is based on a third-
trimester ultrasound, it is difficult to confirm an accurate due date.
Follow-up of interval growth is suggested 2 to 3 weeks following
the ultrasound. (III-C)
T
he accurate dating of pregnancy is critically important
for pregnancy management from the first trimester to
delivery, and is particularly necessary for determining viability
in premature labour and in post-dates deliveries.1 Prior to
the widespread use of ultrasound, caregivers relied on a
combination of history and physical examination to clinically
determine gestational age. Ultrasound gave clinicians a method
to measure the fetus and therefore to estimate gestational
age. Much of our current clinical practice is based on studies
from the 1980s and 1990s. As new information emerges in
fields, such as reproductive biology, perinatal epidemiology,
and medical imaging, our current clinical practice is being
challenged. “Certain” menstrual dating, for example, is less
certain than previously thought.
When ultrasound is performed with quality and precision,
there is evidence to suggest that dating a pregnancy using
ultrasound measurements is clinically superior to using
menstrual dating with or without ultrasound, and this has
been advocated and adopted in other jurisdictions.2–6
GESTATIONAL AGE ESTIMATES
USING CLINICAL DATING
The clinical estimate of gestational age typically relies on
clinical history (menstrual cycle length, regularity, and recall
of the first day of the last menstrual period), followed by
confirmation by physical examination or other signs and
symptoms.7–9

172 l FEBRUARY JOGC FÉVRIER 2014


Dating Based on Menstrual History
Dating by certain menstrual history is inexpensive and
readily available. Typically, the EDD is based on a 280-
day gestation from the first day of the LMP. Certain
menstrual dating criteria assume regular cycles, ovulation
at the midpoint of the cycle, fertilization on the middle
day of the cycle, correct recall of the onset of the LMP,
and the woman having been free of oral contraceptives
for several months prior. Women vary greatly in their
awareness of their internal functions, including ovulation.
Their self-knowledge of ovulation can sometimes be very
accurate; however, the only truly certain clinical history
is one in which the dates of ovulation, fertilization,
and implantation are precisely known, as in ART, in
which records include the date of oocyte retrieval, and
other methods of timed ovulation and fertilization.
Unfortunately, without timed ovulation and fertilization
as in ART and other timed methods, clinical history is
often not reliable.10 Campbell et al. demonstrated that
45% of pregnant women are uncertain of menstrual
dates as a result of poor recall, irregular cycles, bleeding
in early pregnancy, or oral contraceptive use within 2
months of conception.11
Even if menstrual history is correct, the exact time
of ovulation, fertilization, and implantation cannot be
known. Women may undergo several “waves” of follicular
development during a normal menstrual cycle, which
may mean ovulatory inconsistency during any given
cycle.12,13 Sperm may survive for 5 to 7 days in the female
reproductive tract, a “known” conception date is therefore
not completely reliable.14 Recent studies suggest the
ovulation-to-implantation duration can vary by as much as
ABBREVIATIONS
AC abdominal circumference
ART assisted reproductive technology
BPD biparietal diameter
CRL crown-rump length
EDD estimated due date
FL femur length
HC head circumference
ISUOG International Society of Ultrasound in Obstetrics and
Gynecology
LMP last menstrual period
MSD mean sac diameter
PPV positive predictive value
TA transabdominal
TV transvaginal
US ultrasound
Determination of Gestational Age by Ultrasound
11 days, and this may affect fetal size and growth.15 Even
in women who are certain of menstrual dating, delayed
ovulation is an important cause of perceived prolonged
pregnancy and is more likely to occur than early ovulation.16
Some authors have suggested that 282 days should be used
instead of 280 to improve dating accuracy, since it is more
likely that women will ovulate later rather than earlier than
predicted.9 All of these factors conspire to make it difficult
to accurately predict gestational age based on menstrual
history.
Dating Based on Clinical Examination
The size of the uterus, estimated through pelvic or
abdominal examination, can be roughly correlated with
gestational age; however, factors that affect uterine size
(such as fibroids) and maternal body characteristics (such
as obesity) will affect such an estimate. The uterus is
approximately the size of a grapefruit at 10 to 12 weeks.
At 20 weeks the fundus reaches the umbilicus. After 20
weeks the symphysis fundal height, in centimetres, should
correlate with the week of gestation.7,17 Fetal heart tones
are audible at 11 to 12 weeks with electronic Doppler
devices, and this audibility can also assist in the clinical
assignment of gestational age.10
Gestational Age Estimation Based
on Ultrasound Findings
Ultrasound biometric measurements determine
gestational age based on the assumption that the size of
the embryo or fetus is consistent with its age. Biological
variation in size is less during the first trimester than in
the third trimester. Ultrasound estimation of gestational
age in the first trimester is therefore more accurate than
later in pregnancy.18 Full descriptions of each parameter
and published ranges of accuracy are outlined in Table 2.
The determination of gestational age in the first trimester
uses the mean gestational sac diameter and/or the crown–
rump length. During the first 3 to 5 menstrual weeks an
intrauterine pregnancy is first signaled by the presence
of a gestational sac.19 The gestational sac represents the
chorionic cavity, and its echogenic rim represents the
implanting chorionic villi and associated decidual tissue.20
The smallest gestational sac size that can be clearly
distinguished by high frequency transvaginal transducers
is 2 to 3 mm, which corresponds to a gestational age of
about 32 to 33 days.21 The MSD is a commonly used,
standardized, way to estimate gestational age during early
pregnancy. It is less reliable when the MSD exceeds 14 mm
or when the embryo can be identified.22 The growth of
the MSD is approximately 1 mm per day.23 CRL has lower
interobservor variability than MSD, and may thus be better
for dating a pregnancy.24
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SOGC Clinical Practice Guidelines
Yolk Sac
When the yolk sac appears in the gestational sac it provides
confirmation of an intrauterine pregnancy and may be
initially visible as early as the start of the 5th week or as
late as the 6th week. It grows to a maximal size of 6 mm
by 10 weeks and gradually migrates to the periphery of
the chorionic cavity. At the end of the first trimester it
becomes undetectable. Although the presence of the yolk
sac is helpful in determining the presence of an intrauterine
pregnancy, direct measurement of this structure is not
useful in determining gestational age.25
Crown-Rump Length
Direct measurement of the CRL provides the most
accurate estimate of gestational age once the embryo is
clearly seen. Ideally, either the best CRL or the average
of several satisfactory measurements should be used.26
The CRL measurement is reported to be accurate for
dating to within 3 to 8 days.22,27–39 The MSD should not
be used to estimate gestational age once the CRL can be
measured.22,39,40
The narrowest confidence interval appears to be
between 7 and 60 mm for CRL.3,29,30,40 The slope of the
embryonic growth curve is small before this time and it
can be difficult to clearly identify a very early fetus; thus,
it is this committee’s expert opinion that reliability and
measurability is best when the CRL is at least 10 mm. If
more than one scan is performed in the first trimester, the
earliest scan with a CRL of at least 10 mm should be used.
To avoid performing extra ultrasounds, it is acceptable to
time the dating scan to coincide with nuchal translucency
screening (if available).
Several studies have evaluated CRL and BPD between
12 and 14 weeks, with conflicting results. The majority
suggest there is no clinically important difference among
confidence intervals, suggesting that either CRL or BPD
should be used at this gestational age.41–44 The 84 mm
threshold for CRL for estimating gestational age, as
suggested by the ISUOG, seems reasonable.6
Recommendations
1. First-trimester crown-rump length is the
best parameter for determining gestational
age and should be used whenever
appropriate. (I-A)
2. If there is more than one first-trimester scan
with a mean sac diameter or crown-rump length
measurement, the earliest ultrasound with a crown-
rump length equivalent to at least 7 weeks (or
10 mm) should be used to determine the gestational
age. (III-B)
174 l FEBRUARY JOGC FÉVRIER 2014
3. Between the 12th and 14th weeks, crown-rump
length and biparietal diameter are similar in accuracy.
It is recommended that crown-rump length be used
up to 84 mm, and the biparietal diameter be used for
measurements > 84 mm. (II-1A)
Transabdominal Versus
Transvaginal Ultrasonography
Transvaginal ultrasound is typically used to evaluate
early first trimester pregnancy structures, such as the
gestational sac, yolk sac, and embryo. Original studies
comparing transabdominal and transvaginal techniques in
early pregnancy demonstrated that TV was the superior
method.45–47 Perhaps because of better technology, more
recent studies have not found the same result. Grisolia
et al. concluded that the accuracy of TV ultrasound
has not been shown to be superior to TA ultrasound in
dating pregnancies.31 Other authors have found that TA is
comparable to TV in determining gestational age if CRL is
measurable after 6 weeks.31,48–50
Recommendation
4. Although transvaginal ultrasound may better
visualize early embryonic structures than a
transabdominal approach, it is not more accurate
in determining gestational age. Crown-rump length
measurement from either transabdominal or
transvaginal ultrasound may be used to determine
gestational age. (II-1C)
Crown-Rump Length in Pregnancies Conceived
by Assisted Reproductive Technology
When the conception date is known absolutely, as with
timed ovulation/fertilization during ART, the EDD
should be calculated based on the fertilization date.
Studies have demonstrated that the CRL measurements
in IVF pregnancies are those to be expected in naturally
conceived pregnancies, suggesting that study results can be
extrapolated between the 2 populations.30,51,52
Second and Third Trimester
In the second and third trimesters, estimation of gestational
age is accomplished by measuring the biparietal diameter,
head circumference, abdominal circumference, and femur
length. These measurements are only as good as the quality of
the images. Optimal imaging can be difficult in some clinical
situations, such as in a late pregnancy abnormal lie when
the head is deep in the maternal pelvis, maternal obesity, or
multiple gestation. Normal biological variation appears to
have more influence on measurements in the second and
third trimester. Thus, in the second half of pregnancy these
measurements are less reliable than first trimester CRL, and
they become increasingly inaccurate as gestation progresses
 Table 2. Common definitions of ultrasound biometry parameters and estimates of accuracy for predicting gestational age
Approximate
Parameter Description Notes accuracy of dates References
Mean sac diameter The mean of 3 orthogonal sac “inner to inner” diameter Should not be averaged with the 4 to 11 days Grisolia (2003)31
measurements (mm). Cursers should be placed on the CRL. Daya (1993)30
gestational sac and not the surrounding echogenic region. Should not be used once CRL
can be measured.
GA = 30 days plus MSD
measured in mm.
Crown-rump length The crown-rump length is the longest straight line length of the The best CRL or the average 3 to 8 days Grisolia (2003)31
embryo from the outer margin of the cephalic end to the rump. of several satisfactory Daya (1993)30
The neck position should be neutral. measurements should be used.
Sladevickus (2004)42
Biparietal diameter Axial plane through a symmetrical calvarium that includes the 1st T: 3 to 8 days Grisolia (2003)31
third ventricle, thalami, falx cerebrum, and cavum septi pellicidi 2nd T: 7 to 12 days Daya (1993)30
anteriorly and the tentorial hiatus posteriorly.
Sladevickus (2004)42
The calipers should be placed at the maximal diameter from
the outer edge of the proximal skull wall to the inner edge of Bovicelli (1981)28
the distal skull. Hadlock (1984)72
Hadlock (1987)73
Hadlock (1991)54
Chervenak (1998)61
Head circumference The head circumference is obtained in the identical plane to the The cerebellum is not included in 2nd T: 7 to 12 days Hadlock (1984)72
BPD. The trace/ellipse should follow the outer perimeter of the this image. Hadlock (1987)73
bony skull, not the overlying skin, as that will falsely increase
the head circumference Hadlock (1991)54
Chervenak (1998)61
Abdominal circumference True axial plane at the level of the bifurcation of the portal 2nd T: 7 to 15 days Hadlock (1984)72
vein (into right and left branches) and the stomach. The 3rd T: 18 to 35 days Hadlock (1987)73
measurement should be as tight to skin as possible.
Hadlock (1991)54
Chervenak (1998)61
Femur length Both the femoral head or greater trochanter and the femoral Ideally, the ultrasound transducer 2nd T: 7 to 17 days Hadlock (1984)72
condyle are simultaneously visualized. The cursor should be should be aligned perpendicular 3rd T: 21 days Hadlock (1987)73
placed at the junction of bone and cartilage and only the bone to the long axis of the femur.
measured Hadlock (1991)54
Varies with ethnicity.
Chervenak (1998)61
T: trimester

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Determination of Gestational Age by Ultrasound
SOGC Clinical Practice Guidelines
(Table 2).18,53 Maternal and fetal pathology may affect them,
so their inclusion or exclusion in the determination of
gestational age requires clinical judgement.
The BPD is less reliable in determining gestational age when
there are variations in skull shape, such as dolichocephaly
or brachycephaly; hence some authors feel that BPD is less
reliable than HC.9,53–57 As a single parameter, HC correlates
better to gestational age than the other 3 standard parameters
in the second trimester, and as with all others, it becomes
less accurate with increasing gestational age.58–61
It is more challenging to measure the fetal AC than the other
parameters. The abdomen has no bright echoes of bone, it
is not always symmetrical, and its size will vary with fetal
respiration and central body flexion/extension. Of all the
fetal biometric parameters, this measurement has the most
variability as it is somewhat dependant on fetal growth
factors and body position.54,61–63
Femur length varies somewhat with ethnicity. Short femurs
are commonly a normal variant, however this finding may
also indicate fetal growth restriction, aneuploidy, and—
when severely shortened—skeletal dysplasias.53,64–69
Composite Versus Single Biometry Measurement
Using multiple parameters is superior to using a single
second trimester parameter.63,70,71 As more parameters are
used, accuracy improves; however, there is no significant
benefit beyond 3 commonly used parameters.3,61,70–73
Multiple parameters are also useful if any one parameter
is affected by a fetal condition/syndrome, such as
achondroplasia on femur length. It is prudent to evaluate
the etiology of an aberrant measurement to determine its
clinical significance.
Commonly, clinicians use the unweighted mean of all 4
biometric parameters (BPD, HC, AC, and FL). However, it is
clear that all 4 are not equally correlative, thus many authors
have created regression equations using various combinations
of biometric parameters to improve accuracy.54,61,74,75 It is not
clear which method is superior in determining gestational
age.61,72 Until more research is available, it is reasonable to use
either when estimating second or third trimester gestational
age. Up to 23 weeks, second trimester US has a 95% CI of
less than a week for predicting gestational age, comparable
to first trimester US.61 In the late second trimester, clinical
judgement should be exercised.
Since the confidence intervals in the third trimester
are quite large (2 to 2.4 weeks), it is not clear that US
determined gestational age is superior to clinical history
and the application of judicious clinical judgement may be
176 l FEBRUARY JOGC FÉVRIER 2014
warranted. There is also a concern that when gestational
age assessment is based on a third trimester scan only, the
fetus may in fact be growth restricted,61 and gestational
age therefore underestimated. Hence, a follow-up scan
for growth in such circumstances should be considered to
evaluate interval growth.
Recommendations
5. If a second- or third-trimester scan is used to
determine gestational age, a combination of multiple
biometric parameters (biparietal diameter, head
circumference, abdominal circumference, and femur
length) should be used to determine gestational age,
rather than a single parameter. (II-1A)
6. When the assignment of gestational age is based
on a third-trimester ultrasound, it is difficult to
confirm an accurate due date. Follow-up of interval
growth is suggested 2 to 3 weeks following the
ultrasound. (III-C)
Other Biometry
Measurement of the transcerebellar diameter, foot length,
clavicle length, intra/interorbital diameters, kidney length,
sacral length, scapula length, as well as the length of other
long bones of the extremity have also been evaluated to
determine gestational age. Studies have not shown that
these parameters improve the assessment of gestational
age beyond that achieved with standard biometry, however
they may be useful in clinical situations in which traditional
biometry is difficult to attain (such as uteroplacental
insufficiency) or when fetal abnormalities are present.76–86
Signs of Fetal Maturity
Identification of certain US findings suggest that a fetus
has reached the third trimester and may correlate with
fetal lung maturity and gestational age. These parameters
are the epiphyseal ossification centres of the distal femur,
proximal tibia, and proximal humerus. The measurement of
these ossification centres does not precisely correlate with
gestational age; however, their presence may be helpful late
in pregnancy when the gestational age is not known. The
presence of distal femoral epiphysis has a PPV of 96% for
indicating a pregnancy of at least 32 weeks, the proximal
tibial epiphysis has a PPV of 83% for indicating a pregnancy
of at least 37 weeks, and the proximal humeral epiphysis
has a PPV of 100% for indicating a pregnancy of at least
38 weeks.87–91
WHAT IS THE BEST METHOD
FOR ASSIGNING GESTATIONAL AGE?
Currently, most centres in Canada use a combined
approach in which US is used to confirm reliable

menstrual dating. If there is an unreliable menstrual
history, the US prediction of EDD is used. Clinical
judgement is used to resolve conflicting data. However,
centres vary in terms of confidence intervals and
biometry charts used.
Many studies evaluating menstrual dating, compared with
US dating, in the first and second trimesters have found US
dating superior for predicting the actual date of delivery.92–98
No study has shown that it is inferior to menstrual dating.
Menstrual dating underestimates the US-based EDD by
an average of 2 to 3 days.95 Ultrasound dating alone was
significantly better in predicting the actual date of delivery
than any of the dating policies using menstrual dates alone
or in combination with US.9,99
Many studies document that the use of US dates reduces
the rate of post-dates pregnancy by about 70% even in
the face of certain menstrual history.92,96,97,99,100 The most
recent Cochrane systematic review found reduced rates
of induction for post-term pregnancy (OR 0.59; 95% CI
0.42 to 0.83) among women who underwent routine US
in early pregnancy (< 24 weeks) and concluded that early
pregnancy US enables better gestational age assessment, as
well as conferring other benefits.101
Using US-based gestational age assignment would also
result in improved performance of prenatal screening
programs. Using US estimates exclusively would increase
sensitivity for Down syndrome anywhere from 9% to 16%,
and/or decrease false-positive rates (for a set sensitivity)
by 2.6%.102,103 There might be a very slight increase in the
screening positive rate for open neural tube defects, but
this is more than offset by the decrease in false-positive
rates for Down syndrome. The common practice of
using certain menstrual dates confirmed by US is inferior
to using US alone.104 In the context of serum screening,
first and early second-trimester US parameters perform
similarly.100,102,104–106
Some clinicians fear that the exclusive use of US-based
estimates of gestational age would result in pregnancy
complications because of the potential to miss early
growth discordance. A large-for-gestational-age fetus
might be mistakenly assigned a greater gestational age
because of its larger size or an early growth-restricted
fetus may be incorrectly assigned a later due date. This
may potentially mask an underlying fetal or placental
problem leading to pregnancy complications, such
as preterm birth, preeclampsia, and fetuses small for
gestational age, or it may cause a delay in the recognition
of fetal abnormalities. There is disagreement in the
literature as to whether a significant discordance
Determination of Gestational Age by Ultrasound
between menstrual and US estimates of gestational
age is associated with an increased risk of obstetrical
complications.107–114 Interestingly, an unreliable
menstrual history itself confers an increased risk of
adverse pregnancy outcomes.112 Although there may be
a risk in using US dating exclusively, some of this risk
would remain whenever there is discordance between
menstrual and US estimates, regardless of which method
of gestational age assignment is used. Furthermore, the
clinical management of such situations is unclear. More
research is needed in this area.
Summary Statements
1. When performed with quality and precision,
ultrasound alone is more accurate than a “certain”
menstrual date for determining gestational age
in the first and second trimesters (≤ 23 weeks) in
spontaneous conceptions, and it is the best method
for estimating the delivery date. (II)
2. In the absence of better assessment of gestational
age, routine ultrasound in the first or second
trimester reduces inductions for post-term
pregnancies. (I)
SHOULD ROUTINE FIRST TRIMESTER
DATING ULTRASOUNDS BE
OFFERED TO ALL PREGNANT WOMEN?
A routine first trimester US has many advantages: early
identification of gross anomalies and multiple gestations,
more precise dating, improved performance of prenatal
screening, and an opportunity to perform nuchal
translucency as part of prenatal genetic screening. In many
jurisdictions, a dating US is performed routinely in all
women, regardless of menstrual history. The availability,
quality, and health care cost of obstetrical US is a significant
factor in local patterns of practice.2 Crowther et al. found
routine early US (< 17 weeks) provided more precise
estimates of gestational age than later US (18 to 22 weeks),
reduced the need to adjust the EDD in mid-gestation, and
decreased maternal anxiety.115
The balance of the literature supports using first trimester
US to reduce the incidence of induction for post-dates
pregnancy.18,99,100,116–118 Although no comprehensive cost
benefit analysis has been done on routine early US for
dating, the current literature suggests significant benefits
are present. Ideally, where it is readily available, a first
trimester US for dating should be performed. Where
nuchal translucency is available, this scan can serve both
functions. When a first trimester US cannot be obtained,
the available evidence suggests the second trimester US
can be used for similar benefits.101
FEBRUARY JOGC FÉVRIER 2014 l 177
SOGC Clinical Practice Guidelines
Summary Statements
3. Ideally, every pregnant woman should be offered
a first trimester dating ultrasound; however, if the
availability of obstetrical ultrasound is limited, it is
reasonable to use a second trimester scan to assess
gestational age. (I)
4. Notwithstanding Summary Statements 1, 2, and
3, women vary greatly in their awareness of their
internal functions, including ovulation, and this self-
knowledge can sometimes be very accurate. (III)
SUMMARY
The accurate determination of gestational age is required for
many aspects of antenatal care. In the past, it was probably
felt that a few days of inaccuracy was acceptable; however,
emerging data suggests that a few days inaccuracy can
affect things, such as the performance of maternal serum
screening, the assessment of post-dates pregnancy, and
the subsequent induction of labour. Based on the available
research, the use of US-derived dates is the best method
to determine gestational age for clinical use. It is not,
however, intended to be used to determine the exact date of
conception because of biological variability in reproduction,
fetal size, and development. Clinical history may have value
in determining gestational age, and on rare occasions may
supersede US dating; however, in order to achieve the most
clinical benefit, the use of US dating should predominate.
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 SOGC CLINICAL PRACTICE GUIDELINE
Diagnosis, Evaluation, and Management
of the Hypertensive Disorders of Pregnancy:
Executive Summary
The guideline summarized here has been prepared by the
Canadian Hypertensive Disorders of Pregnancy Working
Group, reviewed and approved by the Hypertension
Guideline Committee, reviewed by the Maternal Fetal
Medicine and Family Physician Advisory committees, and
approved by the Executive and Council of the Society of
Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Laura A. Magee, MD, Vancouver BC
Anouk Pels, MSc, Amsterdam, the Netherlands
Michael Helewa, MD, Winnipeg MB
Evelyne Rey, MD, Montreal QC
Peter von Dadelszen, MBChB, Vancouver BC
HYPERTENSION GUIDELINE COMMITTEE
Laura A. Magee, MD (Chair), Vancouver BC
Francois Audibert, MD, Montreal QC
Emmanuel Bujold, MD, Quebec QC
Anne-Marie Côté, MD, Sherbrooke QC
Myrtle Joanne Douglas, MD, Vancouver BC
Genevieve Eastabrook, MD, FRCSC, London ON
Tabassum Firoz, MD, Vancouver BC
Paul Gibson, MD, Calgary AB
Andrée Gruslin, MD, Ottawa ON
Jennifer Hutcheon, PhD, Vancouver BC
Gideon Koren, MD, Toronto ON
Ian Lange, MD, Calgary AB
Line Leduc, MD, Montreal QC
Alexander G. Logan, MD, Toronto ON
Key Words: Hypertension, blood pressure, pregnancy,
preeclampsia, maternal outcome, perinatal outcome, long-term
prognosis
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
416 l MAY JOGC MAI 2014
No. 307, May 2014 (Replaces No. 206, March 2008)
Karen L. MacDonell, PhD, Vancouver BC
Jean-Marie Moutquin, MD, Sherbrooke QC
Ilana Sebbag, MD, Vancouver BC
Disclosure statements have been received from all members of
the committee.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
Abstract
Objective: This executive summary presents in brief the current
evidence assessed in the clinical practice guideline prepared by
the Canadian Hypertensive Disorders of Pregnancy Working
Group and published by Pregnancy Hypertension
(http://www.pregnancyhypertension.org/article/S2210-
7789(14)00004-X/fulltext) to provide a reasonable approach to the
diagnosis, evaluation, and treatment of the hypertensive disorders
of pregnancy.
Evidence: Published literature was retrieved through searches of
Medline, CINAHL, and The Cochrane Library in March 2012
using appropriate controlled vocabulary (e.g., pregnancy,
hypertension, pre-eclampsia, pregnancy toxemias) and key
words (e.g., diagnosis, evaluation, classification, prediction,
prevention, prognosis, treatment, postpartum follow-up). Results
were restricted to systematic reviews, randomized control trials,
controlled clinical trials, and observational studies published in
French or English between January 2006 and February 2012.
Searches were updated on a regular basis and incorporated in the
guideline to September 2013. Grey (unpublished) literature was
identified through searching the websites of health technology
assessment and health technology-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: The quality of evidence in the guideline summarized here
was rated using the criteria described in the Report of the
Canadian Task Force on Preventative Health Care (Table 1).
J Obstet Gynaecol Can 2014;36(5):416–438
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.39
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.39

RECOMMENDATIONS ● Antihypertensive Therapy for Severe Hypertension: 62–68

CHAPTER 1: ● Antihypertensive Therapy for Non-Severe Hypertension
DIAGNOSIS AND CLASSIFICATION OF THE Without Comorbid Conditions: 69–73
MEASUREMENT OF BP FOR HDPs
● For Non-Severe Hypertension (BP of 140–159/
● BP Measurement: 1–10 90–109 mmHg) With Comorbid Conditions: 74–76
● Diagnosis of Hypertension: 11–17 ● Corticosteroids for Acceleration of Fetal Pulmonary Maturity:
● Measurement of Proteinuria: 18–24 77–80

● Classification of HDPs: 25–31 ● Timing of Delivery for Women With Preeclampsia: 81–88
● Investigations to Classify HDPs: 32–37 ● Timing of Delivery for Women With Gestational Hypertension:
89, 90
CHAPTER 2: ● Timing of Delivery for Women with Pre-existing
PREDICTION AND PREVENTION Hypertension: 91
● Predicting Preeclampsia: 38–40
● Mode of Delivery: 92–97
● Preventing Preeclampsia and its Complications in Women
● Anaesthesia: General Principles: 98–101
at Low Risk: 41–46
● Anaesthesia: Fluid Administration: 102–105
● Preventing Preeclampsia and its Complications in Women
at Increased Risk: 47–54 ● Monitoring: 106–108
● Coagulation: 109, 110
CHAPTER 3:
TREATMENT OF THE HDPs ● Aspects of Care Specific to Women Wth Pre-Existing
Hypertension: 111–115
● Dietary and Lifestyle Changes: 55–59
● Aspects of Care for Women With Preeclampsia: Magnesium
● Place of Care: 60, 61
Sulphate for Preventing or Treating Eclampsia: 116–123
● Aspects of Care for Women With Preeclampsia: Plasma
ABBREVIATIONS Volume Expansion: 124
BP blood pressure ● Therapies for HELLP Syndrome: 125–131
HDP hypertensive disorder of pregnancy ● Care in the 6 Weeks Postpartum: 132–142
HELLP hemolysis, elevated liver enzymes, low platelets ● Care Beyond 6 Weeks Postpartum: 143–148
IUGR intrauterine growth restriction ● Effects of Maternal Hypertension and its Therapies on Child
NICU neonatal intensive care unit Neurobehavioural Development: 149, 150

RCT randomized control trial CHAPTER 4:

RDS respiratory distress syndrome PATIENT PERSPECTIVE: 151–153

MAY JOGC MAI 2014 l 417

SOGC CLINICAL PRACTICE GUIDELINE
INTRODUCTION
H ypertensive disorders of pregnancy remain leading
causes of maternal and perinatal morbidity and
mortality.1,2 The guideline summarized here assesses the
quality of the relevant existing evidence and provides
a reasonable approach to the diagnosis, evaluation, and
treatment of the HDP, focusing on Canadian context.
Our purpose is to support evidence-based maternity care
of women who are planning pregnancy and are at risk of
an HDP, have an HDP in the current pregnancy, or are
postpartum and had an HDP. When necessary, we have
provided expert opinion about reasonable clinical care.
Our health intent and aim is to improve short- and long-
term maternal, perinatal, and paediatric outcomes and the
cost-effectiveness of related interventions in pregnancies
complicated by an HDP. The expected benefit of this
guideline is improved outcomes for mother, baby, and child
through evidence-advised practice. Our target users are
multidisciplinary maternity care providers from primary to
tertiary levels of health care.
The questions that this guideline seeks to address are:
•• How, and in what setting, should BP be measured in
pregnancy, and what is an abnormal BP?
•• How should proteinuria be measured in pregnancy?
What constitutes significant proteinuria? Is heavy
proteinuria an indication for delivery?
•• How should the HDPs be diagnosed and classified?
What constitutes severe preeclampsia?
•• What are the prognoses of pregnancies complicated by
pre-existing hypertension, gestational hypertension, or
preeclampsia?
•• How can preeclampsia and its complications be
predicted and/or prevented by lifestyle changes,
medication, and/or care of a specific type or in a
specific location?
•• How should women with an HDP be managed
regarding initial investigations, dietary and lifestyle
changes, place of care, antihypertensive therapy,
aspects of care specific to women with preeclampsia
(such as magnesium sulphate), mode and timing of
delivery, intrapartum care (including BP monitoring and
analgesia/anaesthesia), and postpartum monitoring,
treatment, and counselling regarding the impact of an
HDP on both future pregnancy outcomes and long-
term maternal and paediatric outcomes?
•• What is the patient’s perspective on her diagnosis and
evaluation?
418 l MAY JOGC MAI 2014
•• How can this guideline be implemented into clinical
practice?
This document presents a summary of the
recommendations, along with supporting text for the new
classification of the HDPs, and all of the tables provided
in the full guideline. Because of the breadth of the
topic and the volume of material covered, the methods,
supporting text for all recommendations, and the full list
of references, including those for the tables, have been
published separately as an open-access article in Pregnancy
Hypertension.3
Important changes affect all aspects of care covered in the
2008 guidelines. Notable examples include the addition of
systolic BP in the definition of pregnancy hypertension,
revised HDP classification, new information on
prevention, more direction with respect to timing of
delivery in women with any HDP, information about
magnesium sulphate for fetal neuroprotection at < 32
weeks, a new gestational age cut-off (≤ 34+6 instead of
≤ 33+6 weeks) for administration of steroids, and a
section on knowledge translation with links to useful
tools for women and practitioners.
CHAPTER 1:
DIAGNOSIS OF HDP AND CLASSIFICATION
OF BP MEASUREMENTS
BP Measurement
Recommendations
  1. Blood pressure should be measured with the
woman in the sitting position with the arm at the
level of the heart. (II-2A)
  2. An appropriately sized cuff (i.e., length
1.5 times the circumference of the arm) should
be used. (II-2A)
  3. Korotkoff phase V should be used to designate
diastolic blood pressure. (I-A)
  4. If blood pressure is consistently higher in one arm,
the arm with the higher values should be used for
all blood pressure measurements. (III-B)
  5. Blood pressure can be measured using a mercury
sphygmomanometer, a calibrated aneroid device, or
an automated blood pressure machine that has been
validated for use in preeclampsia. (II-2A)
  6. Automated blood pressure machines that have
not been validated for use in women with
preeclampsia may underestimate or overestimate
blood pressure in those women; a comparison of
readings using mercury sphygmomanometry or a
calibrated aneroid device is recommended. (II-2A)
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
  7. In the office setting, when blood pressure elevation
is non-severe and preeclampsia is not suspected,
ambulatory blood pressure monitoring or home
blood pressure monitoring is useful to confirm
persistently elevated blood pressure. (II-2C)
  8. When home blood pressure monitoring is used,
maternity care providers should ensure that patients
have adequate training in measuring their blood
pressure and interpreting the readings. (III-C)
  9. The accuracy of all blood pressure measurement
devices used in hospitals or offices should be
checked regularly against a calibrated device. (II-3C)
10. The accuracy of all automated devices used
for home blood pressure monitoring should be
checked regularly against a calibrated device. (III-C)
Diagnosis of Hypertension
Recommendations
11. The diagnosis of hypertension should be based
on office or in-hospital blood pressure
measurements. (II-B)
12. Hypertension in pregnancy should be defined as an
office (or in-hospital) systolic blood pressure
≥ 140 mmHg and/or diastolic blood pressure
≥ 90 mmHg, based on the average of at least 2
measurements, taken at least 15 minutes apart, using
the same arm. (II-2B)
13. Resistant hypertension should be defined as the
need for 3 antihypertensive medications for blood
pressure control at ≥ 20 weeks’ gestation. (III-C)
14. A transient hypertensive effect should be defined as
an office systolic blood pressure ≥ 140 mmHg or
a diastolic blood pressure ≥ 90 mmHg that is not
confirmed after rest, on repeat measurement, on the
same or on subsequent visits. (II-2B)
15. A white-coat hypertensive effect refers to blood
pressure that is elevated in the office (i.e., systolic
≥ 140 mmHg or diastolic ≥ 90 mmHg), but
< 135 mmHg (systolic) and < 85 mmHg
(diastolic) on ambulatory or home blood pressure
monitoring. (II-2B)
16. A masked hypertensive effect refers to blood
pressure that is normal in the office (i.e., systolic
< 140 mmHg and diastolic < 90 mmHg) but
elevated on ambulatory or home blood pressure
monitoring (i.e., systolic ≥ 135 mmHg or diastolic
≥ 85 mmHg). (II-2B)
17. Severe hypertension should be defined, in any
setting, as a systolic blood pressure of ≥ 160 mmHg
or a diastolic blood pressure of ≥ 110 mmHg based
on the average of at least 2 measurements, taken at
least 15 minutes apart, using the same arm. (II-2B)
Measurement of Proteinuria
Recommendations
18. All pregnant women should be assessed for
proteinuria. (II-2B)
19. Urinary dipstick testing (by visual or automated
testing) may be used for screening for proteinuria
when the suspicion of preeclampsia is low. (II-2B)
20. Significant proteinuria should be defined as
≥ 0.3 g/d in a complete 24-hour urine collection
or ≥ 30 mg/mmol urinary creatinine in a spot
(random) urine sample. (II-2B)
21. Significant proteinuria should be suspected when
urinary dipstick proteinuria is ≥ 1+. (II-2A)
22. More definitive testing for proteinuria (by urinary
protein:creatinine ratio or 24-hour urine collection)
is encouraged when there is a suspicion of
preeclampsia, including: ≥ 1+ dipstick proteinuria
in women with hypertension and risingblood
pressure and in women withnormal blood
pressure, but symptoms or signs suggestive of
preeclampsia. (II-2A)
23. Proteinuria testing does not need to be repeated
once significant proteinuria of preeclampsia has
been confirmed. (II-2A)
24. There is insufficient information to make a
recommendation about the accuracy of the urinary
albumin:creatinine ratio. (II-2L)
Classification of HDPs
Recommendations
25. Hypertensive disorders of pregnancy should be
classified as pre-existing hypertension, gestational
hypertension, preeclampsia, or “other hypertensive
effects” on the basis of different diagnostic and
therapeutic considerations. (II-2B) (Table 2)
26. The presence or absence of preeclampsia must be
ascertained, given its clear association with more
adverse maternal and perinatal outcomes. (II-2B)
27. In women with pre-existing hypertension,
preeclampsia should be defined as resistant
hypertension, new or worsening proteinuria, one
or more adverse conditions, or one or more severe
complications. (II-2B)
28. In women with gestational hypertension,
preeclampsia should be defined as new-onset
proteinuria, one or more adverse conditions, or one
or more severe complications. (II-2B)
29. Severe preeclampsia should be defined as
preeclampsia complicated by one or more severe
complications. (II-2B)
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SOGC CLINICAL PRACTICE GUIDELINE

Table 2. Classification of the hypertensive disorders of pregnancy

Disorder
Pre-existing (chronic) hypertension
With comorbid condition(s)
With evidence of preeclampsia
Gestational hypertension
With comorbid condition(s)
With evidence of preeclampsia
Preeclampsia
Other hypertensive effects†
Transient hypertensive effect
White-coat hypertensive effect
Masked hypertensive effect
sBP: systolic BP; dBP diastolic BP; ABPM: ambulatory BP monitoring; HBPM: home BP monitoring
*Adverse conditions and severe complications of preeclampsia are defined in Table 3.
†These may occur in women whose BP is elevated at < 20+0 or ≥ 20+0 weeks who are suspected of having pre-existing or gestational hypertension/
preeclampsia, respectively.
Comments
This is defined as hypertension that develops either pre-pregnancy or at < 20+0 weeks' gestation
Comorbid conditions (e.g., pre-gestational type I or II diabetes mellitus or kidney disease)
warrant tighter BP control outside of pregnancy because of their association with heightened
cardiovascular risk.
This is also known as superimposed preeclampsia, and is defined by the development of one or
more of the following at ≥ 20 weeks:
●  resistant hypertension, or
●  new or worsening proteinuria, or
●  one or more adverse conditions,* or
●  one or more severe complications.*
Severe preeclampsia is defined as preeclampsia with one or more severe complications.
This is defined as hypertension that develops for the first time at ≥ 20+0 weeks' gestation.
Comorbid conditions (e.g., pre-gestational type I or II diabetes mellitus or kidney disease)
warrant tighter BP control outside of pregnancy because of their association with heightened
cardiovascular risk.
Evidence of preeclampsia may appear only many weeks after the onset of gestational
hypertension.
Preeclampsia is defined as gestational hypertension with one or more of the following:
●  new proteinuria, or
●  one or more adverse conditions,* or
●  one or more severe complications.*
Severe preeclampsia is defined as preeclampsia with one or more severe complications.
Preeclampsia may arise de novo. It is defined as gestational hypertension with one or more of the
following:
●  new proteinuria, or
●  one or more adverse conditions,* or
●  one or more severe complications.*
Severe preeclampsia is defined as preeclampsia with one or more severe complications.
Elevated BP may be due to environmental stimuli, e.g., the pain of labour.
This is defined as BP that is elevated in the office (sBP ≥ 140 mmHg or dBP ≥ 90 mmHg), but
consistently normal outside of the office (< 135/85 mmHg) by ABPM or HBPM
This is defined as BP that is consistently normal in the office (sBP < 140 mmHg or dBP
< 90 mmHg), but elevated outside of the office (≥ 135/85 mmHg) by ABPM or repeated HBPM.

30. Severe preeclampsia, as defined in this guideline,
warrants delivery. (II-2B)
31. The term PIH (pregnancy-induced hypertension)
should be abandoned, as its meaning in clinical
practice is unclear. (III-D)
Definition of Preeclampsia
Preeclampsia is most commonly defined by new-onset
proteinuria and, potentially, other end-organ dysfunction.
Hypertension and proteinuria are discussed above under
“Diagnosis of Hypertension”’ and “Management of
Proteinuria.” Women with preeclampsia may have a
diminished, or no, nocturnal BP decrease.4 Maternal
end-organ dysfunction and fetal manifestations of
preeclampsia illustrated in the Figure are all non-specific.
In this model of its origins we describe preeclampsia that
arises primarily through imperfect placentation (early-
onset or “placental” preeclampsia [pink]) or through either
a lowered maternal threshold or excessive physiological
placentation (late-onset or “maternal” preeclampsia
[blue]). Some aspects of the preeclampsia process are
specific to it, while others are shared with normotensive
IUGR. A lowered maternal threshold may also influence
the development of early-onset preeclampsia through

420 l MAY JOGC MAI 2014

 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

The origins and consequences of preeclampsia

immunological factors decidual immune cell - normal placentation

antigen exposure EVT interactions (late-onset pre-eclampsia)
• primigravidity ( ) / primipaternity ( ) •macrosomia
• donor gamete(s) ( ) (invasion & uteroplacental •multiple pregnancy
• duration of cohabitation ( ) artery remodelling) •± lowered threshold
• barrier contraception ( ) / fellatio ( )
• prior miscarriage ( )
• smoking ( )
inadequate placentation
(early-onset pre-eclampsia)
genetic factors
• familial risks
• SNPs uteroplacental mismatch
• epigenetics
placental IUGR
intervillous soup (± maternal syndrome)
lowered threshold pre-eclampsia-specific shared with IUGR
• metabolic syndrome •placental debris •angiogenic imbalance
• chronic infection / inflammation •innate immune activation
• pre-existing hypertension •oxidative stress
• chronic kidney disease / DbM •eicosanoids
• high altitude •cytokines

endothelial cell activation

cardiorespiratory CNS renal hepatic haematological

•hypertension •eclampsia •glomerular endotheliosis •periportal inflammation •microangiopathic haemolysis
•ARDS •TIA / RIND / CVA •proteinuria •hepatic dysfunction / failure •thrombocytopoenia
•pulmonary oedema •PRES •ATN •hepatic haematoma / rupture •DIC
•cardiomyopathy / LV dysfunction •GCS<13 •AKI
•intravascular volume constriction
•generalised oedema

maternal syndrome
EVT: extravillous trophoblast; SNP: single nucleotide polymorphism; ARDS: acute respiratory distress syndrome; CNS: central nervous system;
TIA: transient ischemic attack; RIND: reversible ischemic neurological deficit; CVA: cerebrovascular accident; PRES: posterior reversible
encephalopathy syndrome; GCS: Glasgow Coma Scale; ATN: acute tubular necrosis; AKI: acute kidney injury; DIC: disseminated intravascular
coagulation; DbM: diabetes mellitus; LV: left ventricle

direct endothelial cell activation. The consequences of
endothelial cell activation that appear consistent between
all women with preeclampsia include a variable impact
on multiple vulnerable organ systems. Disease severity
generally correlates with the degree and number of organ
dysfunctions. Fetal manifestations may occur before, with,
or in the absence of maternal manifestations.5
Table 3 outlines the end-organ dysfunctions
of preeclampsia: adverse conditions and severe
complications. Adverse conditions consist of maternal
symptoms, signs, and abnormal laboratory results, and
abnormal fetal monitoring results that may herald the
development of severe maternal or fetal complications
(including stillbirth). The adverse conditions are those that
we wait for and respond to (e.g., low oxygen saturation)
in an effort to avoid entirely the severe complications
(e.g., pulmonary edema). That response could be
more intensive maternal or fetal monitoring, specific
treatment, or delivery. Severe maternal complications of
preeclampsia warrant delivery.
The adverse conditions are manifestations of preeclampsia that
increase the risk of adverse maternal or perinatal outcomes.6
Table 3 lists the adverse conditions by maternal organ
system. Of particular importance are preterm preeclampsia,
chest pain or dyspnea, and abnormality of one or more of
oxygen saturation by pulse oximetry, platelet count, serum
creatinine, or aspartate transaminase.6 Proteinuria predicts
neither short-term adverse outcomes nor long-term maternal
renal prognosis.7,8 HELLP syndrome is represented by its
component parts (hemolysis, elevated liver enzymes, and low
platelets), to which we react to by initiating delivery.
How maternal adverse conditions may predict fetal or
neonatal outcomes in preeclampsia is unclear. The perinatal
literature suggests that abnormal fetal monitoring of various
types may identify increased fetal risk. The biophysical
profile has unproven utility in high risk women,9,10 and may
falsely reassure with early-onset IUGR11 or preeclampsia.12
Currently, there is no single fetal monitoring test to
accurately predict fetal compromise in women with

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SOGC CLINICAL PRACTICE GUIDELINE

Table 3. Adverse conditions and severe complications of preeclampsia

Adverse conditions Severe complications
Organ system affected (that increase the risk of severe complications) (that warrant delivery)
Central nervous system Headache/visual symptoms Eclampsia
PRES
Cortical blindness or retinal detachment
Glasgow coma scale < 13
Stroke, TIA, or RIND
Cardiorespiratory Chest pain/dyspnea Uncontrolled severe hypertension (over a period of 12 h
Oxygen saturation < 97% despite use of three antihypertensive agents)
Oxygen saturation < 90%, need for ≥ 50% oxygen for
> 1 h, intubation (other than for Caesarean section),
pulmonary edema
Positive inotropic support
Myocardial ischemia or infarction
Haematological Elevated WBC count Platelet count < 50 × 109/L
Elevated INR or aPTT Transfusion of any blood product
Low platelet count
Renal Elevated serum creatinine Acute kidney injury (creatinine > 150 µM with no prior
Elevated serum uric acid renal disease)
New indication for dialysis
Hepatic Nausea or vomiting Hepatic dysfunction (INR > 2 in absence of DIC or
RUQ or epigastric pain warfarin)
Elevated serum AST, ALT, LDH, or bilirubin Hepatic haematoma or rupture
Low plasma albumin
Feto-placental Abnormal FHR Abruption with evidence of maternal or fetal compromise
IUGR Reverse ductus venosus A wave
Oligohydramnios Stillbirth
Absent or reversed end-diastolic flow by Doppler
velocimetry
PRES: posterior reversible leukoencephalopathy syndrome; TIA: transient ischemic attack; RIND: reversible ischemic neurological deficit (< 48 hr);
WBC: white blood cell; INR: international normalized ratio; aPTT: activated partial thromboplastin time; RUQ: right upper quadrant; AST: aspartate
aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; DIC: disseminated intravascular coagulation; FHR: fetal heart rate.

preeclampsia. Most experts suggest a combination of tests, Other

with emphasis on umbilical artery Doppler when there is
IUGR.9
Other non-specific risk factors for severe complications
of preeclampsia are immigrant status, young maternal
age, nulliparity, lower maternal weight, and in the
index pregnancy, multiple pregnancy and early-onset
preeclampsia.13
Definitions of severe preeclampsia vary, but most include
multi-organ involvement14–16 We modified our definition
of severe preeclampsia to preeclampsia associated with
one or more severe complications. Severe preeclampsia
now warrants delivery regardless of gestational age.
Our definition excludes heavy proteinuria and HELLP
syndrome, which are not absolute indications for delivery,
and includes stroke17 and pulmonary edema, which are
leading causes of maternal death in preeclampsia.2
A transient hypertensive effect is not associated with an
increased risk of adverse outcomes. White-coat effect in
early pregnancy (~30%) is common.18 Forty percent of
women progress to persistent hypertension at ≥ 20 weeks
(i.e., gestational hypertension) and 8% to preeclampsia.
Women with white-coat effect have risks (e.g., severe
hypertension, preterm delivery, and NICU admission)
intermediate between normotension and either pre-
existing or gestational hypertension.19–24
Masked hypertension in early pregnancy (~30%) is also
common,18 but associated perinatal risks are unknown.
Outcomes with masked hypertension at ≥ 20 weeks (~10%)
equate to those of gestational hypertension.25,26 Masked
hypertension could be considered (and ambulatory or
home BP monitoring performed) if there are unexplained
maternal or perinatal complications typically associated
with the HDPs.

422 l MAY JOGC MAI 2014

 Table 4. Investigations to diagnosis or monitor women with a hypertensive disorder of pregnancy
Investigations for diagnosis Description in women with preeclampsia Description in women with other conditions
MATERNAL TESTING
Urine testing
Urinalysis (routine and Proteinuria without RBCs or casts Hemoglobinuria (dipstick “hematuria” without RBCs): hemolytic anemia
microscopy with/ RBCs alone: renal stones, renal cortical necrosis (also associated with back pain and oliguria/anuria)
without additional
RBCs and/or casts are associated with other glomerular disease, with scleroderma renal crisis. and with
tests for proteinuria)
about half of TTP-HUS
Bacteria: UTI or asymptomatic bacteruria
Proteinuria is usually absent in secondary causes of hypertension such as pheochromocytoma,
hyperaldosteronism, thyrotoxicosis, coarctation of the aorta, and withdrawal syndromes
Oxygen saturation
Pulse oximetry SpO2 < 97% associated with a heightened risk of May be decreased in any cardiorespiratory complication (e.g., pulmonary embolism)
severe complications (including non-respiratory)
CBC and blood film
Hemoglobin ↑ due to intravascular volume depletion ↑ due to volume depletion from any cause (e.g., vomiting)
↓ if microangiopathic hemolysis (with HELLP) ↓ if microangiopathic hemolysis from other cause
↓ with any chronic anemia (nutritional or myelodysplasia)
↓ with acute bleeding of any cause
WBC and differential ↔ ↑ due to neutrophilia of normal pregnancy
↑ with inflammation/infection
↑ with corticosteroids
Platelet count ↓ associated with adverse maternal outcome) ↓ with gestational, immune, or thrombotic thrombocytopenia, APS, AFLP, myelodysplasia
Blood film RBC fragmentation Microangiopathy due to mechanical causes (e.g., cardiac valvopathy, cavernous haemangioma), DIC or
other disorders of endothelial function (e.g., APS, TTP-HUS, vasculitis, malignant hypertension)
Tests of coagulation*
INR and aPTT ↑ with DIC, which is usually associated with May be ↑ in APS or in DIC from other causes including sepsis, amniotic fluid embolism, stillbirth,
placental abruption massive haemorrhage, haemangiomas, or shock
↑ is associated with adverse maternal outcome ↑ is prominent in AFLP
Fibrinogen ↔↓ ↓ with all causes of DIC including massive haemorrhage, genetic disorders
↓ more profound with AFLP than with HELLP
Usually normal in TTP-HUS (ADAMTS13 vWF cleaving protein may be moderately decreased in HELLP,
but ADAMTS13 antibody should be absent)

Continued

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Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
 Table 4. Continued
Investigations for diagnosis Description in women with preeclampsia Description in women with other conditions
Serum chemistry
Serum creatinine ↑ due to hemoconcentration and/or renal failure ↑ with other acute or chronic kidney disease
↑ associated with adverse maternal outcome Renal failure prominent in malignant hypertension, TTP-HUS (along with thrombocytopenia), AFLP
(along with liver dysfunction)

424 l MAY JOGC MAI 2014

Serum uric acid ↑ associated with adverse maternal outcome ↑ with dehydration, medication (e.g., HCTZ), genetic causes
Glucose ↔ ↓ with AFLP, insulin therapy
AST or ALT ↑ associated with adverse maternal outcome ↑ with AFLP and other PET imitators,† but to a lesser degree, and usually normal in TTP-HUS
SOGC CLINICAL PRACTICE GUIDELINE

May be increased in other pregnancy-related conditions (e.g., intrahepatic cholestasis of pregnancy) or

conditions not associated with pregnancy (e.g., viral hepatitis or cholecystitis)
LDH ↑ may be prominent; the ↑ is associated with ↑ with AFLP, intravascular hemolysis
adverse maternal outcome ↑ LDH/AST ratio (> 22) with TTP-HUS
Bilirubin ↑ unconjugated from hemolysis or conjugated (early) ↑ in AFLP, ↑ with hemolytic anemia, other liver disease with dysfunction, genetic diseases
from liver dysfunction
Albumin ↓ associated with adverse maternal and perinatal ↓ as negative acute phase reactant with acute severe illness, malnutrition, nephritic syndrome,
outcomes crystalloid infusion

FETAL TESTING Abnormalities are not specific to the cause of poor placentation and/or placental dysfunction
Uterine artery Doppler Unilateral/bilateral notching, or elevated pulsatility index or resistance index may support a diagnosis of placental insufficiency including preeclampsia
velocimetry‡
Fetal monitoring Abnormal or atypical FHR tracing (e.g., decreased variability)
Deepest amniotic fluid Oligohydramnios associated with adverse perinatal outcomes
pocket
Ultrasonographic Usually intrauterine fetal growth restriction (typically asymmetrical but can be symmetrical if early and/or severe)
assessment of fetal growth
Umbilical artery Doppler Increased resistance, absent or reversed end-diastolic flow
Ductus venosus Doppler Increased resistance, especially absent or reverse A wave
Middle cerebral artery Cerebral redistribution (decreased resistance or “brain-sparing effect”). May be lost in extreme cases prior to fetal death
Doppler
RBC: red blood cell; TTP-HUS: thrombotic thrombocytopenic purpur–hemolytic uremic syndrome; UTI: urinary tract infection; SpO2: oxygen saturation; CBC: complete blood count; HELLP: hemolysis, elevated liver
enzyme, low platelet syndrome; WBC: white blood cell; APS: antiphopholipid antibody syndrome; AFLP: acute fatty liver of pregnancy; DIC: disseminated intravascular coagulation; INR international normalized
ratio; aPTT: activated partial thromboplastin time; vWF: von Willebrand Factor; HCTZ: hydrochlorothiazide; AST: aspartate aminotransferase; ALT: alanine aminotransferase; PET: preeclampsia-eclampsia;
LDH: lactate dehydrogenase; FHR: fetal heart rate
*Tests of coagulation are recommended if there is thrombocytopenia or placental abruption.
†“PET imitators” include AFLP, catastrophic APS, TTP-HUS, malignant hypertension, and scleroderma renal crisis.
‡Abnormal uterine artery Doppler velocimetry is practically defined at 22 to 24 weeks as bilateral notching with mean resistance index (RI) > 0.55 (i.e., > 50th centile), unilateral notching with mean RI > 0.65
(> 90th centile), or no notching with mean RI > 0.70 (> 95th centile).
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
Investigations to Classify HDPs
Recommendations
32. For women with pre-existing hypertension, the
following should be performed in early pregnancy
(if not previously documented): serum creatinine,
fasting blood glucose, serum potassium, and
urinalysis (III-D), and EKG. (II-2C)
33. Among women with pre-existing hypertension
or those with a strong clinical risk marker for
preeclampsia, additional baseline laboratory testing
may be based on other considerations deemed
important by health care providers. (III-C)
34. Women with suspected preeclampsia should
undergo the maternal laboratory (II-2B) and
pertinent fetal (II-1B) testing. (Table 4)
35. Doppler velocimetry-based assessment of the fetal
circulation may be useful to support a placental
origin for hypertension, proteinuria, and/or adverse
conditions including intrauterine growth restriction,
(II-2B) and for the timing of delivery. (I-A)
36. There is insufficient evidence to recommend use of
the biophysical profile as part of a schedule of fetal
testing in women with a hypertensive disorder of
pregnancy. (II-2L)
37. If initial testing is reassuring, but there is ongoing
concern about preeclampsia (e.g., change in
maternal and/or fetal condition), maternal and fetal
testing should be repeated. (III-C)
Comments
Most abnormalities found in maternal and fetal testing are
non-specific. When preeclampsia is suspected, interpretation
relies on findings of multiple (not single) abnormalities.
Preeclampsia imitators share manifestations with pre-
eclampsia, but require different treatment.27–31 (Table 5)
CHAPTER 2:
PREDICTION AND PREVENTION
Predicting Preeclampsia
Recommendations
38. Women should be screened for clinical risk markers
of preeclampsia from early pregnancy. (II-2C)
(Table 6)
39. Consultation with an obstetrician or an obstetric inter­
nist, by telephone if necessary, should be con­sidered
for women with a history of previous preeclampsia
or another strong clinical marker of increased
preeclampsia risk, particularly multiple pregnancy,
antiphospholipid antibody syndrome, significant
proteinuria at first antenatal visit (usually early in
pregnancy), or a pre-existing condition of hyper­
tension, diabetes mellitus, or renal disease. (II-2B)
40. Screening using biomarkers or Doppler ultrasound
velocimetry of the uteroplacental circulation cannot
be recommended routinely at present for women
at low or increased risk of preeclampsia until such
screening has been shown to improve pregnancy
outcome. (II-2C)
Preventing Preeclampsia and its
Complications in Women at Low Risk
We based our recommendations on the need to prevent
preeclampsia and/or its associated complications. Pregnant
women are classified as being at either low or increased risk
of preeclampsia, usually by the presence of one or more of
the risk markers in Table 6 (see Predicting Preeclampsia).
Preventative interventions may be best started before 16 weeks’
gestation when most of the physiologic transformation of
uterine spiral arteries occurs. Such early intervention has the
greatest potential to decrease early forms of preeclampsia.32
Women at low risk of preeclampsia have usually been from
unselected populations of nulliparous and multiparous
women.
Recommendations
41. Calcium supplementation of at least 1 g/d, orally,
is recommended for women with low dietary intake
of calcium (< 600 mg/d). (I-A)
42. The following are recommended for other
established beneficial effects in pregnancy: abstention
from alcohol for prevention of fetal alcohol
effects (II-2E), exercise for maintenance of fitness
(I-A), periconceptual use of a folate-containing
multivitamin for prevention of neural tube defects
(I-A), and smoking cessation for prevention of low
birthweight and preterm birth. (I-E)
43. Periconceptual and ongoing use of a folate-
containing multivitamin (I-B) or exercise (II-2B)
may be useful in preventing preeclampsia.
44. Prostaglandin precursors and supplementation
with magnesium or zinc are not recommended for
preeclampsia prevention, but may be useful for
prevention of other pregnancy complications. (I-C)
45. Dietary salt restriction during pregnancy (I-D),
calorie restriction during pregnancy for overweight
women (I-D), low-dose acetylsalicylic acid (I-E),
vitamins C and E (based on current evidence)
(I-E), and thiazide diuretics (I-E) are not
recommended.
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Table 5. Preeclampsia imitators

Pregnancy related
Preeclampsia/HELLP syndrome
Acute fatty liver of pregnancy
Not pregnancy related
Malignant hypertension regardless of the cause
Secondary causes of hypertension when associated with end-organ involvement
(e.g., renal disease, pheochromocytoma)
Disseminated intravascular coagulation (from any cause)
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Vasculitis or other systemic rheumatic condition (systemic lupus erythematous,
scleroderma, cryoglobulinemia, catastrophic antiphospholipids syndrome)
Sepsis
Medications
Cavernous hemangiomas
Malignancy

46. There is insufficient evidence to make a
recommendation about a heart-healthy diet (II-2L);
workload or stress reduction (including bedrest)
(II-2L); supplementation with iron with or without
folate (I-L); vitamin D (I-L); pyridoxine (I-L); or
food rich in flavonoids. (I-L)
Preventing Preeclampsia and its
Complications in Women at Increased Risk
Women at increased risk of preeclampsia are most
commonly identified by a personal or family history of an
HDP, chronic medical disease, and/or abnormal uterine
artery Doppler before 24 weeks’ gestation. Combining
clinical, biochemical, and/or ultrasonographic risk markers
may better identify women at increased preeclampsia risk
(see “Prediction”); however, no intervention trial has used
such an approach to evaluate preventative therapy.33,34
Recommendations
47. Low-dose acetylsalicylic acid and calcium
supplementation (of at least 1 g/d) for women with
low calcium intake are recommended for preventions
of preeclampsia in women at high risk. (I-A)
48. Acetylsalicylic acid should be: taken in a low dose
(75–162 mg/d), (III-B) administered at bedtime,
(I-B) initiated after diagnosis of pregnancy but
before 16 weeks’ gestation, (I-B) and considered for
continuation until delivery. (I-C)
49. Prophylactic doses of low-molecular-weight
heparin may be discussed in women with previous
placental complications (including preeclampsia)
to prevent the recurrence of severe or early-onset
preeclampsia, preterm delivery, and/or infants that
are small for gestational age. (I-B)
50. The following may be useful: L-arginine (I-B),
increased rest at home in the third trimester (I-C),
and reduction of workload or stress. (III-C)
51. The following may be useful for prevention of other
pregnancy complications: prostaglandin precursors
(I-B), magnesium supplementation (I-C), and heparin
to prevent venous thromboembolic disease. (I-B)
52. The following are recommended for other
established beneficial effects in pregnancy (as
discussed for women at low risk of preeclampsia):
abstention from alcohol (II-2E), periconceptual
use of a folate-containing multivitamin (I-A), and
smoking cessation. (I-E)
53. The following are not recommended: calorie
restriction in overweight women during pregnancy
(I-D), weight maintenance in obese women during
pregnancy (III-D), antihypertensive therapy
specifically to prevent preeclampsia (I-D), and
vitamins C and E. (I-E)
54. There is insufficient evidence to make a
recommendation about the usefulness of the
following: the heart-healthy diet (III-L); exercise
(I-L); selenium (I-L); garlic (I-L); zinc, pyridoxine,
iron (with or without folate), vitamin D, or
multivitamins with/without micronutrients. (III-L)
CHAPTER 3:
TREATMENT OF THE HDPs
Dietary and Lifestyle Changes
Recommendations
55. There is insufficient evidence to make a
recommendation about the usefulness of the
following: new severe dietary salt restriction for

426 l MAY JOGC MAI 2014

 Table 6. Risk markers for preeclampsia
Current pregnancy
Demographics and family history Past medical or obstetric history* First trimester Second or third trimester
Previous preeclampsia Multiple pregnancy
Anti-phospholipid antibody syndrome
Pre-existing medical condition(s)
•  Pre-existing hypertension or booking†
•  diastolic BP ≥ 90 mmHg
•  Pre-existing renal disease or booking†
•  proteinuria
•  Pre-existing diabetes mellitus

Maternal age ≥ 40 years‡ Lower maternal birthweight and/or Overweight/obesity Elevated BP (gestational hypertension)¶
Family history of preeclampsia preterm delivery First ongoing pregnancy Abnormal AFP, hCG, inhA, or E3#
(mother or sister) Heritable thrombophilias§ New partner Excessive weight gain in pregnancy
Family history of early-onset cardiovascular Increased pre-pregnancy triglycerides Short duration of sexual relationship Infection during pregnancy
disease Non-smoking with current partner (e.g., UTI, periodontal disease)
Cocaine and metamphetamine use Reproductive technologies‖ Abnormal uterine artery Doppler**
Previous miscarriage at ≤ 10 weeks Inter-pregnancy interval ≥ 10 years IUGR
with same partner Booking† sBP ≥ 130 mmHg, or booking Investigational laboratory markers††
dBP ≥ 80 mmHg
Vaginal bleeding in early pregnancy
Gestational trophoblastic disease
Abnormal PAPP-A or free βhCG
AFP: alfafetoprotein; inhA: inhibin A; E3: estradiol; UTI: urinary tract infection; sBP: systolic BP; dBP: diastolic BP; PAPP-A: pregnancy-associated plasma protein A.
*Women at increased risk (who should be considered for specialty referral) are those with one of the bolded factors, or two or more of the unbolded markers.
†First antenatal visit, usually early in pregnancy.
‡Maternal age was considered as a continuous variable in the SCOPE study.
§Heritable thrombophilia includes factor V Leiden gene mutation and protein S deficiency.
‖Subfertility and its treatment (especially the use of donor eggs, sperm and/or gametes), after correction for multiple gestations.
¶Elevated BP is defined as dBP ≥ 110 mmHg before 20 weeks, 2nd trimester mean arterial pressure of ≥ 85 mmHg, or a 2nd trimester sBP ≥ 120 mmHg. standardized cut-offs for 24-hour ambulatory BP or home BP
monitoring have not been established.
#Decreased first trimester PAPP-A ≤ 5th centile, 110 decreased first or second trimester placental growth factor, unexplained increased second trimester AFP, increased second trimester hCG, increased first or second
trimester inhA, increased second trimester activin.
**Abnormal uterine artery Doppler velocimetry is practically defined at 22 to 24 weeks as bilateral notching with mean resistance index (RI) > 0.55 (i.e., > 50th centile), unilateral notching with mean RI > 0.65 (> 90th
centile), or no notching with mean RI > 0.70 (> 95th centile).
††Investigational markers include, in the first trimester: PAPP-A, PlGF, PP-13, and in the second trimester: elevated sFlt-1/PlGF (soluble fms-like tyrosine kinase, placental growth factor), PAI-1/PAI-2 (plasminogen
activator inhibitor) von Willebrand factor, and leptin.

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Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
SOGC CLINICAL PRACTICE GUIDELINE
Table 7. The most commonly used agents for treatment of blood pressure ≥ 160/110 mmHg
Agent Dosage
Labetalol Start with 20 mg IV; repeat 20 to
80 mg IV q 30 min, or 1 to 2 mg/min,
max 300 mg (then switch to oral)
Nifedipine 5 to 10 mg capsule to be swallowed,
or bitten then swallowed, every 30
min
Hydralazine Start with 5 mg IV; repeat 5 to
10 mg IV every 30 min, or 0.5 to
10 mg/hr IV, to a maximum of
20 mg IV (or 30 mg IM)
IV: intravenous; IM: intramuscular; PA: prolonged action; XL: slow release
women with any HDP, ongoing salt restriction
among women with pre-existing hypertension,
heart-healthy diet, and calorie restriction for obese
women. (III-L)
56. There is insufficient evidence to make a
recommendation about the usefulness of exercise,
workload reduction, or stress reduction. (III-L)
57. For women with gestational hypertension
(without preeclampsia), some bed rest in hospital
(vs. unrestricted activity at home) may be useful
to decrease severe hypertension and preterm
birth. (I-B)
58. For women with preeclampsia who are hospitalized,
strict bed rest is not recommended. (I-D)
59. For all other women with an HDP, the evidence
is insufficient to make a recommendation
about the usefulness of some bed rest, which
may nevertheless be advised based on practical
considerations. (III-C)
The following recommendations apply to women with
either pre-existing or gestational hypertension.
Place of Care
Recommendations
60. In-patient care should be provided for women with
severe hypertension or severe preeclampsia. (II-2B).
61. A component of care through hospital day units or
home care can be considered for women with non-
severe preeclampsia or non-severe pre-existing or
gestational hypertension. (I-B, II-2B)
428 l MAY JOGC MAI 2014
Onset Peak Duration Comments
5 min 30 min 4 hr Best avoided in women with asthma
or heart failure. Neonatology should
be informed if the woman is in labour,
as parenteral labetalol may cause
neonatal bradycardia.
5 to 10 min 30 min ~6 hr Staff should be aware of the
distinction between short-acting
nifedipine capsules used to treat
severe hypertension and both the
intermediate-acting PA tablet (which
can be used for treatment of non-
severe or severe hypertension), and
the slow-release tablets (XL) that are
used for non-severe hypertension.
5 min 30 min May increase the risk of maternal
hypotension.
Antihypertensive Therapy for Severe Hypertension
Recommendations
62. Blood pressure should be lowered to
< 160 mmHg systolic and < 110 mmHg
diastolic. (I-A)
63. Initial antihypertensive therapy in the hospital
setting should be with nifedipine short-acting
capsules, parenteral hydralazine, or parenteral
labetalol. (I-A) (Table 7)
64. Alternative antihypertensive medications include
a nitroglycerin infusion (I-B), oral methyldopa
(I-B), oral labetalol (I-B), oral clonidine (III-B), or
postpartum, oral captopril. (III-B)
65. Refractory hypertension may be treated with
sodium nitroprusside. (III-B)
66. Nifedipine and magnesium sulphate can be used
contemporaneously. (II-2B)
67. Magnesium sulphate is not recommended solely as
an antihypertensive agent. (I-E)
68. Continuous fetal heart rate monitoring is advised
until blood pressure is stable. (III-L)
Antihypertensive Therapy for Non-Severe
Hypertension Without Comorbid Conditions
Recommendations
69. Antihypertensive drug therapy may be used to
keep systolic blood pressure at 130 to
155 mmHg and diastolic blood pressure at
80–105 mmHg. (I-B)
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
Table 8. Doses of the most commonly used agents for treatment of blood pressures 149 to 159/90 to 105 mmHg
Agent Dosage
Methyldopa 250 to 500 mg po bid-qid (max 2 g/d)
Labetalol 100 to 400 mg po bid-tid (max 1200 mg/d)
Nifedipine* XL preparation (20 to 60 mg po OD, max 120 mg/d)
XL: slow release
*The prolonged action nifedipine tablet is no longer available in Canada.
70. The choice of antihypertensive agent for initial
treatment should be based on characteristics of the
patient, contraindications to a particular drug, and
physician and patient preference. (III-C)
71. Initial therapy in pregnancy can be with one of
a variety of antihypertensive agents available in
Canada: methyldopa (I-A), labetalol (I-A), other
beta-blockers (acebutolol, metoprolol, pindolol, and
propranolol), (I-B) and calcium channel blockers
(nifedipine). (I-A) (Table 8)
72. Angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers should not be used
during pregnancy. (II-2E)
73. Atenolol and prazosin are not recommended prior
to delivery. (I-D)
For Non-Severe Hypertension (BP of 140–159/
90–109 mmHg) With Comorbid Conditions
Recommendations
74. For women with comorbid conditions,
antihypertensive drug therapy should be used to
keep systolic blood pressure at < 140 mmHg and
diastolic blood pressure at < 90 mmHg. (III-C)
75. Initial therapy in pregnancy can be with one of
a variety of antihypertensive agents as listed for
women without co-morbidities. (III-C)
76. Captopril, enalapril, or quinapril may be used
postpartum, even during breastfeeding. (III-B)
Corticosteroids for Acceleration of
Fetal Pulmonary Maturity
Recommendations
77. Antenatal corticosteroid therapy should be
considered for all women who present with
preeclampsia at ≤ 34+6 weeks’ gestation. (I-A)
78. Antenatal corticosteroid therapy should be considered
for women who present at ≤ 34+6 weeks’ gestation
with gestational hypertension (despite the absence of
Comments
There is no evidence to support a loading dose of methyldopa.
Some experts recommend a starting dose of 200 mg po bid.
Ensure that the correct form of nifedipine has been prescribed
so that the XL preparation is not confused with the capsules.
proteinuria or adverse conditions) only if delivery is
contemplated within the next 7 days. (III-L)
79. A rescue dose of corticosteroids may be considered
for women at ≤ 34+6 weeks’ gestation who remain
at high risk of preterm delivery 7 days or more after
an initial course of antenatal corticosteroids. (I-C)
80. Antenatal corticosteroids may be considered for
women delivered by elective Caesarean delivery
at ≤ 38+6 weeks’ gestation to reduce respiratory
morbidity. (I-B)
Comments
When administered at ≤ 34+6 weeks’ gestation, antenatal
corticosteroids accelerate fetal pulmonary maturity and
decrease neonatal mortality and morbidity, including among
women with HDPs.35 RCTs that administered steroids at
33+0 to 34+6 weeks resulted in reduced neonatal RDS.35
Prior to elective Caesarean section at ≤ 38+6 weeks’
gestation, antenatal corticosteroids decrease the excess
neonatal respiratory morbidity and NICU admissions.36,37
All subgroup analyses have not necessarily revealed such
benefits following Caesarean or vaginal delivery.35
Timing of Delivery for Women With Preeclampsia
Delivery is the only intervention that initiates resolution of
preeclampsia, and women with gestational hypertension or
pre-existing hypertension may develop preeclampsia.
Recommendations
81. Consultation with an obstetrician (by telephone
if necessary) is mandatory in women with severe
preeclampsia. (III-B)
82. All women with severe preeclampsia should be
delivered immediately (either vaginally or by
Caesarean), regardless of gestational age. (III-C)
83. For women with non-severe preeclampsia at < 24+0
weeks’ gestation, counselling should include, as an
option, information about delivery within days. (II-2B)
84. For women with non-severe preeclampsia at 24+0
to 33+6 weeks’ gestation, expectant management
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SOGC CLINICAL PRACTICE GUIDELINE
should be considered, but only in perinatal centres
capable of caring for very preterm infants. (I-B)
85. For women with non-severe preeclampsia at 34+0
to 36+6 weeks’ gestation, there is insufficient
evidence to make a recommendation about the
benefits or risks of expectant management. (III-L)
86. For women with preeclampsia at ≥ 37+0 weeks’
gestation, immediate delivery is recommended. (I-A)
87. For women with non-severe preeclampsia
complicated by hemolysis, elevated liver enzymes,
low platelets syndrome at 24+0 to 34+6 weeks’
gestation, consider delaying delivery long enough
to administer antenatal corticosteroids for
acceleration of fetal pulmonary maturity if there
is temporary improvement in maternal laboratory
testing. (II-2B)
88. All women with hemolysis, elevated liver enzymes,
low platelets syndrome at ≥ 35+0 weeks’
gestation should be considered for immediate
delivery. (II-2B)
Timing of Delivery for Women With
Gestational Hypertension
Recommendations
89. For women with gestational hypertension (without
preeclampsia) at ≥ 37+0 weeks’ gestation, delivery
within days should be discussed. (I-B)
90. For women with gestational hypertension (without
preeclampsia) at < 37+0 weeks’ gestation, there is
insufficient evidence to make a recommendation
about the benefits or risks of expectant
management. (III-L)
Timing of Delivery for Women With
Pre-Existing Hypertension
Recommendation
91. For women with uncomplicated pre-existing
hypertension who are otherwise well at ≥ 37+0
weeks’ gestation, delivery should be considered at
38+0 to 39+6 weeks’ gestation. (II-1B)
Mode of Delivery
Recommendations
92. For women with any hypertensive disorder of
pregnancy, vaginal delivery should be considered
unless a Caesarean delivery is required for the usual
obstetric indications. (II-2B)
430 l MAY JOGC MAI 2014
93. If vaginal delivery is planned and the cervix is
unfavourable, then cervical ripening should be
used to increase the chance of a successful vaginal
delivery. (1-A)
94. At a gestational age remote from term, women with
a hypertensive disorder of pregnancy with evidence
of fetal compromise may benefit from delivery by
emergency Caesarean section. (II-2B)
95. Antihypertensive treatment should be continued
throughout labour and delivery to maintain systolic
blood pressure at < 160 mmHg and diastolic blood
pressure at < 110 mmHg. (II-2B)
96. The third stage of labour should be actively
managed with oxytocin, 5 units intravenous or 10
units intramuscular, particularly in the presence of
thrombocytopenia or coagulopathy. (I-A)
97. Ergometrine maleate should not be administered
to women with any hypertensive disorder of
pregnancy, particularly preeclampsia or gestational
hypertension; alternative oxytocics should be
considered. (II-3D)
Anaesthesia: General Principles
Recommendations
  98. The anaesthesiologist should be informed when
a woman with preeclampsia is admitted to the
delivery suite. (II-3B)
  99. Early insertion of an epidural catheter (in the
absence of contraindications) is recommended for
control of labour pain. (I-A)
100. In the absence of contraindications, all of the
following are acceptable methods of anaesthesia
for women undergoing Caesarean delivery:
epidural, spinal, combined spinal-epidural, and
general anaesthesia. (I-A)
101. A routine fixed intravenous fluid bolus should not
be administered prior to neuraxialanaesthesia. (I-E)
Anaesthesia: Fluid Administration
Recommendations
102. Intravenous and oral fluid intake should be
minimized in women with preeclampsia, to avoid
pulmonary edema. (II-2B)
103. Fluid should not be routinely administered to
treat oliguria (< 15 mL/hr for 6 consecutive
hours). (III-D)
104. For treatment of persistent oliguria, neither
dopamine nor furosemide is recommended. (I-E)
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
105. Phenylephrine or ephedrine may be used to
prevent or treat hypotension during neuraxial
anaesthesia. (I-A)
Monitoring
Recommendations
106. Arterial line insertion may be used for continuous
arterial blood pressure monitoring when blood
pressure control is difficult or there is severe
bleeding. (II-3B)
107. Central venous pressure monitoring is not
routinely recommended, and if a central venous
catheter is inserted, it should be used to monitor
trends and not absolute values. (II-2D)
108. Pulmonary artery catheterization is not
recommended unless there is a specific associated
indication (III-D), and then only in an intensive
care unit setting. (III-B)
Coagulation
Recommendations
109. Upon admission to delivery suite, women with
preeclampsia should have a platelet count
done. (II-1A)
110. Neuraxial analgesia and/or anaesthesia are
appropriate in women:
a. with preeclampsia, provided there are no
associated coagulation concerns (II-2E)
(Table 9);
b. with a platelet count ≥ 75 × 109/L, (II-2B);
c. taking low-dose acetylsaliclylic acid in
the presence of an adequate platelet
count (I-A);
d. receiving unfractionated heparin in a dose
of ≤ 10 000 IU/d subcutaneously, 4 hours
after the last dose and possibly
immediately after the last dose without
any delay (III-B);
e. receiving unfractionated heparin in a dose
> 10 000 IU/d subcutaneously if they have
a normal activated partial thromboplastin time
4hours after the last dose (III-B);
f. receiving intravenous heparin in a therapeutic
dose if they have a normal activated partial
thromboplastin time 4 hours after the last
dose (III-B); or
g. receiving low-molecular-weight heparin 10 to
12 hours after a prophylactic dose, or 24 hours
after a therapeutic dose. (III-B)
Aspects of Care Specific to Women
With Pre-Existing Hypertension
Recommendations
111. Pre-conceptual counselling for women
with pre-existing hypertension is
recommended. (III-C)
112. The following antihypertensive drugs are all
acceptable for use in the first trimester of
pregnancy: methyldopa, labetalol, and
nifedipine. (II-2B)
113. Angiotensin-converting enzyme inhibitors
and angiotensin receptor blockers should be
discontinued when planning pregnancy or as soon
as pregnancy is diagnosed. (II-2D)
114. Atenolol should be discontinued when pregnancy
is diagnosed. (I-D)
115. Planned changes in antihypertensive agent(s)
for care in pregnancy should be made while
the woman is planning pregnancy if the woman
has uncomplicated pre-existing hypertension,
or, if in the presence of comorbid conditions,
she is likely to conceive easily (within 12
months). (III-L)
Aspects of Care for Women With Preeclampsia:
Magnesium Sulphate for Preventing or
Treating Eclampsia
Recommendations
116. Magnesium sulphate is recommended for first-line
treatment of eclampsia. (I-A)
117. Magnesium sulphate is recommended as
prophylaxis against eclampsia in women with
severe preeclampsia. (I-A)
118. Magnesium sulphate may be considered as
prophylaxis against eclampsia in women with
non-severe preeclampsia but with severe
hypertension, headaches/visual symptoms, right
upper quadrant/epigastric pain, platelet count
< 100 000 × 109/L, progressive renal insufficiency,
and/or elevated liver enzymes, based on cost
considerations. (I-C)
119. Magnesium sulphate should be used in standard
dosing, usually 4 g intravenous loading dose
followed by 1 g/hour. (I-A)
120. Routine monitoring of serum magnesium levels is
not recommended. (I-E)
121. Phenytoin and benzodiazepines should not be
used for eclampsia prophylaxis or treatment,
unless there is a contraindication to magnesium
sulphate or it is ineffective. (I-E)
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Table 9. Eligibility for neuraxial anaesthesia

Abnormal INR or
Treatment with ASA Low platelet count aPTT (regardless of
or heparin Normal platelet count (normal INR and aPTT) platelet count)*
None or low-dose ASA   if platelet count > 75 × 109/L
Unclear if platelet count 50 to 75 × 109/L
X if platelet count < 50 × 109/L
UFH
≤ 10 000 IU/d (SC)†  Unclear
0 to 4 hr after last dose
> 10 000 IU/d (SC)‡  Unclear

Contraindicated
4 hr after last dose and a
normal aPTT
Therapeutic dose (IV)  Unclear

X
4 hr after last dose and a
normal aPTT
LMWH
Prophylactic dose  Unclear
10 to 12 hr after last dose
Therapeutic dose  Unclear
24 hr after last dose
Low dose ASA + prophylactic UFH Unclear║ Unclear
or LMWH§
INR: international normalized ratio; aPTT: activated partial thromboplastin time; UFH: unfractionated heparin; SC: subcutaneous; IV: intravenous;
LMWH: low-molecular-weight heparin
Note: These recommendations are based on the absence of a rapidly falling platelet count or a known platelet dysfunction (e.g., von Willebrand’s disease).
*Other than a lupus anticoagulant
†Prophylactic dosing is defined as ≤ 10 000 IU/d
‡Therapeutic dosing (SC) is defined as > 10 000 IU/d
§Prophylactic doses of UFH are defined as ≤ 10 000 IU/d
║Unless ASA is stopped 7 days or more before delivery

122. In women with pre-existing or gestational
hypertension, magnesium sulphate should be
considered for fetal neuroprotection in the setting
of imminent preterm birth (within the next 24
hours) at ≤ 31+6 weeks. (1-A)
123. Delivery should not be delayed in order to
administer antenatal magnesium sulphate for
fetal neuroprotection if there are maternal
and/or fetal indications of emergency
delivery. (III-E)
There is no international consensus on what defines severe
preeclampsia. This document defines it as preeclampsia
requiring delivery due to serious maternal end-organ
involvement and/or fetal compromise (see “Classification
of HDPs”). For eclampsia prevention in the setting of
non-severe preeclampsia, we have added to the indication
for magnesium sulphate (in Recommendation 120) the
following symptoms/signs as these are included in the
definition of severe preeclampsia by other organizations:
severe hypertension, headaches/visual symptoms, right
upper quadrant/epigastric pain, platelet count < 100 000 ×
109/L, progressive renal insufficiency, and/or elevated
liver enzymes.
Aspects of Care for Women With Preeclampsia:
Plasma Volume Expansion
Recommendation
124. Plasma volume expansion is not recommended for
women with preeclampsia. (I-E)
Therapies for HELLP Syndrome
Recommendations
125. Every obstetrical centre should be aware of
the local delay between ordering and receiving
platelets units. (III-B)
126. For a platelet count of < 20 × 109/L with
hemolysis, elevated liver enzymes, low platelets

432 l MAY JOGC MAI 2014

 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

Table 10. Recommendations for the transfusion of platelets related to mode of delivery
in HELLP
Mode of delivery
Platelet count Caesarean delivery Vaginal delivery
< 20 × 10 /L
9
 
20 to 49 × 109/L  Consider in presence of:
•  excessive active bleeding
•  known platelet dysfunction
•  platelet count falling rapidly
• coagulopathy
≥ 50 × 10 /L
9
Consider in presence of: Consider in presence of:
•  excessive active bleeding •  excessive active bleeding
•  known platelet dysfunction •  known platelet dysfunction
•  platelet count falling rapidly •  platelet count falling rapidly
• coagulopathy • coagulopathy
Regardless of the platelet count No platelets should be transfused if there is a strong suspicion of HIT
or TTP-HUS
HIT: heparin-induced thrombocytopenia; TTP-HUS: thrombotic thrombocytopenic purpura–hemolytic uremic syndrome

syndrome, platelet transfusion is recommended Care in the 6 Weeks Postpartum

regardless of mode of delivery. (III-B) (Table 9)
127. For a platelet count of 20 × 109 to 49 × 109/L
with hemolysis, elevated liver enzymes, low
platelets syndrome, platelet transfusion is
recommended prior to Caesarean delivery. (III-B)
(Table 9)
128. For a platelet count of 20 × 109 to 49 × 109/L
with hemolysis, elevated liver enzymes, low
platelets syndrome, platelet transfusion should
be considered prior to vaginal delivery if there
is excessive active bleeding, known platelet
dysfunction, a rapidly falling platelet count, or
coagulopathy. (II-2D) (Table 10)
129. For a platelet count of ≥ 50 × 109/L with
hemolysis, elevated liver enzymes, low platelets
syndrome, platelet transfusion and/or packed
red blood cells should be considered prior to
either Caesarean or vaginal delivery only if
there is excessive active bleeding, known platelet
dysfunction, a rapidly falling platelet count, or
coagulopathy. (III-B)
130. We do not recommend corticosteroids for
treatment of hemolysis, elevated liver
enzymes, low platelets syndrome until they
have been proven to decrease maternal
morbidity. (II-3L)
131. We recommend against plasma exchange or
plasmapheresis for hemolysis, elevated liver
enzymes, low platelets syndrome, particularly
within the first 4 days postpartum. (II-3E)
Recommendations
132. Blood pressure should be measured during the
time of peak postpartum blood pressure, at days
3 to 6 after delivery. (III-B)
133. Women with postpartum hypertension should
be evaluated for preeclampsia (either arising
de novo or worsening from the antenatal
period). (II-2B)
134. Consideration should be given to continuing
antihypertensive therapy postpartum, particularly
in women with antenatal preeclampsia and those
who delivered preterm. (II-2L)
135. Severe postpartum hypertension must be treated
with antihypertensive therapy to keep systolic
blood pressure < 160 mmHg and diastolic blood
pressure < 110 mmHg. (I-A)
136. In women without co-morbidities,
antihypertensive therapy should be considered to
treat non-severe postpartum hypertension to keep
blood pressure < 140/90 mmHg. (III-L)
137. Women with co-morbidities other than
pre-gestational diabetes mellitus should be treated
to keep blood pressure < 140/90 mmHg (III-C)
138. Women with pre-gestational diabetes mellitus
should be treated to keep blood pressure
< 130/80 mmHg. (III-C)
139. Antihypertensive agents generally acceptable
for use in breastfeeding include the following:
nifedipine XL, labetalol, methyldopa, captopril,
and enalapril. (III-B)

MAY JOGC MAI 2014 l 433

SOGC CLINICAL PRACTICE GUIDELINE
140. There should be confirmation that end-organ
dysfunction of preeclampsia has
resolved. (III-C)
141. Non-steroidal anti-inflammatory drugs should
not be given postpartum if hypertension is
difficult to control, there is evidence of kidney
injury (oliguria and/or creatinine≥ 90 µM), or
platelets are < 50 to 109/L. (III-C)
142. Postpartum thromboprophylaxis should be
considered in women with preeclampsia,
particularly in the presence of other risk
factors. (II-2B)
Care Beyond 6 Weeks Postpartum
Recommendations
143. Women with a history of severe preeclampsia
(particularly those who presented or delivered
before 34 weeks’ gestation) should be screened
for pre-existing hypertension and underlying renal
disease. (II-2B)
144. Referral for internal medicine or nephrology
consultation (by telephone if necessary)
should be considered for women with:
(i) postpartum hypertension that is difficult
to control, or
(ii) women who had preeclampsia and have
at 3-6 months postpartum either ongoing
proteinuria, decreased estimated glomerular
filtration rate (eGFR) (< 60 mL/min), or
another indication of renal disease, such as
abnormal urinary sediment. (III-A)
145. Women who are overweight should be encouraged
to attain a healthy body mass index to decrease
risk in future pregnancy (II-2A) and for long-term
health. (I-A)
146. Women with pre-existing hypertension or
persistent postpartum hypertension should
undergo the following investigations (if not
done previously) at least six weeks postpartum:
urinalysis; serum sodium, potassium and
creatinine; fasting glucose; fasting lipid
profile; and standard 12-lead electrocardio-
graphy. (III-L)
147. Women who are normotensive but who have had
a hypertensive disorder of pregnancy, may benefit
from assessment of traditional cardiovascular risk
markers. (II-2B)
148. All women who have had a hypertensive disorder
of pregnancy should pursue a healthy diet and
lifestyle. (I-B)
434 l MAY JOGC MAI 2014
Effects of Maternal Hypertension and Its Therapies
on Child Neurobehavioural Development
Recommendations
149. Clinicians should be aware that gestational
hypertension and preeclampsia may each be
associated with an increase in adverse paediatric
neurodevelopmental effects, such as inattention
and externalizing behaviours (e.g.,
aggressiveness). (II-2B).
150. Clinicians should be reassured that there is
no compelling evidence that antihypertensive
medications (specifically labetalol, nifedipine, or
methyldopa) are themselves associated with clear
adverse neurodevelopmental effects. (I-B)
CHAPTER 4:
PATIENT PERSPECTIVE
Recommendations
151. Health care providers should be alert to symptoms
of posttraumatic stress following a hypertensive
disorder of pregnancy and refer women for
appropriate evaluation and treatment. (II-2B)
152. Health care providers should inform their patients,
antepartum and postpartum, about preeclampsia,
its signs and symptoms, and the importance of
timely reporting of symptoms to health care
providers. (II-2B)
153. Information should be re-emphasized at
subsequent visits. (III-C)
CHAPTER 5:
KNOWLEDGE TRANSLATION TOOLS AND
IMPLEMENTATION OF THE GUIDELINE
The Appendix (Table 10 in the full document3) lists tools
to support the application of this guideline. Some websites
provide general information about BP measurement for
non-pregnant patients, but the recommendations are
similar enough to those for pregnant women to be useful.
Patients, their partners, and their care providers should be
well educated about the HDP, and relevant sites are listed.
Implementation of any evidence depends on individual
knowledge and beliefs, as well as institutional culture. Strong
recommendations should be incorporated into clinical
practice. In well-resourced settings, almost all preeclampsia-
related maternal deaths involve substandard care.38
Some updates to the 2008 SOGC guidelines on the HDP
may require additional effort to implement.
 Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary
Recommendation 9 states that all measurement devices
used in hospitals or offices should be checked regularly
against a calibrated device may not be possible for all
Canadian hospitals and offices to do on a regular basis.
Physicians should consider the category “other HDP”
(white-coat and masked hypertension) as part of the
classification of hypertensive women and consider using
some form of out-of-office BP measurement to evaluate
women with non-severe pre-existing or gestational
hypertension.
Health care providers should inform pregnant women
about the symptoms and signs of the HDPs and refer
them to appropriate knowledge translation tools.
We recommend the use of corticosteroids for women
≤ 34+6 weeks’ gestation who are at high risk of delivery
within the next seven days. This gestational age cut-off
represents a fundamental change in practice that will require
discussion.
Physicians should be familiar with the blood bank policies
of their own hospital.
Physicians should be aware of postpartum signs of
maternal posttraumatic stress disorder and the maternal
and perinatal long-term effects of HDPs, especially at this
vulnerable time in maternal care when the maternity care
provider is often handing back care to the primary care
physician.
The reader is reminded to refer to the full open-access
guideline published in Pregnancy Hypertension,3 which contains
not only the recommendations and tables presented here,
but also all explanatory text and additional references.
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13. Urquia ML, Ying I, Glazier RH, Berger H, De Souza LR, Ray JG. Serious
preeclampsia among different immigrant groups. J Obstet Gynaecol Can
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JM. The classification and diagnosis of the hypertensive disorders
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23. Villar J, Say L, Shennan A, Lindheimer M, Duley L, Conde-Agudelo A,
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[abstracts of American Society of Hypertension 27th Annual
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27. Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol
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28. Fesenmeier MF, Coppage KH, Lambers DS, Barton JR, Sibai BM. Acute
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Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955–2006.
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31. Mouthon L, Berezne A, Bussone G, Noel LH, Villiger PM, Guillevin
L. Scleroderma renal crisis: a rare but severe complication of systemic
sclerosis. Clin Rev Allergy Immunol 2011;40:84–91.
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32. Ogge G, Chaiworapongsa T, Romero R, Hussein Y, Kusanovic JP, Yeo L,
et al. Placental lesions associated with maternal underperfusion are more
frequent in early-onset than in late-onset preeclampsia. J Perinat Med
2011;39:641–52. doi: 10.1515/JPM.2011.098.
33. Akolekar R, Syngelaki A, Poon L, Wright D, Nicolaides KH. Competing
risks model in early screening for preeclampsia by biophysical and
biochemical markers. Fetal Diagn Ther 2013;33:8–15.
34. Scazzocchio E, Figueras F, Crispi F, Meler E, Masoller N, Mula R,
et al. Performance of a first-trimester screening of preeclampsia
in a routine care low-risk setting. Am J Obstet Gynecol
2013;208(3):203.e1–203.e10.
35. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung
maturation for women at risk of preterm birth. Cochrane Database of
Systematic Reviews 2006;(3)CD004454.
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Caesarean Section (ASTECS) Research Team. Antenatal betamethasone
and incidence of neonatal respiratory distress after elective caesarean
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corticosteroids to reduce neonatal morbidity and mortality.
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38. Shennan AH, Redman C, Cooper C, Milne F. Are most maternal deaths
from pre-eclampsia avoidable? Lancet 2012;379(9827):1686–7.
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2003;169:207–8.
Appendix begins on next page
 APPENDIX. KNOWLEDGE TRANSLATION TOOLS FOR HDP
Tool
BP measurement by patients
Canadian Hypertension Education Program (CHEP)
National Heart Foundation of Australia
Heart and Stroke Foundation
Société Canadienne d/hypertension
Canadian Hypertension Education Program (CHEP)
Brochure
BP measurement and pre-existing hypertension
Heart and Stroke Foundation
Impact of pre-existing hypertension on pregnancy
American Heart Association document: Chronic
Hypertension in Pregnancy
Preeclampsia awareness
Preeclampsia Foundation: Preeclampsia Education
Tool
Preeclampsia Foundation: Educational magnets
and symptom Pads
MAY JOGC MAI 2014 l 437
Resource
PATIENT INFORMATION
http://www.hypertension.ca/measuring-blood-pressure (English)
http://www.hypertension.ca/fr/mesures-dp1 (French)
http://www.heartfoundation.org.au/SiteCollectionDocuments/
Self-Management-BP.pdf
https://ehealth.heartandstroke.ca/heartstroke/bpap.net/
vid_measure_bp.html
http://hypertension.ca/measuring-blood-pressure
http://hypertension.ca/fr/mesures-dp1
https://www.youtube.com/watch?v=eqajdX5XU9Y&feasture=plcp
http://www.RCOG.org.uk
http://www.heartandstroke.ca
https://circ.ahajournals.org/content/115/7/e188.full
http://www.preeclampsia.org/market-place
http://www.preeclampsia.org/market-place
Comment
This website gives patients basic information about
BP measurement and gives instructions on self-
measurement.
This website gives information about the self-
measurement of BP by patients and advice about
buying a machine.
This link refers to a movie that gives instructions for
self-measurement of BP.
This website gives detailed information in English and
French (with a poster in English) although the images
are of older patients.
This website gives detailed video on home BP
measurement (outside pregnancy).
This also includes your risk of recurrence.
This website gives information about hypertension
outside of pregnancy, blood pressure monitoring and
medication.
This document explains in an understandable way
how chronic hypertension and pregnancy influence
each other and what the symptoms of preeclampsia
that women should be aware of.
This tool explains the risks and symptoms of
preeclampsia and how to act on them. This tool has
shown to be effective in improving patient knowledge
in an RCT (120 women).
This website gives quick checklists of signs and
symptoms of preeclampsia.
Continued
Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy: Executive Summary

Tool
438 l MAY JOGC MAI 2014
Patient education once preeclampsia develops
Preeclampsia Foundation Brochures:
•  HELLP syndrome
•  Preeclampsia FAQ
•  Preeclampsia and heart diseases
Hôpital Maisonneuve-Rosemont, Centre affilié à
l’Université de Montréal: Brochure on preeclampsia.
Patient education after preeclampsia
Preeclampsia Foundation; APEC:
Educational pamphlet
BP measurement
WHO document: detecting preeclampsia,
a practical guide, 2005
Approved BP measurement devices
Canadian Hypertension Education Program (CHEP)
Educational Trust
Clinical practice guidelines from other countries
NICE guidelines (UK, 2010)
Australasian guidelines (Australia and New Zealand,
2008)
College of Obstetricians and Gynecologists
WHO guidelines
APPENDIX. Continued
Resource
http://www.preeclampsia.org/market-place
http://biblio.hmr.qc.ca/Publications_pdf/H/hypertension_sfe080.pdf
http://www.preeclampsia.org/market-place
HEALTH CARE PROVIDER INFORMATION
http://www.who.int/reproductivehealth/publications/maternal_
perinatal_health/MSM_92_3_/en/index.html
http://www.hypertension.ca/devices-endorsed-by-hypertension-
canada-dp1
http://www.dableducational.org/sphygmomanometers/devices_1_
clinical.html
http://www.nice.org.uk/nicemedia/live/13098/50475/50475.pdf
http://www.somanz.org/pdfs/somanz_guidelines_2008.pdf
http://www.acog.org/~/media/Task%20Force%20and%20Work%
20Group%20Reports/HypertensioninPregnancy.pdf
http://whqlibdoc.who.int/publications/2011/9789241548335_eng.pdf
Comment
These are available in English and Spanish.
SOGC CLINICAL PRACTICE GUIDELINE
French brochure for patients about preeclampsia.
Educational brochure about cardiovascular risks
associated with preeclampsia.
This document contains instructions how to measure
blood pressure and proteinuria in pregnant women,
and how to diagnose hypertensive disorders in
pregnancy. This tool is for health care providers.
This website gives an oversight of recommended
blood pressure devices.
This website gives an oversight of recommended
blood pressure devices, outside of and during
pregnancy.
Graded recommendations
Very practical but evidence not graded
Graded recommendations
 SOGC CLINICAL PRACTICE GUIDELINES

No. 302, January 2014 (Replaces No. 173, February 2006)

Pregnancy Outcomes After

Assisted Human Reproduction
Abstract
This clinical practice guideline has been prepared by
the Genetics Committee, reviewed by the Reproductive Objective: To review the effect of assisted human reproduction (AHR)
Endocrinology and Infertility Committee and the Family on perinatal outcomes, to identify areas requiring further research
Physicians Advisory Committee, and approved by the with regard to birth outcomes and AHR, and to provide guidelines
Executive and Council of the Society of Obstetricians and to optimize obstetrical management and counselling of prospective
Gynaecologists of Canada. Canadian parents.
Outcomes: This document compares perinatal outcomes of different
PRINCIPAL AUTHORS types of AHR pregnancies with each other and with those of
spontaneously conceived pregnancies. Clinicians will be better
Nanette Okun, MD, Toronto ON
informed about the adverse outcomes that have been documented
Sony Sierra, MD, Toronto ON in association with AHR, including obstetrical complications,
adverse perinatal outcomes, multiple gestations, structural
GENETICS COMMITTEE congenital abnormalities, chromosomal abnormalities, and
imprinting disorders.
R. Douglas Wilson (Chair), MD, Calgary AB
Evidence: Published literature was retrieved through searches
Francois Audibert, MD, Montreal QC of MEDLINE and the Cochrane Library from January 2005 to
Jo-Ann Brock, MD, PhD, Halifax NS December 2012 using appropriate controlled vocabulary and key
words (assisted reproduction, assisted reproductive technology,
Carla Campagnolo, MSc, CCGC, London ON ovulation induction, intracytoplasmic sperm injection, embryo
June Carroll, MD, Toronto ON transfer, and in vitro fertilization). Results were not restricted to
systematic reviews, randomized control trials/controlled clinical
Lola Cartier, MSc, CCGC, Montreal QC trials, and observational studies; studies of all designs published
David Chitayat, MD, Toronto ON in English from January 2005 to December 2012 were reviewed,
and additional publications were identified from the bibliographies
Alain Gagnon, MD, Vancouver BC of these articles. Searches were updated on a regular basis and
Jo-Ann Johnson, MD, Calgary AB incorporated in the guideline to August 2013. Grey (unpublished)
literature was identified through searching the websites of health
Sylvie Langlois, MD, Vancouver BC technology assessment and health technology assessment-
Lynn Murphy-Kaulbeck, MD, Moncton NB related agencies, clinical practice guideline collections, clinical trial
registries, and national and international medical specialty societies.
W. Kim MacDonald, MD, Halifax NS
Values: The quality of evidence in this document was rated using the
Nanette Okun, MD, Toronto ON criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Melanie Pastuck, RN, Cochrane AB
SPECIAL CONTRIBUTORS Summary Statements
Lih Yeen Tan, MD, Toronto ON 01. There is increasing evidence that infertility or subfertility is an
independent risk factor for obstetrical complications and adverse
Valda Poplak, Toronto ON
perinatal outcomes, even without the addition of assisted human
Helen Robson, MA, Toronto ON reproduction. (II-2)
Disclosure statements have been received from all contributors. 02. The relative risk for an imprinting phenotype such as Silver-
Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman
syndrome is increased in the assisted reproduction population, but
the actual risk for one of these phenotypes to occur in an assisted
Key Words: Assisted human reproduction, assisted reproductive
technology, pregnancy outcomes, multiple gestation, imprinting,
congenital anomalies, imprinting disorders.
J Obstet Gynaecol Can 2014;36(1):64–83

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

64 l JANUARY JOGC JANVIER 2014


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.176
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.176
pregnancy is estimated to be low, at less than 1 in 5000. The
exact biological etiology for this increased imprinting risk is likely
heterogeneous and requires more research. (II-2)
Recommendations
01. All men with severe oligozoospermia or azoospermia
(sperm count < 5 million/hpf) should be offered genetic/
clinical counselling, karyotype assessment for chromosomal
abnormalities, and Y-chromosome microdeletion testing prior to in
vitro fertilization with intracytoplasmic sperm injection. (II-2A)
02. All men with unexplained obstructive azoospermia should be
offered genetic/clinical counselling and genetic testing for cystic
fibrosis prior to in vitro fertilization with intracytoplasmic sperm
injection. (II-2A)
03. Multiple pregnancy is the most powerful predictive factor for
adverse maternal, obstetrical, and perinatal outcomes. Couples
should be thoroughly counselled about the significant risks
of multiple pregnancies associated with all assisted human
reproductive treatments. (II-2A)
04. The benefits and cumulative pregnancy rates of elective single
embryo transfer support a policy of using this protocol in couples
with good prognosis for success, and elective single embryo
transfer should be strongly encouraged in this population. (II-2A)
05. To reduce the incidence of multiple pregnancy, health care
policies that support public funding for assisted human
reproduction, with regulations promoting best practice
regarding elective single embryo transfer, should be strongly
encouraged. (II-2A)
06. Among singleton pregnancies, assisted reproductive technology
is associated with increased risks of preterm birth and low
birth weight infants, and ovulation induction is associated with
an increased risk of low birth weight infants. Until sufficient
research has clarified the independent roles of infertility and
treatment for infertility, couples should be counselled about the
risks associated with treatment. (II-2B) There is a role for closer
obstetric surveillance of women who conceive with assisted
human reproduction. (III-L)
Pregnancy Outcomes After Assisted Human Reproduction
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
07. There is growing evidence that pregnancy outcomes are better
for cryopreserved embryos fertilized in vitro than for fresh embryo
transfers. This finding supports a policy of elective single embryo
transfer for women with a good prognosis (with subsequent use of
cryopreserved embryos as necessary), and may reassure women
who are considering in vitro fertilization. (II-2A)
08. Women and couples considering assisted human reproduction
and concerned about perinatal outcomes in singleton pregnancies
should be advised that (1) intracytoplasmic sperm injection does
not appear to confer increased adverse perinatal or maternal risk
over standard in vitro fertilization, and (2) the use of donor oocytes
increases successful pregnancy rates in selected women, but even
when accounting for maternal age, can increase the risks of low
birth weight and preeclampsia. (II-2B)
09. Any assisted reproductive technology procedure should be
prefaced by a discussion of fetal outcomes and the slight
increase in the risk of congenital structural abnormalities, with
emphasis on known confounding factors such as infertility and
body mass index. (II-2B)
10. In pregnancies achieved by artificial reproductive technology,
routine anatomic ultrasound for congenital structural abnormalities
is recommended between 18 and 22 weeks. (II-2A)
11. Pregnancies conceived by intracytoplasmic sperm injection may
be at increased risk of chromosomal aberrations, including sex
chromosome abnormalities. Diagnostic testing should be offered
after appropriate counselling. (II-2A)
12. The possible increased risk for late onset cancer due to gene
dysregulation for tumour suppression requires more long-term
follow-up before the true risk can be determined. (III-A)
13. The clinical application of preimplantation genetic testing in
fertile couples must balance the benefits of avoiding disease
transmission with the medical risks and financial burden of in vitro
fertilization. (III-B)
14. Preimplantation screening for aneuploidy is associated with
inconsistent findings for improving pregnancy outcomes. Any
discussion of preimplantation genetic screening with patients
should clarify that there is no adequate information on the long-
term effect of embryo single cell biopsy. (I-C)
JANUARY JOGC JANVIER 2014 l 65
SOGC Clinical Practice Guidelines
INTRODUCTION
A lthough the definition varies, assisted reproductive
technology is commonly defined as any procedure
that involves handling eggs, sperm, or both outside the
human body (in vitro). ART includes in vitro fertilization,
with or without intracytoplasmic sperm injection, with
fresh or frozen embryos (by cryopreservation or by
vitrification and thawed embryo transfer) and IVF with
donor oocytes, gamete intrafallopian transfer, zygote
intrafallopian transfer, and assisted zona hatching. ART
has expanded to include not only in vitro procedures, but
also intrauterine insemination and OS with gonadotropin
or ovarian stimulating medications1
ART accounts for 1.7% to 4% of pregnancies2 and has
traditionally been used to address primary or secondary
infertility.3 More recently, its use has expanded to allow
ABBREVIATIONS
AHR assisted human reproduction
AHRC Assisted Human Reproduction Canada
aOR adjusted odds ratio
ART assisted reproductive technology
ASRM American Society for Reproductive Medicine
CARTR Canadian Assisted Reproductive Technologies Registry
CBAVD congenital bilateral absence of vas deferens
CFAS Canadian Fertility and Andrology Society
DET double embryo transfer
eSET elective single embryo transfer
ESHRE European Society of Human Reproduction and
Embryology
ET embryo transfer
FET frozen embryo transfer
HFEA Human Fertilisation and Embryology Authority
HR hazard ratio
ISCI intracytoplasmic sperm injection
IUI intrauterine insemination
IVF in vitro fertilization
LBW low birth weight
MSAFP maternal serum alpha-fetoprotein
PAPP-A pregnancy-associated plasma protein-A
PGS preimplantation genetic screening
RR relative risk
OH ovarian hyperstimulation
OI ovulation induction
OS ovarian stimulation
SART Society for Assisted Reproduction Technologies
SGA small for gestational age
TTP time to pregnancy
66 l JANUARY JOGC JANVIER 2014
fertility preservation after gonadotoxic treatments in
reproductive-age patients,4,5 to enable same-sex couples
and single women and men to conceive and have biological
children,6 and to facilitate the services of surrogate
gestational carriers.7 The ethical and philosophical issues
involved in AHR are complex and are handled differently in
different countries, resulting in varying levels of regulation
of these services.8–12
In Canada, the Assisted Human Reproduction Act,13
which covers topics including allowed (surrogacy, gamete
donation) and prohibited (human cloning, buying or selling
human reproductive material) processes, led to the creation
of Assisted Human Reproduction Canada, an agency
responsible for the licensing, monitoring, inspection, and
enforcement of regulations for ART clinics. Following a
2010 Supreme Court decision resulting from a Charter
challenge from Quebec, aspects of the Act relating to
prohibitions (sex selection, selling of human reproductive
material) have remained within the Federal Act, but much
of the regulation of ART services will fall back under
provincial jurisdiction.14 The 2012 Federal budget ordered
the dissolution of AHRC in 2013, with its responsibilities
redirected to Health Canada.4
Data for IVF clinics have been reported by the Canadian
Assisted Reproductive Technologies Registry since 1999,
under the auspices of the Canadian Fertility and Andrology
Society.15 IVF clinics are accredited by Accreditation
Canada.16
The availability of treatment for infertility and subfertility
(a term generally used to name any grade of reduced
fertility in couples unsuccessfully trying to conceive17) is
important to the family health of Canadians.18 Obstetrical
outcome data from pregnancies conceived by AHR and
some long-term follow-up data on offspring suggest
increased adverse outcomes related to AHR techniques.
Care providers and prospective parents should be aware
of these potential adverse outcomes.
This guideline reviews the outcome data of AHR pregnancies
using the Evaluation of Evidence criteria outlined in the
Report of the Canadian Task Force on the Periodic Health
Examination (Table 1). We searched the Cochrane Library
and Ovid MEDLINE for English-language articles related
to assisted reproduction and perinatal outcomes published
from February 2005 to December 2012 (overlapping with
the previous SOGC guideline). Well-conducted randomized
controlled trials were considered evidence of the highest
quality, followed by cohort studies. Key studies and
supporting data for each recommendation are referenced
and summarized with evaluative comments.

OUTCOMES ASSOCIATED WITH
UNTREATED INFERTILITY
Infertility, generally considered to be the inability to conceive
after one year of attempting pregnancy,19 has been identified
as a significant independent predictor of adverse obstetrical
and perinatal outcomes.20–22 Unadjusted analyses suggest a
2-fold increased risk of preeclampsia, placental abruption,
Caesarean section, and vacuum extraction, and a 5-fold
increased risk of placenta previa in spontaneous singleton
pregnancies in women with a history of infertility compared
with women in the general population.23
Table 2 summarizes a number of studies documenting
adjusted obstetrical, perinatal, and neonatal risks in
populations of women with infertility or subfertility
compared with control women.13,23–29 Some of these studies
compared women with various delays in time to pregnancy
who eventually conceived spontaneously to populations of
women with short TTP, and found significant differences
in a number of adverse outcomes, including preterm birth,
LBW, and perinatal mortality. Other studies compared
populations of women with delays in TTP with and
without ART and found insignificant differences between
these 2 groups, but increases in adverse outcomes between
these 2 groups and a control group of women with no
delay in TTP.30,31
Maternal factors related to an increased risk of infertility
also have an independently associated risk of adverse
obstetrical outcomes. Advancing maternal age is associated
with both declining fertility and multiple adverse
outcomes of ongoing pregnancy, as noted recently in
an SOGC committee opinion on delayed childbearing.32
Research shows obesity impairs fertility, 33,34 although
whether this effect is primarily ovarian or endometrial is
controversial.35–37 Obesity is also independently related
to adverse obstetrical outcomes, many of them similar
to those associated with advancing maternal age38 and
overlapping with those associated with AHR.
Although there is little remaining debate about the
association of infertility or subfertility with adverse
obstetrical outcomes following AHR, more specific
associations between ovarian/ovum or testicular/sperm
factors, endometrial factors, or other factors and adverse
outcomes are not well understood.
Summary Statement
1. There is increasing evidence that infertility or
subfertility is an independent risk factor for
obstetrical complications and adverse perinatal
outcomes, even without the addition of assisted
human reproduction. (II-2)
Pregnancy Outcomes After Assisted Human Reproduction
OUTCOMES ASSOCIATED WITH
MALE FACTOR INFERTILITY
Infertility is associated with male factor or abnormal
sperm parameters in approximately 50% of cases.39 Studies
have shown that 4.6% of oligozoospermic men and 13.7%
of azoospermic men have constitutional chromosomal
abnormalities, the most common being sex chromosomal
abnormalities and autosomal translocations.40 Karyotype
analysis of men with fewer than 5 million spermatozoa per
milliliter of semen has been recommended as routine by
the World Health Organization since 2000.41 As expected,
infertile men with chromosomal abnormalities are more
likely to have genetically abnormal spermatozoa and to
father chromosomally abnormal pregnancies.42
Azoospermia can be classified as non-obstructive or
obstructive. The most common cause of obstructive
azoospermia is a congenital bilateral absence of vas deferens,
a feature associated strongly with mutations in the cystic
fibrosis transmembrane conductance regulator genes.43,44 In
either presentation, a consultation with a urologist may lead
to surgical extraction of sperm for use with IVF/ICSI.
Microsurgical testis sperm extraction is estimated to
be successful in 50% of attempts in non-obstructive
azoospermia.45 Success with extracted sperm used in
IVF/ICSI procedures has been documented with a
pregnancy rate approaching 40%.46 A recently published
systematic review summarized the potential reproductive
outcomes of various male reproductive genetic
abnormalities associated with azoospermia. (Table 3).47
Recommendations
1. All men with severe oligozoospermia or azoospermia
(sperm count < 5 million/hpf) should be offered
genetic/clinical counselling, karyotype assessment
for chromosomal abnormalities, and Y-chromosome
microdeletion testing prior to in vitro fertilization with
intracytoplasmic sperm injection. (II-2A)
2. All men with unexplained obstructive azoospermia
should be offered genetic/clinical counselling
and genetic testing for cystic fibrosis prior to in
vitro fertilization with intracytoplasmic sperm
injection. (II-2A)
OBSTETRICAL, PERINATAL, AND
LONG-TERM OUTCOMES ASSOCIATED WITH
ASSISTED REPRODUCTIVE TECHNOLOGY
Multiple Pregnancy and Adverse
Obstetrical and Perinatal Outcomes
Over the last 30 years, multiple birth rates have risen
dramatically internationally, associated partly with increased
maternal age at pregnancy, but mostly with infertility
JANUARY JOGC JANVIER 2014 l 67
 Table 2. Controlled studies of obstetrical outcomes of women undergoing , compared with women conceiving spontaneously. after prolonged time to
pregnancy
Study Adjusted for Population Outcome Odds ratio
24
Henriksen et al. 1997 Parity 860 women with time to pregnancy > 12 months Preterm birth < 37 weeks 1.7 (1.1 to 2.6)
Smoking 6843 control subjects no difference
with/without treatment
Draper et al. 199925 Potential confounders Case-controlled study of 542 women with singleton or Perinatal mortality 2.9 (1.8 to 4.5)
significant in logistic multiple perinatal deaths
regression analysis 972 randomly selected control subjects
Examined treated and untreated infertility in each group
Basso and Baird 200326 Maternal age 3899 (treated and untreated women with time to GA < 37 weeks 1.38 (1.14 to 1.69)

68 l JANUARY JOGC JANVIER 2014

Pre-pregnancy BMI pregnancy > 1 year) GA < 34 weeks 1.51 (1.05 to 2.16)
Smoking 15 302 control subjects Emergency Caesarean section 1.15 (1.00 to 1.32)
SOGC Clinical Practice Guidelines

Social status
Gender of baby
Basso and Olsen 200527 Maternal age 4142 women with TTP > 12 months Neonatal mortality within 28 days 3.32 (1.47 to 7.53)
BMI 16 305 women with TTP < 12 months with no treatment
Smoking 2.21 (0.88 to 5.55)
with treatment
Social class
Thomson et al. 200523 Age 1437 subfertile women Preeclampsia 1.9 (1.5 to 2.5)
Parity 21 688 control subjects Placenta previa 3.9 (2.2 to 7.0)
Abruption 1.8 (1.1 to 3.0)
Induction of labour 1.5 (1.3 to 1.6)
Caesarean section 2.1 (1.8 to 2.4)
Instrumental delivery 2.2 (1.8 to 2.6)
LBW 1.4 (1.3 to 1.7)
Zhu et al. 200628 Maternal age 9727 pregnancies with TTP < 12 months Genital organ malformations hazard ratio:
BMI 50 897 pregnancies with TTP < 12 months 2.32 (1.24 to 4.35)
Alcohol
Smoking
Occupational status

Zhu et al. 200713 Maternal age 10 104 pregnancies with TTP > 12 months SGA < 5th percentile 1.24 (1.10 to 1.40)
Partiy 51 041 pregnancies with TTP < 12 months with no treatment
Smoking 1.40 (1.23 to 1.60)
with treatment
Romundstad et al. 200831 Maternal age 1 127 739 spontaneous conceptions SGA (< 2 SD below mean for GA 1.26 (1.10 to 1.44)
Parity 7474 ART conceptions and sex) 1.31 (1.05 to 1.65)
Offspring sex 2204 women having one spontaneous conception and one Perinatal death 0.99 (0.62 to 1.57)
Year of birth ART conception (comparing outcomes in these pregnancies) 0.36 (0.20 to 0.67) only
Time from previous birth to significant if spontaneous
conception conception preceded ART
conception
continued
 Pregnancy Outcomes After Assisted Human Reproduction

treatments.48,49 Multifetal pregnancy follows ovulation

induction or ovarian hyperstimulation alone at rates
between 5% and 40%.50 The 2011 published rate of multiple
1.29 (1.02 to 1.61)
1.41 (1.05 to 1.89)
2.19 (1.10 to 4.36)
1.37 (1.25 to 1.43)
1.56 (1.37 to 1.77)
1.21 (0.89 to 1.64)
1.28 (0.81 to 2.03)
0.95 (0.65 to 1.39)
1.28 (0.88 to 1.88)
1.19 (0.47 to 3.04)
pregnancies as a result of IVF reported by CARTR in
Canada is approximately 30%.51
Odds ratio

Although most multiple pregnancies following AHR are

dichorionic twins, the incidence of monozygotic twins
(most of whom have a monochorionic placentation) among
all IVF pregnancies is estimated at 0.9% to 2%, compared
with approximately 0.4% of live births from spontaneously
conceived pregnancies.52–54 IVF pregnancies that occur after
Antepartum hemorrhage

transferring blastocyst (5 days after fertilization) embryos

are more often associated with monozygotic twinning (6%)
Caesarean section
Caesarean section
Hypertension/PE

Low Apgar score

than pregnancies that occur after transferring cleavage-

GA < 31 weeks
Perinatal death

Need for NICU

Preterm birth

stage (2–3 days after fertilization) embryos (2%).55

Outcome

Multiple pregnancy is, arguably, the most important

SGA

outcome issue associated with AHR. The increased

incidence of adverse outcomes for fetuses and neonates
of multiple pregnancies has been consistently reported,
with preterm birth and its associated sequelae the most
important. The increasing overall frequency of prematurity
928 spontaneous pregnancies with TTP > 2 years
2171 singletons to subfertile women with no ART

in Canada is related to a significant degree to the increased

4363 spontaneous pregnancy control subjects

rate of multiple pregnancy.49 Much of this increase is

confined to an increase in the proportion of infants born
428 ART pregnancies with TTP > 2 years

between 32 and 36 weeks’ gestation, but there has also

been an increase in the frequency of preterm birth before
18 984 spontaneous pregnancies

32 weeks, from 1% to 1.2%.49 In Canada, the proportion

of preterm births secondary to multiple pregnancies
has increased from approximately 30% in the 1970s to
with TTP < 6 months

58.4% in 2004.49 The risks of perinatal mortality, growth

restriction, cerebral palsy, and congenital anomalies are
also higher in multiples than in singletons, most notably in
Population

monochorionic, but also in dichorionic, twins.49,56,57

The risk of morbidity and mortality increases with each

additional fetus in a multiple gestation.58 A recent two-
No. of previous abortions

year study at one Quebec hospital showed that 17% of

Private/public hospital

all NICU admissions were from multiple pregnancies in

women undergoing ART. Of these, 91% resulted from IVF,
Pre-pregnancy

Scarred uterus
Prior abortion

Maternal age

with 2 to 6 embryos transferred, and 9% from pregnancies

Adjusted for

conceived after OS.59 An Australian study similarly reported

Smoking
Alcohol
status
Parity

Parity

that 12.3 % of NICU admissions between 1994 and 2005

BMI

resulted from assisted reproduction. Of those, 5% were

singletons, 27% were twins, and 65% were triplets.60 There
Raatikainen et al. 201230

is no doubt that the increasing use of AHR has led to

Table 2. Continued

Jaques et al. 201029

increased perinatal morbidity and mortality secondary to

an increase in the incidence of multiple pregnancy.
PE: preeclampsia

Whether AHR multiples pose more risk than spontaneous

Study

multiples for perinatal adverse outcomes is less clear.

Controlled studies of perinatal outcomes comparing

JANUARY JOGC JANVIER 2014 l 69

SOGC Clinical Practice Guidelines
Table 3. Potential reproductive outcomes of various male reproductive genetic abnormalities associated with
azoospermia
Test Finding
Y-chromosome microdeletion AZFc microdeletion
AZFc microdeletions with aberrations in
pseudoautosomal regions (PARs)
gr/gr microdeletion
Karyotype analysis 47, XXY (Klinefelter syndrome)
Isodicentric Y chromosome
Chromosome translocations
CF mutation analysis Congenital bilateral absence of vas
deferens
Sperm morphology Structural aberrations of the spermatozoon
(e.g. Globozoospermia, dysplasia of the
fibrous sheath)
CFTR: Cystic fibrosis transmembrane conductance regulator
Adapted from Harnisch and Oates, 2012.47
twin pregnancies conceived after AHR with those of
spontaneously conceived twins,61–67 as well as 2 systematic
reviews,68,69 reveal data that are somewhat conflicting. The
study quality is hampered by several factors, including small
sample size, retrospective design, and inability to accurately
identify pregnancies conceived by ART (IVF or IVF/ICSI)
versus other forms of AHR (OI, OH, or OI/OH–IUI),
with some studies likely incorrectly classifying the latter in
the “spontaneous” group. As well, the known effects of
chorionicity and subfertility themselves are inconsistently
controlled. Finally, the fact that women undergoing AHR
treatments generally attend prenatal care earlier, and are
followed more closely, could confound the results.
With these limitations in mind, recent studies have suggested
very little independent influence of ART on adverse outcome
between these 2 comparison groups, with some showing
better outcomes within the ART group. Joy et al. found an
increase in preterm birth, lower birth weight, and congenital
anomalies among the spontaneously conceived twins, but
these findings were negated when the monochorionic
twins were removed.70 Morcel et al. found that differences
in outcomes were related to chorionicity and method of
AHR, with higher risk among pregnancies conceived by OI
than by ART,66 and Verstraelen et al. suggest that subfertility
itself plays a significant role in adverse outcomes.64
Maternal complications are more common in multiple
pregnancies than in singletons. Anemia, gestational
hypertension,71 preeclampsia, gestational diabetes, operative
70 l JANUARY JOGC JANVIER 2014
Adverse consequences
Male offspring with severe spermatogenetic failure/
sterility
Male offspring with severe spermatogenetic failure/
sterility; possible skeletal or other anomalies
Male offspring with severe spermatogenetic failure/
sterility; possible skeletal or other anomalies
Hypogonadism, slightly increased rate of autosomal and
sex chromosomal disomy in sperm; offspring with 46XX
or 46XY karyotype with no genetic anomalies
Possible offspring with 45X, Turner’s syndrome, or mixed
gonadal dysgenesis (45,X/46,XY)
Depends on chromosomes involved; recurrant pregnancy
loss or aneuploidy of offspring
Offspring with possible mild cystic fibrosis disease
spectrum if partner is a carrier; renal abnormalities if no
CFTR mutation identified
No obvious congenital anomalies in offspring reported
but possible higher rates of embryo aneuploidy
risks from Caesarean section, and postpartum hemorrhage
are of increased concern with multiple pregnancy.72
As well as medical complications, multiple births
generate significant economic and psychosocial costs.73–75
Interestingly, a recent study found, among parents of both
ART and spontaneous pregnancies, that the mental health
of both parents was more adversely affected by multiples
than by singletons, but that ART did not have an additional
adverse effect.76
Multifetal reduction can be very emotionally difficult
for couples who have gone through fertility treatment,
particularly when the procedure may result in the loss of
the entire pregnancy.77 Although some studies document
a risk of long-term adverse emotional consequences
for the couple,78–80 current evidence supports multifetal
pregnancy reduction of higher order multiples to twins
in order to improve pregnancy outcomes.81,82 Compared
with spontaneously conceived twin pregnancies, twin
pregnancies remaining after fetal reduction continue to
have an increased risk of preterm birth, LBW, very low
birth weight, and fetal growth restriction.62,83
Because of these maternal and perinatal risks, there has
been significant international effort to reduce the incidence
of multiple pregnancy associated with AHR. Transfer of
fewer embryos per cycle will reduce multiple pregnancy
rates, but this beneficial effect may be accompanied by a
less than acceptable pregnancy rate.

Two recent systematic reviews examined this topic. A 2009
Cochrane review compared the live birth rate of elective
DET with that of elective single, triple, or quadruple
embryo transfer. The review concluded that a single cycle
of eSET resulted in a lower live birth rate than DET, but
that the cumulative live birth rate in a fresh eSET cycle
followed by a frozen eSET was not significantly different
from a single DET cycle.84
A second meta-analysis by Grady et al. in 2012 compared
perinatal outcomes between DET and eSET pregnancies.
They found an RCT-based relative risk of 0.37 (0.25 to
0.55) for preterm birth < 37 weeks, and a RCT-based
RR of 0.25 (0.15 to 0.45) for birth weight < 2500 g in
the eSET group.85 Upon consideration of these results, it
appears likely that with a policy of fresh eSET followed, as
necessary, by a cycle of frozen eSET, the cumulative live
birth rate would be very similar to DET.
Many clinicians differentiate between live birth rates
and perinatal outcomes with IVF in women under and
over 40 years of age, but these 2 studies did not. A
recent observational UK study of 33 514 live births in
124 148 IVF cycles examined these outcomes according
to whether 1, 2, or ≥ 3 embryos were transferred in
women aged < 40 or ≥ 40. The study found that the
overall live birth rate was better in the < 40 age group,
that the live birth rate was higher for DET than for SET
in both age groups, that perinatal outcomes were worse
in both age groups for DET than for SET, but, notably,
that the difference in adverse perinatal outcomes in DET
versus SET was less in the > 40 age group. This large
observational study supports consideration of DET for
women ≥ 40. The study showed that transferring more
than 2 embryos did not increase live birth rates in either
age group, and it discouraged transferring 3 or more
embryos at any stage.86
The potential impact of a policy of eSET in appropriately
selected women on perinatal and maternal outcomes is
significant, and such a policy could result in substantial cost
savings. One modelling study examined the cost utility of
this policy,87 and a multi-centre cohort examining the long-
term effects and cost implications of the Dutch policy of
eSET is ongoing.88
Based on this research, ESHRE,89 HFEA,90 ASRM,91 and
SOGC and CFAS (jointly)92 have modified their guidelines
and recently endorsed a policy of eSET for women with
clinical factors predictive of a high chance of success for
cumulative live birth in centres with a good cryopreservation
facility. However, there is no current specific predictive
model to facilitate broad policy recommendations in
Pregnancy Outcomes After Assisted Human Reproduction
terms of number of embryos transferred, and the current
recommendations93 suggest that individual IVF-ET
programs should evaluate their own data to identify patient-
specific, embryo-specific, and cycle-specific determinants
of implantation and live birth in deciding on the number
of embryos to transfer. Updated recommendations will
likely consider the age of the woman or the egg donor to
be paramount in this decision-making process.
Internationally, in some jurisdictions the proportion of
eSET has increased and the multiple birth rate has fallen.
The 2010 US data report an approximate 15% eSET rate94
(twice that of 2000), while 2011 data from the UK report a
16.8% eSET rate.95 The 2011 UK data show a significantly
lower (20.6%) multiple pregnancy rate95 than the 2010 US
rate of 31%.94
Recently, AHRC analyzed the current international and
national state of AHR policy on embryo transfer. An
overriding factor that surfaced as a barrier to a broader
practice of eSET was active government legislation,
often linked to reimbursement. Those jurisdictions with
legislation and funded programs had much higher rates
of eSET; Belgium, Finland, and Australia approach 50%
eSET rates, with funded programs and linked legislation
promoting maximal use of eSET.
In Canada, an expert panel in Ontario has recommended
consideration of legislation and public funding for higher
rates of eSET.96 As of August 5, 2010, the provincial
government of Quebec began funding 3 cycles of IVF
with OS or up to 6 cycles of natural or modified natural
cycles of IVF, with IVF funding tied to eSET for clinically
favourable situations. An initial report on the first 3 months
of the program in 2009 found an increase in the rate of
eSET from 1.6% to 50%, and a reduction in the multiple
pregnancy rate from 25.6% to 3.7%.97 The most recent
report indicates an eSET rate of 49%, a 5.2% multiple
pregnancy rate, and a predicted cumulative pregnancy rate
of 60% per cycle.”98
Although most of the attention in reducing multiple
pregnancy rates has been directed at strategies related to
IVF, studies are increasingly addressing strategies related
to OI and OH with gonadotropin medications. This latter
literature is complicated by heterogeneity in both the
patient population and the medication regimens aimed at
OI or OH, with or without IUI. In addition, unlike ART/
IVF, there is even less regulation and capture of data on
treatment outcomes in this population, as it is not subject
to either mandatory or voluntary AHR reporting in North
America or Europe.
JANUARY JOGC JANVIER 2014 l 71
SOGC Clinical Practice Guidelines
A recent review99 and ASRM committee opinion on ways
to reduce multiple pregnancy rates following OI/OS
reviews several strategies that have been studied, including
longer initial treatment with clomiphene citrate prior to
gonadotropin use, lower doses of gonadotropins, and
monitoring and altering cycle management on the basis of
estradiol levels and follicle size. The committee concludes
that useful work has been done, but larger, prospective
studies are needed prior to the issue of a formal guideline
on this issue.100
Recommendations
3. Multiple pregnancy is the most powerful predictive
factor for adverse maternal, obstetrical, and perinatal
outcomes. Couples should be thoroughly counselled
about the significant risks of multiple pregnancies
associated with all assisted human reproductive
treatments. (II-2A)
4. The benefits and cumulative pregnancy rates of
elective single embryo transfer support a policy
of using this protocol in couples with good
prognosis for success, and elective single embryo
transfer should be strongly encouraged in this
population. (II-2A)
5. To reduce the incidence of multiple pregnancy, health
care policies that support public funding for assisted
human reproduction, with regulations promoting best
practice regarding elective single embryo transfer,
should be strongly encouraged. (II-2A)
Singleton Pregnancies and Perinatal Outcome
AHR resulting in singleton pregnancies has also been shown
to be associated with adverse obstetrical and perinatal
outcomes, but this is challenging literature to analyze.
There are many individual factors that can independently
and significantly contribute to adverse outcomes, but they
are difficult to isolate as they are interrelated with the
couple’s clinical profile (reason for infertility/subfertility)
and treatment regime.
The quality of studies has improved as accumulated data
from large registries have been published, but these still do
not allow the isolation of likely important but interrelated
clinical details, such as maternal and paternal background
factors and individual factors within the treatment regimes.
Different forms of OI versus OH, donor versus own eggs,
timing and/or method of aspiration of eggs, maturation
in an artificially high hormonal milieu in the mother (OH)
or in the laboratory (in vitro maturation), fresh or frozen
embryos, method of freezing embryos or eggs, origin
of sperm (ejaculated, testicular, epididymal), quality of
sperm, number of embryos formed, number of embryos
transferred, stage of transfer (cleavage vs. blastocyst
72 l JANUARY JOGC JANVIER 2014
stage), and the effect of “vanishing” fetuses are some of
the factors that could affect perinatal, obstetrical, and long-
term outcomes in different but significant ways.
There are, however, some evolving trends that continue
to support the association between AHR and increased
risk of adverse obstetrical and perinatal outcomes among
singleton pregnancies.
Preterm Birth
Along with multiple pregnancy, preterm birth and LBW
are the most commonly examined measures of adverse
perinatal outcome in singleton pregnancies conceived after
AHR.101,102 Table 4 summarizes these data.96–99,101,103
Several studies have found an increased risk of preterm
birth, whether defined as birth before 37 weeks, at 32 to
36 weeks, or before 32 weeks, in IVF versus spontaneous
singleton pregnancies. Adjusted odds ratios/relative risks
are between 1.95 and 3.22.104–108 It is not as convincing
that OI alone increases the risk of preterm birth once
other factors are controlled,109,110 although one recent large
Finnish cohort study found an independent effect on
preterm birth in all categories of gestational age cut-offs.111
Low Birth Weight
In almost all studies of singleton pregnancies resulting
from any type of AHR, LBW is found more often than
in spontaneous pregnancies. As in preterm birth, all
systematic reviews have associated IVF with reduced birth
weight, as indicated in Table 4.69,82,105–108 LBW in these cases
reflects not only decreased gestational age, but also less
than optimal growth for a given gestational age.
OI is also quite consistently associated with LBW.109–111
Exposure to gonadotropic stimulation, which produces
increased physiologic levels of circulating estradiol
combined with in vitro culture may be cumulatively
detrimental to normal embryo growth.112
Many emerging studies are attempting to isolate the
causative factors responsible for growth disturbance in
women undergoing AHR by comparing outcomes in various
subsets within cohort studies of the AHR population and
with outcomes in spontaneous pregnancies. Consistent
with the data on the contribution of the diagnosis and
causes of infertility itself, Sasanova et al. performed logistic
regression analysis on 8941 singleton pregnancies after
IVF to determine predictive factors for preterm birth and
LBW. They found that primiparity, smoking, BMI, and the
vanishing twin phenomenon increased the risk of preterm
birth, and that maternal age, smoking, BMI, and duration
of infertility increased the risk of LBW.113
 Pregnancy Outcomes After Assisted Human Reproduction

Table 4. Controlled studies of preterm birth and LBW among singleton pregnancies after
AHR, compared with spontaneously conceived pregnancies
RR ovulation
RR IVF induction alone
Perinatal outcomes (95% CI) (95% CI)
Preterm delivery < 37 weeks 1.98 (1.77 to 2.22)97 1.32 (1.15 to 1.50)104
2.00 (1.70 to 2.20) 98

1.93 (1.36 to 2.74)99

1.84 (1.54 to 2.21)100
1.91 (1.31 to 2.80)101
Preterm delivery 32–36 weeks or 2.3 (1.00 to 5.28)99 1.52 (1.13 to 2.04)104
< 32 weeks
Low birth weight < 2500 g 1.40 (1.01 to 1.95)99 1.43 (1.23 to 1.67)104
2.20 (1.55 to 3.13) 103

1.40 (1.01 to 1.95)100

Very low birth weight < 1500 g 3.78 (2.49 to 5.75)99 3.1 (1.0 to 10.4)102
2.7 (1.8 to 4.1)102 1.78 (1.33 to 2.38)104
SGA < 10th percentile 1.98 (1.21 to 3.24) 103
1.71 (1.09 to 2.69)103

A number of studies that compared IVF cycles with
fresh versus frozen (cryopreserved) embryos found that
frozen embryo transfers result in higher birth weights, a
lower chance of SGA infants, and a lower rate of preterm
birth.114–116 A large Australian cohort study performing
regression analysis to determine predictive factors for
LBW reports a significant increase in LBW with fresh
versus FET, with an aOR of 1.9 (95% CI 1.6 to 2.4).117
A systematic review on the topic also reports that the preterm
birth rate is either unchanged or decreased, and the LBW/
SGA rate is unchanged or improved with cryopreserved
versus fresh IVF cycles.118 A recent American cohort study
of 24 334 singleton fresh IVF pregnancies compared with
13 806 singleton FET IVF pregnancies found no significant
increase in aORs for preterm birth with FET, but an
increase in the overall rate of LBW, with an aOR of 1.35
(95% CI 1.20 to 1.51) among pregnancies of fresh IVF
cycles. In donor oocyte cycles with no OS, the rate of LBW
was not increased.119 These findings suggest that changes
in the uterine environment associated with multiple follicle
production increases the risk of LBW.
An interesting Danish cohort study of sibling singleton
births comparing 5 groups of successive pregnancies
•• fresh IVF-ISCI vs. spontaneous,
•• fresh IVF-ICSI vs. FET,
•• FET vs. FET,
•• fresh IVF-ICSI vs. fresh IVF-ICSI,
•• spontaneous vs. spontaneous
found a higher risk of LBW and lower mean birth weight
in fresh IVF-ICSI pregnancies than in FET, and an overall
lower birth weight with any ART than with spontaneous
pregnancy.120
The most recent data from a cohort of 25 777 births
documents a significant difference in birth weight of 90.9 g
in singletons conceived in frozen versus fresh transfer
cycles.121
There is speculation that the endometrial environment may
be improved by the lower doses of OS agents required
for FET, or that better quality embryos are recruited and
persevere through cryopreservation procedures. However,
another cohort study of 32 416 singleton IVF or ICSI
pregnancies found no independent relationship between
the parameters of OS used in these cycles and birth
weight.122
An interesting study of 292 singletons examined serum
estradiol levels during IVF cycles found that adjusted for
patient age, BMI, parity, number of embryos transferred,
day of transfer, and gonadotropin dose, high serum
estradiol levels (> 3450 pg/mL or > 90th percentile) were
associated with preeclampsia (OR 4.8; 95% CI 1.6 to 14.8)
and SGA (OR 9.4; 95% CI 3.2 to 27.5).123
Other studies have compared pregnancies conceived
after ICSI/IVF to spontaneous pregnancies with regard
to preterm birth and LBW. Two small studies (N = 41
ICSI/147 control subjects124; N = 276 ICSI/273 control
subjects125) comparing IVF/ICSI pregnancies with

JANUARY JOGC JANVIER 2014 l 73

SOGC Clinical Practice Guidelines
spontaneous pregnancies did not find an increase in LBW
or preterm birth. A study comparing 81 singleton ICSI
pregnancies to 81 matched-control IVF pregnancies did
not find any significant difference in preterm birth or
low birth weight.126 A Canadian study comparing ICSI
(n = 104), IVF (n = 133) and in vitro ovum maturation
(n = 31) did not find any significant differences in rates
of preterm birth or LBW.127 The source of sperm for
ICSI (ejaculated, epididymal, or testicular) does not
appear to influence birth weight parameters.128,129 ICSI
itself does not appear to adversely affect preterm birth
or LBW rates.
Use of donor, versus autologous, oocytes has been
reported to increase the risk of preterm birth and LBW. A
small case-controlled study comparing 81 IVF donor cycles
to 77 autologous oocyte IVF cycles found an increased
aOR of 2.6 (95% CI 1.04 to 6.3) for preterm birth.130 A
SART report comparing 60 037 standard IVF cycles with
10 176 donor egg cycles and 1180 gestational carrier cycles
found aORs of 1.21 (95% CI 1.13 to 1.30) for birth weight
< 2500 g and 1.28 (95% CI 1.10 to 1.49) for birth weight
< 1500 g when comparing donor egg with autologous egg
IVF cycles.37
Other Obstetrical Outcomes
There has been some question of whether AHR leads to
placental abnormalities as a mediating factor for some
adverse outcomes, such as LBW, preeclampsia, abnormal
implantation, placenta accreta, antepartum hemorrhage,
and postpartum hemorrhage. Possible early placental
abnormalities are consistent with the finding of altered
levels of maternal serum marker levels for Down syndrome
and open neural tube defects in the first and second
trimester. Several studies, including that reported from
the Danish cohort, found a significantly lower PAPP-A
level among ART pregnancies (except those with FET) of
0.8 MoM131 and an elevated total hCG.132
Several studies report an increased risk of preeclampsia
with AHR. Calhoun reports an aOR of 2.2 (95% CI 1.03
to 4.72), when controlling for factors including multiple
gestation, for preeclampsia with AHR; the risk was greatest
for IVF (aOR 5.3; 95% CI 1.74 to 15.89), and there was
no reported association between IUI and preeclampsia.133
Two separate cohort studies from the same Ontario
database report somewhat contradictory findings. Sun et
al. found a non-significant increased risk of a composite
outcome of placenta-mediated complications (stillbirth,
growth restriction, preeclampsia, and abruption) with IUI
(OR 1.30; 95% CI 0.94 to 1.80) but not with IVF or OI in a
matched-control study in singletons.134 Another analysis on
74 l JANUARY JOGC JANVIER 2014
an overlapping cohort from the same database controlling
for, but not excluding, multiples, reports an increased
risk for preeclampsia with IVF (OR 1.78; 95% CI 1.05 to
3.06), but not for IUI or OI.135 Small studies have linked
donor oocytes with an increased risk of preeclampsia over
autologous oocytes.130,136
Other placental complications reported to occur with
increased frequency with ART include placenta previa,
placental abruption, and antepartum and postpartum
hemorrhage. In a review of 42 placenta accreta cases, the
OR for IVF versus spontaneous pregnancies was 13.2
(95% CI 6.7 to 25.8).137 A large Australian cohort study
of 6730 IVF/ICSI pregnancies compared with 24 619
spontaneous pregnancies found an aOR of 2.0 (95% CI 1.8
to 2.3) for antepartum hemorrhage, 2.3 (95% CI 1.9 to 2.9)
for placenta previa, 2.1 (95% CI 1.4 to 3.0) for abruption,
and 1.3 (95% CI 1.2 to 1.4) for postpartum hemorrhage.138
A recent systematic review of 13 studies did not indicate
an increased risk of postpartum depression associated
with ART.139
The timing of the transfer of the embryo in IVF or IVF/
ICSI may influence the outcome. Optimal timing has
evolved from the cleavage-stage to the blastocyst stage,
as the success rate after blastocyst transfer is higher,
resulting in a higher live birth rate.140 In a meta-analysis
of 4 studies of 1102 blastocyst transfer cycles versus
1485 cleavage-stage cycles, the ratio of males to females
was higher (OR 1.29; 95% CI 1.10 to 1.51) in blastocyst
transfer cycles. In the same report a meta-analysis of 7
studies of 9316 blastocyst cycles versus 31 601 cleavage-
stage cycles found the rate of monozygotic twinning to
be increased with blastocyst transfer (OR 3.04; 95% CI
1.54 to 6.01).141 In another study of 1311 blastocyst transfer
cycles versus 12 562 cleavage-stage cycles, the rate of birth
< 37 weeks was slightly increased in the blastocyst transfer
group (OR 1.35; 95% CI 1.07 to 1.71), but the LBW rate
was unchanged.142
Long-Term Child Outcomes
Several large registry-based studies examining long-term
child outcomes have been published recently. There
appears to be little, if any, increased risk of significant
neurodevelopmental or behavioural adverse outcomes at
2-year124 or 5-year125,143 follow-ups. A 10-year follow-up
study found no significant difference between ICSI and
spontaneously conceived children.144 Physical health, thus
far, appears equal, although there has been a reported
increase in undescended testes and resulting urogenital
surgery in boys after ICSI.145 Although small studies
reported an increase in certain childhood cancers, registry
data do not support this relationship.146

Recommendations
6. Among singleton pregnancies, assisted reproductive
technology is associated with increased risks of
preterm birth and low birth weight infants, and
ovulation induction is associated with an increased
risk of low birth weight infants. Until sufficient
research has clarified the independent roles of
infertility and treatment for infertility, couples
should be counselled about the risks associated with
treatment. (II-2B) There is a role for closer obstetric
surveillance for women who conceive with assisted
human reproduction. (III-L)
7. There is growing evidence that pregnancy outcomes
are better for cryopreserved embryos fertilized in
vitro than for fresh embryo transfers. This finding
supports a policy of elective single embryo transfer
for women with a good prognosis (with subsequent
use of cryopreserved embryos as necessary), and
may reassure women who are considering in vitro
fertilization. (II-2A)
8. Women and couples considering assisted human
reproduction and concerned about perinatal
outcomes in singleton pregnancies should be
advised that (1) intracytoplasmic sperm injection
does not appear to confer increased adverse
perinatal or maternal risk over standard in vitro
fertilization, and (2) the use of donor oocytes
increases successful pregnancy rates in selected
women, but even when accounting for maternal
age, can increase the risk of low birth weight and
preeclampsia. (II-2B)
FETAL STRUCTURAL, CHROMOSOMAL, AND
IMPRINTING ABNORMALITIES ASSOCIATED
WITH ASSISTED HUMAN REPRODUCTION
Structural Abnormalities (Malformations,
Deformations, and Disruptions)
Previous studies of the association between ART and
structural congenital malformations have reported an
elevated risk, but were limited by small sample sizes,
varying definitions of congenital anomalies, and lack
of data on potential confounding variables.147–149 A
longitudinal study of the Danish national birth cohort
found that singletons born to couples with a history
of infertility, but who conceived naturally or with
ART treatment had a higher prevalence of congenital
malformations (HR 1.20; 95% CI 1.07 to 1.35) than
babies born spontaneously with no delay in time to
conception. Babies born of ART in infertile couples had
an increased prevalence of genital organ malformations
(HR 2.32; 95% CI 1.24 to 4.35).27
Pregnancy Outcomes After Assisted Human Reproduction
The National Birth Defects Prevention Study provided a case-
controlled analysis of registered live-born infants versus those
born through ART for congenital defects. Adjustments for
confounders included maternal race, maternal age, smoking,
and parity. ART was associated with septal heart defects (aOR
2.1; 95% CI 1.1 to 4.0); esophageal atresia (aOR 4.5; 95% CI
1.9 to 10.5), and anorectal atresia (aOR 3.7; 95% CI 1.5 to 9.1).
Among multiple births, there was no significant association
between ART and birth defects.150
The findings of a recent retrospective cohort study of IVF/
ICSI patients in a Canadian centre suggest there is a higher
prevalence of infants with congenital heart defects in infants
conceived by IVF/ICSI (1.1%) than in spontaneously
conceived infants (0.4%) (P < 0.01). A maternal BMI of
> 30 kg/m2 was found to increase this prevalence of birth
defects.151
More recent registry data demonstrate a higher risk for
major congenital abnormalities in infants following both
IVF and IVF-ICSI than in spontaneous conceptions,
after adjusting for appropriate confounding factors.152
IVF-ICSI has been shown to have a 2-fold increased risk
for major malformations in singletons (8.9%), compared
with spontaneous conceptions (6.0%), and a 2-fold
risk for major malformations in one or both newborns
among twin gestations following IVF-ICSI, compared
with singletons following IVF-ICSI.149,153 A meta-analysis
reviewing data from 46 different studies, including 124 468
infants conceived with ART, compared with spontaneously
conceived children, showed that the total adjusted RR for
ART procedures versus spontaneous conception was 1.36
(95% CI 1.26 to 1.48), with no difference seen between IVF
and IVF/ICSI.154
Davies et al.38 compared the incidence of birth defects,
including births and terminations of pregnancy, in patients
in South Australia undergoing IVF (with or without ICSI)
with those of spontaneous pregnancies. Among the total
IVF cases (± ICSI), the aOR for IVF ± ICSI was 1.28 (95%
CI 1.16 to 1.41). Comparing IVF alone to spontaneous
pregnancies resulted in the loss of any significant effect of
ART, while IVF/ICSI remained a significant risk factor, with
an aOR of 1.57 (95% CI 1.30 to 1.90). In the same population
(N = 308 974), the incidence of birth defects with a history
of infertility, with or without ART, was higher than among
spontaneous pregnancies without a history of infertility.2
Recommendations
9. Any assisted reproductive technology procedure
should be prefaced by a discussion of fetal
outcomes and the slight increase in the risk of
congenital structural abnormalities, with emphasis
JANUARY JOGC JANVIER 2014 l 75
SOGC Clinical Practice Guidelines
Table 5. Human phenotypes identified and associated with
imprinted genes
Syndrome
1. Beckwith-Wiedemann
2. Angelman
3. Prader-Willi
4. Silver-Russell
5. Transient neonatal diabetes mellitus
6. McCune Albright
7. Familial nonchromaffin paraganglioma
8. Maternal and paternal uniparental disomy
9. Turner
on known confounding factors such as infertility
and body mass index. (II-2B)
10. In pregnancies achieved by assisted reproductive
technology, routine anatomic ultrasound for
congenital structural abnormalities is recommended
between 18 and 22 weeks. (II-2A)
Chromosomal Disorders
The incidence of any chromosomal abnormality in births
and induced terminations, after adjusting for maternal age
and parity, following IVF (0.7%) has been shown to be
similar to those in spontaneously conceived pregnancies
(0.2%), but significantly higher following IVF-ICSI
(1.0%).149 Significantly more de novo chromosomal
aberrations have been diagnosed prenatally in children
conceived by IVF-ICSI than the general newborn
population155 A prospective clinical observation study156
analyzed peripheral and umbilical cord blood samples of
male children born to fathers with normal spermatogenesis.
De novo Y-chromosome microdeletions were identified
in 5.3% of 19 IVF offspring and in 16.7% of 18 ICSI
offspring; both techniques were statistically significantly
associated with a higher rate of de novo Y-chromosome
microdeletions than in male children conceived naturally.
As in spontaneously conceived pregnancies, options for
prenatal diagnosis of aneuploidy (chorionic villus sampling or
amniocentesis) in patients who conceive after AHR should
be determined by results of prenatal screening tests for
aneuploidy,156 except for those resulting from IVF-ICSI.154
Most studies find no significant differences between nuchal
translucency measurements in IVF and IVF-ICSI pregnancies
and in spontaneously conceived pregnancies.158 PAPP-A levels
have been found to be significantly lower after ART.159 MSAFP
is not a reliable marker for neural tube defects following fetal
reduction.160 Elevated MSAFP levels have been observed in
pregnancies conceived with donor oocytes.161
76 l JANUARY JOGC JANVIER 2014
Chromosome location
11p15
15q11-q12 maternal
15q11-q12 paternal
7p11-p13, 7q31-qter, 11p15
6q24
20q13
11q13
2, 14, 16
X
Recommendation
11. Pregnancies conceived by intracytoplasmic sperm
injection may be at increased risk of chromosomal
aberrations, including sex chromosome
abnormalities. Diagnostic testing should be offered
after appropriate counselling. (II-2A)
Imprinting Disorders
Pregnancies using ART are increasing with the availability
of the technology and with patient needs and choices,
and recent estimates indicate that in industrialized and
developed countries 1.7% to 4.0% of all children are born
after ART.2 The first live-born offspring after IVF, FET,
and ICSI were reported in 1978, 1984, and 1992.162–164
The association between adverse pregnancy outcomes
and genetic imprinting errors with the identification
of epimutations is rare, but understanding of the
mechanisms through animal and human research is
quickly expanding.
Genomic imprinting is a process of epigenetic modification
which allows genes to be expressed in a parent-of-origin–
specific manner. These genetic loci are important for
normal growth and development. Imprinting is found
predominately in placental mammals and may have evolved as
a mechanism to balance the allocation of parental resources
to the offspring.16,46 Epigenetics is the modification of the
“complete” DNA structure by methylation or histones that
results in the gene becoming non-transcribed in a time-
specific period or a tissue-specific fashion, but with no
alteration of the actual DNA coding sequence in the gene.
Nine human phenotypes have been identified and associated
with an imprinted gene (Table 5).165,166
The imprinting loci/epimutations in phenotypes that
have been strongly associated with children conceived
with ART are Beckwith-Wiedemann syndrome, Silver-

Russell syndrome, and Angelman syndrome. The reported
evidence of association between these imprinting
phenotypes and various ART techniques, including IVF
and ICSI, have been confined to epimutations.
There are a number of potential mechanisms by which
ART could contribute to the creation of epimutations.
The composition/culture of the media environment,
disruption of maternally-imprinted genes with super-
ovulation, hypomethylation of paternal or maternal genes,
or, as with the other potential adverse outcomes perhaps
incorrectly associated with ART, the underlying condition
responsible for infertility, could all be associated with
imprinting abnormalities.17
While the association between imprinting and ART has
biological plausibility and strong data from animal and
human species, the overall risk for a child to be born with
an imprinting defect following ART is low. The probable
increased imprinting-associated ART risks are related to
the phenotypes Silver-Russell syndrome and Beckwith-
Wiedemann syndrome, with less evidence supporting the
association with Angelman syndrome and Prader-Willi
syndrome.
Studies have proposed that ART children are at a greater
risk of later malignancy, with a possible etiology of reduced
imprinted gene activity leading to dysregulation in tumour
suppression.168 Large follow-up studies suggest an increased
cancer risk in ART children, but other confounding factors,
such as prematurity and asphyxia, may be in play.169 Further
studies are required, as the majority of the ART cohort is
under age 30.169
A 2009 review concluded that “epigenetic aberrations can
result in outcomes as specific as Beckwith-Wiedemann
syndrome or as diffuse as growth restriction.”167
Substantial evidence exists from animal and human studies
that gametogenesis and preimplantation are vulnerable
to epimutations. Whether ART introduces epigenetic
aberrations during these critical times, or whether
epimutations are more frequent in individuals with
infertility, remains unresolved.167
Summary Statement
2. The relative risk for an imprinting phenotype such
as Silver-Russell syndrome, Beckwith-Wiedemann
syndrome, or Angelman syndrome is increased in
the assisted reproduction population, but the actual
risk for one of these phenotypes to occur in an
assisted pregnancy is estimated to be low, at less
than 1 in 5000. The exact biological etiology for this
imprinting risk increase is likely heterogeneous and
requires more research. (II-2)
Pregnancy Outcomes After Assisted Human Reproduction
Recommendation
12. The possible increased risk for late onset cancer
due to gene dysregulation for tumour suppression
requires more long-term follow-up before the true
risk can be determined. (III-A)
Preimplantation Genetic Screening
Recently, more ART cycles have incorporated
preimplantation genetic screening for aneuploidy or
random genetic error at the stage of the embryo to
increase the chance of a successful live birth. The
process includes the microscopic biopsy of embryos at
72 hours of age to isolate a blastomere or trophectoderm
tissue at the blastocyst stage of development. Genomic
analysis is then done using traditional fluorescent in situ
hybridization analysis of 5 to 7 chromosomes or, more
recently, whole genome analysis using comparative
genomic hybridization.170,171 Indications for the
application include advanced maternal age, repeated
IVF failure, recurrent miscarriage, and testicular sperm
extraction.
The literature remains controversial with respect to the
testing’s proven benefit in terms of a healthy live birth
as an outcome and, more specifically, with respect to the
well-being of that infant. A recent report of a series of
581 children born after PGS found that birth weight and
major malformation rates were not statistically different
from those of other IVF/ICSI children.172 The same study
also reported the misdiagnosis rate was less than 1%. A
further prospective blinded follow-up study of children
born to women randomly assigned to receive PGS or not
found that the technique was not associated with impaired
mental, psychomotor, or behavioural outcomes by age 2
years, although there was a suggestion that with detailed
neurological testing, PGS was associated with a less “optimal”
neurological testing score.173 More recently the same group
reported on the follow-up of the same cohort at 4 years
of age. They found no effect of PGS on singletons in the
cohort, but a significant negative difference in neurological
testing scores among twins after PGS.174 Thus the effects of
preimplantation genetic screening on long-term outcomes
are unclear.
A recently published technical update has reviewed
preimplantation screening and diagnosis in more detail.175
Recommendations
13. T he clinical application of preimplantation
genetic testing in fertile couples must balance the
benefits of avoiding disease transmission with
the medical risks and financial burden of in vitro
fertilization. (III-B)
JANUARY JOGC JANVIER 2014 l 77
SOGC Clinical Practice Guidelines
14. Preimplantation screening for aneuploidy
is associated with inconsistent findings for
improving pregnancy outcomes. Any discussion
of preimplantation genetic screening with patients
should clarify that there is no adequate information
on the long-term effect of embryo single cell
biopsy. (I-C)
SUMMARY
As with knowledge of outcomes in other emerging and
developing technologies, there continue to be gaps in our
knowledge of the association of AHR with maternal,
perinatal, and childhood outcomes. A recent discussion
paper prepared for AHRC on reproductive outcomes after
AHR has emp hasized the importance of comprehensive
outcomes surveillance systems that build on the current
CARTR database, with personalized health information,
measurable outcomes including long-term and
developmental outcomes, and the ability to link to other
relevant national and international databases.1
There has been an improvement in the quality of data with
the accumulation and accuracy of large population databases
and improved linkage of AHR parameters to birth and
early childhood outcomes, but ongoing efforts in this area
are critical to further specify the differential association of
underlying infertility factors and details of AHR on outcomes.
The majority of pregnancies resulting from AHR are
uncomplicated and result in the birth of healthy children.
However, it is also clear that when TTP are greater than
one year, a higher proportion of AHR pregnancies than
spontaneous pregnancies are associated with obstetrical
and perinatal complications, whether it be a result primarily
of underlying parental factors leading to infertility or of
specific AHR techniques.
The majority of obstetric and pediatric problems after
AHR arise as a result of multiple pregnancies. Much new
evidence has accumulated to encourage the use of eSET
where appropriate and, when applied, this has been shown
to markedly reduce the multiple pregnancy rate. Counselling
of prospective parents should incorporate this knowledge.
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147. Schieve LA, Rasmussen SA, Buck GM, Schendel DE, Reynolds MA,
Wright VC. Are children born after assisted reproductive technology
at increased risk for adverse health outcomes? Obstet Gynecol
2004;103:1154–63.
148. Ericson A, Kallen BA. Nonsteroidal anti-inflammatory drugs in early
pregnancy. Reprod Toxicol 2001;15:371–5.
149. Wennerholm UB, Bergh C, Hamberger L, Lundin K, Nilsson L,
Wikland M, et al. Incidence of congenital malformations in children
born after ICSI. Hum Reprod 2000;15:944–8.
150. Reefhuis J, Honein MA, Schieve LA, Correa A, Hobbs CA,
Rasmussen SA. Assisted reproductive technology and major structural
birth defects in the United States. Hum Reprod 2009;24:360–6.
151. Wen SW, Leader A, White RR, Léveillé MC, Wilkie V, Zhou J, et al.
A comprehensive assessment of outcomes in pregnancies conceived by in
vitro fertilization/intracytoplasmic sperm injection. Eur J Obstet Gynecol
Reprod Biol 2010;150:160–5.
152. Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth
defects after intracytoplasmic sperm injection and in vitro fertilization.
N Engl J Med 2002;346:725–30.
153. Katalinic A, Rösch C, Ludwig M; German ICSI Follow-Up Study
Group. Pregnancy course and outcome after intracytoplasmic
sperm injection: a controlled, prospective cohort study. Fertil Steril
2004;81:1604–16.
154. Chen T, McDonald A, Shadbolt B, Talaulikar D. Precision of histological
bone marrow staging in follicular lymphoma and diffuse large B-cell
lymphoma. Clin Invest Med 2012;35:E358.
155. Bonduelle M, Van Assche E, Joris H, Keymolen K, Devroey P,
Van Steirteghem A, et al. Prenatal testing in ICSI pregnancies: incidence
of chromosomal anomalies in 1586 karyotypes and relation to sperm
parameters. Hum Reprod 2002;17:2600–14.
156. Feng C, Wang LQ, Dong MY, Huang HF. Assisted reproductive
technology may increase clinical mutation detection in male offspring.
Fertil Steril 2008;90:92–6.
157. Chitayat D, Langlois S, Wilson RD; SOGC Genetics Committee; CCMG
Prenatal Diagnosis Committee. Prenatal screening for fetal aneuploidy in
singleton pregnancies. Society of Obstetricians and Gynaecologists of
Canada Clinical Practice Guideline, No. 261, July 2011. J Obstet Gynaecol
Can 2011;33:736–50.
158. Ranta JK, Raatikainen K, Romppanen J, Pulkki K, Heinonen S. Increased
time-to-pregnancy and first trimester Down’s syndrome screening. Hum
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159. Amor DJ, Xu JX, Halliday JL, Francis I, Healy DL, Breheny S, et al.
Pregnancies conceived using assisted reproductive technologies (ART)
have low levels of pregnancy-associated plasma protein-A (PAPP-A)
leading to a high rate of false-positive results in first trimester screening
for Down syndrome. Hum Reprod 2009;24:1330–8.
160. Shulman LP, Phillips OP, Cervetti TA. Maternal serum analyte levels
after first-trimester multifetal pregnancy reduction. Am J Obstet Gynecol
1996;174:1072–4.
161. Shulman A, Maymon R. Mid-gestation Down syndrome screening
test and pregnancy outcome among unstimulated assisted-conception
pregnancies. Prenat Diagn 2003;23:625–8.

162. Steptoe PC, Edwards RG. Birth after the reimplantation of a human
embryo. Lancet 1978;2:366.
163. Zeilmaker GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC.
Two pregnancies following transfer of intact frozen-thawed embryos.
Fertil Steril 1984;42:293–6.
164. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after
intracytoplasmic injection of single spermatozoon into an oocyte. Lancet
1992;340:17–8.
165. Ishida M, Moore GE. The role of imprinted genes in humans. Mol
Aspects Med 2013;34:826–40.
166. Iliadou AN, Janson PC, Cnattingius S. Epigenetics and assisted
reproductive technology. J Intern Med 2011;270:414–20.
167. Wilkins-Haug L. Epigenetics and assisted reproduction. Curr Opin
Obstet Gynecol 2009;21:201–6.
168. Lim DH, Maher ER. Genomic imprinting syndromes and cancer.
Adv Genet 2010;70:145–75.
169. Savage T, Peek J, Hofman PL, Cutfield WS. Childhood outcomes
of assisted reproductive technology. Hum Reprod
2011;26:2392–400.
170. Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al.
Validation of array comparative genome hybridization for diagnosis of
translocations in preimplantation human embryos. Reprod Biomed Online
2012;24:621–9.
Pregnancy Outcomes After Assisted Human Reproduction
171. Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L,
et al. PGD for reciprocal and Robertsonian translocations using
array comparative genomic hybridization. Hum Reprod
2011;26:1925–35.
172. Liebaers I, Desmyttere S, Verpoest W, De Rycke M, Staessen C,
Sermon K, et al. Report on a consecutive series of 581 children born after
blastomere biopsy for preimplantation genetic diagnosis. Hum Reprod
2010;25:275–82.
173. Middelburg KJ, van der Heide M, Houtzager B, Jongbloed-Pereboom M,
Fidler V, Bos AF, et al. Mental, psychomotor, neurologic, and behavioral
outcomes of 2-year-old children born after preimplantation genetic
screening: follow-up of a randomized controlled trial. Fertil Steril
2011;96:165–9.
174. Schendelaar P, Middelburg KJ, Bos AF, Heineman MJ, Kok JH,
La Bastide-Van Gemert S, et al. The effect of preimplantation
genetic screening on neurological, cognitive and behavioural
development in 4-year-old children: follow-up of a RCT.
Hum Reprod 2013;28:1508–18.
175. Audibert F; SOGC Genetics Committee. Preimplantation genetic testing.
Society of Obstetricians and Gynaecologists Canada, Technical Update
No. 232, August 2009. J Obstet Gynaecol Can 2009;31:761–75.
176. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
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2003;169:207–8.
JANUARY JOGC JANVIER 2014 l 83
 SOGC CLINICAL PRACTICE GUIDELINE
Prenatal Invasive Procedures in Women
With Hepatitis B, Hepatitis C, and/or
Human Immunodeficiency Virus Infections
This guideline has been prepared by the Genetics Committee,
reviewed by the Infectious Disease Committee, and approved
by the Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Alain Gagnon, MD, FRCSC, Vancouver BC
Gregory Davies, MD, FRCSC, Kingston ON
R. Douglas Wilson, MD, FRCSC, Calgary AB
GENETICS COMMITTEE
R. Douglas Wilson (Chair), MD, Calgary AB
Francois Audibert, MD, Montreal QC
Jo-Ann Brock, MD, Halifax NS
Carla Campagnolo, MSc, CCGC, London ON
June Carroll, MD, Toronto ON
David Chitayat, MD, Toronto ON
Alain Gagnon, MD, Vancouver BC
Jo-Ann Johnson, MD, Calgary AB
William MacDonald, MD, Halifax NS
Lynn Murphy-Kaulbeck, MD, Moncton NB
Nanette Okun, MD, Toronto ON
Melanie Pastuck, RN, Cochrane AB
Disclosure statements have been received from all
contributors.
Key Words: Pregnancy, genetics, amniocentesis, chorionic villus
sampling, viral hepatitis, human immunodeficiency virus, prenatal
diagnosis
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
648 l JULY JOGC JUILLET 2014
No. 309, July 2014 (Replaces No. 123, February 2003)
Abstract
Objective: To review the risk of in utero infection through prenatal
invasive procedures in women with hepatitis B, hepatitis C,
and/or human immunodeficiency virus (HIV) infections.
Outcomes: Fetal and neonatal morbidity and mortality.
Evidence: Published literature was retrieved through searches of
Medline, CINAHL, and the Cochrane Library using appropriate
controlled vocabulary (amniocentesis, chorionic villus
sampling, cordocentesis, fetal and neonatal infection) and key
words (hepatitis B, hepatitis C, HIV). Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies from 2002 to 2012 published
in English or French. (Studies from 1966 to 2002 were
previously reviewed in Clinical Practice Guideline No. 123.)
Searches were updated on a regular basis and incorporated in
the guideline to February 2014.
Grey (unpublished) literature was identified through searching
the websites of health technology assessment and health
technology-related agencies, clinical practice guideline
collections, clinical trial registries, and national and
international medical specialty societies.
Values: The quality of evidence in this document was rated using
the criteria described in the Report of the Canadian Task
Force on Preventive Health Care (Table).
Recommendations
1. For women infected with hepatitis B, hepatitis C, and/or
human immunodeficiency virus, the use of non-invasive
methods of prenatal risk assessment is recommended, using
tests with high sensitivity and low false-positive rates, such as
serum screening combined (or not) with nuchal translucency,
anatomic ultrasound, and non-invasive molecular prenatal
testing. (III-B)
J Obstet Gynaecol Can 2014;36(7):648–653
 Prenatal Invasive Procedures in Women With Hepatitis B, Hepatitis C, and/or Human Immunodeficiency Virus Infections
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.35
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.35
2. For women infected with hepatitis B, hepatitis C, and/or human
immunodeficiency virus undergoing an amniocentesis, every effort
should be made to avoid inserting the needle through, or very
close to, the placenta. (II-2B)
3. Little information is available on other prenatal diagnostic
and therapeutic invasive procedures; the risks and benefits
of such procedures should therefore be assessed prior to their
use. (III-C)
4. The rate of neonatal hepatitis B infection attributable to
amniocentesis ranges up to 1.4% in newborns of mothers positive
for hepatitis B surface antigen. However, the rate of neonatal
infection attributable to amniocentesis in newborns of mothers with
a positive hepatitis B e antigen status may be as high as 16%.
Although there is no statistically significant difference between
the rates of infection in newborns exposed to amniocentesis or
not exposed to amniocentesis in these two maternal populations,
knowledge of the mother’s hepatitis B e antigen status may be
valuable in counselling women about the risks associated with
amniocentesis. (II-2A)
5. Amniocentesis in women infected with hepatitis C does not appear
to significantly increase the risk of vertical transmission, but
women should be counselled that very few studies have properly
addressed this possibility (II-2C). More research on this topic is
recommended. (III-L)
6. Amniocentesis in women infected with human immunodeficiency
virus on combination antiretroviral therapy does not appear to
significantly increase the risk of vertical transmission, particularly
if the viral load is undetectable, but women should be counselled
that data on this issue is limited. (II-2B)
7. For women not on combined antiretroviral therapy, the
risk of vertical transmission is increased by performing an
amniocentesis. When possible, combined antiretroviral therapy
should be initiated and the procedure postponed until the
viral load is undetectable. Other case management should be
individualized in consultation with infectious diseases specialists
and obstetricians. (III-B)
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
INTRODUCTION
T hese guidelines are designed to address the risks of in
utero infection (vertical transmission) through prenatal
invasive procedures in women infected with hepatitis B,
hepatitis C, and/or HIV so that obstetric care providers
may better counsel these women about their options.
ASSESSMENT OF RISK AND AMNIOCENTESIS
For women infected with hepatitis B, hepatitis C, or HIV, the
addition of non-invasive methods of prenatal risk screening,
such as serum screening combined (or not) with nuchal
translucency, and anatomic ultrasound, provide the best risk
assessment possible to properly inform women of their risk
of chromosomal anomalies. The best available test should
be used to keep the false-positive rate to a minimum. None
of these infections seems to be associated with a significant
increase in vertical transmission when amniocentesis is
performed in the settings described below. The use of NIPT
using cell-free DNA technology could be based on the same
indications as in women without these chronic infections.
Women whose risk of vertical transmission is significantly
higher than in those not exposed to an invasive procedure
(such as HIV-infected women not on cART) should be
considered for NIPT prior to any confirmatory invasive
testing, after being counselled on the benefits and
limitations of the test. NIPT provides higher sensitivity
(close to 100%) and a lower false-positive rate (around
1%) when screening for trisomy 13, 18, or 21 in a high-
risk population than the most frequently used screening
JULY JOGC JUILLET 2014 l 649
SOGC CLINICAL PRACTICE GUIDELINE
methods (such as serum based screening or first trimester
screening). Because of its lower false-positive rate, it
can therefore reduce the number of amniocenteses
performed. Currently NIPT does not routinely screen
for other chromosomal anomalies that are found more
often in women who screen positive with the first-line
screening approaches. It is often used as a secondary test
prior to invasive testing or as a primary test in a high-risk
population based on age or previous history.1 Data on the
accuracy of the test in a general population is limited. It
has not been studied specifically in a population with a
chronic viral infection or on antiretroviral medications.
In planning for an amniocentesis for women infected
with hepatitis B, hepatitis C, and/or HIV undergoing
amniocentesis, every effort should be made to avoid
inserting the needle through the placenta, as was the case
in all the series described in this guideline.
Limited information is available on procedures other than
amniocentesis in this population, therefore this guideline
focuses specifically on that procedure.
Recommendations
1. For women infected with hepatitis B, hepatitis C,
and/or human immunodeficiency virus, the use of
non-invasive methods of prenatal risk assessment
is recommended, using tests with high sensitivity
and low false-positive rates, such as serum screening
combined (or not) with nuchal translucency,
anatomic ultrasound, and non-invasive molecular
prenatal testing. (III-B)
2. For women infected with hepatitis B, hepatitis C,
and/or human immunodeficiency virus undergoing
an amniocentesis, every effort should be made to
avoid inserting the needle through, or very close to,
the placenta. (II-2B)
3. Little information is available on other prenatal
diagnostic and therapeutic invasive procedures;
the risks and benefits of such procedures should
therefore be assessed prior to their use. (III-C)
ABBREVIATIONS
cART combined antiretroviral therapy
CVS chorionic villus sampling
DNA deoxyribonucleic acid
HBeAg hepatitis B e antigen
HBsAg hepatitis B surface antigen
HCV hepatitis C virus
HIV human immunodeficiency virus
NIPT non-invasive molecular prenatal testing
RNA ribonucleic acid
650 l JULY JOGC JUILLET 2014
HEPATITIS B
In women presenting for prenatal care, hepatitis B has
a prevalence of 0.34% to 1.1%.2–4 The rate of vertical
transmission in HBsAg-positive women without
immunoprophylaxis is approximately 15%, and may be as
high as 90% in those women who are HBsAg- and HBeAg-
positive. With appropriate immunoprophylaxis, the rate of
vertical transmission drops to 1.5% for women who are
HBsAg-positive and to 10% for women who are HBsAg- and
HBeAg-positive.5 Genetic amniocentesis has been reported
in 115 HBsAg positive-women.6–9 Most amniocenteses were
performed with care to avoid a transplacental approach.
All the infants of these pregnancies received hepatitis B
vaccination and immunoprophylaxis commencing at birth.
The overall rate of vertical transmission was 2.9%. This
rate of immunoprophylaxis failure is consistent with rates
seen in women who have not undergone amniocentesis.10
In one series, 3 infants (30%) of mothers who were HBeAg-
positive demonstrated postnatal seroconversion following an
amniocentesis, compared with 14% for those whose HBeAg-
positive mothers did not have an amniocentesis (P > 0.05).9
These findings would suggest that the risk of fetal hepatitis B
infection through amniocentesis is low. However, knowledge
of the mother’s HBeAg-status may be valuable when
counselling on the risks associated with amniocentesis, as the
transmission rate may be higher in HBeAg-positive women.
No available studies report on vertical transmission in
this population using other prenatal invasive procedures
(such as CVS or fetal blood sampling) or assess preventive
strategies (such as hepatitis B immunoglobulin and antiviral
therapies) prior to invasive prenatal procedures.
Recommendation
4. The rate of neonatal hepatitis B infection attributable
to amniocentesis ranges up to 1.4% in newborns
of mothers positive for hepatitis B surface antigen.
However, the rate of neonatal infection attributable to
amniocentesis in newborns of mothers with a positive
hepatitis B e antigen status may be as high as 16%.
Although there is no statistically significant difference
between the rates of infection in newborns exposed
to amniocentesis or not exposed to amniocentesis in
these two maternal populations, knowledge of the
mother’s hepatitis B e antigen status may be valuable
in counselling women about the risks associated with
amniocentesis. (II-2A)
HEPATITIS C
The prevalence of hepatitis C varies greatly between
populations. Generally, the prevalence in women of
 Prenatal Invasive Procedures in Women With Hepatitis B, Hepatitis C, and/or Human Immunodeficiency Virus Infections
reproductive age is 1% to 2%.11,12 A British Columbia
study reported a prevalence of HCV infection of around
0.9% in the pregnant population, although only half of
those women would have been detected through testing
based on risk-factors.13 In women in the Canadian federal
penitentiary system, however, the prevalence is 40%,14 and in
antenatal clinics in Scotland it is 0.6%.14 The rate of vertical
transmission is approximately 5% to 10%.15–18 The exact
timing of vertical transmission is unknown, but elective
Caesarean section does not appear to be preventive.18 The
risk of vertical transmission appears to be increased in
women whose hepatitis C is associated with active liver
disease, in those whose level of HCV RNA is greater than
106/mL, and in women co-infected with HIV.15,18 Only a
few series discuss the use of amniocentesis in pregnant
women infected with HCV. One series reported the use
of amniocentesis in 22 women with hepatitis C, of whom
16 had HCV RNA identified in their serum. All women
(median age 39 years) underwent amniocentesis in the 4th
month of pregnancy.19 The amniotic fluid samples were
tested using polymerase chain reaction for HCV RNA.
Of the 16 viremic women, HCV RNA was detected in the
amniotic fluid of only one, whose placenta was anterior.
On postnatal testing, none of the children from these
pregnancies, including the child from the pregnancy with
HCV RNA-positive amniotic fluid, was found to be HCV
RNA-positive.19 A case–control study, published as an
abstract only, of factors involved in vertical transmission
reported a similar rate of amniocentesis in infected (8/51)
and non-infected (28/110) children.20 In contrast, a case
series of 44 vertically infected children reported a history
of amniocentesis in 10 (22.5%) of the pregnancies, a
rate higher than seen in the general population.21 Finally,
Minola et al. reported a case of a twin pregnancy in which
only one sac was sampled, and only that one fetus was
infected at 12 months of age.22 Although the 2 best studies
are somewhat reassuring, little is learned from these series,
as the various methodologies do not allow for a meta-
analysis. In summary, amniocentesis in women infected
with hepatitis C does not significantly increase the risk of
vertical transmission, but women should be counselled that
very few studies have properly addressed this possibility,
nor have factors that could affect the transmission rate
been well studied.
There are no studies available on other prenatal invasive
procedures such as CVS or fetal blood sampling.
Recommendation
5. Amniocentesis in women infected with hepatitis C
does not appear to significantly increase the risk of
vertical transmission, but women should
be counselled that very few studies have properly
addressed this possibility (II-2C). More research on
this topic is recommended (III-L).
HUMAN IMMUNODEFICIENCY VIRUS
The prevalence of HIV in an obstetric population varies
greatly, depending on the population studied. The reported
prevalence in British Columbia is 0.03%, while in some inner
city populations in the United States, the prevalence is as
high as 1.5%.23,24 The AIDS Clinical Trials Group 076 study
clearly demonstrated a 26% vertical transmission rate, which
was lowered to 8% in patients who received antepartum,
intrapartum, and neonatal zidovudine therapy.25 Many
HIV-positive women are now taking cART.26 In those, the
vertical transmission rate has decreased to less than 1%.27
In a French series of 1632 HIV-positive women, of whom
only 5% received antenatal zidovudine therapy, the rate
of vertical transmission was 19%.28 Amniocentesis was
performed on 13 women and amnioscopy on 26 women, with
a vertical transmission rate of 36%. This rate was significantly
higher than that observed in women who did not have
invasive needling procedures (18%). Five series reporting on
a total of 159 women on cART provide contemporary data
on this topic. No case of vertical transmission was reported in
those series for women having undergone an amniocentesis
while on cART.29 A contemporaneous French cohort of 2528
women on cART who had not had an amniocentesis had a
reported 1.2% transmission rate.30 With this reassuring data,
experts now suggest that indicated amniocentesis should not
be avoided in women with HIV who are on cART, particularly
if their viral loads are low, but that the best non-invasive
screening available should be used prior to invasive testing by
amniocentesis.
López and Coll suggest that 2 weeks of cART prior to
the amniocentesis were sufficient to provide the therapy’s
observed benefit of reduced vertical transmission.29 Others
recommend waiting for an undetectable viral load before
proceeding.31 These factors should be considered in the choice
of antiretroviral, which should be made in consultation with
infectious diseases specialists and obstetrical care providers.
For example, raltegravir could be used to rapidly decrease a
high maternal viral load before the amniocentesis.32
Somigliana et al. reported in their series 3 women having
undergone CVS and 4 having undergone a cordocentesis,
all while on cART.33 No cases of vertical transmission
were reported in those 7 women. With such limited
data, however, the use of these procedures cannot be
recommended if amniocentesis is an option, because more
data is available on amniocentesis.
JULY JOGC JUILLET 2014 l 651
SOGC CLINICAL PRACTICE GUIDELINE
Recommendations
6. Amniocentesis in women infected with human
immunodeficiency virus on combination antiretroviral
therapy does not appear to significantly increase the
risk of vertical transmission, particularly if the viral
load is undetectable, but women should be counselled
that limited data is available on this issue. (II-2B)
7. For women not on combined antiretroviral therapy,
the risk of vertical transmission is increased by
performing an amniocentesis. When possible,
combined antiretroviral therapy should be initiated
and the procedure postponed until the viral load
is undetectable. Other case management should
be individualized in consultation with infectious
diseases specialists and obstetricians. (III-B)
RISK OF AMNIOTIC FLUID
CONTAMINATION AT AMNIOCENTESIS
Contamination of the fetal amniotic cavity with maternal blood
during amniocentesis is common.34 In a study by Giorlandino
et al., 20 women underwent a second amniocentesis 2 weeks
after the original amniocentesis because of cell culture
contamination.34 At the second amniocentesis all 20 were found
to have maternal blood contamination in the amniotic fluid
based on red blood cell and hemoglobin concentrations.34 The
amniotic fluids of women undergoing their first amniocentesis
were used as matched control subjects and no maternal blood
contamination was found at the onset of the procedure. The
amount of maternal blood in the amniotic fluid was significantly
increased when an anterior placenta was present.34
CONCLUSION
There is a critical lack of evidence to determine the impact
of prenatal invasive procedures on the risk of vertical
transmission in women with hepatitis B, hepatitis C,
and/or HIV. For this reason, non-invasive methods of
prenatal risk screening that provide the highest sensitivity
with the lowest false-positive rate should be used to
minimize the number of amniocenteses performed. The
available evidence suggests the risk of vertical transmission
through amniocentesis in women infected with hepatitis B
and hepatitis C is not greatly increased if present at all. In
contrast, the risk of vertical transmission of HIV appears
to be increased through amniocentesis for women not on
cART. For women with HIV treated on cART for at least
2 weeks, the risk of vertical transmission associated with
amniocentesis appears to be negligible if present at all.
Efforts should be made in all cases to avoid inserting the
needle through the placenta.
652 l JULY JOGC JUILLET 2014
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12. Ford PM, White C, Kaufmann H, MacTavish J, Pearson M, Ford S, et al.
Voluntary anonymous linked study of the prevalence of HIV infection
and hepatitis C among inmates in a Canadian federal penitentiary for
women. CMAJ 1995;153:1605–9.
13. Blasig A, Wagner EC, Pi D, Bigham M, Remple VP, Craib KJP, et al.
Hepatitis C infection among pregnant women in British Columbia:
reported prevalence and critical appraisal of current prenatal screening
methods. Can J Public Health 2011;102:98–102.
14. Goldberg D, McIntyre PG, Smith R, Appleyard K, Dunlop J, Taylor A,
et al. Hepatitis C virus among high and low risk pregnant women
in Dundee: unlinked anonymous testing. Br J Obstet Gynaecol
2001;108:365–70.
15. Ohto H, Terazawa S, Sasaki N, Sasaki N, Hino K, Ishiwata C, et al.
Transmission of hepatitis C virus from mothers to infants. The Vertical
Transmission of Hepatitis C Virus Collaborative Study Group. N Engl J
Med 1994;330:744–50.
16. Hillemanns P, Dannecker C, Kimmig R, Hasbargen U. Obstetric risks and
vertical transmission of hepatitis C virus infection in pregnancy.
Acta Obstet Gynecol Scand 2000;79:543–7.
 Prenatal Invasive Procedures in Women With Hepatitis B, Hepatitis C, and/or Human Immunodeficiency Virus Infections
17. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and
clinical course of chronic hepatitis C virus (HCV) infection and rate
of HCV vertical transmission in a cohort of 15,250 pregnant women.
Hepatology 2000;31:751–5.
18. European Paediatric Hepatitis C Virus Network. Effects of mode of
delivery and infant feeding on the risk of mother-to-child transmission of
hepatitis C virus. Br J Obstet Gynaecol 2001;108:371–7.
19. Delamare C, Carbonne B, Heim N, Berkane N, Petit JC, Uzan S, et al.
Detection of hepatitis C virus RNA (HCV RNA) in amniotic fluid:
a prospective study. J Hepatol 1999;31:416–20.
20. Poiraud S, Cohen J, Amiot X, Berkane N, Flahauif A, Dussaix E, et al.
Mother to child transmission of hepatitis C virus: a case-control study of
risk factors. Gastroenterology 2001;(Suppl A):A–366.
21. Cohen J, Dessaix E, Bernard O. Transmission du virus de l’hépatite C
de la mère à l’enfant: une étude de 44 enfants. Gastroenterol Biol Clin
1998;22:A179.
22. Minola E, Maccabruni A, Martinetti M. Amniocentesis as a possible risk
factor for mother-to-infant transmission of hepatitis C virus. Hepatology
2001;33:1341–42.
23. Patrick DM, Money DM, Forbes J, Dobson SR, Rekart ML, Cook DA,
et al. Routine prenatal screening for HIV in a low-prevalence setting.
CMAJ 1998;159:942–7.
24. Guinan ME, Hardy A. Epidemiology of AIDS in women in the United
States. 1981 through 1986. J Am Med Assoc 1987;257:2039–42.
25. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O’Sullivan MJ,
et al. Reduction of maternal-infant transmission of human
immunodeficiency virus type 1 with zidovudine treatment. Pediatric
AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med
1994;331:1173–80.
26. Carpenter CC, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM,
Katzenstein DA, et al. Antiretroviral therapy for HIV infection in 1998:
updated recommendations of the International AIDS Society-USA Panel.
JAMA 1998;280:78–86.
27. Loutfy MR, Margolese S, Money DM, Gysler M, Hamilton S, Yudin MH;
Canadian HIV Pregnancy Planning Guideline Development Team. SOGC
Clinical Practice Guideline, No. 278, June 2012. J Obstet Gynaecol Can
2012;34:575–90.
28. Mandelbrot L, Mayaux MJ, Bongain A, Berrebi A, Moudoub-Jeanpetit Y,
Benifla JL, et al. Obstetric factors and mother-to-child transmission of
human immunodeficiency virus type 1: the French perinatal cohorts.
SEROGEST French Pediatric HIV Infection Study Group. Am J Obstet
Gynecol 1996;175:661–7.
29. López M, Coll O. Chronic viral infections and invasive procedures: risk
of vertical transmission and current recommendations. Fetal Diagn Ther
2010;28:1–8.
30. Ducarme G, Ceccaldi PF, Bernuau J, Luton D. Amniocentesis and
viral risk (hepatitis B, C and HIV). J Gynecol Obstet Biol Reprod
2009;38:469–473.
31. Low-Beer NM, Penn ZJ. Management of HIV in pregnancy. RCOG
Green-top Guideline No. 39. London: Royal College of Obstetricians and
Gynaecologists; 2010.
32. Westling K, Pettersson K, Kaldma A, Navér L. Rapid decline in HIV viral
load when introducing raltegravir-containing antiretroviral treatment late
in pregnancy. AIDS Patient Care STDS 2012;26:714–7.
33. Somigliana E, Bucceri AM, Tibaldi C, Alberico S, Ravizza M, Savasi V,
et al. Early invasive diagnostic techniques in pregnant women who are
infected with the HIV: a multicenter case series. Am J Obstet Gynecol
2005;193:437–42.
34. Giorlandino C, Gambuzza G, D’Alessio P, Santoro ML, Gentili P,
Vizzone A. Blood contamination of amniotic fluid after
amniocentesis in relation to placental location. Prenat Diagn
1996;16:180–2.
35. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
JULY JOGC JUILLET 2014 l 653
 SOGC CLINICAL PRACTICE GUIDELINE
Prenatal Screening, Diagnosis, and Pregnancy
Management of Fetal Neural Tube Defects
This clinical practice guideline has been prepared by
the Genetics Committee, reviewed by Family Physician
Advisory and Diagnostic Imaging Committees, and
approved by the Executive and Council of the Society of
Obstetricians and Gynaecologists of Canada.
PRIMARY AUThOR
SOGC GENETICS COMMITTEE
Francois Audibert, MD, Montreal QC
Lola Cartier, MSc, CCGC, Montreal QC
SPECIAL CONTRIBUTOR
Key words: prenatal screening, congenital anomalies, neural tube
defects, alpha fetoprotein, ultrasound scan, magnetic resonance
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 314, October 2014 (Replaces No. 261, July 2011)
Abstract
Objective: To provide obstetrical and genetic health care practitioners
with guidelines and recommendations for prenatal screening,
diagnosis, and obstetrical management of fetal open and closed
Options: This review includes prenatal screening and diagnostic
including maternal serum alpha fetoprotein screening, ultrasound,
fetal magnetic resonance imaging, and amniocentesis.
Outcomes: To improve prenatal screening, diagnosis, and obstetrical
Evidence: Published literature was retrieved through searches
neural tube defects, alpha fetoprotein, ultrasound scan, magnetic
reviews, randomized control trials/controlled clinical trials, and
observational studies published in English from 1977 to 2012.
Searches were updated on a regular basis and incorporated in
practice guideline collections, clinical trial registries, and national
health care practitioners was also reviewed.
Values:
criteria described in the Report of the Canadian Task Force on
.
This review will provide health
care practitioners with a better understanding of the available
risks associated with each technique to allow evidenced-based
management.
OCTOBER JOGC OCTOBRE 2014 927
SOGC CLINICAL PRACTICE GUIDELINE

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive health Care

A. There is good evidence to recommend the clinical preventive action

controlled trial
II-1: Evidence from well-designed controlled trials without B. There is fair evidence to recommend the clinical preventive action
randomization

more than one centre or research group

D. There is fair evidence to recommend against the clinical preventive action
places with or without the intervention. Dramatic results in
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience,

descriptive studies, or reports of expert committees
decision-making

Preventive Health Care.109

on Preventive Health Care.109

RECOMMENDATIONS
Screening Evaluation

estimated risk of recurrence, and prediction of long-term

abnormalities including open/closed neural tube defects neonatal and childhood outcomes of open/closed neural tube

anatomical ultrasound with detailed fetal intracranial and spinal

of

closed neural tube defects screening should be discontinued

with the limited clinical exceptions of pregnant women with a
2
or when geographical

maternal–fetal medicine, and pediatric neurosurgical counselling

screening, maternal serum alpha fetoprotein can be used as a

4. Positive screening results for open/closed neural tube defect
referral to appropriate experienced providers for genetic review,
Diagnostic Evaluation
5. If the second trimester screening fetal ultrasound indicates a
probable diagnosis of neural tube defects, the women should be
for a more detailed ultrasound examination looking for the
Pregnancy Management
10. Following the detection of an isolated open/closed neural tube
management options after diagnostic and genetic testing results
are available. Options should include information about
or fetal contraindications for prenatal repair at 20–26 weeks’
prognosis, and

6. Prenatal magnetic resonance imaging can be considered as request. For an encephalocele, individualized counselling is
an additional fetal imaging technique if further detailed fetal

Invasive Prenatal Diagnostic Methods

considered in selected MMC vertex presentation cases that have

928 OCTOBER JOGC OCTOBRE 2014

 Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects

oral folic acid supplementation of 5 mg within a multivitamin

preparation should be recommended to the female partner,

INTRODUCTION

O CNTDs are congenital abnormalities or

is declined, fetal magnetic resonance imaging should be
considered to better evaluate fetal abnormalities either in
utero or after postnatal death. If genetic studies have not
been completed prior to the termination, at the minimum,
not performed. This procedure will maximize information for
Pregnancy Follow-up
14. Follow-up consultation is recommended when postnatal genetic
and pathologic studies are complete, to provide the woman with
malformations of the neuraxis. Structural
developmental malformations can affect the thoracic,
(anencephaly or encephalocele). Secondary co-anomalies
(disruption or deformation) can involve the lower limb,
bowel, bladder, cerebellum, and cerebral cortex or cerebral
ventricles (for myelomeningocele).1–3 The human neural
tube normally closes during the 3rd and 4th weeks of
embryonic development (correlating with 5–6 weeks’
gestation from LMP).
The primary method of preventing the majority of
OCNTDs is with increased red blood cell folate by

supplementation, but this increased maternal folate

presumed folic acid-sensitive open/closed neural tube defect strategy must occur before conception and continue

new cell production during rapid cell division.4–6

This biological folic acid factor is important because
embryogenesis has certain folic acid-sensitive anomalies

ABBREVIATIONS trimester development. With the introduction of folic

acid supplementation (1991–1992), there has been a

of OCNTDs in Canada. This reduction and new clinical

AFP alpha fetoprotein
prenatal surgical outcomes for OCNTD highlighted the
need for new clinical care protocols and recommendations
to be developed for prenatal screening, diagnosis, and
FPR false positive rate management of OCNTDs.
LMP last menstrual period
MC meningocele Since the introduction of ONTD screening methods in the
1970s, the total number of reported cases has increased,
MRI magnetic resonance imaging most likely because of advances in prenatal screening and
MSAFP maternal serum alpha fetoprotein early detection.2,7–14 A decrease in birth prevalence is the
result of both primary prevention, in the form of folic

prevention methods (prenatal screening and termination

of an affected pregnancy).4,6,13,14
OCNTD screening and diagnosis are carried out by
OR odds ratio MSAFP measurement, fetal imaging techniques (ultrasound
imaging and MRI), and amniocentesis. It is recommended
RCT randomized controlled trial that prenatal screening be offered and undertaken in the
second trimester between 15 and 22 weeks’ gestation to

OCTOBER JOGC OCTOBRE 2014 929

SOGC CLINICAL PRACTICE GUIDELINE
maximize testing accuracy, achieve a low FPR, and allow
optimal management of affected pregnancies.4,10,15–27
Factors that have been reported to affect the accuracy
and interpretation of OCNTD screening results include
type of NTD malformation, gestational age, maternal
weight, maternal insulin-dependent diabetes, multiple
gestations, ethnicity, environmental factors (prescription
and non-prescription medications), and concurrent fetal
anomalies.1,9,13,17,22
Early prenatal screening for ONTD gives parents and
health care practitioners the ability to evaluate the anomaly
and the overall health of the fetus during the second
trimester. This guideline focuses on NTD screening,
diagnosis, and post-diagnostic pregnancy management.
GENETICS OF NTD
In humans, the neural tube closes between 21 to 28 days
of embryonic development, and abnormal closure is
characterized by the improper fusion of the neural tube in
the developing embryo.1,2,7 NTD prevalence ranges from 1
in 300 to 1 in 1000 pregnancies and is affected by ethnic,
genetic, and dietary factors, with the highest NTD rates in
the United Kingdom and the United States and the lowest
rates in Japan.9,10,28–31
Certain chronic maternal medical conditions will increase the
risk of NTDs, including poorly controlled maternal insulin-
dependent diabetes (OR 11.5), antiepileptic medications
(valproic acid, carbamazepin), therapy with folic acid
antagonists, and maternal obesity (OR 3.5).28–31
NTDs are described by their anatomical location and
neural content type as follows:
93% ONTDs (neural placode at the base of the NTD)
and 7% CNTDs (MC = dural sac only; MMC = neural
elements attached to the dural sac);
2. anencephaly (closure failure of caudal NT folds
causing failure of brain development) 40%;
3. encephalocele (outpouching of the brain through a
bony skull defect; occipital is most common, with
anterior and lateral locations) 8.5%; and
4. inencephaly/craniorachischisis (abnormal skull and
upper spine development) 1.5%.32
Seventy percent of NTDs related to genetic abnormalities
are isolated, non-syndromic anomalies or malformations,
and with current genetic knowledge, are considered to have
a multi-factorial inheritance. Chromosomal abnormalities
associated with an “apparently isolated” NTD have a 2.4% to
930 OCTOBER JOGC OCTOBRE 2014
16.3% incidence.33–37 Syndromes or sequences associated with
NTDs include amniotic band syndrome, cloacal extrophy,
limb body wall complex, OEIS (omphalocele, extrophy,
imperforate anus, spinal) syndrome, cerebrocostomandibular
syndrome, and caudal regression.38 Other syndromic
OCNTDs are associated with single gene disorders such as
(cranial ONTD and holoprosencephaly) genes. Other single
gene disorders reported include Waardenburg syndrome and
Curarino syndrome.38
There are reports of gene mutations or alterations of gene
expression leading to ONTDs, such as polymorphisms
or SNPs in genes responsible for folate transport, the
methionine/homocysteine metabolic cycle, methylation,
and nucleotide biosynthesis. Rare mechanisms contributing
autoantibodies to the folate receptors, and infertility or
assisted reproductive technology therapy.39–42
NON-INVASIVE NTD SCREENING TEChNIQUES
Ultrasound Screening
Ultrasound is the non-invasive screening modality of choice
for the detection of fetal anomalies including NTDs because
4,21,22,43,44
The current generation of ultrasound machines allow for
highly detailed fetal imaging. National screening policy
documents cite detection rates of approximately 68% to
94% for NTDs,9,22,45–47 with EUROCAT reporting a 68%
48
and British
Columbia an 86% detection rate (1997–1999).4
A second trimester screening ultrasound should be offered
to all pregnant women, as recommended in a number of
SOGC guidelines43,49,50 for the detection of congenital
anomalies from 18 to 22 weeks’ gestation, avoiding the
need for a second trimester MSAFP screening test.15,43,45,47,48
Ultrasound is recommended routinely in all second trimester
pregnancies and is a more effective screen for OCNTD
(improved sensitivity with lower FPR although more
expensive) than MSAFP screening, and diagnostically it is
safer than amniocentesis which carries the risk of infection
or spontaneous abortion.9,11,45,47,51–53 In addition, ultrasound
has the major advantage of screening for multiple congenital
anomalies at a single ultrasound imaging visit. The factors
that may affect ultrasound screening for NTDs include
of fetuses, and maternal BMI. Other factors to consider
are parental ethnicity, “at risk” maternal medication use,
maternal diabetic status, and personal, pregnancy, and family
histories.1,15,43,54–61 In a fetus with an OCNTD, features visible
by ultrasound in the second trimester include anencephaly
 Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects
dysmorphology), open spinal anomalies (abnormal skull
shape [lemon sign], abnormal appearance and possible
increased width of the cerebral ventricles, abnormal
appearance of the posterior fossa/cerebellum [banana sign],
and abnormal or incomplete appearance of the posterior
vertebral arches in thoracic, lumbar, or sacral locations),
and closed spinal anomalies (with the possible absence of
the lemon and banana signs and a thick appearing MMC
sac protruding from the posterior vertebral opening).
Abnormal lower limb movement and positioning of the
foot or feet may also be present.43,49,50 Preliminary research
for NTD at 11 to 13 weeks’ gestation, assessing structural
developmental variation, such as the absence of intracranial
translucency, decreased frontomaxillary facial angle, partial
or complete cisterna magna obliteration (brainstem diameter
decreased intracranial CSF volume. 61–65
NTD imaging should be conducted under a research
protocol at the present time.
The experience of the sonographer and up-to-date and
well-maintained equipment are important in screening
evaluation.7,15 The importance of these factors is
highlighted in the recent publication from the rural areas
of China,7 where researchers found that ultrasound did not
meet its full potential as a method of secondary screening
of NTDs; ultrasound was a satisfactory screening method,
but NTD detection rate was low. This study did not report
that ultrasound was a poor method for screening, but
rather that the ultrasound screening skills of the user were
not optimal for the detection of NTD anomalies.7
Fetal MRI
Obstetric application of MRI began approximately 20 years
ago, 10 years after its discovery and initial use.66,67 The main
use of fetal MRI is as an adjunct to the primary ultrasound
detail could be obtained for management planning and
counselling.68–70 Fetal MRIs are usually conducted between
the late second and early third trimesters, between 23 and
32 weeks’ gestation.21,59,70 This gestational age allows for
optimal imaging of the entire fetal brain and subarachnoid
space15,21,67,71; however, late gestation MRI can delay
decisions regarding pregnancy management, including
termination of pregnancy.
The use of fetal MRI, primarily known for its superior
brain imaging capabilities, has now been expanded to
detect non-CNS abnormalities.22,27,67,70 Although there
have been many advances in MRI technology such as the
use of T2-weighted sequences, which allow for better
contrast and spatial resolution, and single-shot rapid
acquisition with relaxation enhancements for decreasing
fetal movement effects,22,69–71 there is no established
standard imaging reference because MRI is not used as a
screening modality.22,67,70,72
by MRI emphasizes the importance of correct imaging
methods and radiologic interpretation. Many new
techniques under development are already commonly
used in the neonatal period, when anatomical structures
order to use them safely during pregnancy.66–70 Operator
interpretation of the MRI requires a thorough knowledge
of normal and abnormal fetal anatomy. As the option
of fetal NTD surgery becomes available in perinatal
CNS evaluation.70,73,74
MRI is considered safe for the fetus, but there are
hypothetical concerns about teratogenesis and acoustic
damage.67,70 While additional fetal MRI research with
neonatal follow-up is needed, an SOGC Diagnostic
Imaging Committee Guideline75 reports that fetal MRI is
safe at 1.5 tesla magnet exposure during the second and
third trimesters.
Ultrasound has the advantage over MRI of easier patient
access to imaging services; it is not hampered by fetal
movement, it is less expensive than MRI, and it provides
good spatial resolution. MRI, however, is not limited by
contrast, and performs well regardless of oligohydramnios,
maternal obesity, or fetal lie.22,27,70,73,74
additional anomalies,76 but its expense, lack of a standard
of reference for imaging, and limited availability are factors
that continue to favour ultrasound as the imaging choice
for the detection of OCNTDs.77,78
Maternal serum AFP
MSAFP screening was once considered the gold standard
of prenatal ONTD screening, but with advances in
technology, research, and knowledge, MSAFP screening
now has limited value when reliable second trimester
ultrasound (screening and diagnostic) is available. Since
the mid-1970s, non-invasive MSAFP has been used for the
detection of ONTDs.10,11,19,27,51,79 MSAFP levels rise early
in the pregnancy, and ONTD screening was optimized
to discern normal from abnormal MSAFP results in the
second trimester between 15 and 18 weeks’ gestation.14,15,18,45
MSAFP levels are measured in multiples of the median,
using unaffected pregnancies of the same gestational age as
OCTOBER JOGC OCTOBRE 2014 931
SOGC CLINICAL PRACTICE GUIDELINE
the control value.11,14,18 To interpret results, it is important
to correctly identify the gestational age, number of fetuses,
maternal ethnicity, and maternal weight. Furthermore, such
factors as a personal or family history of OCNTD, any
maternal “at risk for NTD” medications (epilepsy control
[valproic acid, carbamazepine] or folate antagonists), or
certain chronic medical conditions, such as diabetes, must
be taken into consideration.14,18 First trimester MSAFP
(11 to 13 gestational weeks) levels in normal pregnancies
are affected by maternal race, weight, smoking status, and
method of contraception (oral birth control).46
Second trimester MSAFP detects 71% to 90% of NTDs,
with an FPR of 1% to 3% percent.11,14,18 Elevated levels
of MSAFP can be associated with other conditions, such
as fetal skin disorders, abdominal wall defects, fetal demise,
fetal nephrosis, and pregnancies at an increased risk for
placenta-related adverse events.14,17,19 First trimester MSAFP
10%,55 and it is not recommended of NTD screening.
A detailed fetal structural ultrasound at 18 to 22
gestational weeks and amniocentesis (AFAFP, AFAChE,
and chromosome karyotype analysis) is recommended as
a diagnostic follow-up with an elevated second trimester
MSAFP level (screen-positive result).
A second trimester detailed ultrasound (at 18 to 22 gestational
weeks) is recommended as the standard of care for all
pregnancies to determine the approximate gestational age,
(not usually detected by MSAFP screening), or screen for
other congenital anomalies.43,49,50 Earlier ultrasound imaging
for dating or evaluating the pregnancy may be required, based
on clinical care factors as determined by the primary obstetrical
provider. First trimester dating by crown–rump length has a
± 3 to 5 day standard deviations for estimating the gestational
age, compared to the ± 7 day standard deviations for the 18
to 22 gestational weeks’ ultrasound.
Many recent retrospective studies have shown that
with present screening approaches and new technology
measuring MSAFP is no longer practical for the detection
selecting women for diagnostic testing, such as ultrasound
or amniocentesis.14,16,19,20,51,79
MSAFP screening for ONTDs is less costly than ultrasound
or amniocentesis,11,52 but its cost advantage must be weighed
detect closed NTDs, and the requirement of further testing
that includes detailed second trimester ultrasound when
second trimester screening MSAFP levels are elevated.
932 OCTOBER JOGC OCTOBRE 2014
Recommendations
Screening Evaluation
1. The primary screening test for the detection
of fetal structural abnormalities including
open/closed neural tube defects (anencephaly,
anatomical ultrasound with detailed fetal
intracranial and spinal imaging and
assessment. (II-2A)
2. The primary use of maternal serum alpha
fetoprotein for open/closed neural tube defects
screening should be discontinued with the limited
clinical exceptions of pregnant women with a pre-
2
or when
geographical or clinical access factors limit timely
and good quality ultrasound screening at 18 to
22 weeks’ gestation. (II-2A)
3. When used as a component in maternal serum
genetic aneuploidy screening, maternal serum
alpha fetoprotein can be used as a secondary
screening tool in the second trimester. (II-2A)
4. Positive screening results for open/closed neural
tube defect (ultrasound ± maternal serum alpha
fetoprotein) require timely referral to appropriate
experienced providers for genetic review,
diagnosis, and counselling. (II-2A)
Diagnostic Evaluation
5. If the second trimester screening fetal ultrasound
indicates a probable diagnosis of neural tube
defects, the women should be referred to a tertiary
or regional centre with ultrasound expertise for a
more detailed ultrasound examination looking for
the features associated with a neural tube defect
sequence. (II-2A)
6. Prenatal magnetic resonance imaging can
be considered as an additional fetal imaging
technique if further detailed fetal central nervous
system assessment is required for diagnostic or
management counselling. (II-2A)
INVASIVE PRENATAL DIAGNOSTIC
METhODS (NTD SCREENING/TESTING)
Amniocentesis
AFP from the fetal yolk sac initially and subsequently
only AFP is present in maternal blood.5,14,17,80 Elevated
levels of AFAFP and AFAChE are present is fetuses
14,18,80
 Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects
An amniocentesis is most often performed for the
detection of chromosomal aneuploidy or genetic
the detection of NTDs.18,23,74,81–84 The procedure is
usually conducted between the 15th and 20th gestational
weeks.6,17,45,85–88
karyotype, chromosomal microarray, and AFAFP and
AFAChE levels. When amniocentesis is performed with a
suspicion of OCNTD, the information from the karyotype,
chromosomal microarray, AFAFP, and the AFAChE levels
with counselling regarding prognosis.
If amniocentesis is being performed for aneuploidy
AChE is not routinely required.
aneuploidy still require a routine second trimester screening
ultrasound for fetal congenital anomalies, including NTD
screening if a complete ultrasound anatomic assessment is
Risks associated with amniocentesis include spontaneous
abortion (estimated procedural risk of 0.5% to 1.0%
added to the no-procedure background spontaneous risk
of pregnancy loss), post-procedure spotting, infections,
rupture of membranes, and fetal damage or loss.48,86–88
Amniocentesis for genetic testing is especially important
when considering prenatal or postnatal repair of congenital
fetal genetic factors is important as these factors may
interfere with the neonatal outcome.73,74,81–83
Although an amniocentesis is an important diagnostic
option for high-risk pregnancies in the detection of
chromosomal abnormalities and ONTDs, amniocentesis
should not be used as a method for laboratory NTD
(AFAFP, AFAChE) screening because of the risks and cost
associated with the test.
Recommendations
Invasive Prenatal Diagnostic Methods
amniocentesis (following the ultrasound detection
suspected open/closed neural tube defect),
should be evaluated for a fetal karyotype (and, if
indicated and available, a chromosomal microarray),
acetylcholinesterase. These test results will allow
comprehensive evaluation of the etiology, estimated
risk of recurrence, and prediction of long-term
neonatal and childhood outcomes of open/closed
neural tube defect for family counselling. (II-2A)
8. When a routine diagnostic amniocentesis indicates
only a risk
anomalies, it is not necessary to take an amniotic
fetoprotein and acetylcholinesterase testing to
screen for open neural tube defects. (II-2E)
an open/closed neural tube defect (isolated or in a
more complex multiple-anomaly grouping) requires
referral for comprehensive genetic, maternal–fetal
medicine, and pediatric neurosurgical counselling
for complete patient-focused care. (II-2A)
PREGNANCY MANAGEMENT
Counselling Information for
Continuing Pregnancies
Counselling should be based on the recognition of the
personal impact that a physical or mental disability could
have on a child and its family.
One of the major questions a family asks when their fetus
is given an isolated, non-syndromic, non-chromosomal
myelomeningocele diagnosis is “What will the quality
of life be for my child?” Król et al. reported a follow-
up study of 33 children (19 female; 14 male) with a
myelomeningocele at ages 5 to 20 years. They were
evaluated in 2 age groups: 5 to 12 (n = 17) and 13 to
20 (n = 16) using the Health-Related Quality of Life in
study reported good, very good, and average QoL in
64%, 30%, and 6% of participants respectively. None
of the participants felt their QoL was poor. Issues of
visual perception in the younger group and ambulation
in the older group were related to lower QoL scores. The
vast majority of children had a history of good specialist
care. The most common medical issues were related to
hydrocephalus and neurogenic bladder.89
In a larger study of 119 patients with hydrocephalus and
MMC, Barf et al. reported a near equal overall QoL in the
study group (76%) as in an age-matched peer group (72%),
life, but less satisfaction with their sex lives and abilities to
that the severity of disease and the level of the lesion had
little bearing on self-reported QoL.90
In a retrospective cohort study Hunt and Oakeshott reported
on 117 open MMC patients. The cohort had had 54%
OCTOBER JOGC OCTOBRE 2014 933
SOGC CLINICAL PRACTICE GUIDELINE
mortality and, at evaluation, had an average age of 35 years.
Among the survivors, 40% were independent in activities
of daily living, meeting medical needs, transportation, and
continence care.91
Bowman et al. reported a 25-year follow-up of 118
MMC patients in which 75% lived to early adult age, 85%
had high school or college education, 80% were able to
maintain social bladder continence with catheterization,
90% reported acceptable levels of bowel continence,
and 86% of long-term survivors were shunt-dependent.
childhood or early adulthood was an unrecognized shunt
malfunction.92
For more complete counselling knowledge, the health
care provider could consider an economic assessment of
the cost of continuing care for the MMC patient. Yi et al.
reported across all.93 The lifetime direct medical costs for
being for inpatient care, treatment at initial diagnosis in
childhood, and co-morbidities in adult life. The caregiver
Continuing Pregnancy Surveillance
and Method of Delivery
Pregnancy surveillance and delivery recommendations
for fetuses with OCNTDs are controversial because
increased pregnancy termination has limited the study of
the MMC delivery model for more than 2 decades. The
ACOG Practice Bulletin94 reports that most pregnancies
complicated by MMC will deliver with appropriate lung
maturity at term, and there is no evidence that antenatal
fetal heart rate testing for an MMC indication improves
outcome. It is recognized that anomalous fetuses frequently
interpret.95
Serial ultrasounds for fetal growth, head size, and
ventricular size may be helpful in continued prognosis
counselling and delivery planning. The fetus should be
delivered at a centre with a level III NICU and pediatric
neurosurgery services.90 A latex-free delivery and surgical
repair plan should be considered because individuals with
MMC are at an increased risk of developing a severe and
life-threatening allergy to latex.96
The mode of delivery for an MMC-affected fetus with a vertex
presentation remains controversial. There are no RCTs, but at
least 5 studies representing a total of 400 patients suggested
vaginal delivery does not adversely affect neonatal outcome,
and one large study of 200 patients suggested Caesarean
934 OCTOBER JOGC OCTOBRE 2014
sections as a safer method of delivery for the MMC-affected
fetus.97–102 Breech presentation is common in the MMC-
affected fetus as a result of decreased lower limb neurologic
function and megacephaly, and hence requires delivery by
Caesarean section.
Prenatal in Utero Repair of MMC
The Randomized Trial of Prenatal versus Postnatal Repair
of Myelomeningocele74 showed that prenatal fetal surgery
for MMC reduced the need for ventricular peritoneal
shunting (40% vs. 82%) and showed improved lower limb
motor outcomes at 30 months of age. However, the surgery
was associated with maternal and fetal risks. Additional
improvement in the child composite score for mental
development and motor function at 30 months of age was
score: prenatal surgery [n = 64] 148.6 ± 57.5; postnatal
surgery [n = 70] 122.6 ± 57.2; P = 0.007). Improved
hindbrain herniation at 12 months and ambulation at 30
months was also reported. This landmark study provides
an important treatment option for parents because it clearly
surgery, albeit at the cost of increased maternal risks for
the index and subsequent pregnancies.74 An accompanying
editorial counselled caution regarding the initiation of this
new prenatal treatment in multiple fetal therapy/treatment
centres and emphasized that most women who expressed
an interest in the experimental trial were either ineligible or
declined to participate, with only 15% of screened women
participating in the study.103 A legal and ethical opinion that
drew attention to prioritizing the fetus stated that:
unlike a born child, a fetus is not a patient in the real
sense, but only a metaphor. However, it would be
unethical if a care provider, without the woman’s
informed consent, promoted the interests of the
fetus over those of the woman.104
When considering the consent to fetal surgery
the parents have clear legal responsibilities to provide
or consent to their born children’s necessary medical
care but the maternal duties to fetuses in utero are
not generally recognized.”104
Regarding whether this study was research or a therapeutic
innovation they stated that:
the research component of the study was not in
the prenatal surgical and postnatal management
of each child but in the systematic control of
each case according to the research protocol and
the retrospective comparative review for all the
outcome data.104
 Prenatal Screening, Diagnosis, and Pregnancy Management of Fetal Neural Tube Defects
Their conclusion was that “women, diagnosed with a fetal
MMC and where open fetal surgery is available, will have to
be informed of this treatment option.”104 This prenatal repair
option needs therefore to be presented to families in Canada
as part of the informed consent process because although it is
not available here, it is available in the United States.104
Postnatal Repair of MMC
The decision to perform postnatal repair is the most likely
clinical scenario in Canada for the MMC fetus or neonate
because only mothers who have travelled to in utero MMC
treatment centres in the United States will have received in
utero MMC repair.
The postnatal group in the Randomized Trial of Prenatal
74
is used
as the clinical outcome for comparison because the RCT
study was done in selected Children’s Hospital facilities
with organized and comprehensively controlled pediatric
neurosurgery services. The placement of a shunt within the
group (82%, compared to prenatal group 40%; P = 0.001).
Other abnormal cranial and brain features were higher in the
postnatal group than in the prenatal repair group (degree of
hindbrain herniation, P = 0.001; brainstem kinking, P = 0.001;
abnormal location of the 4th ventricle, P = 0.002).
lower with postnatal repair than with prenatal repair, but this
was mainly due to differences in motor function between the
spinal anatomical levels of the defects (P = 0.001); the Bayley
(P
independently with prenatal repair and 21% with postnatal
repair (relative risk 2.01 ([95% CI 1.16–3.48]; P = 0.01).
lower WeeFIM scores for self-care (P = 0.02) and mobility
(P = 0.003), but not for cognitive ability (P = 0.67).
Immediate postnatal care for MMC is required whether
the birth was by Caesarean section or vaginal delivery.
Neonatology specialists should attend in the labour
room for MMC protection and care, probable neonatal
prematurity (less than 37 weeks’ gestation), and planning
and performing subsequent primary neurosurgical MMC
closure within 24 hours of delivery, especially if the MMC
is open or the MMC sac was ruptured at delivery
Termination of Pregnancy
Over the last 3 decades an estimated 70% to 80% of
women and couples with a fetus affected by OCNTD have
chosen termination of the pregnancy.4,105,106
For families choosing to terminate a pregnancy because of
an MMC, anencephaly, or encephalocele, the health care
provider should discuss fetal autopsy and chromosomal
provide important information about the etiology for
the NTD and the recurrence risk.107 Measures to prevent
recurrence, including maternal supplementation with 5 mg
of preconception folic, are recommended in subsequent
pregnancies because folic acid supplementation has
been shown in an RCT to reduce the isolated recurrence
risk of NTD by 72%, with a resulting reduction of the
non-supplementation prevalence rate of 3% to a post
supplementation recurrence rate of 1%.5,108
Recommendations
Pregnancy Management
10. Following the detection of an isolated open/closed
neural tube defect, families should be offered a
choice of 3 obstetrical care management options
after diagnostic and genetic testing results are
available. Options should include information about
prenatal myelomeningocele repair and prognosis (if
there are no maternal or fetal contraindications for
prenatal repair at 20–26 weeks’ gestation), postnatal
myelomeningocele surgical repair and prognosis,
and pregnancy termination with autopsy. Because
anencephaly is a lethal condition, pregnancy with
anencephaly may be interrupted at any gestational
age on the woman’s request. For an encephalocele,
individualized counselling is recommended because
of the possibly unique circumstances of the
anomaly. (II-2A)
11. Caesarean section is the most common method of
delivery for a fetus with a myelomeningocele (MCC)
in either vertex or breech presentation, but is it
with intrapartum fetal heart rate monitoring can be
considered in selected MMC vertex presentation
cases that have no macrocephaly related to
gestational age and a small or no MMC sac. (II-2A)
12. Delivery management for a fetus with complex
multiple anomalies including a neural tube defect
will need to be individually determined by the
multidisciplinary health care providers at the
anticipated delivery centre based on the differential
testing results, prenatal care requirements, anticipated
neonatal morbidity or mortality, and family
consultation and requests. (III-A)
13. Autopsy is recommended for all cases of prenatal
and postnatal open/closed neural tube defect
(isolated or complex) following either termination
OCTOBER JOGC OCTOBRE 2014 935
SOGC CLINICAL PRACTICE GUIDELINE
of pregnancy or prenatal/postnatal death.
Induction of labour may be the preferred method
for pregnancy termination, allowing for a more
complete autopsy evaluation of the fetal central
nervous system. If autopsy is declined, fetal
magnetic resonance imaging should be considered
to better evaluate fetal abnormalities either in utero
or after postnatal death. If genetic studies have
not been completed prior to the termination, at
the minimum, chromosomal karyotyping and/or
chromosomal microarray should be considered or
encouraged, even if a full autopsy is not performed.
This procedure will maximize information for
postnatal review and counselling. (II-2A)
Pregnancy Follow-up
14. Follow-up consultation is recommended when
postnatal genetic and pathologic studies are
complete, to provide the woman with information
related to the etiology, risk of recurrence,
recurrence prevention, and the possible impact on
other family members of the congenital isolated or
complex anomaly. (II-2A)
15. When a previous pregnancy history is complicated
by a presumed folic acid-sensitive open/closed
neural tube defect (i.e., no karyotype, chromosomal
etiology) for either member of the couple, or
if either member of the couple planning the
pregnancy is personally affected with an isolated
neural tube disorder, oral folic acid supplementation
of 5 mg within a multivitamin preparation should
be recommended to the female partner, starting at
least 3 months prior to pregnancy conception and
SUMMARY
NTDs occur early in embryologic development, secondary
to failure of fusion of the neural groove and formation
of the neural tube. NTDs include malformations or
disruptions in the lower spine and upper cranium and
occur in approximately 1 in 1000 live births. There are
2 methods of prevention: primary prevention with
and secondary prevention with prenatal screening and
pregnancy interruption.
Ultrasound is presently the best screening method for
prenatal detection of fetal anomalies including NTDs
because of its safety, availability, accuracy, and cost-
effectiveness. MSAFP screening should be used in limited
clinical scenarios as an additional screening method.
936 OCTOBER JOGC OCTOBRE 2014
Although it may be cost effective, the MSAFP screen
can detect only open NTDs; it has poor sensitivity and
used as an adjunct to ultrasound when more detail of the
CNS is required or when fetal therapy is being considered.
MRI is more expensive and is not as readily available as
ultrasound; further research is necessary to ensure its
reported safety and to allow the creation of reference
standards.
Amniocentesis is an invasive diagnostic procedure that
is accurate in the detection of ONTDs and in analyses
for chromosomal or genetic abnormalities. With the use
of ultrasound for guidance, amniocentesis performed
by experienced hands, can greatly reduce the risks of
miscarriage, infection, and harm to the fetus. However,
although amniocentesis has a greater than 99% detection
rate for ONTD, it is neither cost effective nor necessary
for the detection of ONTD unless performed for the
Improved prenatal screening and diagnosis will enable
mothers or couples to obtain precise information about
detected anomalies so they can make informed decisions
about whether to continue or interrupt the pregnancy and
what their options are for fetal or postnatal repair.
Our current knowledge and experience indicates that
pregnant woman should be offered 2 prenatal screening
approaches:
1. risk screening for fetal aneuploidy and fetal anomalies,
using a combination of non-invasive techniques that
includes ultrasound (fetal anatomic and structural
detail) and
2. maternal serum testing for placental biochemical
trimester screening approaches) or for placental cell-
free fetal DNA (for future direct fetal molecular DNA
screening or diagnostic testing).
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of labour and delivery on spinal cord function and ambulation in patients
with meningomyelocele. Child Nerv Syst 1991;7:312–5.
section delivery improve diagnosis? Obstet Gynecol 1988;71:532–4.
99. Sakala EP, Andree I. Optimal route of delivery for meningomyelocele.
Obstet Gynecol Surv 1990;45:209–12.
100. Hill AE, Beattie F. Does caesarean section delivery improve neurological
101. Merrill DC, Goodwin P, Burson JM, Sato Y, Williamson R, Weiner CP.
The optimal route of delivery for fetal meningomyelocele. Am J Obstet
Gynecol 1998;179:235–40.
102. Luthy DA, Wardinsky T, Shurtleff DB, Hollenback KA, Hickok DE,
Nyberg DA, et al. Cesarean section before the onset of labor and
subsequent motor function in infants with meningomyelocele diagnosed
antenatally. N Engl J Med 1991;324:662–6.
103. Simpson JL, Greene MF. Fetal surgery for myelomeningocele? N Engl J
Med 2011;364: 1076–7.
104. Dickens BM, Cook RJ. Ethical and legal issues in reproductive
health. Legal and ethical issues in fetal surgery. Int J Gynaecol Obstet
2011;115:80–3.
105. Barry S. Quality of life and myelomeningocele: an ethical and
evidence-based analysis of the Groningen protocol. Pediatr Neurosurg
2010;46:409–14.
EUROCAT working group. Survey of prenatal screening policies in
Europe for structural malformations and chromosome anomalies, and
their impact on detection and termination rates for neural tube defects
and Down’s syndrome. BJOG 2008;115:689–96.
Committees of the Society of Obstetricians and Gynaecologists
of Canada. Fetal and perinatal autopsy in prenatally diagnosed fetal
abnormalities with normal karyotype. SOGC Technical Update,
No. 267, October 2011. J Obstet Gynaecol Can 2011;33:1047–57.
108. Miller EC, Liu N, Wen SW, Walker M. Why do Canadian women fail to
achieve optimal pre-conceptional folic acid supplementation?
An observational study. J Obstet Gynaecol Can 2011;33:1116–23.
109. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
OCTOBER JOGC OCTOBRE 2014 939
 SOGC CLINICAL PRACTICE GUIDELINE

No. 315, November 2014

The Prevention of Ovarian

Hyperstimulation Syndrome
Abstract
This clinical practice guideline has been prepared by the
Reproductive Endocrinology Infertility Committee and Objective: To review the clinical aspects of ovarian hyperstimulation
approved by Executive and Council of the Society of syndrome and provide recommendations on its prevention.
Obstetricians and Gynaecologists of Canada.
Options: Preventative measures, early recognition, and prompt
systematic supportive care will help avoid poor outcomes.
PRINCIPAL AUTHORS
Outcomes: Establish guidelines to assist in the prevention of ovarian
Shannon Corbett, MD, Ottawa ON hyperstimulation syndrome, early recognition of the condition
Doron Shmorgun, MD, Ottawa ON when it occurs, and provision of appropriate supportive measures
in the correct setting.
Paul Claman, MD, Ottawa ON
Evidence: Published literature was retrieved through searches
REPRODUCTIVE ENDOCRINOLOGY of Medline, Embase, and the Cochrane Library from 2011 to
INFERTILITY COMMITTEE 2013 using appropriate controlled vocabulary ([OHSS] ovarian
hyperstimulation syndrome and: agonist IVF, antagonist IVF,
Anthony Cheung, MD (Co-chair), Vancouver BC metformin, HCG, gonadotropin, coasting, freeze all, agonist
Sony Sierra, MD (Co-chair), Toronto ON trigger, progesterone) and key words (ovarian hyperstimulation
syndrome, ovarian stimulation, gonadotropin, human chorionic
Belina Carranza-Mamane, MD, Sherbrooke QC gonadotropin, prevention). Results were restricted to systematic
Allison Case, MD, Saskatoon SK reviews, randomized control trials/controlled clinical trials, and
observational studies published in English. There were no date
Cathie Dwyer, RN, Toronto ON restrictions. Searches were updated on a regular basis and
James Graham, MD, Calgary AB incorporated in the guideline to February 2013.

Jon Havelock, MD, Burnaby BC Grey (unpublished) literature was identified through searching the
websites of health technology assessment and health technology-
Sarah Healey, MD, St. John’s NL related agencies, clinical practice guideline collections, clinical
Robert Hemmings, MD, Montreal QC trial registries, and national and international medical specialty
societies.
Kimberly Liu, MD, Toronto ON
Values: The quality of evidence in this document was rated using the
Tarek Motan, MD, Edmonton AB criteria described in the Report of the Canadian Task Force on
Ward Murdock, MD, Fredericton NB Preventive Health Care (Table 1).

David Smithson, MD, London ON

Summary Statements
Tannys Vause, MD, Ottawa ON
1. The particular follicle-stimulating hormone formulation used
Benjamin Wong, MD, Calgary AB for ovarian stimulation does not affect the incidence of ovarian
hyperstimulation syndrome. (I)
SPECIAL CONTRIBUTOR
2. Coasting may reduce the incidence of severe ovarian
Mathias Gysler, MD, Oakville ON hyperstimulation syndrome. (III)
Disclosure statements have been received from all contributors.

Key Words: Ovarian hyperstimulation syndrome, ovarian

stimulation, gonadotropin, human chorionic gonadotropin,
prevention
J Obstet Gynaecol Can 2014;36(11):1024–1033

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

1024 l NOVEMBER JOGC NOVEMBRE 2014


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.65
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.65
3. Coasting for longer than 3 days reduces in vitro fertilization
pregnancy rates. (II-2)
4. The use of either luteinizing hormone or human chorionic
gonadotropin for final oocyte maturation does not influence the
incidence of ovarian hyperstimulation syndrome. (I)
5. There is no clear published evidence that lowering the human
chorionic gonadotropin dose will result in a decrease in the rate of
ovarian hyperstimulation syndrome. (III)
6. Cabergoline starting from the day of human chorionic
gonadotropin reduces the incidence of ovarian hyperstimulation
syndrome in patients at higher risk and does not appear to lower
in vitro fertilization pregnancy rates. (II-2)
ABBREVIATIONS
ART assisted reproductive technology
CI confidence interval
FSH follicle-stimulating hormone
GnRH gonadotropin-releasing hormone
hCG human chorionic gonadotropin
HES hydroxyethyl starch
IVF in vitro fertilization
LH luteinizing hormone
LPS luteal phase support
OHSS ovarian hyperstimulation syndrome
OR odds ratio
PCOS polycystic ovary syndrome
RCT randomized control study
SC subcutaneously
VEGF vascular endothelial growth factor
The Prevention of Ovarian Hyperstimulation Syndrome
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
7. Avoiding pregnancy by freezing all embryos will prevent severe
prolonged ovarian hyperstimulation syndrome in patients at high
risk. (II-2)
8. Pregnancy rates are not affected when using gonadotropin-
releasing hormone (GnRH) agonists in GnRH antagonist protocols
for final egg maturation when embryos are frozen by vitrification for
later transfer. (II-2)
Recommendations
1. The addition of metformin should be considered in patients with
polycystic ovarian syndrome who are undergoing in vitro fertilization
because it may reduce the incidence of ovarian hyperstimulation
syndrome. (I-A)
2. Gonadotropin dosing should be carefully individualized, taking into
account the patient’s age, body mass, antral follicle count, and
previous response to gonadotropins. (II-3B)
3. Cycle cancellation before administration of human chorionic
gonadatropin is an effective strategy for the prevention of ovarian
hyperstimulation syndrome, but the emotional and financial burden
it imposes on patients should be considered before the cycle is
cancelled. (III-C)
4. Gonadotropin-releasing hormone (GnRH) antagonist stimulation
protocols are recommended in patients at high risk for ovarian
hyperstimulation syndrome (OHSS). The risk of severe OHSS in
patients on GnRH antagonist protocols who have a very robust
ovarian stimulation response can be reduced by using a GnRH
agonist as a substitute for human chorionic gonadotropin to trigger
final oocyte maturation. (I-B)
5. A gonadotropin-releasing hormone (GnRH) antagonist protocol with
a GnRH agonist trigger for final oocyte maturation is recommended
for donor oocyte and fertility preservation cycles. (III-C)
6. Albumin or other plasma expanders at the time of egg retrieval are
not recommended for the prevention of ovarian hyperstimulation
syndrome. (I-E)
7. Elective single embryo transfer is recommended in patients at high
risk for ovarian hyperstimulation syndrome. (III-C)
NOVEMBER JOGC NOVEMBRE 2014 l 1025
SOGC Clinical Practice Guideline

8. Progesterone, rather than human chorionic gonadotropin, should Table 2. Classification of OHSS
be used for luteal phase support. (I-A)
Grade Symptoms
9. Outpatient culdocentesis should be considered for the prevention
of disease progression in severe ovarian hyperstimulation Mild OHSS Abdominal bloating
syndrome. (II-2B) Mild abdominal pain
Ovarian size usually < 8 cm
INTRODUCTION Moderate OHSS Moderate abdominal pain
Nausea with/without vomiting

O HSS is a iatrogenic complication of exogenous

gonadotropin therapy used to mature multiple
follicles for assisted reproductive treatments. The syndrome
Ultrasound evidence of ascites
Ovarian size usually 8–12 cm
Severe OHSS Clinical ascites (occasionally pleural
is only rarely observed with clomiphene citrate treatment effusion)
but has been reported even after spontaneous ovulation.1 Oliguria
Published guidelines already exist on the management Hemoconcentration hematocrit (> 45%)
of patients suffering from severe OHSS.2 The goal of Hypoproteinemia
this guideline is to provide a practical, evidence-based Ovarian size usually > 12 cm
framework for the prevention of OHSS. Critical OHSS Tense ascites or large pleural effusion
Hematocrit (> 55%)
After gonadotropin stimulation for IVF, the reported
White cell count > 25 000/L
incidence of moderate OHSS is 3% to 6%, and for
Oligo/anuria
severe OHSS it is 0.1% to 2%.3,4 The mild form, which
Thromboembolism
has little clinical consequence, occurs in about 20% to
Acute respiratory distress syndrome
33% of IVF cycles3,5 and is of little clinical concern.
Reproduced with permission of the British Fertility Society.1
However, fatalities have been reported in the most severe
cases.6 Except during rare events, OHSS occurs only after
ovulation (i.e. after exposure to an endogenous LH surge,
to exogenous LH or hCG, or to endogenous hCG of turn decreases the clinical burden of OHSS.14 Numerous
pregnancy).7 Early OHSS symptoms may begin as soon other mediators have been implicated in the disease
as 24 hours after hCG administration, but become most process such as angiotensin II, insulin-like growth factor
severe 7 to 10 days after hCG; severe OHSS is usually 1 and interleukin-6.2
associated with the rise of endogenous hCG from an
early pregnancy8 (see Table 2). Risk Factors
Several factors have been demonstrated to independently
Physicians prescribing ovarian stimulation need to identify increase the risk of developing OHSS. These include
patients at increased risk for OHSS in order to apply
•• age < 30 years,15
preventive and active management strategies to minimize
morbidity from this complication of fertility treatment. •• polycystic ovaries (i.e., > 24 antral follicles present on
baseline ultrasound examination),16,17
Pathophysiology of OHSS
•• high serum estradiol at hCG trigger or rapidly rising
OHSS is a systemic disease thought to result from
serum estradiol,15
vasoactive peptides released from the granulosa cells in
hyperstimulated ovaries.7 The fundamental physiological •• previous episodes of OHSS,18
change in severe OHSS is an increase in vascular perme­ •• large number of small follicles (8 to 12 mm) seen on
ability, resulting in a fluid shift from the intravascular spaces ultrasound during ovarian stimulation,17
to third-space compartments such as the peritoneal and
•• use of hCG, as opposed to progesterone, for luteal
thoracic cavities, often resulting in hemoconcentration.9,10
phase support after IVF,18
The most important mediator in this process is thought
to be VEGF.11 Supporting evidence comes from studies •• large number of oocytes retrieved (> 20),19 and
showing that serum VEGF levels correlate with OHSS •• high anti-müllerian hormone (> 3.36 ng/mL).20
severity. Additionally, hCG has been shown to increase
VEGF expression in human granulosa cells, which in PREVENTION
turn raises serum VEGF concentration.12,13 A new body
of clinical data demonstrates how the administration of Physicians providing ART treatment must balance the
dopamine agonist drugs decreases VEGF activity, which in competing interests of trying to sufficiently stimulate the

1026 l NOVEMBER JOGC NOVEMBRE 2014


ovary to optimize the chance of achieving a pregnancy
and minimizing the risk of severe OHSS. To achieve both
of these goals both primary and secondary preventative
measures have been shown to be useful.1
Primary prevention involves identifying risk factors for
OHSS and choosing an appropriate ovarian stimulation
regimen. Secondary prevention involves recognizing
patients who are over-responsive to gonadotropins and
intervening to reduce the risk of OHSS while still trying to
salvage the treatment cycle.
A meta-analysis of 5 RCTs showed a significant reduction
in the incidence of OHSS with the use of metformin in
women with PCOS undergoing IVF (12/216 vs. 44/210;
OR 0.21, 95% CI 0.11 to 0.41, P < 0.01).21 These findings
were later corroborated in a Cochrane review from the
same group.22 Interestingly, a recent RCT showed that
women with polycystic ovarian morphology that does not
meet the criteria for PCOS do not incur the same protective
benefit from metformin of reduced OHSS.23
Metformin should ideally be started 8 weeks before
planned gonadotropin stimulation to be effective in OHSS
prevention. To minimize gastrointestinal side effects we
recommend starting Metformin at a low dose of 500 mg
HS and slowly increasing the dose until the effective dose
of 500 mg × 3 (1500 mg) daily is reached. Metformin
should continue until egg retrieval.
Two separate meta-analyses of RCTs comparing
recombinant FSH and urinary FSH showed no difference
in the incidence of OHSS.24,25
There is no linear positive correlation between
gonadotropin dose and the incidence of severe OHSS.
On the contrary, patients developing OHSS tend to be
those who respond robustly to gonadotropins and are
often prescribed lower than average doses of these drugs
than other women undergoing IVF. Young, thin women,
especially those with polycystic ovaries on ultrasound
(i.e., > 12 antral follicles seen on each ovary) are at
higher risk for OHSS and should receive a lower starting
dose of gonadotropin than would be given to other
women.26 Careful monitoring of these patients during
stimulation is prudent to allow for a decrease in the dose
of gonadotropins if a very robust response is detected
early in the treatment cycle.18
Summary Statement
1. The particular follicle-stimulating hormone
formulation used for ovarian stimulation does not
affect the incidence of ovarian hyperstimulation
syndrome. (I)
The Prevention of Ovarian Hyperstimulation Syndrome
Recommendations
1. The addition of metformin should be considered
in patients with polycystic ovarian syndrome who
are undergoing in vitro fertilization because it may
reduce the incidence of ovarian hyperstimulation
syndrome. (I-A)
2. Gonadotropin dosing should be carefully
individualized, taking into account the patient’s
age, body mass, antral follicle count, and previous
response to gonadotropins. (II-3B)
Coasting
Coasting involves withholding gonadotropins while
maintaining pituitary suppression with a gonadotropin-
releasing hormone agonist or antagonist. Administering
hCG to trigger oocyte maturation once estrogen levels
plateau or drop is thought to reduce the risk for OHSS.
Larger follicles have a lower requirement for FSH than
smaller follicles. Once follicles are > 12 mm in diameter,
stopping all gonadotropins still allows for larger follicles to
continue their growth and maturation, while smaller follicles
undergo atresia, which may result in reduced production
of vasoactive peptides such as VEGF.27 It has been shown
that coasting on a GnRH agonist for up to 3 days does not
adversely affect pregnancy rates.28 The same criteria for
coasting can be applied to GnRH antagonist cycles as to
GnRH agonist cycles with similar IVF outcomes.29
In a systematic review of 12 retrospective studies
examining the benefit of coasting, the coasted patients
had a 2.5% incidence of hospitalization for OHSS,
which is lower than expected for patients at high risk
for OHSS.30 Previous studies have shown a significant
drop in pregnancy rate with longer than 3 to 4 days of
coasting.28,31 Therefore, cycle cancellation should be
considered if estradiol levels do not start to fall by the
fourth day of coasting.
A meta-analysis of 3 RCTs comparing recombinant LH
with urinary hCG for triggering final oocyte maturation
and 11 RCTs comparing recombinant hCG with urinary
LH did not show any difference in the risk of OHSS.32
Summary Statements
2. Coasting may reduce the incidence of severe ovarian
hyperstimulation syndrome. (III)
3. Coasting for longer than 3 days reduces in vitro
fertilization pregnancy rates. (II-2)
4. The use of either luteinizing hormone or human
chorionic gonadotropin for final oocyte maturation
does not influence the incidence of ovarian
hyperstimulation syndrome. (I)
NOVEMBER JOGC NOVEMBRE 2014 l 1027
SOGC Clinical Practice Guideline
The degree of hCG exposure has been associated with the
risk of OHSS.18 It is recognized that hCG has no direct
effect on the vascular system33; however, vasoactive
substances such as VEGF are released in the ovary in
response to hCG administration and are most likely
responsible for inducing vascular hyperpermeability and
third-spacing in high-risk women.34 A retrospective series
of 94 IVF cycles showed that when hCG doses were
lowered, both pregnancy rates and the rate of severe
OHSS remained unchanged.35 However, a lower incidence
of severe OHSS has been observed with the use of lower
doses of hCG for final oocyte maturation in an at-risk
population. Because serum levels of hCG are dependent
on body mass,36,37 one Canadian fertility centre uses hCG
5000 IU SC to trigger final egg maturation in patients at
risk for OHSS who have a BMI < 28 kg/m2, despite the
lack of published data. Women with a BMI ≥ 28 kg/m2
are all given hCG 10 000 IU SC for final egg maturation
because yields of mature eggs have been observed to be
lower with a dose reduction in this population.36
Summary Statement
5. There is no clear published evidence that lowering
human chorionic gonadotropin dose will result in
a decrease in the rate of ovarian hyperstimulation
syndrome. (III)
Cabergoline
VEGF produced by granulosa cells of developing follicles
is thought to be a key mediator in both hCG-dependent
ovarian angiogenesis and the pathophysiology of OHSS.38
Recently, the dopamine agonist cabergoline has been
introduced as a secondary prevention strategy in women
deemed to be at high risk for OHSS because of a very
robust gonadotropin response at the end of a controlled
ovarian stimulation cycle. Dopamine agonists show similar
effects to anti-angiogenic drugs on vascular permeability,
and except for occasional nausea, they appear not to have
undesirable side effects.33,39 Evidence from animal models
shows that cabergoline blocks VEGF-mediated increase
in vascular permeability without affecting angiogenesis.33
Carbergoline’s postulated mechanism of action is partial
inhibition of the phosphorylation of its associated
receptor, the VEGF receptor 2.40
A recent Cochrane review included 2 RCTs addressing
cabergoline and OHSS. In the RCT conducted by Alvarez
et al. on oocyte donors at risk for OHSS (20 to 30 follicles
at > 12 mm and > 20 eggs retrieved), in which the
treatment group received oral cabergoline 0.5 mg daily for
8 days starting on the day of hCG and the control group
received a placebo, the incidence of moderate OHSS was
significantly reduced in the cabergoline group (20% vs.
1028 l NOVEMBER JOGC NOVEMBRE 2014
43.8%, P = 0.04).14 The same first author also showed
that pregnancy rates are not compromised in patients
given cabergoline.41 The second RCT by Carriza et al.
randomized women who were undergoing IVF and at
high risk for OHSS (estradiol ≥ 14 700 pmol/L on day of
hCG trigger) into two groups: the study group received
20 grams of prophylactic intravenous albumin and 0.5 mg
of Cabergoline orally once daily for 3 weeks commencing
the day after oocyte retrieval and the control group received
only albumin.42 The risk of early OHSS (occurring within
the first 9 days after hCG trigger) decreased significantly
(P < 0.001) in the cabergoline group; none of the patients
who had taken cabergoline progressed to early OHSS, but
15.0% of the control group did. The risk of late OHSS did
not decrease. In both of the RCTs examined, the use of
cabergoline did not affect the pregnancy outcome (clinical
pregnancy rate or miscarriage rate), nor was it associated
with an increased risk of adverse events.43
Two published abstracts have demonstrated the safety
and efficacy of using cabergoline at even smaller doses:
0.5 mg twice weekly for 6 doses44 and 0.5 mg twice weekly
for 3 doses.45 Clinicians at one Canadian fertility centre use
a dose of cabergoline 0.5 mg every 3 days to a total of 4
doses starting on the day of oocyte maturation trigger and
a significant reduction in the incidence of severe OHSS
has been anecdotally observed since the introduction of
cabergoline into the prevention strategies for OHSS.
Although still somewhat preliminary, current data suggest
that cabergoline is associated with a reduction in moderate
OHSS in patients at high risk and has no adverse effect on
the pregnancy rate.
Summary Statement
6. Cabergoline starting from the day of human
chorionic gonadotropin reduces the incidence of
ovarian hyperstimulation syndrome in patients at
higher risk and does not appear to lower in vitro
fertilization pregnancy rates. (II-2)
Cycle Cancellation
OHSS will not develop in the absence of exposure to
exogenous hCG or LH or to an endogenous LH surge
as long as a pregnancy does not develop. Therefore,
withholding hCG in cycles at risk for OHSS and cancelling
the cycle is the most effective method of preventing OHSS.
This prevention strategy is especially important in agonist
cycles in which the option to substitute an agonist trigger
for hCG does not exist. However, because the emotional
and financial costs of cancellation are significant, other
prevention strategies should be exhausted before cycle
cancellation is considered.

Recommendation
3. Cycle cancellation before the administration
of human chorionic gonadotropin is an
effective strategy for the prevention of ovarian
hyperstimulation syndrome, but the emotional and
financial burden it imposes on patients should be
considered before the cycle is cancelled. (III-C)
PROTOCOLS
Assisted reproductive technologies, especially IVF
protocols, generally use GnRH agonists or antagonists
to prevent an endogenous LH surge from occurring
before follicular maturation. A Cochrane review of 29
RCTs showed a significantly lower incidence of OHSS
in GnRH antagonist cycles than in GnRH agonist cycles
(OR 0.43; 95% CI 0.33 to 0.57). Differences in rates of
pregnancy or live births were not observed between the
two protocols.46
One important benefit of using GnRH antagonist
protocols in patients at risk for OHSS (e.g., PCOS patients)
is that final oocyte maturation can be achieved using a
GnRH agonist instead of hCG. In a GnRH antagonist
protocol, a GnRH agonist trigger will displace the GnRH
antagonist from the GnRH receptor to induce a controlled
surge of endogenous LH and FSH. This GnRH agonist-
induced LH has a shorter half-life than exogenous hCG,
resulting in a less sustained luteotrophic stimulation and
hence a lower risk for OHSS.47 GnRH agonist triggering
may prevent early OHSS. OHSS is rarely encountered in
IVF egg donors when GnRH agonist is used to trigger
final oocyte maturation.47
An important potential concern when using a GnRH
agonist trigger during GnRH antagonist IVF cycles is the
possible risk of having an inadequate luteal phase. A single
dose of GnRH agonist induces an endogenous LH surge
that has a much shorter half-life than hCG, resulting in
compromised corpus luteum formation48 and a shorter
duration of the luteal phase.49 Initial reports showed
poor clinical outcomes with a higher incidence of early
pregnancy loss and compromised pregnancy rates when a
GnRH agonist was used for final oocyte maturation.50,51
Subsequent transfer of frozen-thawed embryos from
patients with a GnRH agonist trigger showed improved
pregnancy rates and spontaneous abortion rates similar
to those in patients using an hCG trigger. These data
suggest that the etiology of the observed lower success
rates in fresh cycles triggered with GnRH agonist is due to
endometrial problems in the luteal phase rather than to an
effect on embryo quality.52
The Prevention of Ovarian Hyperstimulation Syndrome
More recent studies have addressed these concerns by
employing a more comprehensive LPS protocol after
final oocyte maturation with GnRH agonists. Using
the more aggressive LPS protocol, IVF success rates
with a GnRH agonist trigger were comparable to those
observed when hCG was used for final egg maturation.
In 2011 Humaidan et al. reviewed 6 recent RCTs
employing a protocol of more aggressive LPS (3 RCTs
with aggressive high dose progesterone and estrogen
supplementation LPS, 2 RCTs with the addition of
low-dose hCG LPS, and one RCT with progesterone
and recombinant LH LPS). Importantly, the live birth
rate per fresh IVF embryo transfer cycle improved
significantly when modified luteal support was used.
There were no cases of severe OHSS reported after
GnRH agonist triggering, but a 4.6% incidence of
severe OHSS was observed in the hCG trigger group
for a risk difference of 5% (95% CI −0.07 to 0.02).53
These results support GnRH agonist triggering as an
alternative to hCG triggering when a fresh embryo
transfer is planned, resulting in a reduction of OHSS
and the potential to preserve IVF success rates with
adequate LPS. It is not yet clear whether using a GnRH
agonist trigger with aggressive LPS results in the same
pregnancy rate with fresh embryo transfer as using hCG
to trigger final oocyte maturation.
Although the optimal protocol of luteal supplementation
has not yet been defined, 2 approaches to luteal
phase support in agonist-triggered cycles have been
proposed. The first approach is to use aggressive steroid
supplementation with progesterone and estrogen,
allowing the corpus luteum to degenerate and reduce
the risk of OHSS.54 The second approach is to attempt
rescue of the corpus luteum by administering a low
dose of hCG on the day of oocyte retrieval in addition
to standard LPS with vaginal progesterone and oral
estrogen.55,56 The latter approach may need fine tuning
because hCG may exacerbate the risk of OHSS and
has mostly been examined in a population that was
not at high risk for OHSS.52 For cycles in which an
oocyte donor is stimulated or for fertility preservation
cycles in which embryo transfer is not going to occur,
a GnRH antagonist pituitary suppression protocol is
recommended. This will offer an option for a GnRH
agonist trigger to help obviate OHSS risk without
affecting pregnancy rates, because a compromised luteal
phase is not a concern when embryos are not being
transferred into the patient being stimulated. For oocyte
donors Lupron 3 mg (0.6 mL) intramuscular 36 hours
prior to oocyte retrieval, followed by a repeat dose 10
hours later may be used.
NOVEMBER JOGC NOVEMBRE 2014 l 1029
SOGC Clinical Practice Guideline
Recommendations
4. Gonadotropin-releasing hormone (GnRH)
antagonist stimulation protocols are recommended
in patients at high risk for ovarian hyperstimulation
syndrome (OHSS). The risk of severe OHSS in
patients on GnRH antagonist protocols who have
a very robust ovarian stimulation response can be
reduced by using a GnRH agonist as a substitute
for human chorionic gonadotropin to trigger final
oocyte maturation. (I-B)
5. A gonadotropin-releasing hormone (GnRH)
antagonist protocol with a GnRH agonist trigger for
final oocyte maturation is recommended for donor
oocyte and fertility preservation cycles. (III-C)
Prolonged hospitalization with severe OHSS tends to occur
more commonly in pregnancy cycles. Cryopreservation
of all embryos prevents the possibility of pregnancy
in that cycle. The strategy of freezing all embryos in a
patient at risk for severe OHSS can prevent prolonged
hospitalization, yet still offer hope for a pregnancy with a
subsequent transfer of thawed embryos. Avoiding the risk
of OHSS needs to be balanced against the possibility of
having poor embryo survival, a reduced chance of success
after thawing, and a later embryo transfer. However,
since vitrification has become available at many treatment
centres, the efficiency of cryopreservation programs has
increased dramatically, with significantly increased embryo
survival rates and higher ongoing pregnancy rates than
slow freezing techniques.57,58
A trial comparing cryopreservation of all embryos with fresh
embryo transfer alone found a lower incidence of OHSS in
the group in which all embryos were cryopreserved than in
the fresh embryo transfer group (0/58 vs. 4/67), although
this difference did not reach statistical significance.59
Garcia-Velasco et al. compared their experience with
agonist triggering and oocyte vitrification in patients at
high risk of developing OHSS with coasting in 248 patients
undergoing IVF who were at risk for OHSS.47 Ninety-six
patients were triggered with the agonist, with their eggs
vitrified and then transferred after thawing and fertilization
in a subsequent cycle, and 152 were coasted and then had
a fresh embryo transfer.47 The clinical pregnancy and
implantation rates were significantly higher with transfer
of frozen-thawed embryos in a subsequent cycle than
with fresh embryo transfer after coasting (50% vs. 29.5%,
and 32.1% vs. 19.2%, respectively). There were no cases
of OHSS in the cryopreservation and subsequent embryo
transfer group, but an 18.7% rate of moderate OHSS in
those women who were coasted, with additional cases that
were cancelled for being at extremely high risk for OHSS
even after coasting.
1030 l NOVEMBER JOGC NOVEMBRE 2014
In patients at high risk for OHSS on a GnRH antagonist
protocol, GnRH agonist trigger followed by embryo
cryopreservation of all embryos is a good option for
preventing OHSS.
Summary Statements
7. Avoiding pregnancy by freezing all embryos will
prevent severe prolonged ovarian hyperstimulation
syndrome in patients at high risk. (II-2)
8. Pregnancy rates are not affected when using
gonadotropin-releasing hormone (GnRH) agonists
in GnRH antagonist protocols for final egg
maturation when embryos are frozen by vitrification
for later transfer. (II-2)
A number of clinical trials have yielded conflicting results
on the use of intravenous fluids such as albumin, HES,
Haemaccel, and dextran at the time of egg retrieval as
a possible way to prevent the severe form of OHSS. It
has been speculated that prophylactic intravenous fluid
administration may interrupt the development of OHSS
by increasing the plasma oncotic pressure, restorating
intravascular volume, and deactivating ovarian mediators
involved in the pathogenesis of OHSS.60 Intravenous
administration of fluids such as human albumin, HES,
Haemaccel, and dextran infusion immediately post oocyte
retrieval or shortly thereafter have also been reported.60
In 2011 a Cochrane review of 8 RCTs comparing human
albumin and placebo in 1660 patients and HES and
placebo in 487 patients at risk for OHSS found a borderline
statistically significant decrease in the incidence of severe
OHSS with the administration of human albumin (8
RCTs; OR 0.67; 95% CI 0.45 to 0.99).60 Although there
was also some supportive evidence for the use of HES
in preventing OHSS, the safety of HES has not been
established and more studies are needed to fully address its
use. No RCT compared either dextran or Haemaccel with
placebo or no treatment. The cumulative literature does
not support the use of intravenous albumin around the
time of egg retrieval for the prevention of OHSS.
Recommendation
6. Albumin or other plasma expanders at the time of
egg retrieval are not recommended for the prevention
of ovarian hyperstimulation syndrome. (I-E)
Elective Single Embryo Transfer
It is well-known that endogenous hCG levels are
significantly higher in multiple pregnancies than in singleton
pregnancies.61 If an embryo transfer is being planned in
a young patient who is thought to be at significant risk
for OHSS based on underlying risk factors, elective single

embryo transfer should be advised. This may decrease the
risk of multiple gestations and should in turn decrease the
risk of severe OHSS.
Recommendation
7. Elective single embryo transfer is recommended in
patients at high risk for ovarian hyperstimulation
syndrome. (III-C)
In patients undergoing controlled superovulation with
pituitary suppression and oocyte retrieval, luteal phase
hormonal supplementation is needed to maximize the
chance of pregnancy.53 HCG is effective at providing LPS,
however, it plays a vital role in precipitating OHSS and may
worsen established OHSS. In a meta-analysis of RCTs,
progesterone was established as being equally effective
as hCG for LPS and it is associated with a lower risk of
OHSS.62
Recommendation
8. Progesterone, rather than human chorionic
gonadotropin, should be used for luteal phase
support. (I-A)
Culdocentesis
Active outpatient intervention in the early stages of OHSS
can minimize associated complications.63 Culdocentesis
may alleviate patient discomfort and function to precipitate
diuresis in women who are oliguric.64 Culdocentesis can
be offered in an attempt to prevent disease progression
in severe OHSS and eliminate the need for hospital
admission.63
Recommendation
9. Outpatient culdocentesis should be considered for
the prevention of disease progression in severe
ovarian hyperstimulation syndrome. (II-2B)
SUMMARY
Risk-factors and response to ovarian stimulation are
limited in their ability to assist in the prediction of OHSS
disease occurrence. This becomes evident as some OHSS
cases occur in patients not thought to be at significant
risk, while the majority of high-risk cases do not result in
OHSS.1 Experience with controlled ovarian stimulation
and knowledge of OHSS pathophysiology, risk factors, and
clinical presentation remains essential for the prevention
of severe OHSS.
In spite of limited understanding of the pathophysiology
of OHSS, there is now good evidence that preventive
strategies can profoundly reduce the incidence of severe
OHSS. Prior to the start of controlled ovarian stimulation,
The Prevention of Ovarian Hyperstimulation Syndrome
the addition of metformin in patients with PCOS
undergoing IVF should be considered as it may reduce the
incidence of OHSS. During the treatment cycle, clinical
risk factors should be used in judging the starting doses of
gonadotropins. In patients with a very robust response to
gonadotropins, coasting should be considered to prevent
later OHSS. At the time of hCG trigger, the use of
Cabergoline has been shown to reduce the risk for severe
OHSS in patients at risk for this complication. There is no
strong evidence to support hCG trigger dose as an effective
means to decrease the risk of OHSS. Cycle cancellation by
withholding hCG has consistently been shown to obviate
the risk of OHSS. Avoiding pregnancy by freezing all
embryos will prevent severe prolonged OHSS in patients
at high risk. Evidence also suggests that a GnRH agonist
trigger followed by cryopreservation of all embryos is
comparable to cycle cancellation in its efficacy at preventing
OHSS with little compromise in success rates in those
IVF centres that have a good embryo cryopreservation
program. Finally, progesterone should be used for LPS
rather than hCG. Continued research is required to gain
a better appreciation of the pathophysiology of OHSS,
which may advance our ability to predict and prevent this
potentially serious illness.
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 315, November 2014

The Prevention of Ovarian

Hyperstimulation Syndrome
Abstract
This clinical practice guideline has been prepared by the
Reproductive Endocrinology Infertility Committee and Objective: To review the clinical aspects of ovarian hyperstimulation
approved by Executive and Council of the Society of syndrome and provide recommendations on its prevention.
Obstetricians and Gynaecologists of Canada.
Options: Preventative measures, early recognition, and prompt
systematic supportive care will help avoid poor outcomes.
PRINCIPAL AUTHORS
Outcomes: Establish guidelines to assist in the prevention of ovarian
Shannon Corbett, MD, Ottawa ON hyperstimulation syndrome, early recognition of the condition
Doron Shmorgun, MD, Ottawa ON when it occurs, and provision of appropriate supportive measures
in the correct setting.
Paul Claman, MD, Ottawa ON
Evidence: Published literature was retrieved through searches
REPRODUCTIVE ENDOCRINOLOGY of Medline, Embase, and the Cochrane Library from 2011 to
INFERTILITY COMMITTEE 2013 using appropriate controlled vocabulary ([OHSS] ovarian
hyperstimulation syndrome and: agonist IVF, antagonist IVF,
Anthony Cheung, MD (Co-chair), Vancouver BC metformin, HCG, gonadotropin, coasting, freeze all, agonist
Sony Sierra, MD (Co-chair), Toronto ON trigger, progesterone) and key words (ovarian hyperstimulation
syndrome, ovarian stimulation, gonadotropin, human chorionic
Belina Carranza-Mamane, MD, Sherbrooke QC gonadotropin, prevention). Results were restricted to systematic
Allison Case, MD, Saskatoon SK reviews, randomized control trials/controlled clinical trials, and
observational studies published in English. There were no date
Cathie Dwyer, RN, Toronto ON restrictions. Searches were updated on a regular basis and
James Graham, MD, Calgary AB incorporated in the guideline to February 2013.

Jon Havelock, MD, Burnaby BC Grey (unpublished) literature was identified through searching the
websites of health technology assessment and health technology-
Sarah Healey, MD, St. John’s NL related agencies, clinical practice guideline collections, clinical
Robert Hemmings, MD, Montreal QC trial registries, and national and international medical specialty
societies.
Kimberly Liu, MD, Toronto ON
Values: The quality of evidence in this document was rated using the
Tarek Motan, MD, Edmonton AB criteria described in the Report of the Canadian Task Force on
Ward Murdock, MD, Fredericton NB Preventive Health Care (Table 1).

David Smithson, MD, London ON

Summary Statements
Tannys Vause, MD, Ottawa ON
1. The particular follicle-stimulating hormone formulation used
Benjamin Wong, MD, Calgary AB for ovarian stimulation does not affect the incidence of ovarian
hyperstimulation syndrome. (I)
SPECIAL CONTRIBUTOR
2. Coasting may reduce the incidence of severe ovarian
Mathias Gysler, MD, Oakville ON hyperstimulation syndrome. (III)
Disclosure statements have been received from all contributors.

Key Words: Ovarian hyperstimulation syndrome, ovarian

stimulation, gonadotropin, human chorionic gonadotropin,
prevention
J Obstet Gynaecol Can 2014;36(11):1024–1033

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

1024 l NOVEMBER JOGC NOVEMBRE 2014


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.65
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.65
3. Coasting for longer than 3 days reduces in vitro fertilization
pregnancy rates. (II-2)
4. The use of either luteinizing hormone or human chorionic
gonadotropin for final oocyte maturation does not influence the
incidence of ovarian hyperstimulation syndrome. (I)
5. There is no clear published evidence that lowering the human
chorionic gonadotropin dose will result in a decrease in the rate of
ovarian hyperstimulation syndrome. (III)
6. Cabergoline starting from the day of human chorionic
gonadotropin reduces the incidence of ovarian hyperstimulation
syndrome in patients at higher risk and does not appear to lower
in vitro fertilization pregnancy rates. (II-2)
ABBREVIATIONS
ART assisted reproductive technology
CI confidence interval
FSH follicle-stimulating hormone
GnRH gonadotropin-releasing hormone
hCG human chorionic gonadotropin
HES hydroxyethyl starch
IVF in vitro fertilization
LH luteinizing hormone
LPS luteal phase support
OHSS ovarian hyperstimulation syndrome
OR odds ratio
PCOS polycystic ovary syndrome
RCT randomized control study
SC subcutaneously
VEGF vascular endothelial growth factor
The Prevention of Ovarian Hyperstimulation Syndrome
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
7. Avoiding pregnancy by freezing all embryos will prevent severe
prolonged ovarian hyperstimulation syndrome in patients at high
risk. (II-2)
8. Pregnancy rates are not affected when using gonadotropin-
releasing hormone (GnRH) agonists in GnRH antagonist protocols
for final egg maturation when embryos are frozen by vitrification for
later transfer. (II-2)
Recommendations
1. The addition of metformin should be considered in patients with
polycystic ovarian syndrome who are undergoing in vitro fertilization
because it may reduce the incidence of ovarian hyperstimulation
syndrome. (I-A)
2. Gonadotropin dosing should be carefully individualized, taking into
account the patient’s age, body mass, antral follicle count, and
previous response to gonadotropins. (II-3B)
3. Cycle cancellation before administration of human chorionic
gonadatropin is an effective strategy for the prevention of ovarian
hyperstimulation syndrome, but the emotional and financial burden
it imposes on patients should be considered before the cycle is
cancelled. (III-C)
4. Gonadotropin-releasing hormone (GnRH) antagonist stimulation
protocols are recommended in patients at high risk for ovarian
hyperstimulation syndrome (OHSS). The risk of severe OHSS in
patients on GnRH antagonist protocols who have a very robust
ovarian stimulation response can be reduced by using a GnRH
agonist as a substitute for human chorionic gonadotropin to trigger
final oocyte maturation. (I-B)
5. A gonadotropin-releasing hormone (GnRH) antagonist protocol with
a GnRH agonist trigger for final oocyte maturation is recommended
for donor oocyte and fertility preservation cycles. (III-C)
6. Albumin or other plasma expanders at the time of egg retrieval are
not recommended for the prevention of ovarian hyperstimulation
syndrome. (I-E)
7. Elective single embryo transfer is recommended in patients at high
risk for ovarian hyperstimulation syndrome. (III-C)
NOVEMBER JOGC NOVEMBRE 2014 l 1025
SOGC Clinical Practice Guideline

8. Progesterone, rather than human chorionic gonadotropin, should Table 2. Classification of OHSS
be used for luteal phase support. (I-A)
Grade Symptoms
9. Outpatient culdocentesis should be considered for the prevention
of disease progression in severe ovarian hyperstimulation Mild OHSS Abdominal bloating
syndrome. (II-2B) Mild abdominal pain
Ovarian size usually < 8 cm
INTRODUCTION Moderate OHSS Moderate abdominal pain
Nausea with/without vomiting

O HSS is a iatrogenic complication of exogenous

gonadotropin therapy used to mature multiple
follicles for assisted reproductive treatments. The syndrome
Ultrasound evidence of ascites
Ovarian size usually 8–12 cm
Severe OHSS Clinical ascites (occasionally pleural
is only rarely observed with clomiphene citrate treatment effusion)
but has been reported even after spontaneous ovulation.1 Oliguria
Published guidelines already exist on the management Hemoconcentration hematocrit (> 45%)
of patients suffering from severe OHSS.2 The goal of Hypoproteinemia
this guideline is to provide a practical, evidence-based Ovarian size usually > 12 cm
framework for the prevention of OHSS. Critical OHSS Tense ascites or large pleural effusion
Hematocrit (> 55%)
After gonadotropin stimulation for IVF, the reported
White cell count > 25 000/L
incidence of moderate OHSS is 3% to 6%, and for
Oligo/anuria
severe OHSS it is 0.1% to 2%.3,4 The mild form, which
Thromboembolism
has little clinical consequence, occurs in about 20% to
Acute respiratory distress syndrome
33% of IVF cycles3,5 and is of little clinical concern.
Reproduced with permission of the British Fertility Society.1
However, fatalities have been reported in the most severe
cases.6 Except during rare events, OHSS occurs only after
ovulation (i.e. after exposure to an endogenous LH surge,
to exogenous LH or hCG, or to endogenous hCG of turn decreases the clinical burden of OHSS.14 Numerous
pregnancy).7 Early OHSS symptoms may begin as soon other mediators have been implicated in the disease
as 24 hours after hCG administration, but become most process such as angiotensin II, insulin-like growth factor
severe 7 to 10 days after hCG; severe OHSS is usually 1 and interleukin-6.2
associated with the rise of endogenous hCG from an
early pregnancy8 (see Table 2). Risk Factors
Several factors have been demonstrated to independently
Physicians prescribing ovarian stimulation need to identify increase the risk of developing OHSS. These include
patients at increased risk for OHSS in order to apply
•• age < 30 years,15
preventive and active management strategies to minimize
morbidity from this complication of fertility treatment. •• polycystic ovaries (i.e., > 24 antral follicles present on
baseline ultrasound examination),16,17
Pathophysiology of OHSS
•• high serum estradiol at hCG trigger or rapidly rising
OHSS is a systemic disease thought to result from
serum estradiol,15
vasoactive peptides released from the granulosa cells in
hyperstimulated ovaries.7 The fundamental physiological •• previous episodes of OHSS,18
change in severe OHSS is an increase in vascular perme­ •• large number of small follicles (8 to 12 mm) seen on
ability, resulting in a fluid shift from the intravascular spaces ultrasound during ovarian stimulation,17
to third-space compartments such as the peritoneal and
•• use of hCG, as opposed to progesterone, for luteal
thoracic cavities, often resulting in hemoconcentration.9,10
phase support after IVF,18
The most important mediator in this process is thought
to be VEGF.11 Supporting evidence comes from studies •• large number of oocytes retrieved (> 20),19 and
showing that serum VEGF levels correlate with OHSS •• high anti-müllerian hormone (> 3.36 ng/mL).20
severity. Additionally, hCG has been shown to increase
VEGF expression in human granulosa cells, which in PREVENTION
turn raises serum VEGF concentration.12,13 A new body
of clinical data demonstrates how the administration of Physicians providing ART treatment must balance the
dopamine agonist drugs decreases VEGF activity, which in competing interests of trying to sufficiently stimulate the

1026 l NOVEMBER JOGC NOVEMBRE 2014


ovary to optimize the chance of achieving a pregnancy
and minimizing the risk of severe OHSS. To achieve both
of these goals both primary and secondary preventative
measures have been shown to be useful.1
Primary prevention involves identifying risk factors for
OHSS and choosing an appropriate ovarian stimulation
regimen. Secondary prevention involves recognizing
patients who are over-responsive to gonadotropins and
intervening to reduce the risk of OHSS while still trying to
salvage the treatment cycle.
A meta-analysis of 5 RCTs showed a significant reduction
in the incidence of OHSS with the use of metformin in
women with PCOS undergoing IVF (12/216 vs. 44/210;
OR 0.21, 95% CI 0.11 to 0.41, P < 0.01).21 These findings
were later corroborated in a Cochrane review from the
same group.22 Interestingly, a recent RCT showed that
women with polycystic ovarian morphology that does not
meet the criteria for PCOS do not incur the same protective
benefit from metformin of reduced OHSS.23
Metformin should ideally be started 8 weeks before
planned gonadotropin stimulation to be effective in OHSS
prevention. To minimize gastrointestinal side effects we
recommend starting Metformin at a low dose of 500 mg
HS and slowly increasing the dose until the effective dose
of 500 mg × 3 (1500 mg) daily is reached. Metformin
should continue until egg retrieval.
Two separate meta-analyses of RCTs comparing
recombinant FSH and urinary FSH showed no difference
in the incidence of OHSS.24,25
There is no linear positive correlation between
gonadotropin dose and the incidence of severe OHSS.
On the contrary, patients developing OHSS tend to be
those who respond robustly to gonadotropins and are
often prescribed lower than average doses of these drugs
than other women undergoing IVF. Young, thin women,
especially those with polycystic ovaries on ultrasound
(i.e., > 12 antral follicles seen on each ovary) are at
higher risk for OHSS and should receive a lower starting
dose of gonadotropin than would be given to other
women.26 Careful monitoring of these patients during
stimulation is prudent to allow for a decrease in the dose
of gonadotropins if a very robust response is detected
early in the treatment cycle.18
Summary Statement
1. The particular follicle-stimulating hormone
formulation used for ovarian stimulation does not
affect the incidence of ovarian hyperstimulation
syndrome. (I)
The Prevention of Ovarian Hyperstimulation Syndrome
Recommendations
1. The addition of metformin should be considered
in patients with polycystic ovarian syndrome who
are undergoing in vitro fertilization because it may
reduce the incidence of ovarian hyperstimulation
syndrome. (I-A)
2. Gonadotropin dosing should be carefully
individualized, taking into account the patient’s
age, body mass, antral follicle count, and previous
response to gonadotropins. (II-3B)
Coasting
Coasting involves withholding gonadotropins while
maintaining pituitary suppression with a gonadotropin-
releasing hormone agonist or antagonist. Administering
hCG to trigger oocyte maturation once estrogen levels
plateau or drop is thought to reduce the risk for OHSS.
Larger follicles have a lower requirement for FSH than
smaller follicles. Once follicles are > 12 mm in diameter,
stopping all gonadotropins still allows for larger follicles to
continue their growth and maturation, while smaller follicles
undergo atresia, which may result in reduced production
of vasoactive peptides such as VEGF.27 It has been shown
that coasting on a GnRH agonist for up to 3 days does not
adversely affect pregnancy rates.28 The same criteria for
coasting can be applied to GnRH antagonist cycles as to
GnRH agonist cycles with similar IVF outcomes.29
In a systematic review of 12 retrospective studies
examining the benefit of coasting, the coasted patients
had a 2.5% incidence of hospitalization for OHSS,
which is lower than expected for patients at high risk
for OHSS.30 Previous studies have shown a significant
drop in pregnancy rate with longer than 3 to 4 days of
coasting.28,31 Therefore, cycle cancellation should be
considered if estradiol levels do not start to fall by the
fourth day of coasting.
A meta-analysis of 3 RCTs comparing recombinant LH
with urinary hCG for triggering final oocyte maturation
and 11 RCTs comparing recombinant hCG with urinary
LH did not show any difference in the risk of OHSS.32
Summary Statements
2. Coasting may reduce the incidence of severe ovarian
hyperstimulation syndrome. (III)
3. Coasting for longer than 3 days reduces in vitro
fertilization pregnancy rates. (II-2)
4. The use of either luteinizing hormone or human
chorionic gonadotropin for final oocyte maturation
does not influence the incidence of ovarian
hyperstimulation syndrome. (I)
NOVEMBER JOGC NOVEMBRE 2014 l 1027
SOGC Clinical Practice Guideline
The degree of hCG exposure has been associated with the
risk of OHSS.18 It is recognized that hCG has no direct
effect on the vascular system33; however, vasoactive
substances such as VEGF are released in the ovary in
response to hCG administration and are most likely
responsible for inducing vascular hyperpermeability and
third-spacing in high-risk women.34 A retrospective series
of 94 IVF cycles showed that when hCG doses were
lowered, both pregnancy rates and the rate of severe
OHSS remained unchanged.35 However, a lower incidence
of severe OHSS has been observed with the use of lower
doses of hCG for final oocyte maturation in an at-risk
population. Because serum levels of hCG are dependent
on body mass,36,37 one Canadian fertility centre uses hCG
5000 IU SC to trigger final egg maturation in patients at
risk for OHSS who have a BMI < 28 kg/m2, despite the
lack of published data. Women with a BMI ≥ 28 kg/m2
are all given hCG 10 000 IU SC for final egg maturation
because yields of mature eggs have been observed to be
lower with a dose reduction in this population.36
Summary Statement
5. There is no clear published evidence that lowering
human chorionic gonadotropin dose will result in
a decrease in the rate of ovarian hyperstimulation
syndrome. (III)
Cabergoline
VEGF produced by granulosa cells of developing follicles
is thought to be a key mediator in both hCG-dependent
ovarian angiogenesis and the pathophysiology of OHSS.38
Recently, the dopamine agonist cabergoline has been
introduced as a secondary prevention strategy in women
deemed to be at high risk for OHSS because of a very
robust gonadotropin response at the end of a controlled
ovarian stimulation cycle. Dopamine agonists show similar
effects to anti-angiogenic drugs on vascular permeability,
and except for occasional nausea, they appear not to have
undesirable side effects.33,39 Evidence from animal models
shows that cabergoline blocks VEGF-mediated increase
in vascular permeability without affecting angiogenesis.33
Carbergoline’s postulated mechanism of action is partial
inhibition of the phosphorylation of its associated
receptor, the VEGF receptor 2.40
A recent Cochrane review included 2 RCTs addressing
cabergoline and OHSS. In the RCT conducted by Alvarez
et al. on oocyte donors at risk for OHSS (20 to 30 follicles
at > 12 mm and > 20 eggs retrieved), in which the
treatment group received oral cabergoline 0.5 mg daily for
8 days starting on the day of hCG and the control group
received a placebo, the incidence of moderate OHSS was
significantly reduced in the cabergoline group (20% vs.
1028 l NOVEMBER JOGC NOVEMBRE 2014
43.8%, P = 0.04).14 The same first author also showed
that pregnancy rates are not compromised in patients
given cabergoline.41 The second RCT by Carriza et al.
randomized women who were undergoing IVF and at
high risk for OHSS (estradiol ≥ 14 700 pmol/L on day of
hCG trigger) into two groups: the study group received
20 grams of prophylactic intravenous albumin and 0.5 mg
of Cabergoline orally once daily for 3 weeks commencing
the day after oocyte retrieval and the control group received
only albumin.42 The risk of early OHSS (occurring within
the first 9 days after hCG trigger) decreased significantly
(P < 0.001) in the cabergoline group; none of the patients
who had taken cabergoline progressed to early OHSS, but
15.0% of the control group did. The risk of late OHSS did
not decrease. In both of the RCTs examined, the use of
cabergoline did not affect the pregnancy outcome (clinical
pregnancy rate or miscarriage rate), nor was it associated
with an increased risk of adverse events.43
Two published abstracts have demonstrated the safety
and efficacy of using cabergoline at even smaller doses:
0.5 mg twice weekly for 6 doses44 and 0.5 mg twice weekly
for 3 doses.45 Clinicians at one Canadian fertility centre use
a dose of cabergoline 0.5 mg every 3 days to a total of 4
doses starting on the day of oocyte maturation trigger and
a significant reduction in the incidence of severe OHSS
has been anecdotally observed since the introduction of
cabergoline into the prevention strategies for OHSS.
Although still somewhat preliminary, current data suggest
that cabergoline is associated with a reduction in moderate
OHSS in patients at high risk and has no adverse effect on
the pregnancy rate.
Summary Statement
6. Cabergoline starting from the day of human
chorionic gonadotropin reduces the incidence of
ovarian hyperstimulation syndrome in patients at
higher risk and does not appear to lower in vitro
fertilization pregnancy rates. (II-2)
Cycle Cancellation
OHSS will not develop in the absence of exposure to
exogenous hCG or LH or to an endogenous LH surge
as long as a pregnancy does not develop. Therefore,
withholding hCG in cycles at risk for OHSS and cancelling
the cycle is the most effective method of preventing OHSS.
This prevention strategy is especially important in agonist
cycles in which the option to substitute an agonist trigger
for hCG does not exist. However, because the emotional
and financial costs of cancellation are significant, other
prevention strategies should be exhausted before cycle
cancellation is considered.

Recommendation
3. Cycle cancellation before the administration
of human chorionic gonadotropin is an
effective strategy for the prevention of ovarian
hyperstimulation syndrome, but the emotional and
financial burden it imposes on patients should be
considered before the cycle is cancelled. (III-C)
PROTOCOLS
Assisted reproductive technologies, especially IVF
protocols, generally use GnRH agonists or antagonists
to prevent an endogenous LH surge from occurring
before follicular maturation. A Cochrane review of 29
RCTs showed a significantly lower incidence of OHSS
in GnRH antagonist cycles than in GnRH agonist cycles
(OR 0.43; 95% CI 0.33 to 0.57). Differences in rates of
pregnancy or live births were not observed between the
two protocols.46
One important benefit of using GnRH antagonist
protocols in patients at risk for OHSS (e.g., PCOS patients)
is that final oocyte maturation can be achieved using a
GnRH agonist instead of hCG. In a GnRH antagonist
protocol, a GnRH agonist trigger will displace the GnRH
antagonist from the GnRH receptor to induce a controlled
surge of endogenous LH and FSH. This GnRH agonist-
induced LH has a shorter half-life than exogenous hCG,
resulting in a less sustained luteotrophic stimulation and
hence a lower risk for OHSS.47 GnRH agonist triggering
may prevent early OHSS. OHSS is rarely encountered in
IVF egg donors when GnRH agonist is used to trigger
final oocyte maturation.47
An important potential concern when using a GnRH
agonist trigger during GnRH antagonist IVF cycles is the
possible risk of having an inadequate luteal phase. A single
dose of GnRH agonist induces an endogenous LH surge
that has a much shorter half-life than hCG, resulting in
compromised corpus luteum formation48 and a shorter
duration of the luteal phase.49 Initial reports showed
poor clinical outcomes with a higher incidence of early
pregnancy loss and compromised pregnancy rates when a
GnRH agonist was used for final oocyte maturation.50,51
Subsequent transfer of frozen-thawed embryos from
patients with a GnRH agonist trigger showed improved
pregnancy rates and spontaneous abortion rates similar
to those in patients using an hCG trigger. These data
suggest that the etiology of the observed lower success
rates in fresh cycles triggered with GnRH agonist is due to
endometrial problems in the luteal phase rather than to an
effect on embryo quality.52
The Prevention of Ovarian Hyperstimulation Syndrome
More recent studies have addressed these concerns by
employing a more comprehensive LPS protocol after
final oocyte maturation with GnRH agonists. Using
the more aggressive LPS protocol, IVF success rates
with a GnRH agonist trigger were comparable to those
observed when hCG was used for final egg maturation.
In 2011 Humaidan et al. reviewed 6 recent RCTs
employing a protocol of more aggressive LPS (3 RCTs
with aggressive high dose progesterone and estrogen
supplementation LPS, 2 RCTs with the addition of
low-dose hCG LPS, and one RCT with progesterone
and recombinant LH LPS). Importantly, the live birth
rate per fresh IVF embryo transfer cycle improved
significantly when modified luteal support was used.
There were no cases of severe OHSS reported after
GnRH agonist triggering, but a 4.6% incidence of
severe OHSS was observed in the hCG trigger group
for a risk difference of 5% (95% CI −0.07 to 0.02).53
These results support GnRH agonist triggering as an
alternative to hCG triggering when a fresh embryo
transfer is planned, resulting in a reduction of OHSS
and the potential to preserve IVF success rates with
adequate LPS. It is not yet clear whether using a GnRH
agonist trigger with aggressive LPS results in the same
pregnancy rate with fresh embryo transfer as using hCG
to trigger final oocyte maturation.
Although the optimal protocol of luteal supplementation
has not yet been defined, 2 approaches to luteal
phase support in agonist-triggered cycles have been
proposed. The first approach is to use aggressive steroid
supplementation with progesterone and estrogen,
allowing the corpus luteum to degenerate and reduce
the risk of OHSS.54 The second approach is to attempt
rescue of the corpus luteum by administering a low
dose of hCG on the day of oocyte retrieval in addition
to standard LPS with vaginal progesterone and oral
estrogen.55,56 The latter approach may need fine tuning
because hCG may exacerbate the risk of OHSS and
has mostly been examined in a population that was
not at high risk for OHSS.52 For cycles in which an
oocyte donor is stimulated or for fertility preservation
cycles in which embryo transfer is not going to occur,
a GnRH antagonist pituitary suppression protocol is
recommended. This will offer an option for a GnRH
agonist trigger to help obviate OHSS risk without
affecting pregnancy rates, because a compromised luteal
phase is not a concern when embryos are not being
transferred into the patient being stimulated. For oocyte
donors Lupron 3 mg (0.6 mL) intramuscular 36 hours
prior to oocyte retrieval, followed by a repeat dose 10
hours later may be used.
NOVEMBER JOGC NOVEMBRE 2014 l 1029
SOGC Clinical Practice Guideline
Recommendations
4. Gonadotropin-releasing hormone (GnRH)
antagonist stimulation protocols are recommended
in patients at high risk for ovarian hyperstimulation
syndrome (OHSS). The risk of severe OHSS in
patients on GnRH antagonist protocols who have
a very robust ovarian stimulation response can be
reduced by using a GnRH agonist as a substitute
for human chorionic gonadotropin to trigger final
oocyte maturation. (I-B)
5. A gonadotropin-releasing hormone (GnRH)
antagonist protocol with a GnRH agonist trigger for
final oocyte maturation is recommended for donor
oocyte and fertility preservation cycles. (III-C)
Prolonged hospitalization with severe OHSS tends to occur
more commonly in pregnancy cycles. Cryopreservation
of all embryos prevents the possibility of pregnancy
in that cycle. The strategy of freezing all embryos in a
patient at risk for severe OHSS can prevent prolonged
hospitalization, yet still offer hope for a pregnancy with a
subsequent transfer of thawed embryos. Avoiding the risk
of OHSS needs to be balanced against the possibility of
having poor embryo survival, a reduced chance of success
after thawing, and a later embryo transfer. However,
since vitrification has become available at many treatment
centres, the efficiency of cryopreservation programs has
increased dramatically, with significantly increased embryo
survival rates and higher ongoing pregnancy rates than
slow freezing techniques.57,58
A trial comparing cryopreservation of all embryos with fresh
embryo transfer alone found a lower incidence of OHSS in
the group in which all embryos were cryopreserved than in
the fresh embryo transfer group (0/58 vs. 4/67), although
this difference did not reach statistical significance.59
Garcia-Velasco et al. compared their experience with
agonist triggering and oocyte vitrification in patients at
high risk of developing OHSS with coasting in 248 patients
undergoing IVF who were at risk for OHSS.47 Ninety-six
patients were triggered with the agonist, with their eggs
vitrified and then transferred after thawing and fertilization
in a subsequent cycle, and 152 were coasted and then had
a fresh embryo transfer.47 The clinical pregnancy and
implantation rates were significantly higher with transfer
of frozen-thawed embryos in a subsequent cycle than
with fresh embryo transfer after coasting (50% vs. 29.5%,
and 32.1% vs. 19.2%, respectively). There were no cases
of OHSS in the cryopreservation and subsequent embryo
transfer group, but an 18.7% rate of moderate OHSS in
those women who were coasted, with additional cases that
were cancelled for being at extremely high risk for OHSS
even after coasting.
1030 l NOVEMBER JOGC NOVEMBRE 2014
In patients at high risk for OHSS on a GnRH antagonist
protocol, GnRH agonist trigger followed by embryo
cryopreservation of all embryos is a good option for
preventing OHSS.
Summary Statements
7. Avoiding pregnancy by freezing all embryos will
prevent severe prolonged ovarian hyperstimulation
syndrome in patients at high risk. (II-2)
8. Pregnancy rates are not affected when using
gonadotropin-releasing hormone (GnRH) agonists
in GnRH antagonist protocols for final egg
maturation when embryos are frozen by vitrification
for later transfer. (II-2)
A number of clinical trials have yielded conflicting results
on the use of intravenous fluids such as albumin, HES,
Haemaccel, and dextran at the time of egg retrieval as
a possible way to prevent the severe form of OHSS. It
has been speculated that prophylactic intravenous fluid
administration may interrupt the development of OHSS
by increasing the plasma oncotic pressure, restorating
intravascular volume, and deactivating ovarian mediators
involved in the pathogenesis of OHSS.60 Intravenous
administration of fluids such as human albumin, HES,
Haemaccel, and dextran infusion immediately post oocyte
retrieval or shortly thereafter have also been reported.60
In 2011 a Cochrane review of 8 RCTs comparing human
albumin and placebo in 1660 patients and HES and
placebo in 487 patients at risk for OHSS found a borderline
statistically significant decrease in the incidence of severe
OHSS with the administration of human albumin (8
RCTs; OR 0.67; 95% CI 0.45 to 0.99).60 Although there
was also some supportive evidence for the use of HES
in preventing OHSS, the safety of HES has not been
established and more studies are needed to fully address its
use. No RCT compared either dextran or Haemaccel with
placebo or no treatment. The cumulative literature does
not support the use of intravenous albumin around the
time of egg retrieval for the prevention of OHSS.
Recommendation
6. Albumin or other plasma expanders at the time of
egg retrieval are not recommended for the prevention
of ovarian hyperstimulation syndrome. (I-E)
Elective Single Embryo Transfer
It is well-known that endogenous hCG levels are
significantly higher in multiple pregnancies than in singleton
pregnancies.61 If an embryo transfer is being planned in
a young patient who is thought to be at significant risk
for OHSS based on underlying risk factors, elective single

embryo transfer should be advised. This may decrease the
risk of multiple gestations and should in turn decrease the
risk of severe OHSS.
Recommendation
7. Elective single embryo transfer is recommended in
patients at high risk for ovarian hyperstimulation
syndrome. (III-C)
In patients undergoing controlled superovulation with
pituitary suppression and oocyte retrieval, luteal phase
hormonal supplementation is needed to maximize the
chance of pregnancy.53 HCG is effective at providing LPS,
however, it plays a vital role in precipitating OHSS and may
worsen established OHSS. In a meta-analysis of RCTs,
progesterone was established as being equally effective
as hCG for LPS and it is associated with a lower risk of
OHSS.62
Recommendation
8. Progesterone, rather than human chorionic
gonadotropin, should be used for luteal phase
support. (I-A)
Culdocentesis
Active outpatient intervention in the early stages of OHSS
can minimize associated complications.63 Culdocentesis
may alleviate patient discomfort and function to precipitate
diuresis in women who are oliguric.64 Culdocentesis can
be offered in an attempt to prevent disease progression
in severe OHSS and eliminate the need for hospital
admission.63
Recommendation
9. Outpatient culdocentesis should be considered for
the prevention of disease progression in severe
ovarian hyperstimulation syndrome. (II-2B)
SUMMARY
Risk-factors and response to ovarian stimulation are
limited in their ability to assist in the prediction of OHSS
disease occurrence. This becomes evident as some OHSS
cases occur in patients not thought to be at significant
risk, while the majority of high-risk cases do not result in
OHSS.1 Experience with controlled ovarian stimulation
and knowledge of OHSS pathophysiology, risk factors, and
clinical presentation remains essential for the prevention
of severe OHSS.
In spite of limited understanding of the pathophysiology
of OHSS, there is now good evidence that preventive
strategies can profoundly reduce the incidence of severe
OHSS. Prior to the start of controlled ovarian stimulation,
The Prevention of Ovarian Hyperstimulation Syndrome
the addition of metformin in patients with PCOS
undergoing IVF should be considered as it may reduce the
incidence of OHSS. During the treatment cycle, clinical
risk factors should be used in judging the starting doses of
gonadotropins. In patients with a very robust response to
gonadotropins, coasting should be considered to prevent
later OHSS. At the time of hCG trigger, the use of
Cabergoline has been shown to reduce the risk for severe
OHSS in patients at risk for this complication. There is no
strong evidence to support hCG trigger dose as an effective
means to decrease the risk of OHSS. Cycle cancellation by
withholding hCG has consistently been shown to obviate
the risk of OHSS. Avoiding pregnancy by freezing all
embryos will prevent severe prolonged OHSS in patients
at high risk. Evidence also suggests that a GnRH agonist
trigger followed by cryopreservation of all embryos is
comparable to cycle cancellation in its efficacy at preventing
OHSS with little compromise in success rates in those
IVF centres that have a good embryo cryopreservation
program. Finally, progesterone should be used for LPS
rather than hCG. Continued research is required to gain
a better appreciation of the pathophysiology of OHSS,
which may advance our ability to predict and prevent this
potentially serious illness.
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NOVEMBER JOGC NOVEMBRE 2014 l 1033
 SOGC CLINICAL PRACTICE GUIDELINE
Venous Thromboembolism and
Antithrombotic Therapy in Pregnancy
This clinical practice guideline has been prepared by the
VTE in Pregnancy Guideline Working Group, reviewed by
Maternal Fetal Medicine and Family Physician Advisory
committees, and approved by the Executive and Council of
the Society of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Wee-Shian Chan, MD, Vancouver BC
Evelyne Rey, MD, Montreal QC
Nancy E. Kent, MD, Vancouver BC
VTE IN PREGNANCY GUIDELINE WORKING GROUP
Wee-Shian Chan, MD (Co-Chair), Vancouver BC
Nancy E. Kent, MD (Co-Chair), Vancouver BC
Evelyne Rey, MD (Co-Chair), Montreal QC
Thomas Corbett, MD, Edmonton AB
Michèle David, MD, Montreal QC
M. Joanne Douglas, MD, Vancouver BC
Paul S. Gibson, MD, Calgary AB
Laura Magee, MD, Vancouver BC
Marc Rodger, MD, Ottawa ON
Reginald E. Smith, Pharm D, Victoria BC
Disclosure statements have been received from all contributors.
Abstract
Objective: To present an approach, based on current evidence,
for the diagnosis, treatment, and thromboprophylaxis of venous
thromboembolism in pregnancy and postpartum.
Evidence: Published literature was retrieved through searches of
PubMed, Medline, CINAHL, and The Cochrane Library from
Key Words: Venous thromboembolism, deep vein thrombosis,
pulmonary embolism, thromboprophylaxis, assisted reproductive
technology, heparin, neuraxial analgesia, adverse pregnancy
outcomes, pregnancy or puerperal complications
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 308, June 2014 (Replaces No. 95, September 2000)
November 2011 to July 2013 using appropriate controlled vocabulary
(e.g. pregnancy, venous thromboembolism, deep vein thrombosis,
pulmonary embolism, pulmonary thrombosis) and key words (e.g.,
maternal morbidity, pregnancy complications, thromboprophylaxis,
antithrombotic therapy). Results were restricted to systematic
reviews, randomized control trials/controlled clinical trials, and
observational studies published in English or French. There were no
date restrictions. Grey (unpublished) literature was identified through
searching the websites of clinical practice guideline collections,
clinical trial registries, and national and international medical
specialty societies.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventative Health Care (Table 1).
Recommendations
01. Objective testing is required following clinical suspicion of deep vein
thrombosis or pulmonary embolism. (II-2A)
02. For the diagnosis of deep vein thrombosis, ultrasonography is
recommended, and should be repeated at least once over 7 days if
the initial study is negative. For each examination, the entire length
of the venous system from the external iliac to the popliteal vein
must be visualized and compression manoeuvres performed from
the femoral to the popliteal vein. (II-2B)
03. For the diagnosis of pulmonary embolism, either ventilation-
perfusion scan or computed tomographic angiography can be
used. (II-2A) In pregnant women, a ventilation-perfusion scan is
the preferred test. (III-B)
04. Neither D-dimer alone nor clinical prediction rules should be used
to rule out venous thromboembolism in pregnant women without
objective testing. (III-D)
05. Pregnant women diagnosed with acute venous thromboembolism
should be hospitalized or followed closely as outpatients for the first
2 weeks after the initial diagnosis. (III-C)
06. Low molecular weight heparin is the preferred pharmacologic
agent over unfractionated heparin for the treatment of venous
thromboembolism in pregnancy. (II-2A)
07. Heparin-induced thrombocytopenia in pregnant women is extremely
rare. Consultation with a hematologist or thrombosis specialist is
recommended to consider the use of heparanoids for treatment of
venous thromboembolism if it occurs. (II-3B)
J Obstet Gynaecol Can 2014;36(6):527–553
JUNE JOGC JUIN 2014 l 527
SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.187
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.187
08. Vitamin K antagonists should only be considered in exceptional
circumstances for the treatment of venous thromboembolism in
pregnancy. (II-2A)
09. We recommend against the use of oral Xa inhibitors and
oral direct thrombin inhibitors for the treatment of venous
thromboembolism in pregnancy. (III-D)
10. For the treatment of acute venous thromboembolism in
pregnancy we recommend adhering to the manufacturer’s
recommended dosing for individual low molecular weight
heparins based on the woman’s current weight. (II-1A) Low
molecular weight heparin can be administered once or twice a
day depending on the agent selected. (III-C)
11. For pregnant women initiated on therapeutic low molecular
weight heparin, baseline platelet counts should be done
and repeated a week later to screen for heparin-induced
thrombocytopenia. (III-C)
12. For pregnant women with an acute venous thromboembolism
we recommend therapeutic anticoagulation for a minimum of 3
months. (I-A)
13. Following initial treatment, anticoagulation intensity can be
decreased to intermediate or prophylactic dose for the remainder
of the pregnancy and for at least 6 weeks postpartum. (III-C)
14. In pregnant women with acute proximal leg deep vein thrombosis,
the use of graded compression stockings can be considered for
relief of symptoms. (III-C)
15. Thrombolytic therapy in pregnancy should only be considered
in limb-threatening deep vein thrombosis or massive pulmonary
embolism. (III-C)
16. Vena cava filters should only be used in pregnant women
with acute pulmonary embolism or deep vein thrombosis and
contraindications to anticoagulation. (III-C)
17. Computed tomographic venography and/or magnetic resonance
imaging should be performed to rule out cerebral venous
thrombosis if suspected. (I-C)
528 l JUNE JOGC JUIN 2014
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
18. Therapeutic dose anticoagulation should be initiated for confirmed
cerebral venous thrombosis. (II-2A)
19. Thromboprophylaxis should be considered in future pregnancies
following a cerebral venous thrombosis. (II-1C)
20. For superficial thrombophlebitis, compression ultrasound should be
performed to exclude deep vein thrombosis (II-2A), and it should
be repeated if proximal extension is suspected based on worsening
phlebitis. (III-C)
21. Prophylactic or intermediate dose low molecular weight heparin for
1 to 6 weeks is recommended for women with bilateral superficial
thrombophlebitis, for very symptomatic women, and for superficial
thrombophlebitis located ≤ 5 cm from the deep venous system
(saphenofemoral and saphenopopliteal junctions) or affecting ≥ 5 cm
of vein. (I-A)
22. Observation alone is recommended in women with superficial
thrombophlebitis at low risk of deep vein thrombosis and for those
who do not require symptom control. Clinical follow-up of these
women should occur within 7 to 10 days, with a repeat compression
ultrasound within one week. (I-A)
23. Computed tomography and/or magnetic resonance imaging (with or
without angiography) are the definitive imaging modalities to rule out
ovarian vein thrombosis. (II-2A)
24. For confirmed ovarian vein thrombosis, we recommend parenteral
broad-spectrum antibiotics, continued for at least 48 hours after
defervescence and clinical improvement. (II-2A) Longer antibiotic
therapy is necessary for septicemia or complicated infections. (III-C)
25. For confirmed ovarian vein thrombosis, therapeutic dose
anticoagulation could be considered for 1 to 3 months. (III-C)
26. Routine screening for all inherited thrombophilias in all women with a
first episode of venous thromboembolism diagnosed in pregnancy is
not indicated. (III-C)
27. Testing for protein S, protein C, and antithrombin deficiencies is
indicated following a venous thromboembolism in pregnancy if there
is a family history of these particular thrombophilias, or if thrombosis
occurs in an unusual site. (III-C)
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
28. Testing for antiphospholipid antibodies is indicated if the results
would affect the duration of anticoagulation. (III-C)
29. Individual risk assessment for venous thromboembolism should
be performed prior to all pregnancies, once pregnancy is
achieved, and repeated throughout pregnancy as new clinical
situations arise. The woman’s preferences and values should
be taken into account when considering the use of antepartum
thromboprophylaxis. (III-B)
30. Women at increased risk should be advised of the symptoms and
signs of venous thromboembolism. (III-B)
31. Low molecular weight heparin is the preferred pharmacologic
agent over unfractionated heparin for antepartum
thromboprophylaxis. (III-A) Low molecular weight heparin doses
should be used as per the manufacturer’s recommendation. (III-C)
32. Routine anti-Xa medication and platelet-level monitoring are
not recommended when a patient is on a prophylactic dose of
thromboprophylaxis. (II-2E)
ABBREVIATIONS
APLS antiphospholipid syndrome
aPTT activated partial thromboplastin time
ART assisted reproductive technology
AT antithrombin
ASA acetylsalicylic acid
ASRA American Society of Regional Anesthesia
BMI body mass index
CT computed tomography
CTA CT angiography
CUS compression ultrasound
CVT cerebral venous thrombosis
DVT deep vein thrombosis
FVL factor V Leiden
HIT heparin-induced thrombocytopenia
IUGR intrauterine growth restriction
LDA low-dose ASA
LMWH low molecular weight heparin
MRI magnetic resonance imaging
NSAID non-steroidal anti-inflammatory drug
OHSS ovarian hyperstimulation syndrome
OVT ovarian vein thrombosis
PGM prothrombin gene mutation 20210A
PC protein C
PE pulmonary embolism
PS protein S
SGA small for gestational age
SLE systemic lupus erythematosus
ST superficial thrombophlebitis
UH unfractionated heparin
VQ ventilation/perfusion
VTE venous thromboembolism
33. We recommend therapeutic thromboprophylaxis during
pregnancy in the following situations:
a. long-term therapeutic anticoagulation used prior to pregnancy
for a persistent indication; (III-B)
b. personal history of multiple previous venous
thromboembolism. (III-B)
34. We recommend intermediate or therapeutic thromboprophylaxis
during pregnancy in the following situation:
a. personal history of a previous venous thromboembolism
and a high-risk thrombophilia (antithrombin deficiency,
antiphospholipid syndrome) not previously on
anticoagulation. (III-B)
35. We recommend prophylactic dose thromboprophylaxis during
pregnancy in the following situations (absolute risk > 1%):
a. personal history of a previous unprovoked venous
thromboembolism; (II-2A)
b. personal history of a previous venous thromboembolism
related to oral contraceptives or pregnancy; (II-2A)
c. personal history of a previous provoked venous
thromboembolism and any low risk thrombophilia; (I-A)
d. asymptomatic homozygous factor V Leiden; (II-2A)
e. asymptomatic homozygous prothrombin gene mutation
20210A; (III-B)
f. asymptomatic combined thrombophilia; (III-B)
g. asymptomatic antithrombin deficiency; (III-B)
h. non-obstetrical surgery during pregnancy, with the duration
of thromboprophylaxis being procedure- and patient-
dependent; (III-B)
i. strict antepartum bedrest for ≥ 7 days in a woman with
a body mass index of > 25 kg/m2 at her first antenatal
visit. (II-2B)
36. Antepartum thromboprophylaxis for isolated pregnancy-related
risk factors is not recommended. (III-E)
37. Antepartum thromboprophylaxis should be considered in the
presence of multiple clinical or pregnancy-related risk factors
where the overall absolute risk of venous thromboembolism is
estimated to be > 1%, especially in women admitted to hospital
for bed rest. (II-2B)
38. Routine thromboprophylaxis is not required for all women
undergoing ovulation induction. (III-C)
39. If severe ovarian hyperstimulation syndrome occurs with assisted
reproductive technology, we recommend thromboprophylaxis
with low molecular weight heparin for at least 8 to 12 weeks after
resolution of the syndrome. (III-B)
40. Thromboprophylaxis with low molecular weight heparin should
be considered for any women at increased risk for venous
thromboembolism undergoing assisted reproductive technology
at the time of ovarian stimulation. (III-B)
41. Women who develop a venous thromboembolism in association
with the use of assisted reproductive technology but who do
not conceive in that cycle should be treated with therapeutic
anticoagulation for a minimum of 3 months. (II-3A) Those who
conceive in that assisted reproductive technology cycle should
be treated as per recommendations 12 and 13 for acute venous
thromboembolism in pregnancy. (I-A, III-C)
42. Women on prophylactic dose, intermediate dose, or therapeutic
anticoagulation should have a discussion about options for
analgesia/anaesthesia prior to delivery. (III-B)
JUNE JOGC JUIN 2014 l 529
SOGC CLINICAL PRACTICE GUIDELINE
43. Switching from thromboprophylactic low molecular weight heparin
to a prophylactic dose of unfractionated heparin at term (37
weeks) may be considered to allow for more options with respect
to labour analgesia. (III-L)
44. Discontinue prophylactic or intermediate dose low molecular
weight heparin or unfractionated heparin upon the onset of
spontaneous labour or the day prior to a planned induction of
labour or Caesarean section. (II-3B)
45. A recent platelet count should be available on admission in labour
or before Caesarean delivery in women who have been, or are,
on anticoagulants. (III-B)
46. For women on low molecular weight heparin, neuraxial
anaesthesia can be administered as a:
a. prophylactic dose: a minimum of 10 to 12 hours after the last
dose; (III-B)
b. therapeutic dose: after 24 hours since the last dose. (III-B)
47. For women on unfractionated heparin, neuraxial anaesthesia can
be administered as a:
a. prophylactic dose (maximum 10 000 U/day): after no
delay; (III-B)
b. therapeutic intravenous infusion: at least 4 hours after
stopping the infusion and when the activated partial
thromboplastin time is normal; (III-B)
c. therapeutic subcutaneous unfractionated heparin: when the
activated partial thromboplastin time is normal. This may be
12 hours or longer after the last injection. (III-B)
48. Neuraxial anaesthesia must be avoided in a woman who is
fully anticoagulated or in whom there is evidence of altered
coagulation. (II-3A)
49. Removal of a neuraxial catheter left in situ postpartum should
only be done 4, 10 to 12, or 24 hours following the administration
of prophylactic dose unfractionated heparin (maximum
10 000 U/day), prophylactic low molecular weight heparin (single
daily dose), or therapeutic dose low molecular weight heparin,
respectively, or in the case of therapeutic unfractionated heparin,
when the activated partial thromboplastin time is normal. (II-3B)
50. Prophylactic dose low molecular weight heparin (single daily
dose) may be started or restarted 4 hours after neuraxial catheter
removal, providing there is full neurological recovery and no
evidence of active bleeding or coagulopathy. (III-B)
51. Therapeutic low molecular weight heparin may be started or
restarted at least 24 hours after a single injection neuraxial block
and a minimum of 4 hours after neuraxial catheter removal,
providing there is full neurological recovery and no evidence of
active bleeding or coagulopathy. (III-B)
52. Subcutaneous unfractionated heparin may be started or restarted
at least 1 hour after a single injection neuraxial block, providing
there is full neurological recovery and no evidence of active
bleeding or coagulopathy. (III-B)
53. Do not administer antiplatelet agents (acetylsalicylic acid or non-
steroidal anti-inflammatory drugs) concomitantly with heparin if a
neuraxial catheter is left in situ postpartum. (III-D)
54. Women on therapeutic anticoagulation who have received
neuraxial anesthesia should be monitored closely for the
development of a spinal hematoma. (III-B)
55. Universal postpartum thromboprophylaxis is not
recommended. (III-D)
56. Assess women for increased risk of postpartum venous
thromboembolism based on antepartum, intrapartum, and
530 l JUNE JOGC JUIN 2014
postpartum risk factors after every delivery and repeat as new
clinical situations arise. (II-2B)
57. Low molecular weight heparin is the preferred pharmacologic
agent over unfractionated heparin for postpartum thrombo­
prophylaxis. (III-A) Low molecular weight heparin doses should
be used as per the manufacturer’s recommendation. (III-C)
58. Pharmacologic thromboprophylaxis postpartum is recommended
in the following situations:
Any 1 of the following risk factors (each with an absolute risk of
venous thromboembolism > 1%):
a. history of any prior venous thromboembolism; (II-2A)
b. any high-risk thrombophilia: antiphospholipid syndrome,
antithrombin deficiency, homozygous factor V Leiden
or prothrombin gene mutation 20210A, or combined
thrombophilia; (II-2B)
c. strict bedrest prior to delivery for 7 days or more; (II-2B)
d. peripartum or postpartum blood loss of > 1 litre or
blood product replacement, and concurrent postpartum
surgery; (II-2B)
e. peripartum/postpartum infection. (II-2B)
59. Postpartum thromboprophylaxis should be considered in the
presence of multiple clinical or pregnancy-related risk factors
when the overall absolute risk is estimated to be greater than 1%
drawn from the following groupings:
a. any 2 of the following risk factors (each with an absolute risk
of venous thromboembolism < 1% in isolation):
i. body mass index ≥ 30 kg/m2 at first antepartum
visit; (II-2B)
ii. smoking > 10 cigarettes/day antepartum; (II-2B)
iii. preeclampsia; (II-2B)
iv. intrauterine growth restriction; (II-2B)
v. placenta previa; (II-2B)
vi. emergency Caesarean section; (II–2B)
vii. peripartum or postpartum blood loss of > 1 litre or blood
product replacement; (II-2B)
viii. any low risk thrombophilia: PC or PS deficiency,
heterozygous factor V Leiden, or prothrombin gene
mutation 20210A; (III-B)
ix. maternal cardiac disease, SLE, sickle cell disease,
inflammatory bowel disease, varicose veins, gestational
diabetes; (III-B)
x. preterm delivery; (III-B)
xi. stillbirth. (III-B)
b. Any 3 or more of the following risk factors (each with an
absolute risk of venous thromboembolism < 1%):
i. age > 35 years; (II-2B)
ii. parity ≥ 2; (II-2B)
iii. any assisted reproductive technology; (II-2B)
iv. multiple pregnancy; (II-2B)
v. placental abruption; (II-2B)
vi. premature rupture of membranes; (II-2B)
vii. elective Caesarean section; (II-2B)
viii. maternal cancer. (III-B)
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
60. Intermittent or sequential pneumatic compression devices
are alternatives in women when heparin is contraindicated
postpartum. When the risk of postpartum venous
thromboembolism is high they may be used in combination with
low molecular weight heparin or unfractionated heparin. (III-B)
61. Women with ongoing and persistent risk factors should receive
postpartum thromboprophylaxis for a minimum of 6 weeks
postpartum. (II-3B)
62. Women with transient antepartum or intrapartum risk factors
should receive postpartum thromboprophylaxis until discharged
from hospital or up to 2 weeks postpartum. (III-C)
63. Universal screening for thrombophilias in women experiencing
adverse pregnancy outcomes (severe preeclampsia, intrauterine
growth restriction, stillbirth) is not indicated. (II-2D)
64. Women with recurrent miscarriage or late pregnancy loss should
be screened for antiphospholipid syndrome. (I-B)
65. Low-dose acetylsalicylic acid or low-dose acetylsalicylic acid plus
low molecular weight heparin is recommended in pregnancy in
women with confirmed antiphospholipid syndrome. (I-C)
66. Low-dose acetylsalicylic acid plus low molecular weight heparin
is not recommended for women with a history of recurrent
miscarriage in the absence of confirmed antiphospholipid
syndrome. (I-E)
67. Low molecular weight heparin should not be used routinely to
reduce the risk of recurrent placenta-mediated complications in
women with or without thrombophilia (excluding antiphospholipid
syndrome). (I-C)
INTRODUCTION
T his guideline summarizes the available data and the
quality of the evidence to provide practical approaches
to the diagnosis, management, and prevention of VTE in
pregnancy. VTE remains an important cause of maternal
morbidity and mortality in Canada with an overall incidence
of DVT and PE of 12.1 per 10 000 and 5.4 per 10 000
pregnancies, respectively.1 VTE occurs at a rate of 5.4 per
10 000 antepartum, 7.2 per 10 000 peripartum, and 4.3 per
10 000 pregnancies postpartum.1 These rates are consistent
with published literature from around the world.2–4 The first
and second trimesters of pregnancy convey similar risks
for DVT, with a higher risk in the third trimester and the
first 3 weeks postpartum.5,6 PE occurs more commonly
postpartum, decreasing in incidence after the first 6 weeks.3,7
This guideline sequentially reviews key components in
reducing the risk VTE in pregnancy, which include accurate
diagnosis and treatment of DVT and PE, antepartum
thromboprophylaxis in appropriate patients, peripartum
management of anticoagulants, and postpartum
thromboprophylaxis, and concludes with a discussion of
the use of heparin to prevent adverse pregnancy outcomes.
Making decisions about the management of individual
patients can be challenging and complex. Wherever
possible, this guideline attempts to summarize and organize
the existing evidence that supports the recommendations,
and it is meant to be complementary to other international
guidelines on this topic.8–15
ACUTE VENOUS THROMBOEMBOLISM
IN PREGNANCY
Due to hormonal influences on vascular tone and
compressive effects on veins by the enlarging uterus, DVT
in pregnancy generally presents in the lower extremities,
with a predisposition for the left leg (70 to 80%).16,17 In
contrast to their presentation in non-pregnant patients,
DVTs are often isolated to the iliac and/or femoral vein
during pregnancy (61%).18 Consequently diagnostic
approaches advocated for use in non-pregnant patients
require modification in pregnancy.8
Diagnosis of VTE in Pregnancy
In non-pregnant patients, diagnostic approaches for
VTE use a combination of validated structured clinical
prediction rules with or without the use of D-dimer testing,
followed by objective testing with CUS.8 Extrapolating the
same approach to pregnancy is difficult because:
1. structured prediction rules have not been validated in
pregnant women,
2. the anatomic presentation of lower extremity DVT in
pregnant women could affect the sensitivity of CUS,18
and
3. current validated D-dimer level cut-off points are of
limited utility.19,20
The potential use of a pregnancy-specific structured
prediction rule and pregnancy-specific D-dimer thresholds
has been reported,21–23 but currently neither test should be
used alone or in combination to diagnose or exclude VTE
without further validation studies.
Our recommended diagnostic algorithm for DVT in
pregnancy is shown in Figure 1. When a pregnant woman
presents with a suspected DVT, she should undergo an
ultrasound including direct visualization of the entire
proximal venous system from the iliac to the popliteal
vein.24 Doppler studies should be performed at the level of
the iliac vein to ensure that flow is present. Compression
manoeuvers should be performed along the entire venous
system from the femoral to the popliteal vein. The sensitivity
and negative predictive value of this method are 90.9%
(95% CI 69.4 to 98.4) and 98.9% (95% CI 95.5 to 99.8),
respectively.24 Published evidence is currently insufficient
to support the safety of performing a single ultrasound
examination in pregnant women with suspected DVT.
Hence, we would recommend repeat testing with CUS and
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SOGC CLINICAL PRACTICE GUIDELINE

Figure 1. Algorithm for the diagnosis of deep venous thrombosis in pregnant patients

Suspected DVT

Compression ultrasound of entire proximal venous system from iliac to

popliteal vein and Doppler examination of external iliac vein

DVT DVT not Consider MRI if isolated

diagnosed diagnosed iliac vein DVT is suspected
based on symptoms and
Doppler examination of
external iliac vein

Repeat above ultrasound

examination within 7 days

DVT not diagnosed

DVT diagnosed

Clinical follow-up

Doppler imaging as above at least once again over the next
7 days if the initial study is negative. If isolated iliac vein
obstruction (i.e. absence of flow) is suspected on Doppler
examination, two options are available:
1. institute therapeutic anticoagulation followed by repeat
CUS in 2 to 3 days, or
2. proceed with MRI.
The option chosen depends on patient preference,
availability of expertise, and access to imaging. The
specificity and sensitivity of MRI and the specific technique
used to diagnose DVT in pregnancy remains uncertain.25,26
When PE is suspected clinically, definitive diagnosis requires
diagnostic imaging. Several factors should be considered in
the choice of VQ scan or CTA:
1. the maternal and fetal risks associated with the tests
(radiation and contrast agent),
2. the sensitivity of the tests, and
3. their availability.
For both VQ scan and CTA the calculated radiation risk to
the fetus is low, with levels below the threshold of 50 mGy
for subsequent childhood malignancy.27–29 The calculated
minimum radiation dose to each breast for an average 60 kg
woman is 20 to 35 mGy from CTA and 0.28 mGy from VQ
scan.30,31 While little is known about the long-term effects of
radiation exposure to breast tissue during pregnancy, there
are data linking imaging procedures to an increased risk of
breast cancer.32 The iodinated contrast agent required for
computed tomographic angiography to diagnosis PE crosses
the placenta and can theoretically result in fetal or neonatal
hypothyroidism. However, this risk was not significant in an
observational study of over 300 pregnancies.33
In pregnancy the observed sensitivity and negative
predictive values of CTA and VQ scan appears to be high,
using clinical outcome as a surrogate measure.34–38 The
specificity of a CTA in pregnancy cannot be ascertained,
but studies in non-pregnant patients suggest CTA might
be less specific in younger patients.39 The decision to use
CTA or VQ scan is also dictated by local availability and
expertise. The CTA technique used to diagnose PE in non-
pregnant patients should be modified as 5% to 36% of
scans can be inadequate in pregnancy due to physiological
changes.32,40–42 We currently advocate the use of the VQ
scan as the diagnostic test in pregnancy whenever possible

532 l JUNE JOGC JUIN 2014

 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy

Figure 2. Algorithm for the diagnosis of pulmonary embolism in

pregnant patients using the preferred VQ scan

Suspected PE

Bilateral ultrasound examination of

lower extremity*

DVT DVT not

diagnosed diagnosed

Start
VQ scan
treatment

Normal Non-diagnostic High probability

High/moderate
Low pretest†
pretest†

Serial Spiral CTA PE

ultrasound scan‡ diagnosed
exams of lower
extremity*

*Bilateral US should include examination of the iliac veins with Doppler manoeuvers
†Pretest determined by clinician’s subjective assessment
‡Modification in spiral CT protocol should be considered for pregnant patients

for the reasons listed above. However, if CTA is used, it Recommendations

is important to counsel patients regarding breast radiation
and ensure local awareness for technique modification.
As illustrated in Figure 2, initial testing for PE should
reasonably begin with bilateral CUS. Although the likelihood
of asymptomatic DVT is low, if a DVT is diagnosed in the
presence of unexplained chest pain, shortness of breath or
tachycardia, a PE can be assumed and ventilation-perfusion
scanning avoided. If CUS is negative or if the initial
bilateral leg CUS examination is not available, a ventilation-
perfusion scan should be performed. If the scan is normal,
no further testing is needed; if the scan is high probability,
anticoagulation should be initiated. For non-diagnostic scans,
either CTA or serial CUS testing, based on clinical suspicion
and the presence of risk factors, should be done. If CTA is
selected, a negative scan will rule out a PE while a positive
scan will be diagnostic. When the CTA is inconclusive or
inadequate, serial whole leg ultrasound examination or
repeat testing with a VQ scan is recommended.43
1. Objective testing is required following clinical
suspicion of deep vein thrombosis or pulmonary
embolism. (II-2A)
2. For the diagnosis of deep vein thrombosis,
ultrasonography is recommended, and should be
repeated at least once over 7 days if the initial study
is negative. For each examination, the entire length
of the venous system from the external iliac to the
popliteal vein must be visualized and compression
manoeuvres performed from the femoral to the
popliteal vein. (II-2B)
3. For the diagnosis of pulmonary embolism, either
ventilation-perfusion scan or computed tomographic
angiography can be used. (II-2A) In pregnant women, a
ventilation-perfusion scan is the preferred test. (III-B)
4. Neither D-dimer alone nor clinical prediction rules
should be used to rule out venous thromboembolism
in pregnant women without objective testing. (III-D)

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SOGC CLINICAL PRACTICE GUIDELINE
Table 2. Incidence of side effects related to low molecular weight heparins in pregnancy
Therapeutic dose
Antepartum bleeding 0% to 0.57%
Postpartum bleeding 1.15% to 5.6%
Wound hematoma 1.39%
Major skin reaction/allergy 1.15%
Osteoporosis 0%
HIT 0%
TREATMENT OF ACUTE VTE
Setting
Once an acute VTE is confirmed, therapeutic anti­
coagulation should be instituted promptly. There are no
studies confirming the safety of outpatient management
in pregnancy for women with acute VTE. Given the
additional fetal concerns, pregnant women with an acute
PE and/or a large proximal DVT should be considered
for hospitalization or followed closely as outpatients in
the initial two weeks following diagnosis if they remain
hemodynamically stable.
Recommendation
5. Pregnant women diagnosed with acute venous
thromboembolism should be hospitalized or
followed closely as outpatients for the first 2 weeks
after the initial diagnosis. (III-C)
Choice of anticoagulant
Vitamin K antagonists, such as warfarin, should not be
considered for the treatment of VTE in pregnancy except
in exceptional circumstances. They cross the placenta, and
first trimester exposure can cause warfarin embryopathy
(midfacial and limb hypoplasia, stippled bone epiphyses).44,45
They are also associated with pregnancy loss and fetal
anticoagulation at the time of delivery.46
UH and LMWH do not cross the placenta and do not
cause teratogenicity or fetal bleeding.47–52 HIT occurs
in 3% of non-pregnant patients receiving UH. It has
never been reported in a pregnancy with LMWH, 51 and
outside of pregnancy HIT has been reported only in
rare cases.53
Due to its lower side-effect profile and ease of dosing,
LMWH is recommended over UH for use in pregnant
women. Table 2 outlines the pooled risk estimates of
side effects associated with LMWH use in pregnancy.
The specific LMWH preparation used depends on
availability and costs. There is no current evidence to
534 l JUNE JOGC JUIN 2014
Prophylactic dose Any dose References
0.42% 0% to 0.43% 51, 171 to 173
0.92% 0.94% to 1.6% 51, 171 to 173
0% 0.5% to 0.61% 51, 171 to 173
0.96% 0.5% to 1.8% 51, 173
0.26% 0.04% to 0.2% 51, 173
0% 0% 51, 173
suggest the superiority of one preparation of LMWH
over another.
Danaparoid and fondaparinux are heparanoid molecules
that do not cross-react with HIT antibodies. Both are
treatment options for pregnant women with evidence of
HIT or allergic reactions to heparins.54,55 These agents
should only be used after consultation with an appropriate
specialist.
There are currently no data on the safety in pregnancy of
the oral direct thrombin inhibitors (dabigatran) and factor
Xa inhibitors (rivaroxaban and apixaban). Given their very
low molecular weights, they are likely to cross the placenta
and should be avoided.
Recommendations
6. Low molecular weight heparin is the preferred
pharmacologic agent over unfractionated heparin
for the treatment of venous thromboembolism in
pregnancy. (II-2A)
7. Heparin-induced thrombocytopenia in pregnant
women is extremely rare. Consultation with
a hematologist or thrombosis specialist is
recommended to consider the use of heparanoids
for treatment of venous thromboembolism if it
occurs. (II-3B)
8. Vitamin K antagonists should only be considered
in exceptional circumstances for the treatment of
venous thromboembolism in pregnancy. (II-2A)
9. We recommend against the use of oral Xa
inhibitors and oral direct thrombin inhibitors for
the treatment of venous thromboembolism in
pregnancy. (III-D)
Anticoagulant dosing and monitoring
Recommended doses for anticoagulation medications
are presented in Table 3. The specific LMWH dosing is
as per the manufacturer’s recommendation, based on the
woman’s weight at the time of presentation.

Table 3. Dosing of anticoagulants
Prophylactic dose
UH 5000 U SC twice daily
Obesity: 7500 U SC twice daily
Dalteparin 5000 U SC daily or twice daily
> 20 weeks
Obesity: 7500 U SC daily
Enoxaparin 40 mg SC daily or 30 mg SC twice daily
Obesity: 60 mg SC daily
Nadroparin 2850 U SC daily
Tinzaparin 4500 U SC daily
Obesity: 75 U/kg daily
Danaparoid 750 U SC twice daily
SC: subcutaneously
There are uncertainties surrounding dosing regimens; the
need for monitoring and dose increases with weight gain
associated with therapeutic LMWH use in pregnancy.56
While LMWH is administered as a single daily dose for
non-pregnant patients, twice a day dosing is often used in
pregnancy, especially for the first month when the risk of
recurrence is greatest. This practice stems from the altered
renal elimination of LMWH and the impact of weight
gain, both of which affect anti-Xa activity in pregnant
women.9,14,50,52,57–59 Hence, for the treatment of acute VTE,
especially major proximal VTE and PE, consideration
should be given to initial monitoring of anti-Xa activity,
during the first month of treatment only, to target a level
of 0.6 to 1.0 U/mL 4 hours after injection, bearing in
mind that target levels will vary with the LMWH used.
However, the cost of the assay, the lack of correlation with
clinical events, and the variability between assays makes
the utility of monitoring anti-FXa activity in pregnancy
controversial.9
If UH is selected for initial treatment, it should be
administered initially as a bolus followed by a continuous
infusion, using a weight-based nomogram to estimate
required doses, and adjusting the infusion to keep the aPTT
at 1.5 to 2.5 times baseline. After initial treatment, a switch
to therapeutic subcutaneous LMWH or UH can be made.
If UH is selected, it should be administered subcutaneously
twice daily with doses adjusted to maintain the aPTT at 1.5
to 2.5 times pregnancy baseline at the mid-dosing interval
(i.e., 6 hours after the last dose). For women with significant
renal impairment (GFR < 30 mL/minute) we recommend
UH over LMWH.
Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
Intermediate dose Therapeutic dose
10 000 U SC twice daily IV: 80 U/kg bolus (max 5000 U) followed by
18 U/kg and adjusted according to local
nomogram
SC: 150 to 200 U/kg twice daily
A lower dose should be considered in women
weighing less than 50 kg175
Target aPTT 1.5 to 2.5 × baseline
100 U/kg SC daily or 200 U/kg daily or 100 U/kg SC twice daily
5000 U SC twice daily
40 mg SC twice daily 1 mg/kg SC twice daily or 1.5 mg/kg SC daily
Not applicable 171 U/kg SC daily
4500 U SC twice daily or 175 U/kg SC daily
9000 U SC daily
Not applicable 2000 U SC twice daily
Recommendations
10. For the treatment of acute venous
thromboembolism in pregnancy we recommend
adhering to the manufacturer’s recommended
dosing for individual low molecular weight heparins
based on the woman’s current weight. (II-1A) Low
molecular weight heparin can be administered once or
twice a day depending on the agent selected. (III-C)
11. For pregnant women initiated on therapeutic low
molecular weight heparin, baseline platelet counts
should be taken and repeated a week later to screen
for heparin-induced thrombocytopenia. (III-C)
Duration of therapeutic anticoagulation
If an acute VTE is diagnosed early in pregnancy,
reducing the anticoagulation intensity after 3 months to
intermediate or prophylactic (low) dose LMWH for the
duration of the pregnancy is an option, although evidence
confirming or disputing the safety of this option is
unavailable. In the postpartum period, both LMWH and
warfarin can be used.
Recommendations
12. For pregnant women with an acute venous
thromboembolism we recommend therapeutic
anticoagulation for a minimum of 3 months. (I-A)
13. Following initial treatment, anticoagulation intensity
can be decreased to intermediate or prophylactic
dose for the remainder of the pregnancy and for at
least 6 weeks postpartum. (III-C)
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SOGC CLINICAL PRACTICE GUIDELINE
Prevention of post-thrombotic syndrome
Post-thrombotic syndrome is a constellation of
symptoms (chronic leg swelling, discoloration, pain on
walking or standing) occurring in 20% to 40% of non-
pregnant patients who develop a proximal DVT.60 Graded
compression stockings with 30 to 40 mmHg pressure at
the ankles for 2 years were previously felt to reduce this
rate.61 A recent large placebo-controlled RCT (N = 803)
showed that compression stockings did not prevent post-
thrombotic syndrome, nor did they influence the severity
or rate of recurrence after a first proximal DVT in an
older non-pregnant population.62 Observational studies
are limited in pregnancy, therefore the need for prolonged
use of graded compression stockings in pregnant women
is uncertain and we recommend them for symptom relief
alone.
Recommendation
14. In pregnant women with acute proximal leg deep
vein thrombosis, the use of graded compression
stockings can be considered for relief of
symptoms. (III-C)
Thrombolytic therapy
Thrombolytic therapy has been used successfully in
pregnant women who present with massive PE and
hemodynamic instability.63,64 Streptokinase, r-tPA, and
urokinase do not appear to have direct placental transfer.
The risk of catastrophic bleeding with their use needs to
be weighed against the risk of maternal and fetal death.
The only indication for thrombolytic therapy in pregnancy
is limb-threatening DVT or a massive PE.8
Recommendation
15. Thrombolytic therapy in pregnancy should only be
considered in limb-threatening deep vein thrombosis
or massive pulmonary embolism. (III-C)
Vena cava filters
Vena cava filters are rarely required in pregnancy.65–68
Placement of a retrievable filter can be considered if
a patient presents with an acute PE within 2 weeks of
delivery or if anticoagulation therapy has to be interrupted
due to major bleeding concerns. Careful planning of filter
insertion with interventional radiology is necessary to
minimize fetal exposure to radiation.
Recommendation
16. Vena cava filters should only be used in pregnant
women with acute pulmonary embolism or
deep vein thrombosis and contraindications to
anticoagulation. (III-C)
536 l JUNE JOGC JUIN 2014
CEREBRAL VENOUS THROMBOSIS
The incidence of CVT ranges from 0.01% to 0.04% in
Western countries.69 Pregnancy and the puerperium,
Caesarean section, dehydration, anemia, thrombophilia,
and hypertension are identified risk factors.69–71 Symptoms
and signs include diffuse headache, altered consciousness,
seizures, and focal neurological deficits. CT venography
and/or MRI studies should be performed in suspected
CVT if initial imaging modalities without contrast are
negative or inconclusive.
Once CVT is diagnosed, therapeutic dose anticoagulation
should be initiated. In addition to haematologists and
thrombosis specialists, other medical and surgical
subspecialists may be required depending on neurological
complications.
Recommendations
17. Computed tomographic venography and/or
magnetic resonance imaging should be performed
to rule out cerebral venous thrombosis if
suspected. (I-C)
18. Therapeutic dose anticoagulation should be initiated
for confirmed cerebral venous thrombosis. (II-2A)
19. Thromboprophylaxis should be considered in
future pregnancies following a cerebral venous
thrombosis. (II-1C)
SUPERFICIAL THROMBOPHLEBITIS
Superficial thrombophlebitis is inflammation with or
without thrombosis of a superficial vein, isolated or
associated with peripheral or central catheters. The
incidence in pregnancy is 0.068%.72 ST is usually self-
limiting, but it can extend into the deep venous system
and/or recur. Factors associated with DVT include
bilateral ST, ST presenting near the deep venous system
(saphenofemoral and saphenopopliteal junctions), systemic
infection, absence of varicose veins, and a previous
history of DVT.73,74 Concurrent PE is diagnosed in 4% of
individuals with ST affecting ≥ 5 cm of a vein.75
The preferred treatment of ST is uncertain in pregnant
women. A recent trial in non-pregnant patients showed
that fondaparinux (2.5 mg daily for 45 days) significantly
reduced the incidence of DVT and the extension and
recurrence of the ST.76 A recent Cochrane meta-analysis
showed that LMWH (prophylactic and therapeutic doses)
and NSAIDS for 8 to 12 days were more effective than
placebo in reducing the extension or recurrence of ST, but
without decreasing the occurrence of symptomatic DVT.77
Since safety data on fondaparinux use is limited and
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
extended NSAID use is discouraged in pregnancy after
26 to 28 weeks’ gestation, we recommend prophylactic or
intermediate dose LMWH for 1 to 6 weeks in symptomatic
women and in women with bilateral ST, ST of 5 cm or
more, or ST located less than 5 cm from the deep venous
system. Observation alone is recommended in women
with ST who are at low risk of DVT and for those who do
not require symptom control. Clinical follow-up of these
women should occur within 7 to 10 days, with a repeat
CUS within one week.
Recommendations
20. For superficial thrombophlebitis, compression
ultrasound should be performed to exclude deep
vein thrombosis (II-2A), and it should be repeated
if proximal extension is suspected based on
worsening phlebitis. (III-C)
21. Prophylactic or intermediate dose low
molecular weight heparin for 1 to 6 weeks is
recommended for women with bilateral superficial
thrombophlebitis, for very symptomatic women,
and for superficial thrombophlebitis located ≤ 5 cm
from the deep venous system (saphenofemoral and
saphenopopliteal junctions) or affecting ≥ 5 cm of
vein. (I-A)
22. Observation alone is recommended in women with
superficial thrombophlebitis at low risk of deep
vein thrombosis and for those who do not require
symptom control. Clinical follow-up of these women
should occur within 7 to 10 days, with a repeat
compression ultrasound within one week. (I-A)
OVARIAN VEIN THROMBOSIS
Ovarian vein thrombosis is an uncommon event,
complicating 0.05% to 0.18% of pregnancies and affecting
the right vein in up to 90% of cases.78,79 Risk factors include
Caesarean section, multiple gestation, and infection.79
Complications include extension of the thrombus into the
vena cava and/or renal veins, and sepsis. PE occurs in 13%
of cases.80 Symptoms and signs of OVT include nausea,
vomiting, guarding, constant lower abdominal or flank
pain, palpable sausage-shaped tender abdominal masses,
fever, rigors, and leukocytosis in the first 15 days after a
delivery, abortion, or ruptured ectopic pregnancy. A pelvic
ultrasound should be done initially, followed by CT and/or
MRI in the case of a negative or equivocal result.81
Broad-spectrum parenteral antibiotics should be initiated
with the diagnosis of OVT and continued for at least 48
hours after defervescence and clinical improvement.82,83
A longer treatment course is required in the presence
of septicemia. Even though a small randomized study
(N = 14) did not report a difference in the resolution of the
fever with antibiotics alone versus antibiotics plus UH,78
concurrent anticoagulation is often recommended.79,82–84
We recommend anticoagulation for 1 to 3 months. There
are no studies to guide the risk of recurrence of OVT
and the need for thromboprophylaxis in subsequent
pregnancies. The risk is likely low.84
Recommendations
23. Computed tomography and/or magnetic resonance
imaging (with or without angiography) are the
definitive imaging modalities to rule out ovarian
vein thrombosis. (II-2A)
24. For confirmed ovarian vein thrombosis, we
recommend parenteral broad-spectrum antibiotics,
continued for at least 48 hours after defervescence
and clinical improvement. (II-2A) Longer antibiotic
therapy is necessary for septicemia or complicated
infections. (III-C)
25. For confirmed ovarian vein thrombosis, therapeutic
dose anticoagulation could be considered for 1 to 3
months. (III-C)
THROMBOPHILIA SCREENING AFTER
THE DIAGNOSIS OF ACUTE VTE
There is no consensus as to whether or not patients require
thrombophilia testing following the diagnosis of an acute
VTE in the non-pregnant state. The acute management
of the current or subsequent pregnancies is generally not
altered by knowledge of the thrombophilia status, nor is
counselling regarding subsequent risks of VTE. However,
patients with VTE and a known family history of PS, PC,
or AT deficiency would benefit from screening, as these
might affect the duration of anticoagulation required
for the initial episode.85 Screening for other inherited
thrombophilias is unnecessary because the presence of
these will not change management.86,87
Screening for acquired thrombophilia, i.e. APLS, has been
advocated for non-pregnant patients, since a persistently
positive screen (over 12 weeks) could affect the duration
of anticoagulation.86 There are concerns about applying
this to pregnant women:
1. the risk of a false positive, leading to patient anxiety, is
significant,
2. the need to prolong anticoagulation beyond the usual
recommended duration for pregnant patients with
APLS is uncertain, and
3. repeat testing is required 8 to 12 weeks after delivery.
JUNE JOGC JUIN 2014 l 537
SOGC CLINICAL PRACTICE GUIDELINE
We therefore recommend against routine screening for
APLS during pregnancy, unless thrombosis occurs in an
unusual site or if the results would affect the duration of
anticoagulation.
Recommendations
26. Routine screening for all inherited thrombophilias
in all women with a first episode of venous
thromboembolism diagnosed in pregnancy is not
indicated. (III-C)
27. Testing for protein S, protein C, and antithrombin
deficiencies is indicated following a venous
thromboembolism in pregnancy if there is a family
history of these particular thrombophilias, or if
thrombosis occurs in an unusual site. (III-C)
28. Testing for antiphospholipid antibodies is indicated
if the results would affect the duration of
anticoagulation. (III-C)
MANAGEMENT OF ANTICOAGULATION
THERAPY IN PREGNANT WOMEN
WITH MECHANICAL HEART VALVES
For management of anticoagulation therapy in these
patients, we would refer clinicians to the guidelines
published by American College of Chest Physicians.9
ANTEPARTUM THROMBOPROPHYLAXIS
Recognizing that the pregnant state confers an increased
risk for VTE is only the first step in determining which
women will benefit from thromboprophylaxis during
pregnancy. Although there is a 10-fold increase over
baseline, the absolute risk of VTE during pregnancy
remains low (0.5 per 1000 pregnancies),1 and LMWH
is not a risk-free medication (see Table 2). Hence, the
difficulty in clinical practice is reconciling the low absolute
risk of VTE with the low risk of side effects associated
with thromboprophylaxis.
Determining a reasonable level of absolute risk of VTE
for recommending a need for thromboprophylaxis
was the first step in the development of this guideline.
Most experts would agree that pregnant women with
an estimated absolute risk of VTE above 10% should
receive thromboprophylaxis, while those with an
estimated VTE risk of less than 1% might not. When
the risk falls between 1% and 10% the decision to offer
thromboprophylaxis would depend on the magnitude of
VTE risk, the consequences of having a DVT or PE, the
risks associated with thromboprophylaxis, and the patient’s
and physician’s preferences.88 In this guideline we leaned
538 l JUNE JOGC JUIN 2014
towards the avoidance of VTE during pregnancy, while
minimizing the number of women who would experience
heparin side effects. Hence, we recommend antepartum
thromboprophylaxis when the overall estimated absolute
risk of VTE is greater than 1%.
Unfortunately, the magnitude to which additional biological
factors in the antepartum period increase the risk for a
given patient is imprecisely reported in the literature (see
Table 4). Involvement of appropriate specialists should be
considered in cases of clinical uncertainty.
Previous objectively documented VTEs which were
unprovoked or related to hormonal therapy or pregnancy
confer the highest risk of recurrence during pregnancy and
warrant antepartum thromboprophylaxis.89–92 Unprovoked
or idiopathic VTEs are those occurring in the absence
of clinical risk factors such as surgery, hospitalization or
plaster cast immobilization within one month, and cancer.
Thrombophilias, whether inherited or acquired, have
varying propensities for VTE. High-risk thrombophilias
include AT deficiency, APLS, homozygous FVL or PGM,
and combined thrombophilias.93,94 The more prevalent
inherited thrombophilias, such as heterozygote FVL and
PGM, confer a lower risk of VTE than the rarer ones,
such as PS and PC deficiency.95,96 Since data to guide the
use of thromboprophylaxis in uncommon asymptomatic
thrombophilia are sparse, our recommendations for these
conditions are based on estimated absolute risks for VTE
in the general population97–99 rather than on data from
retrospective family studies,100–103 especially for PC deficiency.
Note that a recent task force on APLS recommended the use
of hydroxychloroquine for thromboprophylaxis in patients
with both SLE and APLS,104 although the benefit of this
recommendation has not been proven in pregnancy.
Screening for thrombophilia in women with a previous
VTE should only be done if the result will modify
management in the current pregnancy, in the presence of a
family history of a high-risk inherited thrombophilia, and
if the woman is fully counselled about the implications
of a positive result prior to testing. Screening specifically
for APLS should be considered in women with a previous
unprovoked VTE or VTEs in unusual sites.
A family history of VTE alone, in the absence of a personal
history or other risk factors for VTE, does not increase the
personal risk of VTE sufficiently to warrant antepartum
thromboprophylaxis.105
The contribution of various clinical and pregnancy-
related risk factors for VTE has been derived from several
population-based observational studies.2,3,106–108 (Table 5)
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy

Table 4. Literature review of incidence of symptomatic VTE antepartum without prophylaxis

according to various biological and clinical risk factors
Incidence of symptomatic VTE*
< 1% 1% to 5% > 5% to 10% > 10%
Personal history of previous VTE
Single unprovoked ••91,92 •89
Pregnancy-related • 92
•91
OCP-related •92 •91 •90
Single provoked (Other than • 91
•• 89,90

OCP- or pregnancy-related)
FVL (hetero- and homozygosity) •100 •89
FVL homozygosity •100
Combined FVL and PGM heterozygosity •94
AT deficiency •• 176,177

Asymptomatic thrombophilia
FVL homozygosity ••••101,178,181,182 •••96,98,179
PGM homozygosity •96
Combined FVL and PGM heterozygosity •• 98,182
••• 94,96,179

AT deficiency ••179,183 ••99,174 ••98,103 ••177,183

FVL heterozygosity ••••••• 96–99,178–180

PGM heterozygosity ••••96,98,101,179 •94

PC deficiency ••• 98,99,179
•• 102,185
••176,183
PS deficiency •••103,183,185 •176
Family history of symptomatic thrombophilia
and unknown status
FVL •••97,101,178
PGM ••102,184
PC deficiency ••99,103
PS deficiency •••103,183,185
Combined pregnancy-related risk factors
Strict bed rest ≥ 7 days + BMI ≥ 25 kg/m2 •109
at first antenatal visit
OCP: oral contraceptive pill
*Each dot represents one study; the superscript numerals are references to those studies.

However, a large case–control study of 613 232 births with
559 cases of antepartum and postpartum VTE (overall
incidence of 1/1000 live births) showed that most previously
identified pregnancy-related risk factors in isolation did not
increase the absolute risk of antepartum VTE above 1%.109
This has recently been supported by a large population-
based cohort study from the UK.4 For example, although
maternal obesity has been identified as a risk factor, the
absolute risk of VTE associated with maternal obesity
alone would not warrant the use of thromboprophylaxis,
even accounting for various definitions of increased BMI
presented in the literature.107,110 Notably, the combination
of antenatal bedrest for ≥ 7 days (defined as > 90% of the
time in bed) and a booking (first antenatal visit) BMI of
≥ 25 kg/m2 increased the risk of antenatal VTE to
approximately 6% in the large case–control study,109 warranting
antepartum thromboprophylaxis with this combination of
clinical factors (see Table 4). While we recognize that strict
bedrest is rarely indicated in hospitalized obstetrical patients
today, the significant increase in risk of VTE incurred when
it is instituted cannot be overemphasized. Hence, antepartum
thromboprophylaxis should be considered in the presence of
multiple clinical or pregnancy-related risk factors when the
overall absolute risk of VTE is estimated to be greater than
1%, especially in patients who are in hospital, where bedrest
is often prescribed.
Due to its lower side-effect profile, LMWH is the
preferred pharmacologic agent over UH for antepartum
thromboprophylaxis. Table 3 presents the doses of

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SOGC CLINICAL PRACTICE GUIDELINE

Table 5. Literature review of incidence of symptomatic VTE antepartum without prophylaxis according to
various clinical or pregnancy-related risk factors
Incidence of symptomatic VTE*
< 0.3% 0.3% to 0.5% > 0.5% to < 1.0%
Maternal pre-pregnancy risk factors
Age > 35 years ••••2,4,108,109
BMI > 30 kg/m2 or weight > 90 kg at first antenatal visit •••••4,106,108–110 •107
Weight > 120 kg at first antenatal visit • 110

Parity ≥ 2 •••• 2,4,106,109

•108
Smoking >10 cigarettes/day or current versus never smoked ••••• 2,4,107–109

Pre-existing diabetes •4
Inflammatory bowel disease •4
Varicose veins • 4

Cancer •4
Risk factors related to present pregnancy
Multiple pregnancy •••2,4,109 •106
ART (singleton) ••3,109 •109
ART (twins) •109
Strict bedrest ≥ 7 days + BMI < 25 kg/m2 at first antenatal visit •186 •109
Preeclampsia/pre-existing hypertension •• 4,109

IUGR •109
Preeclampsia + IUGR •109
Gestational diabetes ••3,109
*Each dot represents one study; the superscript numerals are references to those studies.

the heparins currently available in Canada, as per the
manufacturers’ recommendations. However, some women
may need a dose adjustment because of their weight, and
weight increases as pregnancy progresses.
Women who are known to require antepartum
thromboprophylaxis should start LMWH once the
decision is made and the patient becomes pregnant. For
others, ongoing evaluation of the need for antepartum
thromboprophylaxis should be made throughout pregnancy,
taking into account the patient’s risk factors and preferences
and the side-effects associated with LMWH. Antepartum
thromboprophylaxis should be continued until the onset of
labour, and restarted after delivery (see relevant sections).
Recommendations
29. Individual risk assessment for venous
thromboembolism should be performed
prior to all pregnancies, once pregnancy is
achieved, and repeated throughout pregnancy
as new clinical situations arise. The woman’s
preferences and values should be taken into
account when considering the use of antepartum
thromboprophylaxis. (III-B)
30. Women at increased risk should be advised of
the symptoms and signs of venous
thromboembolism. (III-B)
31. Low molecular weight heparin is the preferred
pharmacologic agent over unfractionated heparin
for antepartum thromboprophylaxis. (III-A) Low
molecular weight heparin doses should be used as
per the manufacturer’s recommendation. (III-C)
32. Routine anti-Xa and platelet level monitoring
are not recommended when a patient is on a
prophylactic dose of thromboprophylaxis. (II-2E)
33. We recommend therapeutic thromboprophylaxis
during pregnancy in the following situations:
a. long-term therapeutic anticoagulation used prior
to pregnancy for a persistent indication; (III-B)
b. personal history of multiple previous venous
thromboembolism. (III-B)
34. We recommend intermediate or therapeutic
thromboprophylaxis during pregnancy in the
following situation:
a. personal history of a previous venous
thromboembolism and a high-risk thrombophilia
(antithrombin deficiency, antiphospholipid

540 l JUNE JOGC JUIN 2014

 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
syndrome) not previously on
anticoagulation. (III-B)
35. We recommend prophylactic dose
thromboprophylaxis during pregnancy in the
following situations (absolute risk > 1%):
a. personal history of a previous unprovoked
venous thromboembolism; (II-2A)
b. personal history of a previous venous
thromboembolism related to oral contraceptives
or pregnancy; (II-2A)
c. personal history of a previous provoked
venous thromboembolism and any low risk
thrombophilia; (I-A)
d. asymptomatic homozygous factor V
Leiden; (II-2A)
e. asymptomatic homozygous prothrombin gene
mutation 20210A; (III-B)
f. asymptomatic combined thrombophilia; (III-B)
g. asymptomatic antithrombin deficiency; (III-B)
h. non-obstetrical surgery during pregnancy, with
the duration of thromboprophylaxis procedure-
and patient-dependent; (III-B)
i. strict antepartum bedrest for ≥ 7 days in a
woman with a body mass index of > 25 kg/m2 at
her first antenatal visit. (II-2B)
36. Antepartum thromboprophylaxis for isolated
pregnancy-related risk factors is not
recommended. (III-E)
37. Antepartum thromboprophylaxis should be
considered in the presence of multiple clinical or
pregnancy-related risk factors where the overall
absolute risk of venous thromboembolism is
estimated to be > 1%, especially in women
admitted to hospital for bedrest. (II-2B)
ASSISTED REPRODUCTIVE TECHNOLOGY
The risk of VTE in women undergoing ART is estimated
to be 0.11% per cycle of in vitro fertilization111; however,
in the presence of severe OHSS it is as high as 0.78%.112
Additionally, up to 70% of VTEs in OHSS involve
the upper extremity, a much higher incidence than
expected.113,114 VTE associated with ART and OHSS may
also present weeks or even months after the resolution of
the OHSS.115 There is currently little to guide clinicians
in the use of thromboprophylaxis in women undergoing
ART. Extrapolating from the observational data from
studies in pregnant women, we believe that in women at
high risk for VTE (those identified in Table 4), instituting
thromboprophylaxis at the start of ovarian stimulation,
and maintaining it for the duration of the ART, would be
sensible. If pregnancy is achieved, thromboprophylaxis
should be continued in the antepartum period.
For women undergoing IVF with no risk factors for
VTE, routine thromboprophylaxis is unnecessary.
However, for women who develop severe OHSS,
thromboprophylaxis should be considered for at least 8 to
12 weeks after resolution of the OHSS. Ongoing need for
thromboprophylaxis would depend on whether pregnancy
is achieved in that cycle and on the presence of other
antepartum risk factors (such as those in Table 5).
Recommendations
38. Routine thromboprophylaxis is not required for all
women undergoing ovulation induction. (III-C)
39. If severe ovarian hyperstimulation syndrome
occurs with assisted reproductive technology
we recommend thromboprophylaxis with low
molecular weight heparin for at least 8 to 12 weeks
after resolution of the syndrome. (III-B)
40. Thromboprophylaxis with low molecular weight
heparin should be considered for any women
at increased risk for venous thromboembolism
undergoing assisted reproductive technology at the
time of ovarian stimulation. (III-B)
41. Women who develop a venous thromboembolism
in association with the use of assisted reproductive
technology but who do not conceive in that cycle
should be treated with therapeutic anticoagulation
for a minimum of 3 months. (II-3A) Those who
conceive in that assisted reproductive technology
cycle should be treated as per recommendations
12 and 13 for acute venous thromboembolism in
pregnancy. (I-A, III-C)
PERIPARTUM ANTICOAGULATION
AND NEURAXIAL ANAESTHESIA
Management Before Delivery and
Neuraxial Anaesthesia
Current consensus guidelines on the use of neuraxial
(epidural, spinal, combined spinal/epidural) analgesia
or anaesthesia in patients on anticoagulants largely refer
to the management of non-obstetric patients.10,116,117
Similar recommendations for obstetric patients are
extrapolated from recommendations for non-obstetric
patients and “weak” evidence (e.g. case reports, case
series, pharmacokinetic studies), and do not take into
account the physiological changes of pregnancy. These
changes generally alter the pharmacokinetics of heparin
(both LMWH and UH) in the third trimester such that a
“prophylactic dose” in the third trimester may be greater
than that used early in pregnancy. The recommendations
in this document are taken mainly from those of the
ASRA.10 It is important to note that guidelines from other
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SOGC CLINICAL PRACTICE GUIDELINE
Table 6. Recommended timing for neuraxial procedures in relation to anticoagulation dosing in
pregnant patients.
Prophylactic dose
Delay between last dose of anticoagulation and neuraxial anesthesia
UH Maximum 10 000 IU/d
No delay unless evidence of abnormal coagulation10
LMWH 10 to 12 hours10
Delay between last dose of anticoagulant and removal of neuraxial catheter
UH 4 hours
LMWH Minimum 10 to 12 hours
Delay between neuraxial anaesthesia and restarting anticoagulant
UH 1 to 8 hours120
LMWH 6 to 8 hours after initiation of neuraxial technique
> 24 hours if bleeding during the neuraxial block
> 4 hours after removal of the neuraxial catheter10,120
societies may differ117 and that the recommendations
regarding timing may not apply to all types of LMWH.
Early consultation with an anaesthesiologist to assess
risks and benefits will inform the patient of her options
for intrapartum anaesthesia. Full informed consent must
be obtained for neuraxial analgesia and the reasons for
deciding whether or not to proceed must be documented.
Whenever possible, women should withhold their
thromboprophylaxis at the onset of labour or after
their dose on the day prior to a planned induction of
labour or Caesarean section. For women on therapeutic
anticoagulation, a planned date and mode of delivery
is recommended to help simplify their peripartum
management.
Switching from thromboprophylactic LMWH to a
prophylactic dose of UH at term (37 weeks) may allow
for more options with respect to labour analgesia, since
neuraxial anaesthesia is contraindicated for at least 10 to
12 hours after LMWH but there is no recommended delay
after a maximum dose of 10 000 units of UH per day.118
Although the ASRA Guidelines suggest no delay following
up to 10 000 units of UH per day, many anaesthesiologists
prefer to wait a minimum of 4 hours. For women on an
intermediate or therapeutic LMWH dose, the risks and
benefits of discontinuing subcutaneous LMWH and
changing to therapeutic subcutaneous or intravenous
UH to allow for neuraxial anaesthesia once the aPTT is
normal could be considered. The switch is not necessarily
advantageous, however, as at these doses coagulation
may be impaired for a duration similar to that with either
heparin. Although not required with women on 10 000
542 l JUNE JOGC JUIN 2014
Therapeutic dose
> 4 hours after stopping IV infusion, when aPTT is
normal.
When aPTT is normal after stopping subcutaneous
UH, may be > 12 hours.
> 24 hours10
When aPTT is normal
Minimum 24 hours
1 to 8 hours120
> 24 hours after initiation of neuraxial technique
> 4 hours after removal of the neuraxial catheter120
units of UH or less, some anaesthesiologists would check
an aPTT prior to neuraxial anaesthesia in all women on
UH.
Recommendations for the interval delay between the
last administered dose of heparin and the insertion or
removal of a neuraxial blockade or catheter are shown in
Table 6. A recent platelet count should be available in the
labour suite or before Caesarean section for women on
anticoagulants. In the exceptional situation of a pregnant
woman who has had a VTE within the past 2 to 4 weeks,
peripartum use of intravenous UH during the latent stage
of labour may be necessary. In these women the risk
of stopping the heparin should be weighed against the
benefit of a neuraxial anaesthesia, based on the anticipated
duration of labour and mode of delivery. In this situation,
neuraxial anaesthesia could be considered 4 hours after
discontinuation of intravenous UH if the platelet count
and aPTT are normal.
Although a spinal hematoma is a rare complication
(estimated incidence is < 1:150 000 with epidural
anaesthesia and < 1:220 000 with spinal anaesthetics in
healthy patients119), it can result in permanent neurological
dysfunction.10,120 If a spinal hematoma is suspected (new
onset or progressive neurological signs, back pain, or
bowel/bladder dysfunction), early confirmation by MRI
should be done and surgical intervention undertaken, if
warranted, to achieve better outcomes.10,121,122 In women
on heparin, the co-existence of any factors that can
increase the risk of spinal hematoma (e.g. NSAIDs, LDA
in combination with heparin, thrombocytopenia, multiple
neuraxial attempts, traumatic tap) should prompt a
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
re-evaluation of the administration of neuraxial anaesthesia,
independent of these guidelines. ASA alone does not
appear to increase the risk of neuraxial hematomas.
However epidural hematomas have been reported in the
non-obstetric literature when patients have received a
combination of heparin and ASA, even with an 81 mg
dose.123 Neuraxial anaesthesia must be avoided in women
who are fully anticoagulated or when there is evidence of
altered coagulation (e.g., petechiae, bruising, altered aPTT
without APLS, disseminated intravascular coagulation in
patients with HELLP syndrome).
Recommendations
42. Women on prophylactic dose, intermediate dose,
or therapeutic anticoagulation should have a
discussion about options for analgesia/anaesthesia
prior to delivery. (III-B)
43. Switching from thromboprophylactic low
molecular weight heparin to a prophylactic dose of
unfractionated heparin at term (37 weeks) may be
considered to allow for more options with respect
to labour analgesia. (III-L)
44. Discontinue prophylactic or intermediate dose low
molecular weight heparin or unfractionated heparin
upon the onset of spontaneous labour or the day
prior to a planned induction of labour or Caesarean
section. (II-3B)
45. A recent platelet count should be available on
admission in labour or before Caesarean delivery
in women who have been, or are, on
anticoagulants. (III-B)
46. For women on low molecular weight heparin,
neuraxial anaesthesia can be administered as a:
a. prophylactic dose: a minimum of 10 to 12 hours
after the last dose; (III-B)
b. therapeutic dose: after 24 hours since the last
dose. (III-B)
47. For women on unfractionated heparin, neuraxial
anaesthesia can be administered as a:
a. prophylactic dose (maximum 10 000 U/day):
after no delay; (III-B)
b. therapeutic intravenous infusion: at least
4 hours after stopping the infusion and when
the activated partial thromboplastin time is
normal; (III-B)
c. therapeutic subcutaneous unfractionated heparin:
when the activated partial thromboplastin time is
normal. This may be 12 hours or longer after the
last injection. (III-B)
48. Neuraxial anaesthesia must be avoided in a woman
who is fully anticoagulated or in whom there is
evidence of altered coagulation. (II-3A)
Postpartum Management of Anticoagulation
After Neuraxial Anaesthesia
After delivery, prophylactic heparin can be initiated or
resumed in women who had neuraxial anesthesia once
hemostasis is confirmed, there are no signs of neurological
complications, and after a minimum of 4 hours following
neuraxial catheter removal (see Table 6 for timing intervals).
For women on intermediate or therapeutic dose LMWH,
the first postpartum dose should be given no sooner than
24 hours postpartum and a minimum of 4 hours following
neuraxial catheter removal. Federal Drug Administration
recommendations for the timing of the first dose of
LMWH following removal of a neuraxial catheter.124
The neuraxial catheter must be removed before the first
LMWH dose.10 For women requiring ongoing therapeutic
heparin our recommendations would be (1) intravenous
UH: restart, without a bolus, at a rate of 18 U/kg/hour
and monitor aPTT every 6 hours, or (2) subcutaneous
LMWH: restart with a low dose (5000 U) at a minimum of
4 hours after removal of the neuraxial catheter and increase
to therapeutic dose LMWH after 24 hours. Assessment of
the risks and benefits of anticoagulation in these patients
should be ongoing within the multidisciplinary team.
Intermittent pneumatic compression devices postpartum
should be considered for these women at higher risk for
venous thrombosis.
Recommendations
49. Removal of a neuraxial catheter left in situ
postpartum should only be done 4, 10 to 12, or
24 hours following the administration of
prophylactic dose unfractionated heparin
(maximum 10 000 U/day), prophylactic low
molecular weight heparin (single daily dose), or
therapeutic dose low molecular weight heparin,
respectively, or in the case of therapeutic
unfractionated heparin, when the activated partial
thromboplastin time is normal. (II-3B)
50. Prophylactic dose low molecular weight heparin
(single daily dose) may be started or restarted 4
hours after neuraxial catheter removal, providing
there is full neurological recovery and no evidence
of active bleeding or coagulopathy. (III-B)
51. Therapeutic low molecular weight heparin may be
started or restarted at least 24 hours after a single
injection neuraxial block and a minimum of 4
hours after neuraxial catheter removal, providing
there is full neurological recovery and no evidence
of active bleeding or coagulopathy. (III-B)
52. Subcutaneous unfractionated heparin may be
started or restarted at least 1 hour after a single
injection neuraxial block, providing there is full
JUNE JOGC JUIN 2014 l 543
SOGC CLINICAL PRACTICE GUIDELINE
Table 7. Literature review of incidence of postpartum thromboprophylaxis recommended for
single risk factors in isolation
Personal history of previous VTE
Single
Asymptomatic thrombophilia
FVL homozygosity
APLS
Risk factors related to present pregnancy
Strict antepartum bedrest ≥ 7 days
Risk factors related to delivery and postpartum period
> 1 L postpartum hemorrhage + postpartum surgery
Peripartum and/or postpartum infection
Incidence of symptomatic VTE postpartum without prophylaxis is > 1%
*Each dot represents one study; the superscript numerals are references to those studies.
neurological recovery and no evidence of active
bleeding or coagulopathy. (III-B)
53. Do not administer antiplatelet agents (acetylsalicylic
acid or non-steroidal anti-inflammatory drugs)
concomitantly with heparin if a neuraxial catheter is
left in situ postpartum. (III-D)
54. Women on therapeutic anticoagulation who
have received neuraxial anesthesia should be
monitored closely for the development of a
spinal hematoma. (III-B)
POSTPARTUM THROMBOPROPHYLAXIS
Postpartum PE is a leading cause of maternal mortality in
Canada, with up to 17 maternal deaths each year.125 The “per
day” risk is 15- to 35-fold greater in the 6 weeks following
delivery than in non-pregnant age-matched control subjects,
with the highest risk being in the first 3 weeks.3,5–7
It is generally agreed that universal postpartum
thromboprophylaxis is neither cost-effective nor
recommended.126,127 In weighing the risks of treatment,
specifically heparin (see Table 2), versus the potential
for a devastating outcome, it seems reasonable again to
use an absolute VTE risk of greater than 1% in
considering postpartum thromboprophylaxis (Table 7).
It is important to carefully evaluate the need for
thromboprophylaxis immediately after every delivery and
re-evaluate it over the puerperium as additional risk factors
present themselves. Women who have been on antepartum
thromboprophylaxis will usually require ongoing
heparin postpartum, but the reasons for continuing
544 l JUNE JOGC JUIN 2014
Incidence of symptomatic VTE*
1% to 5% > 5%
••89,140
••96,181 •183
•140
•109
•109
•109
should be revisited. Ideally, the plan for postpartum
thromboprophylaxis will have been reviewed with these
women prior to delivery. Many women, however, will
require thromboprophylaxis for the first time postpartum.
The risk versus benefits should be continually weighed in
the decision making process.
Observational studies have demonstrated differing
biological and clinical risk factors for antenatal versus
postpartum VTE.3,4,106,129 In the case–control study by
Jacobsen et al.,109 most postpartum risk factors, aside
from strict antepartum bedrest for 7 days or more,
had minimal impact in isolation (Tables 8 and 9). The
strongest associations were seen with combined risks.
Table 8 lists the factors of sufficient risk to warrant
thromboprophylaxis when 2 are present. Table 9 lists
weaker associations, warranting 3 or more to raise the
absolute VTE risk postpartum to > 1%. Operative vaginal
delivery, prolonged labour, extensive perineal trauma, or
prolonged repairs have been flagged as risk factors in
other guidelines.11,13 Evidence to support this is lacking
and there are no RCTs assessing thromboprophylaxis
following vaginal deliveries.
RCTs of heparin after Caesarean section do exist with 236
women randomized over 4 trials.130–133 A Cochrane systematic
review concluded that there was insufficient evidence of
the benefit or harm associated with thromboprophylaxis
after Caesarean section due to the small numbers and
different comparisons.134 Overall the risk associated with any
Caesarean section is modest.4,106,109,129 Hence, we recommend
against thromboprophylaxis following a Caesarean section
in the absence of at least one other risk factor in the case of
an emergency, and at least two other risk factors for elective
Caesarean sections.
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy

Table 8. Literature review of incidence of postpartum thromboprophylaxis recommended for any two
risk factors
Incidence of symptomatic VTE*
< 0.3% 0.3% to 0.5% > 0.5% to > 1.0%
Maternal pre-pregnancy risk factors
BMI > 30 kg/m2 at first antenatal visit •••106,107,109 ••4,140
Smoking > 10 cigarettes/day or current versus •••• 2,4,107,129
•109
never smoked
Maternal cardiac disease •••4,106,140
SLE ••4,140
Sickle cell disease •140
Inflammatory bowel disease • 4

Varicose veins •4
Risk factors related to present pregnancy
Preeclampsia •4 •••2,3,109
Preterm birth • 4
•129
IUGR •109
Gestational diabetes •109
Placenta previa •3
Stillbirth •4
Risk factors related to delivery and postpartum period
Emergency Caesarean section ••3,109
Any Caesarean section ••••4,106,129,140 •2 •170
>1 L postpartum haemorrhage or transfusion postpartum • 4
• 109
•• 129,140

Combined risk factors

Preeclampsia + IUGR • 109
Incidence of symptomatic VTE postpartum without prophylaxis < 1% in isolation.
*Each dot represents one study; the superscript numerals are references to those studies.

Table 9. Literature review of incidence of postpartum thromboprophylaxis recommended for

three or more risk factors
Incidence of symptomatic VTE*
< 0.2% 0.2% to 0.3%
Maternal pre-pregnancy risk factors
Cancer •4
Parity ≥ 2 ••4,109 •2
Age > 35 years •••••2,4,5,106,109
Risk factors related to present pregnancy
ART •109
Multiple pregnancy •••• 2,4,109,140

Placental abruption •3
PROM • 109

Elective Caesarean section •109 •3

Incidence of symptomatic VTE postpartum without prophylaxis < 1% in isolation
*Each dot represents one study; the superscript numerals are references to those studies.

JUNE JOGC JUIN 2014 l 545

SOGC CLINICAL PRACTICE GUIDELINE
As the puerperium is inherently a higher risk period for
VTE than the non-pregnant state, good hydration and
mobilization should be encouraged for every woman
postpartum.
Recommendations
55. Universal postpartum thromboprophylaxis is not
recommended. (III-D)
56. Assess women for increased risk of postpartum
venous thromboembolism based on antepartum,
intrapartum, and postpartum risk factors after
every delivery and repeat as new clinical situations
arise. (II-2B)
57. Low molecular weight heparin is the preferred
pharmacologic agent over unfractionated heparin
for postpartum thromboprophylaxis. (III-A) Low
molecular weight heparin doses should be used as
per the manufacturer’s recommendation. (III-C)
58. Pharmacologic thromboprophylaxis postpartum is
recommended in the following situations:
Any 1 of the following risk factors (each with an
absolute venous thromboembolism risk > 1%):
a. history of any prior venous
thromboembolism; (II-2A)
b. any high-risk thrombophilia: antiphospholipid
syndrome, antithrombin deficiency, homozygous
factor V Leiden or prothrombin gene mutation
20210A, combined thrombophilia; (II-2B)
c. strict bed rest prior to delivery for 7 days or
more; (II-2B)
d. peripartum or postpartum blood loss of > 1 litre
or blood product replacement, and concurrent
postpartum surgery; (II-2B)
e. peripartum/postpartum infection. (II-2B)
59. Postpartum thromboprophylaxis should be
considered in the presence of multiple clinical or
pregnancy-related risk factors when the overall
absolute risk is estimated to be greater than 1%
drawn from the following groups:
a. any 2 of the following risk factors (each with an
absolute risk of venous thromboembolism < 1%
in isolation):
i. body mass index ≥ 30 kg/m2 at first
antepartum visit; (II-2B)
ii. smoking > 10 cigarettes/day
antepartum; (II-2B)
iii. preeclampsia; (II-2B)
iv. intrauterine growth restriction; (II-2B)
v. placenta previa; (II-2B)
vi. emergency Caesarean section; (II-2B)
vii. peripartum or postpartum blood loss of > 1
litre or blood product replacement; (II-2B)
546 l JUNE JOGC JUIN 2014
viii. any low risk thrombophilia: PC or PS
deficiency, heterozygous factor V Leiden, or
prothrombin gene mutation 20210A; (III-B)
ix. maternal cardiac disease, SLE, sickle cell
disease, inflammatory bowel disease,
varicose veins, gestational diabetes; (III-B)
x. preterm delivery; (III-B)
xi. stillbirth. (III-B)
b. any 3 or more of the following risk factors (each
with an absolute risk of venous thromboembolism
< 1% in isolation):
i. age > 35 years; (II-2B)
ii. parity ≥ 2; (II-2B)
iii. any assisted reproductive technology; (II-2B)
iv. multiple pregnancy; (II-2B)
v. placental abruption; (II-2B)
vi. premature rupture of the membranes; (II-2B)
vii. elective Caesarean section; (II-2B)
viii maternal cancer. (III-B)
Mechanical Compression Devices
Mechanical methods of thromboprophylaxis include both
graded compression stockings and intermittent pneumatic
compression devices. Older evidence suggested that
graded compression stockings were beneficial in reducing
post-operative VTE, leading to their widespread use.135
However, their benefit has recently been challenged by
two large trials in stroke patients (N = 5632). Thigh-high
stockings did not reduce symptomatic VTE or proximal
DVT,136 and knee-high stockings increased the risk of
thrombosis.137 In light of this new evidence we do not
advocate the routine use of graded compression stockings
in postpartum women to reduce the risk of VTE.
Intermittent pneumatic compression devices have not
been studied in pregnancy. Following major gynaecologic
surgery associated with a high risk of VTE, they are
effective if left on for 5 days or until hospital discharge,
but not if removed the day after surgery.138 In general
surgery trials, they are associated with fewer major bleeding
episodes than heparin but have a lower VTE risk reduction
rate.9 Most of these RCTs were underpowered to prove
efficacy in preventing PE or mortality postoperatively.139
When pharmacologic treatment is not possible, such as
with active bleeding, thrombocytopenia, known heparin
allergy or HIT, intermittent pneumatic compression
devices are a good alternative. In women at very high risk
for VTE postpartum (> 10%), combined mechanical and
pharmacologic thromboprophylaxis is recommended.
Recommendation
60. Intermittent or sequential pneumatic compression
devices are alternatives in women when heparin
 Venous Thromboembolism and Antithrombotic Therapy in Pregnancy
is contraindicated postpartum. When the risk of
postpartum venous thromboembolism is high they
may be used in combination with low molecular
weight heparin or unfractionated heparin. (III-B)
Postpartum Thromboprophylaxis:
Duration of Anticoagulation
Up to 60% of postpartum PE occurs in the 4 to 6 weeks
after delivery.3,5,7 The duration of thromboprophylaxis
varies with the underlying risk factors. Women with prior
VTE have the highest risk and require a minimum of 6
weeks.89,140 Women with persistent risks that will be present
throughout the puerperium (e.g. high risk thrombophilia
or prolonged immobility), should also have extended
thromboprophylaxis for a full 6 weeks.
There is no evidence to guide the duration of treatment in
women having only transient antepartum or intrapartum
risks. Given the logistics involved in discharging women on
heparin injections, individual institutions and practitioners
may vary with respect to the duration of postpartum
thromboprophylaxis they choose in these cases. Other
guidelines recommend both options: until discharge from
hospital fully mobile as a minimum54,118 or up to 1 to 2
weeks postpartum.11,15
Recommendation
61. Women with ongoing and persistent risk factors
should receive postpartum thromboprophylaxis for
a minimum of 6 weeks postpartum. (II-3B)
62. Women with transient antepartum or intrapartum
risk factors should receive postpartum
thromboprophylaxis until discharged from hospital
or up to 2 weeks postpartum. (III-C)
THROMBOPROPHYLAXIS TO PREVENT
ADVERSE PREGNANCY OUTCOMES
Adverse Pregnancy Conditions: Screening
In the 1990s reports of an increase in placenta-mediated
pregnancy complications (e.g. recurrent miscarriage,
late fetal loss, preeclampsia, placental abruption,
and intrauterine growth restriction) in women with
thrombophilia appeared in the literature.141–144 Whereas
these early studies suggested a weak association between
inherited thrombophilia and placenta-mediated pregnancy
complications, subsequent prospective cohort studies
suggested no association between most thrombophilia and
preeclampsia or SGA infants.127,145–149 Women with APLS
do have an increased risk of recurrent and late pregnancy
loss.127,150 However, there is only a weak association
between these complications and FVL and no association
with PGM.149 Hence, universal thrombophilia screening
in women experiencing adverse pregnancy outcomes is
not indicated.148 What remains unknown is whether more
severe placenta-mediated pregnancy complications (e.g.
severe or early-onset preeclampsia, SGA < 3rd percentile,
major abruption) are more strongly associated with specific
thrombophilia and potentially improved with antenatal
thromboprophylaxis.
Recommendations
63. Universal screening for thrombophilias in women
experiencing adverse pregnancy outcomes (severe
preeclampsia, intrauterine growth restriction,
stillbirth) is not indicated. (II-2D)
64. Women with recurrent miscarriage or late
pregnancy loss should be screened for
antiphospholipid syndrome. (I-B)
LMWH to Prevent Recurrent
Adverse Pregnancy Conditions
The benefit of heparin plus LDA in women with APLS
and recurrent miscarriage or late fetal loss (variably
defined in the different studies) is controversial.151–154 A
meta-analysis looking at 5 trials (N = 334) showed that
LMWH plus LDA significantly increased the live birth rate
(74.3%) compared to LDA alone (55.8%) with a number
needed to treat of 5.6, but with significant heterogeneity.155
This evidence modestly supports screening women with
recurrent miscarriage or late pregnancy loss for APLS and
using LMWH alone or with LDA to prevent recurrent
miscarriage when APLS is confirmed.
Recent RCTs, however, showed no benefit of LMWH
alone or LMWH plus LDA versus no treatment or
LDA alone to prevent recurrent miscarriage in women
without APLS.156–161 Although there were no significant
complications related to LMWH use in these trials, there
were reports of injection site bruising and skin reactions
highlighting the fact that heparin is not a benign treatment
and should not be prescribed in the absence of evidence
to support its use.
Given that placental thrombosis is a part of the common
pathophysiology of placenta-mediated pregnancy
complications, it is plausible that LDA alone, heparin
alone, or the combination of LDA plus LMWH might
prevent recurrence of adverse pregnancy outcomes in
subsequent pregnancies for women with and without
thrombophilia.162–168 A review of 6 trials (N = 848 women)
showed that LMWH, compared to no treatment, reduced
the risk of early-onset preeclampsia (RR 0.16, 95% CI
0.07 to 0.36), birth before 37 weeks (RR 0.77, 95% CI
0.62 to 0.96), and SGA infants (RR 0.42, 95% CI 0.29 to
0.59) without any significant effect on perinatal mortality.
JUNE JOGC JUIN 2014 l 547
SOGC CLINICAL PRACTICE GUIDELINE
There was an overall reduction in a composite outcome of
complications (preeclampsia, abruption, SGA infants, or
fetal loss after 12 weeks) from 42.9% to 18.7% (RR 0.52,
95% CI 0.32 to 0.86).169 A 2013 Cochrane review of 9
trials (N = 979) concluded that prophylactic dose heparin
(UH or LMWH), compared to no treatment, decreased
perinatal mortality (RR 0.40, 95% CI 0.20 to 0.78), preterm
delivery < 34 weeks (RR 0.46, 95% CI 0.29 to 0.73) and
SGA infants (RR 0.41, 95% CI 0.27-0.61) in women at
high risk.170 Although this data appears promising, given
that LMWH is not risk free, it should not be used routinely
to reduce the risk of recurrence of all placenta-mediated
complications in women, with or without thrombophilia,
pending the publication of larger trials or individual
patient data meta-analysis. APLS has been considered the
exception in many centers, extrapolating from experience
with recurrent miscarriage. However, despite the common
usage of LMWH and LDA to prevent other adverse
pregnancy outcomes in women with APLS, there are no
published trials that support this practice.
Recommendations
65. Low-dose acetylsalicylic acid or low-dose
acetylsalicylic acid plus low molecular weight
heparin is recommended in pregnancy in women
with confirmed antiphospholipid syndrome. (I-C)
66. Low-dose acetylsalicylic acid plus low molecular
weight heparin is not recommended for women with
a history of recurrent miscarriage in the absence of
confirmed antiphospholipid syndrome. (I-E)
67. Low molecular weight heparin should not be
used routinely to reduce the risk of recurrent
placenta-mediated complications in women with or
without thrombophilia (excluding antiphospholipid
syndrome). (I-C)
FUTURE DIRECTIONS
As we now better understand the appropriate diagnosis of
DVT in pregnant women, studies elucidating diagnostic
strategies for PE during pregnancy which minimize both
fetal and maternal radiation exposure are still required.
Even as LMWH replaces UH as the anticoagulant of
choice in pregnancy, questions surrounding appropriate
dosing regimens or the need for monitoring anti-Xa
activity still remain.
As we unequivocally accept that VTE prevention is an
important strategy to reduce maternal morbidity and
mortality, we also recognize that thromboprophylaxis is
not without maternal side-effects or costs. In determining
the factors associated with an increased risk of VTE, in
548 l JUNE JOGC JUIN 2014
isolation or in combination, which supersede the risk of
thromboprophylaxis, we extrapolated data mostly from
retrospective studies. Data from further large prospective
registries could yield more information on the absolute
risks associated with various biologic and clinical
factors, or combination of factors, which would warrant
thromboprophylaxis.
We anticipate data from further prospective studies will
become available which will shed light on the effectiveness
of LMWH, plus or minus LDA, in preventing recurrent
adverse pregnancy outcomes in women with or without
inherited thrombophilia.
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180. Hiltunen L, Rautanen A, Rasi V, Kaaja R, Kere J, Krusius T, et al. An
unfavorable combination of Factor V Leiden with age, weight, and blood
group causes high risk of pregnancy-associated venous thrombosis:
a population-based nested case-control study. Thromb Res
2007;119:423–32.
181. Procare G. Risk of venous thromboembolism during pregnancy in
homozygous carriers of the Factor V Leiden mutation: are there any
predictive factors? J Thromb Haemost 2004;2:359–60.
182. Martinelli I, Legnani C, Bucciarelli P, Grandone E, De Stefano V, Mannucci
PM. Risk of pregnancy-related venous thrombosis in carriers of severe
inherited thrombophilia. Thromb Haemost 2001;86:800–3.
183. Conard J, Horellou MH, Van Dreden P, Lecompte T, Samama M.
Thrombosis and pregnancy in congenital deficiencies in AT III, protein C
or protein S: study of 78 women. Thromb Haemost 1990;63:319–20.
184. Tormene D, De Stefano V, Grandone E, Za T, Perlati M, Rossi M, et al.
The G20210A prothrombin variant and the risk of venous
thromboembolism or fetal loss in pregnant women: a family study.
J Thromb Haemost 2007;5:2193–6.
185. Friederich PW, Sanson BJ, Simioni P, Zanadari S, Huisman MV, Kindt I,
et al. Frequency of pregnancy-related venous thromboembolism in
anticoagulant factor-deficient women: implications for prophylaxis.
Ann Intern Med 1996;125:955–60.
186. Carr MH, Towers CV, Eastenson AR, Pircon RA, Iriye BK, Adashek JA.
Prolonged bedrest during pregnancy: does the risk of deep vein thrombosis
warrant the use of routine heparin prophylaxis? J Matern Fetal Med
1997;6:264–7.
187. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
JUNE JOGC JUIN 2014 l 553
 SOGC CLINICAL PRACTICE GUIDELINE

No. 288, March 2013

Cancer Chemotherapy and Pregnancy

assessment and health technology assessment-related agencies,
This clinical practice guideline has been prepared by the clinical practice guideline collections, clinical trial registries, and
Chemotherapy During Pregnancy Working Group and from national and international medical specialty societies.
approved by the Executive and Council of the Society of
Values: The quality of evidence is rated using the criteria described in
Obstetricians and Gynaecologists of Canada.
the Report of the Canadian Task Force on Preventive Health Care
PRINCIPAL AUTHORS (Table 1).
Gideon Koren, MD, Toronto ON Benefits, harms, and costs: This guideline highlights the need to
prevent pregnancy in women who are being treated for cancer and
Nathalie Carey, BSc, Toronto ON
informs health care professionals treating pregnant women with
Robert Gagnon, MD, Montreal QC chemotherapy of the potential risks of the therapy or ameliorated
Cynthia Maxwell, MD, Toronto ON treatment protocols.

Irena Nulman, MD, Toronto ON

Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all authors.
Abstract
Objective: To promote careful education, administration, monitoring
and restricted distribution when prescribing and dispensing
chemotherapeutic and potentially teratogenic medications, as
well as to develop clinical recommendations for the use of cancer
chemotherapy in pregnant women and women of child-bearing
age.
Outcomes: To ensure that women of child-bearing age receiving
chemotherapy can be appropriately counselled on the risks of
becoming pregnant during treatment, and to provide guidance
for health care practitioners treating pregnant women with
antineoplastic agents.
Evidence: Published literature was retrieved through searches of
PubMed or Medline, CINAHL, and The Cochrane Library in 2011,
using appropriate controlled vocabulary (e.g., antineoplastic
agents, neoplasms, pregnancy) and key words (e.g., cancer,
neoplasms, pregnancy, chemotherapy, antineoplastic agents).
Results were restricted to systematic reviews, randomized control
trials/controlled clinical trials, and observational studies. Studies
were restricted to those with available English abstracts or text.
Searches were updated on a regular basis and incorporated in
the guideline to October 2011. Grey (unpublished) literature was
identified through searching the websites of health technology
J Obstet Gynaecol Can 2013;35(3):263–278
SUMMARY STATEMENTS AND RECOMMENDATIONS
Summary Statements
1. As women are postponing child-bearing, more of them are
experiencing cancer in pregnancy. (II-2)
2. Chemotherapeutic agents used to combat cancer cross the
placenta and may adversely affect embryogenesis by affecting cell
division. (II-1)
3. Exposure to such agents after the first trimester of pregnancy
has not been associated with increased risk of malformations but
is associated with increased risk of stillbirth, intrauterine growth
restriction, and fetal toxicities. (II-2)
Recommendations
1. The health care provider should examine the patient’s risk
of pregnancy and desire to prevent pregnancy during
chemotherapy. (I-A)
2. Decisions about the best course of management in pregnancy,
including timing of delivery, should balance maternal and fetal
risks. Most authorities concur that maternal health and well-being
must prevail. (I-A)
3. Women diagnosed with cancer in pregnancy should be
optimally managed by a multidisciplinary team that includes
oncologists and/or hematologists (depending on the malignancy),
perinatologists, family physicians, psychologists, social workers,
and spiritual advisors, if sought by the family. (I-A)

Key Words: Pregnancy prevention, cancer, neoplasms,

pregnancy, chemotherapy, antineoplastic agents

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

MARCH JOGC MARS 2013 l 263

SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.88
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.88
INTRODUCTION
I n Canada, over 9% of the 1.2 million cancers diagnosed
annually in adults are diagnosed in those aged 20 to
44 years, and almost two thirds of these diagnoses are in
women. This is likely because of the tendency for sex-
specific cancers, such as breast and cervical cancer, to
occur at younger ages than other cancers. Demonstrably,
breast and cervical cancers are the 2 most common cancers
to occur in young women, with rates of 34% and 10%,
respectively. Thyroid cancer is the third most common at
around 9%.1 A diagnosis of cancer during this stage of life
may postpone or complicate child-bearing.
Almost all chemotherapeutic agents are teratogenic in
animals. For some drugs only experimental data exist.
Women diagnosed with cancer during their child-
bearing years should therefore be made aware of the
risks associated with the use of cancer chemotherapy in
pregnancy. Information must be provided by the woman’s
health care providers, including the obstetrician, who can
ABBREVIATIONS
ABD doxorubicin, bleomycin, dacarbazine
ABVD doxorubicin, bleomycin, vinblastine, dacarbazine
AVD doxorubicin, vinblastine, dacarbazine
CNS central nervous system
FAC 5-fluorouracil, doxorubicin, cyclophosphamide
IUGR intrauterine growth restriction
MOPP mechlorethamine, vincristine, procarbazine, prednisone
264 l MARCH JOGC MARS 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
engage in an active discussion, answer questions, and
provide any additional clarification required.
Research conducted by Santucci et al.2 suggested that
women want their health care providers to initiate discus­
sions regarding the potential teratogenic/reproductive risks
of exposure to medications. The following are important
principles of effective teratogenic counselling:
1. Timely provision of information
2. Provision of data on all potential effects on a fetus
3. Provision of clear information
4. Repetition of important information
5. Avoidance of assumptions about women’s pregnancy
intentions
6. Explanation of why health care providers are asking
about sexual activity and pregnancy intentions
7. Discussion of consequences for reproductive health.2
These discussions are best conducted by multidisciplinary
teams that include the woman’s family physician, hematologist
and/or oncologist, and obstetrician-gynaecologist.
Providing women with detailed and updated information
about pregnancy-related risks before they begin
chemotherapy is necessary to reduce the risk of fetal
exposure. Since nearly one half of pregnancies are
unplanned, the use of effective methods of contraception
during chemotherapy should be discussed. To date, no
cases of fetal exposure to lenalidomide have been reported,
highlighting the effectiveness of the RevAid program,3 and
supporting the use of such methods.

The occurrence of cancer in pregnancy is a rare and
challenging event, complicating up to 0.02% to 0.1% of
pregnancies annually.4,5 Because of the rise in delayed child-
bearing, the rates of cancer in pregnancy are expected to
rise with the increased incidence of several age-dependent
malignancies.5 The cancers most commonly diagnosed
during pregnancy are breast cancer, cervical cancer,
thyroid cancer, Hodgkin’s lymphoma, and non-Hodgkin’s
lymphoma.4
Although surgery is generally considered safe during
pregnancy, there is little information regarding the safety of
cytotoxic agents, which are often required in the optimal
management of cancer.4,6 Anticancer drugs aim, through
different mechanisms, to arrest cell division and cell growth.
By doing so, they pose direct risk to the developing embryo
during the first trimester of pregnancy. Knowledge of
pregnancy outcomes following cancer treatment has been
limited by the low prevalence of cancer during pregnancy, high
rates of pregnancy terminations in women with cancer, and
the decision not to treat during critical fetal periods. The scarce
evidence regarding the fetal safety of maternal chemotherapy
during pregnancy is limited to small retrospective studies and
case reports that are often underpowered, making their results
difficult to interpret and generalize. Additionally, because
cytotoxic agents are usually administered in multiple-drug
regimens, it is difficult to estimate the potential teratogenic
effects of each individual drug.7 In contrast to this paucity of
information, there is a plethora of animal studies showing high
rates of teratogenicity for most cancer chemotherapeutics.
The main problem in interpreting these experimental data is
the substantially higher dose per kg (or m2) used in the animal
experiments, and inability to extrapolate these data to human
experience.
Several issues highlight the problems of drug therapy
facing pregnant women. An estimated 50% of pregnancies
are unplanned, so many women are exposed to teratogens
before they realize they are pregnant.8 Also, women may
decline treatment, even for life-threatening conditions, for
fear of being exposed to medication that could harm their
fetus.9
Following a diagnosis of cancer in pregnancy, the pregnant
woman, her family, and her medical team are required to
make complex treatment decisions, often in the absence
of definitive evidence. Without standardized guidelines
concerning chemotherapy in pregnant women, a woman
may compromise her health or the health of the developing
fetus.
PREGNANCY PREVENTION
The detrimental impact of thalidomide worldwide in the
late 1950s and early 1960s1 provides clear evidence of the
need for careful education, administration, monitoring
and restricted distribution in prescribing and dispensing
Cancer Chemotherapy and Pregnancy
chemotherapeutic and potentially teratogenic medications.
The devastating effects of fetal exposure to teratogenic
drugs are not limited to thalidomide: diethylstilbestrol was
withdrawn from the Canadian market, and isotretinoin
capsules are available only through a company-sponsored
pregnancy prevention program.2,4,5,10
Beyond awareness and education, the health care
professional and the patient must examine the patient’s
risk of pregnancy, including fertility and/or menopausal
status (with consideration of previous chemotherapy and
age), frequency or potential of sexual activity with a male
partner, and desire to prevent pregnancy.
After completing a pregnancy risk assessment, the patient
and health care provider must fully discuss methods of
contraception, giving careful consideration to the efficacy and
availability of contraceptive options, the patient’s previous
choices and her motivation to adhere to a contraceptive
regimen, the rate of adherence, ease of use, cost, side-
effect profile (considering disease state and chemotherapy
regimen), and access to emergency contraception.
While a contraceptive plan may be in place, health care
providers should check frequently with the patient
to assess adherence and satisfaction with the chosen
methods. Additional considerations may be necessary
for higher risk populations, including teenage patients.
This additional support and optimal prevention of fetal
exposure to teratogens for all women of child-bearing age
can be achieved with the implementation of an effective
controlled distribution program such as RevAid.3
DEFINING TERATOLOGY
Physiological Background
Teratogenesis is defined as the structural or functional
dysgenesis of fetal organs.11 Broadly, exposures that
irreversibly affect the normal growth, structure, or
function of a developing embryo or fetus are defined as
teratogenic.12 Known teratogens include environmental
factors such as radiation, certain viruses such as rubella,
chemicals such as alcohol, and therapeutic drugs such as
thalidomide and isotretinoin.9 Teratogenic effects vary
widely in severity and range, and include death (miscarriage
or stillbirth), malformations, impaired organ functioning,
impaired fertility, and mutagenicity.8
Congenital malformations, defined as defects in organ
structure or function, occur in 1% to 3% of the general
population.9 Of the major defects, about 25% are of
genetic origin and 65% are of unknown etiology.9 Only
2% to 3% of malformations are believed to be associated
with drug treatment.8
The teratogenic potential of any drug depends on a variety
of factors that include the extent of its placental transfer,
MARCH JOGC MARS 2013 l 265
SOGC CLINICAL PRACTICE GUIDELINE
the dose administered, the duration of exposure, the
genetic variability in drug metabolism of the mother and
the fetus, and the timing of exposure.
Teratogens must reach the fetus in sufficient amounts
and during critical time windows to cause adverse fetal
effects.8,9 Most drugs reach the fetus through the maternal
bloodstream, and several factors can affect the fetus’s
exposure to the drug Most molecules with molecular
weights smaller than 500 Da easily diffuse across the
placenta, whereas large molecules with molecular weights
greater than 1000 Da do not easily cross the placental
barrier.8,9 Additionally, factors such as lipid solubility,
polarity, maternal and fetal pH, protein binding, and
maternal drug metabolism profile can affect the amount
of drug reaching the developing fetus.8,9
The timing of the exposure is critical, as the effect produced
by a teratogen depends on the developmental stage.8,9
The all-or-none period
The all-or-none period includes the time from conception
until somite formation (on average 8 to 14 days from
conception). Insult during this phase typically results in
fetal death and miscarriage, or intact survival. Teratogen
exposure at this stage may interrupt processes that
facilitate implantation, leading to miscarriages. However,
if implantation is successful despite teratogen exposure,
the fetus is expected to develop normally. This is due to the
presence of totipotent cells found in the undifferentiated
embryo at this time; these cells enable repair and recovery
of damaged tissue. In general, exposure during this period
does not cause congenital malformations unless the insult
persists beyond this stage.9
Organogenesis
The most sensitive period of drug exposure is during
organogenesis, which occurs roughly 2 to 8 weeks post-
conception during the embryonic period.9 Especially during
gastrulation, which occurs 3 to 5 weeks post-conception,
tissues are differentiating rapidly, and damage becomes
vast and irreparable. Additionally, each organ system has a
period of maximum vulnerability. For example, the neural
tube, heart, and limbs are affected earlier than the palate
and ears. Following organogenesis, the genitals, eyes, CNS,
and hematopoietic system continue to be sensitive to
teratogenic insult.8,9
The fetal phase
The fetal phase, from the end of the embryonic stage to
term, is characterized by growth and functional maturation
of formed organs and systems. Exposures during this
later stage of pregnancy can result in IUGR and low birth
weight, and may affect the size or function of several
organs.8,9
266 l MARCH JOGC MARS 2013
In summary, the teratogenic potential of a drug is dynamic,
affected by the timing, the dose, and the molecular
properties of the teratogens, and by cumulative exposure.
HISTORICAL PERSPECTIVE
The consequences of thalidomide use in the late 1950s
and early 1960s dramatically changed the public perception
regarding fetal exposures during pregnancy, leading to
fear and resistance against pharmacotherapy, as well as to
extensive research in the field. Before this, it was generally
believed that the placenta served as a barrier to prevent
adverse effects of drugs from reaching the fetus.8
Thalidomide, although originally marketed as a safe and
effective sedative and anti-emetic for the management of
nausea and vomiting in pregnancy, was found to cause
malformations at a frequency of 15% to 100%, particularly
when taken between 27 and 50 days post-conception.13,14
Although the rates of malformation for thalidomide were
high and followed a characteristic pattern (phocomelia and
CNS dysmorphology), its teratogenicity was not suspected
for several years. In Canada, 115 children were born with
malformations after exposure to the drug.15 As a result,
thalidomide was withdrawn from Canadian markets on
March 2, 1962, although some pharmacies continued to
have the drug available as late as May 1962.13,14
AVOIDING TERATOLOGICAL RISKS
Although the teratological risks of thalidomide are clear,
this drug and lenalidomide are currently indicated in
treating multiple myeloma. Their effectiveness in treating
this disorder suggests there is a need for them. However,
their high risk for teratogenicity, combined with the high
occurrence of unplanned pregnancies, demands safety
measures in their distribution to ensure they are not used
during pregnancy.
These requirements led to the establishment of the
RevAid program,3 which carefully and effectively controls
the distribution of thalidomide and lenalidomide. Only
prescribers registered with the RevAid program are able
to prescribe lenalidomide and thalidomide to patients.
Physicians registered with RevAid are informed of the
risks of these medications, and especially the risks they
pose during pregnancy. In registering, the physicians must
comply with the requirements of the program, which
include an obligation to inform patients considering
treatment with these drugs of all the risks and benefits of
the drugs and requirements of the RevAid program. All
patients and physicians are required to complete a RevAid
Patient-Physician agreement form. In addition, only
RevAid certified pharmacists may dispense thalidomide or
lenalidomide. These specially trained pharmacists must also
agree to comply with the requirements of the program.

The conditions that must be met for access to thalidomide
or lenalidomide are the most stringent for women of child-
bearing age. Women must be warned of the potential for
birth defects and that, because of the risk to others, they
must never share their medication or give blood up to
4 weeks after ceasing to take the medication. To ensure
prevention of pregnancy, the RevAid program requires
that women use 2 methods of contraception in parallel,
starting 4 weeks before they begin taking the medication
and continuing until 4 weeks after cessation of therapy.
In addition, they must consent to regular pregnancy
tests before and during treatment. Two pregnancy tests
are given before the first prescriptions; a pregnancy test
is done weekly during the first 4 weeks of therapy; and,
with regular therapy, pregnancy tests are performed every
4 weeks with both regular or no periods, and every 2 weeks
if periods are irregular.
The RevAid program represents a safe, controlled way to
provide these useful drugs to people who are not at risk of
suffering their negative effects. As many chemotherapeutic
agents are potentially teratogenic, and as women of
childbearing age often require prompt pharmacological
intervention, guidelines like those of the RevAid program
are necessary to prevent pregnancy during chemotherapy
treatment.
In Canada, a program similar to RevAid outlines the use
of isotretinoin.10 Women are informed of fetal risks, are
prescribed 2 contraceptive methods in parallel, and sign
a document attesting to compliance. However, unlike the
RevAid program, it does not require registration and has
no mandatory follow-up. The lack of these measures has
resulted in unplanned pregnancies and fetal exposures to
this teratogen, highlighting the importance of thorough
guidelines outlining the distribution of all teratogenic
substances in women of child-bearing age.
Currently, no guidelines exist for the use of chemotherapy
in non-pregnant women of child-bearing age. The
development of a program similar to RevAid to monitor
the distribution of chemotherapeutic agents and follow-up
on all women enrolled in the program are needed to ensure
pregnancy prevention during chemotherapy treatment.
Additional guidelines are necessary to address the use of
chemotherapy when it is indicated during pregnancy. The
importance of these guidelines is 2-fold. First, they would
give health care providers a conclusive resource on which
to base their treatment plans. Second, they would help to
dispel common misconceptions patients have about the
use of chemotherapy during pregnancy; this will encourage
pregnant women to pursue care that ensures the best long-
term outcome for themselves and their infants.
Cancer Chemotherapy and Pregnancy
CANCER AND PREGNANCY
The diagnosis of cancer during pregnancy poses difficult
dilemmas for the pregnant patient, her family, and the
medical team. Cancer in pregnancy is rare, complicating up
to 0.02% to 0.1% of pregnancies annually.4,5,16
The cancers most commonly diagnosed in pregnancy are
breast cancer, cervical cancer, thyroid cancer, Hodgkin’s
lymphoma, and non-Hodgkin’s lymphoma. See Table 2 for
details on particular cancers during pregnancy.
ANTINEOPLASTIC AGENTS AND PREGNANCY
The main challenge in managing cancer during pregnancy
is treating the patient with the optimal anti-cancer regimen
without harming the developing fetus. Critically, for the
best chance at survival for the mother, chemotherapy
cannot always be postponed until the end of the
pregnancy, and no current regimen has been confirmed
(by studies with sufficient statistical power) safe for use
during gestation.
Because of their relatively low molecular weight, most
cytotoxic agents cross the placenta and reach the fetus.17,18
The pharmacology of various anti-cancer drugs may be
altered by the normal physiological changes that occur
during pregnancy, such as increased plasma volume,
enhanced renal and hepatic elimination, and decreased
albumin concentration. Dosing similar to that of non-
pregnant women of the same weight may lead to under-
treatment of pregnant women with cancer.18 However, it is
still not clear whether pregnant women should be treated
with different doses of chemotherapy, and no studies
have addressed the effectiveness of treatment regimens in
pregnancy.
Chemotherapy during the first trimester may increase
the risk of spontaneous abortions, fetal death, and
major congenital malformations. The teratogenic effects
depend on the dosage, time of administration, and
cumulative exposure to the chemotherapeutic agent. Fetal
malformations reflect the gestational age at exposure, and
the most vulnerable period is during weeks 2 to 8, when
organogenesis occurs. The eyes, ears, teeth-palate, genitalia,
hematopoietic system, and CNS remain vulnerable to
chemotherapy beyond organogenesis.17
Almost all chemotherapeutic agents are teratogenic in
animals. For many chemotherapeutic agents, the risk of
teratogenesis in humans is unknown. However, the risk of
teratogenesis in humans following cancer treatment appears
to be lower than is commonly estimated from animal data
because of the proportionately larger doses used in animals
First trimester exposure to chemotherapy has been estimated
to have a 10% to 20% risk for major malformations. It
has been suggested that this risk may decline to about 6%
MARCH JOGC MARS 2013 l 267
 Table 2. Cancers during pregnancy
Frequency in
Cancer pregnancy Diagnosis Staging Pathology Prognosis
Bone Unknown •  Pain •  MRI — •  Limited data suggest that
malignancies •  Joint dysfunction •  Ultrasound pregnancy does not exacerbate
•  Pathological fractures •  Biopsy tumour growth or affect the
patient outcome.
Breast 0.01% to 0.3% •  Often delayed in pregnancy, •  Clinical examination •  Invasive ductal carcinoma •  No differences found in survival
9 to 15 months •  Biopsy (75% to 90%) between pregnant and non-
•  Ultrasound •  Ultrasound or MRI •  Inflammatory breast cancer pregnant women with breast

268 l MARCH JOGC MARS 2013

•  Excisional biopsy •  Stage II/III (65% to 90%) (1.5% to 4%) cancer of same nodal status.
(palpable mass) •  However, pregnant women
•  Incisional mass (large mass) have 2.5-fold higher risk for
SOGC CLINICAL PRACTICE GUIDELINE

metastases because of delays in

diagnosis.
Cervical 0.0015% to 0.012% •  Papanicolaou smear •  Clinical examination •  Squamous carcinoma (> 80%) •  Higher proportion of early stage
•  Abnormal cytology •  Biopsy or cone histology •  Adenocarcinoma tumours likely due to increased
•  Colposcopy •  Ultrasound and MRI •  Neuroendocrine screening performed routine
•  Stage I (79%) antenatal care.
•  Stage II/III (21%) •  No differences in survival of
matched pregnant and non-
pregnant women.
Hepatocellular Unknown •  Right upper quadrant pain or •  Liver sonography — •  Small number of published
carcinoma distention and weight loss. •  MRI cases precludes any firm
•  Fine liver aspiration conclusions.

Hodgkin’s 0.016% to 0.1% •  Painless lymph node •  Physical exam •  Nodular sclerosis most common. •  Survival rates found to be similar
Lymphoma enlargement •  Blood tests •  Histological subtypes are the to that of non-pregnant control
•  Lymph node biopsy •  Bone marrow biopsy same as in non-pregnant women matched for age, stage and
•  Abdominal ultrasonography < 40 years. treatment protocol.
or chest X-ray with abdominal
shielding
•  MRI
Intracranial Unknown •  Headache •  MRI — •  Very limited data suggest that
tumours •  Nausea and vomiting pregnancy does not exacerbate
•  Nonspecific symptoms to focal tumour growth or affect the
neurologic deficits such as outcome of the patients.
hemiparesis and visual field
defects.
•  Pregnancy can exacerbate
neurology with the patient
presenting with impending or
actual cerebral herniation.
•  Common symptoms of
intracranial pressure can
potentially be confused with
routine pregnancy-related
conditions.
continued
 Table 2. Continued
Frequency in
Cancer pregnancy Diagnosis
Leukemia 0.001% •  Blood work
•  Bone marrow biopsy
Lung Unknown •  Symptoms such as blood-
streaked sputum, persistent
cough or change in cough
pattern, wheezing, decreased
appetite with poor weight gain,
along with other loco-regional
symptoms are commonly seen.
•  Delays in diagnosis may
occur because of low index of
suspicion, tendency to attribute
symptoms such as fatigue and
dyspnea on the pregnant state
and the reluctance to order chest
radiography during pregnancy.
Malignant 0.014% to 0.28% •  Changes to the shape or
melanoma colour of existing moles or
any pigmented lesion, or the
appearance of a new lump
anywhere on the skin.
Non-Hodgkin’s 0.016% •  Painless lymph node
Lymphoma enlargement
•  Lymph node biopsy
MARCH JOGC MARS 2013 l 269
Staging
•  Ultrasounds
•  MRI
•  Anteroposterior and lateral chest
radiographs.
•  Ultrasound
•  MRI
•  Sputum cytology
•  Fine needle aspiration biopsy
•  Bronchoscopy with biopsy
•  Bronchoalveolar lavage
•  Assessment of tumour site.
•  Ultrasound
•  Fine needle aspiration biopsy.
•  Lymphatic mapping with blue
dye or radio-labelled tracer
injected at tumour site plus
sentinel lymph node biopsy.
•  MRI
•  Physical exam
•  Blood tests
•  Bone marrow biopsy
•  Abdominal ultrasonography
or chest X-ray with abdominal
shielding
•  MRI
Pathology
•  Acute myeloid leukemia
•  Acute lymphoblastic leukemia
•  Chronic myeloid leukemia
•  Chronic lymphocytic leukemia
•  Non-small cell lung cancers, in
order of most to least frequent:
adenocarcinoma, squamous cell,
large cell, and bronchoalveolar.
•  Small cell lung cancer.
•  Superficial spreading
melanomas most common
(41%).
•  Degrees of severity from
indolent to very aggressive.
•  Histological subtypes in
pregnancy appear to be
aggressive with diffuse large
B-cell or peripheral T-cell
lymphomas being the most
common.
Prognosis
•  Spontaneous abortion,
prematurity, IUGR, and death
have been associated with
maternal leukemia.
•  Survival rates found to be similar
to that of non-pregnant control
matched for age, stage and
treatment protocol.
•  No evidence that pregnancy
alters the prognosis of lung
cancer.
•  Maternal outcome for both small
cell and non-small cell lung
cancer has been poor and is a
reflection of the advanced stage
at diagnosis.
•  Malignant melanoma is the
most frequent cancer that
metastasizes to the placenta
or fetus, accounting for 31% of
reported cases.
•  When matched for age,
anatomic site and stage, most
studies have not demonstrated
a difference in survival between
pregnant and non-pregnant
women.
•  Survival rates found to be similar
to that of non-pregnant control
matched for age, stage and
treatment protocol.
•  There may be a trend toward
lower birth weight infants born to
mothers who had non-Hodgkin’s
lymphoma in pregnancy.
continued
Cancer Chemotherapy and Pregnancy
SOGC CLINICAL PRACTICE GUIDELINE

when folate antagonists (which are considered the most

•  Survival rates found to be similar

•  Survival rates found to be similar

teratogenic anti-cancer drugs) are excluded.17,19
to that of non-pregnant control

to that of non-pregnant control

matched for age, stage and

matched for age, stage and

The administration of chemotherapy during the second and
third trimesters has not been associated with major congenital
treatment protocol.

treatment protocol.
malformations but may increase the risk for IUGR, low
birth weight, and stillbirth. A review of 376 cases of fetuses
exposed to chemotherapy in utero, most after organogenesis,
Prognosis

demonstrated 5% fetal death rate and 1% neonatal death rate.

Other complications included preterm delivery (5%), IUGR
(7%), and transient myelosuppression (4%).17
A recent American registry of 152 women exposed to
(dysgerminomas and malignant

accounts for only 5% to 10% of

chemotherapy mostly after the first trimester demonstrated
•  Differentiated thyroid cancer,
diagnosed at an early stage.

follicular, are most common.

masses are benign and are

•  Surface epithelial-stromal

only a single case of intrauterine fetal death and a single case of

•  Medullary thyroid cancer
•  Vast majority of adnexal

subtypes papillary and

neonatal death.20 The malformation rate was 3.8%, with a 7.6%

all thyroid cancers.
•  Germ cell tumours

risk for IUGR. Only 2 of the 159 live born infants suffered
teratomas) (39%)
tumour (50.6%)

transient myelosuppression. A European study compared the

rates of adverse pregnancy outcomes in patients exposed to
Pathology

chemotherapy (117 pregnancies) during the second and third

trimesters and in healthy control patients (58 pregnancies).21
Although the incidences of major and minor malformations
had not increased compared with previous reports, the small
size of the control group prevents extensive conclusions.
•  Fine needle aspiration biopsy

The rate of low birth weight was higher in the chemotherapy

group (17.9%) than in the control group (8.6%). Most of the
infants with low birth weight were born to mothers treated
•  Thyroid function test
•  Pelvic ultrasounds.

for hematological malignancies.21

For cancer diagnosis made late in pregnancy, consideration
•  Ultrasound

can be given to delaying initiation of chemotherapy

Staging

balanced against gestational age and possible delivery

•  MRI

before treatment.
The major message is that most fetuses whose exposure is
•  Significant numbers of patients

limited to the second and third trimester of pregnancy are

enlargement of a pre-existing

•  Horner’s syndrome may be

born healthy.
•  Pain in the neck region,
•  New thyroid nodule or

Specific Cytotoxic Groups

are asymptomatic.
•  Adnexal masses.

Alkylating agents
Alkylating agents are commonly used for the treatment of
hoarseness

a variety of cancers. These compounds act directly on cell

Diagnosis

present
nodule

DNA to prevent rapidly replicating cells from reproducing.

Their action is not specific to a particular phase of the
cell cycle. Cyclophosphamide, dacarbazine, ifosfamide,
mechlorethamine, and procarbazine are among those
0.0036% to 0.014%
0.002% to 0.008%

commonly used.22
Frequency in

Cyclophosphamide is commonly used for the treatment

pregnancy

of breast cancer, ovarian cancer, and non-Hodgkin’s

lymphoma. Avilés et al.,23 reported healthy pregnancy
Table 2. Continued

outcomes in 11 patients treated during the first trimester

with cyclophosphamide-containing protocols.23 A further
5 reported exposures in the first trimester resulted in
several congenital malformations including absent big
Ovarian

Thyroid
Cancer

toes, single coronary artery, imperforate anus, umbilical

hernia, cleft palate, multiple eye defects, and esophageal

270 l MARCH JOGC MARS 2013


atresia.24–28 Included in this, one set of twin infants in
which the male twin, born with congenital anomalies,
later developed thyroid cancer at age 11 and stage III
neuroblastoma at age13.28 His twin sister was unaffected
by the exposure and was developing normally at the time
of the study, suggesting differential pharmacogenetic
effects on the drug metabolism into the active form of
the drug. Cyclophosphamide exposures in the second
and third trimester of pregnancy are more frequent.
One study examined the outcomes of 61 patients treated
for different malignancies during the second and third
trimester and found 59 infants were born with no
malformations.21 One infant whose mother was treated
also with doxorubicin was born with hip subluxation and
another infant who was exposed to the EFC protocol
(epirubicin, cisplatin,  fluorouracil) was born with
rectal atresia. Another 110 patients exposed during the
second and third trimesters to an assortment of multi-
drug protocols, including cyclophosphamide, resulted
in 105 normal births and 5 congenital malformations:
1 intrauterine death with normal autopsy, 1 neonatal death
due to autoimmune disorder, 1 infant with IgA deficiency,
1 with pyloric stenosis, and 1 with holoprosencephaly.20
Intrauterine growth restriction occurred in 7 cases (6%).
An additional 81 women who were treated with the FAC
regimen for breast cancer during the second to third
trimesters demonstrated 3 congenital abnormalities,
including 1 case of Down syndrome, 1 infant with
ureteral reflux, and another with talipes.29,30 Finally,
28 patients treated for breast cancer with different
cyclophosphamide-containing regimens during the
second and third trimesters all had normal deliveries and
outcomes.31 This information suggests that second and
third trimester exposure to cyclophosphamide may not
increase the risk for adverse effects.
Dacarbazine exposures occur most frequently in
pregnancy during administration of ABVD protocols, or
in combination MOPP, ABVD or MOPP/AVD protocols.
In 19 patients treated for lymphoma with ABVD after the
first trimester, 17 healthy infants were born, and 2 with
congenital malformations: 1 infant with plagiocephaly, and
1 infant with fourth and fifth syndactyly.20 In another 12
reports of lymphoma patients treated with ABVD (83.3%),
MOPP/ABVD (8.3%), or MOPP/ABD (8.3%) protocols,
all resulted in normal deliveries and healthy outcomes.32
Through this limited information, it appears that exposure
to dacarbazine during the later stages of pregnancy is not
associated with a specific set of malformations. Use in the
first trimester cannot be recommended.
Two case reports of ifosfamide treatment, combined with
doxorubicin for Ewing sarcoma in pregnancy were located.33,34
One exposure occurred during the second trimester and the
other in the third trimester. Both pregnancies had normal
outcomes. Scarcity of information regarding ifosfamide is a
recommendation for using a better-studied alternative.
Cancer Chemotherapy and Pregnancy
MOPP treatment, involving exposure to alkylating agents
mechlorethamine and procarbazine was reported in 14
patients.21,32,34,35 One patient treated during the first trimester
delivered an infant with hydrocephaly that died 4 hours
after birth.35 A second trimester exposure to MOPP/ABV
resulted in bilateral partial syndactyly of second and third
digits in the fetus.21 Twelve exposures to MOPP/ABV
or ABVD described by Avilés et al., with an unspecified
amount occurring in the first trimester, all resulted in
normal outcomes.32 These data suggest mechlorethamine
and procarbazine are not associated with an increased risk in
the second and third trimesters.
Platinum compounds
Platinum compounds form DNA adducts that result in
DNA crosslinking. DNA crosslinks inhibit replication,
transcription, and other nuclear functions. The combination
of these events arrests cell proliferation and ultimately
tumour growth. Cisplatin and carboplatin are among the
most commonly used platinum compounds.
Cisplatin exposure in the second and third trimesters has
been frequently described. Four patients who had cervical
cancer during pregnancy and who were treated in the
second trimester with cisplatin all delivered healthy infants
with no congenital malformations.36–39 Another 3 patients
treated for small cell lung carcinoma and 2 treated for
ovarian cancer delivered healthy infants after exposures
to cisplatin.40–42 Finally, 6 of 7 infants born to 7 patients
exposed to cisplatin in various regimens for different
malignancies were healthy. Only 1 infant was born with a
congenital malformation, hearing loss that was attributed
to genetic factors from the parents.20 Cisplatin use in the
second and third trimesters of pregnancy has not been
found to be associated with any pattern or increased risk
of adverse fetal effects.
Carboplatin exposure occurred during the second and third
trimesters of 5 patients. Four were women with ovarian
cancer, all of whom delivered healthy infants. The 1 case
of CNS malignancy was the only report of an adverse
pregnancy outcome, with a spontaneous abortion of a
fetus with gastroschisis, as reported by Cardonick et al.20
Although evidence is limited, carboplatin exposure in the
second and third trimesters does not appear to increase the
risk for major malformations.
Antimetabolites
Antimetabolites are small compounds used to treat
leukemia, lymphoma, and breast cancer. They act as false
substrates during DNA or RNA synthesis, resulting in
inhibition of cellular metabolism. This process occurs
independently of the phase of the cell cycle. Common
examples of chemotherapeutic agents of this drug class
are methotrexate, 5-fluorouracil, aminopterin, cytarabine,
tioguanine, and mercaptopurine.22
MARCH JOGC MARS 2013 l 271
SOGC CLINICAL PRACTICE GUIDELINE
Methotrexate exposure during the first trimester of
pregnancy has been associated with malformations similar
to the aminopterin syndrome, including cranial dysostosis
with delayed ossification, hypertelorism, wide nasal bridge,
micrognathia, and ear anomalies.43 In a series of 20
exposures during the first trimester, 7 infants developed
this pattern of anomalies.44–52 In addition, there were 5 cases
of miscarriage and 1 case of skeletal abnormalities with
ambiguous genitalia. Exposure to methotrexate (together
with cyclophosphamide and 5-fluorouracil) in the second
and third trimesters in 12 patients did not show the same
pattern of malformations: all infants were born healthy.31
Because of the suspected teratogenicity of methotrexate,
it should not be considered a first-line therapy, and should
not be used at any stage of pregnancy.
One study reported on 53 exposures to 5-fluorouracil,
with 5 occurring in the first trimester.17 One of these
patients spontaneously miscarried, and there were 6 cases
of IUGR. The rest of the infants had normal outcomes.
A further 12 patients exposed to 5-fluorouracil, along
with cyclophosphamide and methotrexate, in the second
and third trimesters had normal outcomes.31 Similarly,
18 patients treated with 5-fluorouracil for breast and
colorectal cancers during the second and third trimester
all had normal pregnancy outcomes.20 Hahn et al. reported
3 congenital malformations out of 35 exposures to
5-fluorouracil in an FAC protocol during the second and
third trimesters for the treatment of breast cancer.29 One
infant was born with Down syndrome, 1 with clubfoot,
and 1 with congenital bilateral ureteral reflux. As these
are fairly common congenital abnormalities, the authors
compared these rates with expected population frequencies
and determined that the chemotherapy may not have been
the cause. As an antimetabolite, 5-fluorouracil is not one
of the first-line agents recommended, but it has not been
associated with any increased risk for malformation in the
second and third trimesters.
Capecitabine exposure in 1 patient treated during the
first trimester for colorectal cancer resulted in a normal
pregnancy with a healthy outcome.20 Evidence is insufficient
for conclusions to be made about the safety of capecitabine.
In 9 patients treated with various regimens including
cytosine arabinoside for leukemia, 5 of them during the first
trimester, no congenital malformations were reported.23
Two more patients treated during the second and third
trimesters with this antimetabolite for non-Hodgkin’s
lymphoma and acute myeloid leukemia also had healthy
pregnancy outcomes.20 Although information is limited,
there is so far no evidence to indicate that administration
of cytosine arabinoside in pregnancy results in fetal
malformations.
One patient treated with gemcitabine for a pancreatic
tumour during the second and third trimesters had a normal
272 l MARCH JOGC MARS 2013
pregnancy and healthy outcome.20 A second patient treated
for non-small cell lung cancer delivered prematurely, at
28 weeks, but with no congenital malformations.53
Anti-tumour antibiotics
Microorganisms produce these cytotoxic agents that
interact directly with DNA resulting in anti-cancer activity.
The manner in which antibiotics interact with DNA differs
considerably between agents.
Bleomycin creates DNA breaks and is commonly used
in the ABVD protocol. Cardonick et al.20 reported on
23 exposures to bleomycin in pregnancy, with varying
malignancies and regimens.20 Twenty of the women were
being treated for lymphoma, while the remaining 3 had
ovarian cancer. Treatment occurred during the second and
third trimesters, and 3 congenital malformations resulted.
One infant was born with plagiocephaly and another with
fourth and fifth finger syndactyly. A third infant was born
with genetic hearing loss, of which his parents were both
genetic carriers.20 Another patient treated with bleomycin
(in combination with etoposide and cisplatin) for teratoma
during the third trimester had a normal delivery and
healthy infant.42 Bleomycin therapy in the second and
third trimesters of pregnancy was not associated with any
grouping of malformations.
Topoisomerase inhibitors
Anthracyclines
Anthracyclines commonly used are doxorubicin, daunoru­
bicin, epirubicin, idarubicin, and mitoxantrone.
Van Calsteren et al. reported on a number of pregnant
patients treated with topoisomerase inhibitors.18 A total of 36
patients treated for various malignancies with doxorubicin
during the second and third trimester were evaluated. One
infant, also exposed to cyclophosphamide, was born with
hip subluxation. A second infant exposed to FAC regimen
was born with doubled cartilage rings in both ears. The
rest of the infants (34/36) had normal outcomes. Another
25 patients in this series were exposed to daunorubicin-
containing treatments for various malignancies during the
second and third trimesters. Two infants had congenital
malformations: 1 with bilateral partial syndactyly of
second and third digits, and the other with rectal atresia.
The remaining 23 outcomes were normal. Cardonick et al.
detailed the pregnancy outcomes of 118 patients treated
for breast cancer (98) and lymphoma (20) with various
topoisomerase inhibitor-containing regimens, all during
the second and third trimesters.20 A total of 5 abnormal
outcomes were observed: 1 infant with IgA deficiency, 1
neonatal death due to autoimmune disorder, 1 infant with
pyloric stenosis, 1 infant with holoprosencephaly, and 1
intrauterine demise with normal autopsy. In another series
of 11 patients treated with doxorubicin together with

cyclophosphamide during the second and third trimesters
of pregnancy, all infants had normal outcomes.31
Epirubicin exposure was noted in 5 patients concomitant
with cyclophosphamide during the second and third
trimesters. No congenital malformations were reported.31
In 1 case, a patient treated for acute myeloid leukemia
was exposed to idarubicin together with all-trans retinoic
acid during the first trimester and had a normal pregnancy
outcome. 54 A further 9 cases of patients treated for various
malignancies during the second and third trimesters,
however, resulted in 4 congenital malformations,32,55–59
including 1 case of transient dilated cardiomyopathy and 2
cases of permanent dilated cardiomyopathy.55–57 As data on
possible effects to the fetal heart are inconclusive, caution
should be exercised with respect to the use of idarubicin
during pregnancy.
One patient treated for teratoma with mitoxantrone
and bleomycin and cisplatin during the third trimester
had a normal delivery, and the infant had no congenital
malformations.42
Plant alkaloids and taxanes
Plant alkaloids and natural products, such as taxanes, may
inhibit mitosis or inhibit enzymes needed for reproduction
of the cell. These agents are specific to the M phase of
the cell. They include paclitaxel, docetaxel, etoposide,
vinblastine, and vincristine.22
In 19 patients, 2 in the first trimester, exposed to
docetaxel for the treatment of breast cancer, 3 congenital
malformations were noted.60 Two infants had cerebral
ventriculomegaly; however, in both cases the diagnosis was
made before administration of chemotherapy. The only
malformation potentially related to cytotoxicity is 1 case of
pyloric stenosis in an infant whose mother was exposed to
doxorubicin, cyclophosphamide, paclitaxel, and docetaxel.
Therefore, the use of docetaxel appears to be safe in the
second and third trimesters.
Exposures to paclitaxel in multi-drug therapies for various
malignancies in 19 patients resulted in 1 congenital
malformation and 1 intrauterine or postnatal demise.20 Pyloric
stenosis was reported in an infant exposed to paclitaxel,
docetaxel, cyclophosphamide, and doxorubicin as discussed
above. In a patient treated with doxorubicin, vincristine,
cyclophosphamide, prednisone, and rituximab for non-
Hodgkin’s lymphoma, intrauterine fetal demise occurred at
30 weeks. The autopsy results were normal. Twenty-four
more cases of exposure to paclitaxel for the treatment of
breast cancer in the second and third trimester resulted in
23 healthy outcomes. The 1 congenital malformation was
the case of pyloric stenosis following multi-drug exposure
reported previously. Finally, 1 patient treated with paclitaxel
weekly from 20 weeks’ gestation delivered a healthy infant
Cancer Chemotherapy and Pregnancy
with no congenital malformations.61 These data suggest that
paclitaxel may be compatible with therapy in the second and
third trimesters of pregnancy.
Vincristine exposures in 11 patients treated for various cancers
during the second and third trimesters resulted in healthy
outcomes for 10 infants.20 As previously noted, 1 infant
exposed to vincristine, doxorubicin, cyclophosphamide,
prednisone, and rituximab died in utero at 30 weeks, and
the autopsy results were normal. These limited exposures
suggest that vincristine therapy does not increase risk for
malformation during the second and third trimesters.
Of 20 patients treated in the second and third trimesters for
Hodgkin’s lymphoma and non-Hodgkin’s lymphoma with
varying vinblastine-containing regimens, 2 had infants with
malformations.20 After in utero exposure to doxorubicin,
bleomycin, dacarbazine, and vinblastine throughout
second and third trimesters for Hodgkin’s lymphoma,
there was 1 case of plagiocephaly. Another infant exposed
to the same regimen was born with fourth and fifth finger
syndactyly. Although evidence to date suggests there is not
a significant concern with unique vinblastine treatment in
the second and third trimesters, more research is needed.
Etoposide exposure in 6 patients during the second and
third trimesters did not appear to cause any congenital
malformations.20,40,42 One infant was born with genetic
hearing loss ruled unrelated to exposure to etoposide,
cisplatin, and bleomycin. Although there is only limited
experience with etoposide, there were no patterns of
congenital malformations noted with etoposide exposure in
the later stages of pregnancy.
Molecularly targeted agents
Recently, the choice of treatment for the pregnant patient
with cancer has become even more complicated because
of the increasing use of targeted anti-cancer therapies. The
benefit of the targeted agents has been well demonstrated
for various malignancies; however, their safety during
pregnancy has not been established. Currently, significant
experience with exposure during pregnancy is available
only for the tyrosine kinase inhibitor, imatinib and the
monoclonal antibody, rituximab.
The largest report regarding exposure to imatinib during
pregnancy included 180 pregnant women with chronic
myeloid leukemia. Outcome data were available for 125
patients.62 Congenital malformations were identified in
12 infants, 3 of whom had strikingly similar complex
malformations (a combination of omphalocele with severe
renal and skeletal malformations) that are clearly cause for
concern. All congenital malformations were associated with
first trimester exposure to imatinib. It appears that although
most pregnancies exposed to imatinib are likely to have a
successful outcome, this exposure may result in serious fetal
MARCH JOGC MARS 2013 l 273
SOGC CLINICAL PRACTICE GUIDELINE
malformations. These concerns suggest that imatinib should
not be administered during the first trimester.62,63
Rituximab is an anti-CD20 monoclonal B-cell antibody
indicated mainly for diffuse large B cell and follicular
non-Hodgkin’s lymphomas. Recently it has been also
administered to patients with several autoimmune diseases.
A 2011 report described 231 pregnancies associated
with maternal rituximab exposure.64 Most cases were
confounded by the concomitant use of potentially
teratogenic medications (most commonly methotrexate).
Of the 153 pregnancies with outcome data, 90 resulted in
live births. First trimester miscarriages were reported in 33
(21%) cases, and 28 pregnancies were electively terminated.
Twenty-two infants were born prematurely, and there was
1 neonatal death. Eleven neonates had hematological
abnormalities without corresponding infections. Two
congenital malformations were identified: 1 case of
talipes, and 1 of cardiac malformation (a combination of
ventricular septal defect, persistent foramen ovale, and
persistent ductus arteriosus). The limited experience to
date suggests that the administration of rituximab may be
considered safe during the second and third trimesters.
TREATMENT GUIDELINES
Patients with a slowly growing cancer diagnosed during
the first trimester may be followed at short intervals for
signs of disease progression without treatment until the
second trimester. However, when aggressive, advanced,
or progressive disease is diagnosed in the first trimester, a
delay in therapy may adversely affect maternal survival.3,63–67
Therefore, treatment with appropriate, often combination,
chemotherapy should be given promptly. However,
this should be accompanied by detailed counselling to
ensure that the woman and her family understand the
potential teratogenic effects of chemotherapy in the first
trimester. In specific cases, the treatment with single-
agent chemotherapy (preferably a vinca alkaloid or an
anthracycline) during the first trimester followed by
conventional multi-agent therapy at the beginning of the
second trimester may be considered. Such therapeutic
approaches appear to be safe; however, data regarding
their efficacy for the maternal cancer is lacking. Most
multi-drug protocols may be administered during the
second and third trimesters without an apparent increase
in the risk for severe malformations. Regimens based on a
combination of cyclophosphamide and an anthracycline
administered to women with breast cancer or lymphoma
have been most commonly used during pregnancy, and
their administration after the end of the first trimester
found to be safe. Weekly fractionated-dose chemotherapy
may be preferred to allow ease of pregnancy monitoring,
and interruption of treatment if necessary.6
274 l MARCH JOGC MARS 2013
Treatment during the second and third trimesters does not
carry a risk for morphological congenital malformation;
however, infants may be born earlier than expected and
small for gestational age, and some of the agents used in
treatment are neurotoxins, which may theoretically affect
brain development. The timing of delivery should be
planned to avoid myelosuppression, but no long-term
developmental sequelae have been reported. If possible,
delivery should be postponed for 2 to 3 weeks following
anti-cancer treatment to allow bone marrow recovery.4,69
Furthermore, neonates, especially preterm infants, have
limited capacity to metabolize and eliminate drugs because
of liver and renal immaturity. The delay of delivery after
chemotherapy will allow fetal drug excretion by the placenta.
POSTPARTUM CARE
Breastfeeding
As a rule, women using cancer chemotherapeutic agents
after delivery should not be breastfeeding as neither short-
term nor long-term safety has been established. Exceptions
include azathioprine, with which repeated measures failed
to show accumulation in milk.
If the lactating mother requires drug therapy, safety of
breastfed infants is a concern because almost all drugs the
mother ingests are excreted into milk. Of many factors that
determine magnitude of drug excretion into milk, plasma
protein binding, ionization characteristics and lipophilicity
of drug are the most important.70
Recently, expression and function of carrier-mediated drug
transport in the mammary gland have been elucidated. For
example, the lactating mammary gland highly expresses
breast cancer resistant protein (BCRP: ABCG2), which
carries its substrates from maternal circulation into milk.
Initially, its role as a toxin transporter was perplexing as it
appeared to actively contaminate mother’s milk. However,
it was later shown that breast cancer resistant protein in
the mammary gland is a major vitamin B2 transporter.71
Some organic cation transporters carry both xenobiotics
and nutrients, and mammary gland drug transporters
have a nutrient carrier function that is taken over by
maternal xenobiotics. In addition to the above mentioned
attributes of drugs, such as protein binding and ionization
characteristics, transporter affinity as a substrate is another
important factor for defining milk excretion of drugs.70
Risk assessment of drug therapy, including cancer
chemotherapy, during lactation must consider several factors
that are distinct from those of pregnancy. First, average
levels of drug exposure in the infant are usually an order
of magnitude lower in lactation-mediated exposure than in
transplacental exposure. Second, the mother has an option
to discontinue, or temporarily interrupt, breastfeeding if
the risk is perceived to be high. Third, cancer chemotherapy
schedules may allow breastfeeding women to store their

own milk for near-future use. In addition, women with
cancer who are being treated with chemotherapy may
perceive the importance of breastfeeding and the risks
associated with it differently from women who are taking
non-cancer related medications.
Published clinical studies on excretion of cancer
chemotherapy agents into milk, and resultant infant plasma
levels, are very limited. Breastfeeding-related information
is available for the following chemotherapeutic agents
in cancer treatment, but levels of evidence are not high
enough to make firm recommendations.
Cisplatin
There are 3 published case reports on use of cisplatin in
lactating women with cancer.72–74 At various post-dose time
points, plasma cisplatin concentrations were measured as
platinum. The maternal plasma levels ranged from 0.8 mg/
mL to about 3 mg/mL when measured and expressed as
plasma platinum levels, but the maternal plasma ratio varied
widely from nearly zero (milk levels were below the detection
limit of platinum) to 1.1. Cisplatin pharmacokinetic studies in
non-lactating patients indicate that average plasma platinum
concentrations after 100 mg/m2 dosing (a high therapeutic
dose) are about 3.91 ± 1.41 mg/mL.75 Assuming maternal
plasma ratio to be the reported highest (1.1), the infant
would receive 4.3 mg/kg/day of platinum. Taken together,
evidence of cisplatin safety/toxicity in breastfeeding is
weak. Because of the relatively long half-life of cisplatin,
most experts recommend discontinuation of breastfeeding,
but emerging data on benefits of breastfeeding and lack
of clear toxicity data may require revisiting the current
recommendation.
Cyclophosphamide
Three case reports of use of cyclophosphamide during
breastfeeding exist; however, there are no quantitative
data on cyclophosphamide levels in milk.76–78 In one case,
a woman with leukemia received weekly intravenous
doses of cyclophosphamide 800 mg and vincristine 2
mg over a 6-week period, in addition to prednisolone
(30 mg/day). Her 4-month-old infant was breastfed
during this treatment cycle and found to be neutropenic
at the end of the treatment, but returned to normal after
breastfeeding was discontinued.76 Another patient with
Burkitt lymphoma received daily cyclophosphamide
6 mg/kg intravenously. At 23 days of life, her infant
developed neutropenia and thrombocytopenia over a
3-day period. The limited information from these reports
suggests that cyclophosphamide is not compatible with
breastfeeding.77
Doxorubicin
In milk samples of a woman receiving doxorubicin
70 mg/m2 (an intravenous dose of 90 mg), the drug and its
active metabolite, doxorubicinol, were detected. The peak
Cancer Chemotherapy and Pregnancy
milk concentrations of doxorubicin and doxorubicinol
were 128 mg/L (0.24 mM) and 111 mg/L (0.20 mM),
respectively, 24 hours after the dose.72 Anthracyclines may
not be absorbed orally, and the dose to the infant, based
on the peak levels, may be in the low range of 2% of the
weight-adjusted dose. However, safety data are too scant to
make a firm recommendation at this point.
A 28-year-old woman with acute promyelocytic
leukemia received chemotherapy during pregnancy and
breastfeeding.79 After first consolidation therapy, she
delivered healthy baby at 34 weeks’ gestation. After delivery
she received second consolidation therapy. Then she
was treated with intravenous etoposide (80 mg/m2/day:
days 1 to 5) and other drugs including mitoxantrone
(6 mg/m2/day: days 1 to 3) and cytarabine (170 mg/m2/day:
days 1 to 5) as third consolidation therapy. The post-infusion
peak milk concentrations of etoposide ranged from
580 mg/L to 800 mg/L, which quickly declined and became
undetectable in 24 hours. Breastfeeding was resumed 3
weeks after the end of the therapy without incident.
In the same woman described above, mitoxantrone milk
concentration reached 120 mg/mL immediately after the
third dose. Mitoxantrone milk concentrations decreased to
about 20 mg/mL by 7 days after the last (third) dose, and
remained at that level 4 weeks after the last dose.79
After maternal oral doses of imatinib (400 mg/day),
milk concentrations are approximately in the range of
0.5 mg/mL to 3.2 mg/mL. Its active metabolite is also in a
similar range of concentrations (1 mg/mL to 2.5 mg/mL).
One infant was breastfed during the maternal imatinib
treatment without incident.80–83
Methotrexate
A 25-year-old woman with choriocarcinoma received
methotrexate 22.5 mg orally (15 mg/m2/day). Peak
methotrexate concentrations in milk samples were
2.6 ng/mL on 2 different dosing occasions.84 In the case
of a woman who received a single dose of 65 mg of
methotrexate intramuscularly (50 mg/m2) for ectopic
pregnancy, 6 milk samples taken over the following
24-hour period did not show detectable levels of the drug.85
Studies on excretion of cancer chemotherapeutic agents
into human milk are scarce, but accumulating evidence
is overwhelmingly supportive of the tangible benefit of
human milk for many aspects of infant development.
Given the nature of the maternal diseases in question,
risk-benefit assessment of breastfeeding during maternal
chemotherapy needs to be carefully individualized.
Follow-Up
While treating pregnant women during the second and third
trimesters, it is important to bear in mind that the CNS
is still developing and that treatment can have long-term
MARCH JOGC MARS 2013 l 275
SOGC CLINICAL PRACTICE GUIDELINE
side effects on the child’s development. Long-term follow-
up data on children born to mothers treated for leukemia
during pregnancy have been published.32 The children’s
psychological, physical, and neurological development were
reported as normal. The grandchildren of exposed pregnant
women were also followed up in the same study. Even
those children had normal neurological and psychological
development. No congenital malformations were reported.
One review included 111 children born to women treated
during pregnancy, who were followed for up to 19 years. All
the children had normal neurological development.86
Another concern is the possibility of secondary malignancies
in exposed children. Avilés and Neri followed 84 children to
a median age of 18 years: no secondary malignancies and no
fertility issues were reported.32 Yet, in a case of twin exposure
to cyclophosphamide, 1 infant developed 2 different cancers
(neuroblastoma and thyroid) over his lifetime.28
To date, there is no other large-scale follow-up. A recent
registry reported on well-being of infants born to treated
mothers, but the follow-up period is only a few years.20
Ongoing observation is underway to provide a full and
detailed report in the coming years.
At birth, the placenta should be examined for invasion
of malignant cells. Any infant with placental involvement
should be considered high risk and subsequently monitored.
Cardonick et al. recommend follow-up every 6 months for
at least 2 years, with a focus on the primary malignancy.
A physical examination, blood chemistry, and chest X-ray
may also be of value.20
ETHICAL CONSIDERATIONS
When considering the treatment of cancer during
pregnancy with chemotherapeutic agents, it is important
to balance maternal and fetal interests Decisions about
the management of cancer in pregnancy should be made
individually for each patient after careful consideration of
cancer type, cancer stage, gestational age, maternal and
fetal risks, and possible treatment alternatives.
Termination of pregnancy may be indicated but will not
be acceptable in all cases for social and sometimes religious
reasons. Furthermore, most evidence does not suggest
increased maternal survival following therapeutic abortion.87
If the patient desires the pregnancy, and termination is
not an option, the decision to start chemotherapy during
pregnancy should be weighed against the potential impact
on maternal survival.17 Physicians should discuss the
situation with the pregnant patient and her family, providing
all the information available regarding the malignancy,
possible treatment alternatives, and both maternal and
fetal risks.17 A multidisciplinary team, which includes
276 l MARCH JOGC MARS 2013
the family physician, hematologist and/or oncologist,
obstetrician, social worker, psychologist, and in some cases
religious advisors, should be assembled whenever possible
to optimize the physical and mental well-being of the
woman, her baby, and her family.
SUMMARY STATEMENTS AND
RECOMMENDATIONS
Summary Statements
1. As women are postponing child-bearing, more of
them are experiencing cancer in pregnancy. (II-2)
2. Chemotherapeutic agents used to combat cancer
cross the placenta and may adversely affect
embryogenesis by affecting cell division. (II-1)
3. Exposure to such agents after the first trimester of
pregnancy has not been associated with increased
risk of malformations but is associated with
increased risk of stillbirth, intrauterine growth
restriction, and fetal toxicities. (II-2)
Recommendations
1. The health care provider should examine the
patient’s risk of pregnancy and desire to prevent
pregnancy during chemotherapy. (I-A)
2. Decisions about the best course of management
in pregnancy, including timing of delivery, should
balance maternal and fetal risks. Most authorities
concur that maternal health and well-being must
prevail. (I-A)
3. Women diagnosed with cancer in pregnancy should
be optimally managed by a multidisciplinary team
that includes oncologists and/or hematologists
(depending on the malignancy), perinatologists,
family physicians, psychologists, social workers, and
spiritual advisors, if sought by the family. (I-A)
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 SOGC CLINICAL PRACTICE GUIDELINES
Cervical Insufficiency and Cervical Cerclage
This clinical practice guideline has been prepared by the
Maternal Fetal Medicine Committee, reviewed by the Clinical
Practice Obstetrics Committee, and approved by the
Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Richard Brown, MD, Montreal QC
Robert Gagnon, MD, Montreal QC
Marie-France Delisle, MD, Vancouver BC
MATERNAL FETAL MEDICINE COMMITTEE
Robert Gagnon, MD (Chair), Montreal QC
Emmanuel Bujold, MD (Co-Chair), Quebec QC
Melanie Basso, RN, Vancouver BC
Hayley Bos, MD, London ON
Richard Brown, MD, Montreal QC
Stephanie Cooper, MD, Calgary AB
Joan Crane, MD, St John’s NL
Gregory Davies, MD, Kingston ON
Katy Gouin, MD, Quebec QC
Savas Menticoglou, MD, Winnipeg MB
William Mundle, MD, Windsor ON
Christy Pylypjuk, MD, Saskatoon SK
Anne Roggensack, MD, Calgary AB
Frank Sanderson, MD, Saint John NB
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all contributors.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research analyst, Society of Obstetricians and Gynaecologists
of Canada.
Key words: Cervical insufficiency, cervical incompetence, cervical
cerclage, preterm delivery, prematurity, Shirodkar cerclage,
MacDonald cerclage, abdominal cerclage, rescue cerclage,
cervical shortening, trans-vaginal ultrasound, cervical length
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 301, December 2013
Abstract
Objective: The purpose of this guideline is to provide a framework
that clinicians can use to determine which women are at
greatest risk of having cervical insufficiency and in which set of
circumstances a cerclage is of potential value.
Evidence: Published literature was retrieved through searches
of PubMed or MEDLINE, CINAHL, and The Cochrane Library
in 2012 using appropriate controlled vocabulary (e.g., uterine
cervical incompetence) and key words (e.g., cervical insufficiency,
cerclage, Shirodkar, cerclage, MacDonald, cerclage, abdominal,
cervical length, mid-trimester pregnancy loss). Results were
restricted to systematic reviews, randomized control trials/
controlled clinical trials, and observational studies. There were
no date or language restrictions. Searches were updated on a
regular basis and incorporated in the guideline to January 2011.
Grey (unpublished) literature was identified through searching the
websites of health technology assessment and health technology-
related agencies, clinical practice guideline collections, clinical
trial registries, and national and international medical specialty
societies.
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table).
Recommendations
01. Women who are pregnant or planning pregnancy should be
evaluated for risk factors for cervical insufficiency. A thorough
medical history at initial evaluation may alert clinicians to risk
factors in a first or index pregnancy. (III-B)
02. Detailed evaluation of risk factors should be undertaken in
women following a mid-trimester pregnancy loss or early
premature delivery, or in cases where such complications have
occurred in a preceding pregnancy. (III-B)
03. In women with a history of cervical insufficiency, urinalysis for
culture and sensitivity and vaginal cultures for bacterial vaginosis
should be taken at the first obstetric visit and any infections so
found should be treated. (I-A)
04. Women with a history of three or more second-trimester
pregnancy losses or extreme premature deliveries, in whom
no specific cause other than potential cervical insufficiency is
identified, should be offered elective cerclage at 12 to 14 weeks
of gestation. (I-A)
J Obstet Gynaecol Can 2013;35(12):1115–1127
DECEMBER JOGC DÉCEMBRE 2013 l 1115
SOGC Clinical Practice Guidelines
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.156
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.156
05. In women with a classic history of cervical insufficiency in
whom prior vaginal cervical cerclage has been unsuccessful,
abdominal cerclage can be considered in the absence of
additional mitigating factors. (II-3C)
06. Women who have undergone trachelectomy should have
abdominal cerclage placement. (II-3C)
07. Emergency cerclage may be considered in women in whom
the cervix has dilated to < 4 cm without contractions before
24 weeks of gestation. (II-3C)
08. Women in whom cerclage is not considered or justified, but
whose history suggests a risk for cervical insufficiency (1 or
2 prior mid-trimester losses or extreme premature deliveries),
should be offered serial cervical length assessment by
ultrasound. (II-2B)
0 9. Cerclage should be considered in singleton pregnancies in
women with a history of spontaneous preterm birth or possible
cervical insufficiency if the cervical length is ≤ 25 mm before
24 weeks of gestation. (I-A)
10. There is no benefit to cerclage in a woman with an incidental
finding of a short cervix by ultrasound examination but no prior
risk factors for preterm birth. (II-1D)
11. Present data do not support the use of elective cerclage in
multiple gestations even when there is a history of preterm birth;
therefore, this should be avoided. (I-D)
12. The literature does not support the insertion of cerclage in
multiple gestations on the basis of cervical length. (II-1D)
INTRODUCTION
C ervical insufficiency may be present in up to 1% of
obstetric populations, and it therefore represents a
concern frequently enough that a guideline to address the
dilemmas in its management is overdue. Despite having
been part of obstetric practice for over a century, both the
1116 l DECEMBER JOGC DÉCEMBRE 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
role of cervical cerclage and indications for it remain ill-
defined and controversial, with wide practice variations in
different clinical settings. In part, the lack of clarity that
surrounds cerclage is fostered by uncertainty in identifying
those patients who will truly benefit from its use (i.e., those
with true cervical insufficiency or truly increased risk of
early preterm delivery).1,2
Cervical insufficiency has no consistent definition, but is
usually characterized by dilatation and shortening of the
cervix before the 37th week of gestation in the absence
of preterm labour, and is most classically associated with
painless, progressive dilatation of the uterine cervix in
the second or early third trimester resulting in membrane
prolapse, premature rupture of the membranes, mid-
trimester pregnancy loss, or preterm birth.3,4 Cervical
insufficiency arises from the woman’s inability to support a
full-term pregnancy due to a functional or structural defect
of the cervix.1
The incidence of true cervical insufficiency is estimated
at less than 1% of the obstetric population. In Denmark
from 1980 to 1990, cervical insufficiency was diagnosed in
4.6 per 1000 women,2 and it is estimated to occur in 8% of
women with recurrent mid-trimester losses.5 A variety of
risk factors have been identified and are divided here into
those that may be identified from prior maternal history
and those that may arise in the index pregnancy itself.
The classic history that raises the suspicion of cervical
insufficiency is that of recurrent mid-trimester

pregnancy losses. A previous preterm pre-labour
rupture of membranes at less than 32 weeks should be
noted, as should a prior pregnancy with a cervical length
measurement of less than 25 mm prior to 27 weeks
of gestation.6 Any history of prior cervical trauma
(e.g. repeated therapeutic abortion, repetitive cervical
dilatation, cone biopsy, cervical tears and lacerations,
trachelectomy) should also be noted. A risk factor
reducing in incidence is that of the mother herself having
been exposed to diethylstilbestrol in utero. 6 A variety
of other maternal risk factors include the presence of
a congenital uterine anomaly or a maternal connective
tissue disease or abnormalities, e.g. Ehlers-Danlos
syndrome,7 that impacts upon the integrity of normal
collagen development and function. Recently, polycystic
ovarian syndrome has been suggested as a risk factor
for cervical insufficiency, especially in women of South
Asian or Black origin.8 In many cases, especially when
clinical features and findings lead to suspicion of the
diagnosis in the first pregnancy, these risk factors may
not be present and the cause may remain idiopathic.9–12
In the index pregnancy, findings indicative of possible cervical
insufficiency include cervical funnelling, cervical shortening,12
and overt cervical dilatation.13 Even in the absence of
funnelling, a cervical length determined by ultrasound to be
< 25 mm prior to 27 weeks10,11 increases the risk of pregnancy
loss or preterm birth.
Up to 85% of the cervix’s dry weight is collagen. Petersen and
Uldbjerg examined cervical collagen in non-pregnant women
with previous cervical insufficiency and found that they had
markedly lower median cervical hydroxyproline concentrations
than parous women without cervical insufficiency.14 The
causes of this have yet to be ascertained, but this seems to
be a key factor in understanding the mechanism of cervical
failure in such cases.
In addition to its mechanical strength, the cervix may
also play a role in protecting the uterine contents from
ascending infection,4,15 with one key factor in this being
the role of the cervical mucous as a barrier between the
uterus and ascending infection. Data suggest that 80% of
cases of acute cervical insufficiency may be associated with
intra-amniotic infection.16
DIAGNOSIS OF CERVICAL INSUFFICIENCY
There is no diagnostic test for cervical insufficiency.
Although many tests have been reported or are
used (assessment of the cervical canal width by
hysterosalpingogram, assessment of the ease of insertion
of cervical dilators [size 9 Hegar] without resistance, the
Cervical Insufficiency and Cervical Cerclage
force required to withdraw an inflated Foley catheter
through the internal os, the force required to stretch the
cervix using an intracervical balloon) none of these meet
the criteria required for a diagnostic test.17–21 Part of the
diagnosis is based upon the exclusion of other causes
of preterm delivery or mid-trimester pregnancy loss. In
recent practice, transvaginal ultrasonography has been
increasingly used as a demonstrably valid and reproducible
method of cervical assessment, and cervical shortening
correlates with the risk of preterm delivery.12,22–25
Without a reliable diagnostic test, it becomes necessary
to screen for or to predict the likelihood of cervical
insufficiency. This process is based upon the identification
and recognition of key risk factors in the woman’s history
and in the index pregnancy.
The most common factors in the patient history that
indicate she may be at risk are a prior second trimester
pregnancy loss or a prior preterm birth. It should be noted,
however, that although in some situations there may be
a continuum between cervical insufficiency and preterm
labour and delivery, in others these are distinct and
unrelated processes. A history of preterm labour or the
identification of factors that increase the risk for preterm
birth do not always necessarily indicate risk for cervical
insufficiency.26,27
A history of prior cervical surgery, e.g. loop electrosurgical
excision procedure (LEEP), may also present a risk for
cervical insufficiency. In such patients there may also be a
role for cervical length assessment by ultrasound. In patients
who have had a prior LEEP, a 30 mm cervical length has
a positive predictive value for preterm birth of 54%, but
a negative predictive value of 95%.23 However, because of
the low overall frequency of cervical insufficiency even in
this group, some data do not support the routine use of
mid-trimester ultrasound in such women.23 Other forms
of cervical trauma, for example cervical tears, may also be
significant.28
Less frequent in current practice is the identification of
women who were exposed to diethylstilboestrol when in
utero themselves.29–31
The key finding in the current pregnancy is the
identification of cervical shortening. Cervical length
assessment by ultrasound is an established means of
assessing the risk for preterm labour and delivery (cervical
length < 25 mm).11,12,22,25,32,33
Patients may also be found to have cervical dilatation rather
than just shortening, or they may present with preterm
membrane rupture. Identification of cervical dilatation in
DECEMBER JOGC DÉCEMBRE 2013 l 1117
SOGC Clinical Practice Guidelines
the absence of a maternal history of contractions, with
or without membrane rupture, is considered tantamount
to a diagnosis of cervical insufficiency. Models based on
the recognition of these two main risk factors (cervical
shortening and cervical dilatation) have been described
and may be of value in determining which patients are
at greatest risk, but further assessment of such screening
tools is required.34
Recommendations
1. Women who are pregnant or planning pregnancy
should be evaluated for risk factors for cervical
insufficiency. A thorough medical history at initial
evaluation may alert clinicians to risk factors in a first
or index pregnancy. (III-B)
2. Detailed evaluation of risk factors should be
undertaken in women following a mid-trimester
pregnancy loss or early premature delivery, or in
cases where such complications have occurred in a
preceding pregnancy. (III-B)
MANAGEMENT OF CERVICAL INSUFFICIENCY
The management of cervical insufficiency can be viewed
as falling broadly into two main types: those in which it is
clear that surgical intervention in the form of cerclage is
indicated, and those in which a conservative path will be
pursued.
Indications for the insertion of a cerclage may arise from
the clinical history or the finding of cervical shortening
and/or dilatation in the index pregnancy, and therefore may
be divided into prophylactic cerclage versus therapeutic
cerclage. Alternatives to cerclage include the cervical
pessary; some data suggest this may be of benefit in some
cases, but these data are sparse and conflicting. Further
investigation of such techniques is required before they can
be considered as part of a guideline for the management
of cervical insufficiency.35
Prophylactic Transvaginal Cerclage
Consider elective cerclage if there appears to be a high risk
of cervical insufficiency based on the woman’s obstetric
history. The level of risk is typically determined by
identifying and assessing the significance of the risk factors
described in the “Diagnosis of Cervical Insufficiency”
section. Most frequently the assessment of risk will be
founded upon a history of second-trimester pregnancy
losses or early preterm deliveries in the absence of other
mitigating risk factors.36–38 Therefore a detailed evaluation
of risk factors should be undertaken in women presenting
with a history of a mid-trimester pregnancy loss or early
premature delivery.
1118 l DECEMBER JOGC DÉCEMBRE 2013
Data from the UK  MRC/RCOG  RCT36 did not
demonstrate the benefit of cerclage after 1 or 2 prior
deliveries preceding 33 weeks’ gestation; however, the
numbers were small and this might have had an impact
on the observed effect, particularly in the case of mid-
trimester losses as opposed to premature deliveries. The
benefit of cerclage after 2 or 3 mid-trimester losses alone,
as opposed to losses and deliveries up to and including
33 weeks, is undefined. The findings of this UK study
might be influenced by the inclusion of cases in which
the treating obstetrician was unsure that the cerclage
would be of benefit. However, other smaller studies
also failed to demonstrate the benefit of cerclage.37,38 A
recent Cochrane review analyzed data from 12 studies
of women considered at sufficient risk to justify cerclage
who were randomized to cerclage, alternative treatments
(e.g., progesterone), or no treatment. This analysis
presents somewhat conflicting findings in reporting that
cerclage has a statistically significant effect on reducing
gestational age at delivery and no significant impact on
perinatal morbidity and mortality, but it is associated with
increased maternal morbidity and Caesarean section rates
(the latter perhaps also accounting for a non-significant
increase in respiratory morbidity amongst infants born to
women with a cerclage).39
A prophylactic cerclage is normally placed between 12 and
14 weeks’ gestation. Although placement can be delayed,
the gestational age of prior pregnancy losses should be
taken into account, particularly in women whose losses
present at progressively earlier gestations.
Prerequisites for prophylactic cerclage placement
Prior to placement of a cerclage it is essential to confirm the
viability of the pregnancy by ultrasound. It is wise therefore,
at the same time to exclude significant malformations
and determine whether there is a significantly elevated
aneuploidy risk by first trimester ultrasound nuchal
translucency screening, if possible combined with serum
marker screening. In cases found to be at elevated risk
for aneuploidy or with fetal malformations, placement
may be delayed until after karyotype results are obtained
(using chorionic villus sampling for earlier karyotype
determination than amniocentesis, where available) or until
a more detailed ultrasound assessment is performed.
Before admission for cerclage, urinalysis for culture and
sensitivity and vaginal cultures for bacterial vaginosis should
be taken and any infections found should be treated.16,40–46
Microbial invasion of the amniotic cavity has been reported
to occur in around 50% of women with cervical insufficiency
and exposed fetal membranes.45,47 Amniocentesis has therefore
been suggested for evaluating and treating such colonization

prior to cerclage placement; however, no clear benefit in
prolonging pregnancy has been shown for amniocentesis over
cerclage alone, and therefore its routine use is not advised.48
Cerclage techniques and materials
The two main techniques of transvaginal cerclage involve
the MacDonald approach and the Shirodkar approach. In
the McDonald approach the suture is inserted as close as
possible to the junction of the cervix with the vagina, with no
dissection of tissue planes.49 In the Shirodkar approach a sub-
epithelial suture is inserted above the junction of the cervix
with the vagina with dissection of the bladder and rectum;
this allows for higher placement (closer to the internal cervical
os) of the suture than the McDonald approach.50
There are no data to indicate an advantage of one
technique over another, so the choice between a McDonald
approach or modification thereof or a Shirodkar approach
or modification thereof should be left to the discretion
and skills of the surgeon.51–55 Both techniques, influenced
by patient selection, are associated with an increased
Caesarean section rate, which is perhaps marginally higher
following the Shirodkar approach, although this data has
not been replicated.56
Two forms of double cerclage are also described. The first
simply involves the insertion of two cervical cerclages in
an attempt to buttress the cervix more strongly. This has
been shown to be of no benefit.57 In the second double
cerclage, a second occlusive suture is placed at the external
os to retain the mucous plug and help the cervix maintain
itself as a barrier to infection. Only limited data regarding
this are available at present.58
No data indicate any advantage or disadvantage of particular
suture materials. The most frequently used is a braided
Mersilene tape, although some surgeons use Prolene.
Meshes are also reportedly used, but no comparisons have
been made with existing techniques.59,60 There are data
indicating that delayed absorbable suture materials may
also be used, but the benefits or disadvantages of different
materials still require greater evaluation.61
Unless it is contraindicated, regional anaesthesia is usually
preferred to general anaesthesia in light of its lesser
associated risks.62,63
It should be noted that for prophylactic cerclage, no
randomized trials have presented findings free of
confounding variables to support the routine use of
tocolytics,64,65 corticosteroids, or antibiotics,66–68 although
for cerclages placed in gestations close to fetal viability,
corticosteroid usage should be considered. Similarly,
data on the use of progesterone in women who have a
Cervical Insufficiency and Cervical Cerclage
cerclage in place are limited. The use of progesterone
with cerclage is not new, but despite more recent data
for the use of progesterone therapy in women at risk of
preterm delivery, overall data do not presently support
this approach. Although one early study implied a benefit
to progesterone, it was an uncontrolled cohort study,69
and a contemporaneous controlled cohort evaluation
demonstrated a reduction in hospital admission, but not
in the rate of pregnancy loss.70 A more recent study of
17-alpha-hydroxyprogesterone caproate in women with
cerclage essentially demonstrated no advantage, although
this study was retrospective and the criteria for cerclage
placement were ill-defined.71 Two further studies also
indicated that 17-alpha-hydroxyprogesterone caproate
injections do not provide additional benefit for the
prevention of preterm birth in women who received an
ultrasound-indicated cerclage.72,73
There are no specific data comparing the efficacy of systemic
and vaginal progesterones in women with a cerclage in place.
Complications
Three randomized clinical trials have shown that cerclage
is associated with increased medical interventions and
doubles the risk of puerperal pyrexia.36–38 The use of
tocolytics increases with cerclage, as does the rate of
hospital admissions, and one study found a higher rate
of Caesarean sections.37 However, the risk and nature of
complications is influenced by whether the cerclage is
inserted electively or as an emergency with membranes
bulging through the cervix. The complications reported
with cerclage include sepsis, premature rupture of
membranes, premature labour, cervical dystocia,
cervical laceration at delivery (11% to 14%),74–76,77 and
hemorrhage.
However, meta-analysis of a number of studies has not
confirmed higher rates of chorioamnionitis or preterm
pre-labour membrane rupture in women managed with
cerclage than in those managed by other means.78 Although
cervical dystocia is frequently cited as a complication of
cerclage due to cervical scarring,79 data do not support
its being truly attributable to cerclage80; the increased risk
of cervical laceration, however, although it appears to be
unrelated to the timing of the removal of the cerclage, can
be attributed to the cerclage.74–76,81
Recommendations
3. In women with a history of cervical insufficiency,
urinalysis for culture and sensitivity and vaginal
cultures for bacterial vaginosis should be taken at
the first obstetric visit and any infections so found
should be treated. (I-A)
DECEMBER JOGC DÉCEMBRE 2013 l 1119
SOGC Clinical Practice Guidelines
4. Women with a history of three or more second
trimester pregnancy losses or extreme premature
deliveries, in whom no specific cause other than
potential cervical insufficiency is identified, should
be offered elective cerclage at 12 to 14 weeks of
gestation. (I-A)
Cerclage follow-up
Lengthening of the cervix following cerclage has been
observed, and the immediate assessment of the cervix
following suture placement may correlate with gestational
age at delivery82–84; however, the data are inconsistent on
the efficacy of continued cervical length assessment post
cerclage in determining when delivery might occur.85,86
This is somewhat supported by the inconsistency in
studies evaluating whether the placement of a second
suture is beneficial in women whose cervix is found to
shorten further post cerclage placement, with two studies
demonstrating contradictory effects of such a measure.87,88
Therefore at present routine post-cerclage follow-up by
ultrasound is not recommended. The positive predictive
value of fibronectin as a predictor of preterm delivery
appears to be adversely affected by a cerclage, although the
negative predictive value is not.89
Removal of cerclage
The cerclage is generally removed electively at 36 to 38
weeks’ gestation. Removal can usually be performed
without anaesthesia or with only short-acting narcotics,
such as Fentanyl administered intravenously. The onset of
premature labour unresponsive to tocolysis and or a strong
suspicion of sepsis are indications for emergency removal
of the cerclage.
A number of studies have addressed the question of
cerclage removal with premature membrane rupture and
no associated contractions. Meta-analysis has shown an
increased neonatal mortality rate with delayed removal,
with sepsis the principal cause; therefore a policy of
removal within 48 hours (allowing time for corticosteroid
administration if appropriate) is advocated.90–93 C-reactive
protein estimation may be used as a predictor of
chorioamnionitis following preterm membrane rupture
and may therefore aid the decision between immediate
or delayed (< 48 hours) suture removal.94,95 Incidentally, it
should be noted that clear documentation of the cerclage
placement, specifically knot placement and number, will
facilitate the removal of the cerclage prior to delivery.
Prophylactic Transabdominal Cerclage
In women with a good history of cervical insufficiency
in whom prior vaginal cerclage has been unsuccessful,
abdominal cerclage can be considered in the absence of
1120 l DECEMBER JOGC DÉCEMBRE 2013
additional mitigating factors.96–100 This should also be
considered for women who have undergone trachelectomy
or who have had an effective trachelectomy.101,102 The
placement of an abdominal suture may be undertaken by
either laparoscopic or open surgical techniques. The former
is generally preferred in current practice,103,104 although both
techniques are associated with higher maternal morbidity
than a transvaginal cerclage approach. Abdominal cerclage
should be undertaken by a surgeon experienced in the
placement of such sutures. A prophylactic abdominal
cerclage is often inserted at the same time as a trachelectomy
is performed in women of reproductive age who plan to
pursue the option of childbirth.105
Recommendations
5. In women with a classic history of cervical
insufficiency in whom prior vaginal cerclage has
been unsuccessful, abdominal cerclage can be
considered in the absence of additional mitigating
factors. (II-3C)
6. Women who have undergone trachelectomy should
have abdominal cerclage placement. (II-3C)
Emergency Cerclage
An emergency (or salvage or rescue) cerclage is typically one
placed in a woman whose cervix is already dilated. Emergency
should be considered when there is clinical or sonographic
identification of a cervix dilated > 1 to 2 cm with no
perceived uterine contractions (with or without membranes
bulging through the external os).106,107 It is important to note
that there must be no clinical evidence of chorioamnionitis.
Although some groups advocate amniocentesis prior to
emergency cerclage in order to both exclude infection and
aid in reducing intrauterine pressure, no randomized studies
confirm the effect of this approach.108,109
A small randomized clinical trial has shown prolongation
of pregnancies by 4 weeks with emergency cerclage
placement,110 and other observational studies have reported
pregnancy prolongation of between 6 and 9 weeks with
emergency cerclage placement compared with under 4
weeks with conservative management (bed rest).111–114
Scoring systems have been considered to evaluate which
cases will benefit from emergency cerclage (based on cervical
effacement, dilatation, and membrane prolapse).115,116 The
benefit of cerclage even with cervical dilatation to 4 cm
has been shown and should be considered, and the scoring
systems can be used to counsel patients about the likely
outcome of undergoing emergency cerclage.
Adjunctive measures
The administration of a course of indomethacin prior to
cerclage placement might reduce protruding membranes

through its effect on reducing fetal urine production
(thereby reducing intrauterine pressure) and through its
tocolytic value.110 Bed rest with or without Trendelenburg
may further help to reduce bulging membranes and
facilitate suture placement, as may using a Foley balloon
inserted into the cervix and then inflated to mechanically
reduce the membranes.117 Broad-spectrum antibiotic
coverage is usually prescribed, although there are no data
to support this.
Amniocentesis may have a greater role to play in emergency
cerclage than in prophylactic cerclage. The first potential
benefit of amniocentesis in emergency cases is in identifying
those women who may not benefit from cerclage, based
upon evidence of infection109 or on a more complex
evaluation of proteonomic markers that investigates
infection as well as other factors believed to affect the
efficacy of cerclage.109,118 Its second benefit is in removing
a larger volume of amniotic fluid (cf. amniodrainage),
permitting bulging membranes to withdraw into the cervix
by reducing intrauterine pressure and thereby facilitating
cerclage placement.119–121
Cerclage removal
The criteria for removal of an emergency cerclage are the
same as for a prophylactic cerclage.
Recommendation
7. Emergency cerclage may be considered in women
in whom the cervix has dilated to < 4 cm without
contractions before 24 weeks of gestation. (II-3C)
Cervical Pessary
The use of pessaries in the management of cervical
insufficiency or preterm delivery is not new, with the use
of a glass pessary having first been described in 1977.122
Since then various designs and materials have been used
and reported.123–129 Although many of these reports and
reviews showed promise, a Cochrane review found no
studies suitable for inclusion in an analysis of the benefits
of this technique.35 Since then a number of studies have
been undertaken, some of which are still in progress. Two
recent studies have again suggested a benefit of cervical
pessaries in the management of cervical insufficiency,
preterm delivery, or short cervix.130,131 However, to date the
data supporting such techniques in the routine management
of cervical insufficiency remain insufficient.
CONSERVATIVE OBSERVATIONAL MANAGEMENT
A conservative strategy including cervical length assess­
ment may be adopted in the management of women
considered to have cervical insufficiency, but whose
Cervical Insufficiency and Cervical Cerclage
history is not considered to indicate enough risk to
warrant immediate prophylactic cerclage.132 In such
women, ultrasound cervical length assessment will
identify a cohort who is at increased risk of a further
pregnancy loss or preterm delivery, some of whom
may then benefit from the subsequent placement of a
cerclage. Conservative management should be based on
and include the following steps:
1. Urine for culture and sensitivity and vaginal cultures
for bacterial vaginosis40–42 should be taken at the first
obstetric visit, and any infections found should be
treated.16,40–46
2. Serial transvaginal ultrasonography should be
performed every 7 to 14 days from 16 weeks of
gestation or at least 2 weeks prior to the gestational age
of the earliest preceding pregnancy loss.133
3. Consider advising the patient to reduce physical
activity, especially those with physical employment,
prolonged periods of standing, or frequent and
repetitive lifting, although there are no data to
confirm or deny the efficacy of bed rest in such
cases.134
4. Strongly encourage the cessation of smoking with
referral to support programs.
5. Beyond 23 weeks consider the prophylactic
use of corticosteroids if there are signs or
symptoms suggestive of an increased risk of
preterm delivery.
Ultrasound assessment of cervical length
Ultrasound has been shown reliably and reproducibly to
allow estimation of cervical length. The length of the cervix
as measured by ultrasound has in turn been demonstrated
to be a useful tool in the prediction of the risk of preterm
delivery.12,25,33,135 Transvaginal ultrasonography is the gold
standard technique of assessment, but if this cannot
be performed then an assessment may be made either
abdominally or transperineally.136
Assessment of the cervix typically reports the cervical
length and identifies any evidence of cervical funnelling.
Although funnelling is typically reported when the cervix
is assessed, it should be noted that data do not support
the placement of a cerclage on the basis of funnelling, but
rather on residual cervical length.12 Transfundal pressure
created by applying fundal pressure in the direction of
the uterine axis for 15 seconds is more effective than
coughing or standing in eliciting cervical changes and signs
of progressive second trimester cervical shortening during
active assessment of the cervix.137–139
DECEMBER JOGC DÉCEMBRE 2013 l 1121
SOGC Clinical Practice Guidelines

Flow diagram

Women with prior history suggestive of cervical insufficiency

or
presenting with cervical shortening or dilatation in the absence of contractions

1 or 2 mid-trimester Cervix more than 1 cm

Women presenting in the first or early dilated
second trimester with 3 or more losses or pretem
deliveries
mid-trimester losses or preterm births

Consider abdominal
suture if previous
Vaginal cerclage
vaginal cerclage
unsuccessful or if
inadequate cervical
tissue to place
cerclage
If no chorioamnionitis If contracting manage
Expectant or contractions as threatened preterm
management
consider emergency labour
Serial cervical length cerclage Consider tocolysis and
assessment Consider steroids steroids depending on
depending on the gestational age
gestational age

If cervical length below

2.5 cm at less than
24 weeks, consider
cervical cerclage OR
progesterone therapy

Recommendations insufficiency if the cervical length is ≤ 25 mm

8. Women in whom cerclage is not considered or
justified, but whose history suggests a risk for
cervical insufficiency (1 or 2 prior mid-trimester
losses or extreme premature deliveries), should
be offered serial cervical length assessment by
ultrasound. (II-2B)
Cerclage Based on Ultrasound
Measurement of Cervical Length
Data do not support the placement of a cerclage in women
in whom there is an incidental finding by ultrasound of
cervical shortening (≤ 25 mm) and who are not otherwise
considered to be at risk of mid trimester loss or of preterm
delivery.140–142 Women considered to be at risk (because,
e.g., of a history of mid-trimester loss or early preterm
delivery) should be offered cerclage if their cervical length
is ≤ 25 mm before 24 weeks of gestation.140,143–147
Recommendations
9. Cerclage should be considered in singleton
pregnancies in women with a history of
spontaneous preterm birth or possible cervical
before 24 weeks of gestation. (I-A)
10. There is no benefit to cerclage in a woman with an
incidental finding of a short cervix by ultrasound
examination but no prior risk factors for preterm
birth. (II-1D)
Progesterone
Progesterones have been used historically and more
recently in the prevention of preterm birth. The possible
efficacy of progesterones in cervical insufficiency has
often been extrapolated from that in preterm birth, but
this may not be appropriate.
At present no data support the use of progesterone together
with cerclage. The data comparing cerclage and progesterone
in isolation are limited and perhaps inapplicable to the
question of using progesterones for cervical insufficiency.
One study reported no significant difference in the rate of
preterm birth between women treated with progesterone
or by cerclage; however, the indication for intervention was
a short cervix on ultrasound screening, and by the criteria
presented in this guideline, cerclage would not have been

1122 l DECEMBER JOGC DÉCEMBRE 2013


indicated in many of the cases included.148 However, a study
evaluating the effects of progesterone on cervical length in
women considered at risk of preterm birth suggests that
progesterone helps preserve cervical length,70 and thereby
reduces the risk of preterm birth; this finding also supports the
use of vaginal progesterones.149,150 The role of progesterone
in mid-trimester loss remains unclear, therefore its routine use
is not recommended and further evaluation is needed. Further
information regarding the use of progesterones to prevent
preterm birth may be found in the SOGC guideline, “The
Use of Progesterone for Prevention of Preterm Birth.”151
Multiple Gestations
Because twins and higher-order multiple gestations are at
increased risk of preterm delivery, it has been speculated
that cerclage placement may improve their perinatal
outcomes. However, elective cerclage placement in multiple
pregnancies without additional risk factors has not been
shown to benefit pregnancy outcomes in this group.152
Furthermore, although ultrasound cervical length
assessment in this group may predict an increased risk
of early delivery,153 in contrast to singleton gestations,
data have shown no benefit in the placement of cerclage
in multiple gestations with ultrasound-identified cervical
shortening.143,154,155 Indeed, a meta-analysis has shown a
relative risk increase of 2.15 for preterm delivery (< 35
weeks) in such pregnancies with an ultrasound-indicated
(cervical length < 25 mm) cerclage.143
Recommendations
11. Present data do not support the use of elective
cerclage in multiple gestations even when there is a
history of preterm birth; therefore, this should be
avoided. (I-D)
12. The literature does not support the insertion of
cerclage in multiple gestations on the basis of
cervical length. (II-1D)
SUMMARY
The decision on how best to minimize the risk of
recurrent mid-trimester pregnancy loss (loss between 14
and 26 weeks) or extreme preterm birth in women who are
deemed at increased risk, either by virtue of their medical
history or the findings of a short or dilated cervix, should
be personalized, based on the clinical circumstances, the
skills and expertise of the clinical team, and the woman’s
informed consent (Figure).
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Hanley ML. The natural history of a positive response to transfundal
pressure in women at risk for cervical incompetence. Am J Obstet Gynecol
1997;176:634–8.
139. Guzman E, Rosenberg J, Houlihan C, Ivan J, Waldron R, Knuppel R.
A new method using vaginal ultrasound and transfundal pressure to
evaluate the asymptomatic incompetent cervix. Obstet Gynecol
1994;83:248–52.
140. Berghella V, Keeler SM, To MS, Althuisius SM, Rust OA. Effectiveness of
cerclage according to severity of cervical length shortening: a meta-analysis.
Ultrasound Obstet Gynecol 2010;35:468–73.
141. Incerti M, Ghidini A, Locatelli A, Poggi SH, Pezzullo JC. Cervical length
< or = 25 mm in low-risk women: a case control study of cerclage with rest
vs rest alone. Am J Obstet Gynecol 2007;197:315e1–e4.
142. To MS, Alfirevic Z, Heath VC, Cicero S, Cacho AM, Williamson PR, et al.
Cervical cerclage for prevention of preterm delivery in women with short
cervix: randomised controlled trial. Lancet 2004;363:1849–53.
143. Berghella V, Odibo AO, To MS, Rust OA, Althuisius SM. Cerclage for short
cervix on ultrasonography: meta-analysis of trials using individual patient-
level data. Obstet Gynecol 2005;106:181–9.
144. Berghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage for
short cervix on ultrasonography in women with singleton gestations
and previous preterm birth: a meta-analysis. Obstet Gynecol
2011;117:663–71.

145. Heath VC, Souka AP, Erasmus I, Gibb DM, Nicolaides KH. Cervical length
at 23 weeks of gestation: the value of Shirodkar suture for the short cervix.
Ultrasound Obstet Gynecol 1998;12:318–22.
146. Hibbard JU, Snow J, Moawad AH. Short cervical length by ultrasound and
cerclage. J Perinatol 2000;20:161–5.
147. Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A,
et al. Multicenter randomized trial of cerclage for preterm birth prevention
in high-risk women with shortened midtrimester cervical length. Am J
Obstet Gynecol 2009;201:375 e1-e8.
148. Keeler SM, Kiefer D, Rochon M, Quinones JN, Novetsky AP, Rust O.
A randomized trial of cerclage vs. 17 alpha-hydroxyprogesterone caproate
for treatment of short cervix. J Perinat Med 2009;37:473–9.
149. Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M,
et al. Vaginal progesterone reduces the rate of preterm birth in
women with a sonographic short cervix: a multicenter, randomized,
double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol
2011;38:18–31.
150. Romero R, Nicolaides K, Conde-Agudelo A, Tabor A, O’Brien JM,
Cetingoz E, et al. Vaginal progesterone in women with an asymptomatic
sonographic short cervix in the midtrimester decreases preterm delivery
and neonatal morbidity: a systematic review and meta-analysis of individual
patient data. Am J Obstet Gynecol 2012;206:124 e1–e19.
Cervical Insufficiency and Cervical Cerclage
151. Farine D, Mundle WR, Dodd J, Basso M, Delisle MF, Farine D, et al.
The use of progesterone for prevention of preterm birth. J Obstet
Gynaecol Can 2008;30:67–77.
152. Dor J, Shalev J, Mashiach S, Blankstein J, Serr DM. Elective
cervical suture of twin pregnancies diagnosed ultrasonically in
the first trimester following induced ovulation. Gynecol Obstet
Invest 1982;13:55–60.
153. Yang JH, Kuhlman K, Daly S, Berghella V. Prediction of preterm birth
by second trimester cervical sonography in twin pregnancies. Ultrasound
Obstet Gynecol 2000;15:288–91.
154. Newman RB, Krombach RS, Myers MC, McGee DL. Effect of cerclage
on obstetrical outcome in twin gestations with a shortened cervical length.
Am J Obstet Gynecol 2002;186:634–40.
155. Zucchini S, Borghesani F, Soffriti G, Chirico C, Vultaggio E,
Di Donato P. Transvaginal ultrasound diagnosis of twin reversed arterial
perfusion syndrome at 9 weeks’ gestation. Ultrasound Obstet Gynecol
1993;3:209–11.
156. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
DECEMBER JOGC DÉCEMBRE 2013 l 1127
 Clinical Practice Guidelines

No. 299, November 2013

Female Genital Cutting

This clinical practice guideline has been prepared by the
Social Sexual Issues Committee and the Ethics Committee,
and reviewed by the Clinical Practice Gynaecology
Committee, the Canadian Paediatric and Adolescent
Gynaecology and Obstetricians Committee, and the Family
Physicians Advisory Committee, and approved by the
Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Liette Perron, MSW, Ottawa ON
Vyta Senikas, MD, Ottawa ON
Margaret Burnett, MD, Winnipeg MB
Victoria Davis, MD, Scarborough ON
SOCIAL SEXUAL ISSUES COMMITTEE
Margaret Burnett, MD (Chair), Winnipeg MB
Anjali Aggarwal, MD, Toronto ON
Jeanne Bernardin, MD, Moncton NB
Virginia Clark, MD, Golden BC
Victoria Davis, MD, Scarborough ON
William Fisher, BA, MS, PhD, London ON
Rosana Pellizzari, MD, Peterborough ON
Viola Polomeno, RN, PhD, Ottawa ON
Maegan Rutherford, MD, Halifax NS
Jeanelle Sabourin, MD, Edmonton AB
ETHICS COMMITTEE
Jodi Shapiro, MD (Chair), Toronto ON
Saima Akhtar, MD, London ON
Bruno Camire, MD, Quebec QC
Jan Christilaw, MD, Vancouver BC
Julie Corey, RM, St Jacobs ON
Key words: Female genital cutting, female genital mutilation,
female circumcision, pregnancy, gynecological care, adolescents,
Canada.
Erin Nelson, LLB, LLM, Edmonton AB
Marianne Pierce, MD, Halifax NS
Deborah Robertson, MD, Toronto ON
Anne Simmonds, RN, PhD, Scotsburn NS
Disclosure statements have been received from all members of
the committees.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
Abstract
Objective: To strengthen the national framework for care of
adolescents and women affected by female genital cutting
(FGC) in Canada by providing health care professionals with:
(1) information intended to strengthen their knowledge and
understanding of the practice; (2) directions with regard to the
legal issues related to the practice; (3) clinical guidelines for the
management of obstetric and gynaecological care, including
FGC related complications; and (4) guidance on the provision of
culturally competent care to adolescents and women with FGC.
Evidence: Published literature was retrieved through searches of
PubMed, CINAHL, and The Cochrane Library in September
2010 using appropriate controlled vocabulary (e.g.,
Circumcision, Female) and keywords (e.g., female genital
mutilation, clitoridectomy, infibulation). We also searched Social
Science Abstracts, Sociological Abstracts, Gender Studies
Database, and ProQuest Dissertations and Theses in 2010 and
2011. There were no date or language restrictions. Searches
were updated on a regular basis and incorporated in the
guideline to December 2011. Grey (unpublished) literature was
identified through searching the websites of health technology
assessment and health technology-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: The quality of evidence in this document was rated using
the criteria described in the Report of the Canadian Task Force
on Preventive Health Care (Table 1).
J Obstet Gynaecol Can 2013;35(11):e1–e18

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

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Clinical Practice Guidelines
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.59
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.59
Summary Statements
01. Female genital cutting is internationally recognized as a harmful
practice and a violation of girls’ and women’s rights to life,
physical integrity, and health. (II-3)
02. The immediate and long-term health risks and complications of
female genital cutting can be serious and life threatening. (II-3)
03. Female genital cutting continues to be practised in many
countries, particularly in sub-Saharan Africa, Egypt, and
Sudan. (II-3)
04. Global migration patterns have brought female genital cutting to
Europe, Australia, New Zealand, and North America, including
Canada. (II-3)
05. Performing or assisting in female genital cutting is a criminal
offense in Canada. (III)
06. Reporting to appropriate child welfare protection services
is mandatory when a child has recently been subjected to
female genital cutting or is at risk of being subjected to the
procedure. (III)
07. There is concern that female genital cutting continues to be
perpetuated in receiving countries, mainly through the act of
re-infibulation. (III)
ABBREVIATIONS
BMA British Medical Association
FGC female genital cutting
FGM female genital mutilation
FIWG Federal Interdepartmental Working Group (on Female
Genital Mutilation)
HIV human immunodeficiency virus
IUD intrauterine device
SERC Sexuality Education Resource Centre (Manitoba)
e2 l NOVEMBER JOGC NOVEMBRE 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
08. There is a perception that the care of women with female genital
cutting is not optimal in receiving countries. (III)
09. Female genital cutting is not considered an indication for
Caesarean section. (III)
Recommendations
01. Health care professionals must be careful not to stigmatize
women who have undergone female genital cutting. (III-A)
02. Requests for re-infibulation should be declined. (III-B)
03. Health care professionals should strengthen their understanding
and knowledge of female genital cutting and develop greater
skills for the management of its complications and the provision
of culturally competent care to adolescents and women who
have undergone genital cutting. (III-A)
04. Health care professionals should use their knowledge and
influence to educate and counsel families against having female
genital cutting performed on their daughters and other family
members. (III-A)
05. Health care professionals should advocate for the availability of
and access to appropriate support and counselling services. (III-A)
06. Health care professionals should lend their voices to community-
based initiatives seeking to promote the elimination of female
genital cutting. (III-A)
07. Health care professionals should use interactions with patients
as opportunities to educate women and their families about
female genital cutting and other aspects of women’s health and
reproductive rights. (III-A)
08. Research into female genital cutting should be undertaken to
explore women’s perceptions and experiences of accessing
sexual and reproductive health care in Canada. (III-A) The
perspectives, knowledge, and clinical practice of health care
professionals with respect to female genital cutting should also
be studied. (III-A).
09. Information and guidance on female genital cutting should
be integrated into the curricula for nursing students, medical

students, residents, midwifery students, and students of other
health care professions. (III-A)
10. Key practices in providing optimal care to women with female
genital cutting include:
a. determining how the woman refers to the practice of
female genital cutting and using this terminology throughout
care; (III-C)
b. determining the female genital cutting status of the
woman and clearly documenting this information in her
medical file; (III-C)
c. ensuring the availability of a well-trained, trusted, and neutral
interpreter who can ensure confidentiality and who will not
exert undue influence on the patient–physician interaction
when providing care to a woman who faces language
challenges; (III-C)
d. ensuring the proper documentation of the woman’s medical
history in her file to minimize the need for repeated medical
histories and/or examinations and to facilitate the sharing of
information; (III-C)
e. providing the woman with appropriate and well-timed
information, including information about her reproductive
system and her sexual and reproductive health; (III-C)
f. ensuring the woman’s privacy and confidentiality by limiting
attendants in the room to those who are part of the health
care team; (III-C)
g. providing woman-centred care focused on ensuring that
the woman’s views and wishes are solicited and respected,
including a discussion of why some requests cannot be
granted for legal or ethical reasons; (III-C)
h. helping the woman to understand and navigate the
health system, including access to preventative care
practices; (III-C)
i. using prenatal visits to prepare the woman and her family for
delivery; (III-C)
j. when referring, ensuring that the services and/or practitioners
who will be receiving the referral can provide culturally
competent and sensitive care, paying special attention to
concerns related to confidentiality and privacy. (III-C)
Epub ahead of print.
This document will be published in:
J Obstet Gynaecol Can 2013;35(11)
INTRODUCTION
T here is no international consensus on what to call the
practice of physically altering girls’ and women’s genitals.
The current most commonly used terms in the literature
are “female circumcision,” “female genital mutilation,” and
“female genital cutting.” Although “female circumcision”
is used in many communities where FGC is prevalent, it is
problematic because it tends to equate the practice with male
circumcision. “Female genital mutilation,” formally adopted
and used in advocacy documents by the UN and WHO,
calls attention to the gravity and harm of the act, but some
consider the term judgemental and stigmatizing, especially
Female Genital Cutting
of the communities that practice FGC. In French, FGC is
often referred to as “excision”—a general term covering all
types of the practice. The term “female genital cutting” was
chosen for this document because it is considered medically
correct, neutral, and culturally sensitive. When reference
material or direct quotations from other authors are used,
their original terminology is retained.
Definition of Female Genital Cutting
WHO defines female genital mutilation as “all procedures
involving partial or total removal of the external female
genitalia or injury to the female genital organs for non-
medical reasons.”1 Genital tattooing, piercing, hair removal,
and labiaplasty could technically be included in the WHO
definition of Type IV FGM, but for the purpose of this
document, we define FGC as WHO Types I, II, and III.
Glossary
Cultural competence: “A set of congruent behaviors,
attitudes, and policies that come together in a system,
agency, or among professionals that enables the system
or professionals to work effectively in cross-cultural
situations.”2
Defibulation: Incision of the vulva to open the vagina of
a woman who has undergone infibulation.
Infibulation: Excision of part of the external genitalia and
stitching of the vulvovaginal opening to partially cover the
vaginal opening.
Medicalization: The “situations in which FGM is
practiced by any category of trained healthcare provider,
whether in a public or a private clinic, at home or
elsewhere. It also includes the surgical procedure of re-
infibulation at any time in a woman’s life.” (WHO, 2010).3
Re-infibulation: The re-suturing of the vulvar opening
that has been opened with defibulation.
Classification
WHO classifies FGM procedures into 4 types
(Table 2).1 The types of procedure vary considerably
across countries, within countries, and between ethnic
groups. It is estimated that most women with FGC
are subjected to clitorectomy (Type I), excision (Type
II), or “nicking,” in which no flesh is removed (Type
IV).1 Approximately 10% of women are subjected to
infibulation (Type III), the most severe form of the
procedure, practiced in Djibouti, Eritrea, Ethiopia,
Somalia, and Sudan.4
WHO recognizes that the definition of Type IV raises
a number of unresolved issues because some of the
NOVEMBER JOGC NOVEMBRE 2013 l e3
Clinical Practice Guidelines

Table 2. WHO modified typology, 2007

Type I Partial or total removal of the clitoris and/or the prepuce (clitoridectomy).
When it is important to distinguish between the major variations of Type 1 mutilation, the following subdivisions are proposed:
Type Ia, removal of the clitoral hood or prepuce only;
Type Ib, removal of the clitoris with the prepuce.
Type II Partial or total removal of the clitoris and the labia minora, with or without excision of the labia major (excision).
When it is important to distinguish between the major variations of Type II that have been documented, the following subdivision
are proposed:
Type IIa, removal of the labia minora only;
Type IIb, partial or total removal of the clitoris and labia minora;
Type IIc, partial or total removal of the clitoris, the labia minora, and the labia majora.
Type III Narrowing of the vaginal orifice with creation of a covering seal by cutting and appositioning the labia minora and/or the labia
majora, with or without excision of the clitoris (infibulations).
When it is important to distinguish between variations in infibulations, the following subdivisions are proposed:
Type IIIa, removal and apposition of the labia minora;
Type IIIb, removal and apposition of the labia majora.
Type IV Unclassified: all other harmful procedures to the female genitalia for non-medical purposes (e.g., pricking, piercing, incising,
scraping, and cauterization).
Reproduced with permission from the World Health Organization (WHO. Eliminating female genital mutilation: an interagency statement.
Geneva: WHO; 2008: p 24).

practices listed are legally accepted and not generally
considered FGM in many countries (e.g., genital cosmetic
surgery, hymen repair, piercing). WHO recommends
that in determining whether genital practices should be
categorized as FGM, human rights principles should
be applied, including the right of health, the rights of
children, and the right to non-discrimination on the basis
of sex.1
Prevalence in Canada
Although the magnitude of the practice of FGC in
Canada remains unknown, literature from as early as the
1990s confirms that FGC has been found among certain
immigrant communities.5–11 Table 3 brings together two
sets of data:
1. a list of countries in which FGC of Types I, II, III,
and IV has been documented as a traditional practice,1
and
2. Canadian immigration data related to the number of
permanent and temporary residents received in Canada
from 2005 to 2009 from countries in which FGC has
been documented.12
Although the Canadian immigration data should be
considered with caution, it provides insight into the
continual arrival in Canada of newcomers from countries
where the practice is prevalent, including adolescents and
women who may have undergone FGC and girls who may
be at risk.
While there is no evidence that any type of FGC is practiced
in Canada, there is concern that girls from practising
communities may still be at risk. In their exploratory study of
the perceptions of Somali women of their earlier experience
of FGC, Chalmers and Omer-Hashi13 found that only one
third of respondents supported the Canadian law prohibiting
the practice, while two thirds reported ambivalent feelings.
Furthermore, when asked “whether or not they would
(hypothetically) wish to have [their daughters] circumcised,”
almost half said they would. In their study exploring FGC as
it relates to gender identity and the acculturation process in
Canada, Vissandjée et al. were unable to determine whether
these practices had been abandoned by new arrivals to Canada;
their findings suggested that “the need to maintain a status
equal to that of the country of origin potentially increased
the risk of the practices being performed [on girls].”11 Finally,
SERC Manitoba, in their work with immigrants affected
by FGC, reported that women were split in their opinions
of the issue; although some women strongly supported
discontinuation of the practice, others either supported it
or remained conflicted about what should be done about
it.14 These findings are supported by a number of European
studies that show the practice is not necessarily abandoned
with migration and that girl children remain at risk.15–17
Summary Statement
1. Female genital cutting is internationally recognized
as a harmful practice and a violation of girls’
and women’s rights to life, physical integrity, and
health. (II-3)

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 Female Genital Cutting

Table 3. Countries in which female genital mutilation of Types I, II, III, and IV has been
documented as a traditional practice, and number of permanent and temporary residents
(both sexes) received in Canada from those countries in the years 2005 to 2009
Estimated prevalence of
FGM in girls and women Residents received
15 to 49 years in Canada
Country Year* % (2005 to 2009)12
Benin 2001 16.8 815
Burkina Faso 2005 72.5 632
Cameroon 2004 1.4 3790
Central African 2005 25.7 88
Chad 2004 44.9 481
Cote d’Ivoire 2005 41.7 2766
Djibouti 2006 93.1 313
Egypt 2005 95.8 10 482
Eritrea 2002 88.7 2391
Ethiopia 2005 74.3 7126
Gambia 2005 78.3 178
Ghana 2005 3.8 4071
Guinea 2005 95.6 1643
Guinea-Bissau 2005 44.5 N/A
Kenya 2003 32.2 3389
Liberia† 45.0 424
Mali 2001 91.6 629
Mauritania 2001 71.3 272
Niger 2006 2.2 298
Nigeria 2003 19.0 11 259
Senegal 2005 28.2 1878
Sierra Leone 2005 94.0 406
Somalia 2005 97.9 4596
Sudan, Northern (approx. 80% of 2000 90.0 3752
total population in survey)
Togo 2005 5.8 701
Tanzania 2004 14.6 1115
Uganda 2006 0.6 1113
Yemen 1997 22.6 888
*Year of national data reports from which the data were derived.
†Estimate derived from a variety of local and sub-national studies.
Columns 1, 2, and 3 reproduced with permission of the World Health Organization. (WHO. Eliminating female genital mutilation:
an interagency statement. Geneva: WHO; 2008: p 29).

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Clinical Practice Guidelines

Table 4. Recognized complications and risks of female genital cutting1

Immediate risks of Types I, II, and III
Pain due to the cutting of the nerves and
sensitive genital tissues
Shock caused by pain and/or hemorrhage
Excessive bleeding
Difficulty in passing urine/ passing feces
Infections
Increased risk of blood borne viral
infections including hepatitis and HIV
due to the use of unsterilized and shared
instruments
Death
Psychological consequences
Unintended labial fusion
Re-infibulation due to unsuccessful healing
Long-term risks of Types I, II, and III Additional risks associated with Type III
Chronic pain due to trapped or unprotected Surgery to enable penetration during sexual
nerves intercourse and for childbirth, and sometimes
re-infibulation
Epithelial inclusion cysts
Inability to have intercourse
Infections (i.e. abscesses and genital
ulcers; chronic pelvic infections; urinary Infertility
tract infections)
Dysmenorrhea due to outflow obstruction
Keloid formation
Endometriosis
Sexually transmitted infections, especially
Difficulty voiding
genital herpes
Difficulty using tampons, diaphragms,
Increased risk of blood-borne viral
pessaries, etc.
infections including hepatitis and HIV
due to genital trauma during intercourse Difficulty with speculum examinations
(especially for Type III)
Difficulty accessing Pap smear screening and
Sexual dysfunction (i.e. decreased sexual other gynaecological procedures requiring
pleasure, pain during sex) vaginal access (cervical cultures, endometrial
biopsy, IUD placement, etc.)
Vulvar or vaginal lacerations with
intercourse or childbirth
Increased Caesarean section rates,
obstructed labour
Psychological consequences (i.e. fear of
sexual intercourse, post traumatic stress
disorder, anxiety, depression and memory
loss)

Immediate and Long-term Complications Impact on Women and Adolescents

FGC is usually performed on girls between the ages
of 5 and 12, although infants and adult women are
sometimes subjected to the procedure. Typically, the
child is forcibly held while the excision is done using a
razor blade, piece of broken glass, or knife. Infibulation
may involve stitching or pinning the labia. The girl’s legs
are usually bound together to promote closure of the
cut edges of the incision(s). Anaesthetic is not typically
used, and the struggles of the child may aggravate the
genital trauma. It should be noted that many women do
not experience any long-term complications from the
procedure.
The immediate health risks and consequences of FGC
can, however, be serious and life-threatening to girls
and women. Complications vary according to the type
of procedure conducted and the conditions under
which FGC is performed (e.g., hygienic conditions,
instruments used, experience of the practitioner).1,18
Table 4 provides a synopsis of the immediate and
long-term health complications of FGC/FGM from
types I, II, and III as compiled by WHO.1 Health care
professionals in receiving countries tend to address
the long-term complications of FGC, especially those
related to Types II and III.18
Living in Receiving Countries
While the health and psychological effects of FGC have
been documented in sub-Saharan Africa, research on the
impact of the practice on women’s well-being and health
outcomes in countries of migration is limited. Berggren et
al.19 found that women who had undergone FGC and were
now living in Sweden “expressed a double shame at being
different”: shame in their countries of origin if they had
not undergone the procedure, but also shame in Sweden
if they had been subjected to it. These feelings of shame
contributed to their increased sense of vulnerability in
their encounters with Swedish maternity care and to their
further negative experiences in accessing care. In a study
exploring the birthing experiences of Somali women in
Ontario, Chalmers and Omer-Hashi reported a Caesarean
section rate of over 50%.13 Vangen et al., in reviewing the
Norwegian Medical Registry data, found the frequency of
emergency Caesarean section among ethnic Somalis (15%)
was triple that of ethnic Norwegians.20 Other perinatal
complications in immigrant Somali women in Norway
included induction of labour, fetal distress, secondary
arrest, prolonged second stage of labour, and perinatal
death. Although both authors recognized difficulties in
ascertaining whether the adverse birth outcomes were

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caused by FGC or other factors, their findings suggested
that Somali women represented a higher risk group in
obstetrics.20 Finally, Bragg,21 in reviewing the results of the
2003–2005 UK Confidential Enquiry into Maternal and
Children Health noted that maternal mortality was 6 times
higher in black African women than in white women in
the United Kingdom. Among the new factors documented
as potential contributing causes were unsatisfactory
arrangements for interpretation and lack of health care
provider awareness of FGC.
Little is known of how FGC affects the psychological
well-being of girls and adolescents.22,23 Anecdotal evidence
suggests that the girls and/or adolescents’ concerns about
the practice “are very much intertwined with other concerns
common to all adolescents regarding sexuality, body image,
attractiveness, identity, belonging and conforming with
peers.”22
Traditional and Cultural Beliefs, Values,
and Attitudes Upholding the Practice
The practice continues to be perpetuated due to an array of
complex social, religious, and cultural reasons intrinsically
linked to traditional beliefs, values, and attitudes related
to women’s sexuality and the perceived need to control
their sexual and reproductive capacity.24 Parents submit
their daughters to FGC not as means of punishment or
abuse, but as a way to protect them and give them “the
best possible chance to have a future that will ensure
[their] social acceptance and economic security.”25 FGC
is performed in order to prepare girls for adulthood and
marriage, to ensure their virginity until marriage, to ensure
their fidelity in marriage, to make them clean, beautiful,
and pure, and to maintain the family’s honour. In certain
communities, it is seen as a rite of passage or an initiation
into a secret women’s society; in others it is thought to
increase fertility and to enhance the sexual pleasure of
men.
FGC is often performed by “older women who carry on
the tradition and make sure girls in their family undergo
the practice.”15 Men play a role by remaining passive
and not intervening in matters related to the practice, by
preferring to marry a woman who has undergone FGC,
or by insisting that it is performed on their daughters.11,15,26
Summary Statements
2. The immediate and long-term health risks and
complications of female genital cutting can be
serious and life threatening. (II-3)
3. Female genital cutting continues to be practised in
many countries, particularly in sub-Saharan Africa,
Egypt, and Sudan. (II-3)
Female Genital Cutting
4. Global migration patterns have brought female
genital cutting to Europe, Australia, New Zealand,
and North America, including Canada. (II-3)
Recommendations
1. Health care professionals must be careful not to
stigmatize women who have undergone female
genital cutting. (III-A)
2. Requests for re-infibulation should be declined. (III-B)
3. Health care professionals should strengthen
their understanding and knowledge of female
genital cutting and develop greater skills for the
management of its complications and the provision
of culturally competent care to adolescents and
women who have undergone genital cutting. (III-A)
Legal Issues Related to FGC in Canada
FGC is illegal in Canada and anyone who performs or
assists with the practice can be criminally charged and
convicted. The Criminal Code also makes it a crime for
parents or family members to take a girl out of Canada for
the purpose of having FGC/FGM performed elsewhere.
Appendix 1 provides the main sections of the Canadian
Criminal Code that state that anyone who “wounds” or
“maims” a female person by excision, infibulation, or
mutilation of the labia or clitoris is committing aggravated
assault. Exceptions are made for surgery conducted for
legitimate medical reasons.
Although not explicitly mentioned in any Canadian provincial
child welfare legislation, the Federal Interdepartmental
Working Group on Female Genital Mutilation considered
FGC “a form of child physical abuse and as such, any child
suspected of being at risk of the practice would justify
intervention by child protection authorities.”8 Because FGC
is a recognized violation of human rights, a child or woman
at risk for FGC has a legitimate claim for asylum.8
Statements and Policies of
Provincial Medical Organizations in Canada
Appendix 2 provides information related to the position
statements or directives issued by provincial medical
organizations that have addressed the subject of FGC.
These professional organizations have consistently
condemned the practice of FGC and make it clear that
a physician who engages in this practice is guilty of
professional misconduct.
Challenges in Responding to the Health
Needs of Women and Adolescents with FGC
In a study exploring the birthing experience of Somali
women in Ontario, Chalmers and Omer-Hashi found
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Clinical Practice Guidelines
that although not all women had negative experiences
in accessing health care, many considered the care not
optimal, and further reported that “they were treated in
ways that they perceived harsh and even offensive to [their]
cultural values.”13 Women’s reported concerns were mainly
with lack of services and care including assistance with
baby care, especially when they were in pain due to their
FGC; warm, caring, and sympathetic staff; privacy during
labour and in the wards; confidence in the capacity of the
clinicians to provide adequate care; and appropriate clinical
care, including the ability to refuse what they considered
unwarranted Caesarean sections.
A consultation process undertaken in 2000 by the FIWG
with community and health care providers identified the
following as key health care issues affecting women with
FGC in Canada: their lack of knowledge of the health
consequences of the practice and the relation of FGC to
their own health symptoms; differences in their health-
seeking behaviours and practices from those of other
women in Canada; their reluctance to seek health care due to
lack of knowledge of how the system works; their distrust
of authority figures (especially if they have experienced
political prosecution); past adverse experience with health
care providers; preference for women physicians; financial
barriers; difficult and traumatic experiences in accessing care
due to language and cultural barriers; lack of confidentiality
and health care providers’ lack of training of in how to
deal with complications of FGC; and issues related to
what affected women considered the high Caesarean
section rate at childbirth.8 These factors deter women with
FGC and their families from seeking care until absolutely
necessary.8,10,27 Studies exploring the perceptions of women
with FGC in the United States, Europe, and Australia of the
perinatal care they received report similar findings.28–33
Recent European studies shed light on the experiences
and clinical practices of health providers providing care
to women with FGC and how these contribute to the
quality of care provided. Vangena et al. (2002)28 found
that health care providers in Norway faced difficulties
initiating discussion about the practice with women; lacked
clinical skills in how and when to defibulate women and
in determining the extent of repair after delivery; and at
times performed Caesarean sections because they lacked
knowledge related to care management. Widmark et al.34
and Johansen35 reported that health care providers found
providing care to infibulated women at childbirth especially
stressful and emotionally challenging. Of particular
concern were the strong emotional and sometimes
contradictory feelings of health providers, which included
“deep empathy, protectiveness and the desire to treat the
e8 l NOVEMBER JOGC NOVEMBRE 2013
circumcised women with extra care”, but also anger and
hatred “towards tradition, religion, men and especially the
husbands.”34 Significant gaps in both theoretical knowledge
and practice related to FGC were found among health
professionals in United Kingdom, Sweden, Spain, and the
United States.36–39
Summary Statements
5. Performing or assisting in female genital cutting is a
criminal offense in Canada. (III)
6. Reporting to appropriate child welfare protection
services is mandatory when a child has recently been
subjected to female genital cutting or is at risk of
being subjected to the procedure. (III)
7. There is concern that female genital cutting
continues to be perpetuated in receiving countries,
mainly through the act of re-infibulation. (III)
8. There is a perception that the care of women with
female genital cutting is not optimal in receiving
countries. (III)
CLINICAL MANAGEMENT OF
WOMEN LIVING WITH FGC
Gynaecologic Care
Women experiencing distressing symptoms related to vaginal
obstruction or mass effect, or those considering intercourse
or pregnancy can be offered surgery, defibulation, or excision.
For defibulation, under general anaesthesia, the infibulated
scar is incised in the midline from the neo-introitus to the
level of the urethral orifice using scissors, coagulation/
cutting, or laser.40 The labial edges may need interrupted
sutures to ensure hemostasis and/or approximation of
the ipsilateral labial edges. Postoperatively, topical analgesic
gels can help with pain relief, as can generous application
of lubricants and frequent sitz baths. Estrogen cream
and topical antibiotic ointment may also be helpful.
Unfortunately, because FGC is not reversible some of its
complications may not be amenable to therapy. Vaginal
dilators may be appropriate for some women. Vaginal calibre
is best sustained, postoperatively, when the woman is willing
to use gentle vaginal dilation to help prevent re-stenosis of
the introitus. Additional guidance related to defibulation is
available in the online WHO document entitled Management
of Pregnancy, Childbirth and the Postpartum Period in the
Presence of Genital Mutilation.41
Contraceptive measures remain the same as for other
women. Infertility rates may be higher in women who have
undergone FGC.42 The incidence of infertility appears
to be related to the extent of FGC. Introital stenosis can
make intercourse difficult or impossible, and there may be
tubal damage from infection or endometriosis. Artificial

reproductive technologies can be more challenging in
a woman with FGC because of the need for a vaginal
approach (hysterosonogram, intrauterine insemination,
trans-vaginal ovum retrieval).
It is important for health care professionals to avoid
verbal and non-verbal reactions to women with FGC
that may make the women feel stigmatized. Well-woman
examinations and cervical screening need to be fully
explained so the woman understands the need for the tests.
A wide variety of small, narrow specula should be available
to perform the exam with the least amount of discomfort.
The use of a lubricant is encouraged.
Obstetrical Care
Most forms of FGC do not directly impact obstetrical
care. Infibulation may cause obstructed labour and
is associated with an increased risk of vaginal/vulvar
lacerations. When treating pregnant and labouring women
it is important to demonstrate a professional and non-
judgemental approach to FGC. Many of these women
originate from communities where FGC is the norm. They
are used to the way their genitals feel and look. They may
be fearful of the changes that may occur as a result of
the delivery, particularly if the delivery is conducted by
someone who is not familiar with FGC. If defibulation will
be necessary to allow vaginal birth, it can be performed in
advance or at the time of delivery. There may be medical
indications to offer defibulation in advance to decrease the
incidence of Caesarean section.43 However, many women
prefer to wait until delivery and have defibulation only if
absolutely necessary to facilitate the birth.44 If defibulation
is performed intrapartum, an episiotomy performed at
the same time facilitates delivery and minimizes vaginal
tearing. Possible scenarios should be discussed in advance
so the woman has ample opportunity to state her views, ask
questions, and understand the reasoning behind common
interventions such as analgesia in labour, defibulation,
episiotomy, and Caesarean section. It is advisable to discuss
hospital policies on labour companions, rooming in, and
visiting hours because local practices may be at odds with
the expectations of the woman and her family. Sympathetic
post-delivery care, good analgesia, and assistance with care
of the newborn are essential given the likelihood of vulvar
pain experienced by women with FGC.13
It is vital that women who have had FGC are treated with
respect and sensitivity. In some communities, it is customary
to re-infibulate the genitals after each childbirth.45 WHO
and other international health organizations strongly
oppose all medicalization of FGC including re-infibulation
because it may legitimize the practice of FGC/M in
general.3 Re-infibulation is not specifically prohibited
Female Genital Cutting
by the Canadian Criminal Code; however, requests for
re-infibulation should be declined on medical grounds
because repetitive cutting and suturing of the vulva is
likely to increase scar tissue, thus causing or perpetuating
dyspareunia or voiding difficulties. If incisions are made or
tearing occurs during childbirth, it is reasonable to repair
defects in a way that will promote good hemostasis, vaginal
support, and normal appearance. Typically, high vaginal
tears should be sought and sutured first; it is important
to keep in mind that obstructed labour secondary to
infibulation may be associated with “blow out” lacerations
of the vagina and vulva. Episiotomy incisions and
perineal tears may then be repaired in the usual manner.
Infibulated tissue may be tough and relatively avascular.
A small anterior tear or incision may not require suturing.
In other cases, re-approximation of the cut edges may be
appropriate. Alternatively, the raw edges can be over-sewn
with interrupted, delayed absorbable suture in an effort to
preserve the capacity of the vulvar opening. The vulvar
tissues have a tendency to heal together as the raw edges
sit in apposition. Gentle self-dilatation after defibulation
may be required while the edges heal in the postpartum
period. It is common for women to be concerned about
the appearance of their genitals and to request that their
appearance be preserved or restored as much as possible.
Reassurance and information sharing are important. A
patient-centred approach requires us to hear our patients’
requests and to be sensitive to the cultural context in which
these requests are made. The health care professional
should support a culturally competent approach in which
the autonomy of the patient is honoured as much as
possible without compromising her health or breaching
the ethical principle of non-maleficence.
Caesarean section seems to be more common in women
with FGC than in the general population. Caesarean section
rates in low-resource countries tend to be considerably
lower than in North America and cultural differences
exist in women’s acceptance of Caesarean. Health care
professionals should be aware that FGC is not an indication
for Caesarean delivery. Frequency of Caesarean delivery
may be reduced if defibulation is performed antenatally.43
Population studies have suggested that women with FGC
have statistically increased risks of perinatal mortality,
postpartum hemorrhage, and fetal distress. Currently there
is insufficient data to determine whether these findings
are related to FGC or to socioeconomic factors affecting
health care access and quality of care.46
Summary Statement
9. Female genital cutting is not considered an indication
for Caesarean section. (III)
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Clinical Practice Guidelines
Sexual Health
Sexual function may be normal in women with FGC even in
the absence of the clitoris and/or labia, especially in those
women with Type I or II FGC (Table 2). Currently accepted
treatment for sexual dysfunction should be considered for
those women with FGC. Women with Type III FGC are
significantly affected in terms of sex drive, arousal, and
orgasm.47 There is some evidence that defibulation can
improve sexual function in the domains of desire, arousal,
satisfaction, and pain, but not lubrification and orgasm.48
The use of lubricants, self-stimulation, and dilators may
improve sexual function. The need for defibulation may
be considered, by some cultural groups, an indication of
male sexual dysfunction. In cultures that practice Type
III FGC the husband may be instructed in how to open
(cut) or stretch the introitus to facilitate intercourse. Sexual
dysfunction may occur in men secondary to the association
of sex causing pain in their wife and their own physical
discomfort when attempting intercourse.19,49
Adolescent Care
The physical complications and management of FGC in
adolescents are the same as those in adult women. Some
adolescents request revision of their FGC to feel more
“normal” or less “different.” This should not be denied as
long as there is a full discussion of the risks and benefits,
both physical and psychological (the risk of alienation from
her society). Young women often have no recollection of
FGC performed at an early age; however, once integrated
into Canadian society they may feel self-conscious when
they realize that they were subjected to the practice as
children. One study suggests significantly higher rates of
post-traumatic stress disorder (30%) and other psychiatric
syndromes (48%) in women living with FGC than in the
general population.50 As in relations with all adolescents,
the health care provider should be sensitive to sexual issues
that may be exacerbated by FGC. Discussion about healthy
sexual choices, contraception, and avoidance of sexually
transmitted infections is always important, as is attention
to any self-destructive behaviours (sexual promiscuity,
substance abuse, eating disorders, suicidality). Well-woman
examinations should also be discussed.
Working with Families with Daughters at Risk
All health professionals providing care to families from
communities that practise FGC should educate the parents
about the illegality of the practice in Canada and its harmful
effects. This is especially true when parents are suspected to be
planning to have the procedure carried out on their daughter
or are struggling with the decision. It is also important
to remember that health care professionals have legal
responsibilities to protect children, and thus to report their
e10 l NOVEMBER JOGC NOVEMBRE 2013
suspicions of a child at risk of FGC to provincial child welfare
agencies. Practical guidance for health care professionals can
be found in the BMA’s latest guideline related to FGM.45
SERC Manitoba has developed more information for
professionals on how to provide culturally sensitive counselling
when working with families with young daughters.51
Recommendations
4. Health care professionals should use their knowledge
and influence to educate and counsel families against
having female genital cutting performed on their
daughters and other family members. (III-A)
5. Health care professionals should advocate for the
availability of and access to appropriate support and
counselling services. (III-A)
6. Health care professionals should lend their voices to
community-based initiatives seeking to promote the
elimination of female genital cutting. (III-A)
7. Health care professionals should use interactions with
patients as opportunities to educate women and their
families about female genital cutting and other aspects
of women’s health and reproductive rights. (III-A)
8. Research into female genital cutting should be
undertaken to explore women’s perceptions and
experiences of accessing sexual and reproductive
health care in Canada. (III-A) The perspectives,
knowledge, and clinical practice of health care
professionals with respect to female genital cutting
should also be studied. (III-A).
9. Information and guidance on female genital cutting
should be integrated into the curricula for nursing
students, medical students, residents, midwifery
students, and students of other health care
professions. (III-A)
PROVIDING CULTURALLY COMPETENT
CARE TO WOMEN AND ADOLESCENTS
WITH FEMALE GENITAL CUTTING
Preamble
The experience of FGC/FGM is only one event in
a woman’s life, which may or may not be affecting
her currently.51
The SOGC recognizes that the experience of a woman
living with FGC must be considered within her experience
as an immigrant and/or a visible minority women living
in Canada, and possibly a refugee or asylum seeker. FGC
(with or without complication) is but one of many issues
and concerns a woman faces in her attempt to establish a
life for herself and her family in Canada. Her experience will
vary from other women depending on a number of factors

including her race, nationality, socioeconomic background,
length of time in Canada or in other Western countries,
education, religion, and sexual orientation. If she is a refugee
or an asylum seeker, her experience may also differ from
immigrant women by the possibility that she left her home
under extreme circumstances, may be separated from her
family, and may have been subjected to significant personal
trauma such as rape or other violence. Consequently, in their
interaction with women with FGC, health care professionals’
focus should be directed towards addressing the woman’s
health concerns as a priority and taking a holistic approach.
Key Care Practices in Providing
Care to Women with FGC
The following provides a summary of 10 key care practices
which may assist health care professionals in the provision
of culturally competent care to women with FGC. These
are not meant to be prescriptive and are presented as good
practices to guide you in your work with women who have
undergone the FGC. The following have been adapted
from a number of sources.18,22,23,30,34,52–56
Terminology when providing care
Women who have undergone the practice of FGC may
not see themselves as different or mutilated, and many
may be offended by the use of the term “female genital
mutilation.” The term “female circumcision” is frequently
used by practicing communities and may be the terminology
of choice of the woman and her family.57 The health care
professional in interaction with a woman with FGC should
determine how the woman refers to the practice and then,
use the woman’s choice of terminology throughout care.
Identification of the woman’s FGC status
Identifying as early as possible the FGC status of women
will ensure the delivery of effective care, especially maternity
care. Determining the place of origin of women can provide
insight into their potential status. When completing the
medical history of a woman potentially at risk of having
undergone the practice, the health care professional should
sensitively enquire if she has had genital surgery or if she
has been cut. Further to the pelvic examination, the health
care professional should document the type of FGC clearly
in the medical file, using diagrams if necessary.
Examples of simple and sensitive questions to
discover whether a woman has undergone FGC
and is experiencing any complications related to
the practice54
•• Many women from your country have been
circumcised or “closed” as children. If you do not
mind telling me, were you circumcised or closed as a
child?
Female Genital Cutting
•• Do you have any problems passing your urine? Does
it take you a long time to urinate? (Note that women
with obstruction may take several minutes to pass
urine.)
•• Do you have any pain with menstruation? Does your
menstrual blood get stuck?
•• Do you have any itching or burning or discharge from
your pelvic area?
•• (If sexually active) Do you have any pain or difficulty
when having relations?
Communication
Effective communication is considered paramount in the
provision of culturally competent care to women with FGC
and their families. Not only will it ensure that women have
access to the information needed to make an informed
choice about their health and the care they need, but it
will also enhance their care experience and may positively
influence their “perceptions of themselves, their bodies and
their decision to seek future health care.”22 Communication
within health care teams is also essential to ensure continuity
of care and care that meets the women’s needs.
In interactions with a woman with FGC, the health care
professional should (if necessary, possible, and appropriate),
ensure the availability of a well-trained, trusted, and neutral
female interpreter who can ensure confidentiality and who
will not exert undue influence on the patient–physician
interaction. If interpretation services are not available,
choose an adult family member (preferably a female); avoid
using the women’s children as interpreters. If a child is the
only option possible, avoid discussing very sensitive issues
at the first encounter and inquire whether she can bring an
adult (preferably female) at her next visit. It is important
also to remember that facial expressions, body language,
and tone of voice play an important role in establishing
effective communications.
When working in a health care team, the health care
professional should be sure to document findings in detail
to minimize the need for repeated medical histories and/or
examinations and to facilitate the sharing of information.
Care should also be taken to ensure that all case discussions
are conducted in a professional manner and that no language
is used that can be construed as insensitive or patronizing.
Providing women with appropriate
and well-timed information
Women from countries where FGC is practiced may
not have been exposed to reproductive care discussions
and be unfamiliar with their anatomy, in particular their
reproductive organs, and they may never have had a
NOVEMBER JOGC NOVEMBRE 2013 l e11
Clinical Practice Guidelines
physical, breast, or internal examination. As in all health
professional–patient interactions, the way the information
is shared (i.e., what is said and how it is said) will
influence the outcome of the treatment. Communicating
in a professional manner can contribute to creating a
safe environment for women who find obstetrical and
gynaecological care difficult and stressful.
To ensure adequate information is provided to the
woman, the health care professional should be sure to
speak slowly and clearly and to use simple but accurate
terms. If the woman’s knowledge of reproductive care is
limited, the health care professional should make use of
the interaction to share information with her. Pictures,
diagrams, or anatomical models may be used to facilitate
these discussions. Consideration should also be given to
making longer appointments available.
Confidentiality and privacy
In many countries where FGC is practiced, sex and
sexuality including issues related to FGC are considered
very private matters and are not openly discussed. Some
women refrain from seeking care because of their fear of
being humiliated and judged when they disclose that they
have undergone the practice. Finally, many women may
experience embarrassment when asked to disrobe and
uncover their bodies in front of a health care practitioner.
In many cultures affected by FGC women prefer to be
cared for by female attendants.
The health care professional should ensure the woman’s
privacy and confidentiality by limiting the attendants in
the room (including delivery room) to those who are part
of the health care team. Respect of a woman’s wish for
modesty can be expressed by offering her a long-sleeved
gown, knocking and waiting before entering the room,
and draping the woman carefully when examining her.
Care should be taken to ensure that the examination is
done using a gentle touch, especially when examining the
woman’s sensitive areas. Telling her what you are about
to do, what you are doing, and what you have observed
(good or bad) can be calming and reassuring for her.
Finally, it is important to ensure that the woman is not part
of a teaching session unless informed consent has been
obtained. Trainees should be introduced and the reasons
for their presence and their role in the health care of the
woman should be explained.
Woman-centred care
In many cultures where FGC is practiced, women who
seek care may be accompanied by their husbands and other
family members such as mothers-in-law and male relatives
and these may expect to be involved in the decision-
e12 l NOVEMBER JOGC NOVEMBRE 2013
making process. In some other cultures, birth is considered
women’s business and consequently, men are not expected
to participate in the pregnancy nor the birth, nor are they
the birth companion of choice of many women.58
The health care professional in his/her interactions
with the woman should explore and assess the decision-
making process of the woman and her family and be sure
to solicit the woman’s views and wishes. The health care
professional should also enquire who the woman’s choice
of birth companion is, and respect it.
Health-seeking behaviours and practices
and preventative care
The health-seeking behaviours and practices of many
immigrant women, including women with FGC, often
vary from Canadian norms. They may be unfamiliar
with health services for screening and illness prevention
and be more accustomed to seeking care when ill. They
may also continue to use traditional medicine or health
methods in their health care practices. Many may find our
health care services difficult to understand and navigate,
and frightening and intimidating, especially if they do not
speak English or French.
The health care professional should assist the woman in
understanding how the health system works and help her
navigate it. Every opportunity should be taken to educate
the woman about preventive care practices important
for herself and potentially for her daughters. Culturally
appropriate educational pamphlets should also be made
available.
Preparation for delivery
In many countries where FGC is practiced, prenatal
care similar to that in Canada may not be available,
and many births take place without skilled attendants.
Health care may only be sought when complications
arise. Many women with FGC prefer natural childbirth
and fear Caesarean section and other unfamiliar medical
procedures. The health care professional should take
advantage of the prenatal visits to properly prepare the
woman and her family for the delivery. The focus should
be on developing a detailed birth plan with her and her
family. Attention should be given to sharing information
verbally and in other formats (if available) about when
to come to the hospital, admission procedures, hospital
policies, what to expect in the delivery room, who
will be part of the health care team, the care she can
expect from hospital nurses and staff, how interpreters
are used at the hospital, length of stay, etc. Providing
information about when and why defibulation will take
place, when and why Caesarean sections are performed,

the pain medication options available (during and
after labour), other medical procedures that might be
necessary, and the call schedule also help the woman
prepare for delivery.
Referrals
Referrals to other health care professionals and/or services
are integral to the provision of quality and comprehensive
care. Many women, however, may consider referrals for
counselling to be foreign, not beneficial, and a waste of
their time.
When referring a woman, the health care professional
should ensure that the services and/or practitioners who
receive the referral can provide culturally appropriate and
sensitive care to women with FGC. The professional should
also explain to the woman beforehand why and where the
referral has been made. A woman should be referred to
counselling when she requests the referral, when the health
care professional feels that counselling is necessary for a
favourable outcome of treatment (e.g. when an infibulated
pregnant woman shows signs of anxiety about defibulation
and may be experiencing flashbacks of her FGC), or when
the presenting symptoms are primarily psychological or
sexual in nature.
Recommendation
10. Key practices in providing optimal care to women
with female genital cutting include:
a. determining how the woman refers to the
practice of female genital cutting and using this
terminology throughout care; (III-C)
b. determining the female genital cutting status
of the woman and clearly documenting this
information in her medical file; (III-C)
c. ensuring the availability of a well-trained,
trusted, and neutral interpreter who can ensure
confidentiality and who will not exert undue
influence on the patient–physician interaction
when providing care to a woman who faces
language challenges; (III-C)
d. ensuring the proper documentation of the
woman’s medical history in her file to minimize
the need for repeated medical histories and/
or examinations and to facilitate the sharing of
information; (III-C)
e. providing the woman with appropriate and well-
timed information, including information about
her reproductive system and her sexual and
reproductive health; (III-C)
f. ensuring the woman’s privacy and confidentiality
by limiting attendants in the room to those who
are part of the health care team; (III-C)
Female Genital Cutting
g. providing woman-centred care focused on
ensuring that the woman’s views and wishes are
solicited and respected, including a discussion of
why some requests cannot be granted for legal
or ethical reasons; (III-C)
h. helping the woman to understand and
navigate the health system, including access to
preventative care practices; (III-C)
i. using prenatal visits to prepare the woman and
her family for delivery; (III-C)
j. when referring, ensuring that the services and/
or practitioners who will be receiving the referral
can provide culturally competent and sensitive
care, paying special attention to concerns related
to confidentiality and privacy. (III-C)
REFERENCES
1. World Health Organization, Department of Reproductive Health and
Research. Eliminating female genital mutilation: an interagency statement.
Geneva: WHO; 2008. Available at: http://www.who.int/
reproductivehealth/publications/fgm/9789241596442/en/index.html.
Accessed on July 25, 2013.
2. Nova Scotia Department of Health. A cultural competence guide
for primary health care professionals in Nova Scotia. Halifax:
Nova Scotia Department of Health; 2005. Available at:
http://www.healthteamnovascotia.ca/cultural_competence/
Cultural_Competence_guide_for_Primary_Health_Care_
Professionals.pdf. Accessed on July 25, 2013.
3. UNAIDS, UNDP, UNFPA, UNHCR, UNICEF, UNIFEM, et al.
Global strategy to stop health care providers from performing female
genital mutilation. Geneva: World Health Organization; 2010.
Available at: http://www.who.int/reproductivehealth/publications/
fgm/rhr_10_9/en/index.html. Accessed on March 11, 2011.
4. Yoder PS, Khan S; USAID. Numbers of women circumcised in Africa:
the production of a total. DHS Working Paper 39. Claverton MD:
Macro International; 2004. Available at: http://www.measuredhs.com/
pubs/pdf/WP39/WP39.pdf. Accessed on July 25, 2013.
5. Lalonde A. Clinical management of female genital mutilation must be
handled with understanding, compassion. CMAJ 1995;152(6):949–50.
Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1337778/
pdf/cmaj00066-0153.pdf. Accessed on July 25, 2013.
6. MacLeod TL. Female genital mutilation. J SOGC 1995;17:333–42.
7. Omer-Hashi K, Entwistle MR. Female genital mutilation.
Can J Public Health 1997;88(2):137.
8. Federal Interdepartmental Working Group on Female Genital
Mutilation. FGM and health care: current situation and legal
status—recommendations to improve health care of affected
women. Ottawa: Health Canada; 2000. Available at:
http://www.cwhn.ca/en/resource_en/results/FGM.
Accessed on August 20, 2013.
9. Ontario Human Rights Commission. Policy on female genital
mutilation (FGM). Toronto: OHRC: Toronto; 2000. Available at:
http://www.ohrc.on.ca/en/resources/Policies/PolicyFGM2/pdf.
Accessed on August 20, 2013.
10. Chalmers B, Hashi KO. 432 Somali women’s birth experiences in Canada
after earlier female genital mutilation. Birth 2000;27:227–34.
NOVEMBER JOGC NOVEMBRE 2013 l e13
Clinical Practice Guidelines
11. Vissandjée B, Kantiebo M, Levine A, N’Dejuru R. The cultural context
of gender, identity: female genital excision and infibulation. Health Care
Women Int 2003;24(2):115–24.
12. Citizenship and Immigration Canada. Canada—facts and figures
(immigration overview—permanent and temporary residents).
Ottawa: CIC; 2009. Available at: http://www.cic.gc.ca/English/
resources/statistics/menu-fact.asp#tphp idtphp.
Accessed on August 2, 2013.
13. Chalmers B, Omer-Hashi K. What Somali women say about giving birth
in Canada. J Reprod Infant Psychol 2002;20:267–82.
14. Sexuality Education Resource Center (SERC). Our selves, our daughters:
community-based education addressing female genital cutting (FGC) with
refugee and immigrant women in Winnipeg—final activity and evaluation
report. Winnipeg: SERC; 2010.
15. Almroth L, Elmusharaf S. Genital mutilation of girls. Womens Health
(Lond Engl) 2007;3:475–85.
16. Dorkenoo E, Morison L, Macfarlane A; Foundation for Women’s Health,
Research and Development (FORWARD); The London School of
Hygiene and Tropical Medicine; The Department of Midwifery,
City University. A statistical study to estimate the prevalence of female
genital mutilation in England and Wales: summary report. London:
FORWARD; 2007. Available at: http://www.forwarduk.org.uk/
download/96. Accessed on August 13, 2013.
17. Litorp H, Franck M, Almroth L. Female genital mutilation among
antenatal care and contraceptive advice attendees in Sweden. Acta Obstet
Gynecol Scand 2008;87:716–22.
18. Nour NM. Female genital cutting: clinical and cultural guidelines.
Obstet Gynecol Surv 2004;59(4):272–9.
19. Berggren V, Musa Ahmed S, Hernlund Y, Johansson E, Habbani B,
Edberg A-K. Being victims or beneficiaries? Perspectives on female
genital cutting and reinfibulation in Sudan. Afr J Reprod Health
2006;10(2):24–36.
20. Vangen S, Stollenberg C, Johansen REB, Sundby J, Stray-Perderson B.
Perinatal complications among ethnic Somalis in Norway. Acta Obstet
Gynecol Scand 2002;81:317–22.
21. Bragg R. Maternal deaths and vulnerable migrants. Lancet
2008;371:879–81. Available at: http://www.uic.edu/orgs/womenshealth/
Maternal%20deaths%20and%20Vulnerable%20migrants.pdf.
Accessed on August 3, 2013.
22. Toubia N. Caring for women with circumcision: a technical manual for
health care providers. New York: Rainbow Publications; 1999.
23. Strickland JL. Female circumcision/female genital mutilation. J Pediatr
Adolesc Gynecol 2001;14(3):109–12.
24. UNICEF Office of Research. Changing a harmful social convention:
female genital mutilation/cutting. New York: UNICEF; 2005. Available at:
http://www.unicef-irc.org/publications/396. Accessed on August 3, 2013.
25. UNICEF Office of Research. The Dynamics of social change: towards
the abandonment of FGM/C in five African countries. New York:
UNICEF; 2010. Available at: http://www.unicef-irc.org/publications/618.
Accessed on August 3, 2013.
26. Morison LA, Dirir A, Elmi S, Warsame J, Dirir S. How experiences
and attitudes relating to female circumcision vary according to age on
arrival in Britain: a study among young Somalis in London. Ethn Health
2004;9:75–100.
27. Buckland RL. The everyday experience of Somali women in Canada:
implications for health. Thesis. Ottawa: University of Ottawa; 1997.
28. Vangena S, Johansen RE, Sundby J, Traeen B, Stray-Pedersen B.
Qualitative study of perinatal care experiences among Somali women and
local health care professionals in Norway. Eur J Obstet Gynecol Reprod
Biol 2004;15;112:29–35.
e14 l NOVEMBER JOGC NOVEMBRE 2013
29. Herrel N, Olevitch L, DuBois DK, Terry P, Thorp D, Kind E, et al.
Somali refugee women speak out about their needs for care during
pregnancy and delivery. J Midwifery Womens Health 2004;49:345–9.
30. Theirfelder C, Tanner C M, Bodiang K. Female genital mutilation in the
context of migration: experience of African women with the Swiss health
care system. Eur J Public Health 2005;15(1):86–90.
31. Murray L, Windsor C, Parker E, Tewifik O. The experiences of african
women giving birth in Brisbane, Australia. Health Care Women Int
2010;31:458–72.
32. Lundberg P, Gerezgiher A. Experiences from pregnancy and childbirth
related to female genital mutilation among Eritrean immigrant women in
Sweden. Midwifery 2008;24:214–25.
33. Upvall MJ, Mohammed K, Dodge PD. Perspectives of Somali Bantu
refugee women living with circumcision in the United States. Int J Nurs
Stud 2009;46:360–8.
34. Widmarck C, Tishelman C, Ahlberg BM. A study of Swedish midwives’
encounters with infibulated African women in Sweden. Midwifery
2002;1:113–25.
35. Johansen REB. Care for infibulated women giving birth in Norway: an
anthropological analysis of health workers’ management of a medically
and culturally unfamiliar issue. Med Anthropol Q 2006;20:516–44.
36. Zaidi N, Khalil A, Roberts C, Browne M. Knowledge of female
genital mutilation among healthcare professionals. Contemp Nurse
2007;25:22–30.
37. Widmark C, Levál A, Tishelman C, Ahlberg BM. Obstetric care at the
intersection of science and culture: Swedish doctors’ perspectives on
obstetrical care of women who have undergone female genital cutting.
J Obstet Gynaecol 2010;30:553–8.
38. Kaplan-Marcusán A, Fernández del Rio N, Moreno-Navarro J,
Castany Fàbregas MJ, Muñoz-Ortiz L. Perception of primary health
professionals about female genital mutilation: from healthcare to
intercultural competence. BMC Health Services Research; 2009;9:11.
39. Hess R, Neinland J, Saalinger N. Knowledge of female genital cutting and
experience with women who are circumcised: a survey of nurse-midwives
in the United States. J Midwifery Womens Health 2010;55:45–54.
40. Abdulcadir J, Margairaz C, Boulvain M, Irion O. Care of women with
female genital mutilation / cutting. Swiss Med Wkly 2011;140:w13137.
41. World Health Organization, Department of Reproductive Health
and Research. Management of pregnancy, childbirth and the
postpartum period in the presence of genital mutilation. Available at:
http://www.who.int/reproductivehealth/publications/
maternal_perinatal_health/RHR_01_13_/en/index.html.
Accessed on August 3, 2013.
42. Almroth L, Elmusharaf S, El Hadi N, Obeid A, El Sheikh MA,
Elfadil SM, et al. Primary infertility after genital mutilation in girlhood
in Sudan: a case-control study. Lancet 2005;366:385–91.
43. Raouf SB, Ball T, Hughes A, Holder R, Papaioannou S. Obstetric and
neonatal outcomes for women with reversed and non-reversed type III
female genital mutilation. Int J Gynaecol Obstet 2011;113:141–3.
44. Wuest S, Rajo L, Wyssmueller MD, Muller M, Stadlmaryr W, Surbek DV,
et al. Effects of female genital mutilation on birth outcomes in
Switzerland. BJOG 2009;116:1204–9.
45. BMA Ethics. Female genital mutilation: caring for patients and
safeguarding children. BMA Guideline. 2011. Available at:
http://bma.org.uk/search?query=Female%20genital%20mutilation.
Accessed on August 3, 2013.
46. Ndiaye P, Diongue M, Faye A. Ouedraogo D, Tal Dia A. [Female genital
mutilation and complications in childbirth in the province of Gourma
(Burkina Faso)]. Sante Publique 2010;22:563–70.

47. Okonofu FE, Larsen U, Oronsaye F, Snow RC, Slanger TE. The
association between female genital cutting and correlates of sexual and
gynaecological morbidity in Edo State, Nigeria. BJOG 2002;109:1089–96.
48. Krause E, Brandner S, Mueller MD, Kuhn A. Out of Eastern Africa:
defibulation and sexual function in woman with female genital mutilation.
J Sex Med 2011;8:1420–5.
49. Almroth L, Almroth-Bergren V, Hassanein OM, Al-Said SSE, Hasan SSA,
Lithell UB, et al. Male complications of female genital mutilation. Soc Sci
Med 2001;53:1455–60.
50. Berendt A, Moritz S. Post-traumatic stress disorder and memory problems
after female genital mutilation. Am J Psychiatry 2005;162:1000–2.
51. Sexuality Education Resource Centre Manitoba. Working
with women and girls who have experienced female genital
cutting/female genital mutilation. Winnipeg: SERC; 2000.
Available at: http://www.serc.mb.ca/content/dload/
WorkingWithWomenAnd GirlsWhoHaveExperiencedFemaleGenital
CuttingFemaleGenitalMutiliationCulturallySensitiveCounselling/file.
Accessed on March 13, 2011.
52. Adamson F. Female genital mutilation: a counselling guide for
professionals. London: FORWARD; 1995.
Female Genital Cutting
53. Horowitz C, Jackson JC. Female “circumcision”: African women confront
American medicine. J Gen Intern Med 1997;12:513–5.
54. Carroll J, Epstein R, Fiscella K, Gipson T, Volpe E, Jean-Pierre P. Caring
for Somali women: implications for clinician–patient communication.
Patient Educ Couns 2007;66:337–45.
55. Turner D. Female genital cutting: implications for nurses. Nurs Womens
Health 2007;11:366–72.
56. London Safeguarding Children Board. London FGM resource pack.
London: London Safeguarding Children Board; 2009. Available at:
http://www.londonscb.gov.uk/fgm. Accessed on August 20, 2013.
57. Omer-Hashi K. Commentary: female genital mutilation: perspectives from
a Somalian midwife. Birth 1994;21:224–6.
58. Ford AR, Legault P, Russell J, Van Wagner V; Equity Committee of the
Interim Regulatory Council on Midwifery. Midwifery care for immigrant
and refugee women in Ontario. Can Womens Stud 1994;14:83.
59. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
Appendices begin on next page
NOVEMBER JOGC NOVEMBRE 2013 l e15
Clinical Practice Guidelines

APPENDIX 1. Criminal Code of Canada

Sections of the Criminal Code of Canada that address or could be used to address FGC (Criminal Code of Canada, December 14, 2011)1

Aggravated assault
268. (1) Every one commits an aggravated assault who wounds, maims, disfigures or endangers the life of the complainant.

Punishment
(2) Every one who commits an aggravated assault is guilty of an indictable offence and liable to imprisonment for a term not
exceeding fourteen years.

Excision
(3) For greater certainty, in this section, “wounds” or “maims” includes to excise, infibulate or mutilate, in whole or in part, the labia
majora, labia minora or clitoris of a person, except where
(a) a surgical procedure is performed, by a person duly qualified by provincial law to practise medicine, for the benefit of the
physical health of the person or for the purpose of that person having normal reproductive functions or normal sexual
appearance or function; or
(b) the person is at least eighteen years of age and there is no resulting bodily harm.

Consent
(4) For the purposes of this section and section 265, no consent to the excision, infibulation or mutilation, in whole or in part, of the
labia majora, labia minora or clitoris of a person is valid, except in the cases described in paragraphs (3)(a) and (b).

Removal of child from Canada

273.3 (1) No person shall do anything for the purpose of removing from Canada a person who is ordinarily resident in Canada and who is
(a) under the age of 16 years, with the intention that an act be committed outside Canada that if it were committed in Canada
would be an offence against section 151 or 152 or subsection 160(3) or 173(2) in respect of that person;
(b) 16 years of age or more but under the age of eighteen years, with the intention that an act be committed outside Canada that
if it were committed in Canada would be an offence against section 153 in respect of that person; or
(c) under the age of eighteen years, with the intention that an act be committed outside Canada that if it were committed in
Canada would be an offence against section 155 or 159, subsection 160(2) or section 170, 171, 267, 268, 269, 271, 272 or
273 in respect of that person.

Criminal negligence
219. (1) Every one is criminally negligent who
(a) in doing anything, or
(b) in omitting to do anything that it is his duty to do, shows wanton or reckless disregard for the lives or safety of other persons.

Accessory after the fact

23. (1) An accessory after the fact to an offence is one who, knowing that a person has been a party to the offence, receives, comforts or
assists that person for the purpose of enabling that person to escape.

Duty of persons to provide necessaries

215. (1) Every one is under a legal duty
(a) as a parent, foster parent, guardian or head of a family, to provide necessaries of life for a child under the age of sixteen
years;
(b) to provide necessaries of life to their spouse or common-law partner; and
(c) to provide necessaries of life to a person under his charge if that person
(i) is unable, by reason of detention, age, illness, mental disorder or other cause, to withdraw himself from that charge, and
(ii) is unable to provide himself with necessaries of life

REFERENCE

1. Department of Justice. Consolidation Criminal Code (R.S.C., 1985, c. C-48). Act current to 2011-12-14. Available at: http://laws-lois.justice.gc.ca/eng/
acts/C-46. Accessed on August 2, 2013.

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 Female Genital Cutting

APPENDIX 2. Statements and Policies Provided by Provincial Medical Bodies

The Provincial Medical Board of Nova Scotia

During the past few years, attention has been drawn to the practice of female genital mutilation (FGM). There has been an increase in
immigration to Canada from those areas of the world which allow this practice.
Female genital mutilation is irreversible and imposed on young girls without their consent. While this practice is entertained for cultural
reasons, there are severe long-term physical and psychological complications for these young girls. Many groups, including UNICEF, WHO,
and African women’s groups have spoken forcefully against FGM.
In 1992, the College of Physicians and Surgeons of British Columbia and Alberta endorsed the World Health Organization position which
condemns militating procedures.
The Provincial Medical Board of Nova Scotia (PMB) would like to add its voice to these groups. The Board considers the practice of FGM
such as excision of female genitalia, female circumcision, and infibulation as unacceptable medical procedures. FGM is an inhumane
practice and physicians in Nova Scotia are advised not to perform this surgery nor to attempt to reconstruct the infibulations after a vaginal
delivery. The PMB considers FGM outside the acceptable standards of medical care in Nova Scotia and Canada.
In addition, the practice of FGM is illegal according to Canada’s Criminal Code as advised by the Federal Minister of Justice (1994).
(Statement provided by College of Physicians and Surgeons of Nova Scotia on November 30, 2010.)

Le Collège des médecins du Québec

Notice published in the BULLETIN, Vol. XXXIV, No. 3 – September 1994.
In the last few years, female genital cutting has made headlines around the world. Canada has recently welcomed immigrants and refugees
originating from regions where female genital cutting is practiced.
Female genital cutting is irreversible. Some cultures may view it as an important ritual, but it nevertheless results in long-term physical and
psychological traumas for young women.
It’s not the first time that this topic has been debated. Such a practice is unacceptable, particularly in view of articles 2.03.01, 2.03.14,
2.03.17, and 2.03.23 of the Code of ethics of physicians. It is also proscribed by the Criminal Code.
The Corporation wishes to remind its members that they must refuse to collaborate or participate in such procedures. Physicians called
upon to treat victims of such mutilations must show these patients respect and empathy.
(Statement provided by Le Collège des médecins du Québec representative on November 29, 2010.)

The College of Physicians and Surgeons of Ontario

Female Cutting (Mutilation)1
PRINCIPLES
The practice of medicine is guided by the values of compassion, service, altruism and trustworthiness. These values form the basis of
professionalism.
The physician–patient relationship is the foundation of the practice of medicine and a physician has the duty to always act in the patient’s
best interest.
Good communication is a fundamental component of a trusting physician–patient relationship. Physicians should demonstrate cultural
sensitivity in their communication with patients and families. [3]

POLICY
Physicians must not perform any FGC/M procedures. Further, physicians must not refer patients to any person for the performance of
FGC/M procedures.
The performance of, or referral for, FGC/M procedures by a physician will be regarded by the College as professional misconduct.
Where there is doubt if a procedure is considered to be FGC/M physicians should seek advice from the Canadian Medical Protective
Association and/or legal counsel.
During the course of a vaginal delivery of a woman who has been previously subjected to an FGC/M procedure, a physician may find it
necessary to surgically disrupt the scar tissue resulting from the earlier procedure. In this circumstance, at the conclusion of the delivery,
the physician must confine activities to repairing the surgical incision or laceration required during the delivery, and must not, for example,
endeavour to reconstruct an infibulation. Wherever possible, the physician should advise the patient of this limitation prior to delivery; ideally
this conversation should be had prior to pregnancy and during the course of prenatal care.
Reporting
The performance of FGC/M procedures on a female under the age of 18 by any person may constitute child abuse. Physicians who have
reasonable grounds to believe than an FGC/M procedure has been performed on, or is being contemplated for, any female under the age of
18, must notify the appropriate child protection authorities, regardless of where the procedure has been or will be undertaken. [4]
In the event that a physician has reasonable grounds to believe that another physician is performing FGC/M procedures, the matter should
immediately be brought to the attention of the College. This expectation is based in professionalism and ethics, and is distinct from the legal
obligation to report child abuse discussed above.

Continued

NOVEMBER JOGC NOVEMBRE 2013 l e17

Clinical Practice Guidelines

APPENDIX 2. Continued

Care of Patients
As appropriate, physicians should provide culturally sensitive counseling regarding the dangers related to performing FGC/M procedures.
As part of their commitment to treat patients with compassion, physicians who encounter patients subjected to FGC/M procedures should
educate themselves on the appropriate management of possible complications, in order to provide appropriate counsel and care.

Endnotes
3. See the CPSO’s Practice Guide at http://www.cpso.on.ca under Policies and Publications.
4. Pursuant to Child and Family Services Act, R.S.O. 1990, c.C11, s.72(1) and the Criminal Code, R.S.C. 1985, c. C-46, s 273(1) and the
CPSO’s Mandatory Reporting policy.

The College of Physicians and Surgeons of Manitoba

Female Circumcision (Revised 2001)2
Female circumcision is not an appropriate medical practice under any circumstance and if performed by a physician, represents professional
misconduct. If a physician is aware of a proposal to perform female circumcision on a child, the incident must be reported pursuant to the
requirement to report child abuse set forth in The Child and Family Services Act.

The College of Physicians and Surgeons of Alberta

Directive provided by the Council to its members (1994)
THAT physicians, as well as other providers of women’s health care, be made aware of the issues involved in Female Genital Mutilation
(FGM).
Specifically, physicians must not perform FGM.
Where physicians encounter medical complications of FGM, they shall manage these in a culturally sensitive and ethical manner; this may
require individualized consideration of secondary reconstruction of the previous FGM.
(Statement provided by CPSA representative on December 1, 2010.)

The College of Physicians and Surgeons of British Columbia

College’s Position3
The College endorses the position of the World Health Organizational (WHO), and many other medical organizations, regarding female
genital mutilation, as having no health benefits, and both immediate and long-term negative health consequences.
– A physician must decline to perform female genital mutilation and must not make a referral for the purpose of female genital
mutilation.
– An adult parent or guardian cannot consent to the excision, infibulation or mutilation of the labia majora, labia minora or clitoris on
behalf of a child, except in the circumstances described under section 268(3) of the Criminal Code.
– Urgent action must be taken if a physician considers that a child may be at risk of female genital mutilation.

Duty to Report3
A physician must report to the College and the Ministry of Children and Family Development if:
– A physicians learns of another physician performing female genital mutilation;
– A physician is requested to perform female genital mutilation or learns that these procedures may be performed on a child or person
under 18 years of age; or
– A physician considers that a child may be at risk in relation to the practice of female genital mutilation.

REFERENCES

1. The College of Physicians and Surgeons of Ontario. Female genital cutting (mutilation). Policy #2-11. Available at:
http://www.cpso.on.ca/policies/policies/default.aspx?ID=1596. Accessed on August 2, 2013.
2. The College of Physicians and Surgeons of Manitoba. Female circumcision (2011 rev.) Statement 111. Available at:
http://cpsm.mb.ca/cjj39alckF30a/wp-content/uploads/st111.pdf. Accessed on August 2, 2013.
3. College of Physicians and Surgeons of British Columbia. Professional standards and guidelines: female genital mutilation. Available at:
https://www.cpsbc.ca/files/u6/Female-Genital-Mutilation.pdf. Accessed on August 2, 2013.

e18 l NOVEMBER JOGC NOVEMBRE 2013

 SOGC CLINICAL PRACTICE GUIDELINE
SOGC CLINICAL PRACTICE GUIDELINE
Guideline for the Management of Postoperative
Nausea and Vomiting
This guideline has been approved by Executive and Council of the
Society of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Geoff McCracken, MB, BCh, Toronto ON
Patricia Houston, MD, Toronto ON
Guylaine Lefebvre, MD, Toronto ON
Abstract
Objective: To provide recommendations for the management of
postoperative nausea and vomiting (PONV), which may affect as
many as 30% of patients.
Methods and Evidence: Medline, PubMed, and the Cochrane
Database were searched for articles published in English from
1995 to 2007. Recognizing that we must work as a team to
optimize the care of our patients perioperatively, this guideline was
written in partnership with anaesthesiologists.
Options: The areas of clinical practice considered in formulating this
guideline are prevention and prophylaxis, treatment, both medical
and alternative, and patient education.
Outcomes: Implementation of this guideline should optimize the
prevention of and prophylaxis against PONV and the prompt
treatment of women who suffer from PONV following gynaecologic
surgery. Increased awareness of options for management should
help minimize the effects of PONV.
Benefits, Harms, and Costs: PONV results not only in increased
patient discomfort and dissatisfaction but also in increased costs
related to length of hospital stay. Cost of medications to prevent
and treat PONV must be weighed against improved surgical
experience for the patient and decreased costs to the system.
Values: Recommendations were made according to the guidelines
developed by the Canadian Task Force on Preventive Health
Care.
Recommendations
1. Physicians should be aware of the risk factors associated with
PONV, and the baseline risks should be reduced whenever
possible. (III-A)
Key Words: Postoperative nausea, postoperative vomiting
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
600 l JULY JOGC JUILLET 2008
No. 209, July 2008
2. When the choice is available, patients should be advised that the
risk of PONV decreases when regional rather than general
anaesthesia is administered. (III-A)
3. The perioperative use of opioids should be minimized. Surgeons
should evaluate the risks/benefits of opioid administration in light
of the increased risk of PONV. (III-B)
4. Prophylactic antiemetics should be administered to patients with
moderate or high risk of developing PONV. (II-1A)
5. In patients with a high risk of developing PONV, combination
antiemetic therapy should be considered. (III-B)
6. Acupoint electrical stimulation may be used as an alternative or
adjuvant therapy for prevention of PONV. (II-1A)
7. For patients with PONV who did not receive prophylaxis or in
whom prophylaxis failed, antiemetic treatment should be
administered as soon as feasible. (III-A)
8. When prophylaxis with one drug has failed, a repeat dose of this
drug should not be initiated as a rescue therapy; instead, a drug
from a different class of antiemetic drugs should be
administered. (III-A)
9. As patients who undergo surgery in surgical daycare units may
have PONV after they are discharged, they should be given
instructions for its management. (III-B)
10. Patients at high risk of developing PDNV should be provided with
rescue treatment. (III-B)
J Obstet Gynaecol Can 2008;30(7):600–607
INTRODUCTION
ostoperative nausea and vomiting, defined as nausea
P and/or vomiting occurring within 24 hours after sur-
gery, affects between 20% and 30% of patients.1–4 As many
as 70% to 80% of patients at high risk may be affected.5 The
etiology of PONV is thought to be multifactorial, involving
individual, anaesthetic, and surgical risk factors.2,5,6 PONV
results in increased patient discomfort and dissatisfaction6
and in increased costs related to length of hospital stay. One
study revealed that the time to discharge was increased by
25% in patients with PONV.7 Serious medical complica-
tions such as pulmonary aspiration, although uncommon,
are also associated with vomiting.6
 Guideline for the Management of Postoperative Nausea and Vomiting
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of Evidence Assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.75
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
Task Force on Preventive Health Care.75
PONV is a significant problem for patients: in one study,
patients were more concerned about PONV than about
postoperative pain8; in another, patients were willing to
spend up to US $100 for an effective antiemetic treatment.9
Several thousand studies examining PONV have been pub-
lished, and several hundred new papers are published each
year on the topic. Guidelines for the prevention and man-
agement of PONV have been published by anaesthetic
journals and societies.10–12
Management of PONV for gynaecological patients in most
hospitals continues to be on an ad hoc basis. The aim of
these guidelines is to provide information on the manage-
ment of PONV in gynaecological patients.
PHYSIOLOGY OF NAUSEA AND VOMITING
Primary control of nausea and vomiting arises from the
vomiting centre, located in the medulla. The five primary
ABBREVIATIONS
CTZ chemoreceptor triggering zone
NK-1 neurokinin-1 receptor antagonist
NNT number needed to treat
NSAIDs nonsteroidal anti-inflammatory drugs
PDNV post-discharge nausea and vomiting
PONV postoperative nausea and vomiting
Classification of Recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
afferent pathways involved in stimulating the vomiting cen-
tre are:
1. the chemoreceptor triggering zone,
2. the vagal mucosal pathway in the gastrointestinal system,
3. neuronal pathways from the vestibular system,
4. reflex afferent pathways from the cerebral cortex C2,3,
and
5. midbrain afferents.
Stimulation of one of these afferent pathways can activate
the vomiting centre via cholinergic (muscarinic),
dopaminergic, histaminergic, or serotonergic receptors.
MANAGEMENT OF PONV
Reduction in Baseline Risk Factors
Blanket use of PONV prophylaxis is not cost-effective and
unnecessarily risks drug-related adverse effects. Most
guidelines are in agreement that patients at low risk for
PONV are unlikely to benefit from prophylaxis and that it
should be reserved for patients at moderate to high risk.
Patients with no more than one risk factor are considered
low risk. Identifying patient risks remains a challenge.
Apfel et al.13 devised a simplified risk score for predicting
PONV. They concluded that there are 4 main risk factors:
1. female sex,
2. prior history of motion sickness or PONV,
JULY JOGC JUILLET 2008 l 601
SOGC CLINICAL PRACTICE GUIDELINE
3. non-smoker, and
4. the use of postoperative opioids.
The estimated probability of PONV was 10%, 21%, 39%,
and 78% with 0, 1, 2, 3, and 4 risk factors, respectively.
Risk Factors for PONV
These can de divided into 3 main groups:
• Patient-specific: female sex8,13; non-smoker13,14;
history of PONV or motion sickness.13–15
• Anaesthetic: use of volatile anaesthetics within 0 to
2 hours16; use of nitrous oxide17; use of intraoperative
and postoperative opioids13,18–21; high doses of
neostigmine.
• Surgical: duration of surgery, with each 30-minute
increase in duration increasing the risk of PONV by
60%.22
Recommendation
1. Physicians should be aware of the risk factors associated
with PONV, and the baseline risks should be reduced
whenever possible. (III-A)
Optimization in the Perioperative Period
A number of perioperative factors have been shown to
reduce the risk of PONV.
When possible, regional anaesthetic should be administered
as general anaesthetic is associated with an 11-fold
increased risk of PONV.22 When general anaesthetic is
required, the use of propofol as the induction agent is effec-
tive in reducing early PONV incidence when compared
with other induction agents. The number needed to treat
with propofol to reduce PONV is approximately 5.23
Avoidance of intraoperative and postoperative opioids has
been shown to reduce PONV. Moiniche et al. showed that
treatment with NSAIDs as compared with opioids
decreased the risk of PONV.20 The use of supplemental
oxygen perioperatively has been shown to reduce PONV by
50%.24,25 possibly by reducing gastrointestinal hypoxia.
However, there is conflicting evidence, and a recent study
by Turan et al. demonstrated no benefit associated with
supplemental oxygen.26
Perioperative intravenous fluid administration has been
shown to reduce PONV.27,28 The mechanism is unclear but
may be related to the release of serotonin due to decreased
intestinal perfusion, which can be caused by the drop in sys-
tolic blood pressure seen with some induction agents.
Neostigmine, a reversal agent for non-depolarising muscle
relaxants, is associated with increased PONV, especially in
large doses (> 2.5 mg),29 and should be avoided if possible.
602 l JULY JOGC JUILLET 2008
Recommendations
2. When the choice is available, patients should be advised
that the risk of PONV decreases when regional rather
than general anaesthesia is administered. (III-A)
3. The perioperative use of opioids should be minimized.
Surgeons should evaluate the risks/benefits of opioid
administration in light of the increased risk of PONV. (III-B)
Pharmacological Prophylaxis
Prophylactic doses and timing for the administration of
antiemetics are shown in Table 2.
Serotonin (5-HT3) receptor antagonists exert their effects in
the chemoreceptor trigger zone and at vagal afferents in the
gastrointestinal tract. Ondansetron was the first of this class
of drug to be marketed; others include dolasetron,
tropisetron, and granisetron.
In 2003, an expert panel agreed that there was no evidence
of any difference in the efficacy and safety profiles of the
different 5-HT3 receptor antagonists in the prophylaxis
against PONV.10 Ondansetron 4 mg has a NNT of 7 for the
prevention of nausea and 6 for the prevention of vomiting.
The number needed to harm with a single dose of
ondansetron is 36 for headache, 31 for increased liver
enzymes, and 23 for constipation.30
Dexamethasone, a corticosteroid, administered at a dose of
8–10 mg IV, prevents PONV with a NNT of 4.38 Smaller
doses of 2.5–5 mg have been shown to be as effective13,40
The precise mode of action is not well understood, but may
be due to the release of endorphins that elevate mood and
stimulate appetite.16 There are no reports of adverse effects
in the doses used for the management of PONV.38
Droperidol blocks dopamine receptors in the CTZ. The
efficacy of droperidol is equivalent to that of ondansetron,
with a NNT of 5 for prevention of PONV. The FDA issued
a “black box” warning about droperidol, stating that it may
cause death associated with QT prolongation and torsades
de pointes. In Canada, droperidol is still available but its use
is limited by Health Canada.48
Metoclopramide blocks dopamine receptors in the CTZ
and vomiting centre. It also shortens bowel transit time and
in high doses blocks serotonin receptors. When used in
standard clinical doses of 10 mg, metoclopramide was
found to be ineffective for PONV prophylaxis.49 A dose of
50 mg intravenous metoclopramide has been shown to sig-
nificantly reduce late (> 12 hours) PONV, but the side
effect profile is unsatisfactory.47 The guidelines produced
by Gan et al. do not recommend metoclopramide as a
perioperative antiemetic.10
Dimenhydrinate, a commonly used antihistaminic, has sim-
ilar efficacy to 5-HT3 receptor antagonists.43 Its efficacy is
 Guideline for the Management of Postoperative Nausea and Vomiting

Table 2. Prophylactic doses and timing for the administration of antiemetics

Drug Dose Timing Adverse effects

30 31
Ondansetron 4–8 mg IV At end of surgery Headache, lightheadedness, elevated
liver enzymes
Dolasetron 12.5 mg IV32 At end of surgery32 Headache, lightheadedness, elevated
liver enzymes
Granisetron 0.35–1mg IV33–35 At end of surgery33,35 Headache, lightheadedness, elevated
liver enzymes
Tropisetron 5 mg IV36,37 At end of surgery36,37 Headache, lightheadedness, elevated
liver enzymes
Dexamethasone 5–10 mg IV38–40 Before induction41 Vaginal itching or anal irritation with IV
bolus
Droperidol 0.625–1.25 mg IV36,37 At end of surgery42 Sedation, dizziness, anxiety,
hypotension, EPS
Dimenhydrinate 1–2mg/kg IV43 Sedation, dry mouth, blurred vision,
dizziness, urinary retention
Prochlorperazine 5–10mg IV44 At end of surgery44 Sedation, hypotension, EPS
44
Promethazine 12.5–25mg IV At end of surgery44 Sedation, hypotension, EPS
45,46
Scopolamine Transdermal patch Prior evening or 4 hours Sedation, dry mouth, visual
before end of surgery46 disturbances; CNS effects in elderly
patients, renal or hepatic impairment
Metoclopramide 25 or 50 mg IV for Sedation, hypotension, EPS
prophylaxis47
Diclectin 10 mg doxylamine Before induction
succinate and 10 mg
Prior evening, 2 tablets
pyridoxine hydrochloride
Before induction, morning of
surgery, 1 tablet
After surgery, 1 tablet
Aprepitant 40 mg PO 1–3 hours prior to induction Headache, fatigue, dizziness elevated
of anaesthesia liver enzymes

presumably due to the high concentration of histamine and
muscarinic cholinergic receptors within the vestibular
system.50
Promethazine and prochlorperazine belong to a group of
drugs known as phenothiazines, which act primarily via a
central antidopaminergic mechanism in the CTZ. The use
of these drugs has decreased because of their significant
side effects: sedation, dizziness, and extrapyramidal
symptoms.
Scopolamine is an anticholinergic that blocks emetic
muscarinic receptors in the cerebral cortex.51 It is very
effective, with a NNT of 3.8 for prevention of PONV.52 Its
use is limited because of its two- to four-hour onset of
effect and side effect profile as listed above.
A recent publication has shown Diclectin to be as effective
as ondansetron for the prevention of late postoperative
vomiting in women undergoing laparoscopic tubal ligation,
with an average NNT of 5.9.53
Diclectin is an antiemetic medication that contains 10 mg
doxylamine succinate (a common antihistamine with
antiemetic properties found in over-the-counter sleeping
medication) and 10 mg pyridoxine hydrochloride (vitamin
B6), in a delayed release formulation. Pyridoxine may have
intrinsic antiemetic properties and also may be synergistic
with the antinauseant property of antihistamines.54–56
Diclectin has been used since the 1950s and is considered to
be a safe treatment for nausea and vomiting associated with
pregnancy.57 The International Cochrane Collaboration has
systematically reviewed randomized trials of Diclectin and
concluded that it safely provides considerable relief for nau-
sea and vomiting in pregnancy.58
Aprepitant was the first neurokinin-1 (NK-1) receptor
antagonist approved for the treatment of PONV. This drug
blocks NK1 receptors in the central and peripheral nervous
systems thus preventing emesis. In one study, patients given
oral aprepitant alone or in combination with intravenous
ondansetron had significantly fewer emetic episodes than
those given ondansetron alone.59 In a report of combined
data from 2 large trials, oral aprepitant 40 mg was superior
to intravenous ondansetron 4 mg for the prevention of
PONV.60 Complete response (no nausea, vomiting, or need

JULY JOGC JUILLET 2008 l 603

SOGC CLINICAL PRACTICE GUIDELINE
for rescue therapy) was achieved in 37.9% of the aprepitant
group compared with 31.2% of the ondansetron group. Its
acquisition cost is relatively high, making it less appealing as
a first line agent.
None of the available agents is entirely effective for pre-
venting PONV, particularly for high-risk patients. As there
are four major receptor systems involved in the etiology of
PONV, a combination of agents that act on different recep-
tors results in better prophylaxis.61,62 The most commonly
studied combinations have included 5-HT3 receptor antag-
onists with droperidol or dexamethasone, and both are
equally efficacious.63,64 The Figure illustrates a proposed
algorithm for the management of PONV
Recommendations
4. Prophylactic antiemetics should be administered to
patients with moderate or high risk of developing
PONV. (II-1 A)
5. In patients with a high risk of developing PONV, combi-
nation antiemetic therapy should be considered. (III-B)
604 l JULY JOGC JUILLET 2008
Non-pharmacologic Prophylaxis
Acupuncture has been shown to be effective in the manage-
ment of PONV. Coloma et al.65 compared acustimulation
with ondansetron for the treatment of established PONV
in outpatient laparoscopic surgery patients. They concluded
that acustimulation may be a satisfactory alternative to
ondansetron for established PONV, and that ondansetron
seems to enhance the efficacy of acustimulation for treat-
ment of established PONV.
Ginger root is a commonly used non-medical therapy
but is not effective for PONV prophylaxis.66 Similarly,
cannabinoids have not been confirmed to be effective in the
management of PONV.
Recommendation
6. Acupoint electrical stimulation may be used as an
alternative or adjuvant therapy for prevention of
PONV. (II-1 A)
 Guideline for the Management of Postoperative Nausea and Vomiting
Rescue Treatment for PONV
In the presence of persistent nausea and vomiting, possible
contributing factors, such as patient-controlled morphine
analgesia, presence of blood in the pharynx, or an abdomi-
nal obstruction, should be excluded before rescue therapy
may be initiated.
When prophylaxis with one drug has failed, a repeat dose of
this drug should not be initiated as a rescue therapy. Instead
a drug from a different class of antiemetics should be
administered.67 However, if the PONV occurs more than 6
hours after surgery, repeat dosing of the initial prophylactic
drug may be considered. Repeat doses of dexamethasone
and transdermal scopolamine should not be administered
regardless of the time interval.10
If a patient has received no prophylaxis, treatment with a
5-HT3 receptor antagonist may be considered.68 Rescue
treatment doses for 5-HT3 receptor antagonists are
approximately 25% the dose of those used for prophylaxis
(e.g., 1 mg ondansetron).
Recommendations
7. For patients with PONV who did not receive prophylaxis
or in whom prophylaxis failed, antiemetic treatment
should be administered as soon as feasible. (III-A)
8. When prophylaxis with one drug has failed, a repeat dose
of this drug should not be initiated as a rescue therapy;
instead, a drug from a different class of antiemetic drugs
should be administered. (III-A)
Post-discharge Nausea and Vomiting
PDNV is nausea and/or vomiting that occur after discharge
from the health care facility, but within the 24-hour period
immediately following surgery. Post-discharge nausea and
vomiting that occurs after the initial 24-hour postoperative
period is considered delayed PDNV.69 Post-discharge nau-
sea and vomiting is becoming more common as more
patients are being operated on in an ambulatory setting, and
it has been reported in 35% to 50% of patients.70,71
In a recent meta-analysis, the NNT to prevent post dis-
charge nausea following ambulatory surgery was 12.9, 12.2,
and 5.2 following the prophylactic administration of
ondansetron 4 mg, dexamethasone, and a combination of
two antiemetics, respectively. For post-discharge vomiting,
the NNT was 13.8 for ondansetron 4 mg and 5 for combi-
nation treatment. These results suggest that ondansetron
alone should not be used routinely in ambulatory patients at
low risk and that patients at high risk are best managed with
a combination strategy.72
Optimal management of PDNV is unsupported by scien-
tific evidence, and the choice of medication for PDNV is
left to the clinician.
In a study by Gan et al.73 4 mg IV ondansetron for PONV
prophylaxis was administered. Patients were then random-
ized to receive either ondansetron oral disintegrating tablet
(ODT) 8 mg or placebo immediately before discharge from
the ambulatory surgery centre and again 12 hours later.
Patients who received ondansetron ODT had less severe
nausea and fewer vomiting episodes (3% vs. 23%) after
discharge.
Al-Sadi et al.74 assessed the efficacy of acupuncture as a pro-
phylactic antiemetic. They found a significant difference
between groups before and after discharge, with the pla-
cebo group four times more likely to have post-discharge
nausea and vomiting than the acupuncture group.
Recommendations
9. As patients who undergo surgery in surgical daycare units
may have PONV after they are discharged, they should
be given instructions for its management. (III-B)
10. Patients at high risk of developing PDNV should be
provided with rescue treatment. (III-B)
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antagonists combined with droperidol for PONV prophylaxis is similar to
their combination with dexamethasone. A meta-analysis of randomized
controlled trials. Can J Anesth 2004;51:311–19.
65. Coloma M, White PF, Ogunnaike BO, Markowitz SD, Brown PM, Lee AQ,
et al. Comparison of acustimulation and ondansetron for the treatment of
established postoperative nausea and vomiting. Anesthesiology
2002;97:1387–92.
66. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting:
a systematic review of randomized clinical trials. Br J Anaesth
2000;84:367–71.
67. Hill RP, Soppitt AJ, Gan TJ. The effectiveness of rescue antiemetics in
patients who received a prophylactic antiemetic. Anesth Analg 2000;90:S8
(abstract).
68. Tramèr M, Moore RA, Reynolds DJM, McQuay HJ. A quantitative systemic
review of ondansetron in treatment of established postoperative nausea and
vomiting. BMJ 1997;314:1088–92.
69. American Society of PeriAnesthesia Nurses PONV/PDNV Strategic Work
Team. ASPAN’S evidence-based clinical practice guideline for the
prevention and/or management of PONV/PDNV. J Perianesth Nurs
2006;21:230–50.
70. Carroll NV, Miederhoff P, Cox FM, Hirsch JD. Postoperative nausea and
vomiting after discharge from outpatient surgery centers. Anesth Analg
1995;80:903–9.
71. Gan TJ. Postoperative nausea and vomiting: Can it be eliminated? JAMA
2002; 13:1233–6.
72. Polati E, Verlato G, Finco G, Mosaner W, Grosso S, Gottin L, et al.
Ondansetron versus metoclopramide in the treatment of postoperative
nausea and vomiting. Anesth Analg 1997;85:395–9.
73. Gan TJ, Franiak R, Reeves J. Ondansetron orally disintegrating tablet versus
placebo for the prevention of postdischarge nausea and vomiting after
ambulatory surgery. Anesth Analg 2002;94:1199-200.
74. al-Sadi M, Newman B, Julious SA. Acupuncture in the prevention of
postoperative nausea and vomiting. Anaesthesia 1997;52:658-61.
75. Woolf SH, Battista RN, Anderson GM, Logan AG, Eel W. Canadian Task
force on Preventive Health Care. New grades for recommendations from
the Canadian Task force on Preventive Health Care. CMAJ 2003;169:207–8.
JULY JOGC JUILLET 2008 l 607
 SOGC CLINICAL PRACTICE GUIDELINE

No. 296, September 2013 (Reviewed March 2015)

Induction of Labour: Review

This clinical practice guideline review has been prepared
by Clinical Practice Obstetrics Committee and approved by
the Executive and Board of the Society of Obstetricians and
T he issue of induction of labour and risk of Caesarean
section has been a topic of recent discussion, catalyzed
by the publication of a new review paper in the Canadian
Gynaecologists of Canada. Medical Association Journal.1 In response to an influx of queries
regarding the CMAJ paper and its potential effect on SOG
PRINCIPAL AUTHORS
guidelines, the Clinical Practice Obstetrics Committee has
Dean Leduc, MD, Ottawa ON
reviewed the SOGC Induction of Labour guidelines published
Anne Biringer, MD, Toronto ON in 20132 and concluded that no update or revision to the
Lily Lee, RN, MSN, Vancouver BC SOGC is required at this time. The committee emphasized
Jessica Dy, MD, Ottawa ON that the CMAJ meta-analysis included no new information or
studies that were not used in the 2013 SOGC guideline.
CLINICAL PRACTICE OBSTETRICS COMMITTEE
Hussam Azzam (Chair), MD, Thompson MB It is also important to note that results from the CMAJ
Jon Barrett, MD, Toronto ON
review paper report on an induction group encompassing all
indications for induction of labour, with term labour defined
Anne Biringer, MD, Toronto ON
as 37 to 42 weeks’ gestation and measured outcomes limited
Kim Campbell, RM, Vancouver BC to Caesarean section. The SOGC guideline recommends
Louise Duperron, MD, Montreal QC requiring an obstetrical or medical indication (e.g. premature
Jessica Dy, MD, Ottawa ON rupture of membranes, hypertension, intrauterine growth
Ellen Giesbrecht, MD, Vancouver BC restriction) for induction of labour before 41 weeks. This is
consistent with guidelines published by the Royal College of
Lisa Graves, MD, Hamilton ON
Obstetricians and Gynaecologists and the American Congress
Michael Helewa, MD, Winnipeg MB
of Obstetricians and Gynecologists.
Ian Lange, MD, Calgary AB
Lily Lee, RN, MSN, Vancouver BC
The data does confirm that induction of labour for specific
indications is not associated with higher risk of Caesarean
Suzanne Muise, MD, Camana Bay, Grand Cayman
section and in some indications, such as post-term induction,
Barbara Parish, MD, Halifax NS it lowers the risk of Caesarean section. It is important to note
Disclosure statements have been received from all contributors. that these study findings should not be generalized to any
and all inductions of labour, especially when no indications
exist; SOGC stands by its recommendation that induction of
labour should be carried out only after careful discussion with
women who have specific indications.
The SOGC is aware of two clinical trials underway that
are examining induction of labour versus expectant
J Obstet Gynaecol Can 2015;37(4):380–381 management.3,4 The outcomes of these studies will be

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

380 l APRIL JOGC AVRIL 2015


monitored by the Clinical Practice Obstetrics Committee
for potential change of practice implications.
It is to be noted that, to ensure the best quality of care, the
SOGC is currently developing a standard of practice under
which evidence will be reviewed on a regular basis to decide
whether all or part of a guideline should be updated based
on new robust (Canadian Task Force on Preventive Health
Care5 level I) evidence.
REFERENCES
1. Mishanina E, Rogozinska E, Thatthi T, Uddin-Khan R, Khan KS,
et al. Use of labour induction and risk of cesarean delivery: a systematic
review and meta-analysis. CMAJ 2014;186:665–73.
Induction of Labour: Review
2. Leduc D, Biringer A, Lee L, Dy J; Clinical Practice Obstetrics
Committee, Society of Obsetricians and Gynaecologists of
Canada. Induction of labour. SOGC Clinical Practice Guideline
No. 296, September 2013. J Obstet Gynaecol Can 2013;36:248–52.
3. Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD). A Randomized Trial of Induction
Versus Expectant Management (ARRIVE). Bethesda, MD: US National
Institute of Health; 2014. Available at: http://clinicaltrials.gov/ct2/show/
NCT01990612?term=ARRIVE&rank=2. Accessed on December 10, 2014.
4. Nottingham Clinical Trials Unit. Induction of labour versus
expectant management for women over 35 years of age. Nothingham, GB:
NCTU; 2013. Available at: http://www.35-39trial.org.
Accessed on December 10, 2014.
5. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W;
Canadian Task Force on Preventive Health Care. New grades for
recommendations from the Canadian Task Force on Preventive
Health Care. CMAJ 2003;169:207–8.
APRIL JOGC AVRIL 2015 l 381
 SOGC Clinical Practice Guideline

No. 296, September 2013 (Replaces No. 107, August 2001)

Induction of Labour
Abstract
This clinical practice guideline has been prepared by the
Clinical Practice Obstetrics Committee, reviewed by the Objective: To review the most current literature in order to provide
Maternal Fetal Medicine and Family Practice Advisory evidence-based recommendations to obstetrical care providers
Committees, and approved by the Executive and Council on induction of labour.
of the Society of Obstetricians and Gynaecologists of
Options: Intervention in a pregnancy with induction of labour.
Canada.
Outcomes: Appropriate timing and method of induction,
PRINCIPAL AUTHORS appropriate mode of delivery, and optimal maternal and
Dean Leduc, MD, Ottawa ON perinatal outcomes.
Evidence: Published literature was retrieved through searches
Anne Biringer, MD, Toronto ON
of PubMed, CINAHL, and The Cochrane Library in 2010
Lily Lee, MSN, Vancouver BC using appropriate controlled vocabulary (e.g., labour, induced,
Jessica Dy, MD, Ottawa ON labour induction, cervical ripening) and key words (e.g.,
induce, induction, augmentation). Results were restricted
to systematic reviews, randomized control trials/controlled
CLINICAL PRACTICE OBSTETRICS COMMITTEE
clinical trials, and observational studies. There were no
Thomas Corbett, MD (Co-chair), Edmonton AB date or language restrictions. Searches were updated on a
Dean Leduc, MD (Co-chair), Ottawa ON regular basis and incorporated in the guideline to the end of
2010. Grey (unpublished) literature was identified through
Anne Biringer, MD, Toronto ON searching the websites of health technology assessment and
Louise Duperron, MD, Kirkland QC health technology-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
Jessica Dy, MD, Ottawa ON medical specialty societies.
Ian Lange, MD, Calgary AB Values: The evidence in this document was rated using criteria
Lily Lee, MSN, Vancouver BC described in the Report of the Canadian Task Force on
Preventative Health Care (Table 1).
Suzanne Muise, MD, St. Thomas ON
Barbara Parish, MD, Halifax NS Summary Statements
Lexy Regush, MD, Saskatoon SK 01. Prostaglandins E2 (cervical and vaginal) are effective
agents of cervical ripening and induction of labour for an
Kathi Wilson, RM, Ilderton ON
unfavourable cervix. (I)
Grace Yeung, MD, London ON 02. Intravaginal prostaglandins E2 are preferred to intracervical
prostaglandins E2 because they results in more timely vaginal
SPECIAL CONTRIBUTORS deliveries. (I)
Joan Crane, MD, St. John’s NL
Robert Gagnon, MD, Montreal QC
Diane Sawchuck, RN, PhD, Vancouver BC
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all contributors. J Obstet Gynaecol Can 2013;35(9)

The literature searches and bibliographic support for this

guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada. Key Words: Induction, labour, cervical ripening, post-dates

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

SEPTEMBER JOGC SEPTEMBRE 2013 l S1

SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.111
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.111
Recommendations
01. The indication for induction must be documented, and discussion
should include reason for induction, method of induction, and
risks, including failure to achieve labour and possible increased
risk of Caesarean section. (III-B)
02. If induction of labour is unsuccessful, the indication and method
of induction should be re-evaluated. (III-B)
03. Inductions should not be performed solely for suspected fetal
macrosomia. (III-D)
04. Inductions should not be performed solely because of patient
or care provider preference. (III-D)
05. Health care providers should assess the cervix (using the
Bishop score) to determine the likelihood of success and to
select the appropriate method of induction. (II-2A)
06. The Bishop score should be documented. (III-B)
ABBREVIATIONS
ARM artificial rupture of membranes
ART artificial reproductive technologies
CFAS Canadian Fertility and Andrology Society
FHR fetal heart rate
GBS group B streptococcus
NNT number needed to treat
NST non-stress test
PG prostaglandins
PGE1 prostaglandins E1
PGE2 prostaglandins E2
PROM pre-labour rupture of membranes
S2 l SEPTEMBER JOGC SEPTEMBRE 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
07. Care providers need to consider that induction of women with
an unfavourable cervix is associated with a higher failure rate
in nulliparous patients and a higher Caesarean section rate in
nulliparous and parous patients. (II-2A)
08. Every woman should ideally have an ultrasound, preferably in
the first trimester, to confirm gestational age. (I-A)
09. Institutions should have quality assurance programs and
induction policies, including safety tools such as checklists,
to ensure that inductions are performed only for acceptable
indications. (II-2B)
10. Women should be offered induction of labour between
41+0 and 42+0 weeks as this intervention may
reduce perinatal mortality and meconium aspiration
syndrome without increasing the Caesarean section
rate. (I-A)
11. Women who chose to delay induction > 41+0 weeks
should undergo twice-weekly assessment for fetal
well-being. (I-A)
12. Intracervical Foley catheters are acceptable agents (II-2B)
that are safe both in the setting of a vaginal birth after
Caesarean section (I-B) and in the outpatient setting. (II-2B)
13. Double lumen catheters may be considered a second-line
alternative. (II-2B)
14. Prostaglandins E2 (cervical and vaginal) should not be used in
the setting of vaginal birth after Caesarean section due to the
increased risk of uterine rupture. (II-2D)
15. Vaginal prostaglandins E2 may be considered with ruptured
membranes at term and can be used in this setting. (I-A)
16. Misoprostol can be considered a safe and effective agent for
labour induction with intact membranes and on an inpatient
basis. (I-A)
17. Misoprostol should not be used in the setting of vaginal birth
after Caesarean section due to the increased risk of uterine
rupture. (II-3D)
 Induction of Labour

18. Oxytocin should be started no earlier than 4 hours after the DEFINITIONS
last dose of misoprostol. (III-B)
19. Amniotomy should be reserved for women with a favourable Induction of labour is the initiation of contractions in a
cervix. Particular care should be given in the case of
unengaged presentation because there is a risk of cord
pregnant woman who is not in labour to help her achieve a
prolapse. (III-B) vaginal birth within 24 to 48 hours.
20. After amniotomy, oxytocin should be commenced early in
order to establish labour. (III-B)
Successful induction is defined as a vaginal delivery
within 24 to 48 hours of induction of labour.
21. In the setting of ruptured membranes at term, oxytocin should
be considered before expectant management. (I-A)
Elective induction is the induction of labour in the
22. Women positive for group B streptococcus should be started
absence of acceptable fetal or maternal indications.
on oxytocin as early as possible after ruptured membranes in
order to establish labour within 24 hours. (III-B)
Cervical ripening is the use of pharmacological or other
23. Both high- and low-dose oxytocin may be considered within a
hospital protocol. (III-B)
means to soften, efface, or dilate the cervix to increase the
likelihood of a vaginal delivery.
24. Because of the various concentrations, oxytocin infusion rates
should always be recorded in mU/min rather than mL/hr. (III-L)
Tachysystole refers to > 5 contractions per 10-minute
25. Oxytocin induction maybe considered in the hospital setting of period averaged over 30 minutes. This is further subdivided
vaginal birth after Caesarean section. (II-3B)
into two categories, one with and one without fetal heart
rate changes.4
Epub ahead of print.
This document will be published in: Hypertonus refers to excessive uterine contractions lasting
J Obstet Gynaecol Can 2013;35(9) > 120 seconds without FHR changes. This term should
be abandoned and has been replaced in this guideline by
tachystole without FHR changes.4

INTRODUCTION Hyperstimulation refers to excessive uterine contractions

(tachysystole or hypertonus) with abnormal FHR changes.

I nduction of labour is the artificial initiation of labour

before its spontaneous onset to deliver the feto-placental
unit. The frequency of induction varies by location
and institution. The rate of induction in Canada has
increased steadily from 12.9% in 1991–1992 to 19.7% in
1999–2000.1 The rate reached a high of 23.7% in 2001–2002,
decreased slightly to 21.8% in 2004–2005, and has since
remained steady.2 The 2010 BC Perinatal Health Registry
reveals a similar trend and rate, with post-term pregnancies
(> 41+0 weeks) representing 34%, the largest group, of the
total inductions in BC.3 When undertaken for appropriate
reasons, and by appropriate methods, induction is useful
and benefits both mothers and newborns.
The goal of induction is to achieve a successful vaginal
delivery that is as natural as possible. The objectives of this
guideline are to summarize the indications for induction,
review current methods of cervical ripening and labour
induction, and evaluate the safety and effectiveness of agents
and methods used in cervical ripening and labour induction.
Treatment and care should take into account women’s
individual needs and preferences. Women who are
having or being offered induction of labour should have
the opportunity to make informed choices about their
care and treatment in partnership with their health care
providers.
This term has been used in multiple induction studies.
It should be abandoned and has been replaced in this
guideline by tachystole with FHR changes.4
INDICATIONS
Induction is indicated when the risk of continuing the
pregnancy, for the mother or the fetus, exceeds the
risk associated with induced labour and delivery. The
indication must be convincing, compelling, consented
to, and documented. The reason for and method of
induction should be discussed between the care provider
and the woman in order to obtain clear consent. These
conditions are not met when induction is proposed solely
for the convenience of the care provider or patient.
Induction should be prioritized by the health care team
according to the urgency of the clinical situation and the
availability of resources. The following list of indications
for induction of labour is not meant to be exhaustive or
absolute:
High Priority
•• Preeclampsia ≥ 37 weeks
•• Significant maternal disease not responding to
treatment
•• Significant but stable antepartum hemorrhage

SEPTEMBER JOGC SEPTEMBRE 2013 l S3

SOGC Clinical Practice Guideline
•• Chorioamnionitis
•• Suspected fetal compromise
•• Term pre-labour rupture of membranes with
maternal GBS colonization
Other Indications
•• Postdates (> 41+0 weeks) or post-term
(> 42+0 weeks) pregnancy
•• Uncomplicated twin pregnancy ≥ 38 weeks
•• Diabetes mellitus (glucose control may dictate
urgency)
•• Alloimmune disease at or near term
•• Intrauterine growth restriction
•• Oligohydramnios
•• Gestational hypertension ≥ 38 weeks
•• Intrauterine fetal death
•• PROM at or near term, GBS negative
•• Logistical problems (history of rapid labour,
distance to hospital)
•• Intrauterine death in a prior pregnancy (Induction may
be performed to alleviate parental anxiety, but there is
no known medical or outcome advantage for mother
or baby.)
Unacceptable Indications
•• Care provider or patient convenience
•• Suspected fetal macrosomia (estimated fetal weight
> 4000 gm) in a non-diabetic women is an
unacceptable indication because there is no reduction
in the incidence of shoulder dystocia but twice the risk
of CS.5–7
CONTRAINDICATIONS
Induction should be avoided if there are any contraindications
to labour or vaginal delivery. They include, but are not
limited to the following:
•• placenta or vasa previa or cord presentation
•• abnormal fetal lie or presentation (e.g. transverse lie
or footling breech)
•• prior classical or inverted T uterine incision
•• significant prior uterine surgery (e.g. full thickness
myomectomy)
•• active genital herpes
•• pelvic structural deformities
S4 l SEPTEMBER JOGC SEPTEMBRE 2013
•• invasive cervical carcinoma
•• previous uterine rupture
Whenever possible, for patients with prior uterine incision
or surgery, the operative report or the opinion of the
surgeon should be obtained and reviewed.
Induction of labour using various methods may be
associated with an increased risk of:
•• failure to achieve labour
•• Caesarean section
•• operative vaginal delivery
•• tachysystole with or without FHR changes
•• chorioamnionitis
•• cord prolapse with ARM
•• inadvertent delivery of preterm infant in the case of
inadequate dating
•• Uterine rupture in scarred and unscarred uteri
Recommendations
1. The indication for induction must be documented,
and discussion should include reason for induction,
method of induction, and risks, including failure
to achieve labour and possible increased risk of
Caesarean section. (III-B)
2. If induction of labour is unsuccessful, the
indication and method of induction should be
re-evaluated. (III-B)
3. Inductions should not be performed solely for
suspected fetal macrosomia. (III-D)
4. Inductions should not be performed solely because
of patient or care provider preference. (III-D)
PRE-INDUCTION ASSESSMENT
The goal of labour induction is to achieve a successful
vaginal delivery, although induction exposes women to
a higher risk of a CS than spontaneous labour. Before
induction, there are several clinical elements that need to
be considered to estimate the success of induction and
minimize the risk of CS. Factors that have been shown
to influence success rates of induction include the Bishop
score, parity (prior vaginal delivery), BMI, maternal age,
estimated fetal weight, and diabetes.
The Bishop score was developed in 1964 as a predictor of
success for an elective induction. The initial scoring system
used 5 determinants (dilatation, effacement, station,
position, and consistency) that attributed a value of 0 to
2 or 3 points each (for a maximum score of 13). Bishop
 Induction of Labour

showed that women with a score of > 9 were equally likely Table 2. Modified Bishop Scoring System9
to deliver vaginally whether induced or allowed to labour Score
spontaneously.8 In 1966, Burnett modified the scoring Factor 0 1 2
scheme (still in use and still known as the Bishop score) Dilatation, cm 0 1–2 3–4
so that each variable was assigned a maximum value of 2
Effacement, % 0–30 40–50 60–70
points (for a maximum score of 10).9 A favourable pre-
Length, cm >3 1–3 <1
induction Bishop score of > 6 is predictive of a successful
Consistency Firm Medium Soft
vaginal delivery. Initial studies were limited to parous
Position Posterior Mid Anterior
women, but the score was later found also to be applicable
Station Sp −3 or above Sp −2 Sp −1 or 0
to nulliparous women (Table 2).

Assessment of cervical status is fundamental for the

clinician to estimate the likelihood of a successful vaginal
delivery. Of the Bishop score criteria for predicting Rates of failed induction (A) and Caesarean delivery
successful induction, the most important is cervical (B) in women undergoing induction and stratified by
parity and Bishop score at entry.17
dilatation, followed by effacement, station, and position,
with the least important being consistency.10,11 A
Several studies have shown an increased rate of failed Bishop
16
induction and CS when women are induced with an 13.5 0–3
14
unfavourable cervix.12–16 Xenakis’s prospective study of % Failed induction >3
597 pregnancies stratified by low (4 to 6) and very low 12
9.4
(0 to 3) Bishop scores found the highest risk of CS in 10
both nulliparous and parous women with scores of 0 to 3 8
versus those with a Bishop score > 3. Even women with 6
6.1
a score of 4 to 6 had a significantly higher risk of CS
4
than those with spontaneous labour (Figure). The rate 0.8
0.7 0.7
of failed induction was higher for women with a very 2

low Bishop score (0 to 3) in both nulliparous and parous 0

Overall
Primipara Multipara
women.17

The clinician may consider other non-modifiable factors

in the pre-induction counselling period with the woman. B
Elevated BMI (> 40 kg/m2),13–15 maternal age > 35 years,14,15,18 Bishop
40
estimated fetal weight > 4 kg,13,18 and diabetes mellitus13,18 34 0–3
35
have been shown to increase the CS rate when labour is 29
>3
% Cesaream delivery

induced. The presence of these negative predictive factors for 30 Spont

23
a successful induction may play a role in the mutual decision 25
20
to delay intervention and to allow for the opportunity of a 20
spontaneous labour. These factors should not be used as 13 15
15 12
a deterrent to vaginal delivery. In studies of women with a 8
10
favourable cervix, the CS rate of induced pregnancies was 6
equivalent to those managed expectantly.19–21 5
0
Several studies have compared the ability of the Bishop Primipara Multipara Overall

score to predict successful labour induction with ultrasound Reprinted with permission from Wolters Kluwer Health: Xenakis EM,
assessment of the cervix with conflicting results. Peregrine Piper JM, Conway DL, Langer O. Induction of labor in the nineties:
conquering the unfavorable cervix. Obstet Gynecol 1997;90(2):235–9.
et al. reported cervical length > 1 cm to be a predictor for
CS with induction of labour.22 In contrast, Hatfield et al.
found that cervical length was not predictive of successful
labour induction,23 and Rozenberg et al. reported that the
Bishop score was a better predictor of time interval from
induction to delivery.24 Using ultrasound to assess cervical

SEPTEMBER JOGC SEPTEMBRE 2013 l S5

SOGC Clinical Practice Guideline
ripeness, Bartha et al. found that fewer women were
induced with PG with no difference in outcomes.25
Fetal fibronectin and transvaginal ultrasound have been
shown to predict successful induction, but neither have
been shown to be superior to the Bishop score.10
Recommendations
5. Health care providers should assess the cervix
(using the Bishop score) to determine the likelihood
of success and to select the appropriate method of
induction. (II-2A)
6. The Bishop score should be documented. (III-B)
7. Care providers need to consider that induction of
women with an unfavourable cervix is associated
with a higher failure rate in nulliparous patients and
a higher Caesarean section rate in nulliparous and
parous patients. (II-2A)
PREVENTION OF INDUCTION
Routine antenatal ultrasound for confirmation of expected
date of delivery has been shown to reduce induction rates
for postdates (> 41+0 weeks) pregnancies after correction
of dates (OR 0.68, 95% CI 0.57 to 0.82).26–28
There is evidence that routine sweeping (stripping) of
membranes promotes the onset of labour and that this
simple technique decreases induction rates. It is believed
that the technique results in an increase of local production
of prostaglandins.29
Membrane sweeping involves the insertion of a digit past
the internal cervical os followed by three circumferential
passes of the digit causing separation of the membranes
from the lower segment. In clinical studies when the
cervix was closed, a massage of the cervical surface with
the forefinger and middle finger for 15 to 30 seconds
was performed. The woman should be informed of the
discomfort and pain and the possibility of bleeding post-
procedure before consent is obtained.
A 2005 Cochrane review including 32 trials found that
routine sweeping performed weekly after 38 weeks resulted
in a reduced duration of pregnancy beyond 41 and 42
weeks. The number needed to treat to prevent 1 induction
at 41 weeks was 8.30 This procedure has been associated with
maternal discomfort during vaginal examination and other
minor adverse effects (e.g. bleeding, irregular contractions).
Since the publication of the Cochrane review by Boulvain
et al.,30 several studies have been published evaluating the
sweeping of membranes. Yildirim et al. found that women
(> 38 weeks’ gestation) who underwent sweeping in the case
S6 l SEPTEMBER JOGC SEPTEMBRE 2013
of an open cervix or cervical massage rather than a pelvic
exam had more spontaneous labour within 7 days (73.7% vs.
45.5%, OR 0.2 95%, CI 0.18 to 0.46, P < 0.0001) and a greater
number of women went into spontaneous labour before
41 weeks (90.5% vs. 70.7%, OR 2.46, 95% CI 1.22 to 4.95).31
An RCT by de Miranda et al. involving 742 low-risk women
showed that sweeping every 2 days starting at 41+0 weeks
reduced the number of pregnancies reaching 42 weeks.
(NNT = 6).32
In the case of a planned VBAC, Hamdam studied
108 women who underwent serial sweeping at term and
found there was no significant effect on the onset of labour,
duration of pregnancy, induction of labour, or repeat CS.33
The effect of coitus on promoting labour is unclear.
A 2006 prospective study of 200 women by Tan et al.
used patient reported data of sexual intercourse after 36
weeks to estimate effect on gestational age and mode of
delivery.34 Coitus at term was independently associated
with earlier onset of labour (reduction of postdates
pregnancy and less requirement for induction at 41 weeks).
However, a second prospective study of 210 women by
the same researcher compared a coitus-advised group to a
no-advice group scheduled to have labour induction. The
coitus-advised group reported more sexual activity before
delivery than the non-advised group, but there was no
significant difference in spontaneous labour.35
Care provider use of appropriate or inappropriate indications
for induction has an impact on resources for performing
induction and on the overall CS rate. Lydon-Rochelle et al.
reviewed the records of 4541 induced pregnancies and found
that 15% of inductions were either not clinically indicated
or not documented.36 Le Ray et al. measured an increase in
CS rate (OR 4.1, 95% CI 1.3 to 12.9) when care providers
violated guidelines for inductions by inducing labour before
38 weeks or with a Bishop score < 5 without an indication.37
Quality improvement programs have been shown to
reduce the number of elective inductions and unplanned
CS. Several studies have shown a significant reduction in
the number of elective inductions after the implementation
of an induction committee. The role of the committee
was to review each request and enforce the use of proper
indications for induction.38–40
Institutional factors may play a role in the CS rate of
induced labours. Brennan et al. compared CS rates in
10 different groups defined by the Robson criteria. In
the group of low-risk women induced at term, the low
induction centres had a lower overall CS rate than the
higher induction centres (17.7% vs. 27.8%, P < 0.008).41

Recommendations
8. Every woman should ideally have an ultrasound,
preferably in the first trimester, to confirm
gestational age. (I-A)
9. Institutions should have quality assurance programs
and induction policies, including safety tools such as
checklists, to ensure that inductions are performed
only for acceptable indications. (II-2B)
POST-DATES INDUCTION
Postdates induction is the leading indication for induction
and deserves special consideration. The goal is the
prevention of post-term (> 42+0 weeks) pregnancy with
its associated increased perinatal morbidity, mortality, and
operative delivery rates.42,43
The multi-centre study by Hannah et al. published in 1992
compared elective induction to serial monitoring (daily
kick counts; non-stress test 3 times per week; amniotic
fluid volume 2 to 3 times per week) after 41 weeks in
3407 women with cephalic singleton pregnancies.44 The
induction group had a lower rate of CS for abnormal fetal
heart tracing (5.7% vs. 8.3%, P = 0.003) with no difference
in perinatal mortality and morbidity. Women with a cervix
dilated ≥ 3 cm were excluded. The method of induction
differed between groups: the induction group was induced
with intracervical PG gel, the serial monitoring group was
induced with amniotomy or oxytocin, or had CS regardless
of cervical status. After publication of this study, the
SOGC recommended that induction was preferred for
pregnancies completing 41+0 weeks.45
A 2006 Cochrane meta-analysis that included 19 trials
(7984 women) found that labour induction after 41+0 weeks
was associated with fewer perinatal deaths but no difference
in CS rate.28 Individual analysis for inductions done at
41+0 weeks (10 trials; RR 0.25, 95% CI 0.05 to 1.18,
NNT = 369) and 42+0 weeks (2 trials; RR 0.41, 95% CI
0.06 to 2.73) revealed a trend towards reduction of perinatal
deathineachgroupbutwasnotstatisticallysignificant.Whenthe
41-week and 42-week trials were analyzed together, the relative
risk reached significance at RR 0.30 (95% CI 0.09 to 0.99,
NNT = 339). In trials where induction occurred after 41 weeks,
there was a reduced risk of meconium aspiration syndrome
(RR 0.29; 95% CI 0.12 to 0.68, 4 trials, 1325 women) but
there was no difference in the risk of CS (10 trials at 41 weeks,
N = 5755, RR 0.92, 95% CI 0.76 to 1.12; and 5 trials at 42 weeks,
N = 810, RR 0.97, 95% CI 0.72 to 1.31), assisted vaginal
delivery, or Apgar scores of < 7 at 5 minutes.
For women who decide to delay induction, fetal well-
being should be evaluated. Delaney et al. published
Induction of Labour
a review of the management of this group and
recommended measurement of amniotic fluid and
conducting an NST.26 Biophysical profile is another
acceptable option.
Recommendations
10. Women should be offered induction of labour
between 41+0 and 42+0 weeks as this intervention
may reduce perinatal mortality and meconium
aspiration syndrome without increasing the
Caesarean section rate. (I-A)
11. Women who chose to delay induction
> 41+0 weeks should undergo twice-weekly
assessment for fetal well-being. (I-A)
OPTIONS FOR CERVICAL
RIPENING/INDUCTION: UNFAVOURABLE CERVIX
To increase the success of a vaginal delivery with an
unfavourable cervix, several effective cervical ripening
methods can be applied that include mechanical and
pharmacologic options. Neither amniotomy nor oxytocin
are effective cervical ripening agents and should not be
used as such.
Mechanical Options
Mechanical options of cervical ripening include balloon
devices (Foley catheter with and without extra-amniotic
saline infusion) that apply pressure on the internal os
of the cervix to stretch the lower uterine segment and
increase the release of local PG. Simplicity of use, potential
for reversibility, reduction in certain side effects such as
excessive uterine activity, and low cost are advantages of
these methods.
Balloon Devices: Foley Catheter
For a single balloon catheter, a no. 18 Foley is introduced
under sterile technique into the intracervical canal past
the internal os. The bulb is then inflated with 30 to
60 cc of water. The catheter is left in place until either it
falls out spontaneously or 24 hours have elapsed. Some
practitioners apply a small degree of traction on the
catheter by taping it to the inside of the leg.46 Low-lying
placenta is an absolute contraindication to the use of a
Foley catheter. Relative contraindications to its use include
antepartum hemorrhage, rupture of membranes, and
evidence of lower tract genital infection.
A 2001 Cochrane review reported mechanical methods
resulted in less tachysystole with fetal heart changes than PG
and misoprostol but no difference in CS rates. Compared
with oxytocin alone in women with an unfavourable cervix,
the CS rate was reduced with mechanical methods.47
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SOGC Clinical Practice Guideline
A 2009 RCT of 330 term (pregnancies > 36 weeks)
nulliparous women with an unfavourable cervix (Bishop
0 to 4) compared single (16F Foley) and double balloon
catheters and vaginal PGE2.48 The overall CS rate was
high but not significantly different between groups
(43% double balloon, 36% single balloon, and 37% in the
PGE2 group P = 0.567). The single balloon catheter had
the shortest induction to delivery interval (single balloon =
25.8 h, PGE2 = 25.8 h, double balloon = 30.6 h). Uterine
tachysystole occurred in 14% (9% with normal fetal heart
tracing; 4% with atypical fetal heart tracing; and 1% with
abnormal fetal heart tracing requiring delivery) of the PGE2
group compared to none in the mechanical cervical ripening
group. Cervical ripening with the single balloon catheter
was associated with significantly less pain than the double
balloon or vaginal PGE2.48
Heinemann et al. systematic review of 30 RCTs showed
an increased risk of both maternal infection (defined as
pyrexia of 38°C, chorioamnionitis, peripartum infection, or
chorioamnionitis and/or endomyometritis), and neonatal
infection when all (Foley catheters, hydroscopic dilators,
laminaria) mechanical methods were analyzed. Studies
limited to Foley catheters compared with pharmacological
agents for cervical ripening had similar rates for maternal
infection and there was no increased risk of neonatal
infection.49
The indications and methods of induction should not be
altered in the case of women known to be colonized with
GBS.50
A prospective, randomized trial compared in-patient
versus outpatient use of a Foley catheter for 111 term
pregnancies with an indication for induction of labour.
Indications included elective (n = 48), post-dates (n = 44),
macrosomia (n = 14), gestational diabetes (n = 3), and
chronic hypertension (n = 2). The mean Bishop score was
3 for each group. There was no significant difference in the
two groups for change in Bishop score, maximum dose of
oxytocin, time of oxytocin, epidural rate, induction time,
1-minute and 5-minute Apgar scores, and cord pH. The
outpatient group spent an average of 9.6 hours less in
hospital.51
The use of a trans-cervical Foley catheter for induction of
labour in women who had a previous CS is not associated
with an increased risk of uterine rupture.52 Foley catheters
have shown to be efficacious with a shorter induction-
to-delivery time than PG for induction of labour with an
unfavourable cervix.53,54 Both agents have similar CS rates,
but Foley catheters result in increased need for oxytocin
stimulation and there is more tachysystole with PG.55
S8 l SEPTEMBER JOGC SEPTEMBRE 2013
Recommendations
12. Intracervical Foley catheters are acceptable agents
(II-2B) that are safe both in the setting of a vaginal
birth after Caesarean section (I-B) and in the
outpatient setting. (II-2B)
13. Double lumen catheters may be considered a
second-line alternative. (II-2B)
Practice Points
•• There is an increased need for oxytocin when Foley
catheters are used.
•• In comparison with prostaglandins, Foley catheters
cause much less uterine tachysystole.
•• Foley catheters are not associated with increased
rates of maternal infection (chorioamnionitis and
endometritis) or neonatal infection.
•• Use of Foley catheters does not reduce the rate of CS
from that of PG.
PHARMACOLOGICAL OPTIONS
Prostaglandins
Prostaglandin E2 acts on the cervix by dissolving the
collagen structural network of the cervix. Prostaglandin
E2, dinoprostone, is available in 3 different preparations
as a cervical ripening agent: controlled-release gel 10 mg
(Cervidil), intravaginal 1 mg and 2 mg gel (Prostin), and
intracervical 0.5 mg gel (Prepidil). Vaginal preparations
(Prostin, Cervidil) are easier to administrate than
intracervical (Prepidil) preparations. The controlled-release
gel preparation (Cervidil) allows easier removal in case of
uterine tachysystole with FHR changes and requires only a
30-minute delay before the initiation of oxytocin upon its
removal compared with an interval of 6 hours for the gel.
Advantages of PGE2 include patient acceptance, a lower
operative rate than oxytocin, and less need for oxytocin
augmentation when used with an unfavourable cervix
(Bishop < 7). Cost savings may be realized by a reduction
in operative deliveries and/or lengths of stay. PGE2 is
a bronchodilator and is not contraindicated in women
who suffer from asthma. In a prospective study of 2513
women with known asthma and who received PG, none
had evidence of an exacerbation of their condition.56
A 2009 Cochrane review including 63 studies (10 441
women) reported that compared with placebo vaginal
PGE2 reduced both the likelihood of not achieving a vaginal
delivery within 24 hours (18% vs. 99%, RR 0.19, 95% CI
0.14 to 0.25) and the use of oxytocin stimulation (21.6%
vs. 40.3%).57 There was no difference in CS, but there
was an increase with vaginal PGE2 in uterine tachysystole

with FHR changes (4.6% versus 0.51%, RR 4.14, 95% CI
1.93 to 8.90). The tablet, pessary, and gel were equivalent,
although the sustained released PGE2 insert was associated
with a decrease in instrumental deliveries.
A 2008 Cochrane review of intracervical gel versus placebo
included 28 trials with 3764 women undergoing cervical
ripening or induction regardless of membrane status.58
There were fewer women in the PG group who did not
achieve vaginal delivery within 24 hours (RR 0.61 95% CI
0.47 to 0.79). There was a non-significant reduction in the
overall risk of CS for all women (RR 0.88, CI 0.77 to 1.00),
but there was a statistically significant reduction of CS
(RR 0.82, 95% CI 0.68 to 0.98) in women with an
unfavourable cervix and intact membranes, suggesting
that oxytocin alone can and should be used for induction
after term PROM. There was an increased risk of uterine
tachysystole without changes in FHR (RR 1.59 95% CI 1.09
to 2.33) but no increase tachysystole with FHR changes.58
The same review compared intracervical and intravaginal
interventions in 3881 women in 29 trials. The risk of not
achieving vaginal delivery at 24 hours was greater in the
intracervical group (RR 1.26, 95% CI 1.12 to 1.41) but
there were no differences in the risk of CS and tachysystole
with or without fetal heart changes.58
PGs have been used to induce labour with PROM at term.
A 2006 Cochrane review included 12 trials (6814 women,
PROM > 37 weeks) and compared planned management
with either oxytocin or vaginal prostaglandin with expectant
management. Overall, there was no difference for mode of
birth; results were similar for CS and vaginal delivery. For
women who underwent planned delivery, there was less
chorioamnionitis or endometritis and fewer admissions to
NICU, but no difference in neonatal infection rates. One
trial found that women in the planned group were more
likely to perceive the experience as being more positive.59
The timing of insertion may have an influence on
interventions. One study of 620 women (nulliparous and
parous) compared admission in the morning versus the
evening and found that morning inductions were less likely
to need oxytocin infusion (45% vs. 54%, RR 0.83, 95% CI
0.70 to 0.97). Nulliparous women admitted in the morning
had fewer operative vaginal births (16.1% vs. 34.2%,
RR 0.47, 95% CI 0.25 to 0.90).60 Adverse effects with the
use of prostaglandin E2 include uterine tachysystole and
maternal effects (i.e. fever, chills, vomiting, diarrhea). Care
must be taken to avoid application of the higher dose vaginal
preparations into the cervical canal. Rare, idiopathic adverse
cardiovascular events may occur, but they almost always
occur immediately after the administration of the agent.
Induction of Labour
In the event of tachysystole, attempts should be made to
remove the prostaglandin from the vagina. Intrauterine
rescue may be required and use of a tocolytic agent may
be considered (intravenous Nitroglycerin 50 mcg given
over 2 to 3 minutes and repeated every 3 to 5 minutes to a
maximum of 200 mcg). To date, the evidence for safety and
efficacy remains inconclusive. Another option is the use of
nitroglycerin spray (0.4 mg, 1 to 2 puffs sublingual), which
has the advantage of a simple and rapid administration and
uptake, although there have been no clinical trials assessing
dosing.61
Outpatient PG is an attractive option for reducing the use of
health care resources. Large studies are lacking to determine
their overall safety, in particular for rare but serious adverse
effects. A 2003 RCT of 300 women evaluated outpatient
versus in-patient induction with Cervidil. Three hundred
eligible patients with uncomplicated, low-risk pregnancies
and a Bishop score ≤ 6, parity ≤ 5, gestation > 37 weeks,
a reactive NST, and singleton cephalic pregnancy with
intact membranes. Cervidil was inserted and the patient
monitored for 1 hour before being allowed to go home.
Use of oxytocin, epidural rate, operative delivery rate, CS
rate, and median time to labour and delivery within 24
hours were the same for each group. The outpatient group
spent a median of 8 hours at home and reported a higher
satisfaction during the initial 12 hours (56% vs. 39%).62
Current recommendations for outpatient induction in
low-risk pregnancies suggest continuous electronic fetal
monitoring for 1 to 2 hours after administration of PG
and the use of intermittent auscultation when labour is
active.63
A 2010 Cochrane review including 28 RCTs with
2616 women who were induced with mechanical and
pharmacological methods concluded that the outpatient
setting was feasible, but that there was insufficient evidence
to recommend which method was most effective and safe.64
Sweeping of the membranes during induction of labour
increases success rates. Two randomized trials recruited
women with term, cephalic, nulliparous and parous
pregnancies and intact membranes scheduled for induction
with PG vaginal gel if the cervix was unfavourable (Bishop
≤ 4) or with amniotomy if the cervix was favourable
(Bishop > 4 or cervix > 3 cm). Both groups were treated
according to institutional protocols for active management
of labour. Both studies showed that membrane sweeping
at the time of induction resulted in shorter induction to
delivery time, lower use of oxytocin, and a higher rate
of spontaneous vaginal deliveries. Tan et al.35 benefit
applied to both nulliparous and parous women, while
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SOGC Clinical Practice Guideline
Foong et al.65 found that the benefit of sweeping was
limited to nulliparous women with an unfavourable cervix.
Tan et al. also found both higher maternal satisfaction in
the birth process and higher post-sweeping pain.35
Summary Statements
1. Prostaglandins E2 (cervical and vaginal) are effective
agents of cervical ripening and induction of labour
for an unfavourable cervix. (I)
2. Intravaginal prostaglandins E2 are preferred to
intracervical prostaglandins E2 because they results
in more timely vaginal deliveries. (I)
Recommendations
14. Prostaglandins E2 (cervical and vaginal) should
not be used in the setting of vaginal birth after
Caesarean section due to the increased risk of
uterine rupture. (II-2D)
15. Vaginal prostaglandins E2 may be considered with
ruptured membranes at term and can be used in
this setting. (I-A)
Practice Points
•• PGE2 reduce CS rates of women with an unfavourable
cervix and result in greater maternal satisfaction.
•• Oxytocin can be started 30 minutes after removal of a
dinpoprostone insert (Cervidil) and 6 hours hours after
gel (Prostin, Prepidil).
•• PGE2 in the setting of ruptured membranes had more
maternal but no more neonatal infections.
•• Care must be taken to avoid the insertion of the higher
dose of vaginal PGE2 (2 mg) into the cervical canal.
•• Uterine tachysystole without FHR changes is more
common with PGE2 but does not lead to a higher
CS rate.
•• Nitroglycerin can be used to treat uterine tachysystole
but requires more study.
Misoprostol is a synthetic PGE1 analog that has been
approved and marketed for the prevention and treatment
of gastric ulcers associated with the use of non-steroidal
anti-inflammatory drugs.66 Misoprostol has also been
found to be an effective agent for cervical ripening and
labour induction, and those off-label uses have been widely
adopted.
The first study to describe the successful induction of
labour in the case of intrauterine fetal demise was published
in 1987.67 Since then, there have been over 100 randomized
trials studying the efficacy and safety of induction in viable
term inductions.
S10 l SEPTEMBER JOGC SEPTEMBRE 2013
Benefits of misoprostol include its stability at room
temperature, rapid onset of action, multiple potential
routes of administration (oral, buccal, sublingual, vaginal,
rectal), and low cost. These potential benefits make it an
attractive alternative to PGE2.
Dosing of misoprotol:
•• Give 50 mcg orally with a drink of water (ensure that it
is swallowed quickly to avoid sublingual absorption) or
give 25 mcg vaginally.
•• Repeat every 4 hours as long as contractions are absent
or non-painful.
•• Oxytocin can only be used 4 hours after the last dose.
Serious adverse events with the use of misoprostol
are similar to those of other PG and include uterine
tachysystole with its potential fetal and maternal effects
and meconium staining of liquor. It is generally agreed
that it is a potent uterotonic and should not be used in
women with a previous CS because it will increase the risk
of uterine rupture.68,69 In general, large studies are required
to assess the rare, but life-threatening, uterine rupture that
has been reported anecdotally in women with and without
a previous CS.70 A 2010 Cochrane review of vaginal
misoprostol for cervical ripening and induction of labour
included 121 trials that compared misoprostol to placebo/
no treatment or to other methods (vaginal PG, cervical
PG, and oxytocin) of induction. Vaginal misoprostol
was superior to placebo with a reduced failure to achieve
vaginal delivery within 24 hours (RR 0.51, 95% CI 0.37 to
0.71) but increased tachysystole without fetal heart changes
(RR 3.53, 95% CI 1.78 to 6.99).71
Several studies have compared 25 mcg and 50 mcg doses.
Most have found that lower doses of misoprostol resulted
in more need for oxytocin augmentation and less uterine
tachysystole, with and without FHR changes, compared
to higher doses.7,71 The induction to delivery time was
shorter with the higher 50 mcg dose.66,72 An RCT of
124 women using several different doses (25, 50, 100,
200 mcg) resulted in more vaginal deliveries at 12 and
24 hours, more tachysystole, and less need for oxytocin
with each incremental dose.73 A double-blind RCT of
374 women (> 36 weeks, Bishop ≤ 4) administered either
100 mcg or 200 mcg misoprostol vaginal insert had similar
findings with the higher dose resulting in significantly more
women achieving vaginal delivery within 24 hours (24%
vs. 36%), shorter induction to delivery time (1181 vs. 1744
minutes), and less use of oxytocin (49% vs. 71%), but an
increased rate of tachysystole (41% vs. 19.5%). There was a
non-significant reduction of CS in the higher 200 mcg dose
group (22.9% vs. 32.4%).74

A 2006 Cochrane review including 4 trials (474 women)
comparing oral misoprostol with placebo found the
misoprostol group was less likely to have long labour
(RR 0.16, 95% CI 0.05 to 0.49), had less need for oxytocin
(RR 0.32, 95% CI 0.24 to 0.43), and had a lower CS rate
(RR 0.62, 95% CI 0.40 to 0.96). The author recommended
that the oral misoprostol dose should not exceed 50 mcg.75
The same Cochrane review included 16 trials (3645 women)
and found that women who were given oral misoprostol
had a lower incidence of uterine tachysystole without FHR
changes (RR 0.37, 95% CI 0.23 to 0.59) and more need
for oxytocin (RR 1.28, 95% CI 1.11 to 1.48), but more
meconium stained liquor (RR 1.27, 95% CI 1.01 to 1.60)
than women given vaginal misoprostol.75 A prospective
RCT of 204 women comparing 25 mcg oral versus 50 mcg
vaginal given every 4 hours up to 4 doses found that the
lower oral dose had lower incidence of tachysystole with
FHR changes (2.2% vs. 5.4%) and a lower CS rate (19.4%
vs. 32.4%), but no difference in induction to delivery time
or side effects (nausea, vomiting, shivering, or diarrhea)
than the higher vaginal dose.76 An RCT of 120 women that
compared 12.5 mcg oral misoprostol with 25 mcg vaginal
found no difference in outcomes in terms of mode of
delivery, induction to delivery time, need for oxytocin, or
complications.77
A 2008 RCT of 205 women comparing oral (20 mcg every
hour for up to 4 doses until 3 contractions in 10 minutes)
and vaginal (25 mcg every 4 hours until Bishop > 7)
misoprostol found that the oral group had a higher rate
of vaginal deliveries at 12 hours (74.4% vs. 25.5%) and a
lower rate of tachysystole (0% vs. 11.3%), but more nausea
(11% vs. 0%). This study was limited because the staff was
not blinded and the average total dose of misoprostol was
higher in the oral group (180 mcg vs. 50 mcg).78
A 2009 systemic review included 9 studies (2937 women)
comparing low-dose oral misoprostol (20 to 25 mcg) to
dinoprostone (PGE2), vaginal misoprostol, and oxytocin.
Two of the trials compared oral and low-dose vaginal
misoprostol and found that the oral route resulted in less
uterine tachysystole with FHR changes.79
Misoprostol (PGE1) versus Dinoprostone (PGE2)
A 2006 Cochrane review included 9 trials (2627 women)
that compared oral misoprostol to vaginal dinoprostone
and found that women who received oral misoprostol
were less likely to have a CS.75 However, this only reached
significance in women with intact membranes (RR 0.78,
95% CI 0.66 to 0.94). There was more uterine tachysystole
in the oral group, but this was not associated with adverse
fetal outcomes.
Induction of Labour
A 2009 systemic review that compared oral misoprostol
to vaginal dinoprostone included 5 studies (2281 women),
only 1 of which was blinded, and found that women who
had oral misoprostol had fewer CS (2% vs. 26%) but their
need for oxytocin stimulation, incidence of tachysystole
without FHR changes, and maternal adverse effects were
similar to those who had vaginal dinoprostone.79 A similar
review found that the CS rate was the same, but that the
misoprostol group had a higher rate of vaginal deliveries
within 24 hours, a lower rate of oxytocin use, and a trend
towards higher meconium staining.80
A 2010 Cochrane review concluded that vaginal misoprostol
was also superior to other induction agents (vaginal
prostaglandin, intracervical prostaglandin, and oxytocin),
with less epidural use and fewer failures to achieve vaginal
delivery within 24 hours, but more tachysystole with FHR
changes.71
Several studies have reported on efficacy of sublingual
misoprostol to be comparable to the oral route. An RCT
of 212 women compared 50 mcg to 100 mcg sublingual
doses and reported the higher dose to be more effective
but to result in more tachysystole.81 A double blind RCT of
140 women found that 50 mcg of sublingual misoprostol
had a similar efficacy to 25 mcg vaginal misoprostol.82 A
systemic review that included 5 studies (740 women) found
no difference between sublingual (25 to 50 mcg every
4 hours) and vaginal misoprostol (25 to 50 mcg every
4 hours) in the rates of vaginal deliveries at 24 hours,
uterine tachysystole, or CS.83 Two studies reported that
patient satisfaction was higher using the sublingual route
than the vaginal route.84,85
A prospective randomized study of 96 patients with an
unfavourable cervix underwent cervical ripening with
either vaginal misoprostol (50 mcg dose) or Foley catheter.
The misoprostol group achieved a favourable cervix
(Bishop ≥ 6) faster than the Foley group (98% vs. 69%,
P < 0.001), although the induction to delivery interval
was equivalent. There was lower use of oxytocin in the
misoprostol group, part of which could be attributed to
the 6-hour wait required before starting oxytocin after the
last dose.86
Another study of 100 women comparing a higher single
dose of misoprostol (100 mcg vaginal) to Foley catheter
for cervical ripening found that misoprostol had a shorter
induction to delivery time (11.8 h vs. 20.0 h, P < 0.05).
There were two uterine ruptures, both in the misoprostol
group. One occurred in a 39-year-old parous woman with 3
previous deliveries induced at term because of an impaired
glucose tolerance that developed persistent fetal tachycardia
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SOGC Clinical Practice Guideline
7 hours post-insertion without uterine tachysystole. The
second woman with uterine rupture was a nulliparous
32-year-old induced because of prolonged pregnancy
complicated by second stage dystocia due to cephalopelvic
disproportion who developed uterine tachysystole with
abnormal FHR changes 11 hours post-insertion. Both
infants were delivered with Apgar ≥ 7 at 5 minutes.87
Few studies have used misoprostol in the case of PROM.
An open RCT of 150 women with PROM at term
compared vaginal misoprostol (25 mcg every 6 hours ×
4 doses) to expectant management followed by oxytocin
induction if labour did not begin. The misoprostol group
had a shorter latency time to achieve labour (9.4 vs. 15.8
hours), shorter recruitment to delivery time (18.9 vs. 27.5
hours), a trend towards lower oxytocin use, and lower CS.88
An RCT of 758 women compared low dose (25 mcg)
oral (Bishop > 6) or vaginal (Bishop ≤ 6) misoprostol to
vaginal dinoprostone with rupture of membranes > 34
weeks’ gestation. There was no difference in CS and vaginal
delivery rates but there was a trend towards the misoprostol
group requiring less oxytocin, less epidural use, and less
CS for failure to progress. Misoprostol also seemed to
be more effective than dinoprostone in the setting of
an unfavourable cervix, whereas oxytocin seemed to be
more effective than misoprostol in a favourable cervix.
Unfortunately, the predetermined sufficient sample size
of 1890 women to provide meaningful results could not
be reached due to lack of funding. Larger studies with
sufficient numbers are required to complete the analysis.89
Recommendations
16. Misoprostol can be considered a safe and effective
agent for labour induction with intact membranes
and on an inpatient basis. (I-A)
17. Misoprostol should not be used in the setting of
vaginal birth after Caesarean section due to the
increased risk of uterine rupture. (II-3D)
18. Oxytocin should be started no earlier than 4 hours
after the last dose of misoprostol. (III-B)
Practice Points
•• Misoprostol is more effective than PGE2 to achieve
vaginal delivery and results in less epidural use but
more uterine tachysystole.
•• PGE1 and PGE2 both reduce CS rates in an
unfavourable cervix.
•• The oral and vaginal routes have a similar reduction
of CS rates. The oral route needs more oxytocin
stimulation but the vaginal route will have more
tachysystole.
S12 l SEPTEMBER JOGC SEPTEMBRE 2013
•• The lower vaginal dose (25 mcg) tends to need more
oxytocin stimulation and the higher vaginal dose
(≥ 50 mcg) tends to have more uterine tachysystole.
•• All doses of misoprostol can cause uterine
tachysystole.
•• Fetal well-being is required before administration of
misoprostol. Electronic fetal monitoring should be
performed for 30 minutes after administration of
misoprostol and for 60 minutes after any tachysystole.
OPTIONS FOR INDUCTION
WITH A FAVOURABLE CERVIX
Amniotomy
Amniotomy can be a simple and effective component
of labour induction when the membranes are accessible
and the cervix is favourable. This intervention creates a
commitment to delivery and must be done for convincing
and compelling reasons. However, the time interval from
amniotomy to established labour may not be acceptable
to clinicians or to women, and in a number of cases, after
amniotomy alone, labour will not commence.
Contraindications include placenta previa, vasa previa, and
active genital infection except for women colonized with
GBS. Cord prolapse is a risk of amniotomy, especially in a
high presentation or unstable lie. After the membranes are
ruptured, the care provider should continue to palpate the
presenting part until it rests against the cervix to ensure
there has been no cord prolapse. The amount, colour, and
consistency of the fluid as well as fetal well-being should
be assessed.
There are no studies comparing amniotomy alone to
placebo.
Amniotomy can be used for induction when the cervix is
favourable, but the onset of labour is unpredictable and
often requires oxytocin. A 2007 Cochrane meta-analysis
of 17 trials with 2566 women measured the safety of
amniotomy and intravenous oxytocin for induction of
labour. Amniotomy alone resulted in fewer vaginal deliveries
in 24 hours then amniotomy plus oxytocin (RR 0.03,
95% CI 0.01 to 0.49). Amniotomy and oxytocin resulted in
fewer instrumental deliveries than placebo (RR 0.18, 95%
CI 0.05 to 0.58). However, there was more postpartum
hemorrhage (RR 5.5, 95% CI 1.26 to 24.07) and maternal
dissatisfaction (RR 53, 95% CI 3.32 to 846.51) with
amniotomy and oxytocin than with vaginal PG.90
A more recent small RCT of amniotomy and immediate
oxytocin infusion versus amniotomy and delayed oxytocin
infusion for induction of labour in 123 women at term

found that women in the immediate group were more
likely to be in established labour 4 hours post amniotomy,
have a shorter amniotomy to delivery interval (P < 0.001),
and achieve vaginal delivery within 12 hours (RR 1.5;
95% CI 1.2 to 12.6).91 There was no difference between
the groups with regard to mode of delivery or incidence
of uterine tachysystole with abnormal FHR recording.
Although the study was underpowered to provide an
adequate statistical analysis, women in the immediate
group were more likely to be satisfied with the induction
process (RR 4.1, 95% CI 1.1 to 16.1) and the duration of
labour (RR 1.8, 95% CI 1.0 to 3.3).
Recommendations
19. Amniotomy should be reserved for women with a
favourable cervix. Particular care should be given in
the case of unengaged presentation because there is
a risk of cord prolapse. (III-B)
20. After amniotomy, oxytocin should be commenced
early in order to establish labour. (III-B)
Practice Point
•• Amniotomy creates a commitment to delivery
and should be performed when the indication for
induction is convincing and the reasons compelling
and documented.
Oxytocin
Intravenous oxytocin, available since the 1950s, has been
the most commonly used method of induction for women
with a viable pregnancy and favourable cervix. Oxytocin is a
peptide produced naturally in the posterior hypothalamus that
binds to uterine receptors to produce uterine contractions,
but it has no direct effect on the cervix. It has a half-life
of 5 to 12 minutes,92 a time to steady plasma concentration
of 40 minutes,93 and a steady-state uterine response of 30
minutes or longer.94 The uterus is increasingly responsive
to oxytocin as pregnancy progresses.95 Other areas of the
body that respond to oxytocin include the breast, vascular
smooth muscle, and kidney. At dosages typically used for
the induction of labour, there is not a demonstrable effect
on renal function or vascular smooth muscle tone. However,
IV boluses of as little as 0.5 U can transiently decrease
peripheral vascular tone, leading to hypotension.96 Due to its
antidiuretic activity, water intoxication is possible with high
doses (> 40 mU/min).
The physiological dose of oxytocin to produce regular
uterine contraction is 8 to 12 mU/min. The ideal dosing
regimen of oxytocin is not known and there are both low-
dose and high-dose protocols. The low-dose regimen begins
with 1 to 2 mU/min, increased incrementally by 1 to 2 mU
at 30-minute intervals. The high-dose regimen commences
Induction of Labour
with a dose of 4 to 6 mU/min, with dose increments of
4 to 6 mU/min every 15 to 30 minutes. The benefits of
the low-dose regimen include less risk of tachysystole and
the use of a smaller overall dose. However, the high-dose
oxytocin regimen has been shown to reduce the length of
labour with no appreciable increase in neonatal morbidity97.
High-dose oxytocin has been associated with an increase
in uterine tachysystole with associated FHR changes.61
Continuous fetal monitoring is recommended with the use
of oxytocin.98 Because mixing methods vary, the rate of
infusion should always be documented in mU/min rather
than ml/hour.
Example of low-dose protocol:
Initial dose of oxytocin..................................1 to 2 mU/min
Increase interval......................................................30 minutes
Dosage increment....................................................1 to 2 mU
Usual dose for good labour.........................8 to 12 mU/min
Maximum dose before reassessment.................30 mU/min
Example of high-dose protocol:
Initial dose of oxytocin..................................4 to 6 mU/min
Increase interval............................................15 to 30 minutes
Dosage increment...........................................4 to 6 mU/min
Usual dose for good labour.........................8 to 12 mU/min
Maximum dose before reassessment.................30 mU/min
A 2009 Cochrane review included 61 studies (12 819
women) of the methods of cervical ripening and labour
induction.99 Oxytocin alone versus vaginal prostaglandins
was associated with an increase in unsuccessful vaginal
delivery within 24 hours (70% vs. 21%). Oxytocin versus
intracervical prostaglandins also had fewer vaginal deliveries
(51% vs. 35%) and increase in CS rates (19.1% vs. 13.7%).
For all women with an unfavourable cervix regardless of
membrane status, the CS rates were increased (19.0% vs.
13.1%, RR 1.42, 95% CI 1.11 to 1.82) when labour was
induced.99
In the case of a favourable cervix, the CS rate was no
different whether the pregnancy was induced or managed
expectantly.8,17,21 Osmundson et al. measured a significantly
higher rate of oxytocin use in the elective induction group
than in the group managed expectantly (99.3 % vs. 30.6 %,
P < 0.001).21
Term PROM
A 2006 Cochrane analysis reviewed the advantages of early
intervention with either oxytocin or prostaglandin versus
expectant management in the setting of term PROM.59
SEPTEMBER JOGC SEPTEMBRE 2013 l S13
SOGC Clinical Practice Guideline
Planned delivery resulted in less chorioamnionitis and
endometritis and fewer admissions to neonatal ICU, with
no difference in neonatal infection rates or mode of
delivery.
PROM with GBS
The 2009 Cochrane review included women with
ruptured membranes. In this setting, there was some
evidence of less chorioamnionitis (RR 0.66, CI 0.47 to
0.92) and use of antibiotics in the neonatal period with
the use oxytocin alone than with vaginal PGE2.99 The
authors stated the data should be viewed with caution
because the infection had not been not pre-specified. In
the setting of term PROM and GBS, the Term PROM
trial showed that GBS colonization was predictive
of neonatal infection for induction with vaginal PG
(OR 5.13, 95% CI 2.54 to 10.37) and in expectant
groups (OR 4.12, 95% CI 2.00 to 8.52) but not in the
group induced with oxytocin.100
VBAC
Oxytocin can be used in women with a previous CS, but
caution, care, and diligence should be used as it has been
shown to increase the risk of rupture.69,101
Recommendations
21. In the setting of ruptured membranes at term,
oxytocin should be considered before expectant
management. (I-A)
22. Women positive for group B streptococcus should
be started on oxytocin as early as possible after
ruptured membranes in order to establish labour
within 24 hours. (III-B)
23. Both high- and low-dose oxytocin may be
considered within a hospital protocol. (III-B)
24. Because of the various concentrations, oxytocin
infusion rates should always be recorded in
mU/min rather than mL/hr. (III-L)
25. Oxytocin induction maybe considered in the
hospital setting of vaginal birth after Caesarean
section. (II-3B)
Practice Points
•• With PROM, oxytocin stimulation is more effective
than expectant management to reduce maternal
infection and increase vaginal deliveries within 24
hours, but it may increase CS rate.
•• In the setting of PROM, women preferred oxytocin
induction over expectant management.
The care provider should maintain a higher level of
vigilance for uterine dehiscence and rupture when using
oxytocin in an attempted VBAC.
S14 l SEPTEMBER JOGC SEPTEMBRE 2013
UTERINE RUPTURE
Uterine rupture is a rare but potentially devastating
complication for both mother and fetus. Uterine rupture is
possible during induced labour in the absence of a scarred
uterus, and is usually associated with aggressive use of
uterotonic agents in the presence of obstructed labour (e.g.
brow or posterior presentation). A population-based study
in the Netherlands comparing induced and spontaneous
labour found 210 cases of uterine rupture with an incidence
of 5.9 per 10 000 pregnancies. Ruptures occurred in both
scarred and unscarred uteri. The overall relative risk of
uterine rupture with induction of labour was 3.6 (95% CI
2.7 to 4.8) with an absolute risk of 1 in 629. For women with
a previous CS, PG conferred the greatest risk for rupture of
all uterotonic agents.69 Lydon-Rochelle et al. also reported
the greatest risk of rupture in women with a previous CS
when PG were used, with an incidence of 24.5 per 1000
(RR 15.6, 95% CI 8.1 to 30.0).36 Oxytocin is considered a
safe uterotonic agent for use in the presence of a scarred
uterus, but it should be used with due care and diligence.102
INDUCTION OF LABOUR
AND ADVANCED MATERNAL AGE
Advanced maternal age (35 years or older) now accounts
for 17% of all pregnancies and 17.44% all live births in
Canada.103 It has been well documented that these women
are at risk of several adverse outcomes in pregnancy
including stillbirth. Rates have been stated to be 1/116
in women 40 and older from 37 weeks’ gestation and
greater. Population-based studies showed higher perinatal
mortality rates among women aged 35 to 39 and those
40 years or older than in women aged 20 to 24.104–106
Given the increased risk of stillbirth in women with
advanced maternal age some experts suggest that women
≥ 40 years of age be considered biologically post-term
at 39 weeks’ gestation and that delivery be considered at
this gestation.107
A single study was found comparing induction of labour
with misoprostol to oxytocin in women of advanced
maternal age (≥ 35) with an unfavourable cervix (Bishop
< 6). The results were consistent with other studies showing
the benefit of PG over oxytocin in an unripe cervix.108
INDUCTION OF LABOUR AND ARTIFICIAL
REPRODUCTIVE TECHNOLOGIES
ART has been shown to be associated with adverse
outcomes in pregnancy including gestational hypertension,
gestational diabetes, placenta previa and placental
abruption, stillbirth, neonatal death, preterm delivery, low

and very low birth weight, small for gestational age, and
NICU admission as illustrated in a recent SOGC-CFAS
guideline.109 A prospective database review by the FASTER
Research Consortium showed an adjusted OR (95% CI)
of 2.1 (1.3 to 3.6) for fetal loss or demise (> 24 weeks).110
Many women undergoing ART are older, which increases
their risk of the adverse perinatal outcomes listed above.
Until there is more evidence available, induction should be
considered on an individual basis.
SUMMARY
The rate of labour induction has increased significantly
since the early 1990s and continues to involve a significant
percentage of pregnancies, removing women from the
advantageous natural process of labour. While there
are indications to recommend induction, postdates
pregnancies remain a large contributor to the induction
rates. Practitioners need to apply clinical judgement
and evidence-based medicine to justify that induction is
superior to continuation of pregnancy. The benefit of
induction over the continuation of a pregnancy is not
always clear, but the clinician has some tools to evaluate
the likelihood of a successful vaginal delivery. The clinician
should consider all of the tools available to optimize a safe
process towards achieving a successful vaginal delivery.
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101. Martel M-J, McKinnon CJ: Clinical Practice Obstetrics Committee.
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2005;27:164–74.
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107. Johnson J-A, Tough S. Delayed child-bearing SOGC Committee Opinion
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 295, August 2013

Intrauterine Growth Restriction:

Screening, Diagnosis, and Management
Abstract
This clinical practice guideline has been prepared by the
Maternal Fetal Medicine Committee and approved by the Background: Intrauterine growth restriction (IUGR) is an obstetrical
Executive and Council of the Society of Obstetricians and complication, which by definition would screen in 10% of fetuses
Gynaecologists of Canada. in the general population. The challenge is to identify the subset
of pregnancies affected with pathological growth restriction in
PRINCIPAL AUTHORS order to allow intervention that would decrease morbidity and
mortality.
Andrea Lausman, MD, Toronto ON
Objective: The purpose of this guideline is to provide summary
John Kingdom, MD, Toronto ON statements and recommendations and to establish a framework
for screening, diagnosis, and management of pregnancies
MATERNAL FETAL MEDICINE COMMITTEE affected with IUGR.
Robert Gagnon, MD (Chair), Verdun QC Methods: Affected pregnancies are compared with pregnancies
Melanie Basso, RN, Vancouver BC in which the fetus is at an appropriate weight for its gestational
age. History, physical examination, and laboratory investigations
Hayley Bos, MD, London ON including biochemical markers and ultrasound characteristics of
IUGR are reviewed, and a management strategy is suggested.
Joan Crane, MD, St. John’s NL
Evidence: Published literature in English was retrieved through
Gregory Davies, MD, Kingston ON
searches of PubMed or MEDLINE, CINAHL, and The Cochrane
Marie-France Delisle, MD, Vancouver BC Library in January 2013 using appropriate controlled vocabulary
via MeSH terms (fetal growth restriction and small for gestational
Lynda Hudon, MD, Montreal QC
age) and key words (fetal growth, restriction, growth retardation,
Savas Menticoglou, MD, Winnipeg MB IUGR, low birth weight, small for gestational age). Results
were restricted to systematic reviews, randomized control
William Mundle, MD, Windsor ON
trials/controlled clinical trials, and observational studies. Grey
Annie Ouellet, MD, Sherbrooke QC (unpublished) literature was identified through searching the
websites of health technology assessment and health technology-
Tracy Pressey, MD, Vancouver BC related agencies, clinical practice guideline collections, clinical
Christy Pylypjuk, MD, Saskatoon SK trial registries, and national and international medical specialty
societies.
Anne Roggensack, MD, Calgary AB
Values: The quality of evidence in this document was rated using the
Frank Sanderson, MD, Saint John NB criteria described in the Report of the Canadian Task Force on
Disclosure statements have been received from all members of Preventive Health Care (Table).
the committee. Benefits, harms, and costs: Implementation of the
recommendations in this guideline should increase clinician
recognition of IUGR and guide intervention where appropriate.
Optimal long-term follow-up of neonates diagnosed as IUGR may
improve their long-term health.

Key Words: intrauterine growth restriction (IUGR), screening,

diagnosis, management, ultrasound, Doppler, placenta.
J Obstet Gynaecol Can 2013;35(8):741–748

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

AUGUST JOGC AOÛT 2013 l 741

SOGC Clinical Practice Guideline
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.
Summary Statements
01. The definition of small-for-gestational age for a fetus in utero
is an estimated fetal weight that measures < 10th percentile
on ultrasound. This diagnosis does not necessarily imply
pathologic growth abnormalities, and may simply describe a
fetus at the lower end of the normal range. (III)
02. Intrauterine growth restriction refers to a fetus with an
estimated fetal weight < 10th percentile on ultrasound
that, because of a pathologic process, has not attained
its biologically determined growth potential. (III) A clinical
estimation of fetal weight or symphysis-fundal height has poor
sensitivity and specificity and should not be relied upon to
diagnose intrauterine growth restriction. Intrauterine growth
restriction should be considered in the differential diagnosis
when the fetus is found to be small for gestational age. (II-1)
03. Effective screening for intrauterine growth restriction requires
accurate dating and includes a review of the mother’s
ABBREVIATIONS
AC abdominal circumference
AFV amniotic fluid volume
BPP biophysical profile
DV ductus venosus
DVP deepest vertical pocket
EFW estimated fetal weight
IUGR intrauterine growth restriction
MCA middle cerebral artery
NST non-stress test
SFH symphysis fundal height
742 l AUGUST JOGC AOÛT 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
menstrual history, relevant assisted reproductive technology
information, and either a first trimester or early second
trimester dating ultrasound. (I)
04. Symphysis-fundal height determination is of limited value in
routine obstetrical care, but continues to be the only physical
examination screening test available. (I)
05. Fetal weight determination in fetuses between the 10th and
90th percentiles by ultrasound biometry alone has at least
a 10% error rate across gestation, but is effective equally
when measuring with abdominal circumference alone or
in combination with head size (biparietal diameter or head
circumference) and/or femur length to establish an estimated
fetal weight. (II-2)
06. Determining whether intrauterine growth restriction is
symmetric or asymmetric is of less clinical importance
than careful re-evaluation of fetal anatomy and uterine and
umbilical artery Doppler studies. (I)
07. In women with risk factors for intrauterine growth restriction,
uterine artery Doppler screening at 19 to 23 weeks may
identify pregnancies at risk of antepartum stillbirth and
preterm delivery due to intrauterine growth restriction and
placental disease. (II-2)
08. In pregnancies in which intrauterine growth restriction due to
uteroplacental vascular insufficiency is diagnosed, maternal
surveillance for the development of severe preeclampsia with
adverse features is warranted. (II-1)
09. Once surveillance of a fetus with intrauterine growth
restriction is instituted, umbilical artery Doppler studies
and biophysical profile scoring can be used as short-term
predictors of fetal well-being. (I)
10. In the presence of abnormal umbilical artery Doppler studies,
further investigation of the fetal circulatory system by Doppler
 Intrauterine Growth Restriction: Screening, Diagnosis, and Management
examination of the middle cerebral artery, ductus venosus,
and umbilical vein can be considered. (II-2)
11. For a fetus with intrauterine growth restriction, the decision
for obstetrical intervention, including Caesarean section, in
cases of abnormal fetal heart rate or malpresentation is largely
based on fetal viability, as assessed by ultrasound. (II-2)
12. Maternal surveillance for the development of preeclampsia is
warranted. (II-2)
Recommendations
01. Women should be screened for clinical risk factors for
intrauterine growth restriction by means of a complete
history. (II-2B)
02. Women should be counselled on smoking cessation at any
time during pregnancy. (II-2A)
03. First and second trimester screening tests for aneuploidy
maybe useful tests of placental function. If two screening
test results are abnormal, health care providers should be
aware that the fetus is at increased risk of preterm intrauterine
growth restriction and associated stillbirth. (II-1A)
04. If intrauterine growth restriction is suspected, further
assessment can assist in making the diagnosis. If available,
detailed ultrasound examination of the placenta (looking
for evidence of a small, thickened placenta, or abnormal
morphology) and uterine artery Dopplers should be considered
at 19 to 23 weeks. In the absence of available diagnostic
testing, closer surveillance should be offered. A maternal–
fetal medicine consultation can be considered if the placenta
appears abnormal on ultrasound, especially in the context of
a growth-restricted fetus and abnormal uterine artery Doppler.
In a rural setting, the caregiver needs to decide whether the
patient should be delivered immediately, or whether transfer to
a tertiary centre is appropriate. A telephone consultation and
telemedicine may help. (II-2A)
05. In women without risk factors for intrauterine growth
restriction, comprehensive third trimester ultrasound
examination including biophysical profile, fetal biometry,
amniotic fluid volume, and umbilical artery Doppler studies is
not recommended. (II-2D)
06. Low-dose aspirin should be recommended to women with a
previous history of placental insufficiency syndromes including
intrauterine growth restriction and preeclampsia. It should be
initiated between 12 and 16 weeks’ gestation and continued
until 36 weeks. (I-A)
07. Low-dose aspirin should also be recommended to women with
two or more current risk factors in pregnancy including, but
not limited to, pre-gestational hypertension, obesity, maternal
age > 40 years, history of use of artificial reproductive
technology, pre-gestational diabetes mellitus (type I or II),
multiple gestation, previous history of placental abruption, and
previous history of placental infarction. It should be initiated
between 12 and 16 weeks’ gestation and continued until 36
weeks. (I-A)
08. Umbilical artery Doppler studies are not recommended as a
routine screening test in uncomplicated pregnancies. (I-E)
09. An ultrasound examination for estimated fetal weight
and amniotic fluid volume should be considered after
26 weeks if the symphysis-fundal height measurement
in centimetres deviates by 3 or more from the gestational
age in weeks or there is a plateau in symphysis-fundal
height. (II-2B)
10. In cases in which the fetus measures < 10th percentile
by estimated fetal weight or abdominal circumference
measurement, the underlying cause of intrauterine growth
restriction may be established by an enhanced ultrasound
examination to include a detailed review of fetal anatomy,
placental morphology, and Doppler studies of the uterine and
umbilical arteries. (II-2A)
11. In cases of intrauterine growth restriction, determination
of amniotic fluid volume should be performed to aid in
the differential diagnosis of intrauterine growth restriction
and increase the accuracy of the diagnosis of placental
insufficiency. (II-2B)
12. Umbilical artery Doppler should be performed in all fetuses
with an estimated fetal weight or an abdominal circumference
< 10th percentile. (I-A)
13. In pregnancies affected by intrauterine growth restriction,
umbilical artery Doppler studies after 24 weeks may prompt
intervention that reduces perinatal mortality and severe
perinatal morbidity due to intrauterine growth restriction. (I-A)
14. In pregnancies in which intrauterine growth restriction has
been identified, invasive testing to rule out aneuploidy may
be offered where fetal abnormalities are suspected, soft
markers are seen, or no supportive evidence of underlying
placental insufficiency is evident. (II-2A)
15. In patients presenting with intrauterine growth restriction,
maternal screening for infectious etiology may be
considered. (II-2A)
16. When intrauterine growth restriction is diagnosed,
surveillance should be initiated. Serial ultrasound estimation
of fetal weight (every 2 weeks), along with umbilical artery
Doppler studies should be initiated. If available, a placental
assessment and other Doppler studies such as middle
cerebral artery, umbilical vein, and ductus venosis can be
performed. Increased frequency of surveillance may be
required. (II-2A)
17. If fetal growth starts to plateau, amniotic fluid index starts to
decline, or fetal tone or gross movements are diminished or
absent, then more intensive surveillance (e.g., 2 to 3 times
per week) or admission to hospital and delivery planning is
required. (II-2A)
18. Abnormal umbilical cord Doppler (e.g., absent or reversed
end-diastolic flow) in the presence of intrauterine growth
restriction is an ominous finding that requires intervention
and possible delivery. (I-A)
19. Cardiotocography (non-stress testing) performed antenatally
as a test of fetal well-being should not be used in isolation to
monitor fetuses with intrauterine growth restriction. (II-2E)
20. Maternal administration of corticosteroids is indicated if there
is a significant possibility of delivery at < 34 weeks’ gestation,
as administration may positively affect umbilical Doppler
studies. (I-A)
21. If delivery was not indicated prior to 37 weeks in a
patient diagnosed with intrauterine growth restriction,
expectant management with close fetal and maternal
surveillance versus delivery should be discussed after
37 weeks. (I-A)
22. Site of planned delivery should take into consideration
facilities and expertise available at each institution
including obstetricians, pediatricians or neonatologists
as appropriate, anaesthesiologists, and access to Caesarean
section. (III-A)
AUGUST JOGC AOÛT 2013 l 743
SOGC Clinical Practice Guideline
INTRODUCTION
I
ntrauterine growth restriction is a problem faced by
obstetrical care providers on a daily basis. Neonatal
mortality in both term and pre-term neonates is significantly
increased in those diagnosed antenatally with IUGR.
Despite the importance of the topic, there is a paucity of
level I evidence. The purpose of this guideline is to provide
summary statements and recommendations and to establish
a framework for screening, diagnosis, and management of
pregnancies affected with IUGR. A previously published
review (Lausman et al., 2012) provides further background.
Summary Statements
1. The definition of small-for-gestational age for
a fetus in utero is an estimated fetal weight that
measures < 10th percentile on ultrasound. This
diagnosis does not necessarily imply pathologic
growth abnormalities, and may simply describe a
fetus at the lower end of the normal range. (III)
2. Intrauterine growth restriction refers to a fetus
with an estimated fetal weight < 10th percentile
on ultrasound that, because of a pathologic
process, has not attained its biologically determined
growth potential. (III) A clinical estimation of
fetal weight or symphysis-fundal height has
poor sensitivity and specificity and should not
be relied upon to diagnose intrauterine growth
restriction. Intrauterine growth restriction should
be considered in the differential diagnosis when the
fetus is found to be small for gestational age. (II-1)
3. Effective screening for intrauterine growth
restriction requires accurate dating and includes a
review of the mother’s menstrual history, relevant
assisted reproductive technology information, and
either a first trimester or early second trimester
dating ultrasound. (I)
4. Symphysis-fundal height determination is of limited
value in routine obstetrical care, but continues to
be the only physical examination screening test
available. (I)
5. Fetal weight determination in fetuses between the
10th and 90th percentiles by ultrasound biometry
alone has at least a 10% error rate across gestation,
but is effective equally when measuring with
abdominal circumference alone or in combination
with head size (biparietal diameter or head
circumference) and/or femur length to establish an
estimated fetal weight. (II-2)
6. Determining whether intrauterine growth
restriction is symmetric or asymmetric is of less
clinical importance than careful re-evaluation of
744 l AUGUST JOGC AOÛT 2013
fetal anatomy and uterine and umbilical artery
Doppler studies. (I)
7. In women with risk factors for intrauterine growth
restriction, uterine artery Doppler screening at
19 to 23 weeks may identify pregnancies at risk
of antepartum stillbirth and preterm delivery due
to intrauterine growth restriction and placental
disease. (II-2)
8. In pregnancies in which intrauterine growth
restriction due to uteroplacental vascular
insufficiency is diagnosed, maternal surveillance
for the development of severe preeclampsia with
adverse features is warranted. (II-1)
9. Once surveillance of a fetus with intrauterine
growth restriction is instituted, umbilical artery
Doppler studies and biophysical profile scoring
can be used as short-term predictors of fetal
well-being. (I)
10. In the presence of abnormal umbilical artery
Doppler studies, further investigation of the fetal
circulatory system by Doppler examination of
the middle cerebral artery, ductus venosus, and
umbilical vein can be considered. (II-2)
11. For a fetus with intrauterine growth restriction,
the decision for obstetrical intervention, including
Caesarean section, in cases of abnormal fetal heart
rate or malpresentation is largely based on fetal
viability, as assessed by ultrasound. (II-2)
12. Maternal surveillance for the development of
preeclampsia is warranted. (II-2)
Recommendations
1. Women should be screened for clinical risk factors
for intrauterine growth restriction by means of a
complete history. (II-2B)
2. Women should be counselled on smoking cessation
at any time during pregnancy. (II-2A)
3. First and second trimester screening tests for
aneuploidy maybe useful tests of placental function.
If two screening test results are abnormal, the fetus
is at increased risk of preterm intrauterine growth
restriction and associated stillbirth. (II-1A)
4. If intrauterine growth restriction is suspected,
further assessment can assist in making the
diagnosis. If available, detailed ultrasound
examination of the placenta (looking for evidence
of a small, thickened placenta, or abnormal
morphology) and uterine artery Dopplers should
be considered at 19 to 23 weeks. In the absence
of available diagnostic testing, closer surveillance
should be offered. A maternal–fetal medicine
 Intrauterine Growth Restriction: Screening, Diagnosis, and Management
consultation can be considered if the placenta
appears abnormal on ultrasound, especially in the
context of a growth-restricted fetus and abnormal
uterine artery Doppler. In a rural setting, the
caregiver needs to decide whether the patient
should be delivered immediately, or whether
transfer to a tertiary centre is appropriate. A
telephone consultation and telemedicine may
help. (II-2A)
5. In women without risk factors for intrauterine
growth restriction, comprehensive third trimester
ultrasound examination including biophysical
profile, fetal biometry, amniotic fluid volume,
and umbilical artery Doppler studies is not
recommended. (II-2D)
6. Low-dose aspirin should be recommended to
women with a previous history of placental
insufficiency syndromes including intrauterine
growth restriction and preeclampsia. It should be
initiated between 12 and 16 weeks’ gestation and
continued until 36 weeks. (I-A)
7. Low-dose aspirin should also be recommended
to women with two or more current risk factors
in pregnancy including, but not limited to, pre-
gestational hypertension, obesity, maternal age
> 40 years, history of use of artificial reproductive
technology, pre-gestational diabetes mellitus
(type I or II), multiple gestation, previous history
of placental abruption, and previous history of
placental infarction. It should be initiated between
12 and 16 weeks’ gestation and continued until
36 weeks. (I-A)
8. Umbilical artery Doppler studies are not
recommended as a routine screening test in
uncomplicated pregnancies. (I-E)
9. An ultrasound examination for estimated fetal
weight and amniotic fluid volume should be
considered after 26 weeks if the symphysis-fundal
height measurement in centimetres deviates by 3 or
more from the gestational age in weeks or there is a
plateau in symphysis-fundal height. (II-2B)
10. In cases in which the fetus measures < 10th
percentile by estimated fetal weight or abdominal
circumference measurement, the underlying
cause of intrauterine growth restriction may be
established by an enhanced ultrasound examination
to include a detailed review of fetal anatomy,
placental morphology, and Doppler studies of the
uterine and umbilical arteries. (II-2A)
11. In cases of intrauterine growth restriction,
determination of amniotic fluid volume should be
performed to aid in the differential diagnosis of
intrauterine growth restriction and increase
the accuracy of the diagnosis of placental
insufficiency. (II-2B)
12. Umbilical artery Doppler should be performed
in all fetuses with an estimated fetal weight or an
abdominal circumference < 10th percentile. (I-A)
13. In pregnancies affected by intrauterine growth
restriction, umbilical artery Doppler studies after
24 weeks may prompt intervention that reduces
perinatal mortality and severe perinatal morbidity
due to intrauterine growth restriction. (I-A)
14. In pregnancies in which intrauterine growth
restriction has been identified, invasive testing to
rule out aneuploidy may be offered where fetal
abnormalities are suspected, soft markers are seen,
or no supportive evidence of underlying placental
insufficiency is evident. (II-2A)
15. In patients presenting with intrauterine growth
restriction, maternal screening for infectious
etiology may be considered. (II-2A)
16. When intrauterine growth restriction is diagnosed,
surveillance should be initiated. Serial ultrasound
estimation of fetal weight (every 2 weeks), along
with umbilical artery Doppler studies should be
initiated. If available, a placental assessment and
other Doppler studies such as middle cerebral
artery, umbilical vein, and ductus venosis can be
performed. Increased frequency of surveillance
may be required. (II-2A)
17. If fetal growth starts to plateau, amniotic fluid
index starts to decline, or fetal tone or gross
movements are diminished or absent, then more
intensive surveillance (e.g., 2 to 3 times per week)
or admission to hospital and delivery planning is
required. (II-2A)
18. Abnormal umbilical cord Doppler (e.g., absent
or reversed end-diastolic flow) in the presence of
intrauterine growth restriction is an ominous finding
that requires intervention and possible delivery. (I-A)
19. Cardiotocography (non-stress testing) performed
antenatally as a test of fetal well-being should
not be used in isolation to monitor fetuses with
intrauterine growth restriction. (II-2E)
20. Maternal administration of corticosteroids is
indicated if there is a significant possibility of
delivery at < 34 weeks’ gestation, as administration
may positively affect umbilical Doppler studies. (I-A)
21. If delivery was not indicated prior to 37 weeks
in a patient diagnosed with intrauterine growth
restriction, expectant management with close fetal
and maternal surveillance versus delivery should be
discussed after 37 weeks. (I-A)
AUGUST JOGC AOÛT 2013 l 745
SOGC Clinical Practice Guideline
22. Site of planned delivery should take into
consideration facilities and expertise available at
each institution including obstetricians, pediatricians
or neonatologists as appropriate, anaesthesiologists,
and access to Caesarean section. (III-A)
FRAMEWORK FOR APPROACHING INTRAUTERINE
GROWTH RESTRICTION IN CLINICAL PRACTICE
Screening for intrauterine growth restriction
History: maternal, fetal, and placental risk factors; establish
dates by first trimester ultrasound and last menstrual period
Physical: SFH measurement
Investigations to consider:
•• biochemical screening tests for Trisomy 21 as a test of
placental insufficiency;
•• first trimester ultrasound for dating and nuchal
translucency;
•• uterine artery Doppler at 19 to 23 weeks if
biochemical markers are abnormal;
•• if SFH (in centimetres) is less than gestational age
(in weeks) by > 3, arrange ultrasound for EFW, AFV
or DVP, biophysical profile, and/or umbilical Doppler
studies.
Diagnosis of intrauterine growth restriction
EFW or AC < 10th percentile
Management of intrauterine growth restriction
Investigations:
•• Offer amniocentesis if there is high risk of aneuploidy;
•• Consider TORCH screen.
Maternal management:
•• Conduct ongoing monitoring for preeclampsia;
•• Encourage patient to quit smoking;
•• Consider adding low-dose aspirin early in the
pregnancy if patient fulfills the criteria for its use.
Fetal management:
•• If pre-viable (< 500 g ± < 24 weeks): offer counselling
by multi-disciplinary health care team regarding fetal
monitoring and obstetrical intervention until viability.
•• If viable (> 500 g and > 24 weeks): conduct initial
ultrasound assessment: EFW, AFV, umbilical Doppler;
in third trimester (~ 26 weeks) consider weekly BPP
and growth every 2 weeks.
•• If growth continues along growth curve: conduct
weekly biophysical profile and umbilical artery
746 l AUGUST JOGC AOÛT 2013
Doppler; add growth every 2 weeks; consider delivery
near term (38 to 40 weeks) if no other issues.
•• If growth plateaus or stops < 34 weeks:
–– Administer corticosteroids; increase surveillance
to 2 to 3 times per week; consider hospitalization;
consider maternal–fetal medicine consultation;
consider pediatric consultation.
–– If abnormal umbilical artery Doppler studies: add
MCA and DV studies.
–– If abnormal umbilical artery, MCA, and DV
Doppler studies and abnormal NST: deliver. NST
can be used selectively if the BPP is abnormal.
–– If abnormal Doppler studies (e.g., absent or
reversed end-diastolic flow) and normal BPP and
NST: continue intensive monitoring with BPP and
umbilical Dopplers 2 to 3 times per week; deliver if
BPP or umbilical Dopplers worsen or if MCA/DV
are abnormal.
•• If > 34 weeks:
–– If normal AFV and DVP, BPP, and Doppler
studies: conduct weekly surveillance and discuss
delivery or ongoing monitoring after 37 weeks.
–– If abnormal fluid (AFV < 5 cm or DVP < 2 cm),
BPP, and/or Doppler studies: consider delivery.
DISCUSSION
IUGR is a problem associated with significant perinatal
morbidity and mortality. Level 1 evidence to direct clinicians
in practice does exist, but is limited to a few high quality trials.
Several demographic factors, including advanced maternal
age, assisted conception technologies, and pregnancy with
maternal comorbidities, interact to steadily increase the
risk of IUGR and stillbirth in the third trimester. More
effective use of current evidence may reduce this risk, but
further studies, especially to evaluate the role of systematic
screening of placental function in the second trimester, are
needed to improve the perinatal prognosis of IUGR due
to placental insufficiency. Since IUGR has many additional
causes, when it is suspected, a detailed fetal anatomical
ultrasound examination should be performed including
further testing when fetal abnormalities are suspected,
soft markers are seen, or there is no apparent supportive
evidence of underlying placental insufficiency.
In uncomplicated IUGR attributed to placental
insufficiency, no pharmacological interventions are of
proven benefit, although the accumulated data from several
trials and meta-analyses of low-dose aspirin demonstrate
 Intrauterine Growth Restriction: Screening, Diagnosis, and Management
some preventive benefit. By contrast, no evidence currently
exists to support the preventive use of the parenteral
anticoagulant drug heparin for either the prevention or
treatment of IUGR. After 36 weeks of gestation, IUGR
due to suspected placental insufficiency can be managed
equally effectively by early delivery or delayed delivery with
increased fetal surveillance.
Further research is needed to define optimum management
of early-onset IUGR. Following delivery, pathological
examination of the placenta may provide key insights into
the underlying cause and form the basis of an effective
postpartum counselling visit to discuss that cause. Since
the events leading up to and following delivery of an infant
with severe IUGR may trigger significant emotional stress,
a review of mental health status and family circumstances
at this visit is prudent.
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Ultrasound Obstet Gynecol 2013; 41: 102–113
Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.12342
isuog .org
ISUOG Practice Guidelines: performance of first-trimester
fetal ultrasound scan
Clinical Standards Committee
The International Society of Ultrasound in Obstetrics
and Gynecology (ISUOG) is a scientific organization that
encourages safe clinical practice and high-quality teach-
ing and research related to diagnostic imaging in women’s
healthcare. The ISUOG Clinical Standards Committee
(CSC) has a remit to develop Practice Guidelines and Con-
sensus Statements that provide healthcare practitioners
with a consensus-based approach for diagnostic imaging.
They are intended to reflect what is considered by ISUOG
to be the best practice at the time at which they are issued.
Although ISUOG has made every effort to ensure that
Guidelines are accurate when issued, neither the Society
nor any of its employees or members accept any liability
for the consequences of any inaccurate or misleading data,
opinions or statements issued by the CSC. The ISUOG
CSC documents are not intended to establish a legal stan-
dard of care because interpretation of the evidence that
underpins the Guidelines may be influenced by individ-
ual circumstances, local protocol and available resources.
Approved Guidelines can be distributed freely with the
permission of ISUOG (info@isuog.org).
INTRODUCTION
Routine ultrasound examination is an established part of
antenatal care if resources are available and access possi-
ble. It is commonly performed in the second trimester1 ,
although routine scanning is offered increasingly dur-
ing the first trimester, particularly in high-resource set-
tings. Ongoing technological advancements, including
high-frequency transvaginal scanning, have allowed the
resolution of ultrasound imaging in the first trimester to
evolve to a level at which early fetal development can be
assessed and monitored in detail.
The aim of this document is to provide guidance for
healthcare practitioners performing, or planning to per-
form, routine or indicated first-trimester fetal ultrasound
scans. ‘First trimester’ here refers to a stage of pregnancy
starting from the time at which viability can be confirmed
(i.e. presence of a gestational sac in the uterine cavity with
an embryo demonstrating cardiac activity) up to 13 + 6
weeks of gestation. Ultrasound scans performed after this
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
GUIDELINES
gestational age are not considered in these Guidelines.
Throughout these Guidelines we use the term ‘embryo’
for before 10 weeks and ‘fetus’ thereafter, to reflect the
fact that after 10 weeks of gestation organogenesis is
essentially complete and further development involves
predominantly fetal growth and organ maturation2,3 .
GENERAL CONSIDERATIONS
What is the purpose of a first-trimester fetal ultrasound
scan?
In general, the main goal of a fetal ultrasound scan is
to provide accurate information which will facilitate the
delivery of optimized antenatal care with the best possible
outcomes for mother and fetus. In early pregnancy, it is
important to confirm viability, establish gestational age
accurately, determine the number of fetuses and, in the
presence of a multiple pregnancy, assess chorionicity and
amnionicity. Towards the end of the first trimester, the
scan also offers an opportunity to detect gross fetal abnor-
malities and, in health systems that offer first-trimester
aneuploidy screening, measure the nuchal translucency
thickness (NT). It is acknowledged, however, that many
gross malformations may develop later in pregnancy or
may not be detected even with appropriate equipment and
in the most experienced of hands.
When should a first-trimester fetal ultrasound scan be
performed?
There is no reason to offer routine ultrasound simply to
confirm an ongoing early pregnancy in the absence of
any clinical concerns, pathological symptoms or specific
indications. It is advisable to offer the first ultrasound
scan when gestational age is thought to be between 11
and 13 + 6 weeks’ gestation, as this provides an oppor-
tunity to achieve the aims outlined above, i.e. confirm
viability, establish gestational age accurately, determine
the number of viable fetuses and, if requested, evaluate
fetal gross anatomy and risk of aneuploidy4 – 20 . Before
starting the examination, a healthcare provider should
counsel the woman/couple regarding the potential bene-
fits and limitations of the first-trimester ultrasound scan.
(GOOD PRACTICE POINT)
ISUOG GUIDELINES
ISUOG Guidelines
Who should perform the first-trimester fetal ultrasound
scan?
Individuals who perform obstetric scans routinely should
have specialized training that is appropriate to the practice
of diagnostic ultrasound for pregnant women. (GOOD
PRACTICE POINT)
To achieve optimal results from routine ultrasound
examinations it is suggested that scans should be per-
formed by individuals who fulfill the following criteria:
1. have completed training in the use of diagnostic ultra-
sonography and related safety issues;
2. participate in continuing medical education activities;
3. have established appropriate care pathways for suspi-
cious or abnormal findings;
4. participate in established quality assurance
programs21 .
What ultrasonographic equipment should be used?
It is recommended to use equipment with at least the
following capabilities:
– real-time, gray-scale, two-dimensional (2D) ultrasound;
– transabdominal and transvaginal ultrasound
transducers;
– adjustable acoustic power output controls with output
display standards;
– freeze frame and zoom capabilities;
– electronic calipers;
– capacity to print/store images;
– regular maintenance and servicing.
How should the scan be documented?
An examination report should be produced as an elec-
tronic and/or paper document (see Appendix for an
example). Such a document should be stored locally and,
in accordance with local protocol, made available to
the woman and referring healthcare provider. (GOOD
PRACTICE POINT)
Is prenatal ultrasonography safe during the first
trimester?
Fetal exposure times should be minimized, using the short-
est scan times and lowest possible power output needed to
obtain diagnostic information using the ALARA (As Low
As Reasonably Achievable) principle. (GOOD PRAC-
TICE POINT)
Many international professional bodies, including
ISUOG, have reached a consensus that the use of B-
mode and M-mode prenatal ultrasonography, due to its
limited acoustic output, appears to be safe for all stages of
pregnancy22,23 . Doppler ultrasound is, however, associ-
ated with greater energy output and therefore more poten-
tial bioeffects, especially when applied to a small region of
interest24,25 . Doppler examinations should only be used in
the first trimester, therefore, if clinically indicated. More
details are available in the ISUOG Safety Statement22 .
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
103
What if the examination cannot be performed in
accordance with these Guidelines?
These Guidelines represent an international benchmark
for the first-trimester fetal ultrasound scan, but consider-
ation must be given to local circumstances and medical
practices. If the examination cannot be completed in
accordance with these Guidelines, it is advisable to doc-
ument the reasons for this. In most circumstances, it will
be appropriate to repeat the scan, or to refer to another
healthcare practitioner. This should be done as soon as
possible, to minimize unnecessary patient anxiety and
any associated delay in achieving the desired goals of the
initial examination. (GOOD PRACTICE POINT)
What should be done in case of multiple pregnancies?
Determination of chorionicity and amnionicity is impor-
tant for care, testing and management of multifetal preg-
nancies. Chorionicity should be determined in early preg-
nancy, when characterization is most reliable26 – 28 . Once
this is accomplished, further antenatal care, including the
timing and frequency of ultrasound examinations, should
be planned according to the available health resources
and local guidelines. (GOOD PRACTICE POINT)
GUIDELINES FOR EXAMINATION
1. Assessment of viability/early pregnancy
In this Guideline, ‘age’ is expressed as menstrual or ges-
tational age, which is 14 days more than conceptional
age. Embryonic development visualized by ultrasound
closely agrees with the ‘developmental time schedule’
of human embryos described in the Carnegie staging
system3 . The embryo is typically around 1–2 mm long
when first detectable by ultrasound and increases in length
by approximately 1 mm per day. The cephalic and caudal
ends are indistinguishable until 53 days (around 12 mm),
when the diamond-shaped rhombencephal cavity (future
fourth ventricle) becomes visible18 .
Defining viability
The term ‘viability’ implies the ability to live indepen-
dently outside the uterus and, strictly speaking, cannot be
applied to embryonic and early fetal life. However, this
term has been accepted in ultrasound jargon to mean that
the embryonic or fetal heart is seen to be active and this is
taken to mean the conceptus is ‘alive’. Fetal viability, from
an ultrasound perspective, is therefore the term used to
confirm the presence of an embryo with cardiac activity at
the time of examination. Embryonic cardiac activity has
been documented in normal pregnancies at as early as 37
days of gestation29 , which is when the embryonic heart
tube starts to beat30 . Cardiac activity is often evident
when the embryo measures 2 mm or more31 , but is not
evident in around 5–10% of viable embryos measuring
between 2 and 4 mm32,33 .
Ultrasound Obstet Gynecol 2013; 41: 102–113.
104
Defining an intrauterine pregnancy
The presence of an intrauterine gestational sac clearly
signifies that the pregnancy is intrauterine, but the cri-
teria for the definition of a gestational sac are unclear.
The use of terms such as an ‘apparently empty’ sac, the
‘double-decidual ring’ or even ‘pseudosac’ do not accu-
rately confirm or refute the presence of an intrauterine
pregnancy. Ultimately, the decision is a subjective one
and is, therefore, influenced by the experience of the
person performing the ultrasound examination. In an
asymptomatic patient, it is advisable to wait until the
embryo becomes visible within the intrauterine sac as this
confirms that the ‘sac’ is indeed a gestational sac. (GOOD
PRACTICE POINT)
2. Early pregnancy measurements
The mean gestational sac diameter (MSD) has been
described in the first trimester from 35 days from the
last menstrual period onwards. The MSD is the average
of the three orthogonal measurements of the fluid-filled
space within the gestational sac34 . Nomograms for both
crown–rump length (CRL) and MSD are available, but,
in the presence of the embryo, the CRL provides a more
accurate estimation of gestational age because MSD values
show greater variability of age prediction35,36 .
3. First-trimester fetal measurements
Which measurements should be performed in the first
trimester?
CRL measurements can be carried out transabdominally
or transvaginally. A midline sagittal section of the whole
embryo or fetus should be obtained, ideally with the
embryo or fetus oriented horizontally on the screen. An
image should be magnified sufficiently to fill most of the
width of the ultrasound screen, so that the measurement
line between crown and rump is at about 90◦ to the
ultrasound beam37,38 . Electronic linear calipers should be
used to measure the fetus in a neutral position (i.e. neither
flexed nor hyperextended). The end points of crown and
rump should be defined clearly. Care must be taken to
avoid inclusion of structures such as the yolk sac. In order
to ensure that the fetus is not flexed, amniotic fluid should
be visible between the fetal chin and chest (Figure 1).
However, this may be difficult to achieve at earlier ges-
tations (around 6–9 weeks) when the embryo is typically
hyperflexed. In this situation, the actual measurement rep-
resents the neck–rump length, but it is still termed the
CRL. In very early gestations it is not usually possible to
distinguish between the cephalic and caudal ends and a
greatest length measurement is taken instead.
The biparietal diameter (BPD) and head circumfer-
ence (HC) are measured on the largest true symmetrical
axial view of the fetal head, which should not be dis-
torted by adjacent structures or transducer pressure. At
about 10 weeks’ gestation, structures such as the mid-
line third ventricle, interhemispheric fissure and choroid
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
ISUOG Guidelines
Figure 1 Crown–rump length (CRL) measurement technique in a
fetus with CRL 60 mm (12 + 3 weeks). Note neutral position of
neck.
plexuses should be visible. Towards 13 weeks, the thala-
mus and third ventricle provide good landmarks. Correct
axial orientation is confirmed by including in the image
both anterior horns and low occipital lobes of the
cerebral ventricles, whilst keeping the plane above the
cerebellum1,38 – 41 .
For BPD measurement, caliper placement should follow
the technique used to produce the selected nomogram.
Both outer-to-inner (leading edge) and outer-to-outer
measurements are in use1,39,42,43 (Figure 2).
Other measurements
Nomograms are available for abdominal circumference
(AC), femur length and most fetal organs, but there is no
reason to measure these structures as part of the routine
first-trimester scan.
4. Assessment of gestational age
Pregnant women should be offered an early ultrasound
scan between 10 + 0 and 13 + 6 weeks to establish accu-
rate gestational age. (Grade A recommendation)
Ultrasound assessment of embryonic/fetal age (dating)
uses the following assumptions:
– gestational (menstrual age) represents post-conception
age + 14 days;
– embryonic and fetal size correspond to post-conception
(post fertilization) age;
– structures measured are normal;
– measurement technique conforms to the reference
nomogram;
– measurements are reliable (both within and between
observers);
– the ultrasound equipment is calibrated correctly.
Accurate dating is essential for appropriate follow-up
of pregnancies and has been the primary indication
for routine ultrasound in the first trimester. It provides
valuable information for the optimal assessment of fetal
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ISUOG Guidelines
Figure 2 Fetal head. (a) Biparietal diameter (BPD) measurement
(calipers). Note true axial view through head and central position
of third ventricle and midline structures (T indicates third ventricle
and thalamus). Head circumference would also be measured in this
plane. (b) Normal choroid plexuses (C) and midline falx and
interhemispheric fissure (arrows). Note that choroid plexuses
extend from the medial to the lateral border of the posterior horn.
Lateral walls of anterior horns are indicated by arrowheads.
growth later in pregnancy, appropriate obstetric care in
general and management of preterm or post-term preg-
nancies in particular44,45 . Except in pregnancies arising
following assisted reproductive technology, the exact day
of conception cannot be determined reliably and, there-
fore, dating a pregnancy by ultrasound appears to be the
most reliable method with which to establish true gesta-
tional age39,46 . It has been recommended, therefore, that
all pregnant women be offered an early ultrasound scan
between 10 and 13 completed weeks (10 + 0 to 13 + 6
weeks) to determine gestational age and to detect multiple
pregnancies47 . In the first trimester, many parameters are
related closely to gestational age, but CRL appears to be
the most precise, allowing accurate determination of the
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
105
day of conception, to within 5 days either way in 95% of
cases48 – 52 .
At very early gestations, when the fetus is relatively
small, measurement errors will have a more significant
effect on gestational age assessment; the optimal time for
assessment appears, therefore, to be somewhere between
8 and 13 + 6 weeks48 . (GOOD PRACTICE POINT)
At 11 to 13 + 6 weeks, the CRL and BPD are the two
most commonly measured parameters for pregnancy dat-
ing. Many authors have published nomograms for these
variables. Measurements can be made transabdominally
or transvaginally. Singleton nomograms remain valid and
can be applied in the case of multiple pregnancy27,53 .
Details of a few published nomograms are provided in
Table 1. It is recommended that CRL measurement should
be used to determine gestational age unless it is above 84
mm; after this stage, HC can be used, as it becomes slightly
more precise than is BPD41 . (GOOD PRACTICE POINT)
5. Assessment of fetal anatomy
The second-trimester ‘18–22-week’ scan remains the
standard of care for fetal anatomical evaluation in both
low-risk and high-risk pregnancies54 – 57 . First-trimester
evaluation of fetal anatomy and detection of anoma-
lies was introduced in the late 1980s and early 1990s
with the advent of effective transvaginal probes58,59 . The
introduction of NT aneuploidy screening in the 11 to
13 + 6-week window has rekindled an interest in early
anatomy scanning (Table 2). Reported advantages include
early detection and exclusion of many major anomalies,
early reassurance to at-risk mothers, earlier genetic diag-
nosis and easier pregnancy termination if appropriate.
Limitations include need for trained and experienced
personnel, uncertain cost/benefit ratio and late devel-
opment of some anatomical structures and pathologies
(e.g. corpus callosum, hypoplastic left heart), which make
early detection impossible and can lead to difficulties in
counseling due to the uncertain clinical significance of
some findings54 – 56,60 – 62 .
Head
Cranial bone ossification should be visible by 11 com-
pleted weeks (Figure 2a). It is helpful to look specifically
for bone ossification in the axial and coronal planes. No
bony defects (distortion or disruption) of the skull should
be present.
The cerebral region at 11 to 13 + 6 weeks is dom-
inated by lateral ventricles that appear large and are
filled with the echogenic choroid plexuses in their
posterior two thirds (Figure 2b). The hemispheres
should appear symmetrical and separated by a clearly
visible interhemispheric fissure and falx. The brain
mantle is very thin and best appreciated anteriorly,
lining the large fluid-filled ventricles, an appearance
which should not be mistaken for hydrocephalus. At
this early age, some cerebral structures (e.g. corpus
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106 ISUOG Guidelines

Table 1 Biometry nomograms for consideration in first trimester to around 13 + 6 weeks

Reference Structure measured Age range (weeks) Notes

Robinson & Fleming52 (1975); quoted CRL 9 to 13 + 6 Selected for use by British Medical
by Loughna et al.41 (2009) Ultrasound Society41
Hadlock et al.83 (1992) CRL 5.0 to 18.0
Daya84 (1993) CRL 6.1 to 13.3
Verburg et al.43 (2008) CRL 6 + 2 to 15 + 0 Includes BPD, HC, AC, femur,
cerebellum
McLennan & Schluter85 (2008) CRL 5 to 14 Includes BPD to 14 weeks
Hadlock et al.86 (1982) BPD 12 to 40 In early pregnancy 1982 chart more
accurate than 1984 chart
Altman & Chitty39 (1997); quoted by BPD 12 + 6 to 35 + 4 Selected for use by British Medical
Loughna et al.41 (2009) Ultrasound Society41
Verburg et al.43 (2008) BPD 10 to 43 Includes CRL, HC, AC, femur,
cerebellum

Measurements should be performed according to techniques described in these articles and tested on the local population before being
adopted into practice. BPD, biparietal diameter; CRL, crown–rump length.

Table 2 Suggested anatomical assessment at time of 11 to However, in absence of obvious anomaly, failure to exam-
13 + 6-week scan ine the fetal face at this time should not prompt further
examination earlier than the mid-trimester scan.
Organ/anatomical
area Present and/or normal ?
Head Present
Neck
Cranial bones
Midline falx
Sonographic assessment of NT is part of the screening for
Choroid-plexus-filled ventricles chromosomal anomalies and is discussed below. Atten-
Neck Normal appearance tion should be paid to proper alignment of the neck with
Nuchal translucency thickness (if accepted the trunk and identification of other fluid collections such
after informed consent and as hygromas and jugular lymph sacs28,65 .
trained/certified operator available)*
Face Eyes with lens*
Nasal bone*
Normal profile/mandible* Spine
Intact lips*
Spine Vertebrae (longitudinal and axial)* Longitudinal and axial views should be obtained to show
Intact overlying skin* normal vertebral alignment and integrity, and an attempt
Chest Symmetrical lung fields should be made to show intact overlying skin (Figure 4).
No effusions or masses However, in the absence of obvious anomaly, failure to
Heart Cardiac regular activity examine the spine at this time should not prompt further
Four symmetrical chambers*
Abdomen Stomach present in left upper quadrant
examination earlier than the mid-trimester scan. Particu-
Bladder* lar attention should be paid to the normal appearance of
Kidneys* the spine when BPD < 5th centile66 .
Abdominal wall Normal cord insertion
No umbilical defects
Extremities Four limbs each with three segments Thorax
Hands and feet with normal orientation*
Placenta Size and texture The chest normally contains lungs of homogeneous
Cord Three-vessel cord* echogenicity on ultrasound, without evidence of pleural
*Optional structures. Modified from Fong et al.28 , McAuliffe
effusions or cystic or solid masses. Diaphragmatic conti-
et al.87 , Taipale et al.60 and von Kaisenberg et al.88 . nuity should be evaluated, noting normal intra-abdominal
position of stomach and liver.

callosum, cerebellum) are not sufficiently developed to

allow accurate assessment. It has been proposed that the
posterior fossa intracranial translucency can be evaluated
between 11 and 13 + 6 weeks as a screening test for open
neural tube defect, but this is not a standard63 . At 11 to
13 + 6 weeks, an attempt can be made to visualize the
eyes with their lenses, interorbital distances, the profile
including the nose, the nasal bone and mandible as well
as the integrity of the mouth and lips28,64,65 (Figure 3).
Heart
The normal position of the heart on the left side of
the chest (levocardia) should be documented (Figure 5).
More detailed sonographic assessment of cardiac anatomy
has been demonstrated to be feasible at 11 to 13 + 6
weeks67,68 , but this is not part of routine assessment. For
safety reasons, use of Doppler is not indicated during
routine scanning.

Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 102–113.
ISUOG Guidelines
Figure 3 Fetal face. (a) Normal profile showing nasal bones (NB).
Note normal length of maxilla and mandible. (b) Normal eyes with
globes and lenses (arrows) visible. (c) Fetal lips at 13 weeks. Note
intact upper lip and line between the lips (arrow). Nasal detail (N)
is limited.
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
107
Figure 4 Fetal spine. Intact skin (short thick arrow) is visible
posterior to the vertebrae from neck to sacrum in a true median
view. Note vertebral bodies show ossification, but neural arches,
which are still cartilaginous, are isoechoic or hypoechoic. In
cervical region (long arrow) the vertebral bodies have not yet
ossified and the cartilaginous anlage is hypoechoic; this is normal.
Figure 5 Axial section of the fetal thorax at the level of the
four-chamber view of the heart, with the cardiac apex pointing to
the left (L). Note atria and ventricles are symmetrical on either side
of the septum (arrow). Lung fields are of homogeneous
echogenicity and symmetrical. Aorta is just to left side of spine (S).
Abdominal content
At 11 to 13 + 6 weeks, the stomach and bladder are
the only hypoechoic fluid structures in the abdomen
(Figure 6a and 6b). The position of the stomach on the left
side of the abdomen together with levocardia helps con-
firm normal situs visceralis. The fetal kidneys should be
noted in their expected paraspinal location as bean-shaped
slightly echogenic structures with typical hypoechoic cen-
tral renal pelvis (Figure 6b). By 12 weeks of gestation, the
fetal bladder should be visible as a median hypoechoic
round structure in the lower abdomen.
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108
Figure 6 Fetal abdomen. (a) Axial view of abdomen at level at
which abdominal circumference is measured (dashed line), showing
stomach (S) and umbilical vein (UV). (b) Coronal view of abdomen
showing kidneys with central hypoechoic renal pelvis (K, arrows),
stomach (S) and diaphragm (Diaph, lines). (c) Umbilical cord
insertion (arrow). Note that the two umbilical arteries are visible.
Abdominal wall
The normal insertion of the umbilical cord should be
documented after 12 weeks (Figure 6c). The physi-
ological umbilical hernia is present up to 11 weeks
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
ISUOG Guidelines
Figure 7 Fetal limbs. (a) Normal arm showing normal alignment
of hand and wrist. (b) Normal leg showing normal orientation of
foot with respect to lower leg. Also visible are kidney (K) and
stomach (S).
and should be differentiated from omphalocele and
gastroschisis28,65,69 .
Limbs
The presence of each bony segment of the upper and lower
limbs and presence and normal orientation of the two
hands and feet should be noted at the 11 to 13 + 6-week
ultrasound scan. The terminal phalanges of the hands
may be visible at 11 weeks, especially with transvaginal
scanning (Figure 7a).
Genitalia
The evaluation of genitalia and gender is based upon
the orientation of the genital tubercle in the mid-sagittal
plane, but is not sufficiently accurate to be used for clinical
purposes.
Umbilical cord
The number of cord vessels, cord insertion at the
umbilicus and presence of cord cysts should be noted.
Brief evaluation of the paravesical region with color or
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ISUOG Guidelines
power Doppler can be helpful in confirming the presence
of two umbilical arteries, but this is not part of the routine
assessment.
Role of three-dimensional (3D) and 4D ultrasound
Three-dimensional (3D) and 4D ultrasound are not cur-
rently used for routine first-trimester fetal anatomical
evaluation, as their resolution is not yet as good as that
of 2D ultrasound. In expert hands, these methods may be
helpful in evaluation of abnormalities, especially those of
surface anatomy70 .
6. Chromosomal anomaly assessment
Ultrasound-based screening for chromosomal anomalies
in the first trimester may be offered, depending on pub-
lic health policies, trained personnel and availability of
healthcare resources. The first-trimester screening should
include NT measurement71,72 . Screening performance is
further improved by the addition of other markers, includ-
ing biochemical measurement of free beta or total human
chorionic gonadotropin (hCG) and pregnancy-associated
plasma protein-A (PAPP-A)73 . In appropriate circum-
stances, additional aneuploidy markers, including nasal
bone, tricuspid regurgitation, ductal regurgitation and
others, may be sought by personnel with appropriate
training and certification74 – 76 . Most experts recommend
that NT should be measured between 11 and 13 + 6
weeks, corresponding to a CRL measurement of between
45 and 84 mm. This gestational age window is chosen
because NT as a screening test performs optimally and
fetal size allows diagnosis of major fetal abnormalities,
thus providing women who are carrying an affected fetus
with the option of an early termination of pregnancy77 .
NT implementation requires several elements to be in
place, including suitable equipment, counseling and man-
agement as well as operators with specialized training and
continuing certification. Further details can be obtained
from relevant national bodies and charities such as The
Fetal Medicine Foundation (www.fetalmedicine.com).
However, even in the absence of NT-based screening
programs, qualitative evaluation of the nuchal region of
any fetus is recommended and, if it appears thickened,
expert referral should be considered.
How to measure NT
NT measurements used for screening should only be done
by trained and certified operators. NT can be measured
by a transabdominal or transvaginal route. The fetus
should be in a neutral position, a sagittal section should
be obtained and the image should be magnified in order
to include only the fetal head and upper thorax. Fur-
thermore, the amniotic membrane should be identified
separately from the fetus. The median view of the fetal
face is defined by the presence of the echogenic tip of
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
109
Figure 8 Sonographic measurement of nuchal translucency
thickness.
the nose and rectangular shape of the palate anteriorly,
the translucent diencephalon in the center and the nuchal
membrane posteriorly. If the section is not exactly median,
the tip of the nose will not be visualized and the ortho-
gonal osseous extension at the frontal end of the maxilla
will appear. The ultrasound machine should allow mea-
surement precision of 0.1 mm. Calipers should be placed
correctly (on-on) to measure NT as the maximum dis-
tance between the nuchal membrane and the edge of
the soft tissue overlying the cervical spine (Figure 8). If
more than one measurement meeting all the criteria is
obtained, the maximum one should be recorded and used
for risk assessment. Multiple pregnancy requires special
considerations, taking into account chorionicity.
How to train and control for the quality of NT
measurement
A reliable and reproducible measurement of NT requires
appropriate training. A rigorous audit of operator perfor-
mance and constructive feedback from assessors has been
established in many countries and should be considered
essential for all practitioners who participate in NT-based
screening programs. (GOOD PRACTICE POINT)
7. Other intra- and extrauterine structures
The echostructure of the placenta should be evaluated.
Clearly abnormal findings, such as masses, single or mul-
tiple cystic spaces or large subchorionic fluid collection
(> 5 cm), should be noted and followed up. Position of
the placenta in relation to the cervix is of less importance
at this stage of pregnancy since most ‘migrate’ away from
the internal cervical os78 . Placenta previa should not be
reported at this stage.
Special attention should be given to patients with a
prior Cesarean section, who may be predisposed to scar
pregnancy or placenta accreta, with significant complica-
tions. In these patients, the area between the bladder and
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110
the uterine isthmus at the site of the Cesarean section scar
should be scrutinized. In suspected cases, consideration
should be given to prompt specialist referral for further
evaluation and management79,80 . Although the issue of
routine scans in women with a history of Cesarean section
may be raised in the future81,82 , there is currently insuf-
ficient evidence to support inclusion of such a policy in
routine practice.
Gynecological pathology, both benign and malignant,
may be detected during any first-trimester scan. Abnor-
malities of uterine shape, such as uterine septa and
bicornuate uteri, should be described. The adnexa should
be surveyed for abnormalities and masses. The relevance
and management of such findings are beyond the scope of
these Guidelines.
GUIDELINE AUTHORS
L. J. Salomon*, Department of Obstetrics and Fetal
Medicine and SFAPE (Société Française d’Amélioration
des Pratiques Echographique), Paris Descartes University,
Assistance Publique-Hopitaux de Paris, Hopital Necker
Enfants, Paris, France
Z. Alfirevic*, Department for Women’s and Children’s
Health, University of Liverpool, Liverpool, UK
C. M. Bilardo, Fetal Medicine Unit, Department of
Obstetrics and Gynaecology, University Medical Centre
Groningen, Groningen, The Netherlands
G. E. Chalouhi, Department of Obstetrics and Fetal
Medicine and SFAPE (Société Française d’Amélioration
des Pratiques Echographique), Paris Descartes University,
Assistance Publique-Hopitaux de Paris, Hopital Necker
Enfants, Paris, France
T. Ghi, Department of Obstetrics and Gynaecology,
Policlinico S.Orsola-Malpighi, University of Bologna,
Bologna, Italy
K. O. Kagan, Department of Obstetrics and Gynecology,
University of Tuebingen, Tuebingen, Germany
T. K. Lau, Fetal Medicine Centre, Paramount Clinic,
Central, Hong Kong
A. T. Papageorghiou, Fetal Medicine Unit, St George’s,
University of London, London, UK
N. J. Raine-Fenning, Division of Obstetrics & Gynaecol-
ogy, School of Clinical Sciences, University of Notting-
ham, Nottingham, UK
J. Stirnemann, Obstetrics and Fetal Medicine, GHU
Necker-Enfants Malades, University Paris Descartes,
Paris, France
S. Suresh, Mediscan Systems & Fetal Care Research Foun-
dation, Mylapore, Chennai, India
A. Tabor, Fetal Medicine Unit, Department of Obstetrics,
Rigshospitalet, Copenhagen University Hospital, Copen-
hagen, Denmark
I. E. Timor-Tritsch, Department of Obstetrics and Gyne-
cology, New York University School of Medicine, New
York, NY, USA
A. Toi, Medical Imaging and Obstetrics and Gynaecology,
Mount Sinai Hospital, University of Toronto, Toronto,
ON, Canada
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
ISUOG Guidelines
G. Yeo, Department of Maternal Fetal Medicine, Obstet-
ric Ultrasound and Prenatal Diagnostic Unit, KK Women’s
and Children’s Hospital, Singapore
*L. J. S. and Z. A. contributed equally to this article.
CITATION
These Guidelines should be cited as: ‘Salomon LJ,
Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T, Kagan
KO, Lau TK, Papageorghiou AT, Raine-Fenning NJ,
Stirnemann J, Suresh S, Tabor A, Timor-Tritsch IE, Toi
A, Yeo G. ISUOG Practice Guidelines: performance of
first-trimester fetal ultrasound scan. Ultrasound Obstet
Gynecol 2013; 41: 102–113.’
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34. Oh JS, Wright G, Coulam CB. Gestational sac diameter in very
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41. Loughna P, Chitty L, Evans T, Chudleigh T. Fetal size and
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49. Bagratee JS, Regan L, Khullar V, Connolly C, Moodley J.
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51. Robinson HP. Sonar measurement of fetal crown-rump length
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52. Robinson HP, Fleming JE. A critical evaluation of sonar
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53. Dias T, Mahsud-Dornan S, Thilaganathan B, Papageorghiou A,
Bhide A. First-trimester ultrasound dating of twin pregnancy:
are singleton charts reliable? BJOG 2010; 117: 979–984.
54. Saltvedt S, Almstrom H, Kublickas M, Valentin L, Grunewald
C. Detection of malformations in chromosomally normal fetuses
Ultrasound Obstet Gynecol 2013; 41: 102–113.
112
by routine ultrasound at 12 or 18 weeks of gestation-a ran-
domised controlled trial in 39,572 pregnancies. BJOG 2006;
113: 664–674.
55. Chen M, Lee CP, Lam YH, Tang RYK, Chan BCP, Wong SF,
Tse LH, Tang MH. Comparison of nuchal and detailed mor-
phology ultrasound examinations in early pregnancy for fetal
structural abnormality screening: a randomized controlled trial.
Ultrasound Obstet Gynecol 2008; 31: 136–146; discussion
146.
56. Timor-Tritsch IE, Fuchs KM, Monteagudo A, D’Alton ME.
Performing a fetal anatomy scan at the time of first-trimester
screening. Obstet Gynecol 2009; 113: 402–407.
57. Abu-Rustum RS, Daou L, Abu-Rustum SE. Role of first-
trimester sonography in the diagnosis of aneuploidy and struc-
tural fetal anomalies. J Ultrasound Med 2010; 29: 1445–1452.
58. Timor-Tritsch IE, Bashiri A, Monteagudo A, Arslan AA. Qual-
ified and trained sonographers in the US can perform early fetal
anatomy scans between 11 and 14 weeks. Am J Obstet Gynecol
2004; 191: 1247–1252.
59. Bronshtein M, Zimmer EZ. Transvaginal ultrasound diagnosis
of fetal clubfeet at 13 weeks, menstrual age. J Clin Ultrasound.
1989; 17: 518–520.
60. Taipale P, Ammälä M, Salonen R, Hiilesmaa V. Learning
curve in ultrasonographic screening for selected fetal struc-
tural anomalies in early pregnancy. Obstet Gynecol 2003; 101:
273–278.
61. Cedergren M, Selbing A. Detection of fetal structural abnormal-
ities by an 11–14-week ultrasound dating scan in an unselected
Swedish population. Acta Obstet Gynecol Scand 2006; 85:
912–915.
62. Fisher J. First-trimester screening: dealing with the fall-out.
Prenat Diagn 2011; 31: 46–49.
63. Chaoui R, Nicolaides KH. From nuchal translucency to
intracranial translucency: towards the early detection of spina
bifida. Ultrasound Obstet Gynecol 2010; 35: 133–138.
64. Sepulveda W, Wong AE, Martinez-Ten P, Perez-Pedregosa J.
Retronasal triangle: a sonographic landmark for the screening
of cleft palate in the first trimester. Ultrasound Obstet Gynecol
2010; 35: 7–13.
65. Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides KH.
Challenges in the diagnosis of fetal non-chromosomal abnor-
malities at 11–13 weeks. Prenat Diagn 2011; 31: 90–102.
66. Bernard J-P, Cuckle HS, Stirnemann JJ, Salomon LJ, Ville Y.
Screening for fetal spina bifida by ultrasound examination in
the first trimester of pregnancy using fetal biparietal diameter.
Am J Obstet Gynecol 2012; 207: 306.e1–5.
67. DeVore GR. First-trimester fetal echocardiography: is the future
now? Ultrasound Obstet Gynecol 2002; 20: 6–8.
68. Yagel S, Cohen SM, Messing B. First and early second trimester
fetal heart screening. Curr Opin Obstet Gynecol 2007; 19:
183–190.
69. van Zalen-Sprock RM, Vugt JM, van Geijn HP. First-trimester
sonography of physiological midgut herniation and early diag-
nosis of omphalocele. Prenat Diagn 1997; 17: 511–518.
70. Bhaduri M, Fong K, Toi A, Tomlinson G, Okun N. Fetal
anatomic survey using three-dimensional ultrasound in conjunc-
tion with first-trimester nuchal translucency screening. Prenat
Diagn 2010; 30: 267–273.
71. Nicolaides KH, Azar G, Byrne D, Mansur C, Marks K.
Fetal nuchal translucency: ultrasound screening for chromo-
somal defects in first trimester of pregnancy. BMJ; 1992; 304:
867–869.
72. Nicolaides KH, Snijders RJ, Gosden CM, Berry C, Campbell S.
Ultrasonographically detectable markers of fetal chromosomal
abnormalities. Lancet 1992; 340: 704–707.
(Guideline review date: June 2015)
The authorship of this article was incomplete as initially published. This version of the article correctly acknowledges
all authors who contributed to the development of the Guidelines.
Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd.
ISUOG Guidelines
73. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH.
Screening for trisomy 21 by maternal age, fetal nuchal translu-
cency thickness, free beta-human chorionic gonadotropin and
pregnancy-associated plasma protein-A. Ultrasound Obstet
Gynecol 2008; 31: 618–624.
74. Kagan KO, Cicero S, Staboulidou I, Wright D, Nicolaides KH.
Fetal nasal bone in screening for trisomies 21, 18 and 13 and
Turner syndrome at 11–13 weeks of gestation. Ultrasound
Obstet Gynecol 2009; 33: 259–264.
75. Kagan KO, Valencia C, Livanos P, Wright D, Nicolaides
KH. Tricuspid regurgitation in screening for trisomies 21, 18
and 13 and Turner syndrome at 11 + 0 to 13 + 6
weeks of gestation. Ultrasound Obstet Gynecol 2009; 33:
18–22.
76. Maiz N, Valencia C, Kagan KO, Wright D, Nicolaides KH. Duc-
tus venosus Doppler in screening for trisomies 21, 18 and 13
and Turner syndrome at 11–13 weeks of gestation. Ultrasound
Obstet Gynecol 2009; 33: 512–517.
77. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13
weeks. Prenat Diagn 2011; 31: 7–15.
78. Mustafá SA, Brizot ML, Carvalho MHB, Watanabe L, Kah-
hale S, Zugaib M. Transvaginal ultrasonography in predicting
placenta previa at delivery: a longitudinal study. Ultrasound
Obstet Gynecol 2002; 20: 356–359.
79. Timor-Tritsch IE, Monteagudo A, Santos R, Tsymbal T, Pineda
G, Arslan AA. The diagnosis, treatment, and follow-up of
cesarean scar pregnancy. Am J Obstet Gynecol 2012; 207:
44.e1–13.
80. Timor-Tritsch IE, Monteagudo A. Unforeseen consequences of
the increasing rate of cesarean deliveries: early placenta accreta
and cesarean scar pregnancy. A review. Am J Obstet Gynecol
2012; 207: 14–29.
81. Stirnemann JJ, Chalouhi GE, Forner S, Saidji Y, Salomon LJ,
Bernard J-P, Ville Y. First-trimester uterine scar assessment
by transvaginal ultrasound. Am J Obstet Gynecol 2011; 205:
551.e1–6.
82. Stirnemann JJ, Mousty E, Chalouhi G, Salomon LJ, Bernard
J-P, Ville Y. Screening for placenta accreta at 11–14
weeks of gestation. Am J Obstet Gynecol 2011; 205: 547.
e1–6.
83. Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-
rump length: reevaluation of relation to menstrual age (5–18
weeks) with high-resolution real-time US. Radiology 1992; 182:
501–505.
84. Daya S. Accuracy of gestational age estimation by means of
fetal crown-rump length measurement. Am J Obstet Gynecol
1993; 168: 903–908.
85. McLennan AC, Schluter PJ. Construction of modern Australian
first trimester ultrasound dating and growth charts. J Med
Imaging Radiat Oncol 2008; 52: 471–479.
86. Hadlock FP, Deter RL, Harrist RB, Park SK. Fetal biparietal
diameter: a critical re-evaluation of the relation to menstrual
age by means of real-time ultrasound. J Ultrasound Med 1982;
1: 97–104.
87. McAuliffe FM, Fong KW, Toi A, Chitayat D, Keating S,
Johnson J-A. Ultrasound detection of fetal anomalies in
conjunction with first-trimester nuchal translucency screen-
ing: a feasibility study. Am J Obstet Gynecol 2005; 193:
1260–1265.
88. von Kaisenberg CS, Kuhling-von Kaisenberg H, Fritzer E,
Schemm S, Meinhold-Heerlein I, Jonat W. Fetal transab-
dominal anatomy scanning using standard views at 11 to
14 weeks’ gestation. Am J Obstet Gynecol 2005; 192:
535–542.
Ultrasound Obstet Gynecol 2013; 41: 102–113.
ISUOG Guidelines 113

APPENDIX: ROUTINE ULTRASOUND WORKSHEET (EXAMPLE)

Patient: ID number: SONOGRAPHIC N Ab* NV

APPEARANCE OF FETAL
Date of birth (DD/MM/YYYY): ANATOMY:
Referring physician: (N = Normal; Ab = Abnormal*;
NV = Not visualized)
Date of exam (DD/MM/YYYY): Gray = optional
Sonographer / Supervisor: Head
Indication for scan and relevant clinical information: Shape
Cranial ossification
LMP Midline falx
Choroid plexus
Technical conditions: Good / Limited by: Face
Singleton / Multiple (use 1 sheet/fetus) Orbits
=> Chorionicity: Profile
Neck
ADNEXA:
Thorax
Appearance Normal Abnormal*
Pulm. area
Anomaly:
Diaphragm
MEASUREMENTS mm Centile (Reference range) Heart
Crown–rump Heart activity
length Size
Nuchal Cardiac axis
translucency (optional) Four-chamber view
Biparietal diameter Abdomen
Head Stomach
circumference Bowel
Abdominal Kidneys
circumference Urinary bladder
Femoral diaphysis Cord insertion /
length abdominal wall
*Abnormal findings (please detail): Cord vessels
Spine
Limbs
Ultrasound-based estimate of GA: Right arm (incl. hand)
Right leg (incl. foot)
………..weeks + ………..days Left arm (incl. hand)
Left leg (incl. foot)
Gender (optional): M F
CONCLUSION: Other:
Normal and complete examination.
Normal but incomplete examination.
Abnormal examination*
Plans: No further ultrasound scans required
Follow up planned in ….. weeks.
Referred to ……………
Produced Printed Stored
Other:
No. of images

Copyright  2013 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2013; 41: 102–113.
 SOGC CLINICAL PRACTICE GUIDELINE

No. 297, October 2013

Investigation and Management of

Non-immune Fetal Hydrops
Abstract
This clinical practice guideline has been prepared by the
Genetics Committee, reviewed by Maternal Fetal Medicine Objective: To describe the current investigation and management of
Committee, and approved by the Executive and Council of non-immune fetal hydrops, with a focus on treatable or recurring
the Society of Obstetricians and Gynaecologists of Canada. etiologies.
Outcomes: To provide better counselling and management in cases
PRINCIPAL AUTHORS
of prenatally diagnosed non-immune hydrops.
Valérie Désilets, MD, Montreal QC
Evidence: Published literature was retrieved through searches
François Audibert, MD, Montreal QC of PubMed or MEDLINE, CINAHL, and The Cochrane Library
in 2011 using key words (non-immune hydrops fetalis, fetal
GENETICS COMMITTEE hydrops, fetal therapy, fetal metabolism). Results were restricted
R. Wilson, MD (Chair), Calgary AB to systematic reviews, randomized controlled trials/controlled
clinical trials, observational studies, and significant case reports.
Francois Audibert, MD, Montreal QC Additional publications were identified from the bibliographies
Jo-Ann Brock, MD, Halifax NS of these articles. There were no date or language restrictions.
Searches were updated on a regular basis and incorporated in the
June Carroll, MD, Toronto ON guideline to May 2012. Grey (unpublished) literature was identified
Lola Cartier, MSc, Montreal QC through searching the websites of health technology assessment
and health technology-related agencies, clinical practice guideline
Alain Gagnon, MD, Vancouver BC
collections, clinical trial registries, and national and international
Jo-Ann Johnson, MD, Calgary AB medical specialty societies.
Sylvie Langlois, MD, Vancouver BC Benefits, harms, and costs: These guidelines educate readers
about the causes of non-immune fetal hydrops and its prenatal
William MacDonald, MD, Halifax NS
counselling and management. It also provides a standardized
Lynn Murphy-Kaulbeck, MD, Moncton NB approach to non-immune fetal hydrops, emphasizing the search
Nanette Okun, MD, Toronto ON for prenatally treatable conditions and recurrent genetic etiologies.

Melanie Pastuck, RN, Cochrane AB
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all contributors.
Key Words: Non-immune hydrops fetalis, fetal hydrops, fetal
therapy, fetal metabolism
J Obstet Gynaecol Can 2013;35(10):923–936
Values: The quality of evidence in this document was rated using the
criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Recommendations
1. All patients with fetal hydrops should be referred promptly to a
tertiary care centre for evaluation. Some conditions amenable to
prenatal treatment represent a therapeutic emergency after 18
weeks. (II-2A)
2. Fetal chromosome analysis and genetic microarray molecular
testing should be offered where available in all cases of
non-immune fetal hydrops. (II-2A)
3. Imaging studies should include comprehensive obstetrical
ultrasound (including arterial and venous fetal Doppler) and fetal
echocardiography. (II-2A)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

OCTOBER JOGC OCTOBRE 2013 l 923

SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.78
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.78
4. Investigation for maternal–fetal infections, and alpha-thalassemia
in women at risk because of their ethnicity,
should be performed in all cases of unexplained fetal
hydrops. (II-2A)
5. To evaluate the risk of fetal anemia, Doppler measurement
of the middle cerebral artery peak systolic velocity should
be performed in all hydropic fetuses after 16 weeks of
gestation. In case of suspected fetal anemia, fetal blood sampling
and intrauterine transfusion should be offered
rapidly. (II-2A)
6. All cases of unexplained fetal hydrops should be referred to a
medical genetics service where available. Detailed postnatal
evaluation by a medical geneticist should be performed on all
ABBREVIATIONS
AF amniotic fluid
CBC complete blood count
CMV cytomegalovirus
FISH fluorescent in situ hybridization
Hb hemoglobin
HbH hemoglobin H
MCA middle cerebral artery
MPS mucopolysaccharidosis
NICHD National Institute of Child Health and
Human Development
NIHF non-immune hydrops fetalis
QF-PCR quantitative fluorescent polymerase chain reaction
RT-PCR real-time polymerase chain reaction
TORCH toxoplasmosis, rubella, cytomegalovirus,
herpes simplex
UA umbilical artery
VZV Varicella-zoster virus
924 l OCTOBER JOGC OCTOBRE 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
cases of newborns with unexplained
non-immune hydrops. (II-2A)
7. Autopsy should be recommended in all cases of fetal or neonatal
death or pregnancy termination. (II-2A) Amniotic fluid and/or fetal
cells should be stored for future genetic testing. (II-2B)
INTRODUCTION
H ydrops fetalis is defined as the accumulation
of abnormal fluid in at least two different fetal
compartments. It implies an excess of total body water,
which is usually evident as extracellular accumulation of
fluid in tissues and serous cavities.1,2 It generally presents as
subcutaneous edema, accompanied by effusions in two or
more serous cavities including pericardial or pleural effusions,
and ascites. Polyhydramnios or placental thickening (> 6 cm)
are often associated. When the fluid accumulation is limited
to one cavity, for example isolated ascitis or pleural effusion,
the situation should be described in terms of the involved
site, since this may be helpful in narrowing the differential
diagnosis. The three primary mechanisms associated with
hydrops are intrauterine anemia, intrauterine heart failure,
and hypoproteinemia. In addition to these three basic
mechanisms, fetal hydrops has a causal relationship with
a variety of structural abnormalities that interfere with
the fetoplacental circulation. Chromosomal anomalies
(aneuploidy, deletion, duplication, genetic mutation) and
skeletal dysplasia may also be associated with hydrops
through a variety of mechanisms.1,2
Fetal hydrops carries a poor prognosis; however, several
etiologies can be treated in utero with potential good

results. The growing number of recognized etiologies
requires a comprehensive and systematic search for causes,
in particular for treatable or recurrent conditions.
Recommendation
1. All patients with fetal hydrops should be referred
promptly to a tertiary care centre for evaluation. Some
conditions amenable to prenatal treatment represent a
therapeutic emergency after 18 weeks. (II-2A)
DEFINITIONS
Immune versus Non-Immune Fetal Hydrops
Immune hydrops
Maternal red cell alloimmunization occurs when a
pregnant woman has an immunological response to a
paternally-derived antigen that is foreign to the mother
and inherited by the fetus.3 The maternal antibodies may
cross the placenta, bind to antigens present on the fetal
erythrocytes, and cause hemolysis, hydrops fetalis, and
fetal death. The prognosis of this condition has been
considerably improved over the last decades, due to
interventions including antenatal and postpartum Rhesus
immune globulin, non-invasive prenatal surveillance
with cerebral Doppler, and intrauterine transfusion. The
complete description and management of this condition is
beyond the scope of this guideline.3,4
Non-immune hydrops
Non-immune hydrops fetalis refers to hydrops in the
absence of maternal circulating red-cell antibodies.5 With the
introduction of widespread immunoprophylaxis for red cell
alloimmunization and the use of in utero transfusions for
immune hydrops therapy, non-immune causes have become
responsible for at least 85% of all cases of fetal hydrops.6 The
reported incidence is around 3 per 10 000 births; however,
the incidence is much higher at the first- and second-trimester
ultrasounds because of higher fetal death rates.7
Hydrops in the First Trimester and Cystic Hygroma
Signs of hydrops can be found as early as in the first
trimester. This is usually seen in association with increased
nuchal translucency and/or cystic hygroma,8,9 a septated
cystic structure in the occipitocervical region and sometimes
the axillary region. The evaluation of increased nuchal
translucency and cystic hygromas with or without fetal
hydrops differs from that of non-immune fetal hydrops
and is beyond the scope of this guideline. Pertinent SOGC
guidelines can be found elsewhere.10–12
Twin Gestation as a Different Situation
Non-immune fetal hydrops in one or both twins may imply
a different etiology, especially in monochorionic twins, given
Investigation and Management of Non-immune Fetal Hydrops
the possibility of twin-to-twin transfusion syndrome. Review
articles discussing the assessment and management of twin-
to-twin transfusion syndrome and other complications
specific to twin pregnancies are available elsewhere.13–17
ETIOLOGIES
Despite extensive investigations, the etiology of non-
immune fetal hydrops may remain unknown in 15% to
25% of patients.1,6,18–20 The goal of this guideline is to
propose a standardized approach to the investigation
and management of non-immune fetal hydrops with
a focus on the rare treatable or potentially recurring
causes. A growing number of conditions can result in
NIHF. A systematic review has recently analyzed a total
of 225 relevant articles describing 5437 individual cases
of NIHF.21 All cases were sub-classified into one of the
following diagnostic categories: cardiovascular (21.7%),
hematologic (10.4%), chromosomal (13.4%), syndromic
(4.4%), lymphatic dysplasia (5.7%), inborn errors of
metabolism (1.1%), infections (6.7%), thoracic (6.0%),
urinary tract malformations (2.3%), extra-thoracic
tumours (0.7%), twin-to-twin transfusion or placental
(5.6%), gastrointestinal (0.5%), miscellaneous (3.7%), and
idiopathic (17.8%). See Table 2 for details.
Chromosomal Abnormalities
Chromosomal abnormalities are the cause of NIHF in 25%
to 70% of cases.22 The risk of fetal aneuploidy is higher
when identified earlier in gestation or when fetal structural
anomalies are seen.5,23 Standard fetal chromosome analysis
is indicated in all cases of hydrops. Additional genetic
microarray molecular testing should be considered in all
NIHF cases as the NICHD Microarray Study has shown
additional genetic chromosomal anomalies (smaller than
can be seen by standard cytogenetic studies) in 7% of
fetuses with congenital anomalies and standard normal
karyotype.24
Recommendation
2. Fetal chromosome analysis and genetic microarray
molecular testing should be offered where available
in all cases of non-immune fetal hydrops where
available. (II-2A)
Cardiac Etiologies
Cardiac etiologies account for 10% to 20% of cases of
NIHF.2,25 These include not only structural abnormalities,
but also cardiac arrhythmias, tumours, physiological
dysfunction due to infection, inflammation, infarction,
and arterial calcification. Cardiac and intrathoracic
lesions that result in right atrial pressure or volume
OCTOBER JOGC OCTOBRE 2013 l 925
SOGC Clinical Practice Guideline

overload seem to be most commonly associated with

Various*
hydrops fetalis. Fetal cardiac tumours, cardiomyopathy,
455
8.4
and other myocardial conditions probably result
in hydrops fetalis by a similar mechanism. Fetal
tachyarrhythmia has been shown to result in elevation
Idiopathic

of atrial pressure and is the most treatable of cardiac

17.8
966

No

causes of hydrops fetalis.26 Fetal bradyarrhythmias are

less easily treatable and a rare causative mechanism
of hydrops fetalis, except when the fetal heart rate is
Lymphatic
dysplasia

persistently below 50 per minute.

310
5.7
No

Infectious Diseases
Intrauterine infections are a common cause of fetal
laser therapy)

hydrops (4 to 15%), with parvovirus B19 infection and

(Placental
Placental
(TTTS)

secondary anemia the most frequent.27 Fetal toxoplasmosis,

304

Yes
5.6

syphilis, cytomegalovirus, and varicella can also present

as fetal hydrops, with commonly associated findings such
as hepatomegaly, splenomegaly, or ascites.2,28 (Tables 2
Syndromic

and 3) Strategies for the prenatal screening and diagnosis

237
4.4
No

of maternal–fetal infections are detailed below.

Hematological Disorders
Hematological disorders can be identified in 7% of
(Thoraco-

shunting)
Thoracic

amniotic

cases of NIHF. Ethnicity at increased risk of fetal

327

Yes
6.0

*including: inborn storage diseases, urinary tract malformations, extra-thoracic tumours, gastro-intestinal, miscellaneous

thalassemia may affect this frequency. For example,

homozygous alpha-thalassemia accounted for 55.1% of
NIHF diagnosed after 20 weeks in Southern China.29
parvovirus)
Infection

(IUT for
366

Yes
6.7

Structural Congenital Anomalies

Structural congenital anomalies should be evaluated
as they represent a large group of disorders that
can be identified through detailed fetal imaging and
Chromosomal

may be treatable. A list of congenital anomalies

Table 2. Conditions associated with non-immune fetal hydrops

13.4
727

No

associated with fetal hydrops is presented in Table 2.

Primary chylothorax,2,30 congenital cystic adenomatoid
malformation,31 various fetal tumours,32 and metabolic
IUT: intrauterine transfusion; TTTS: twin-to-twin transfusion syndrome

diseases have been also described as causal factors of

Hematologic

hydrops.33,34
(IUT)
10.4
564

Yes

Single Gene Disorders

Known single-gene disorders affecting metabolic
pathways, hematological conditions, skeletal dysplasia,
Cardiovascular

(anti-arrythmic

Based on a total number of 5437 cases of NIHF

neurologic disorders, cardiomyopathies, congenital

drugs)
Yes†
1181
21.7

nephrosis, congenital lymphedema, and mitochondrial

mutations have been reported as causes of potentially
recurring fetal hydrops.26 However, many families have
†For fetal tachyarrythmias only
Adapted from Bellini et al.18,26

had more than one child with fetal or neonatal hydrops

Potential fetal therapy

in whom the underlying genetic defect has not been

discovered. Some genes may be expressed specifically
during fetal development, while others may represent
an early-onset form of a known pediatric disorder (e.g.,
Cases, n

Gaucher, fetal akinesia, glycogen storage disorder type

IV).35,36 The identification of a single gene disorder not
%

926 l OCTOBER JOGC OCTOBRE 2013


Table 3. Ultrasound findings in fetal infections causing fetal hydrops
Infection CNS Cardiac
Toxoplasmosis + +
Syphilis
Rubella + +
Parvovirus + +
CMV + +
Varicella + +
Adapted from Klein et al.52
CNS: central nervous system; IUGR: intrauterine growth restriction
only helps in predicting the outcome of the current
pregnancy, but also has an impact on the management
or screening of future pregnancies in the family.26
Recent data suggest that metabolic disorders may be
responsible for some idiopathic NIHF. Lysosomal
storage disorders are the group of disorders most
commonly involved in NIHF. Hydrops fetalis is a
relatively common presentation in mucopoly-
saccharidosis type VII,37 infantile galactosialidosis,38 type
2 Gaucher disease, and infantile free sialic acid storage
disease. At least 15 other inborn errors of metabolism
may cause NIHF34,39: GM1 gangliosidosis, Niemann-
Pick type A, Niemann-Pick type C, MPS I, MPS IVA,
mucolipidosis II, sialidosis, multiple sulfatase deficiency,
Farber disease, Wolman disease, I cell disease, glycogen
storage disease IV,36 transaldolase deficiency,40 Pearson
syndrome (mitochondrial disorder), and congenital
disorders of glycosylation. Specific enzyme assays
are available to test for these disorders on cultured
amniocytes or specific metabolite measurement in
amniotic fluid supernatant.41,42
Diagnosing or ruling out a metabolic disorder as the
causal factor for NIHF is important because these
single gene disorders carry a 25% risk of recurrence,
and their identification may allow for prenatal diagnosis
at an earlier stage in future pregnancies. Prenatal
diagnosis of such conditions also facilitates postnatal
management. Despite thorough investigations, earlier
reports conclude that at least 28% of cases of NIHF
remain unexplained2; a recent systematic review of the
literature found that 17.8% were considered idiopathic.21
PRENATAL MANAGEMENT
Fetal hydrops mandates urgent referral to a maternal–
fetal medicine specialist for rapid evaluation because
some situations must be considered true prenatal
medical emergencies, particularly after 16 to 18 weeks.
Investigation and Management of Non-immune Fetal Hydrops
Abdominal Placental/AF IUGR
+ Rare
+ + Rare
+ +
+
+ + +
+ +
Triage depends on gestational age, etiology, and severity.
Ultrasound examination including umbilical artery
and middle cerebral artery Doppler studies may guide
lifesaving treatments such as in utero transfusions, fetal
cardioversion, or placement of diversion shunts. Table 4
outlines the baseline investigations for all fetal hydrops.
One should not wait for complete results before initiating
referral, invasive diagnostic procedures, or treatments.
Clinical Evaluation
A detailed history should be taken focusing on the mother’s
past medical and reproductive history, including previous
fetal, neonatal, or infantile deaths. A clear determination
of gestational age and history of viral exposure/illness,
travelling, bleeding, or use of medication during the
pregnancy should be obtained. Parental past medical
history, ethnic background, and consanguinity should be
documented. A 3-generation pedigree, including specific
questions on fetal loss, death in infancy, developmental
delay, congenital malformation, genetic syndrome,
skeletal dysplasia, chronic infantile illness, inherited
cardiomyopathies, and neurodegenerative disorders should
be completed. Maternal history, physical examination, and
laboratory tests should be used to rule out developing
preeclampsia (mirror syndrome) and underlying chronic
illness associated with fetal hydrops (e.g., Sjogren, lupus,
uncontrolled diabetes, Graves disease).
Non-invasive Testing
Timely referral to a maternal–fetal medicine specialist
allows for detailed and comprehensive ultrasound
examination and the early identification of any treatable
causes. A careful search for structural fetal anomalies or
genetic syndromes, signs of fetal infection, and evidence
of umbilical cord or placental anomalies may rapidly
indicate the cause of hydrops.
Multiple mechanisms of hydrops may coexist and the
primary cause is often not obvious. Determination of
prognosis is important and may be achieved by a semi-
OCTOBER JOGC OCTOBRE 2013 l 927
SOGC Clinical Practice Guideline

Table 4. Step-wise investigation of non-immune fetal hydrops

STEP 1: Urgent
Fetal imaging
•  Detailed morphology obstetrical ultrasound in a tertiary care centre and the assessment of the fetal venous and arterial circulation
•  Doppler (MCA, venous, arterial)
•  Fetal echocardiogram
Maternal blood
• CBC
• Kleihauer-Betke
•  ABO blood type and antigen status
•  Indirect Coombs (antibody screen)
•  Venereal disease research laboratory test for syphilis
•  Acute phase titres (parvovirus, toxoplasmosis, cytomegalovirus, rubella)
•  Liver function tests, uric acid, coagulation tests (suspected mirror syndrome)
•  SS-A, SS-B antibodies (fetal bradyarrhythmia)
•  Depending on ethnic origin: hemoglobin electrophoresis, G6PD deficiency screen

STEP 2: Invasive / referral / treatment

Amniotic fluid
•  FISH or QF-PCR on uncultured amniocytes, followed by karyotype or microarray analysis
•  PCR for CMV
•  PCR for parvovirus-B19/toxoplasmosis (selected cases)
•  CMV and bacterial cultures in selected cases
•  Inform the laboratory to keep the amniotic cells and supernatant for future studies
•  DNA extraction if alpha-thalassemia suspected
•  Fetal lung maturity testing (depending on gestational age)
Fetal blood sampling (maternal fetal medicine specialist)
•  CBC, white blood cell count differential, platelets
•  Direct Coombs’ test
•  Blood group and type
•  Karyotype (standard) with genetic microarray consideration
•  TORCH/viral serologies
•  Protein/albumin/liver function tests (not on all cases)
•  Hemoglobin electrophoresis (depending on ethnicity)
Cavity aspiration (may be done at the time of amniocentesis)
•  Lymphocyte count
• Protein/albumin
•  Creatinin/ionogram (ascites)
•  PCR for CMV and viral and bacterial cultures
Consider consultation with neonatalogy (depending on gestational age)

STEP 3: Post-delivery
Examination of the placenta
Neonatal survival
•  Detailed physical examination
•  Cardiac monitoring
•  Cranial ultrasound
•  Abdominal ultrasound
•  Cardiac monitoring
• Echocardiography
•  CBC, liver function tests, creatinine kinase, albumin, protein
•  TORCH, viral culture
•  Specialized testing guided by results of prenatal work-up
Neonatal / fetal demise
•  Clinical pictures
•  Fetal cells culture (skin, others)
•  Freeze fetal tissues and AF supernatant
•  Bank fetal DNA
•  Skeletal survey
•  Placental pathology
• Autopsy10

928 l OCTOBER JOGC OCTOBRE 2013


quantitative measure of heart failure. Specific questions
may be addressed through arterial and venous Doppler
ultrasound in conjunction with fetal echocardiogram.43
Doppler Ultrasound
The measurement of MCA peak systolic velocity to
assess fetal anemia is essential to the management of
fetuses with NIHF. After 16 weeks of gestation, there is
a significant association between delta-MCA peak flow
and delta hemoglobin concentration, especially when
the fetal Hb concentration is very low.44 A peak systolic
above 1.5 multiples of the median has a 100% (95% CI
86 to 100%) sensitivity for detecting fetal anemia from
various causes.4,45
An abnormal ductus venosus waveform helps both to
identify a fetus at risk for cardiac anomalies and to predict
prognosis.46 In a group of fetuses with congenital heart
defects and hydrops, abnormal hepatic vein and ductus
venosus blood velocities, along with umbilical venous
pulsations were strongly associated with mortality.47 The
most useful predictor of perinatal death in fetal hydrops
is the presence of umbilical venous pulsations, because
the most common pathway of perinatal demise is fetal
congestive heart failure.43
Arterial Doppler is an indicator of the redistribution of fetal
cardiac output affecting the blood flow in the descending
aorta and in the UA. Absent or reversed end diastolic flow
in the umbilical artery reflects elevated placental resistance.
Absent end diastolic flow is common in non-survivors,
and often associated with increased cardiac afterload.47
Changes in UA Doppler appear later than venous Doppler
and cardiac function alterations.
Fetal Echocardiogram
Fetal echocardiogram is used to assess cardiac anatomy
and function. Congenital cardiac malformations are
common with an underlying genetic syndrome or a
chromosome anomaly. Depending on the type of the
cardiac malformation, a syndromic differential diagnosis
should be considered and investigated.48
Cardiac arrhythmia may be primary or may occur secondary
to a systemic etiology such as hyperthyroidism or in mothers
with autoimmune conditions associated with high titres of
circulating anti–SS-A or anti–SS-B antibodies.49,50 The two
most common important fetal arrhythmias are supra­
ventricular tachyarrythmias and severe bradyarrhythmias
associated with complete heart block.50 Finally, congestive
heart failure may be secondary to other systemic causes
that need to be evaluated. In fact, when identifying a
cardiac component in the context of NIHF, this important
Investigation and Management of Non-immune Fetal Hydrops
finding should not be considered a final diagnosis in and
of itself. A careful search for underlying maternal illness or
single-gene disorder is indicated.
Enlargement of the cardiac chambers is a common sign
of heart failure.50 The right atrium is the final pathway
for venous return and frequently shows enlargement
in situations of relative foramen obstruction, volume
overload, tricuspid valve regurgitation, and increased
afterload. Normally, the ratio of the cardiac circumference
over the thoracic circumference at the level of the
4-chamber view should be less than 0.5.51
Recommendation
3. Imaging studies should include comprehensive
obstetrical ultrasound (including arterial and venous
fetal Doppler) and fetal echocardiography. (II-2A)
Search for Fetal Infections
This section describes the different laboratory tests for
infectious disorders that may present as fetal hydrops,
mainly to review the limitations of these tests. Tests need
to be prioritized as shown in the algorithm presented in
Table 4. Fetal ultrasound may reveal a pattern of findings
typical of a particular infectious agent.
Laboratory methods for the assessment of viral infections
are in two categories: serology and virus or parasite
detection.52 Serology is very sensitive but often cannot
conclusively determine the time of infection, which may
be critical for risk assessment. Traditional serological tests,
which measure antibody levels including immunoglobulin
M and immunoglobulin G, usually require two samples
separated by a significant time period for determination
of seroconversion or a substantial rise in titre.52 IgM
identification is more indicative than IgG of a recent
infection; however, IgM may persist several months or
even years in some cases. IgM can also be negative at
the time of fetal hydrops if the seroconversion occurred
several weeks earlier. Various tests may distinguish
between IgG and IgM and may allow diagnosis in one
serum sample, but biological and technical difficulties are
common and may cause false-positive and false-negative
results.53
Maternal toxoplasmosis, rubella, cytomegalovirus, herpes
simplex, and parvovirus B19 serologies are commonly
searched for suspicion of fetal infection. A study of
476 patients in the United Kingdom found that, among
TORCH agents, only CMV was commonly found as a
cause of fetal ultrasound findings.54 The archived serum
from routine first-trimester baseline tests is very useful,
OCTOBER JOGC OCTOBRE 2013 l 929
SOGC Clinical Practice Guideline
when available, to establish prior immune status and to
document seroconversion. Testing for rare infectious
diseases (syphilis, enterovirus) may be considered in
particular clinical situations (ultrasound findings, HIV
positive mother, clinical symptoms).
Parvovirus B19
Infection during pregnancy may affect the fetus, resulting
in hydrops or fetal demise.55 The predominant ultrasound
feature in fetuses infected by Parvovirus B19 is ascites,44
sometimes associated with poorly contractile echogenic
myocardium. Early diagnosis of maternal infection will
allow fetal assessment and treatment by intrauterine blood
transfusion. Unfortunately, mothers are often unaware of
their infection until fetal signs are observed. Confirmation
of B19 infection requires laboratory assessment, which is
complicated by the nature of the viral infection and immune
response. Serology, using enzyme-linked immunosorbent
assays, relies on recombinant antigens, and concordance is
low among all commercial assays available. In the absence
of a “gold standard” assay, false positive and false negative
results prevail.
Furthermore, maternal IgM may have dropped below the
detection limit by the time fetal hydrops is identified.56
Viral culture is difficult and virus detection is based on
various molecular assays. In spite of several studies there
is no consensus regarding the most appropriate clinical
specimen and method for detection of viral DNA.
Currently, on practical grounds, it is recommended to
use ELISA IgM and IgG assays based on recombinant
conformational epitopes of polyomavirus capsid proteins
1 and 2 or polyomavirus capsid protein 2 alone, and to use
amniotic fluid or fetal serum for detection of fetal infection
by the most sensitive molecular methods available (nested
PCR or RT-PCR).56 Recommendations for evaluation and
treatment of parvovirus infection during pregnancy have
been published by the SOGC Maternal–Fetal Medicine
and Infectious Diseases Committees.57
Rubella
If the patient is not immune to rubella, serial IgG and
IgM titres should be done. If congenital rubella is
strongly suspected, amniotic fluid culture or fetal blood
sampling for IgM determination is indicated as infection
leads to severe fetal morbidity. Postnatal determination is
achieved through evaluation of IgG and IgM levels, along
with viral isolation.
Cytomegalovirus
CMV is excreted in the urine of the infected fetus, so
detection of the virus in AF has proven to be a highly
sensitive and reliable method.58 Numerous studies have
930 l OCTOBER JOGC OCTOBRE 2013
focused on the most appropriate timing for performing
amniocentesis to yield the best sensitivity for detection
of fetal infection. These studies clearly indicated that AF
should be collected after 21 gestational weeks and after at
least 6 weeks maternal infection. Most studies state that
the timing of amniocentesis is more critical for sensitivity
in detecting the virus in AF than the laboratory methods
used. If invasive testing is performed, PCR is the preferred
method for detection of CMV in amniotic fluid. Problems
with molecular contamination (false positive results) and the
need to address prognostic issues led to the development
of quantitative PCR assays; the highly advanced real-time
PCR is the most up-to-date method.58,59
Laboratory testing to determinate intrauterine CMV
infection involves several steps that should be done
simultaneously in fetal hydrops. Maternal primary or
recurrent infection is assessed by serology using IgM,
IgG, and IgG-avidity assays. A second blood sample
should be sought to demonstrate antibody kinetics typical
of the current infection and not of a remote infection or
a non-specific reaction. If maternal primary infection has
been established and the pregnancy continues, prenatal
diagnosis follows at 21 to 23 weeks gestation or at 6 to
9 weeks after seroconversion (if known). Detection of
CMV in AF is achieved by virus culturing and/or PCR.
Quantitative PCR in the amniotic fluid can determine the
viral load and could be useful for the assessment of fetal
impact and prognosis, although the clinical value of this
test is still under investigation.60 Further information on
CMV infection in pregnancy is available in a previously
published SOGC guideline.58
Varicella-zoster virus
VZV is rarely found as a cause of fetal hydrops.61 The
primary tool for assessing maternal infection is isolation
of the virus from maternal lesions. Type-specific IgG
assays must be applied to determine recurrent maternal
infections. Antigen detection or DNA detection by PCR
in skin lesion samples are additional tools for the rapid
and sensitive diagnosis of symptomatic current infection.
Prenatal diagnosis can be performed by PCR detection
of the virus in AF, but false negative results are common
and positive results do not necessarily correlate with
fetal damage.62 Neonatal infection is diagnosed by virus
culture or PCR in skin lesions or other clinical specimens
in case of a disseminated form.
Other viral infections
A few studies report fetuses with NIHF caused by various
subtypes of Coxsackie virus and adenovirus identified
through targeted PCR amplification in affected fetal
tissues.19,63

Testing for Alpha-thalassemia
The most severe form of alpha-thalassemia is called
Bart’s disease.64 The absence of normal copies of alpha-
hemoglobin genes in a fetus causes severe anemia leading
to hydrops during fetal life.64 This autosomal recessive
condition occurs at a higher frequency in some ethnic
groups such as Mediterranean, African, and South-East
Asian populations.64 From a practical point of view in
Canada, one can take the approach that any patient who
is not Japanese, Korean, Caucasian of Northern European
ancestry, First Nations, or Inuit should be screened.64
Carriers are suspected on the basis of the presence of low
red blood cell volume (microcytosis) with normal ferritin.
HbH bodies identified on blood smear examination are
characteristic of alpha-thalassemia carrier status. Even in
the absence of HbH bodies, when microcytosis is present,
molecular testing should be performed in both parents to
look for the frequent deletion and rarer point mutations.
In cases suspected of alpha-thalassemia, MCA Doppler
should be done to confirm anemia. When anemia
is suspected, it should be confirmed by fetal blood
sampling for rapid initiation of treatment (intrauterine
transfusion). The diagnosis should be further confirmed
by fetal DNA testing through amniocentesis or placental
biopsy.64 If fetal blood is taken by cordocentesis, Hb
Bart’s can be identified. When confirmed, parents should
be informed of the poor prognosis and counselled about
the 25% recurrence risk and the availability of invasive
prenatal diagnosis for future pregnancies. Intrauterine
transfusion in affected fetuses has been reported with
various results.65
Invasive Investigation
Fetal karyotyping and genetic microarray molecular
testing should be conducted in all cases of unexplained
NIHF. Cytogenetic laboratories can provide a preliminary
result of the fetal karyotype within 24 to 48 hours using
QF-PCR or FISH techniques (amniotic fluid), direct
analysis (placental biopsy), or conventional karyotyping
(fetal blood).
Amniotic fluid should also be obtained for viral and
bacterial cultures, viral/parasitic-specific PCR studies,
and karyotyping. In selected cases, the supernatant can
be used for biochemical studies.34,66 Amniotic cells should
be kept in culture for future studies and DNA extraction
or frozen for later analysis.
Fetal blood sampling to determine fetal hemoglobin
levels may be performed under the following
circumstances: MCA Doppler results suggestive of fetal
anemia, documented parvovirus B19 seroconversion,
Investigation and Management of Non-immune Fetal Hydrops
parental microcytic anemia from at risk-ethnicity, and
documented fetal bleeding. Baseline studies to consider
on fetal blood sampling include CBC, platelets, direct
Coombs’ test, blood group, karyotype, TORCH/
parvovirus B19 (IgM), and albumin. If fetal anemia is
strongly suspected, O-negative CMV-negative maternally
cross-matched blood should be ready for transfusion.
In specific situations (positive family history, recurring
hydrops), targeted metabolic investigations may also be
performed. For example, fetal blood sample was used to
diagnose a congenital disorder of glycosylation type Ia
in a 27-week fetus with NIHF.67 The fetal loss rate after
cordocentesis was 11.32% in a group of hydropic fetuses,
probably due in part to the high loss rate associated with
hydrops itself.68
Specific enzyme assays are available to test for
lysosomal storage disorders on cultured amniocytes
(N-acetylglalactosamine-6S-sulfatase, beta-glucoronidase,
beta-galactosidase, beta-glucosidase, alpha-iduronidase,
a-D-neuraminidase, sphigomyelinase) or specific
metabolite measurement in amniotic fluid supernatant (total
hexosaminidase, betaglucoronidase, alpha-mannosidase,
chitotriosidase).41,42 These assays must be performed
by a specialized biochemical genetics laboratory. The
recommended metabolic investigation for unexplained
fetal hydrops is shown in Table 5. The laboratory should
be informed of the need to keep frozen supernatant and
amniotic cells for future studies. Diagnosing a metabolic
disorder as the causal factor for NIHF is important because
these single-gene disorders carry a 25% recurrence risk.
Their identification may allow for prenatal diagnosis at an
earlier stage in future pregnancies.26,41 Prenatal diagnosis
of such conditions also facilitates postnatal management.
Fetal cavity aspiration may be used as a diagnostic and
therapeutic measure. A lymphocyte count (pleural effusion,
cystic hygroma), biochemical studies, protein/albumin
determination, histology, and viral and bacterial cultures
are indicated.26,41
Recommendations
4. Investigation for maternal–fetal infections, and
alpha-thalassemia in women at risk because of
their ethnicity, should be performed in all cases of
unexplained fetal hydrops. (II-2A)
5. To evaluate the risk of fetal anemia, Doppler
measurement of the middle cerebral artery peak
systolic velocity should be performed in all
hydropic fetuses after 16 weeks of gestation.
In case of suspected fetal anemia, fetal blood
sampling and intrauterine transfusion should be
offered rapidly. (II-2A)
OCTOBER JOGC OCTOBRE 2013 l 931
SOGC Clinical Practice Guideline
Table 5. Lysosomal enzymatic assays used for NIHF
a. Beta-galactosidase (GM1)
b. Beta-glucuronidase (MPS VII)
c. Beta-glucosidase (Gaucher)
d. Neuraminidase (sialidose)
e. Beta-galactosidase and neuraminidase (galactosialidose)
f. Sphyngomyelinase (Niemann-Pick A and B)
g. Mucolipidosis type II
PROGNOSIS
NIHF from all causes has a high mortality rate. Fetal
chromosomal anomaly, gestational age < 24 weeks and
fetal structural anomalies other than chylothorax are
indicators of a poor prognosis. However, fetal treatment
has significantly improved survival in selected cases.
When a pregnancy is continued with known fetal hydrops,
the occurrence of maternal “mirror” syndrome should
be carefully monitored. Mirror syndrome, also referred to
as Ballantyne’s syndrome, is defined as the development
of maternal edema secondary to fetal hydrops.21,69 Severe
preeclampsia is usually associated with the syndrome.
Because the maternal prognosis can be poor, the option
of continuing a pregnancy with fetal hydrops should be
carefully discussed.
Excluding chromosomal abnormalities, the survival rate of
NIHF is about 31% to 48%.7 Most of the causes, a large
proportion of which are lethal disorders, respond poorly
to therapy. Without treatment the prognosis is generally
poor, except in the rare case of spontaneous resolution of
parvovirus B19 infection.70
In a series of 38 cases of NIHF, Negishi et al. reported a
23% survival rate in the treatment group.30 The presence
of a chromosomal anomaly, along with an earlier age
at detection of NIHF, was associated with a poorer
outcome. In a series of 30 cases of NIHF diagnosed
between 10 and 14 weeks of gestation, all cases resulted
in spontaneous abortion, intrauterine fetal death, or
pregnancy termination.23 In another series of 45 cases
diagnosed between 11 and 17 weeks, only 2 resulted in a
normal outcome.71 McCoy et al. reported a survival rate of
< 5% for infants with hydrops diagnosed before 24 weeks
of gestation and 20% survival for infants diagnosed after
24 weeks of gestation.19
In a report on 23 women with NIHF, termination of
pregnancy was performed for 10 chromosomal and 5
structural abnormalities, and there was one intrauterine
932 l OCTOBER JOGC OCTOBRE 2013
fetal death.72 One baby with diaphragmatic hernia died in
the neonatal period from pulmonary hypoplasia despite
reversal of hydrops by in utero shunting, and one baby
with treated polyhydramnios was born at 30 weeks and died
on day 5. The remaining 5 cases, in which structural and
chromosomal abnormalities were excluded, had fetal therapy
between 22 and 32 weeks’ gestation (4 shunt insertions, 1
blood transfusion) and in all the hydrops reversed and the
pregnancy continued to at least 35 weeks’ gestation. All 5
neonates were discharged from hospital alive and well.
Fetal therapy in cases of NIHF with normal structure and
karyotype was associated with a very good outcome.72
Two recent studies address the issues of postnatal survival in
live-born neonates with hydrops. Data from a large national
database73 reveals that mortality rates were highest among
neonates with congenital anomalies (57.7%) and lowest
among neonates with congenital chylothorax (5.9%). Factors
associated with death were younger gestational age, low
5-minute Apgar score, and need for high levels of support
during the first 24 hours of life (high oxygen needs and
high-frequency ventilation). Of the 597 neonates included
in the study, 115 were transferred from another hospital, 215
died before discharge, and 267 were discharged from the
hospital.73 Huang et al. reported a 50% survival rate in a group
of 28 live-born neonates with NIHF.74 The survival rate was
83% in infants with lymphatic malformations. Preterm birth
at less than 34 weeks and low serum albumin concentration
were two poor prognostic factors for survival.74
Few studies have examined the long-term outcome of
NIHF identified prenatally. Breur et al. reported normal
neurodevelopmental outcomes in 5 children who presented
with fetal heart block and hydrops fetalis. In his series of 10
fetuses, 3 died in utero, 2 died from dilated cardiomyopathy
at age 9 months and 4 years, and 5 survived.75
These results demonstrate that the prognosis of NIHF
differs markedly between different etiological groups. It
is essential to attempt to identify the etiology to better
predict prognosis, offer prenatal treatment when available,
and deliver in a tertiary perinatal care centre to improve
postnatal outcome.
Recommendation
6. All cases of unexplained fetal hydrops should be
referred to a medical genetics service where available.
Detailed postnatal evaluation by a medical geneticist
should be performed on all cases of newborns with
unexplained non-immune hydrops. (II-2A)
 Investigation and Management of Non-immune Fetal Hydrops

Table 6. Fetal therapies for non-immune hydrops

1. Intrauterine transfusion for anemia
–  Maternal acquired pure red cell aplasia
–  Maternal fetal hemorrhage
–  Fetal hemolysis (G6PD)
–  Fetal parvovirus infection
2. Repeated centesis or shunt insertion
–  Pleural effusion
– Ascitis
–  Thoracic cystic lesions
–  Congenital cystic adenomatoid malformation
–  Pulmonary sequestration
–  Pulmonary lymphangiectasia
3. Intravascular or maternal treatment with anti-arrhythmic drugs
–  Fetal tachyarrythmia
–  Atrioventricular block (anti–SS-A/SS-B)
4. Fetal procedures: open fetal surgery or laser vessel ablation/radio frequency ablation
–  Congenital cystic adenomatoid malformation
– Sequestration
–  Sacrococcygeal teratoma
–  Twin-to-twin transfusion syndrome (stage IV)
5. Others
–  Antithyroid drugs (fetal thyrotoxicosis)

PERINATAL MANAGEMENT Fetuses diagnosed with a treatable cause of NIHF should be

Fetal Treatment
Fetal hydrops is a medical emergency that mandates urgent
referral to a maternal–fetal medicine specialist and a
medical geneticist for rapid evaluation. The hydropic fetus
is usually in a precarious state and even minimal delays may
prevent access to life-saving procedures.
Fetal treatment options for NIHF depend on the etiology
and the gestational age at diagnosis. A maternal–fetal
specialist should undertake this evaluation. Options
available consist of:
1. intrauterine transfusion for anemia,
2. repeated centesis or shunt insertion for pleural
effusion, ascites, or thoracic cystic lesions,
3. intravascular or maternal treatment with anti-
arrhythmic drugs to treat fetal tachyarrythmia, in close
collaboration with cardiologists,
4. laser surgery for severe and early twin-to-twin
transfusion syndrome with hydrops (stage IV), and
5. open fetal surgery where available, or laser or
radiofrequency ablation for major structural anomalies
associated with NIHF (Table 6).
delivered in a tertiary care centre with prenatal consultation
with appropriate subspecialties including maternal–
fetal medicine specialists, geneticists, neonatologists,
and pediatric surgeons. Antenatal consultation allows
for parental counselling, adequate preparation of the
resuscitation team, and planning of specialized equipment
required in the delivery room. Pre-delivery cavity aspiration
(pleural effusions, severe ascitis, severe polyhydramnios) by
the perinatologist may facilitate neonatal management and
reduce maternal complications. Postnatal therapy begins
with vigorous resuscitation including thoracocentesis and/
or paracentesis to establish adequate lung expansion; this is
followed by efforts to determine the cause and correct the
condition responsible for the hydrops. Once the neonate
is stabilized, a detailed physical examination, cardiac
monitoring, chest radiograph, and ultrasound examinations
(head, cardiac, and abdominal) are performed. Additional
testing is guided by the investigation initiated antenatally.5
Postmortem Evaluation (Fetus and Placenta)
It is mandatory to continue the investigation after the death
of the fetus or newborn with NIHF. Referral to a genetic
service should be made to plan for additional investigation.
Clinical photography and fetal X-rays should be obtained

OCTOBER JOGC OCTOBRE 2013 l 933

SOGC Clinical Practice Guideline
to evaluate possible dysmorphic syndrome or skeletal
dysplasia. Autopsy should be strongly recommended, at
least for non-chromosomal cases.10,76 Storage of fetal blood,
tissue, DNA, and amniotic fluid supernatant should be
collected in the appropriate tube and setting (i.e. frozen
at –70˚C). The preservation of a potentially dividing fetal
cell line (amniocytes, skin biopsy) is indicated for future
biochemical or molecular genetic testing. Extensive sampling
from various sources is necessary to test for tissue-specific
enzymatic activity or gene expression. Placental examination
(microscopy, histopathology) focusing on tumours, fetal
anemia, infection, and metabolic disorder is indicated.77
Recommendation
7. Autopsy should be recommended in all cases of fetal
or neonatal death or pregnancy termination. (II-2A)
Amniotic fluid and/or fetal cells should be stored for
future genetic testing. (II-2B)
CONCLUSION
The prognosis of NIHF differs markedly between
different etiological groups. Recent progress in prenatal
genetics and maternal–fetal medicine provides us with
newer tools to identify the underlying etiology. Prompt
access to maternal–fetal medicine units for fetal evaluation
and treatment has improved outcomes. It is essential to
attempt to identify the etiology to better predict prognosis,
offer treatment when appropriate, and assess recurrence
risk to plan for the management of future pregnancies.
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 SOGC CLINICAL PRACTICE GUIDELINE
Menstrual Suppression in Special Circumstances
This clinical practice guideline has been prepared by the
Canadian Paediatric and Adolescent Gynaecology and
Obstetricians (CANPAGO) Committee, reviewed by the
Family Practice Advisory Committee, and approved by the
Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Yolanda A. Kirkham, MD, Toronto ON
Melanie P. Ornstein, MD, Toronto ON
Anjali Aggarwal, MD, Toronto ON
Sarah McQuillan, MD, Calgary AB
CANPAGO COMMITTEE
Lisa Allen, MD (Co-chair), Toronto ON
Debra Millar, MD (Co-chair), Vancouver BC
Nancy Dalziel, RN, Ottawa ON
Suzy Gascon, MD, Montreal QC
Julie Hakim, MD, Ottawa ON
Julie Ryckman, MD, Ottawa ON
Rachel Spitzer, MD, Toronto ON
Nancy Van Eyk, MD, Halifax NS
Disclosure statements have been received from all contributors.
Abstract
Objective: To provide a Canadian consensus document for health
care providers with recommendations for menstrual suppression
in patients with physical and/or cognitive challenges or those who
are undergoing cancer treatment in whom menstruation may have
a deleterious effect on their health.
Key Words: menstruation, menstrual suppression, amenorrhea,
chemotherapy, radiation, disability, contraception
J Obstet Gynaecol Can 2014;36(10):915–924
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 313, October 2014
Options: This document reviews the options available for menstrual
suppression, its specific indications, contraindications, and side
effects, both immediate and long-term, and the investigations and
monitoring necessary throughout suppression.
Outcomes: Clinicians will be better informed about the options and
indications for menstrual suppression in patients with cognitive
and/or physical disabilities and patients undergoing chemotherapy,
radiation, or other treatments for cancer.
Evidence: Published literature was retrieved through searches
of Medline, EMBASE, OVID, and the Cochrane Library using
appropriate controlled vocabulary and key words (heavy menstrual
bleeding, menstrual suppression, chemotherapy/radiation,
cognitive disability, physical disability, learning disability). Results
were restricted to systematic reviews, randomized controlled trials,
observation studies, and pilot studies. There were no language or
date restrictions. Searches were updated on a regular basis and
new material was incorporated into the guideline until September
2013. Grey (unpublished) literature was identified through
searching websites of health technology assessment and health
technology-related agencies, clinical practice guideline collections,
clinical trial registries, and national and international medical
specialty societies.
Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Care (Table 1).
Benefits, harms, and costs: There is a need for specific guidelines
on menstrual suppression in at-risk populations for health care
providers.
Recommendations
1. Menstrual suppression and therapeutic amenorrhea should be
considered safe and viable options for women who need or want
to have fewer or no menses. (II-2A)
2. Menstrual suppression should not be initiated in young women with
developmental disabilities until after the onset of menses. (II-2B)
3. Combined hormonal or progesterone-only products can be
used in an extended or continuous manner to obtain menstrual
suppression. (I-A)
4. Gynaecologic consultation should be considered prior to the
initiation of treatment in all premenopausal women at risk for
abnormal uterine bleeding from chemotherapy. (II-1A)
5. Leuprolide acetate or combined hormonal contraception
should be considered highly effective in preventing abnormal
uterine bleeding when initiated prior to cancer treatment in
premenopausal women at risk for thrombocytopenia. (II-2A)
OCTOBER JOGC OCTOBRE 2014 l 915
SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.62
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.62
INTRODUCTION
M enstrual suppression involves the use of various
hormonal regimes prescribed in an extended or
continuous fashion to achieve therapeutic amenorrhea.
This can involve decreasing the blood loss and the number
of menstrual cycles per year or eliminating menses
altogether. The goal may also include management of
associated menstrual side effects, such as bloating, nausea
and vomiting, headaches, mood and behavioural changes,
and cyclic exacerbation of seizures or migraines. The
ultimate goals of menstrual suppression are to reduce
morbidity and improve quality of life for women and/
or their caregivers.1,2 Menstrual suppression is often
ABBREVIATIONS
AUB abnormal uterine bleeding
BMD bone mineral density
CHC combined hormonal contraception
DEXA dual X-ray absorptiometry
DMPA depot medroxyprogesterone acetate
GnRH gonadotropin releasing hormone
IM intramuscular
IUD intrauterine device
IV intravenous
LA leuprolide acetate
LNG-IUS levonorgestrel intrauterine system
OCP oral contraceptive pill
POP progestin-only pill
916 l OCTOBER JOGC OCTOBRE 2014
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
medically indicated. The Canadian Consensus Guideline
on Continuous and Extended Hormonal Contraception
describes many indications for suppression.2 These
include social choice, severe dysmenorrhea associated with
endometriosis, abnormal uterine bleeding, hemorrhagic
diatheses, hormone withdrawal symptoms, and
premenstrual dysphoric disorders. This guideline focuses
on the needs of women with developmental disabilities
and women undergoing cancer treatment and at risk for
iatrogenic thrombocytopenia. Both of these conditions
present commonly in adolescence. For management of
women with inherited bleeding disorders, please refer to
SOGC Clinical Practice Guideline No. 163.3 The following
guideline will address each indication for menstrual
suppression (disabilities and cancer treatment) separately.
CONSIDERATIONS AND OPTIONS FOR
MENSTRUAL SUPPRESSION IN WOMEN
WITH DISABILITIES
Women with developmental challenges and disabilities
are a varied group. Patients may have cognitive and/or
physical impairments, various levels of communication
and independence in activities of daily living, numerous
comorbidities, polypharmacy, and differences in their
abilities to participate in informed consent. Families of
adolescents with disabilities often present for counselling
before or after menarche, which usually occurs at the
same age as in the general population.4,5 There is some
indication that women with cerebral palsy undergo puberty
earlier, but reach menarche slightly later, than the general

population,5,6 people with neurologic impairment have a
higher risk of precocious puberty,7 and neuroleptic drugs
can lead to hyperprolactinemia and amenorrhea.5,7 While
menstrual irregularities are common in the first 2 to 3
years post menarche because of anovulatory cycles, AUB
and dysmenorrhea in women with disabilities require the
same investigations as those undertaken in the general
population. In a retrospective study of 300 adolescents
with developmental disabilities, 30% experienced heavy,
painful, or irregular menstrual bleeding, and rates of
behavioural or mood symptoms approached 22%.8
In 2 retrospective studies, 32% to 43% of caregivers
approached physicians for information on menstrual
suppression prior to the young woman’s menarche because
of their anxiety and concerns about coping with hygiene
and possible behavioural changes.4,8 Behavioural concerns
can include mood changes, aggression, and self-mutilation,6
which may also reflect pain.9 Defining the reasons for
intervention can assist in the formation of treatment
goals.1 Table 2 outlines the pertinent points to elicit from
history prior to initiation of therapy when considering
menstrual suppression. There is a general consensus that
menstrual suppression therapy should not commence until
menarche.4 Often, education and support of the normal
progression through puberty and menarche are all that
is required.4,8,9 Awaiting menarche also confirms normal
hormonal function and the absence of an obstructive
anomaly. Once a decision is made to pursue treatment,
medical interventions that are the least intrusive, are
reversible, and have the lowest side effect profile are
desirable. Surgical or permanent interventions are rarely
required and are fraught with ethical and legal issues if the
individual is unable to participate fully in consent.1,5,7,9,10
All of the available options for reversible contraception
are acceptable for menstrual suppression (Table 3) and
satisfaction can be achieved in most disabled adolescents
and their families with 1 or 2 hormonal methods.8
Recommendations
1. Menstrual suppression and therapeutic amenorrhea
should be considered safe and viable options for
women who need or want to have fewer or no
menses. (II-2A)
2. Menstrual suppression should not be initiated in
young women with developmental disabilities until
after the onset of menses. (II-2B)
Combined Hormonal Options
Decreased number of periods or complete menstrual
suppression, with control of menstrual-related side
effects, can be achieved with extended or continuous use
of CHC. There have been several studies in the general
Menstrual Suppression in Special Circumstances
population that examine the different routes for delivering
extended or continuous CHC, and no single regimen has
been recognized as superior to the others.11–13 Unscheduled
bleeding generally decreases over time.1,2
For patients without contraindications to estrogen, the
OCP, contraceptive patch, or vaginal ring can be used to
prevent cyclical or abnormal menstrual bleeding. The safety,
efficacy, and acceptability of extended or continuous use
have been studied in randomized controlled studies14,15 and
are similar to rates for contraceptives used cyclically. The
extended use of hormones for menstrual suppression for
dysmenorrhea, endometriosis, heavy menstrual bleeding,
and menstrual-related symptoms is also well established.
For specific details, please refer to SOGC Clinical Practice
Guideline no. 195.2 There are no data on the long-term
safety of CHC in patients with cognitive or physical
impairments.
The prescription of extended use of CHC has been
shown to be acceptable in adolescents16 and patients
with disabilities.4,8 CHC also suppresses ovulation,
which improves menstrual-related mood symptoms or
behaviours. These are common presenting complaints in
adolescents with Down syndrome, autism, and cerebral
palsy.6 Adjustment to a higher dose estrogen-containing
formulation or to an alternate antiepileptic may be
required because enzyme-inducing anti-epileptic drugs
can interfere with the cytochrome p450 system and
metabolism of CHC.17 The need for frequent courses of
antibiotics may affect the efficacy of hormonal therapy.
Malnutrition or gastric feeding tubes can affect the route
of drug administration and absorption.5 Immobile and
wheelchair-bound individuals may be at increased risk of
venous thromboembolism.6,18 In a recent cohort study
of adolescents with disabilities, none of the permanent
wheelchair users who used an OCP or the patch developed
thromboembolisms during the study period.8
The choice of a monophasic or triphasic combined
contraception pill is often at the discretion of the prescriber.
Similarly, the dose of the pill should depend on the side
effects experienced or the comorbidities and polypharmacy
of the patient. There is some concern regarding a decrease
in the expected gain in BMD in adolescents who use 20 mcg
ethinyl estradiol formulations.19 For adolescents with heavy
or irregular menstrual bleeding, it may be appropriate
to consider starting with cyclic use prior to extended or
continuous use to minimize breakthrough spotting and
discontinuation.16 In a recent retrospective study, OCP
was the most commonly selected initial and second-choice
method for menstrual suppression in adolescents with
disabilities.8
OCTOBER JOGC OCTOBRE 2014 l 917
SOGC Clinical Practice Guideline

Table 2. Considerations for menstrual The contraceptive patch delivers 35 mcg of ethinyl
suppression in girls and women with estradiol and 150  mcg of norelgestromin daily and requires
developmental disabilities weekly replacement. The patch may be considered in
Menarchal status patients with gastrointestinal issues (difficulty swallowing
Premenarchal: counselling and education or malabsorption) or in those with poor compliance using
Postmenarchal: menstrual suppression options daily oral contraceptives.1 In a randomized controlled
Quality of life trial evaluating continuous use of the patch in the general
Hygiene population, menstrual bleeding was delayed to 54 days
Degree of anxiety and amenorrhea rates of 28% and 12% were achieved
Activity restrictions through extended use to 8 and 12 weeks, respectively.11
Caregiver concerns The side effect profile is similar to that of OCP,20,21
Treatment goals with spotting as a common initial side effect. Based on
Degree of suppression or amenorrhea desired data analyzed for pregnancy outcome, the efficacy of
Contraceptive needs the patch appears to be reduced in patients who weigh
Type of disability or risk 90 kg or more.22 In a cohort study of adolescents with
Cognitive disabilities, 20% of patients and their families elected
Physical to use the patch as their first choice for menstrual
Communicative suppression.8 Disadvantages of the transdermal patch
Abuse included skin irritation, behavioural or mood concerns,
Degree of required support breast tenderness, and attempted removal of the patch by
Ambulatory vs. wheelchair user the disabled adolescent.
Support required with activities of daily living
The transvaginal ring is a preparation with daily delivery
Access to support (home, school, and respite care)
of 15 mcg ethinyl estradiol and 120 mcg etonogestrel.22
Menstrual symptoms
One randomized controlled trial in the general population
Menstrual bleeding patterns
evaluated continuous use of the ring versus extended use
Dysmenorrhea
with a 4-day ring-free interval, with the latter resolving
Behavioural, mood, and/or premenstrual symptoms
breakthrough bleeding or spotting.23 Continuous or
Medical history and comorbidities
extended use had high continuation rates and reduced
Cerebrovascular disease
menstrual flow and pelvic pain. An advantage of the
Complicated valvular heart disease
ring is that it can be used for one month before requiring
Diabetes with end-organ disease
replacement. Although the use of the transvaginal ring
Decreased BMD
has not been studied in the developmentally delayed
Liver disease
population, this option can be presented to patients with
Malnutrition or feeding tube
minor cognitive delay and familiarity with tampon use or
Migraines with neurological symptoms
no physical impairment to ring insertion.
Obesity
Seizure disorder Progestin-only Options
Thromboembolic risk or history Progestin-only options for menstrual suppression
Thyroid dysfunction offer alternatives to estrogen-containing contraceptives
Uncontrolled hypertension and can be administered by intramuscular, oral, or
Medications intrauterine routes. The progestin implant is not
Antiepileptics available in Canada.
Antibiotics
Neuroleptics
Oral progestins (0.35  mg norethindrone tablets) are
Steroids
prescribed daily without a pill-free interval. The POP
does not confer the same degree of amenorrhea (10% of
patients),24 but it is effective contraception with a failure
rate of only 0.5% with perfect use.22 Side effects are much
less common with POP than with OCP, but may include
breakthrough bleeding, emotional disturbances, acne, and
breast tenderness. POP treatment has not been studied
exclusively in patients with disabilities.

918 l OCTOBER JOGC OCTOBRE 2014

 Table 3. Reversible therapeutic hormonal options for menstrual suppression
Type of contraception Benefits Difficulties Risks
OCP Oral or feeding tube administration Compliance with daily administration Venous thromboembolism
Extended or continuous regimen Breakthrough bleeding Gallbladder disease
Reduced menstrual flow and dysmenorrhea Contraindicated in patients with hepatic
Reduction in ovarian, endometrial, colorectal cancer disease or hormone-dependent cancers
on chemotherapy
Contraceptive patch Weekly transdermal application Skin irritation Same as OCP
Avoids first pass metabolism Removal (inadvertant or deliberate)
Same as OCP Reduced efficacy in patients > 90kg
Vaginal ring Administration every 3 weeks Insertion by woman or caregiver Same as OCP
Avoids first pass metabolism Not studied in disabled population
Same as OCP
DMPA injection Administration every 10–12 weeks Injection Reduced BMD during treatment
Amenorrhea within 1 year in 50% of patients Breakthrough bleeding (reversible)

Safe for patients with contraindications to estrogen Weight gain

Requires dietary calcium and vitamin D
supplementation
Oral progesterone Oral or feeding tube administration Compliance with daily administration Minimal
Safe for patients with contraindications to estrogen Breakthrough bleeding
Weight gain
LNG-IUS 5-year effectiveness Insertion may require general anaesthesia Perforation
Minimal systemic effects Initial irregular bleeding Expulsion
Progressive reduction in menstrual flow and pain Minimal uterine length of 5–6 cm Infection (first 21 days)
Amenorrhea within 1 year in 50% of patients Post-operative ultrasound for placement in patients
with disabilities
GnRH analogue Administration every 4 (3.75 mg im) or 12 weeks Cost Reduced BMD during treatment; add-back
leuprolide (11.25 mg im) Intramuscular injection therapy or adequate dietary calcium and
Amenorrhea rates of 73–96% vitamin D supplementation are
Ideal administration 3–4 weeks prior to chemotherapy recommended
Effective for prevention of heavy menstrual bleeding in luteal phase
with iatrogenic thrombocytopenia Long-term use requires add-back therapy* to prevent
hypoestrogenic symptoms of endometriosis
None of these methods protect against sexually transmitted infections.
*Various add-back therapy regimens (estrogen and/or progestin) are available.

OCTOBER JOGC OCTOBRE 2014 l 919

Menstrual Suppression in Special Circumstances
SOGC Clinical Practice Guideline
DMPA is an injectable progesterone of 150  mg
administered intramuscularly every 12 weeks. Despite
American and Canadian advisories in 2004 and 2005,
respectively, regarding concerns over loss of BMD, the
advantages of DMPA have led to its continued use. Prior
to evidence of the association between DMPA and bone
loss, DMPA was the most commonly prescribed method
of menstrual suppression (59%) in adolescents with
developmental delay.4 Recent Canadian data have shown a
shift in prescribing methods to the extended combined oral
contraceptive, although DMPA remains a popular initial
choice in 12% of adolescent patients with disabilities.8
The dosing schedule of DMPA, administered every 12 weeks
or sometimes every 10 weeks in patients on anti-epileptic
medications,25,26 confers a possible advantage in patients with
disabilities. DMPA also minimizes concerns over compliance
and is acceptable in patients who are unable to swallow pills or
tolerate a vaginal ring or transdermal patch. DMPA may also
be considered for the quick initial induction of amenorrhea,
to be followed by the use of alternative longer-term methods
of menstrual suppression. Rates of amenorrhea at 12 to
24 months reach 55% to 70% in the general population,25,27
with irregular bleeding as a common initial side effect that
diminishes over time. It is an extremely effective contraceptive
with a failure rate of 0.3%.24 Additional advantages include a
relative lack of drug interactions and reductions in seizures28
and sickle cell crises.29
The reduction in estrogen levels from the use of DMPA
during adolescence is associated with bone loss of 3.1% at
the lumbar spine and 6.1% at the hip.19,30 Fortunately, studies
suggest that loss of BMD is transient and its recovery has been
demonstrated in adult and adolescent patients with cessation
of the injection.30–33 Modifiable factors such as dietary calcium
intake, even at levels lower than the daily recommended intake
of 1300 mg per day, contribute to BMD gain in the femoral
neck and lumbar regions in adolescents.34 The DEXA scan can
be used to quantify bone mass during DMPA treatment. Age
appropriate norms should be used. However, whether this
surrogate marker for bone strength translates into a measure
of fracture risk has yet to be elucidated. Considerations of
bone density are particularly important in wheelchair-bound
and immobile patients or those on systemic steroids, who
are already at risk for lower BMD. Regular appointments
to readdress the need for continued DMPA, to consider
alternatives, and to encourage adequate dietary calcium with
vitamin D supplementation and weight-bearing exercise are
strongly encouraged.35
Weight gain of 1 to 2 kg per year of use is also a possible
side effect of DMPA through appetite stimulation.36 Obese
young women are more susceptible to increased weight
920 l OCTOBER JOGC OCTOBRE 2014
gain on DMPA,36 and weight gain may be an important
issue in individuals who require assistance with transfers.6
Levonorgestrel Intrauterine System
The LNG-IUS is indicated for control of heavy menstrual
bleeding and long-acting reversible contraception.
Through daily delivery of 20 mcg of levonorgestrel, the
local effects of the device lead to inhibition of endometrial
proliferation, thickening of cervical mucus, and impaired
sperm mobility.37 In the general population, menstrual
blood loss is reduced by 85% in 3 months,38 and rates of
amenorrhea reach nearly 50% in 6 months39 and continue
to increase over time, while irregular spotting, particularly
in the months following insertion, diminishes. In a
randomized controlled trial, LNG-IUS was shown to be
more effective in reducing menstrual bleeding than a 10-
day regimen of 10 mg oral medroxyprogesterone acetate
per month.40 In adolescents, the most common indication
for use of the LNG-IUS was heavy menstrual bleeding,
which occurred in 17% of patients.41
A significant benefit of the LNG-IUS is its length of
treatment (5 years), after which it can be removed and
alternatives can be re-evaluated or a new IUS can be
reinserted. Side effects are few and complications such as
perforation, expulsion, and infection are rare in adult and
adolescent populations,18,40–42 with high rates of continuation
in adolescents of 75% to 85%.41,43 In one study of 14 young
women with disabilities,44 50% achieved amenorrhea with
LNG-IUS and there was 1 expulsion, which is in keeping
with the low rates of expulsion (7 to 8%) of IUDs in young
women with or without disabilities.41,43 In another study
of adolescents with cognitive and physical challenges,8 the
LNG-IUS was a popular second-line option for menstrual
suppression in 19% of patients who switched from alternate
methods. Ovulation is not suppressed by the LNG-IUS, and
thus hormonal cycling and associated mood symptoms or
behaviours may not be ameliorated.
Insertion in virginal or young women with disabilities may
require general anaesthesia or conscious sedation. Pre-
insertion considerations include vaginal and cervical swabs
in patients at risk for infection, screening for pregnancy,
ultrasound for vertical length of the uterine cavity (5 to 6
cm is recommended), and administration of oral or vaginal
misoprostol.44,45 Long-term menstrual suppression with
LNG-IUS offers effective reduction in menstrual blood loss,
high rates of amenorrhea, and low rates of complications.8,41,44
Recommendation
3. Combined hormonal or progesterone-only
products can be used in an extended or continuous
manner to obtain menstrual suppression. (I-A)

MENSTRUAL SUPPRESSION FOR
ONCOLOGY PATIENTS
Each year in Canada there are approximately 600 new
cancer cases and 80 deaths from cancer in girls and women
aged 0 to 19 years and 12 450 new cases and 4800 deaths in
women aged 20 to 49 years.46 This constitutes a substantial
number of women of reproductive age who will develop
cancer and require treatment, such as chemotherapy,
radiation, or hematopoietic stem cell or bone marrow
transplantation. Ablative therapy may induce pancytopenia
with thrombocytopenia and result in moderate to severe
uterine bleeding in nearly 40% of oncology patients.47
AUB in premenopausal women with malignancy is caused by
thrombocytopenia from the cancer itself and can be further
exacerbated by cancer treatment. The resulting bleeding
worsens thrombocytopenia through increased platelet
consumption. Heavy bleeding may result in the need for
transfusion and delay or interrupt their treatment regime.47,48
These immunosuppressed women are also at increased risk
of infection from both neutropenia and prolonged bleeding.
Iatrogenic thrombocytopenia necessitates prevention of
heavy menstrual bleeding through menstrual suppression.
Recommendation
4. Gynaecologic consultation should be considered
prior to the initiation of treatment in all
premenopausal women at risk for abnormal uterine
bleeding from chemotherapy. (II-1A)
GnRH Analogues
Most of the data on menstrual suppression in women
with malignancies focus on the use of the GnRH agonist
LA. Heavy menstrual bleeding can be mitigated through
induced hypo-estrogenism and gonadal suppression. The
first reported study by Ghalie et al. (1993) compared LA
administered 1 mg IV daily or 7.5 mg IM monthly prior
to bone marrow transplant at different times during the
menstrual cycle in 34 patients.48 No adverse effects were
observed and menstruation was prevented in 73% of patients.
When LA was started at least 2 weeks prior to the onset
of thrombocytopenia, the failure rate was 6%; when it was
initiated at a later time, the failure rate was 33%.48 Prospective
studies with different doses or routes of administration
of LA, such as 3.75 mg IM prior to chemotherapy,49–51
showed similar relations between the success of therapeutic
amenorrhea and the timing of the treatment. The efficacy
of GnRH analogues in preventing bleeding has been shown
in 85% to 100% of patients when initiated at least 1 month
prior to chemotherapy.49,50 Duration of therapy is usually
directed by the risk or presence of thrombocytopenia or is
dependent on the duration of myelosuppressive therapy.
Menstrual Suppression in Special Circumstances
Recommendation
5. Leuprolide acetate or combined hormonal
contraception should be considered highly effective
in preventing abnormal uterine bleeding when
initiated prior to cancer treatment in premenopausal
women at risk for thrombocytopenia. (II-2A)
In 2007, Quaas and Ginsburg published a systematic review
on the prevention and treatment of uterine bleeding in
premenopausal patients with malignancies. They concluded
that GnRH agonists are very effective for the prevention of
uterine bleeding in these patients. The prevention of bleeding
was recommended over the acute treatment of bleeding and
a consultation with a gynaecologist prior to starting any
treatments was encouraged.52 Prophylactic management with
LA was recommended in a 2011 review.53 Tranexamic acid,
medroxyprogesterone or OCP, or IV estrogen followed by
danazol or recombinant factor V11a with desmopressin were
recommended as escalated treatment for heavy menstrual
bleeding. In a worldwide survey, mainly of oncologists of
pediatric bone marrow transplant patients, GnRH agonists
were preferentially chosen by 41% of respondents over
CHC (29%), progesterone-only oral medication (21%),
DMPA (6%), and ethinyl estradiol/norelgestromin patch
(3%) for the induction of amenorrhea.54 There are no studies
comparing GnRH agonists directly to OCPs to demonstrate
superior effectiveness. Neither GnRH agonists nor OCPs
have been shown conclusively to confer protection against
ovarian insufficiency.55,56
Oral Contraceptive Pills
Although the OCP is often referred to as a standard
method for menstrual suppression in women with
malignancies, there is little published in this area.53 Only
one small retrospective series of oral contraceptives
for prevention of heavy menstrual bleeding in women
undergoing stem cell transplantation has been published.57
Gynaecologic consultation occurred at a median of 12 days
after transplantation. Prior to consultation, 21 (64%) of
33 patients had been on OCP; most of the other patients
had no hormonal treatments and a small minority were on
medroxyprogesterone alone or combined with conjugated
estrogens. Heavy menstrual bleeding resolved in 97%
of patients, but 21% required more than one form of
hormonal therapy and 12% required progressive treatment
with higher dose OCP and/or IV conjugated estrogen.57
OCP is an important option for patients who cannot
tolerate IM injections or who show evidence of
osteoporosis. However, oral contraceptives may increase
both liver toxicity following stem cell transplant and the
frequency of venous thromboembolic events, which are
OCTOBER JOGC OCTOBRE 2014 l 921
SOGC Clinical Practice Guideline
already increased in patients with malignancy. OCP may
also be poorly tolerated or absorbed due to mucositis,
vomiting, or diarrhea secondary to radiation enterocolitis
or chemotherapy.57
In a prospective cohort trial by Sica et al.,58 16 premenopausal
women with acute leukemia were administered OCP alone
(n = 8) or OCP with LA (n = 8) for the prevention of vaginal
bleeding during chemotherapy. There were no statistical
differences in red blood cell or platelet transfusions or
duration of vaginal bleeding, nor were there any flares
in either group. Liver toxicity was noted in both groups.
However, once the OCP was discontinued, liver damage
resolved and menses also resumed in 6 of the 8 patients
on OCP versus none in the combined group for whom
the OCPs were administered to prevent flares. The authors
attributed these findings to the more profound induction
of amenorrhea by LA than by OCP alone.
Depot Medroxyprogesterone Acetate
In 2006, Meirow et al. compared D-tryptophan-6-luteinizing
hormone-releasing hormone (a GnRH agonist) to DMPA
or no treatment in patients prior to myelosuppresive
chemotherapy retrospectively in 101 patients.47 Significantly
fewer urgent gynaecologic consultations were required in
the patients who were administered GnRHa. In the DMPA
group 20% experienced moderate or severe menstrual
bleeding. Urgent treatment with conjugated estrogens was
required in untreated patients and in patients on DMPA,
but not in any of the patients who received GnRH agonists.
The authors of this and other studies52 emphasize the
importance of gynaecologic evaluation prior to the initiation
of treatment and conclude that GnRH agonist treatment is
more effective than DMPA for menstrual suppression and
the reduction of heavy menstrual bleeding.
Levonorgestrel Intrauterine System
No studies have been published regarding menstrual
management by LNG-IUS in patients undergoing cancer
treatment. However, according to the World Health
Organization’s medical eligibility criteria for contraceptive
use, the IUS is acceptable in immunosuppressed patients
(such as those with lupus undergoing immunosuppressive
treatment and patients with HIV) and patients at risk for
venous thromboembolism.59
Surgical Options
There are no case reports or trials assessing prophylactic
surgical techniques such as uterine artery embolization,
endometrial ablation, or hysterectomy to prevent menstrual
bleeding in hematologic malignancy. Case reports describe the
use of uterine artery embolization to control chemotherapy-
induced heavy menstrual bleeding unresponsive to medical
management.60,61
922 l OCTOBER JOGC OCTOBRE 2014
SUMMARY
Menstrual suppression is often medically indicated. The
Canadian Consensus Guideline on Continuous and Extended
Hormonal Contraception2 describes many indications for
suppression, including social choice, severe dysmenorrhea
associated with endometriosis, abnormal uterine bleeding,
hemorrhagic diatheses, hormone withdrawal symptoms, and
premenstrual dysphoric disorders. This guideline focuses
on 2 groups who often benefit significantly from reduced
menstrual bleeding or amenorrhea: women with cognitive
and/or physical impairments and women undergoing
cancer therapy. While there is a paucity of data from large
trials to dictate clinical practice, several options are available
to induce therapeutic amenorrhea in women with disabilities
or prophylactic menstrual suppression in women with
malignancies prone to thrombocytopenia.
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Contraception 2010;81:281–91.
33. Isley MM, Kaunitz AM. Update on hormonal contraception and
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34. de Oliveria MRM, da Silva CC, Kurokawa CS, Fortes CMT, Capela RC,
Teixeira AS, et al. Bone mineral density in healthy female adolescents
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35. Pitts SA, Feldman HA, Dorale A, Gordon CM. Bone mineral density,
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36. Bonny AE, Britto MT, Huang B, Succop P, Slap GB. Weight gain,
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37. Jensen JT. Contraceptive and therapeutic effects of the levonorgestrel
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40. Kaunitz, AM, Bissonnette F, Monteiro I, Lukkari-Lax E, Muysers C,
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 SOGC COMMITTEE OPINION
Current Status in Non-Invasive Prenatal
Detection of Down Syndrome, Trisomy 18,
and Trisomy 13 Using Cell-Free DNA in
Maternal Plasma
This committee opinion has been prepared by the Genetics
Committee and approved by the Executive of the Society of
Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Sylvie Langlois, MD, Vancouver BC
Jo-Ann Brock, MD, Halifax NS
GENETICS COMMITTEE
R. Douglas Wilson, MD (Chair), Calgary AB
François Audibert, MD, Montreal QC
Jo-Ann Brock, MD, Halifax NS
June Carroll, MD, Toronto ON
Lola Cartier, MSc, CCGC, Montreal QC
Alain Gagnon, MD, Vancouver BC
Jo-Ann Johnson, MD, Calgary AB
Sylvie Langlois, MD, Vancouver BC
William MacDonald, MD, Halifax NS
Lynn Murphy-Kaulbeck, MD, Moncton NB
Nanette Okun, MD, Toronto ON
Melanie Pastuck, RN, Cochrane AB
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all members of
the committee.
Abstract
Objective: To provide a review of published studies on the use
of cell-free fetal DNA in maternal plasma for the non-invasive
diagnosis of Down syndrome, trisomy 18, and trisomy 13.
Evidence: PubMed was searched for articles published between
2006 and October 2012, using appropriate key words
(e.g., non-invasive prenatal diagnosis, Down syndrome, cell-free
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 287, February 2013
fetal DNA, aneuploidy screening). Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. Searches were updated on
a regular basis and incorporated in the guideline to October
31, 2012. Grey (unpublished) literature was identified through
searching the websites of health technology assessment and
health technology assessment-related agencies, clinical practice
guideline collections, clinical trial registries, and national and
international medical specialty societies.
Values: The studies reviewed were classified according to criteria
described by the Canadian Task Force on Preventive Health Care,
and the recommendations for practice were ranked according to
this classification (Table 1).
Recommendations
1. Non-invasive prenatal testing using massive parallel sequencing
of cell-free fetal DNA to test for trisomies 21, 18, and 13 should
be an option available to women at increased risk in lieu of
amniocentesis. Pretest counselling of these women should
include a discussion of the limitations of non-invasive prenatal
testing. (II-2A)
2. No irrevocable obstetrical decision should be made in pregnancies
with a positive non-invasive prenatal testing result without
confirmatory invasive diagnostic testing. (II-2A)
3. Although testing of cell-free fetal DNA in maternal plasma
appears very promising as a screening test for Down syndrome
and other trisomies, studies in average-risk pregnancies and a
significant reduction in the cost of the technology are needed
before this can replace the current maternal screening approach
using biochemical serum markers with or without fetal nuchal
translucency ultrasound. (III-A)
J Obstet Gynaecol Can 2013;35(2):177–181
Key Words: Non-invasive prenatal diagnosis, prenatal screening,
Down syndrome, trisomy 18, trisomy 13, cell-free fetal DNA
FEBRUARY JOGC FÉVRIER 2013 l 177
SOGC COMMITTEE OPINION
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.21
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.21
INTRODUCTION
U ntil recently, prenatal genetic diagnosis, either for
increased risk of chromosome aneuploidy or for
specific gene testing, has required a sample of fetal tissue
obtained through invasive diagnostic procedures (CVS,
amniocentesis, or umbilical blood sampling) that have
associated fetal and maternal procedural risks including
pregnancy loss. The finding of intact fetal cells and
cffDNA in maternal blood has allowed the development
of non-invasive prenatal diagnosis of certain fetal
conditions. Several studies have validated the use of
cffDNA in maternal plasma fetal sex determination1 and
fetal Rh typing.2,3 Molecular testing of cffDNA has also
been carried out for the detection of paternally inherited
mutations in single genes.4
The presence of cffDNA in maternal plasma in all
pregnancies, along with the development of new molecular
technologies, has prompted research into the use of
maternal plasma testing to detect fetal Down syndrome.
As fetal DNA represents only 10% to 20% of the total
DNA found in maternal plasma, the primary challenge
of developing an accurate assay has been discriminating
between a DNA sample with a fetal complement that
ABBREVIATIONS
cffDNA cell free fetal DNA
CVS chorionic villus sampling
NIPT non-invasive prenatal testing
178 l FEBRUARY JOGC FÉVRIER 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
contributes 3 and one that contributes 2 copies of
chromosome 21 to the total amount of plasma cell-
free DNA of the mother. A recently developed massive
parallel shotgun sequencing technology, in conjunction
with sophisticated sequencing data analyses, has been used
successfully to detect fetal Down syndrome in women with
pregnancies at high risk for chromosomal abnormalities.
In essence, millions of small fragments of cffDNA (either
random or specific to chromosomes of interest) from
maternal plasma (containing both fetal and maternal
cell-free DNA) are amplified and sequenced. After the
fragments are mapped to the human genome and analyzed
for frequency/density along each chromosome, fetal Down
syndrome is detected with a high degree of accuracy by
observing an over-representation of chromosome 21. The
same approach can be taken for the detection of other
chromosomal abnormalities.
REVIEW OF REPORTED NIPT STUDIES USING
MASSIVELY PARALLEL SEQUENCING TO DETECT
DOWN SYNDROME, TRISOMY 18, AND TRISOMY 13
Studies comparing the detection rate of Down syndrome
by cffDNA testing with the detection rate by cytogenetic
analysis of chorionic villus samples or amniocytes have
been limited to high-risk pregnancies to enrich the cohort
with cases that would indeed have Down syndrome
and therefore allow validation of the technology being
developed. Although the initial work was done in small
cohorts of patients as proof of feasibility of this new
technology,5–7 more recent studies validated its use in larger
Current Status in Non-Invasive Prenatal Detection of Down Syndrome, Trisomy 18, and Trisomy 13 Using Cell-Free DNA in Maternal Plasma

Table 2. Results of validation studies for non-invasive detection of fetal trisomy 21

Number Sequencing Detection False-
Study samples tested Failure rate* approach rate positive rate
Chiu et al. 20118 764 1.4% 8-plex, shotgun 79.1% (68/86) 1.1%
232 N/A 2-plex shotgun 100% (86/86) 2.1%
Palomaki et al. 20119 1696 0.8% 4-plex shotgun 98.6% (209/212) 0.2%
95% CI 95.9 to 99.7 95% CI < 0.1 to 0.6
Ehrich et al. 201110 467 3.9% 4-plex shotgun 100% (39/39) 0.2%
95% CI 89 to 100 95% CI 0.1 to 1.5
Lau et al. 201111 108 0 12-plex shotgun 100% (11/11) 0
Sehnert et al. 201112 47 0 1-plex shotgun 100% (13/13) 0
Sparks et al. 201213 167 0† 96-plex selective 100% (36/36) 0.8%
Ashoor et al. 201214 400 0.75% 96-plex selective 100% (50/50) 0
Bianchi et al. 201215 532 3% 6-plex 100% (89/89) 0
95% CI 95.9 to 100
Norton et al. 201216 3228 4.5% 96-plex selective 100% (81/81) 0.03%
95% CI 95.5 to 100 95% CI 0.002 to 0.2
*Percentage of samples that did not meet quality control requirements for the sequencing so that no results could be obtained.
†5% failure in their training set.
N/A: not applicable—only samples that passed original sequencing quality control were retested with the 2-plex.

cohorts of pregnant women who had undergone an invasive
procedure (CVS or amniocentesis).8–16 The indications for
invasive diagnostic testing included advanced maternal
age, abnormal aneuploidy screening results, and/or
sonographically diagnosed fetal abnormalities. Results of
these clinical trials are summarized in Table 2. Only trials
that collected maternal blood samples before invasive
procedures are included. While all studies used massive
parallel sequencing, there were differences in methodology
and sequencing data analysis between studies that prevent
summing of the results. However, the detection rate for
Down syndrome in all studies was, or approached, 100%
with a false-positive rate less than 1%. The focus of studies
so far has been the detection of Down syndrome; however,
this technology has also been used to detect trisomy 18
and trisomy 13, although initially with less success because
of a larger coefficient of variation and therefore lower
precision in estimating the proportion of chromosomes
18 or 1311,17 to the total chromosomes. However, recent
publications suggest that this can be overcome by using
a targeted sequencing approach13,14,16 and/or a different
sequencing data analysis approach.15,18 This is leading to the
utilization of this technology for the detection of trisomy
18 and trisomy 13 in addition to Down syndrome. Results
of those studies are presented in Table 3.
screening. Before these methods can replace current prenatal
screening options, validation studies using them in average-
risk pregnancies need to be done. Only one cohort study
of 2049 women has so far been done in women at average
risk.19 As the cost of the technology is high compared
with current screening methods, cost-effectiveness studies
are also needed. Given the demonstrated value of NIPT
in high risk pregnancies, this testing should be an option
available to pregnant women found to be at increased
risk of fetal Down syndrome, trisomy 18, and trisomy
13 on the basis of currently available screening tests or
ultrasound findings. It is important for these women to
receive detailed pretest counselling that explains the
benefits and limitations of the test.20 Counselling should
include the following points:
•• Non-invasive cffDNA testing should not be
considered equivalent to conventional cytogenetic
analysis of CVS or amniocytes.
•• Cytogenetic testing of CVS or amniocytes detects
100% of cases of Down syndrome, trisomy 18, and
trisomy 13 (thus is diagnostic), whereas the test done
on cffDNA does miss some cases (see Table 2 and
Table 3, detection rate).

•• The currently available tests screen only for Down

ISSUES FOR CONSIDERATION
The development of new screening methods to detect
Down syndrome through testing of cffDNA in maternal
plasma offers promising opportunities to improve prenatal
syndrome, trisomy 18, and trisomy 13. Other trisomies,
triploidy, and structural chromosomal abnormalities
would not be detected by the commercially available
ccfDNA test.

FEBRUARY JOGC FÉVRIER 2013 l 179

SOGC COMMITTEE OPINION

Table 3. Results of validation studies for non-invasive detection of fetal trisomy 18 and trisomy 13
Sequencing Trisomy 18 Trisomy 18 Trisomy 13 Trisomy 13
Study approach detection rate false-positive rate detection rate false-positive rate
Lau et al. 201111 12-plex shotgun 90% (9/10) 0 100% (2/2) 0
Sehnert et al. 2011 12
1-plex shotgun 100% (8/8) 0 No data No data
Sparks et al. 201213 96-plex selective 100% (8/8) 0.8% No data No data
Ashoor et al. 201214 96-plex selective 98% (49/50) 0 No data No data
Bianchi et al. 2012 15
6-plex 97.2% (35/36) 0 78.6% (11/14) 0
Norton et al. 201216 96-plex selective 97.4% (37/38) 0.07% No data No data
Palomaki et al. 201218 4-plex shotgun 100% (59/59) 0.28% 91.7% (11/12) 0.97%

•• cffDNA testing has a higher rate of false-positive
results than current diagnostic tests based on
cytogenetic analysis of amniocytes or chorionic villi.
(Tables 2 and 3, false positive rate).
•• Some women will have a cffDNA positive result and
not carry a fetus with Down syndrome, trisomy 18, or
trisomy 13 (false positive). No irrevocable obstetrical
decision should be made in pregnancies with a
positive cffDNA test for Down syndrome without
confirmatory invasive diagnostic testing.
•• cffDNA testing fails to provide a result in a small
percentage of women.
CONCLUSION
NIPT using massive parallel sequencing for the detection
of Down syndrome, trisomy 18, and trisomy 13 has shown
promising results in clinical trials of women identified by
2. No irrevocable obstetrical decision should be
made in pregnancies with a positive non-invasive
prenatal testing result without confirmatory invasive
diagnostic testing. (II-2A)
3. Although testing of cell-free fetal DNA in maternal
plasma appears very promising as a screening test
for Down syndrome and other trisomies, studies in
average-risk pregnancies and a significant reduction
in the cost of the technology are needed before this
can replace the current maternal screening approach
using biochemical serum markers with or without
fetal nuchal translucency ultrasound. (III-A)
REFERENCES
1. Avent ND, Chitty LS. Non-invasive diagnosis of fetal sex; utilisation
of free fetal DNA in maternal plasma and ultrasound. Prenat Diagn
2006;26:598–603.
2. Minon JM, Gerard C, Senterre JM, Schaaps JP, Foidart JM. Routine
fetal RHD genotyping with maternal plasma: a four-year experience in
Belgium. Transfusion 2008; 48:373–81.

screening as having a high-risk pregnancy. NIPT should be
an option as a second-level contingent screening test (after
a positive result from currently used serum and ultrasound
screening techniques) for women wishing to avoid invasive
testing. Further studies are needed to determine if this
approach can be reliably used as a first-tier screening test in
average-risk pregnancies. Finally, cost-effectiveness studies
are needed before this cffDNA approach can replace
current screening options.
Recommendations
1. Non-invasive prenatal testing using massive
parallel sequencing of cell-free fetal DNA to test
for trisomies 21, 18, and 13 should be an option
available to women at increased risk in lieu of
amniocentesis. Pretest counselling of these women
should include a discussion of the limitations of
non-invasive prenatal testing. (II-2A)
3. Finning K, Martin P, Summers J, Massey E, Poole G, Daniels G. Effect of
high throughput RHD typing of fetal DNA in maternal plasma on use of
anti-RhD immunoglobulin in RhD negative pregnant women; prospective
feasibility study. Br Med J 2008;336:816–8.
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blood for non-invasive prenatal diagnosis. Hum Reprod Update
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5. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Noninvasive
diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal
blood. PNAS 2008;105:16266–71.
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FEBRUARY JOGC FÉVRIER 2013 l 181
 SOGC CLINICAL PRACTICE GUIDELINE

No. 298, October 2013 (Replaces No. 149, September 2004)

The Prevention of Early-Onset

Neonatal Group B Streptococcal Disease
Abstract
This Clinical Practice Guideline has been prepared by the
Infectious Disease Committee, reviewed by the Infectious Objective: To review the evidence in the literature and to provide
Diseases and Immunization and the Fetus and Newborn recommendations on the management of pregnant women
Committees of the Canadian Paediatric Society, and the in labour for the prevention of early-onset neonatal group B
SOGC Family Practice Advisory Committee, and approved streptococcal disease. The key revisions in this updated guideline
by the Executive and Council of the Society of Obstetricians include changed recommendations for regimens for antibiotic
and Gynaecologists of Canada. prophylaxis, susceptibility testing, and management of women
with pre-labour rupture of membranes.
PRINCIPAL AUTHORS
Outcomes: Maternal outcomes evaluated included exposure to
Deborah Money, MD, Vancouver BC antibiotics in pregnancy and labour and complications related to
antibiotic use. Neonatal outcomes of rates of early-onset group B
Victoria M. Allen, MD, Halifax NS
streptococcal infections are evaluated.
INFECTIOUS DISEASES COMMITTEE Evidence: Published literature was retrieved through searches of
MEDLINE, CINAHL, and The Cochrane Library from January
Mark H. Yudin, MD (Chair), Toronto ON
1980 to July 2012 using appropriate controlled vocabulary
Victoria M. Allen, MD, Halifax NS and key words (group B streptococcus, antibiotic therapy,
Celine Bouchard, MD, Quebec QC infection, prevention). Results were restricted to systematic
reviews, randomized control trials/controlled clinical trials,
Marc Boucher, MD, Montreal QC and observational studies. There were no date or language
Sheila Caddy, MD, Edmonton AB restrictions. Searches were updated on a regular basis and
incorporated in the guideline to May 2013. Grey (unpublished)
Eliana Castillo, MD, Calgary AB literature was identified through searching the websites of health
Deborah Money, MD, Vancouver BC technology assessment and health technology-related agencies,
clinical practice guideline collections, clinical trial registries, and
Kellie E. Murphy, MD, Toronto ON national and international medical specialty societies.
Gina Ogilvie, MD, Vancouver BC Values: The quality of evidence in this document was rated using the
Caroline Paquet, RM, Trois-Rivieres QC criteria described in the Report of the Canadian Task Force on
Preventive Health Care (Table 1).
Vyta Senikas, MD, Ottawa ON
Benefits, Harms, and Costs: The recommendations in this guideline
Julie van Schalkwyk, MD, Vancouver BC
are designed to help clinicians identify and manage pregnancies
Disclosure statements have been received from all members of at risk for neonatal group B streptococcal disease to optimize
the committees maternal and perinatal outcomes. No cost-benefit analysis is
provided.

Key Words: Group B streptococcus, antibiotic therapy, infection,

prevention
J Obstet Gynaecol Can 2013;35(10):939–948

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

OCTOBER JOGC OCTOBRE 2013 l 939

SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.73
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.73
Summary Statement
There is good evidence based on randomized control trial data that
in women with pre-labour rupture of membranes at term who are
colonized with group B streptococcus, rates of neonatal infection are
reduced with induction of labour. (I) There is no evidence to support
safe neonatal outcomes with expectant management in this clinical
situation.
Recommendations
1. Offer all women screening for colonization with group B
streptococcus at 35 to 37 weeks’ gestation with culture taken
from one swab first to the vagina and then to the rectum (through
the anal sphincter). (II-1A) This includes women with planned
Caesarean delivery because of their risk of labour or ruptured
membranes earlier than the scheduled Caesarean delivery. (II-2B)
2. Because of the association of heavy colonization with early
onset neonatal disease, provide intravenous antibiotic prophylaxis
for group B streptococcus at the onset of labour or rupture of the
membranes to:
• any woman positive for group B streptococcus by
vaginal/rectal swab culture screening done at 35 to
37 weeks’ gestation (II-2B);
• any woman with an infant previously infected with group
B streptococcus (II-3B);
ABBREVIATIONS
CDC Centers for Disease Control and Prevention
GBS group B streptococcus
IV intravenous
PCR polymerase chain reaction
PPROM preterm pre-labour rupture of membranes
PROM pre-labour rupture of membranes
940 l OCTOBER JOGC OCTOBRE 2013
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
• any woman with documented group B streptococcus
bacteriuria (regardless of level of colony-forming units) in the
current pregnancy. (II-2A)
3. Manage all women who are < 37 weeks’ gestation and in
labour or with rupture of membranes with intravenous group
B streptococcus antibiotic prophylaxis for a minimum of 48 hours,
unless there has been a negative vaginal/rectal swab culture or
rapid nucleic acid-based test within the previous 5 weeks. (II-3A)
4. Treat all women with intrapartum fever and signs of
chorioamnionitis with broad spectrum intravenous antibiotics
targeting chorioamnionitis and including coverage for group B
streptococcus, regardless of group B streptococcus status and
gestational age. (II-2A)
5. Request antibiotic susceptibility testing on group B
streptococcus-positive urine and vaginal/rectal swab cultures in
women who are thought to have a significant risk of anaphylaxis
from penicillin. (II-1A)
6. If a woman with pre-labour rupture of membranes at ≥ 37 weeks’
gestation is positive for group B streptococcus by vaginal/rectal
swab culture screening, has had group B streptococcus
bacteriuria in the current pregnancy, or has had an infant
previously affected by group B streptococcus disease, administer
intravenous group B streptococcus antibiotic prophylaxis.
Immediate obstetrical delivery (such as induction of labour) is
indicated, as described in the Induction of Labour guideline
published by the Society of Obstetricians and Gynaecologist in
September 2013. (II-2B)
7. At ≥ 37 weeks’ gestation, if group B streptococcus colonization
status is unknown and the 35- to 37-week culture was not
performed or the result is unavailable and the membranes have
been ruptured for greater than 18 hours, administer intravenous
group B streptococcus antibiotic prophylaxis. (II-2B)
8. If a woman with pre-labour rupture of membranes at < 37 weeks’
gestation has an unknown or positive group B streptococcus culture
status, administer intravenous group B streptococcus prophylaxis
for 48 hours, as well as other antibiotics if indicated, while awaiting
spontaneous or obstetrically indicated labour. (II-3B)
 The Prevention of Early-Onset Neonatal Group B Streptococcal Disease
INTRODUCTION
T he purpose of this guideline is to review the literature
and evidence for management of pregnant women in
Canada in order to minimize the risk of early-onset neonatal
disease due to group B streptococcus. Since publication of
the 2004 SOGC guideline “The Prevention of Early-onset
Neonatal Group B streptococcal Disease,”1 there has been
ongoing evaluation of screening, intrapartum antibiotic
management, and neonatal outcomes.
BACKGROUND
Group B streptococci (streptococcus agalactiae) are gram-
positive, aerobic diplococci that typically produce a
narrow zone of beta hemolysis on 5% sheep blood agar.
These organisms are divided into 10 types on the basis
of capsular polysaccharides (Ia, Ib, II, and III through
IX). Types Ia, Ib, II, III, and V account for approximately
95% of cases in infants in the United States. Type III
is the predominant cause of early-onset meningitis and
the majority of late-onset infections in infants. Pilus-like
structures are important virulence factors and potential
vaccine candidates.2
Neonatal GBS disease can be classified as early- or late-
onset. Early-onset disease occurs less than 7 days after
birth and is associated with a mortality rate of 5% to
20%.3 Davies et al. reviewed the distribution of early-onset
disease in neonates in Canada and found 71% developed
bacteremia, 11% meningitis, and 19% pneumonia.4
The introduction of universal GBS screening in 2002
was associated with a reduction in rates of early-onset
GBS disease to approach rates of late-onset disease.5,6
Infection with GBS remains a significant cause of
neonatal morbidity and mortality in North America.2,6
Associated with the introduction of systematic intrapartum
chemoprophylaxis, the incidence of neonatal disease in
Canada and the United States has decreased from 1 to 3
per 1000 in the early 1990s to 0.35 to 0.5 per 1000 since the
adoption of universal screening.6–8 A Centers for Disease
Control and Prevention surveillance study estimated that
the use of intrapartum chemoprophylaxis has prevented
4500 cases per year of GBS sepsis and 225 deaths per
year in the United States.9 A Canadian population-based
study demonstrated an overall incidence of neonatal GBS
infections of 0.64 per 1000 live births, 57% of which were
early-onset disease. This study demonstrated a case fatality
rate from early-onset GBS infection of 9%, with 11% of all
cases of GBS disease ending in stillbirth.4 Case fatality rates
of 20% to 30% are seen in infants with GBS disease born
preterm, compared with 2% to 3% among term infants.9
Group B streptococcus is part of the normal vaginal
microbiome, and in North America 10% to 30% of
women are colonized.10 A Canadian study published
in 1998 showed an overall colonization rate of 11%,11
while a study in a different Canadian population showed
a colonization rate of 30% at time of delivery.12 An
estimated 1% to 2% of infants born to colonized women
develop early-onset GBS disease.13 The overall case fatality
rate is currently 5% to 9% compared with 70% three
decades ago.3,11,14 The prevalence of GBS colonization
appears to differ among different populations. In the
United Kingdom, the incidence of early-onset GBS
disease, in the absence of systematic screening or wide-
spread intrapartum antibiotic prophylaxis, is lower than in
Canada, with a rate of 0.5 per 1000 births.15 In addition,
there was a comparable incidence of 0.4 per 1000 live
births in Sweden,16 supporting subsequent European
clinical practice guidelines recommending a risk factor-
based approach to prevention of GBS disease.
Lower urogenital tract colonization with GBS may be
chronic, transient, or intermittent. The presence of GBS
in clean-catch urine cultures reflects heavy genital tract
maternal colonization, which is associated with neonatal
disease.17,18 Vaginal colonization in early pregnancy
does not predict colonization at delivery,19 but vaginal
colonization has generally been associated with young
maternal age,20 sexual activity, tampon use, infrequent
handwashing,21 high temperatures, and humidity.22
Most of these data are from small studies and require
confirmation.
Risk factors for neonatal infection include <  37
completed weeks of gestation at birth, prolonged rupture
of membranes (> 18 hours), intra-amniotic infection,
low socioeconomic status, and low maternal levels of
anticapsular antigen.14,23–27 A UK study found the main
risk factors to be prematurity, rupture of membranes for
longer than 18 hours, and maternal fever in labour.28 Of
note, diabetes in pregnancy is associated with higher rates
of GBS colonization.29,30 One study using Canadian data
has implicated intrauterine fetal monitoring (fetal scalp
electrode) as an independent risk factor for neonatal GBS
disease.27 When birth weight is accounted for, maternal
carriage of GBS has been shown to be independently
associated with early-onset GBS disease (OR 6.9; 95%
CI 2.8 to 17.1).31 Recent information demonstrates
that known antepartum or intrapartum predisposing
risk factors for GBS disease are lacking in 30% to 50%
of women with infants with GBS disease.27,32–34 The
diagnosis of GBS sepsis in infants with risks for or signs
of sepsis, therefore, should not be ruled out because
OCTOBER JOGC OCTOBRE 2013 l 941
SOGC Clinical Practice Guideline
of negative maternal GBS screening. This emerging
information from European and Canadian populations
was not available at the time of the Canadian Task Force on
Preventative Health Care’s 2001 report on the prevention
of early-onset group B streptococcal infection in the
newborn, which recommended that universal screening
with selective intrapartum chemoprophylaxis be given to
colonized women with risk factors.35
Heavy colonization with GBS has been associated with
adverse pregnancy outcomes including preterm labour
and preterm pre-labour rupture of membranes.36,37 GBS
bacteriuria occurs in 2% to 4% of pregnancies and is
associated with both maternal urinary tract disease and an
increased risk of neonatal disease.17 Maternal colonization
with GBS has been associated with endometritis and
wound infection.38,39 There is no convincing evidence that
GBS bacteriuria with low colony counts (< 108 CFU/L
or < 105 CFU/mL) is associated with increased risks for
pyelonephritis, chorioamnionitis, or preterm birth, and
antepartum treatment (prior to the onset of labour or
rupture of membranes) for low colony counts is therefore
not recommended. Intrapartum IV antibiotic prophylaxis
is still recommended for GBS bacteriuria in the current
pregnancy, regardless of colony count.40 Laboratory
reporting of any colony count of GBS in the urine in
pregnancy is variable among centres in Canada.
STRATEGIES TO PREVENT NEONATAL GBS
Chemoprophylaxis before the onset of labour or rupture
of membranes has been shown to be ineffective;41
antepartum antibiotic prophylaxis of colonized women
results in a 67% recurrence of GBS colonization later
in pregnancy.42 Intrapartum therapy has been found to
be effective in preventing neonatal GBS disease.39,43
Immunization strategies have been proposed as a
preferred prevention approach but vaccine development
has been challenging, however, a multivalent capsular
antigen based vaccine is in clinical trials at present.44
The pivotal randomized controlled trial of Boyer
and Gotoff in 1985 showed that use of intrapartum
antibiotics decreased the risk of early-onset disease in
neonates and decreased perinatal febrile morbidity in
colonized women.45 An early meta-analysis of 7 studies
(5 controlled trials and 2 cohort studies) demonstrated a
30-fold reduction in early-onset GBS disease with the use
of intrapartum penicillin prophylaxis for GBS-colonized
women.46
This culminated in screening and prophylaxis
recommendations from the CDC in 1996.8 These
942 l OCTOBER JOGC OCTOBRE 2013
recommendations advised one of two approaches:
a universal screening or a risk-factor approach. The
screening approach involved performing a rectovaginal
swab at 35 to 37 weeks and culturing in selective broth. All
women colonized with GBS were to receive intrapartum
antibiotics, and women with negative cultures were
to receive antibiotics only if they developed signs of
chorioamnionitis. A risk-factor approach (onset of labour
at < 37 weeks’ gestation, membrane rupture > 18 hours,
intrapartum temperature > 38.0°C) was considered an
acceptable alternative. If women had GBS bacteriuria
in the current pregnancy or a previous infant who had
invasive GBS disease, they were to receive intrapartum
chemoprophylaxis regardless of current colonization
status, and would not require a vaginal/anal swab for
GBS culture at 35 to 37 weeks’ gestation.
In June 1997, the Society of Obstetricians and
Gynaecologists of Canada presented guidelines which
were congruent to those recommended by the CDC.47
The Canadian guideline stated that two methods were
acceptable, either universal screening at 35 to 37 weeks
by combined vaginal/rectal swab and intrapartum
chemoprophylaxis of all colonized women, or intrapartum
chemoprophylaxis of women with risk factors. It was
acknowledged that additional research was required to
evaluate the prevention of neonatal GBS disease.
The influence of the 1996 CDC and 1997 SOGC guidelines
can be evaluated by the epidemiologic changes which
occurred following their implementation. There has been
a decline in perinatal GBS disease, with a 70% decrease in
early-onset disease to 0.5 per 1000 live births.25,26 Maternal
infection also declined by 21% from 0.29 to 0.23 per 1000
deliveries from 1993 to 1998.26 While multiple studies
have provided data demonstrating a general reduction
of neonatal GBS rates with concomitant maternal
benefits, health-care providers’ difficulties in complying
with the complex protocol was often commented upon
in the studies.4,9,48–52 Improved management of preterm
deliveries and improved collection, processing, and
reporting of culture results were recently identified as
potential areas for improved prevention of early-onset
GBS disease.53
Despite a comment on the lack of quality of the
studies reviewed, a Cochrane Review performed in
2000 concluded that the use of intrapartum antibiotic
prophylaxis of women colonized with GBS reduces
neonatal infection.43 A more recent Cochrane Review
suggested that intrapartum antibiotic prophylaxis
showed no statistically significant reduction in the risk
for neonatal all-cause mortality, or mortality from
 The Prevention of Early-Onset Neonatal Group B Streptococcal Disease
GBS and non-GBS organisms (primary outcome
analyses).54 However, analysis of secondary outcomes
suggested a statistically significant reduction (80%)
in the incidence of both confirmed early-onset GBS
disease (RR 0.17, 95% CI 0.04 to 0.74, number needed
to benefit 25) and probable early-onset GBS disease
(RR 0.17, 95% CI 0.03 to 0.91, number needed to
benefit 20) in neonates following intrapartum antibiotics
compared to no prophylaxis. There was no reduction in
the incidence of late-onset GBS neonatal disease. The
trials included in this meta-analysis were of poor quality
and had significant methodological biases.54
RISK-BASED VERSUS SCREENING APPROACH
No randomized trials have evaluated intrapartum antibiotic
prophylaxis based on risk factors versus universal screening
approaches, although a number of non-randomized
studies have attempted to evaluate the merits of screening
versus a risk-based approach.55,56 In most studies, the
screening approach included intrapartum prophylaxis
for all women who were colonized at the time of labour
or rupture of membranes. A large CDC multistate study
of a stratified random sample of 626 912 live births in
1998 and 1999 demonstrated that of 5144 births, the risk
of early-onset disease was significantly lower among the
infants of screened women compared to those born to
mothers managed with the risk-based approach (adjusted
RR 0.46; 95% CI 0.36 to 0.60).56 This information
prompted the development of revised guidelines by the
CDC in 2002.57 The most significant recommendation
in the CDC guideline at that time included a change
from a dual approach to universal prenatal culture-based
screening for vaginal and rectal GBS colonization of all
pregnant women at 35 to 37 weeks’ gestation. Updated
prophylaxis regimens for women with a penicillin allergy
were provided, including cefazolin if not at high risk for
anaphylaxis, clindamycin or erythromycin if high risk for
anaphylaxis and GBS susceptible, or vancomycin if GBS
resistant or susceptibility unknown. Clindamycin can only
be utilized for erythromycin-resistant isolates if inducible
clindamycin resistance has been excluded. Intrapartum
antibiotic GBS prophylaxis for GBS-colonized women
undergoing planned Caesarean delivery before the onset
of labour with intact membranes was not recommended.57
A further update by the CDC in 2010 has included a
change in the recommended dose for penicillin G for
prophylaxis (acceptable dose range of 2.5 to 3.0 million
units for doses subsequent to the initial dose), changes to
prophylaxis regimens for women with penicillin allergy
(removal of erythromycin as an acceptable alternative
due to an increase in resistance in GBS seen recently),
and updated and separate algorithms for women with
preterm labour (discontinue GBS prophylaxis if not
in labour) and PPROM (provide GBS prophylaxis
intravenously for 48 hours [or less if the swab for GBS
culture is subsequently negative], as well as antibiotics for
latency if other antibiotic regimens are usually used).13
Economic analyses of risk-based and universal culture-
based approaches have been conducted and showed that
universal culture-based is equivalent in cost to risk-based
approach if one considers the cost savings involved with
reduction of morbidity and mortality. It has also been
shown that a risk-based versus screening approach is
essentially equivalent in cost and in the number of women
receiving antibiotics prophylaxis.58
Recommendations
1. Offer all women screening for colonization with
group B streptococcus at 35 to 37 weeks’ gestation
with culture taken from one swab first to the vagina
and then to the rectum (through the anal sphincter).
(II-1A) This includes women with planned
Caesarean delivery because of their risk of labour
or ruptured membranes earlier than the scheduled
Caesarean delivery. (II-2B)
2. Because of the association of heavy colonization
with early onset neonatal disease, provide
intravenous antibiotic prophylaxis for group B
streptococcus at the onset of labour or rupture of
the membranes to:
• any woman positive for group B streptococcus by
vaginal/rectal swab culture screening done at 35
to 37 weeks’ gestation (II-2B);
• any woman with an infant previously infected
with group B streptococcus (II-3B);
• any woman with documented group B
streptococcus bacteriuria (regardless of
level of colony-forming units) in the current
pregnancy. (II-2A)
3. Manage all women who are < 37 weeks’ gestation
and in labour or with rupture of membranes with
intravenous group B streptococcus antibiotic
prophylaxis for a minimum of 48 hours, unless there
has been a negative vaginal/rectal swab culture or
rapid nucleic acid-based test within the previous 5
weeks. (II-3A)
4. Treat all women with intrapartum fever and
signs of chorioamnionitis with broad spectrum
intravenous antibiotics targeting chorioamnionitis
and including coverage for group B streptococcus,
regardless of group B streptococcus status and
gestational age. (II-2A)
OCTOBER JOGC OCTOBRE 2013 l 943
SOGC Clinical Practice Guideline

Table 2. Recommended antibiotic regimens for intrapartum prophylaxis

1. Penicillin G 5 million units IV, then 2.5 to 3.0 million every 4 hours until delivery
or
2. If the woman is allergic to penicillin but has a low risk of anaphylaxis: cefazolin 2 g IV then
1 g every 8 hours until delivery
or
3. If the woman is allergic to penicillin and at risk of anaphylaxis: clindamycin 900 mg IV every
8 hours until delivery (if isolate is susceptible to clindamycin with no inducible resistance)
or vancomycin 1 g IV every 12 hours until delivery

PRACTICAL ASPECTS OF THE
SCREENING METHODS
A vaginal/rectal (not vaginal/perianal) swab is taken at 35
to 37 weeks’ gestation to screen women and detect GBS
colonization of the genital tract. This is done by using
a single swab first in the vagina then in the rectum and
transporting it at room temperature to the laboratory
in a non-nutritive transport medium; Amies or Stuart’s
medium is recommended.59 These specimens should be
labelled clearly to inform the laboratory of the need to
perform specific GBS culturing. In addition, if the woman
is allergic to penicillin and is at a high risk for anaphylaxis,
this should be stated and a request made to perform
susceptibility testing (see Table 2).60,61 The laboratory
can then culture the organism in selective broth media to
maximize the isolation of GBS. Self-sampling for GBS
at 35 to 37 weeks’ gestation, with appropriate instruction
in the clinical examination room or washroom, has been
shown to be accurate and acceptable when compared with
physician sampling in a Canadian population.62
Recommendation
5. Request antibiotic susceptibility testing on group B
streptococcus-positive urine and vaginal/rectal
swab cultures in women who are thought to have a
significant risk of anaphylaxis from penicillin. (II-1A)
Antenatal GBS cultures at 35 to 37 weeks’ gestation have
been shown in a recent systematic review to have acceptable
positive and negative predictive values for colonization
at delivery (mean positive predictive value 69%, mean
negative predictive value 94%).63 A preferable method may
be a rapid accurate test to detect the presence of GBS
at the actual time of delivery. The use of a polymerase
chain reaction has been shown to have a sensitivity of
97% and a negative predictive value of 98.8%.64 The one
negative PCR in the 33 women evaluated was in a woman
with ruptured membranes prior to testing. In a Canadian
single-centre study evaluating the use of rapid PCR (IDI-
Strep B assay) in the labour and delivery suite, 85% of the
190 women enrolled had results of the standard screen at
35 to 37 weeks available for comparison.12 The sensitivity
and specificity of the standard 35- to 37-week screen were
84.3% (95% CI 71.4% to 93.0%) and 93.2% (95% CI
86.5% to 97.2%), respectively, whereas the sensitivity and
specificity of the rapid PCR were 90.7% (95% CI 79.7% to
96.9%) and 97.6% (95% CI 93.1% to 99.5%), respectively.
The median reporting time for the rapid PCR test was 99
minutes (range 50 to 255). Results were available more
than 4 hours before delivery in 81% of cases.12
The advantage of PCR screening is the rapid, real-time result;
the disadvantages are the lack of antibiotic susceptibility
data, potentially false-negative results related to rupture of
membranes, and the fact that there is insufficient time for use
of selective enrichment broth for at least 4 hours prior to PCR
in the intrapartum setting. The 2010 CDC guideline suggests
that a useful intrapartum screening test should be simple, have
a turn-around time of < 30 minutes, and have a sensitivity and
specificity of ≥ 90%.13 This technique would be reserved for
hospitals that had diagnostic laboratory capabilities of real-
time PCR testing, validated PCR performance, and appropriate
quality controls. A study comparing the estimated direct
costs (including screening test costs and hospital costs) and
consequences of intrapartum PCR screening for early-onset
GBS disease (Xpert GBS test) with antenatal lower vagina
culture screening demonstrated a higher detection rate of GBS
colonization with PCR (16.7% versus 11.7%). The average total
cost per delivery was US$1759 ± 1209 for antenatal screening
in 2009 and US$1754 ± 842 for intrapartum screening in 2010
(P = 0.9).65 With improved techniques, therefore, in some
institutions GBS screening may be replaced by intrapartum
PCR assessment.
ANTIBIOTIC CHOICES
Since GBS appears to be uniformly susceptible to the
penicillins, it is recommended that IV penicillin G be
used instead of IV ampicillin because of penicillin G’s
narrow spectrum of action, which diminishes the risk of
selective pressure on other organisms and decreases the

944 l OCTOBER JOGC OCTOBRE 2013

 The Prevention of Early-Onset Neonatal Group B Streptococcal Disease
risk of ampicillin resistance.66,67 The efficacy of alternatives
to penicillin to prevent early-onset GBS disease (such as
cephalosporins, clindamycin, or vancomycin) has not
been evaluated in controlled trials.13 Intravenous cefazolin
is recommended as the alternative for penicillin-allergic
women who are at low risk for anaphylaxis (do not have a
history of anaphylaxis, angioedema, respiratory distress, or
significant urticaria). It has a relatively narrow spectrum,
with similar pharmacokinetics to penicillin, and achieves
high intra-amniotic concentrations.13 The risk of allergic or
anaphylactic reaction to penicillins is between 4 per 10 000
and 4 per 100 000.56 For first-generation cephalosporins,
the risk of cross-reaction with penicillins is 0.5%; the risk
with second- and third-generation cephalosporins appears
to be even lower.68
Erythromycin and clindamycin were previously proposed
as alternative antibiotics for women at high risk for
anaphylaxis; however, the prevalence of resistance
among invasive GBS isolates has increased over the last
20 years and ranges from 25% to 32% for erythromycin
and from 13% to 20% for clindamycin.13,60,69 Although
efficacy data is limited, the 2010 CDC guidelines
recommend intravenous vancomycin and clindamycin for
women (if susceptible) at high risk for anaphylaxis from
penicillin; clindamycin susceptibilities including a search
for inducible clindamycin resistance should be performed
if possible on prenatal GBS isolates from penicillin-
allergic women.13 If susceptibilities are not available for
these women, intravenous vancomycin is the preferred
intrapartum prophylaxis. Oral antibiotic preparations are
not adequate for GBS prophylaxis, as they do not show
satisfactory rates of clearance of GBS from the genital
tract in the time frame of labour. Table 2 summarizes
the recommended regimens for intravenous intrapartum
antibiotic prophylaxis for the prevention of early-onset
GBS disease.
The implementation of a screening protocol will result in
approximately 10% to 25% of women in labour receiving
antibiotics for the prevention of GBS neonatal disease.
Concern that the use of antibiotics for GBS prophylaxis
may result in the selection of other organisms such as
E. coli is certainly an issue in theory; however, a study
of trends in neonatal sepsis has been reassuring, with no
increase in the rate of neonatal sepsis overall in the post-
GBS prophylaxis era, but some increase in E. coli sepsis
in preterm or low-birth-weight infants only.70 It would
be prudent to continue to be vigilant in tracking trends
in sepsis and antibiotic resistance as new prophylactic
antibiotic regimens are implemented.
PRE-LABOUR RUPTURE OF MEMBRANES
In the term PROM study, Hannah et al. reviewed their
outcomes in GBS-colonized women versus GBS-negative
women.71 In that study, 4834 women were randomized
to induction versus expectant management. Researchers
found that 10.7% of women were GBS positive by vaginal/
rectal swab culture and 127 infants had neonatal infections,
of which 10 were due to GBS, all in the expectant arm;
there was one death due to GBS in the expectant group.
The analysis revealed that for GBS-positive women,
induction of labour at term decreased the risk of neonatal
infection (OR 0.29; 95% CI 0.08 to 1.05, P = 0.06). In the
expectant management group, GBS-positive women had
a significantly greater risk of neonatal infection (OR 4.12;
95% CI 2.00 to 8.52, P < 0.001). The conclusion of the
study was that for GBS-colonized women with PROM at
term, immediate induction with oxytocin results in a lower
risk of infection than expectant management or induction
with prostaglandin E2 (if there are no contraindications to
vaginal delivery).
Summary Statement
There is good evidence based on randomized control
trial data that in women with pre-labour rupture of
membranes at term who are colonized with group B
streptococcus, rates of neonatal infection are reduced
with induction of labour. (I) There is no evidence
to support safe neonatal outcomes with expectant
management in this clinical situation.
Recommendations
6. If a woman with pre-labour rupture of
membranes at ≥ 37 weeks’ gestation is positive
for group B streptococcus by vaginal/rectal swab
culture screening, has had group B streptococcus
bacteriuria in the current pregnancy, or has
had an infant previously affected by group B
streptococcus disease, administer intravenous
group B streptococcus antibiotic prophylaxis.
Immediate obstetrical delivery (such as induction
of labour) is indicated, as described in the
Induction of Labour guideline published by the
Society of Obstetricians and Gynaecologist in
September 2013. (II-2B)
7. At ≥ 37 weeks’ gestation, if group B streptococcus
colonization status is unknown and the 35- to 37-
week culture was not performed or the result is
unavailable and the membranes have been ruptured
for greater than 18 hours, administer intravenous
group B streptococcus antibiotic prophylaxis. (II-2B)
OCTOBER JOGC OCTOBRE 2013 l 945
SOGC Clinical Practice Guideline
The 2010 CDC guideline provides an updated and separate
algorithm for women with PPROM. It recommends
providing GBS prophylaxis intravenously for 48 hours
(or less if the swab for GBS culture proves negative) and
additional antibiotics to prolong the latency period when
the standard of care would suggest that increased latency
and expectant management might show improved maternal
and fetal/neonatal outcomes over indicated obstetrical
delivery (such as induction of labour).13
Recommendation
8. If a woman with pre-labour rupture of membranes
at < 37 weeks’ gestation has an unknown or positive
group B streptococcus culture status, administer
intravenous group B streptococcus prophylaxis for
48 hours, as well as other antibiotics if indicated,
while awaiting spontaneous or obstetrically indicated
labour. (II-3B)
NEONATAL MANAGEMENT
Information related to the current management of the
infant at increased risk of sepsis, including risk of GBS
disease, may be found on the website of the Canadian
Paediatric Society (Fetus and Newborn Committee).72
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38. Krohn MA, Hillier SL, Baker CJ. Maternal peripartum complications
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41. Baker CJ, Edwards MS. Group B streptococcal infections: perinatal
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50. Gibbs RS, McDuffie RS, McNabb F, Fryer GE, Miyoshi T,
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Craig AS, et al. Evaluation of universal antenatal screening for group B
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56. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al.
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57. Centers for Disease Control and Prevention. Prevention of
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58. Yancey MK, Duff P. An analysis of the cost-effectiveness of selected
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Obstet Gynecol 2003;83:367–71.
59. Fenton LJ, Harper MH. Evaluation of colistin and nalidixic acid in
Todd-Hewitt broth for selective isolation of group B streptococci. J Clin
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60. Bland ML, Vermillion ST, Soper DE. Antibiotic resistance patterns for
group B streptococci in late third-trimester rectovaginal cultures. Am J
Obstet Gynecol 2001;184:1125–6.
61. Silverman NS, Morgan M, Nichols WS. Antibiotic resistance patterns
of group B streptococcus in antenatal genital cultures. J Reprod Med
2000;45:979–82.
62. Price D, Shaw E, Howard M, Zazulak J, Waters H, Kaczorowski J.
Self-sampling for group B streptococcus in women 35 to 37 weeks
pregnant is accurate and acceptable: a randomized cross-over trial.
J Obstet Gynaecol Can 2006;28:1083–8.
63. Valkenburg-van den burg AW, Houtman-Roelofsen RL, Oostvogel PM,
Dekker FW, Dörr PJ, Sprij AJ. Timing of group B streptococcus screening
in pregnancy: a systematic review. Gynecol Obstet Invest 2010;69:174–83.
64. Bergeron MG, Ke D, Menard C, Picard FJ, Gagnon M, Bernier M, et al.
Rapid detection of group B streptococci in pregnant women at delivery.
N Engl J Med 2000;343:175–9.
65. El Helali N, Giovangrandi Y, Guyot K, Chevet K, Gutmann L,
Durand-Zaleski I. Cost and effectiveness of intrapartum group B
streptococcus polymerase chain reaction screening for term deliveries.
Obstet Gynecol 2012;119:822–9.
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SOGC Clinical Practice Guideline
66. Amstey MS, Gibbs RS. Is penicillin G a better choice than ampicillin for
prophylaxis of neonatal group B streptococcal infections? Obstet Gynecol
1994;84:1058–9.
67. Johnson JR, Columbo DF, Gardner D, Cho E, Fan-Havard P, Shellhaas CS.
Optimal dosing of penicillin G in the third trimester for the prophylaxis
against group B streptococcus. Am J Obstet Gynecol 2001;185:850–3.
68. Pichichero ME. A review of evidence supporting the American Academy
of Pediatrics recommendation for prescribing cephalosporin antibiotics for
penicillin-allergic patients. Pediatrics 2005:115:1048–57.
69. Mitchell TF, Pearlman MD, Chapman RL, Bhatt-Mehta V, Faiz RG.
Maternal and transplacental pharmacokinetics of cefazolin. Obstet Gynecol
2001;98:1075–9.
70. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et
al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight
infants. N Engl J Med 2002;347:240–7.
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71. Hannah ME, Ohlsson A, Wang EE, Matlow A, Foster GA,
Willan AR, et al. Maternal colonization with group B streptococcus
and prelabor rupture of membranes at term: the role of induction
of labor. Term PROM Study Group. Am J Obstet Gynecol
1997;177:780–5.
72. KJ Barrington; Canadian Paediatric Society, Fetus and Newborn
Committee. Position statement: management of the infant at increased
risk for sepsis. Paediatr Child Health 2007;12:893–8. Available at:
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73. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
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recommendations from the Canadian Task Force on Preventive Health
Care. CMAJ 2003;169:207–8.
 JOINT SOGC-GOC-SCC CLINICAL PRACTICE GUIDELINE

No. 290, April 2013

The Role of Adjuvant Therapy in

Endometrial Cancer
Abstract
This clinical practice guideline has been prepared by the
SOGC-GOC-SCC Policy and Practice Guidelines Committee Objective: To review the evidence relating to the use of adjuvant
and approved by the Executive and Council of the Society therapy after surgical treatment for endometrial cancer.
of Gynecologic Oncology of Canada and the Executive and
Options: Women with endometrial cancer can be given the option of
Council of the Society of Obstetricians and Gynaecologists
receiving adjuvant radiotherapy and/or chemotherapy according to
of Canada.
pathologic findings at time of surgery.
PRINCIPAL AUTHORS
Outcomes: The outcomes measured are postoperative progression-
Rachel Kupets, MD, Toronto ON free and overall survival in endometrial cancer patients.
Tien Le, MD, Ottawa ON Evidence: Published literature was retrieved through searches of
SOGC-GOC-SCC POLICY AND PubMed, CINAHL, and The Cochrane Library, using appropriate
PRACTICE GUIDELINES COMMITTEE controlled vocabulary (e.g., endometrial neoplasms) and key
words (e.g., endometrium cancer, endometrial carcinoma).
Tien Le, MD (Chair), Ottawa ON Results were restricted to systematic reviews, randomized
James Bentley, MB ChB, Halifax NS control trials/controlled clinical trials, and observational studies.
There were no date or language restrictions. Searches were
Scott Farrell, MD, Halifax NS
updated on a regular basis and incorporated in the guideline to
Michel P. Fortier, MD, Quebec QC December 31, 2011. Grey (unpublished) literature was identified
Christopher Giede, MD, Saskatoon SK through searching the websites of health technology assessment
and health technology assessment-related agencies, clinical
Rachel Kupets, MD, Toronto ON practice guideline collections, clinical trial registries, national and
Marie Plante, MD, Quebec QC international medical specialty societies, and recent conference
abstracts.
Patti Power, MD, St. John’s NL
Values: The quality of evidence was rated using the criteria described
Marie-Claude Renaud, MD, Quebec QC
in the Report of the Canadian Task Force on Preventive Health
Alexandra Schepansky, MD, Edmonton AB Care (Table).
Vyta Senikas, MD, Ottawa ON Benefits, harms, and costs: This guideline is intended to help
SPECIAL CONTRIBUTORS standardize postoperative treatment of endometrial cancer and
minimize undertreatment and overtreatment.
Janice Kwon, MD, Vancouver BC
Validation: The guideline was reviewed for accuracy by content
Michel Préfontaine, MD, London ON
experts in pathology, radiation oncology, and medical oncology.
Isabelle Germain, MD, Quebec QC Guideline content was also compared with relevant documents
Robert Pearcey, MD, Edmonton AB from the American Congress of Obstetricians and Gynecologists.

David D’Souza, MD, London ON

Mary Senterman, MD, Ottawa ON
Paul Hoskins, MD, Vancouver BC
Disclosure statements have been received from all contributors. J Obstet Gynaecol Can 2013;35(4):375–376

The literature searches and bibliographic support for this

guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada. Key Words: Endometrial cancer, radiation therapy, chemotherapy

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

APRIL JOGC AVRIL 2013 l 375



Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.

SUMMARY STATEMENTS benefit demonstrated. Patients who are managed expectantly

Stage I Intermediate-Risk Endometrial Cancers
External beam pelvic radiotherapy
1. Pelvic radiation has been shown to reduce local recurrence in low-
to intermediate-risk endometrial carcinoma. (II-1)
2. Pelvic radiation has been shown to reduce local pelvic and
vaginal recurrences in intermediate- to high-risk endometrial
carcinoma. (II-1)
report higher scores in quality of life studies because of less
gastrointestinal toxicity. (II-3)
Advanced Stage (II to IV) Endometrial Cancer
7. Chemotherapy with cisplatin and doxorubicin or carboplatin and
paclitaxel has demonstrated efficacy in advanced uterine cancer
in published phase III studies. (II-2)

RECOMMENDATIONS
Vaginal brachytherapy
3. Vaginal brachytherapy alone in the treatment of women with Stage I Low-Risk Endometrial Cancers
intermediate- to high-risk endometrial cancer has been shown to 1. As risk for recurrent disease is low in this patient group, no further
have outcomes in local control and overall survival that are similar treatment should be given after definitive surgery. Regular follow-
to those of pelvic radiotherapy in a well-defined intermediate- to up should be performed to monitor for signs and symptoms of
high-risk group. (I) recurrences. (II-1B)
4. Vaginal brachytherapy has the same outcome as external beam
radiotherapy with respect to overall survival in the defined Advanced Stage (II to IV) Endometrial Cancer
intermediate- to high-risk group. (I)
2. Treatment of these patients should be tailored according to
disease distribution and local treatment practices. (II-2C)
Chemotherapy
5. Chemotherapy has not been well studied in stage I intermediate-
to high-risk endometrial cancers. There is no strong evidence
for or against chemotherapy in this population at present. The
benefits of chemotherapy in addition to adjuvant radiotherapy
specifically in surgically stage I patients with high-risk features are
not clearly defined. (III)

Expectant Management The full version of this document

6. Patients in the intermediate-risk category who are managed is available online at
expectantly have a higher recurrence rate than those who http://www.sogc.org and http://www.jogc.com.
are treated, although there has not been a lack of survival

376 l APRIL JOGC AVRIL 2013

 SOGC CLINICAL PRACTICE GUIDELINE

No. 286, January 2013

Surgical Safety Checklist in Obstetrics

and Gynaecology
Values: The quality of evidence was rated with use of the criteria
This clinical practice guideline has been reviewed by the described by the Canadian Task Force on Preventive Health
Clinical Practice Gynaecology Committee and reviewed and Care. Recommendations for practice were ranked according to
approved by the Executive and Council of the Society of the method described by the Task Force (Table).
Obstetricians and Gynaecologists of Canada.
Benefits, harms, and costs: Implementation of the guideline
PRINCIPAL AUTHORS recommendations will improve the health and well-being of
Sukhbir S. Singh, MD, Ottawa ON women undergoing obstetrical or gynaecologic surgery.
Neeraj Mehra, MD, Ottawa ON
Laura Hopkins, MD, Ottawa ON SUMMARY STATEMENTS AND RECOMMENDATIONS
CLINICAL PRACTICE GYNAECOLOGY COMMITTEE Summary Statements
Nicholas Leyland, MD (Co-Chair), Ancaster ON
1. Surgery may account for up to 40% of all hospital adverse
Wendy Wolfman, MD (Co-Chair), Toronto ON events. (II-2)
Catherine Allaire, MD, Vancouver BC 2. Good communication is essential for safer surgical care, as
Alaa Awadalla, MD, Winnipeg MB communication failure is common in the operating room. (III)
Sheila Dunn, MD, Toronto ON 3. The concept of a surgical safety checklist has been studied
Mark Heywood, MD, Vancouver BC globally, and there have been decreases in complications and
Madeleine Lemyre, MD, Quebec QC mortality when the checklist has been implemented. (II-1)

Violaine Marcoux, MD, Ville Mont-Royal QC 4. Emergency cases such as a “crash” Caesarean section will
require a modified approach that is centre- and situation-
Chantal Menard, RN, Ottawa ON
dependent. (III)
Frank Potestio, MD, Thunder Bay ON
5. The SOGC endorses the adoption of the surgical safety checklist
David Rittenberg, MD, Halifax NS
in obstetrics and gynaecology. (III)
Sukhbir S. Singh, MD, Ottawa ON
Vyta Senikas, MD, Ottawa ON Recommendations
Disclosure statements have been received from all members of 1. The surgical safety checklist should be adopted by all surgical
the committee. care providers and their respective institutions to improve patient
safety. (II-1A)
2. Surgeons should be familiar with, advocate for the use of, and
Abstract participate in all 3 parts of the surgical safety checklist. (II-1A)

Objective: To provide guidance on the implementation of a surgical 3. The surgical safety checklist may be modified and adapted for
safety checklist in the practice of obstetrics and gynaecology. use in surgical obstetrics cases. (II-2A)
Outcomes: Outcomes evaluated include the impact of the surgical
safety checklist on surgical morbidity and mortality.
Evidence: Medline databases were searched for articles on subjects J Obstet Gynaecol Can 2013;35(1):82–83
related to “surgical safety checklist” published in English from
January 2001 to January 2011. Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. Searches were updated on a Key Words: Patient safety, surgical safety checklist
regular basis and incorporated in the guideline to January 2012.

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

82 l JANUARY JOGC JANVIER 2013

 Surgical Safety Checklist in Obstetrics and Gynaecology

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.

The full version of this document

is available online at
http://www.sogc.org and http://www.jogc.com.

JANUARY JOGC JANVIER 2013 l 83

 JOINT SOGC-GOC-SCC CLINICAL PRACTICE GUIDELINE

No. 291, April 2013 (Replaces no. 51, November 1996)

Epidemiology and Investigations for

Suspected Endometrial Cancer
Abstract
This clinical practice guideline has been prepared by the
SOGC-GOC-SCC Policy and Practice Guidelines Committee, Objective: To review the evidence relating to the epidemiology of
reviewed by the Clinical Practice Gynaecology Committee endometrial cancer and its diagnostic workups.
and approved by the Executive and Council of the Society
Options: Women with possible endometrial cancer can undergo an
of Gynecologic Oncology of Canada and the Executive and
endometrial evaluation by office biopsy, hysteroscopy, or dilatation
Council of the Society of Obstetricians and Gynaecologists
and curettage. To assist in treatment planning, pelvic ultrasound,
of Canada.
CT scan, or MRI may be considered.
PRINCIPAL AUTHORS
Outcomes: The identification of optimal diagnostic tests to evaluate
Marie-Claude Renaud, MD, Quebec QC patients with possible endometrial cancer.
Tien Le, MD, Ottawa ON Evidence: Published literature was retrieved through searches of
SOGC-GOC-SCC POLICY AND PubMed, CINAHL, and The Cochrane Library, using appropriate
PRACTICE GUIDELINES COMMITTEE controlled vocabulary (e.g., endometrial neoplasms) and key
words (e.g., endometrium cancer, endometrial carcinoma).
Tien Le, MD (Chair), Ottawa ON
Results were restricted to systematic reviews, randomized
James Bentley, MB ChB, Halifax NS control trials/controlled clinical trials, and observational studies.
Scott Farrell, MD, Halifax NS There were no date or language restrictions. Searches were
updated on a regular basis and incorporated in the guideline to
Michel P. Fortier, MD, Quebec QC December 31, 2011. Grey (unpublished) literature was identified
Christopher Giede, MD, Saskatoon SK through searching the websites of health technology assessment
Rachel Kupets, MD, Toronto ON and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, national and
Marie Plante, MD, Quebec QC international medical specialty societies, and recent conference
Patti Power, MD, St. John’s NL abstracts.
Marie-Claude Renaud, MD, Quebec QC Values: The quality of evidence was rated using the criteria described
Alexandra Schepansky, MD, Edmonton AB in the Report of the Canadian Task Force on Preventive Health
Care (Table).
Vyta Senikas, MD, Ottawa ON
Benefits, harms, and costs: This document is intended to guide
SPECIAL CONTRIBUTORS the development of a standardized cost-effective investigation of
Janice Kwon, MD, Vancouver BC patients with suspected endometrial cancer.
Michel Préfontaine, MD, London ON Validation: The guideline was reviewed for accuracy by experts in
Isabelle Germain, MD, Montreal QC pathology, radiation oncology, and medical oncology. Guideline
content was also compared with relevant documents from the
Robert Pearcey, MD, Edmonton AB American Congress of Obstetricians and Gynecologists.
David D’Souza, MD, London ON
Mary Senterman, MD, Ottawa ON
Paul Hoskins, MA, Vancouver BC J Obstet Gynaecol Can 2013;35(4):380–381
Disclosure statements have been received from all contributors.
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical Key Words: Endometrial cancer, diagnostic workup, endometrial
Research Analyst, Society of Obstetricians and Gynaecologists evaluation, ultrasound, magnetic resonance imaging, MRI,
of Canada. postmenopausal bleeding

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

380 l APRIL JOGC AVRIL 2013

 Epidemiology and Investigations for Suspected Endometrial Cancer

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.

Recommendations 4. Histologic evaluation of the endometrium should be done in all

patients in whom endometrial cancer is suspected. (II-1A)
1. A complete focused history should be taken and a physical
examination carried out in patients with suspected endometrial 5. Hysteroscopic examination should be considered in patients with
cancer. Attention should be paid to predisposing factors for excess persistent uterine bleeding with benign endometrial sampling or
estrogen stimulation of the endometrium such as long history of insufficient endometrial sampling after ultrasound. (II-2B)
anovulation, obesity, menstrual irregularity, or long-term use of
6. Formal review of the histopathology should be considered in
unopposed estrogen or tamoxifen. Patients with a strong family
patients with high grade tumours or rare histologic types such as
history of endometrial, ovarian, and colorectal cancers might have
serous, clear cell, or mucinous types. (III-B)
inherited Lynch syndrome (hereditary non-polyposis colorectal
cancer syndrome) that increases their lifetime risk of developing 7. Additional tumour markers, CT scan, and MRI scan should not be
endometrial cancer. Genetic counselling and testing can be used used routinely. (III-D)
to individualize risk-management interventions including screening
strategies and treatment options. (III-B)
2. Endometrial cancer should be ruled out in perimenopausal and
postmenopausal patients with abnormal vaginal bleeding. (II-1A)
3. Depending on access, histologic endometrial evaluation The full version of this document
and transvaginal ultrasound are the preferred initial is available online at
diagnostic investigations for patients with suspected http://www.sogc.org and http://www.jogc.com.
endometrial cancer. (II-1B)

APRIL JOGC AVRIL 2013 l 381

 SOGC TECHNICAL UPDATE

No. 294, July 2013

Technical Update on Pessary Use

Abstract
This technical update has been prepared by the
Urogynaecology Committee, reviewed by the Family Objective: To review the use, care, and fitting of pessaries.
Practice Advisory Committee, and approved by
Options: Pessaries are an option for women presenting with prolapse
the Executive of the Society of Obstetricians and
and/or urinary incontinence.
Gynaecologists of Canada.
Outcomes: Pessaries can be successfully fitted in the majority of
PRINCIPAL AUTHORS women with excellent satisfaction rates and minimal complications.
Magali Robert, MD, Calgary AB Evidence: PubMed and Medline were searched for articles published
Jane A. Schulz, MD, Edmonton AB in English to September 2010, using the key words pessary,
prolapse, incontinence, fitting, and complications. Results were
Marie-Andrée Harvey, MD, Kingston ON
restricted to systematic reviews, randomized control trials/
UROGYNAECOLOGY COMMITTEE controlled clinical trials, and observational studies. Searches were
updated on a regular basis, and articles were incorporated in the
Danny Lovatsis, MD (Co-Chair), Toronto ON
guideline to May 2012. Grey (unpublished) literature was identified
Jens-Erik Walter, MD (Co-Chair), Montreal QC through searching the websites of health technology assessment
Queena Chou, MD, London ON and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, and national
William A. Easton, MD, Scarborough ON
and international medical specialty societies.
Annette Epp, MD, Saskatoon SK
Values: The quality of evidence was rated with use of the criteria
Scott A. Farrell, MD, Halifax NS described by the Canadian Task Force on Preventive Health Care.
Roxana Geoffrion, MD, Vancouver BC Recommendations for practice were ranked according to the
method described by the Task Force (Table 1).
Lise Girouard, RN, Winnipeg MB
Benefits, harms, and costs: Women may choose a pessary for
Chander K. Gupta, MD, Winnipeg MB
management of their prolapse and/or stress incontinence rather
Marie-Andrée Harvey, MD, Kingston ON than opt for surgery. Major complications have been seen only
Annick Larochelle, MD, St-Lambert QC with neglected pessaries. Minor complications such as vaginal
discharge, odour, and erosions can usually be successfully
Kenny D. Maslow, MD, Winnipeg MB
treated.
Grace Neustaeder, RN, Calgary AB
Dante Pascali, MD, Ottawa ON SUMMARY STATEMENTS AND RECOMMENDATION
Marianne Pierce, MD, Halifax NS Summary Statements
Magali Robert, MD, Calgary AB 1. Most women can be successfully fitted with a pessary when they
Sue Ross, PhD, Calgary AB present with prolapse. (II-2)
Joyce Schachter, MD, Ottawa ON 2. Complications of pessary use are usually minor, and vaginal
Jane A. Schulz, MD, Edmonton AB discharge is the most common complaint. (II-3)

Vyta Senikas, MD, Ottawa ON
David H.L. Wilkie, MD, Vancouver BC
Disclosure statements have been received from all contributors.
Scott Farrell is Vice-President Medical and a major stakeholder
of EastMed Inc. (Halifax, NS), the company marketing Uresta.
Roxana Geoffrion is a shareholder of EastMed Inc.
3. Vaginal erosions can be treated with removal of the pessary and
optional vaginal estrogen supplementation. (II-2)
4. Satisfaction rates with pessary use are very high. (II-2)
Recommendation
1. Pessaries should be considered in all women presenting with
symptomatic prolapse and/or urinary stress incontinence. (II-1A)

Key Words: Pessary, prolapse, incontinence, fitting, complications

J Obstet Gynaecol Can 2013;35(7):664–674

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

664 l JULY JOGC JUILLET 2013


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.54
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.54
INTRODUCTION
P elvic organ prolapse is seen in up to 50% of parous
women.1 Although often asymptomatic, it may
present with symptoms of bulging, pelvic pressure, and
occasionally backache. It is often associated with bladder,
bowel, and sexual dysfunction. Treatment options include
pelvic floor exercises,2 expectant management, use of
mechanical vaginal devices (pessaries), and surgical
correction. This technical update guides care providers on
the use of pessaries.
A pessary is a device placed into the vagina to support the
prolapsing vaginal walls or to provide urinary continence.
Pessaries have the distinct advantage of being minimally
invasive, and they provide immediate relief of symptoms.
Although in the past, pessaries were reserved for the
frail and elderly, they are also an excellent alternative for
symptomatic women who have not finished child-bearing
and for those who choose a non-surgical intervention
or who wish symptomatic relief while awaiting surgery.
Pessaries are experiencing a resurgence in popularity
and are an option for the treatment of prolapse and
incontinence for women in any age group.
Pessaries are made primarily of medical grade silicone;
only the largest sizes are made of surgical steel with a
covering of silicone. This has the advantage of making
them inert and less likely to have an odour or cause an
allergic reaction.3 Pessaries used for the treatment of
prolapse can be classified as support pessaries or space-
Technical Update on Pessary Use
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
occupying pessaries.4 The support pessaries sit in the
posterior fornix and generally rest above the pubic bone
and/or pelvic floor. The commonly used types include ring
pessaries (with or without diaphragms, Figure 1) and the
Shaatz pessaries (Figure 2). The space-occupying pessaries
include the cube (Figure 3), Inflatoball (Figure 4), and
donut (Figure 5) pessaries. The cube works by bringing the
vaginal walls towards the midline, and the others occupy a
larger space than the introitus.4 They are most often used
for more severe prolapse. The commonly used Gellhorn
pessary (Figure 6) works as a combination of these 2
methods.4 There are many other styles to address specific
defects, but their use is not often reported in the literature.
Incontinence pessaries are often designed as support
pessaries with extra support anteriorly (Figure 7) to elevate
and slightly constrict the urethra.5 The ring incontinence
pessary (Figure 8) and the incontinence dish (Figure 9) are
specifically designed to treat stress urinary incontinence.
If a woman develops stress incontinence after being fitted
with a prolapse pessary, switching to an incontinence
pessary may be beneficial.3
INDICATIONS
Pessaries can be used for diagnostic or therapeutic purposes.
Pessaries are often used to relieve symptoms of prolapse6
and of urinary stress incontinence. They are cost-effective in
the treatment of prolapse.7 Women choosing pessary for the
treatment of prolapse are as likely to be satisfied and to have
improved pelvic floor function as those selecting surgery.8
JULY JOGC JUILLET 2013 l 665
SOGC TECHNICAL UPDATE

Figure 1. Ring pessary with support Figure 2. Shaatz pessary

Figure 3. Cube pessary Figure 4. Inflatoball pessary

Figure 5. Donut pessary Figure 6. Gellhorn pessary

666 l JULY JOGC JUILLET 2013


Figure 7. Ring pessary with support and
continence knob at 12 o’clock
Figure 9. Incontinence dish
Figures 1 to 9 are reproduced with permission from CooperSurgical Inc., Trumbull CT, and Figure 10 is reproduced with permission from
EastMed Inc., Halifax NS
Pessaries can also be used for the preoperative evaluation
of women with prolapse by unmasking latent stress
incontinence9 and providing information on postoperative
voiding dysfunction.10,11 This could be revealed during the use
of a pessary, or during the performance of urodynamic testing
with and without pessary. Although urodynamic testing has
poor sensitivity, its specificity is high (93%), and the absence
of occult incontinence has an excellent negative predictive
value (91% to 98%) for postoperative continence.12,13
Pessaries can also be used as a temporary treatment of
symptoms while patients are waiting for surgery, and they
can help to heal vaginal ulcers that result from erosions due
to a large prolapse. They may also play a role in preventing
progression of prolapse.
Technical Update on Pessary Use
Figure 8. Incontinence ring
Figure 10. Uresta kit
Prolapse
Women can be successfully fitted with a pessary 71% to
90% of the time.14–19 Symptoms of bulging and pressure
are relieved in 70% to 90% and 29% to 49% of women,
respectively.15,16 When pessaries are successful at the 4-week
point, most women continue to use them at 5 years.20
Ring pessaries are the most commonly used and widely
available, followed by Gellhorn and cube or donut
pessaries.15,16,21 In a randomized crossover trial, there was no
difference in patient satisfaction or symptom relief between
those using the ring and those using the Gellhorn pessary.19
Ring pessaries may be open or covered (also referred to as
“with support” or “with diaphragm”). The purpose of the
covered ring pessary is to support the cervix; perforations
JULY JOGC JUILLET 2013 l 667
SOGC TECHNICAL UPDATE
Table 2. Change in symptoms after pessary fitting
Stress urinary incontinence
Urge urinary incontinence
Voiding difficulties
Incomplete evacuation of bowel
Fecal urgency
Fecal incontinence
Frequency of sexual activity
Satisfaction of sexual activity
allow the escape of vaginal secretions. Open and covered
ring pessaries are best used in POP-Q (pelvic organ prolapse
quantification) stage I and II prolapse (mild to moderate
prolapse), although they often work well with a more
advanced degree of prolapse if there is an adequate perineal
body to ensure the pessary is retained.3 It has the advantage
of ease of insertion and removal, and comfort.
If the pessary fails to remain in position or there continues to
be protrusion, a stiffer pessary such as a Shaatz or a Gellhorn,
or a space-occupying pessary such as a cube or a donut may
be used. Cube pessaries have been successfully used in severe
prolapse. However, they may be more prone to erosion, and
they require frequent removal, nightly in some cases. Patients
can learn to remove and re-insert a cube pessary.
Successful use of a pessary is dependent on both adequate
fit and patient satisfaction.
The most common reasons women choose to use a pessary
are to improve lower urinary tract symptoms secondary
to pelvic organ prolapse, such as bulging, and to improve
activity and general health.22 Pessary use can also alleviate
other symptoms, including difficulty with bladder emptying,
urinary urgency symptoms, and defecatory symptoms.15,16
Contrary to common belief, sexual activity is not a predictor
for discontinued pessary use15,23; in fact, pessary use may
enhance sexual activity and satisfaction.17,24 Table 2 shows
the change in symptoms after pessary fitting.
Predictors for unsuccessful fitting include a short vagina
(< 6 cm),18,25 a wide introitus (> 4-finger breadth),18,25 the
presence of a rectocele,26 previous vaginal surgery,14,16,17,25,27,28
and coexisting stress urinary incontinence.27
Predictors of discontinuation include posterior wall
pro­lapse,14,16 younger age (<  65 years old),15 urinary
incontinence, and discomfort. However, in one study,
15 28
women who had previously undergone pelvic reconstructive
surgery were more likely to continue pessary use.27
668 l JULY JOGC JUILLET 2013
Improved, % Worsened, %
22 to 45 15,16
17 to 2115,16
28 to 46 15,16
6 to 1315,16
39 to 5315,16 4 to 1415,16
27 16
1816
2216 916
19 16
916
1616 316
1116
516
Urinary Incontinence
Some pessaries have been specifically designed to treat urinary
stress incontinence. These include the ring pessary with
support and knob (Figure 7), the incontinence ring (Figure 8),
the incontinence dish (Figure 9) and the Uresta device (Figure
10). They appear to stabilize the urethra and increase urethral
resistance.5 Initial successful fitting varies between 60% and
92%29,30 with an incontinence ring. Continued use drops to
55% by 6 months.31 By 1 year, the overall continuation may be
as low as 16%, but this finding was from a study in which an
incontinence ring pessary with diaphragm was used, and most
women discontinued use because of lack of efficacy.32 In a
retrospective chart review33 of 100 women successfully fitted
with pessaries, 59% were continent or mostly continent at
11 months. Reasons for discontinuation included persistent
incontinence, pessary falling out, or pain and bleeding. One
crossover study showed that the incontinence ring was more
effective than no treatment for the management of stress
urinary incontinence, significantly decreasing the number of
incontinence episodes and improving quality of life.34 Eighty
percent of women saw an improvement of their incontinence,
and 20% were dry.
Using the new Uresta device, continuation rates at
1 year were 50%.35 In that case series (n = 32), continence
was obtained by 31% of women, and incontinence was
improved in a further 34%.35
There is insufficient evidence to state that pessaries are more
effective in treating urinary incontinence than other devices
or other treatments,36 including pelvic floor exercises.37
Pregnancy
Women who develop prolapse3,38,39 during pregnancy or
who develop urinary retention because of an incarcerated
uterus40 can be fitted with a pessary, although not always
successfully.41 By 18 weeks, when the uterus lifts out of
the pelvis, symptoms often resolve, and pessary use can
be discontinued. The use of an incontinence pessary in
pregnancy has not yet been described.

In small cohort studies, pessaries placed around the cervix,
such as the Arabin pessary,42 have been shown to have some
benefit in preventing preterm birth in women with cervical
incompetence.43,44 Multiple randomized clinical trials, some
international and multicentre, are ongoing.45 An RCT by
Goya et al.,46 published in 2012, found that the use of the
Arabin pessary was associated with a significant reduction
of premature birth (< 34 weeks) from 27% to 6% in women
identified as having a short cervix (< 25 mm) on ultrasound
at 22 weeks, as well as with a decrease in premature rupture
of membrane (9% to 2%) and a decrease in composite
neonatal severe outcomes from 16% to 3%, mostly for
sepsis and respiratory distress syndrome. However, until the
results of this trial are reproduced, the use of pessary for
prevention of premature birth cannot be recommended, as
its safety for this indication remains to be established.47  A ring pessary with incontinence knob is placed like a
GUIDELINES FOR FITTING
Successful fitting and continued use is dependent on
adequate patient education (Appendix). It is imperative
that the woman and/or her caregiver commit to proper
care of the pessary.48
As part of the history, health care providers should
inquire about symptoms of prolapse, bladder and bowel
dysfunction, and sexual activity. This is followed by a
comprehensive examination: assessing vaginal mucosal
health; assessing the degree and compartment of prolapse,
including genital hiatus and vaginal length; and measuring
pelvic floor strength. It is common but not essential49 to
begin vaginal estrogen therapy in postmenopausal women
to improve the health of the vaginal epithelium.3,4
The approximate size of pessary required is determined
by assessing the width of the vaginal canal by separating
the 2 examining fingers at the vault in a sagittal plane
and estimating their separation distance. A ring pessary is
usually fitted initially, as it is easy to use and tends to be
more comfortable. The pessary is folded, and the leading
edge is lubricated. It is inserted by directing it towards the
sacrum, and it is unfolded above the pelvic floor, with the
anterior edge just behind the symphysis. There should
be a finger’s breadth between the pessary (edge) and the
symphysis anteriorly and between the side of the pessary
and the lateral vaginal wall. The ring pessary should be
turned one quarter turn in either direction following
placement to ensure the foldable edge is not placed in
front of the introitus, thus potentially limiting spontaneous
expulsion. Once the pessary has been fitted, the patient
should ambulate in the clinic and perform activities such
as squatting and Valsalva manoeuvre to ensure it will not
Technical Update on Pessary Use
fall out. It is necessary to ensure that patients are able to
void and that they are given appropriate education before
leaving the clinic with their new pessary (Appendix). A
post-void residual can be done to rule out the possibility of
obstruction. Dental floss can be attached to aid in removal
of difficult pessaries.
An incontinence ring is fitted by assessing the distance
between the posterior cul-de-sac and the mid urethra.
Because the incontinence ring is more flexible, it will
adapt to the configuration of the vagina. The health care
provider must ensure that the knob is centred underneath
the mid-urethra and that the proximal ring is placed in the
posterior cul-de-sac and not in front of the cervix in the
anterior fornix.50
regular ring, but once it is opened, the knob will be facing
the sidewall: it must therefore be rotated one quarter turn
to place the knob under the mid-urethra.50
If the vaginal introitus is more than the width of 3 or 4
fingers, a space-occupying pessary is the most likely to be
successful. A Shaatz pessary is fitted similarly, with the
convex portion placed anteriorly. A Gellhorn pessary is fitted
by folding of the disc as above when possible with the stem
folded down for ease of insertion. The stem will be directed
caudally (pointing out), and it should be possible to pass a
finger between the disc and the vaginal side wall. Because of
its shape, a cube pessary need not be as large as the width of
the vagina (as measured with the examining fingers spread
apart), but approximately one half that width. Insertion
simply involves compressing the edge that is introduced
into the vaginal opening, and pushing it up and back. Donut
pessaries also require compression for insertion.
Follow-up Pessary Care
Following a successful fitting, the woman is seen again
within 2 to 4 weeks to see if she is satisfied or whether
another size or style is required. If possible, instruction
on removal and care should be given.3 Although there are
no clear guidelines for pessary care, women who are able
to perform self-care are advised to remove the pessary
once a week and to wash it with water or mild soapy water.
Women who are not able to perform self-care should be
followed at 3-month intervals. Maintenance of pessary
care by a health care professional rather than the patient
is often required with Gellhorn, cube, or donut pessaries.
Some pessaries may be difficult to remove. The Gellhorn
pessary is easier to remove when the health care professional
uses a ring or packing self-closing forceps on the base of
the stem to apply outwards traction, and then uses one
JULY JOGC JUILLET 2013 l 669
SOGC TECHNICAL UPDATE
finger to break the suction and fold the round disc along
the stem. A cube pessary requires removal and cleaning
more often than every 3 months, because a greater amount
of discharge is usually trapped within the suction cups
(although the cube is available with drainage holes). The
frequency of cleaning required for a cube pessary will vary
among patients, from as often as every few days to every
few weeks.
Once removed, the pessary should be washed using plain
soap and water. The perforations of the Gellhorn and
Shaatz pessaries are best cleansed using a cytobrush or
a small cotton swab. The vaginal epithelium should be
inspected for erosions or ulcerations, and special attention
should be paid to the posterior and lateral fornices of the
vagina. This is best accomplished using a large cotton swab
to displace the cervix to the contralateral direction.
If no complications arise and the patient is able to
perform self-care, the interval between visits can be
increased to 6 months or 1 year.30 Women can be sexually
active with the ring or Shaatz pessary in place. A cube,
donut, or Gellhorn pessary must generally be removed
before intercourse.
COMPLICATIONS
Published complication rates vary, which likely reflects
a difference in reporting. In a study by Hanson et al.
88.5% of 1216 women did not develop complications.17
Common complications included erosions (8.9%) and
vaginal infections (2.5%).17 This is in contrast to the study
by Bai et al., in which 73% of women had complications,
including bleeding, erosions, or foul odour.51 Despite this
relatively high rate, over 70% reported being satisfied with
the pessary and wanted to continue its use,51 suggesting
that these complications are minor.
Local pressure from the pessary can lead to focal
devascularisation and cause erosions. Reported rates
range from 2% to 9%.8,10 Erosions may present as vaginal
bleeding, odour, or increased discharge, which is typically
brown. A strong odour is usually present upon removal
of the pessary. When such strong odour is detected
during routine pessary care, careful examination of the
vagina should be performed, often facilitated by the use
of large swabs to push the cervix and sidewalls apart.
If neglected, erosions can progress to ulcers or a fistula.
Other causes of vaginal bleeding cannot be excluded in
pessary users, and endometrial or ulcer biopsy may be
indicated if they persist. Therapy consists of pessary
removal for a period of 2 to 4 weeks and local estrogen
use (tablet or cream). Resolution of erosions may also
670 l JULY JOGC JUILLET 2013
occur without local estrogen.17 For ongoing problems,
more frequent visits and a change in pessary type or size
may be required. Vaginal cancer is a rare association with
neglected pessary use but should be considered with non-
healing ulcers.Vaginal discharge is a common complaint
of pessary users. It can be caused by a physiologic
response to friction of the pessary on the vaginal mucosa,
bacterial vaginosis, or yeast. Bacterial vaginosis can cause
malodorous vaginal discharge, which can be problematic
but is not related to the appearance of an ulcer.17 Alnaif
and Drutz showed that in matched women, pessary users
had a 32% rate of diagnosed bacterial vaginosis compared
with 10% in non-users.52 The use of estrogen cream did
not appear to have a protective effect. More frequent
pessary removal can often alleviate this problem. The use
of Trimo-San cream (Cooper Surgical) or Replens may
decrease the odour and discharge.3 Antibiotic treatment
with oral or vaginal metronizadole is also effective. Often
simple reassurance that the problem is physiologic may
be sufficient. Yeast can be treated in conventional ways.
Often it is recommended to keep the pessary removed
during treatment, although there is no evidence that this
makes a difference.
If a pessary is repeatedly dislodged, women often
discontinue use. This is best averted by preventing
constipation and avoiding straining in general.
Major complications are uncommon with pessary use.
In case reports documenting complications including
vesicovaginal fistulae, bowel fistulae, incarcerated pessaries
etc.,53 91% were related to neglected pessaries. This stresses
the importance of continued and diligent follow-up.
CONCLUSION
Pessaries have a high success rate and minimal complication
rate for the treatment of both incontinence and prolapse.
When successfully fitted, they are associated with high
patient satisfaction. They should therefore be considered
as first-line treatment for all women presenting with pelvic
prolapse and/or stress urinary incontinence.
Summary Statements
1. Most women can be successfully fitted with a pessary
when they present with prolapse. (II-2)
2. Complications of pessary use are usually minor,
and vaginal discharge is the most common
complaint. (II-3)
3. Vaginal erosions can be treated with removal
of the pessary and optional vaginal estrogen
supplementation. (II-2)
4. Satisfaction rates with pessary use are very high. (II-2)

Recommendation
1. Pessaries should be considered in all women
presenting with symptomatic prolapse and/or
urinary stress incontinence. (II-1A)
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28. Mutone MF, Terry C, Hale DS, Benson JT. Factors which influence the
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32. Robert M, Mainprize TC. Long-term assessment of the incontinence ring
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33. Farrell SA, Singh B, Aldakhil L. Continence pessaries in the management of
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39. De Vita D, Giordano S. Two successful natural pregnancies in a patient
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40. Yohannes P, Schaefer J. Urinary retention during the second trimester of
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41. Brown HL. Cervical prolapse complicating pregnancy. J Natl Med Assoc
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42. Quaas L, Hillemanns HG, Du BA, Schillinger H. The
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43. Dharan VB, Ludmir J. Alternative treatment for a short cervix: the cervical
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44. Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical
pessary for preventing preterm birth. Cochrane Database Syst Rev
2010;(9):CD007873.
45. Hegeman MA, Bekedam DJ, Bloemenkamp KW, Kwee A, Papatsonis DN,
van der Post JA, et al. Pessaries in multiple pregnancy as a prevention of
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(PECEP): an open-label randomised controlled trial. Lancet
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47. Jorde A, Kastli K, Hamann B, Pockrandt H. Changes in the vaginal flora
caused by supporting pessary treatment in pregnancy [article in German].
Zentralbl Gynakol 1983;105(13):855–62.
48. Wu V, Farrell SA, Baskett TF, Flowerdew G. A simplified protocol for
pessary management. Obstet Gynecol 1997;90(6):990–4.
49. Ramsay S, Bouchard F, Tu LM. Long term outcomes of pessary use in
women with pelvic organ prolapse. Neurourol Urodyn 2011;30(6):1105–6.
50. Farrell SA. Pessaries for the management of stress urinary incontinence.
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51. Bai SW, Yoon BS, Kwon JY, Shin JS, Kim SK, Park KH, et al. Survey of
the characteristics and satisfaction degree of the patients using a pessary.
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52. Alnaif B, Drutz HP. Bacterial vaginosis increases in pessary users.
Int Urogynecol J Pelvic Floor Dysfunct 2000;11(4):219–22.
53. Arias BE, Ridgeway B, Barber MD. Complications of neglected vaginal
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 Technical Update on Pessary Use

APPENDIX. SAMPLE PATIENT CARE GUIDELINE AND INFORMATION

Courtesy:  Pelvic Floor Clinic, Calgary

Pessary Care Guidelines and Follow-Up

                     Date:                           Size:                    Type:                    

After your pessary fitting, book a follow-up appointment in weeks.

• This visit is to see if the pessary is helping you, and to examine your vagina to make sure it remains healthy looking.
• Further follow-up appointments are very important. When you are comfortable with caring for your pessary, the follow-up appointments
will be less often.
• You may learn to care for your pessary yourself. If you can remove and insert your pessary yourself, then you should remove your
pessary overnight at least once a week and clean it with warm water. Book regular follow-up visits to check on the health of your
vaginal tissue.

Occasional Problems and Suggestions

Problem Suggestions
•  Pessary falls out Reinsert your pessary if you are able to. Go to your scheduled appointment, and bring your
pessary with you.
•  You have pelvic pain If you feel that your pessary is the cause of the pain, remove it and bring it with you to your next
appointment. If you are unable to remove your pessary, contact the clinic.
•  Vaginal odour and/or discharge Some odour and discharge is normal. If the odour is very foul, remove the pessary if you can,
and go to your scheduled appointment. If you are unable to remove your pessary, contact the
clinic.
•  Vaginal bleeding This may be a sign that the pessary is irritating your vaginal lining. Remove the pessary if you
can, and go to your scheduled appointment. If you are unable to remove your pessary, contact
the clinic.
•  Leaking urine If you feel that the pessary is making your leakage worse, remove it. Go to your scheduled
appointment. If you are unable to remove your pessary, contact the clinic.

If you are having urgent problems, phone the Pessary Clinic at:
This material is designed for information purposes only. It should not be used in place of medical advice, instruction, and/or treatment.
If you have specific questions, please consult your doctor or appropriate health care professional.

Discharge and Odour

Some women find that they have an increased vaginal discharge, with or without an odour, when using a pessary. Usually this is normal.
It is the body’s reaction to wearing a foreign body inside of you. This can be controlled with various creams or gels—speak to a doctor or
nurse about it.

Insertion and Removal

Most women are able to insert and remove the pessary on their own. The clinic nurse will teach you some way to do this, but you may find
a way that works best for you over time.
We suggest that you should try to remove your pessary at least once each week. Leave it out overnight to give your tissues a break.
Some women remove it nightly and others leave it out longer. Everyone’s vaginal tissues have a different tolerance level for the pessary,
in the same way that everyone’s skin varies in its sensitivity. How often you remove your pessary also depends on whether you are on
hormones, and the type of pessary you wear.
Some women are unable to remove or insert the pessary due to arthritis or for other reasons. The clinic nurse can help you work out what
works best for you, along with helping you find a schedule that works best for you.

Insertion of Your Pessary

Fold the pessary and insert it through the vaginal opening, aiming down towards your tailbone, and pushing down on the back of the
vaginal wall.
Using your forefinger, guide the pessary as far back as you can, then push the pessary up and behind the pubic bone.

JULY JOGC JUILLET 2013 l 673

SOGC TECHNICAL UPDATE

APPENDIX. Continued

Removing Your Pessary

Hook your forefinger under the edge of ring, or in a hole, and pull it down and out of the vagina.

PESSARIES: INFORMATION FOR WOMEN

What Are They?
A pessary is a device that can be used to help control your leakage problem, or for support of sagging or prolapsing pelvic organs such
as your bladder, uterus, or rectum. They are made of silicone and are worn inside the vagina.
• Pessaries are not a new invention. They have been used for centuries and come in many styles and sizes. They are being used more
today as an effective and simple option for pelvic organ prolapse and/or urinary incontinence.
• Pessaries can be used for years.
• They should fit comfortably. If you have the right style and size, you should not be aware you are using one.
• Once fitted, they can be worn once in a while or most of the time. Pessaries are a tool used to help you, and each woman can use
them differently.
• Pessaries work very well for many women, offer some help for others, and do not seem to be helpful for other women. You can try
different styles and sizes to find the one that works best for you.

Cleaning
Use warm tap water and mild soap (for example, Sunlight dish detergent). Make sure that you rinse the pessary well. Store it in a clean,
dry place. Do not boil or disinfect the pessary. Remember that your hands, and the pessary, must be clean before insertion.

Sex
The pessary may be left in or may be removed before intercourse, depending on your comfort level. This is a trial and error process.
Some styles must be removed before intercourse.

Bowel movements
Most women wearing a pessary have no trouble or interference when having bowel movements. Women who tend to be constipated
may have some problems. It is important that you keep your stools soft and regular. Some women may find it necessary to remove their
pessary before they have a bowel movement.

This material is designed for information purposes only. It should not be used in place of medical advice, instruction, and/or treatment.
If you have specific questions, please consult your doctor or appropriate health care professional.

674 l JULY JOGC JUILLET 2013

 JOINT SOGC-GOC-SCC CLINICAL PRACTICE GUIDELINE

No. 289, April 2013

The Role of Surgery in Endometrial Cancer

Abstract
This clinical practice guideline has been prepared by the
SOGC-GOC-SCC Policy and Practice Guidelines Committee, Objective: To review current practice and make recommendations for
reviewed by the SOGC Clinical Practice Gynaecology the management and treatment of endometrial cancer.
Committee and approved by the Executive and Council of
Outcomes: This guideline makes recommendations with respect to
the Society of Gynecologic Oncology of Canada and the
extended surgical staging, which provides important prognostic
Executive and Council of the Society of Obstetricians and
information and aids in determining the need for adjuvant
Gynaecologists of Canada.
treatments.
PRINCIPAL AUTHORS
Evidence: Published literature was retrieved through searches of
Christopher Giede, MD, Saskatoon SK PubMed, CINAHL, and The Cochrane Library, using appropriate
Tien Le, MD, Ottawa ON controlled vocabulary (e.g., endometrial neoplasms) and key
words (e.g., endometrium cancer, endometrial carcinoma). Results
Patti Power, MD, St. John’s NL were restricted to systematic reviews, randomized control trials/
SOGC-GOC-SCC POLICY AND controlled clinical trials, and observational studies. There were no
PRACTICE GUIDELINES COMMITTEE date or language restrictions. Searches were updated on a regular
basis and incorporated in the guideline to December 31, 2011.
Tien Le, MD (Chair), Ottawa ON
Grey (unpublished) literature was identified through searching the
James Bentley, MB ChB, Halifax NS websites of health technology assessment and health technology
Scott Farrell, MD, Halifax NS assessment-related agencies, clinical practice guideline
collections, clinical trial registries, national and international
Michel P. Fortier, MD, Quebec QC medical specialty societies, and recent conference abstracts
Christopher Giede, MD, Saskatoon SK Benefits, harms, and costs: This guideline reviews the benefit of
Rachel Kupets, MD, Toronto ON extended surgical staging compared with the potential harm of a
limited surgery in grade 2 and 3 disease.
Marie Plante, MD, Quebec QC
Values: The quality of evidence is rated and recommendations are
Patti Power, MD, St. John’s NL
made using the criteria described by the Canadian Task Force on
Marie-Claude Renaud, MD, Quebec QC Preventive Health Care (Table).
Alexandra Schepansky, MD, Edmonton AB
SUMMARY STATEMENTS
Vyta Senikas, MD, Ottawa ON
SPECIAL CONTRIBUTORS Low-risk disease (grade 1 adenocarcinoma on biopsy)

Janice Kwon, MD, Vancouver BC 1. In low-risk disease, there is no evidence that lymphadenectomy
improves survival in grade 1 adenocarcinoma. (I)
Michel Préfontaine, MD, London ON
2. Endometrial cancer requires a coordinated multidisciplinary team
Isabelle Germain, MD, Montreal QC approach for management. (III)
Robert Pearcey, MD, Edmonton AB 3. The purpose of lymphadenectomy is to guide adjuvant therapy
David D’Souza, MD, London ON that may affect survival in high-risk populations or prevent
treatments that may result in unnecessary toxicity. (III)
Mary Senterman, MD, Ottawa ON
Paul Hoskins, MA, Vancouver BC
Disclosure statements have been received from all contributors. J Obstet Gynaecol Can 2013;35(4):370–371
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists Key Words: Endometrial cancer, lymphadenectomy, surgical
of Canada. staging, sentinel nodes for endometrial cancer

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

370 l APRIL JOGC AVRIL 2013


Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.
Extent of lymph node evaluation
4. Decisions regarding adjuvant therapy in endometrial cancer are
dependent on both histopathologic risk factors for recurrences
post-hysterectomy and the status of retroperitoneal lymph nodes
when lymphadenectomy is performed. (III)
RECOMMENDATIONS
Low-risk disease
1. Surgery may be limited to hysterectomy and bilateral salpingo-
oophorectomy as an acceptable alternative to staging patients
with grade 1 disease. However, relying on preoperative tumour
grading will underestimate high-risk status in a proportion of
patients and may subject these women to either second surgery
or a more liberal use of external beam adjuvant radiation. (III-B)
2. Additional risk assessment can include preoperative or
intraoperative evaluation of depth of myometrial invasion. For final
histopathological stage and grade, regional multidisciplinary teams
should come to consensus on the use of prognostic factors to
guide adjuvant therapy. (III-B)
High-risk disease (grade 2 or 3 adenocarcinoma /
clear cell / papillary serous on biopsy)
3. Consideration should be given to performing pelvic and/or para-
aortic lymphadenectomies in patients with preoperative grade 2
and 3 disease to facilitate accurate planning of adjuvant therapy,
The Role of Surgery in Endometrial Cancer
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
which is often required postoperatively. The survival benefit of
lymphadenectomy in this specific group of patients has not been
studied. (II-2B)
4. Patients with high-risk histological subtypes of endometrial cancer
such as clear cell and papillary serous adenocarcinomas should
receive full staging surgery that includes pelvic and/or para-aortic
lymphadenectomy and omentectomy. (II-2B)
5. A coordinated multidisciplinary team approach should be used for
management of high-risk endometrial cancer. (III-B)
6. Regional multidisciplinary teams should come to local consensus
on the use of prognostic factors to guide adjuvant therapy. (III-B)
7. Performing lymphadenectomy on the basis of palpation for “bulky”
nodes is inaccurate and should not be done. (II-2E)
Advanced disease
8. Patients presenting with advanced disease should be referred to
gynaecologic oncologists at a regional cancer centre for treatment
planning. (II-2B)
The full version of this document
is available online at
http://www.sogc.org and http://www.jogc.com.
APRIL JOGC AVRIL 2013 l 371
 SOGC CLINICAL PRACTICE GUIDELINE

No. 285, January 2013

Toxoplasmosis in Pregnancy:
Prevention, Screening, and Treatment
This clinical practice guideline has been prepared by the
Infectious Disease Committee, reviewed by the Family
Practice Advisory Committee and the Maternal Fetal
Medicine Committee, and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists
of Canada.
PRINCIPAL AUTHORS
Caroline Paquet, RM, Trois-Rivières QC
Mark H. Yudin, MD, Toronto ON
INFECTIOUS DISEASE COMMITTEE
Mark H. Yudin, MD (Chair), Toronto ON
Victoria M. Allen, MD, Halifax NS
Céline Bouchard, MD, Quebec QC
Marc Boucher, MD, Montreal QC
Sheila Caddy, MD, Edmonton AB
Eliana Castillo, MD, Calgary AB
Deborah M. Money, MD, Vancouver BC
Kellie E. Murphy, MD, Toronto ON
Gina Ogilvie, MD, Vancouver BC
Caroline Paquet, RM, Trois-Rivières QC
Julie van Schalkwyk, MD, Vancouver BC
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all members of
the committee.
Abstract
Background: One of the major consequences of pregnant women
becoming infected by Toxoplasma gondii is vertical transmission
to the fetus. Although rare, congenital toxoplasmosis can cause
severe neurological or ocular disease (leading to blindness),
as well as cardiac and cerebral anomalies. Prenatal care must
include education about prevention of toxoplasmosis. The low
prevalence of the disease in the Canadian population and
limitations in diagnosis and therapy limit the effectiveness of
screening strategies. Therefore, routine screening is not currently
recommended.
Objective: To review the prevention, diagnosis, and management of
toxoplasmosis in pregnancy.
Outcomes: Outcomes evaluated include the effect of screening
on diagnosis of congenital toxoplasmosis and the efficacy of
prophylaxis and treatment.
Evidence: The Cochrane Library and Medline were searched for
articles published in English from 1990 to the present related to
toxoplasmosis and pregnancy. Additional articles were identified
through references of these articles.
Values: The quality of evidence is rated and recommendations made
according to guidelines developed by the Canadian Task Force on
Preventive Health Care (Table).
Benefits, harms, and costs: Guideline implementation should assist
the practitioner in developing an approach to screening for and
treatment of toxoplasmosis in pregnancy. Patients will benefit from
appropriate management of this condition.
Sponsor: The Society of Obstetricians and Gynaecologists of
Canada.
Recommendations
01. Routine universal screening should not be performed for
pregnant women at low risk. Serologic screening should be
offered only to pregnant women considered to be at risk for
primary Toxoplasma gondii infection. (II-3E)
02. Suspected recent infection in a pregnant woman should be
confirmed before intervention by having samples tested at a
toxoplasmosis reference laboratory, using tests that are as
accurate as possible and correctly interpreted. (II-2B)
03. If acute infection is suspected, repeat testing should be
performed within 2 to 3 weeks, and consideration given to
starting therapy with spiramycin immediately, without waiting for
the repeat test results. (II-2B)
04. Amniocentesis should be offered to identify Toxoplasma gondii
in the amniotic fluid by polymerase chain reaction (a) if maternal
primary infection is diagnosed, (b) if serologic testing cannot
J Obstet Gynaecol Can 2013;35(1):78–79
Key Words: Toxoplasmosis, pregnancy, congenital, prenatal,
disease transmission, mass screening, counselling

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

78 l JANUARY JOGC JANVIER 2013

 Toxoplasmosis in Pregnancy: Prevention, Screening, and Treatment

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.
Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task Force on Preventive Health Care. New grades for recommendations from the
Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.

confirm or exclude acute infection, or (c) in the presence
of abnormal ultrasound findings (intracranial calcification,
microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or
severe intrauterine growth restriction). (II-2B)
05. Amniocentesis should not be offered for the identification of
Toxoplasma gondii infection at less than 18 weeks’ gestation and
should be offered no less than 4 weeks after suspected acute
maternal infection to lower the occurrence of false-negative
results. (II-2D)
06. Toxoplasma gondii infection should be suspected and screening
should be offered to pregnant women with ultrasound findings
consistent with possible TORCH (toxoplasmosis, rubella,
cytomegalovirus, herpes, and other) infection, including but not
limited to intracranial calcification, microcephaly, hydrocephalus,
ascites, hepatosplenomegaly, or severe intrauterine growth
restriction. (II-2B)
07. Each case involving a pregnant woman suspected of having
an acute Toxoplasma gondii infection acquired during gestation
should be discussed with an expert in the management of
toxoplasmosis. (III-B)
08. If maternal infection has been confirmed but the fetus is not
yet known to be infected, spiramycin should be offered for fetal
prophylaxis (to prevent spread of organisms across the placenta
from mother to fetus). (I-B)
09. A combination of pyrimethamine, sulfadiazine, and folinic acid
should be offered as treatment for women in whom fetal infection
has been confirmed or is highly suspected (usually by a positive
amniotic fluid polymerase chain reaction). (I-B)
10. Anti-toxoplasma treatment in immunocompetent pregnant women
with previous infection with Toxoplasma gondii should not be
necessary. (I-E)
11. Women who are immunosuppressed or HIV-positive should
be offered screening because of the risk of reactivation and
toxoplasmosis encephalitis. (I-A)
12. A non-pregnant woman who has been diagnosed with an acute
Toxoplasma gondii infection should be counselled to wait 6
months before attempting to become pregnant. Each case should
be considered separately in consultation with an expert. (III-B)
13. Information on prevention of Toxoplasma gondii infection in
pregnancy should be made available to all women who are
pregnant or planning a pregnancy. (III-C)
The full version of this document
is available online at
http://www.sogc.org and http://www.jogc.com.

JANUARY JOGC JANVIER 2013 l 79

 SOGC Committee Opinion

No. 273, March 2012

Genetic Considerations for a Woman’s

Annual Gynaecological Examination
This committee opinion has been prepared by the Genetics
Committee, reviewed by the Family Physicians Advisory
Committee and approved by the Executive of the Society of
Obstetricians and Gynaecologists of Canada (SOGC).
PRINCIPAL AUTHORS
R. Douglas Wilson, MD, Calgary AB
Sylvie Langlois, MD, Vancouver BC
Abstract
Objective: To provide the physician with an overview of common
genetic conditions that should be considered during a women’s
annual gynaecological assessment to determine the patient’s risk
or to initiate specific testing or referral to another subspecialty
service, depending on personal or family history.
Options: This genetic information can be used for patient education
and possible disease and/or mutation screening or diagnosis.

SOGC GENETICS COMMITTEE Outcomes: The use of this genetic information may allow improved
risk-benefit assessment and management at the annual
R. Douglas Wilson, MD (Chair), Calgary AB gynaecological examination.
François Audibert, MD, Montreal QC Evidence: Studies published in English up to and including May
2010 were retrieved through searches of PubMed and the
Jo-Ann Brock, MD, Halifax NS
Cochrane Library, using appropriate controlled vocabulary
June Carroll, MD, Toronto ON (gynaecological diagnosis, genetic inheritance) and key words
(genetic risk, genetic mutation, inheritance, family history, uterus,
Lola Cartier, MSc, Montreal QC ovary, endometrial, vagina, colon, gastric, renal, breast, cardiac,
Valérie A. Désilets, MD, Montreal QC thrombophilia, diabetes, epilepsy, leiomyomata uteri). Other
literature sources were identified through searching the web
Alain Gagnon, MD, Vancouver BC sites of health technology assessment and health technology
Jo-Ann Johnson, MD, Calgary AB assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
Sylvie Langlois, MD, Vancouver BC medical specialty societies.
Lynn Murphy-Kaulbeck, MD, Moncton NB Values: The levels of evidence are not adequate for evidence-based
recommendations to be made.
Nanette Okun, MD, Toronto ON
Benefits, harms, and costs: This committee opinion will enhance
Melanie Pastuck, RN, Calgary AB
the use of new genetic knowledge and its application to the annual
Vyta Senikas, MD, Ottawa ON gynaecological care of women. Risk management and diagnostic
opportunities for genetic gynaecological conditions will be
Disclosure statements have been received from all members of improved. A more complete understanding of genetic conditions
the committee. may increase anxiety and psychological stress for women and
their families.
Sponsors: Society of Obstetricians and Gynaecologists of Canada.

Recommendations
The levels of evidence are not adequate for evidence-based
Key Words: Genetic risk, genetic mutation, gynaecology, recommendations to be made.
inheritance, family history, uterus, ovary, endometrial, vagina,
colon, gastric, renal, breast, cardiac, thrombophilia, diabetes,
epilepsy, uterine leiomyomata uteri, uterine leiomyomas
J Obstet Gynaecol Can 2012;34(3):276–284

This document reflects the emerging clinical and scientific advancement on the date issued and is subject to change. The
information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions
can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents
may be reproduced in any form without prior written permission of the SOGC.

276 l MARCH JOGC MARS 2012

 Genetic Considerations for a Woman’s Annual Gynaecological Examination
INTRODUCTION
T he objective of this committee opinion is to
provide physicians with an overview of genetic
conditions that should be considered during a woman’s
annual gynaecological assessment. This will help to
determine whether the patient has any specific genetic
risk conditions so that specific testing can be initiated or
referral made to another specialty service, depending on
the patient’s personal or family history. New genes and
other genetic factors are being rapidly identified, and a
basic understanding of the common medical and surgical
conditions that arise from them will help clinicians when
they conduct systematic reviews at a woman’s annual or
semi-annual gynaecological visit or when these conditions
are discovered incidentally during other gynaecological
investigations or surgeries.
This committee opinion reviews medical and surgical
conditions with a genetic etiology that have gynaecological
or obstetrical implications, and cancer and hereditary
cancer syndromes that require annual follow-up.
MEDICAL OR SURGICAL CONDITIONS WITH A
GENETIC ETIOLOGY THAT HAVE GYNAECOLOGICAL
OR OBSTETRICAL IMPLICATIONS
Table 1 shows common medical and surgical conditions
that have a multifactorial or single gene mode of inheritance
that may be part of a woman’s personal or family history.
Diabetes Mellitus
The teratogenic risks associated with glucose imbalance in
insulin-dependent diabetes were reviewed in a 2007 SOGC
clinical practice guideline and in a 2002 review article.1,2
Maternal Cardiac Disease
Genetic cardiac disease can be considered as either
congenital heart disease, with multifactorial, chromosomal,
or genetic etiology, or coronary artery disease, with genetic
and lifestyle risk factors.3 Congenital heart disease is
typically identified in childhood, but with improved cardiac
ABBREVIATIONS
AD autosomal dominant
AR autosomal recessive
CRC colorectal cancer
FAP familial adenomatous polyposis
HLRCC hereditary leiomyomatosis and renal cell cancer
HNPCC hereditary nonpolyposis colon cancer
MRKH Mayer-Rokitansky-Kuster-Hauser
MTHFR methylenetetrahydrofolate reductase
care, patients with congenital heart disease now live longer,
frequently reaching child-bearing age. Chromosomal
deletions (22q DiGeorge syndrome) and single gene
disorders associated with congenital heart disease are
summarized in Tables 2 and 3. Depending on the age
of the patient and when the genetic association with the
cardiac anomaly was recognized, testing for the specific
gene mutation or chromosomal deletions may not have
been completed when a patient presents for prenatal care.
Pre-conception counselling issues may be identified at an
annual gynaecological visit. Patients should be made aware
that if mutation/deletion is present in either parent, there
is a risk it may be transmitted to the fetus. The availability
of prenatal evaluation by invasive testing (amniocentesis,
chorionic villus sampling) as indicated or by non-invasive
screening/diagnosis by fetal echocardiography should be
discussed with the prospective parents before pregnancy.
Parents whose chromosome complement is “normal”
according to test results (dependent on the cytogenetic/
molecular level or detail of genetic testing) and who
have an isolated congenital heart defect have an empiric
increased risk of having a child with a congenital heart
defect because of the multifactorial inheritance nature
of the cardiac defect. This recurrence risk for isolated
non-syndromic heart defects is estimated at 6.5% for
an affected mother and 2.2% for an affected father.4 A
fetal echocardiogram should be considered when either
parent or a previous child was born with a congenital
heart defect.
Factors related to screening and treatment of
atherosclerotic heart disease are beyond the scope of
this committee opinion, but if a strong family history
is identified, the patient’s primary care physician and
cardiology care provider should be notified that this is an
area for evaluation and potentially for primary prevention
Epilepsy
Women with epilepsy have specific fertility and sexual issues
that include a higher incidence of anovulatory cycles and
infertility, ovarian cysts, and seizures related to changes in
hormones of the hypothalamic pituitary axis (luteinizing
hormone, prolactin).5 A woman with epilepsy may be up
to 50% less likely to conceive spontaneously than a sibling
without a seizure disorder. The exact etiology for this
decreased fertility is unclear. Pre-conception counselling
should be considered at a woman’s annual visits. For an
epileptic woman who becomes pregnant, there are increased
risks for birth defects secondary to the antiepileptic drugs
she may be using. The teratology of prescription drugs
was reviewed in a 2007 SOGC clinical practice guideline.6
Congenital malformations are estimated at 4% to 8% in
MARCH JOGC MARS 2012 l 277
SOGC Committee Opinion

Table 1. Common conditions with genetic contribution

Medical multifactorial Atherosclerotic heart disease
Diabetes mellitus
Hypertension
Seizure disorders
Oncology (indirect) Cancer (breast, ovarian, endometrial, colon)
multifactorial or single gene
Genetic (single gene inheritance) Bleeding disorder – hemophilia XL
– von Willebrand AD
Clotting disorder – antithrombin III AD
– protein C or S AD
– factor V Leiden AD
Cystic fibrosis AR
Familial hypercholesterolemia AD
Fragile-X XL
Glucose-6-phosphate dehydrogenase def XL
Hemoglobinopathies – sickle cell AR
– thalessemia AR
Huntington disease AD
Marfan syndrome AD
Muscular dystrophy XL
Myotonic dystrophy AD
Neural tube defect MF
Neurofibromatosis AD
Polycystic kidney AD/AR
XL: X linked inheritance; MF: multifactorial

Table 2. Estimated 22q11 deletion frequency in women with epilepsy and fetal antiepileptic drug exposure.
congenital heart disease The majority of defects are identified in the central nervous,
Estimated deletion orofacial, cardiovascular, and urogenital systems. Congenital
Cardiac defect frequency, % anomaly screening in pregnancy should include a detailed
Interrupted aortic arch 50 to 89 ultrasound to identify structural defects in the fetus from
VSDs 10 18 to 20 weeks, and possibly maternal serum alpha fetoprotein
With normal aortic arch* 3 screening for open neural tube defects specifically. Joint
With aortic arch anomaly† 45 SOGC-Motherisk guidelines indicate that women with
Truncus arteriosus 34 to 41 epilepsy should supplement their diets with 5 mg of folic
Tetralogy of Fallot 8 to 35 acid daily and a multivitamin to minimize the teratogenic
Isolated aortic arch anomalies 24 component of the antiepileptic drugs.7 Monotherapy for
Double-outlet right ventricle <5
epilepsy should be reviewed with the patient and her other
Transposition of the great arteries <1
physicians as a treatment option minimizing teratogenic risks.
VSD: ventricular septal defect.
Uterine Leiomyomas
*Left-sided aortic arch with normal branching pattern.
Uterine leiomyomas are the most common benign
†Includes right aortic arch and/or abnormal branching pattern, cervical
location, and/or discontinuous branch pulmonary arteries. neoplasia developing within the uterus. It is not known
Table adapted with permission from Pierpont ME, Basson CT, Benson W, whether a leiomyoma actually transforms into a malignant
Gelb BD, Giglia TM, Goldmuntz E, et al.3 leiomyosarcoma, but the incidence of leiomyosarcoma is
extremely low in premenopausal women when compared
with the incidence in older postmenopausal women in
whom they account for < 1% of uterine malignancies.8,9

278 l MARCH JOGC MARS 2012

 Genetic Considerations for a Woman’s Annual Gynaecological Examination

Genetic factors are now being identified. Somatic Table 3. Genes associated with congenital heart
mutations and, less frequently, molecular alterations in defects
the X chromosome must occur for the initiation and Chromosome
subsequent development of a myoma. The high prevalence Condition location
of leiomyomas suggests that they result from stable Congenital heart defects
mutations. Very specific genetic risks have been identified Familial congenital heart disease 5q
for HLRCC,10 which is inherited in an autosomal dominant (ASD, atrioventricular block)
fashion. Affected individuals demonstrate an increased D-TGA, DORV 2q
risk for leiomyomas of the skin and uterus, as well as D-TGA 12q
renal cancers. As leiomyomas have a prevalence of 30% Tetralogy of Fallot 8q
in the female population (although this varies according 5q
to ethnicity), it is important for clinicians, gynaecologists, 20p
and other caregivers to be aware that HLRCC-associated Atrioventricular septal defect 3p
kidney tumours are often biologically aggressive. Although ASD/VSD 8p
screening for this mutation or for renal tumour in all women Xq
with leiomyomas is not recommended, clinicians should Heterotaxy 2q
have a high index of suspicion when women present with 3p
hematuria suggestive of a renal tumour.
1q

Thrombophilias Syndromes
Thrombophilias can be inherited or acquired.11–14 The DiGeorge syndrome 22q11
most common inherited disorders are mutations of factor Holt-Oram syndrome 12q24
V Leiden, prothrombin gene (G20210A mutation), and Alagille syndrome (PPS) 20p12
MTHFR mutation or homozygosity to MTHFR C677T, but Char syndrome (PDA) 6p12
the complete list of inherited disorders includes deficiencies Noonan syndrome 12q24
in protein S, C, and Z or antithrombin III, homozygosity 12p1.21
to 4G/4G mutation in PAI-1 gene, and polymorphisms 2p21
in thromobomodulin gene. People of Caucasian heritage CHARGE association 8q12
have a higher rate of genetic thrombophilias than other Ellis-van Creveld syndrome 4p16
ethnic groups. Marfan syndrome 15q21.1

Several large studies have identified the association

11–14 Marfan-like syndrome 3p22

between thrombophilias and adverse pregnancy outcomes. Cardiofaciocutaneous syndrome 12p12.1

Maternal problems are venous thromboembolism 7q34
with deep vein thrombosis, pulmonary embolism, and 15q21
cerebral vein thrombosis; peripheral and cerebral arterial 7q32
thrombosis; and severe preeclampsia. Fetal and placental Costello syndrome 11p15.5
issues are thrombosis/infarction, placental abruption, William syndrome/supravalvar aortic stenosis 7q11
recurrent miscarriage, fetal growth restriction, death, and ASD: atrial septal defect; D-TGA: D-transposition of great arteries;
stroke. In the presence of an inherited thrombophilia, the VSD: ventricular septal defect; DORV: double-outlet right ventricle;
PPS: peripheral pulmonary stenosis; PDA: patent ductus arteriosus;
risk of developing preeclampsia has an estimated frequency CHARGE: coloboma, heart anomaly, choanal atresia, retardation, and genital
and ear anomalies.
of 4% to 27% with factor V Leiden, 0% to 11% with the
Table adapted with permission from Pierpont ME, Basson CT, Benson W,
prothrombin gene mutation, 1% to 25% with protein S Gelb BD, Giglia TM, Goldmuntz E, et al.3
deficiency, and 8% to 24% with the MTHFR variant. As
some studies show the risk as being similar to baseline
and others show a significantly increased risk, it remains
unclear whether this association is significant.

Screening for inherited thrombophilias should be

considered for women with a history of thromboembolism,
including deep vein thrombosis. There have been few
randomized trials, so definitive treatment and prophylaxis
regimens have not been established. Within the genetic

MARCH JOGC MARS 2012 l 279

SOGC Committee Opinion
Table 4. Estimated number and lifetime risk of women
who would develop or die of various types of cancer
in 2007
Lifetime risk of Lifetime risk of
Type of cancer developing, 1 in dying of, 1 in
Breast 008 034
Lung 017 030
Colorectal 018 045
Endometrial 038 196
Skin 077 500
Ovarian 068 095
Cervical 135 385
Data from Adams Hillard PJ and Berek JS,20 Jemal A, Siegel R, Ward E,
Murray T, Xu J, Thun MJ,21 American Cancer Society.22
thrombophilia group, most studies are observational with
small, heterogeneous groups. A single RCT15 is available in
which 160 women with at least 1 fetal loss after 10 weeks
and heterozygosity for a single thrombophilia mutation
(factor V Leiden, prothrombin G20210A mutation, protein
S) were randomized to enoxparin 40 mg or low-dose ASA
100 mg daily. The enoxparin group had an increased live
birth rate (86% vs. 29%), higher birth weight, and lower
intrauterine growth restriction rates (10% vs. 30%) than
the low-dose ASA group. Other thrombophilia treatment
protocols are available.16,17 Referral to a treatment centre
with expertise in the topic should be considered before
anticoagulant treatment is initiated before or during
pregnancy.
Pre-conception discussion with a woman with a
thrombophilia and a past history of poor pregnancy
outcome should include increased fetal surveillance
starting at 24 weeks, with serial ultrasound (every 4 weeks)
for fetal growth, umbilical artery Doppler, non-stress test
and/or biophysical profile used as clinically required, and
consideration of delivery by 39 weeks.11
Contraception with estrogen-containing products is
contraindicated unless long-term anticoagulation is used.
Progestin-only products do not increase thromboembolic
risks. Estrogen-containing hormone therapy may
increase the risk of stroke and thromboembolic disease.
Surgery on a woman with factor V Leiden requires
thromboprophylaxis according to published protocols to
decrease her thrombotic risk.18
Congenital Mullerian Anomalies
Women with agenesis of the uterus and vagina but normal
ovarian function and secondary sexual characteristics have
280 l MARCH JOGC MARS 2012
Mayer-Rokitansky-Kuster-Hauser syndrome.19 A 2006
report of a cohort of 106 consecutive women with the
MRKH syndrome reviewed other congenital anomalies
associated with MRKH syndrome.18 Hypoplastic vagina
was present in 61 women. Laterally displaced Mullerian
remnants were present in 92 women, and 26% of the
remnants had a cavity with endometrial mucosa. Ovaries
were extrapelvic in 16%. Urinary tract abnormalities were
present in 30%, with unilateral renal agenesis (18%),
pelvic kidney (11%), and horseshoe kidney (2%) being
the most common anomalies. The recognition of this
wide variability of anatomical presentations is important
for appropriate surveillance, diagnosis, and treatment of
gynaecological problems in women with MRKH syndrome.
A renal ultrasound is recommended to assess urinary tract
anomalies, particularly before abdominal or pelvic surgery.
RISK ASSESSMENT FOR CANCER AND
HEREDITARY CANCER SYNDROMES
(BACKGROUND, PERSONAL, FAMILY)
Recent estimates of lifetime risk of a woman developing
or dying from various types of cancer are shown in
Table 4.20–22 Breast cancer occurs most frequently. It has a
lifetime presentation risk of 1 in 8 and a death risk of 1 in
34 compared with cervical cancer, which has a presentation
risk of 1 in 135 and a death risk of 1 in 385.
Despite these risks, a recent publication23 reported that a
financially stable and well-educated population of women
had very little knowledge or understanding of hereditary
cancer risks. Cancers studied in this population included
hereditary breast cancer, Lynch syndrome, and p16-related
melanoma. Although approximately 11% were identified
as being at high-risk for at least 1 of the 3 syndromes
(breast cancer 88.5%, Lynch syndrome 6.1%, p16-related
melanoma 3.8%), < 3% had ever had genetic counselling
or testing.
The discovery of genes responsible for hereditary cancer
syndrome has led to specific recommendations for genetic
testing for mutations in BRCA1 and BRCA2, responsible
for hereditary breast and ovarian cancer, and the mismatch-
repair genes responsible for the hereditary nonpolyposis
colon cancer also known as Lynch syndrome.24 A 2007
commentary25 emphasized the need for more public
education. A 2005 US Preventive Services Task Force
recommendation26 indicates that women whose family
history (first and second degree relatives) is indicative of
an increased risk for deleterious mutations in BRCA10r
BRCA2 genes should be referred for genetic counselling
and evaluation for these mutations. These women would
benefit from obtaining information that would allow
 Genetic Considerations for a Woman’s Annual Gynaecological Examination
informed choice about testing and further prophylactic
treatment and risk-reduction surgery. This counselling
should be done within a genetic oncology program by
trained health care providers. There is increasing evidence
to consider the benefits of chemoprevention or intensive
screening in improving health outcomes in women who test
positive for deleterious BRCA1 or BRCA2 mutations.27,28
However, there is fair evidence that risk-reduction surgery
for these women significantly decreases breast and ovarian
cancer incidence. In 2007, the American Cancer Society
issued guidelines29 for offering screening breast MRI
in women with a lifetime risk of breast cancer of 20%
to ≥ 25% (based on models of family history) using an
annual breast MRI examination beginning at age 30. A
more recent study30 indicates that although family history
is a strong predictor of risk, it is not always required, as
a cohort of women with apparently sporadic (no first or
second degree relatives with breast or ovarian cancer) and
early onset breast cancer had a 9.5% incidence BRCA1 or
BRCA2 mutation.
For women with BRCA1 or BRCA2 mutations, the risk
of breast cancer is up to 87% by the age of 70. Clinicians
should ensure that women at risk are given tools to help
them make the difficult decision about prophylactic
salpingo-oophorectomy or bilateral mastectomy and the
increased lifetime risks for BRCA-associated gynaecologic
(ovarian, fallopian tube, and primary peritoneal) cancers.31
Recent reviews27,28 of ovarian cancer prevention in patients
with BRCA1 or BRCA2 germline mutations indicate
that although chemoprevention (tamoxifen, raloxifene)
and screening (twice yearly vaginal ultrasound and
serum CA-125) both have a role, neither is efficacious
enough to eliminate the need for risk reducing salpingo-
oophorectomy in women with an inherited predisposition
to ovarian cancer; therefore, risk reducing salpingo-
oophorectomy will remain an important component of
gynaecologic cancer risk reduction.
Although BRCA1 and BRCA2 account for the largest
proportion of genetic susceptibility to breast cancer, other
rare disorders make up approximately 10% to 20% of the
genetic susceptibility. These include ataxia-telangiectasia
(AR), oculocutaneous telangiectasia, cerebellar ataxia,
variable immunodeficiency, lymphoid and epithelial cancers,
Li-Fraumeni syndrome (AD), childhood bone or soft-
tissue sarcomas, early onset breast cancer, acute leukemias,
brain tumours, carcinoma of the lung or pancreas,
melanoma, Cowden disease (AD), mucocutaneous
lesions, thyroid, breast, hamartomatous polyps of the GI
tract, macrocephaly, uterine leiomyomas), and very rare
syndromes such as Gorlin syndrome (AD), Muir-Torre
syndrome (AD), Peutz-Jeghers syndrome (AD), and partial
androgen insensitivity syndrome (X-linked recessive).
For women with BRCA1 or BRCA2 mutations who have
not undergone risk-reduction mastectomy, intensive breast
screening with both annual mammogram and annual breast
MRI beginning at age 25 years could be considered. American
Cancer Society guidelines29 for breast cancer screening with
MRI as an adjunct to mammography recommend that an
annual MRI could also be used not only for the high-risk
BRCA mutation carrier and first degree relative cohort but
also for screening other high-risk breast cancer groups,
such as women with a history of therapeutic radiation (e.g.,
for Hodgkin’s disease) to the chest between the ages of 10
and 30 years, women with Li-Fraumeni syndrome and first
degree relatives, and women with Cowden or Bannayan-
Riley-Ruvalcaba syndrome and first degree relatives.
In 2010, the Public Health Agency of Canada produced
a “Decision Aid for Breast Cancer Screening in Canada.”
It provides information on mammography to assist
women aged ≥ 40 in making decisions about screening.
The document recommends that women aged 50 to
69 years who are at average risk should have screening
mammograms every 2 years.32
Endometrial cancers can also be a component of an
inherited cancer susceptibility syndrome. For example,
endometrial cancer is associated with HNPCC/Lynch
syndrome. HNPCC is likely the most common hereditary
cancer syndrome, causing about 1 in 20 cases of colorectal
cancer.33 The mutation confers a lifetime risk of about
80% that a carrier will develop CRC. Men with these
mutations appear to have a greater risk of developing CRC
than women. The mutation confers a 30% to 60% lifetime
risk for endometrial cancer in female carriers. This is an
inherited autosomal dominant mutation, and there are 4
known genes: hMLH1, hMSH2, hMSH6, PMS2.
Decision models for Lynch/HNPCC34 have compared
3 management strategies: (1) annual gynaecological
examination alone; (2) annual examination with screening
(ultrasound, endometrial biopsy, CA 125); and (3) hyster­
ectomy with bilateral salpingo-oophorectomy. The third
option may be considered for appropriately counselled
women with Lynch/HPNCC to prevent gynaecologic
cancers and their associated morbidities. The same
research group has reported that this surgical approach is
cost effective.35
Recommendations for presymptomatic women with
documented HPNCC/Lynch mutations include
colonoscopic screening starting at age 25 and continuing as
MARCH JOGC MARS 2012 l 281
SOGC Committee Opinion

Table 5. Routine cancer screening clinical approach (American Congress of Obstetricians and Gynecologists,
The Society of Obstetricians and Gynaecologists of Canada, and The Society of Gynecologic Oncologists of
Canada)
Topic Guideline
Breast Cancer ACOG: Mammography should be performed every 1 to 2 years beginning at age 40 years and yearly beginning at
age 50 years. All women should have an annual clinical breast examination as part of the physical examination.
Despite a lack of definitive data for or against breast self-examination, it has the potential to detect palpable breast
cancer and can be recommended.
SOGC/GOC: Age 40 to 49, clinical breast examination by trained professional every 2 years; age 50 to 69, clinical
breast examination by trained professional and mammogram every 2 years; > age 70, personal plan discussed with
trained professional
Colorectal Cancer ACOG: Beginning at age 50 years, 1 of 5 screening options should be selected:
1.  Yearly patient-collected FOBT or FIT,* or
2.  Flexible sigmoidoscopy every 5 years, or
3.  Yearly patient-collected FOBT or FIT* plus flexible sigmoidoscopy every 5 years, or
4.  Double-contrast barium enema every 5 years, or
5.  Colonoscopy every 10 years
SOGC/GOC: Women at low risk > age 50 fecal occult blood every 2 years; Women at high risk (first degree relative
affected with CRC, FAP, HNPCC, history of inflammatory bowel disease, benign polyps in colon or rectum) should
discuss surveillance such as colonoscopy with trained gastrointestinal professional
Ovarian Cancer ACOG and SOGC/GOC: Currently, there are no effective techniques for the routine screening of asymptomatic,
women at low risk for ovarian cancer. It appears that the best way to detect early ovarian cancer is for both the patient
and her clinician to have a high index of suspicion of the diagnosis in the symptomatic woman, and both should be
aware of the symptoms commonly associated with ovarian cancer. Persistent symptoms such as an increase in
abdominal size, abdominal bloating, fatigue, abdominal pain, indigestion, inability to eat normally, urinary frequency,
pelvic pain, constipation, back pain, urinary incontinence of recent onset, or unexplained weight loss should be
evaluated, with ovarian cancer included in the differential diagnosis.
Research in progress: combining CA125 and transvaginal ultrasound in a small study detected 34/38 ovarian cancers
with 50% in stage I or II.
FIT: fecal immunochemical testing; FOBT: fecal occult blood testing; CA125 blood test for cancer screening.
*Both FOBT and FIT require 2 or 3 samples of stool collected by the patient at home and returned for analysis. A single stool sample for FOBT or FIT obtained
by digital rectal examination is not adequate for the detection of CRC.
Table adapted from Adams Hillard PJ and Berek JS,20 Canadian Cancer Society.46,47

Table 6. Primary and preventive care: periodic assessments in women who have
a family history
Periodic assessment Leading causes of death
Age range (consider family history/risk) (genetic disease) Rank
13 to 18 years genetic testing/counselling malignant neoplasms 2
congenital conditions 6
19 to 39 years genetic testing/counselling malignant neoplasms 1
cardiovascular risk cardiac 3
diabetes 8
40 to 64 years CRC screening malignant neoplasms 1
lipid/cholesterol profile cardiac 2
diabetes diabetes 6
breast cancer
thyroid (TSH)
≥ 65 years as above cardiac 1
malignant neoplasms 2
Alzheimer’s disease 5
diabetes 7
TSH: thyroid stimulating hormone
Table adapted from ACOG Committee Opinion No. 452.48

282 l MARCH JOGC MARS 2012

 Genetic Considerations for a Woman’s Annual Gynaecological Examination
frequently as once per year.36 Gynaecological surveillance
should start at age 30 (17% of endometrial cancers and 42%
of ovarian cancers in these patients cohort are diagnosed
by age 40). Women with Lynch syndrome do not have an
increased risk for breast cancer, so they may benefit from
estrogen-replacement therapy after oophorectomy to
prevent or minimize the potential sequelae of surgically
induced menopause.
Other genetic gastrointestinal cancers, including
hamartomatous polyposis syndromes, gastric cancer, and
CRC/familial adenomatous polyposis, are described in the
Appendix.37–45
Table 5 summarizes general approaches for cancer
screening of breast, colon and ovary20,46,47 considering both
Canadian and American sources.
Table 6 summarizes the primary and preventive care
periodic assessments by female age groups.48
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2. McLeod L, Ray LJ. Prevention and detection of diabetic embryopathy.
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5. Shulman LP, Montouris G. Women with epilepsy: clinical guidelines.
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November 2007. J Obstet Gynaecol Can 2007;23:911–7.
7. Wilson RD; SOGC Genetics Committee; Motherisk. Pre-conceptional
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combination with a multivitamin supplement for the prevention of neural
tube defects and other congenital anomalies. Joint SOGC-Motherisk
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8. Blake RE. Leiomyomata uteri: hormonal and molecular determinants of
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clinicians need to know. Obstet Gynecol 2006;107:917–21.
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11. Sibai BM, How HY, Stella CL. Thrombophilia in pregnancy: whom to
screen, when to treat. OBG Management 2007;19:50–64.
12. James AJ, Brancazio LR. Factor V Leiden thrombophilia. Female Patient
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EA, et al.; South Australian Cerebral Palsy Research Group. Associations
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14. Spector EB, Grody WW, Matteson CJ, Palomaki G, Bellissino DB,
Wolff DJ, et al. Technical standards and guidelines: venous
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15. Gris JC, Mercier E, Quéré I, Lavigne-Lissalde G, Cochery-Nouvellon E,
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16. Qaseem A, Snow V, Barry P, Hornbake ER, Rodnick JE, Tobolic T,
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17. De Carolis S, Gerrazzani S, DeStefano V, Garofalo S, Fatigante G,
Rossi E, et al. Inherited thrombophilia: treatment during pregnancy. Fetal
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18. Marik PE, Plante LA. Venous thromboembolic disease and pregnancy.
N Engl J Med 2008;359:2025–33.
19. Fedele L, Bianchi S, Frontino G, Ciappina N, Fontana E, Borruto F.
Laparoscopic findings and pelvic anatomy in Mayer-Roitansky-Küster-
Hauser syndrome. Obstet Gynecol 2007;109:1111–5.
20. AdamsHillard PJ, Berek JS, eds. Guidelines for women’s healthcare.
A resource manual. 3rd ed. Washington DC: American College of
Obstetricians and Gynecologists: 2007.
21. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics,
2007. CA Cancer J Clin 2007;57:43–66.
22. American Cancer Society. Lifetime probability of developing or dying
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23. Manuel M, Kieran S, Lilja J. Cancer risk assessment in a community
setting: prevalence of patients with high risk family histories. Gynecol
Oncol 2007 Mar;104(3 Suppl 1):S2–35. Abstract 15, presented at the 38th
Annual Meeting on Women’s Cancer, Society of Gynecologic Oncologists,
March 3–7, 2007, San Diego CA.
24. Karlan BY, Berchuck A, Mutch D. The role of genetic testing for cancer
susceptibility in gynecologic practice. Obstet Gynecol 2007;110:155–67.
25. Nisker JA. The need for public education: surveillance and risk reduction
strategies for women at risk for carrying BRCA gene mutations. J Obstet
Gynaecol Can 2007;29:510–1.
26. US Preventive Services Task Force. Genetic risk assessment and
BRCA mutation testing for breast and ovarian cancer susceptibility:
recommendation statement. Ann Intern Med 2005;143:355–61.
27. Metcalfe KA, Poll A, O’Connor A, Gershman S, Armel S, Finch A, et al.
Development and testing of a decision aid for breast cancer prevention
for women with BRAC1 or BRAC2 mutation. Clin Genet 2007;72:208–17.
28. Kauff ND, Barakat RR. Risk-reducing salpingo-oophorectomy in
patients with germline mutations in BRCA1 and BRCA2. J Clin Oncol
2007;25:2921–7.
29. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al.
American Cancer Society guidelines for breast screening with MRI as an
adjunct to mammography. CA Cancer J Clin 2007;57:75–89.
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30. Weitzel JN, Lagos VI, Cullinane CA, Gambol PJ, Culver JO, Blazer KR, et
al. Limited family structure and BRCA gene mutation status in single cases
of breast cancer. JAMA 2007;297:2587–95.
31. Kauff ND, Barakat RR. Surgical risk-reduction in carriers of BRCA
mutations: where do we go from here? Gynecol Oncol 2004;93:277–9.
32. Public Health Agency of Canada. Information on mammography for
women aged 40 and older: a decision aid for breast cancer screening in
Canada. Ottawa: Public Health Agency of Canada;2009. Available at:
http://www.phac-aspc.gc.ca/cd-mc/mammography-mammographie-eng.php.
Accessed August 10, 2011.
33. Feero G. Inherited cancer syndromes. Guest Editorial. Ob Gyn News
2007;42(17):10.
34. Chen L-M, Yang KY, Little SE, Cheung MK, Caughey AB. Gynecologic
cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal
cancer families. Obstet Gynecol 2007;110:18–25.
35. Yang KY, Caughey AB, Little SE, Cheung MK, Chen L-M. A cost-
effectiveness analysis of prophylactic surgery versus gynecologic
surveillance for women from hereditary nonpolyposis colorectal cancer
(HNPCC) families. Gynecol Oncol 2007;104(3 Suppl 1): Abstract 68.
Presented at the 38th Annual Meeting of the Society of Gynecologic
Oncologists, San Diego, CA. March 3–7, 2007.
36. Offit K, Kauff ND. Reducing the risk of gynecologic cancer in the lynch
syndrome. N Engl J Med 2006;354:293–5.
37. Zbuk KM, Eng C. Hamartomatous polyposis syndromes. Nat Clin Pract
Gastroenterol Hepatol 2007;4:492–502.
38. Kaurah P, MacMillan A, Boyd N, Senz J, DeLuca A, Chun N, et al.
Founder and recurrent CDH1 mutations in families withy hereditary
diffuse gastric cancer. JAMA 2007;297:2360–72.
39. Lynch HT, Grady W, Suriano G, Huntsman D. Gastric cancer: new genetic
developments. J Surg Oncol 2005;90:114–33.
40. Joint Test and Technology Transfer Committee Working Group. Genetic
testing for colon cancer: joint statement of the American College of
Medical Genetics and American Society of Human Genetics. Genet Med
2000;2:362–6.
41. Ramsoekh D, van Leerdam ME, Tops CMJ, Dooijes D, Steyerberg EW,
Kuipers EJ, et al. The use of genetic testing in hereditary colorectal cancer
syndromes: genetic testing in HNPCC, (A)FAP and MAP. Clin Genet
2007;72:562–7.
42. Zarychanski R, Chen Y, Bernstein CN, Hébert PC. Frequency of
colorectal cancer screening and the impact of family physicians on
screening behavior. CMAJ 2007; 177:593–7.
43. Barkun A, Flegel K. Outliving colorectal cancer. CMAJ 2007;177:545.
44. Leddin D, Hunt R, Champion M, Cockeram A, Flook N, Gould M, et al.
Canadian Association of Gastroenterology and the Canadian Digestive
Health Foundation. Guidelines on colon cancer screening. Can J
Gastroenterol 2004;18:93–9.
45. Kahi CJ, Rex DK. Primer: applying the new postpolypectomy surveillance
guidelines in clinical practice. Nature 2007;4:571–8.
46. Canadian Cancer Society. Breast cancer screening guideline. Available at:
http://www.cancer.ca/Canada-wide/Prevention/Getting%20checked/
Breast%20cancer%20NEW.aspx?sc_lang=en. Accessed August 8, 2011.
47. Canadian Cancer Society. Colorectal cancer recommendations. Available
at: http://www.cancer.ca/Canada-wide/Prevention/Getting%20checked/
Colorectal%20cancer%20NEW.aspx?sc_lang=en. Accessed August 8,
2011.
48. American College of Obstetricians and Gynecologists Committee on
Gynecologic Practice. Primary and preventative care periodic assessments.
ACOG Committee Opinion No. 452, December 2009. Obstet Gynecol
2009;114:1444–51.

Appendix. Additional Gastrointestinal Cancer Information

The hamartomatous polyposis syndromes are a heterogeneous group of disorders that share an autosomal-dominant pattern of inheritance and
are characterized by hamartomatous polyps of the gastrointestinal tract.37 These syndromes include juvenile polyposis syndrome, Peutz-Jeghers
syndrome, and PTEN hamartoma tumour syndrome. The frequency and location of the polyps vary considerably, as does the predisposition
for the development of gastrointestinal and other malignancies. In addition, there are non-malignant manifestations, such as bleeding,
intussusception, and bowel obstruction. Surveillance guidelines for these rare syndromes were published in 2007.37
Gastric cancer is the second most common cause of cancer death worldwide. A germline mutation in the epithelial cadherin (CDH1) has an
increased risk for diffuse gastric cancer and lobular breast cancer. A recent publication indicates the presence of a founder mutation from
Newfoundland pedigrees.38 Published guidelines39,40 recommend providing genetic counselling to the family and beginning screening in the late
teens or early 20s. The timing of prophylactic gastrectomy is an individual decision.
Colorectal cancer is the second leading cause of cancer death in North America. CRC evolves in an adenoma to carcinoma sequence during
which a series of somatic alterations accumulate in the DNA of the tumour tissue.40 About 75% of these molecular changes are sporadic
events, but the remaining 25% arise in individuals with a family history of colon cancer. HNPCC (etiology for 1 in 20 CRC) has been discussed
previously. The other hereditary cancer (much rarer with 100 to thousands of polyps) is FAP, which is an autosomal dominant syndrome with
germline mutations. Clinical onset is at a young age (12 to 15 years) with hundreds of adenomatous polyps in the colon and increased risk for
gastric polyps, duodenal cancer, thyroid cancer, and desmoids tumours. There is an attenuated variety, AFAP, that has fewer than 100 adenomas
with a proximal predominance and a later age of onset (55 years).40
Cancer genetic risk assessment for hereditary colon cancer would include HNPCC and FAP.41 A recent mutation was identified specifically in
the Ashkenazi Jewish population. A 2002 statement from American College of Medical Genetics and the American Society of human Genetics
presents guidelines for screening and tumour analysis.40 Identification of this colorectal family history should allow discussion with the patient
about counselling, possible testing and referral to a hereditary cancer program through medical or provincial cancer agencies.41 Recently
published results42,43 from a 2003 survey indicate only 23.5% of Canadians at risk for colon cancer reported receiving screening, but this dropped
to 17.6% when only up-to-date screening was considered. Canadian recommendations44 are that screening involves geographic availability and
patient discussion with the screening options of fecal occult blood testing every 2 years; flexible sigmoidoscopy every 5 years; double contrast
barium enema every 5 years; colonoscopy every 10 years. The use of colonoscopy as a screening test for CRC has indentified increased
numbers of patients with polyps requiring follow-up. A recent review45 reports that most patients do not require intensive surveillance, as patients
with 1 or 2 small (< 1 cm) adenomas can safely repeat colonoscopy after 5 to 10 years.

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 SOGC CLINICAL PRACTICE GUIDELINE

No. 275, April 2012

Antibiotic Prophylaxis in Gynaecologic

Procedures
Abstract
This clinical practice guideline has been prepared by the
Infectious Diseases Committee, reviewed by the Family Objective: To review the evidence and provide recommendations on
Physician Advisory Committee, and approved by the antibiotic prophylaxis for gynaecologic procedures.
Executive and Council of the Society of Obstetricians and
Outcomes: Outcomes evaluated include need and effectiveness of
Gynaecologists of Canada.
antibiotics to prevent infections in gynaecologic procedures.
PRINCIPAL AUTHORS
Evidence: Medline and The Cochrane Library were searched for
Nancy Van Eyk, MD, Halifax NS articles published between January 1978 and January 2011 on the
Julie van Schalkwyk, MD, Vancouver BC topic of antibiotic prophylaxis in gynaecologic procedures. Results
were restricted to systematic reviews, randomized control trials/
INFECTIOUS DISEASES COMMITTEE controlled clinical trials, and observational studies. Searches were
Mark H. Yudin, MD (Chair), Toronto ON updated on a regular basis and incorporated in the guideline to
June 2011. Grey (unpublished) literature was identified through
Victoria M. Allen, MD, Halifax NS
searching the websites of health technology assessment and
Céline Bouchard, MD, Quebec QC health technology assessment-related agencies, clinical practice
Marc Boucher, MD, Montreal QC guideline collections, clinical trial registries, and national and
international medical specialty societies.
Sheila Caddy, MD, Edmonton AB
Values: The quality of evidence obtained was rated using the
Eliana Castillo, MD, Calgary AB criteria described in the Report of the Canadian Task Force on
Deborah M. Money, MD, Vancouver BC Preventative Health Care (Table 1).
Kellie E. Murphy, MD, Toronto ON Benefits, harms, and costs: Guideline implementation should result
in a reduction of cost and related harm of administering antibiotics
Gina Ogilvie, MD, Vancouver BC
when not required and a reduction of infection and related
Caroline Paquet, RM, Trois-Rivières QC morbidities when antibiotics have demonstrated a proven benefit.
Julie van Schalkwyk, MD, Vancouver BC
Recommendations
Vyta Senikas, MD, Ottawa ON
01. All women undergoing an abdominal or vaginal hysterectomy
Disclosure statements have been received from all members of should receive antibiotic prophylaxis. (I-A)
the committee.
02. All women undergoing laparoscopic hysterectomy or
The literature searches and bibliographic support for this laparoscopically assisted vaginal hysterectomy should receive
guideline were undertaken by Becky Skidmore, Medical prophylactic antibiotics. (III-B)
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada. 03. The choice of antibiotic for hysterectomy should be a single dose
of a first-generation cephalosporin. If patients are allergic to
cephalosporin, then clindamycin, erythromycin, or metronidazole
should be used. (I-A)

J Obstet Gynaecol Can 2012;34(4):382–391
Key Words: Antibiotics, prophylaxis, hysterectomy, hysteroscopy,
gynaecologic surgery
04. Prophylactic antibiotics should be administered 15 to 60 minutes
prior to skin incision. No additional doses are recommended. (I-A)
05. If an open abdominal procedure is lengthy (e.g., > 3 hours), or if
the estimated blood loss is > 1500 mL, an additional dose of the
prophylactic antibiotic may be given 3 to 4 hours after the initial
dose. (III-C)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

382 l APRIL JOGC AVRIL 2012


06. Antibiotic prophylaxis is not recommended for laparoscopic
procedures that involve no direct access from the abdominal
cavity to the uterine cavity or vagina. (l-E)
07. All women undergoing surgery for pelvic organ prolapse and/or
stress urinary incontinence should receive a single dose of first-
generation cephalosporin. (III-B)
08. Antibiotic prophylaxis is not recommended for hysteroscopic
surgery. (II-2D)
09. All women undergoing an induced (therapeutic) surgical abortion
should receive prophylactic antibiotics to reduce the risk of post-
abortal infection. (I-A)
10. Prophylactic antibiotics are not suggested to reduce infectious
morbidity following surgery for a missed or incomplete
abortion. (I-E)
11. Antibiotic prophylaxis is not recommended for insertion of an
intrauterine device. (I-E) However, health care professionals
could consider screening for sexually transmitted infections in
high-risk populations. (III-C)
12. There is insufficient evidence to support the use of antibiotic
prophylaxis for an endometrial biopsy. (III-L)
13. The best method to prevent infection after hysterosalpingography
is unknown. Women with dilated tubes found at the time of
hysterosalpingography are at highest risk, and prophylactic
antibiotics (e.g., doxycycline) should be given. (II-3B)
14. Antibiotic prophylaxis is not recommended for urodynamic
studies in women at low risk, unless the incidence of urinary
tract infection post-urodynamics is > 10%. (1-E)
15. In patients with morbid obesity (BMI > 35 kg/m2), doubling the
antibiotic dose may be considered. (III-B)
16. Administration of antibiotics solely to prevent endocarditis is
not recommended for patients who undergo a genitourinary
procedure. (III-E)
INTRODUCTION
I nfectious complications following gynaecologic surgical
procedures are a significant source of morbidity and
potential mortality. They include urinary tract infection,
endometritis, wound infection, vaginal cuff cellulitis, perineal
infection, and sepsis, which lead to prolonged hospital stays and
increased health care costs. Much work has been done to study
the effect of prophylactic antibiotics in reducing infectious
morbidity. A plethora of antibiotic types, dosing schedules,
and routes of administration have been investigated. There
is evidence to support the use of prophylactic antibiotics for
a number of procedures in gynaecology. Unfortunately, few
comparative trials have been conducted, leaving the clinician
with uncertainty as to which regimen is superior.
ABBREVIATIONS
BV bacterial vaginosis
HSG hysterosalpingography
PID pelvic inflammatory disease
STI sexually transmitted infection
UTI urinary tract infection
Antibiotic Prophylaxis in Gynaecologic Procedures
The presence of antibiotic resistant organisms is a reality
in Canadian health care facilities.1 These organisms include
methicillin resistant Staphylococcus aureus, vancomycin
resistant Enterococcus, and extended-spectrum beta-
lactamase-producing organisms.
Both morbidity and mortality are increased in infections
involving these organisms, as they may be more virulent and
are more difficult to treat because therapeutic options are
limited. Antibiotic resistance development results mainly
from the inappropriate use of antibiotics. Incomplete
courses of antibiotic therapies and the unnecessary use
of broader spectrum regimens play a role.2 Adherence
to treatment and prophylaxis guidelines likely assists in
reducing infection and antibiotic resistance. Physician
adherence to antibiotic prophylaxis guidelines is variable
and frequently at odds with published guidelines.3,4
In addition to antibiotic prophylaxis, all factors that
affect infectious risk reduction in our specialty must
be reviewed. Sterile surgical fields must be ensured, and
ongoing quality assessment of sterilization technique, air
ventilation, and postoperative wound care are needed.
Consistent infection control surveillance and reporting of
infectious complications track ability to minimize these
morbidities and possibly to identify clusters of infection
and the emergence of antibiotic resistant organisms. This
will dictate changes to operative routines to respond to
evolving microbial diversity that seems inevitable.
PRINCIPLES OF ANTIBIOTIC PROPHYLAXIS
The purpose of antibiotic prophylaxis in surgical procedures
is not to sterilize tissues but to reduce the colonization
pressure of microorganisms introduced at the time of
operation to a level that the patient’s immune system is
able to overcome.5 Prophylaxis does not prevent infection
caused by postoperative contamination. Prophylactic
antibiotic use differs from treatment with antibiotics in
that the former is intended to prevent infection, whereas
the latter is intended to resolve an established infection,
typically requiring a longer course of therapy. Prophylaxis
is intended for elective procedures in which the incision
will be closed in the operating room.
Before an agent can be considered for use as a prophylactic,
there must be evidence that it reduces postoperative
infection. It must also be safe and inexpensive, and it must
be effective against organisms likely to be encountered in
the surgical procedure. The agent must be administered
in a way that ensures that serum and tissue levels are
adequate before an incision is made and that therapeutic
levels of the agent can be maintained in serum and tissue
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SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.56
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.56
during surgery and for a few hours (at most) after the
incision is closed.5
Wound infections—surgical site infections—in the form
of cellulitis, abscess, or dehiscence can occur following
laparotomy. Pelvic infections, such as an abscess or infected
hematoma, are a risk with any surgical procedure that
enters the abdominal cavity. Cuff cellulitis is a specific risk
for hysterectomy. Endometritis can result from Caesarean
section or surgical abortion. Urinary tract infections
can occur as a result of any procedure that involves
catheterization of the bladder.
A 1999 guideline published by the United States Centers
for Disease Control and Prevention lists the specific and
stringent criteria that must be met for diagnosis of a
surgical site infection.5 Accurate surveillance for surgical
site infection monitoring requires follow-up for 30 days
postoperatively, and the trend towards early discharge from
hospital makes surveillance a challenge. It is estimated
that up to 84% of surgical site infections occur following
discharge from hospital.5
If prophylactic antibiotics are to be given, they should be
administered shortly before or at bacterial inoculation.6,7
This should be done 15 to 60 minutes before skin incision.
The majority of studies suggest that a single dose is
effective but that for lengthy procedures (> 3 hours) the
dose should be repeated at intervals 1 or 2 times the half-
life of the drug. It has also been suggested that with large
blood loss (> 1500 mL), a second dose should be given.8
384 l APRIL JOGC AVRIL 2012
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
SURGICAL PROCEDURES
Vaginal Hysterectomy
A hysterectomy is considered a “class II or clean-
contaminated” wound (Table 2).5 The method of
hysterectomy may modify the inherent risk of postoperative
infection. A Cochrane review suggested that vaginal
hysterectomy results in fewer unspecified infections or
febrile episodes (OR 0.42; 95% CI 0.21 to 0.83) than
abdominal hysterectomy.9
There is no meta-analysis or systematic review regarding
antibiotic prophylaxis for vaginal hysterectomy. A review
by Duff and Park10 included 20 studies, the majority of
which were prospective randomized trials (18/20) and
many of which were double-blinded (13/20). Without
prophylaxis, the incidence of febrile morbidity averaged
40% to 50% but was reduced to 5% to 20% with
prophylactic antibiotics.10 The type, dose, and duration of
antibiotics used were highly variable, but a first-generation
cephalosporin was used in the majority of studies.
A randomized trial comparing amoxicillin-clavulanic acid
with cefazolin (n = 178) showed no difference in infection
rates.11 Another trial comparing use of cefuroxime,
metronidazole, or both showed an increased morbidity
when metronidazole was added.12
Treating bacterial vaginosis with metronidazole rectally
for at least 4 days prior to vaginal hysterectomy appears to
reduce the incidence of vaginal cuff infection (n = 59; 0 vs.
27%) but may be impractical given the possibility of surgery
 Antibiotic Prophylaxis in Gynaecologic Procedures

Table 2. Centers for Disease Control and Prevention surgical wound classification
Class I/Clean:  An uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary,
genital, or uninfected urinary tract is not entered. In addition, clean wounds are primarily closed and, if
necessary, drained with closed drainage. Operative incisional wounds that follow nonpenetrating (blunt)
trauma should be included in this category if they meet the criteria.
Class II/Clean-Contaminated:  An operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled
conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix,
vagina, and oropharynx are included in this category, provided no evidence of infection or major break in
technique is encountered.
Class III/Contaminated:  Open, fresh, accidental wounds. In addition, operations with major breaks in sterile technique (e.g., open
cardiac massage) or gross spillage from the gastrointestinal tract, and incisions in which acute, nonpurulent
inflammation is encountered are included in this category.
Class IV/Dirty-Infected:  Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or
perforated viscera. This definition suggests that the organisms causing postoperative infection were present
in the operative field before the operation.
Centers for Disease Control and Prevention. Guideline for Prevention of Surgical Site Infection, 1999.5

cancellation.13 It is also difficult to comment on the cost- Laparoscopic Hysterectomy

benefit of screening all women for BV prior to surgery.
Abdominal Hysterectomy
There are 3 meta-analyses exploring the efficacy of
antibiotic prophylaxis for abdominal hysterectomy. The
most recent, by Tanos and Rojansky in 1994,14 compared
17 trials (n = 2752) that used single dose or up to 24 hours
of intramuscular or intravenous cephalosporins. There was
a significant reduction in the incidence of infection in the
treatment groups (OR = 0.35; 95% CI 0.3 to 0.4). Febrile
morbidity was prevented by first-generation cephalosporins
but not by some second- and third-generation choices. The
authors concluded that a single dose of a first- or second-
generation cephalosporin was efficacious and cost-effective.
Mittendorf et al.15 (1993) meta-analyzed 25 RCTs (n = 3604)
with varying antibiotic choice, duration, and routes of
administration. They found that serious infections were less
common in the treatment groups (9% vs. 21.1%, P = 0.001).
Among those who received cefazolin or metronidazole,
11.4% and 6.3% respectively had serious postoperative
infections. Lastly, Wttewaall-Evelaar16 (1990) examined 17
RCTs, the majority of which (14 of 17) used first- or second-
generation cephalosporins. Infections were significantly
reduced in the treatment groups (P < 0.001).
A randomized trial with women undergoing a gynaecologic
procedure via laparotomy (which included abdominal
hysterectomy) comparing amoxicillin-clavulanic acid with
cefazolin (n = 511) showed no difference in infection
rates.17 A randomized trial (n = 321) comparing placebo,
ampicillin, and cefazolin, demonstrated significant
superiority of cefazolin to reduce postoperative infection.18
A randomized study comparing a single dose versus
24-hour regimen of cefuroxime plus metronidazole,
showed no difference.19
A Cochrane review showed that laparoscopic hysterectomy
(laparoscopically assisted vaginal hysterectomy or laparo­
scopic subtotal hysterectomy) results in fewer wound
or abdominal wall infections (OR 0.32; 95% CI 0.12 to
0.85) and fewer unspecified infections or febrile episodes
(OR 0.65; 95% CI 0.49 to 0.87) than abdominal hysterectomy.
There was no difference in any infections between
laparoscopic hysterectomy and vaginal hysterectomy.9
There are no trials assessing the use of prophylactic
antibiotics for any types of laparoscopic hysterectomy.
Given that this is a clean-contaminated procedure with a
rate of postoperative infections similar to that of vaginal
hysterectomy, it would seem reasonable to treat these
patients in a similar fashion.
A single dose of cefazolin was determined to be as effective
as multiple doses in a study of 310 women who underwent
laparoscopically assisted vaginal hysterectomy.20
Laparoscopy not Entering the Uterus and/or Vagina
These procedures are considered clean (Table 2), as the
genital tract is not entered. A randomized non-blinded
trial of 450 women undergoing laparoscopy for various
indications (not hysterectomy), found no difference in
infection rates between those who received a single dose
of cefazolin and those who did not.21
Recommendations
1. All women undergoing an abdominal or
vaginal hysterectomy should receive antibiotic
prophylaxis. (I-A)
2. All women undergoing laparoscopic hysterectomy
or laparoscopically assisted vaginal hysterectomy
should receive prophylactic antibiotics. (III-B)

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SOGC CLINICAL PRACTICE GUIDELINE
3. The choice of antibiotic for hysterectomy should
be a single dose of a first-generation cephalosporin.
If patients are allergic to cephalosporin, then
clindamycin, erythromycin, or metronidazole should
be used. (I-A)
4. Prophylactic antibiotics should be administered 15
to 60 minutes prior to skin incision. No additional
doses are recommended. (I-A)
5. If an open abdominal procedure is lengthy (e.g., > 3
hours), or if the estimated blood loss is > 1500 mL,
an additional dose of the prophylactic antibiotic may
be given 3 to 4 hours after the initial dose. (III-C)
6. Antibiotic prophylaxis is not recommended for
laparoscopic procedures that involve no direct
access from the abdominal cavity to the uterine
cavity or vagina. (I-E)
Surgery for Pelvic Organ Prolapse and/or
Stress Urinary Incontinence
A randomized double-bind, placebo-controlled trial
enrolled 449 patients to receive nitrofurantoin monohydrate
monocrystals or placebo preoperatively. Procedures
included surgery for pelvic organ prolapse and/or stress
incontinence with suprapubic catheterization. Positive urine
cultures were significantly reduced (46% vs. 61%), as was
symptomatic urinary tract infection (7.2% vs. 19.8%).22
There are no studies assessing prophylactic antibiotics prior
to these surgeries without use of a suprapubic catheter.
There are also no studies regarding isolated sub-urethral
sling procedures (e.g., transvaginal or transobturator tapes),
but given the very poor outcomes associated with mesh
infection, administration of a single preoperative dose of a
first-generation cephalosporin is common practice.
Recommendation
7. All women undergoing surgery for pelvic organ
prolapse and/or stress urinary incontinence
should receive a single dose of first-generation
cephalosporin. (III-B)
Hysteroscopic Surgery
A Cochrane review of prophylactic antibiotics for
transcervical intrauterine procedures did not identify
any randomized trials that met their criteria.23 A
pseudorandomized study that used centre-specific
antibiotic prophylaxis analyzed 631 infertile women who
underwent office hysteroscopy. Two hundred sixty-six
women received amoxicillin-clavulanate and doxycycline
2 hours pre-procedure. There was no difference in post-
procedural infection (1 in the antibiotic group).24 A
randomized trial of amoxicillin and clavulanate versus
placebo for hysteroscopic ablation (n = 116) found a
386 l APRIL JOGC AVRIL 2012
significant difference in the occurrence of bacteremia (16%
vs. 2%); however, the authors comment that the majority
of organisms were of dubious clinical significance and
that contamination could not be excluded in 7 of 10 cases.
No significant difference was found for women treated
for presumed infection (11.4% vs. 9%), but no objective
measures were used.25 A case series of 568 women
suggests that the infection risk is low (< 1%).26 There are
no studies addressing prophylactic antibiotics in the setting
of hysteroscopic myomectomy.
Recommendation
8. Antibiotic prophylaxis is not recommended for
hysteroscopic surgery. (II-2D)
Induced (Therapeutic) Abortion
A meta-analysis that included 12 randomized clinical trials,
demonstrated that prophylactic antibiotics significantly
reduced post-abortal infection (at < 16 weeks), compared
with placebo.27 The relative risk of upper genital tract
infection following surgical abortion was 0.58 (95% CI
0.47 to 0.71) with antibiotics. The benefit was seen in
women considered to be at high risk and in those at low
risk for infection; thus, the authors conclude that universal
prophylaxis should be given and that no more placebo-
controlled trials should be performed. The most appropriate
antibiotic regimen, however, is yet to be determined, as
no comparative or superiority trials have been conducted.
The largest trial to date (n = 1074), which had the most
statistically significant reduction in postoperative infection
rates (RR 0.12; 95% CI 0.08 to 0.38), used doxycycline 100
mg orally before the procedure followed by 200 mg after
the procedure.28 Other regimens that have been effective
in a randomized trial include metronidazole 400 mg
orally 1 hour before the procedure and then repeated 4
and 8 hours after the procedure (RR 0.19; 95% CI 0.10
to 0.83)29 and doxycycline 400 mg orally 10 to 12 hours
before the procedure (RR 0.33; 95% CI 0.22 to 0.73)30
A cost-effectiveness study looking at universal screening
for sexually transmitted infections versus prophylactic
azithromycin (1 g) showed that prophylactic treatment
provided a significant cost savings.31 Disadvantages of not
screening include the lack of case identification and the
inability to complete therapy or conduct contact tracing.
Some authors have questioned whether the presence of BV
influences the rate of postoperative infection after induced
abortion. In a double-blind placebo-controlled trial,
treatment using 2% vaginal clindamycin for at least 3 days
preoperatively did not decrease the risk of postoperative
infection in patients with or without documented BV.
The only statistically significant difference was seen when
the authors combined the women who had intermediate

flora with those who had BV (RR = 4.2 in untreated
group; 95% CI 1.2 to 15.9).32 Another randomized
blinded trial found that giving a single 2 g metronidazole
suppository preoperatively to women who had confirmed
bacterial vaginosis33 did not make a significant difference
(RR = 0.53; P = 0.055). Screening and treating for bacterial
vaginosis prior to surgery also may be impractical, and the
cost-effectiveness is not known.
Recommendation
9. All women undergoing an induced (therapeutic)
surgical abortion should receive prophylactic
antibiotics to reduce the risk of post-abortal
infection. (I-A)
Missed or Incomplete Abortion
There are two randomized placebo-controlled trials that
assess the effectiveness of prophylactic antibiotics to
reduce infectious morbidity following uterine evacuation
for incomplete abortion. One trial involving 240 women
used a preoperative intravenous dose of doxycycline or
placebo.34 Chlamydia and gonorrhea rates were low (3%
to 6%) in this population. No difference in postoperative
infectious morbidity rates occurred up to 2 weeks post-
procedure. A second study of 300 women investigated
the use of 200 mg oral doxycycline at 30 to 60 minutes
pre-procedure. Again, no significant difference between
groups was found.35 A 2007 Cochrane Review on this topic
concluded there is not enough evidence to recommend
routine antibiotic prophylaxis for incomplete abortion at
the time of evacuation of the uterus.36
Recommendation
10. Prophylactic antibiotics are not suggested to reduce
infectious morbidity following surgery for a missed
or incomplete abortion. (I-E)
OFFICE PROCEDURES
Intrauterine Device Insertion
Various authors have demonstrated that the risk of
IUD-related infection is limited to the first few weeks to
months after insertion.37,38 It is therefore likely related to
contamination of the endometrial cavity at the time of
insertion, rather than the IUD or strings themselves.39
A 1999 Cochrane Review that included 4 randomized
control trials found no difference in the occurrence
of PID after IUD insertion in patients who were given
prophylactic doxycycline or azithromycin and in those
given placebo (OR 0.89; 95% CI 0.53 to 1.51). Use of
these antibiotics also did not affect whether the IUD was
removed within 90 days of insertion (OR 1.05; 95% CI
0.68 to 1.63).40 However, if the patient is considered at
Antibiotic Prophylaxis in Gynaecologic Procedures
high risk for sexually transmitted infections, it would be
reasonable to consider screening before IUD placement.
Recommendation
11. Antibiotic prophylaxis is not recommended for
insertion of an intrauterine device. (I-E) However,
health care professionals could consider screening
for sexually transmitted infections in high-risk
populations. (III-C)
Endometrial Biopsy
There are no studies that assess the use of prophylactic
antibiotics given before an endometrial biopsy procedure,
and this is not considered standard of care.
Recommendation
12. There is insufficient evidence to support the
use of antibiotic prophylaxis for an endometrial
biopsy. (III-L)
Hysterosalpingography
There are many options for preventing infection that may
occur as a result of HSG:
1. Universal screening for STIs could be carried out, and
patients treated as necessary.
2. Only patients at high risk (determined by history)
could be screened.
3. All patients could receive prophylactic antibiotics.
4. Antibiotics could be given to patients at high risk
(determined by history and/or as indicated by the
presence of tubal obstruction at the time of HSG).
Many of the patients may already have had screening
performed as part of an infertility work-up. If infection is
found, treatment should follow the Canadian Guidelines
for STIs.41 There are no prospective studies that investigate
any of these options. A retrospective study found that
among 278 women who did not receive antibiotics, the
incidence of PID after HSG was 1.4% (4/278), and all 4
patients had dilated tubes; 31 other patients with dilated
tubes did not develop infection. A second group of patients
(n = 326) received a single dose of oral doxycycline before
HSG; no patient (including 56 who had dilated tubes)
developed PID. This study suggests that the incidence
of PID with normal tubes is very low, regardless of
prophylactic antibiotics (0/398) and that the highest-risk
group of women with dilated tubes at the time of HSG did
benefit from prophylactic doxycycline.42
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SOGC CLINICAL PRACTICE GUIDELINE

Table 3. Cardiac conditions associated with the highest risk of adverse outcome
from endocarditis
Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous infective endocarditis
Congenital heart disease (CHD)
Unrepaired cyanotic CHD (including palliative shunts and conduits)
Completely repaired CHD with prosthetic material < 6 months after procedure
Repaired CHD with residual defects at/near site of prosthetic material
Cardiac transplant recipient with cardiac valvulopathy
Adapted from Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. Prevention of Infective
Endocarditis: Guidelines From the American Heart Association: A Guideline From the American Heart Association
Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the
Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality
of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116:1736–54.54
Used with permission of Wolters Kluwer Health.

Recommendation DOSAGE OF ANTIBIOTIC PROPHYLAXIS

13. The best method to prevent infection after
hysterosalpingography is unknown, Women
with dilated tubes found at the time of
hysterosalpingography are at highest risk, and
prophylactic antibiotics (e.g., doxycycline) should be
given. (II-3B)
URODYNAMIC STUDIES
A systematic review in 2008 included 8 RCTs, with 995
patients, most of whom were women.43 The prophylactic
antibiotics differed in type, dose, and duration and
were compared with either placebo or no treatment.
The authors noted that most of the trials had poor
methodology. They concluded that there was a 40%
reduction in the risk of bacteriuria (OR 0.39; 95% CI
0.24 to 0.61), correlating to a number needed to treat of
13. This study assessed only the occurrence of bacteriuria
and not that of symptomatic UTI; therefore, the clinical
significance is unknown. It has been estimated that
only 8% of women develop a symptomatic UTI within
1 week of a diagnosis of asymptomatic bacteriuria.44
On the basis of the results of a decision-analysis that
incorporated reasonable estimates of benefits and
adverse events from the published literature, the authors
concluded that prophylactic antibiotics after urodynamics
in women at low risk should be administered only when
the background rate of UTIs after urodynamics without
prophylaxis is higher than 10%.45
Recommendation
14. Antibiotic prophylaxis is not recommended for
urodynamic studies in women at low risk, unless
the incidence of urinary tract infection post-
urodynamics is > 10%. (1-E)
IN OBESE PATIENTS
Increased BMI is associated with higher rates of surgical
infectious complications. Expert opinion recommends
twice the normal dose of prophylaxis for morbidly obese
patients (BMI > 35 km/m2).46 However, controlled trials
assessing the required dosage for antibiotic prophylaxis
based on patient BMI have not been assessed in our
specialty, and future research is needed.
Recommendation
15. In patients with morbid obesity (BMI > 35 kg/m2),
doubling the antibiotic dose may be considered. (III-B)
RECOMMENDATIONS FOR PENICILLIN/
CEPHALOSPORIN ALLERGY
Penicillin allergy is self-reported by up to 10% of patients,
yet only 10% of those who report themselves as allergic
are allergic when skin testing is performed.47–49 True
anaphylactic response to penicillin is rare, occurring in
1 to 4 per 10 000 administrations.50 Allergic reaction
to a cephalosporin occurs at rates of 0.17% to 8.4% in
those with a penicillin allergy.51–53 Alternative prophylactic
antibiotics for those deemed truly penicillin allergic include
clindamycin 600 mg IV and erythromycin 500 mg IV.
PREVENTION OF INFECTIVE ENDOCARDITIS
The American Heart Assocation guideline published in
200754 found no evidence that genitourinary procedures
cause infectious endocarditis or that administration of
antibiotics prevents infectious endocarditis following such
procedures. The American Heart Assocation therefore
does not recommend prophylactic antibiotics for patients
undergoing genitourinary procedures; this is a change from

388 l APRIL JOGC AVRIL 2012

 Antibiotic Prophylaxis in Gynaecologic Procedures

Table 4. Prophylactic antibiotics recommendations for gynaecologic procedures

Procedure Antibiotic Dosage Level
Vaginal hysterectomy First- or second-generation Single dose, IV I-A
cephalosporin
Abdominal hysterectomy First- or second-generation Single dose, IV I-A
cephalosporin
Laparoscopic hysterectomy First- or second-generation Single dose, IV III-B
cephalosporin
Laparoscopy (uterus and/or vagina not entered) None recommended I-E
Pelvic organ prolapse and/or stress urinary First-generation cephalosporin Single dose, IV III-B
incontinence surgery
Hysteroscopy None recommended II-2D
Therapeutic abortion doxycycline 100 mg po pre-procedure and I-A
200 mg po post-procedure
Missed/incomplete abortion None recommended I-E
IUD insertion None recommended* I-E
Endometrial biopsy None recommended III-L
Hysterosalpingogram 1. Consider screening for STIs† 1. Rx as per STI guidelines‡ III-B
2. Antibiotics if dilated tubes 2. e.g., doxycycline II-3B
Urodynamic testing None recommended§ I-E
IV: intravenous
*Considering screening for sexually transmitted infections in high risk populations
†Evidence for/against screening unknown
‡Canadian guidelines on sexually transmitted infections—2006 edition43
§In patients at low risk with a background risk of UTI < 10% after urodynamics

the 1997 American Heart Assocation guideline. The 2007
guideline identifies 4 conditions that are at highest risk of
adverse outcome (Table 3). For patients with the conditions
listed in Table 3 who have an established gastrointestinal or
genitourinary infection, or for those who receive antibiotic
therapy for another reason (e.g., to prevent wound
infection), it may be reasonable that the antibiotic used
also be active against enterococci (ampicillin, piperacillin,
or vancomycin). The guidelines also suggest that it may
be reasonable for patients at high risk of infectious
endocarditis who have a known enterococcal urinary tract
infection or colonization to receive antibiotic treatment
prior to any urinary tract manipulation. A review of this
recommendation change has recently been published.55
Recommendation
16. Administration of antibiotics solely to prevent
endocarditis is not recommended for patients who
undergo a genitourinary procedure. (III-E)
the utility of prophylactic antibiotics is either unclear or not
studied. Appropriate antibiotics used at the correct dose
and time and with the appropriate frequency will reduce
infectious postoperative complications and minimize the
development of antibiotic resistant organisms.
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Irminger K, et al. Treatment with 2% clindamycin vaginal cream prior to
first trimester surgical abortion to reduce signs of postoperative infection:
a prospective, double-blinded, placebo-controlled, multicenter study. Acta
Obstet Gynecol Scand 2000;79:390–6.
33. Crowley T, Low N, Turner A, Harvey I, Bidgood K, Horner P. Antibiotic
prophylaxis to prevent post-abortal upper genital tract infection in
women with bacterial vaginosis: randomised controlled trial. BJOG
2001;108:396–402.
34. Prieto JA, Eriksen NL, Blanco JD. A randomized trial of prophylactic
doxycycline for curettage in incomplete abortion. Obstet Gynecol
1995;85(5 Pt 1):692–6.
35. Ramin KD, Ramin SM, Hemsell PG, Nobles BJ, Heard MC, Johnson VB,
et al. Prophylactic antibiotics for suction curettage in incomplete abortion.
Infect Dis Obstet Gynecol 1995;2:213–7.
36. May W, Gülmezoglu AM, Ba-Thike K. Antibiotics for incomplete
abortion. Cochrane Database Syst Rev 2007;Issue 4. Art. No.: CD001779.
DOI: 10.1002/14651858.CD001779.pub2.
37. Lee NC, Rubin GL, Ory HW, Nurkman RT. Type of intrauterine
device and the risk of pelvic inflammatory disease. Obstet Gynecol
1983:96:119–26.
38. Farley TMM, Rosenberg MJ, Rowe P, Chen J-H, Meirik O. Intraterine
devices and pelvic inflammatory disease: an international perspective.
Lancet 1992;339:785–8.
39. Mishell DR Jr, Bell JH, Good RG, Moyer DL. The intrauterine device:
a bacteriologic study of the endometrial cavity. Am J Obstet Gynecol
1966;96:119–26.
40. Grimes DA, Lopez LM, Schulz KF. Antibiotic prophylaxis for intrauterine
contraceptive device insertion. Cochrane Database Syst Rev 1999; Issue 3.
Art. No.: CD001327. DOI: 10.1002/14651858.CD001327.

41. Public Health Agency of Canada. Canadian Guidelines on Sexually
Transmitted Infections; 2006. Available at:
http://www.publichealth.gc.ca/sti. Accessed January 30, 2012.
42. Pittaway DE, Winfield AC, Maxson W, Daniell J, Herbert C, Wentz AC.
Prevention of acute inflammatory disease after hysterosalpingography:
efficacy of doxycycline prophylaxis. Am J Obstet Gynecol 1983;147:623–6.
43. Latthe P, Foon R, Toozs-Hobson P. Prophylactic antibiotics in urodynamics:
a systematic review of effectiveness and safety. Neurol Urodyn
2008;27:167–73.
44. Hooton TM, Scholes D, Stapleton AE, Roberts PL, Winter C, Gupta K, et
al. A prospective study of asymptomatic bacteriuria in sexually active young
women. N Engl J Med 2000;343:992–7.
45. Lower J, Burrows L, Howden N, Weber A. Prophylactic antibiotics
after urodynamics in women: a decision analysis. Int Urogynecol J
2007;18:159–64.
46. Gordon SM. Antibiotic prophylaxis against postoperative wound infections.
Cleve Clin J Med 2006;73(Suppl 1):S42–5.
47. Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA,
Peterson LR, et al. The incidence of antimicrobial allergies in hospitalized
patients: implications regarding prescribing patterns and emerging bacterial
resistance. Arch Intern Med 2000;160:2819–22.
48. del Real GA, Rose ME, Ramirez-Atamoros MT, Hammel J, Gordon SM,
Arroliga AC, et al. Penicillin skin testing in patients with a history of beta-
lactam allergy. Ann Allergy Asthma Immunol 2007;98:355–9.
49. Sogn DD, Evans R 3rd, Shepherd GM, Casale TB, Condemi J, Greenberger
PA, et al. Results of the National Institute of Allergy and Infectious
Diseases collaborative clinical trial to test the predictive value of skin testing
with major and minor penicillin derivatives in hospitalized adults. Arch
Intern Med 1992;152:1025.
Antibiotic Prophylaxis in Gynaecologic Procedures
50. International Rheumatic Fever Study Group. Allergic reactions to
long-term benzathine penicillin prophylaxis for rheumatic fever. Lancet
1991;337(8753):1308–10.
51. Dash, CH. Penicillin allergy and the cephalosporins. J Antimicrob
Chemother 1975;1:107.
52. Daulat, S, Solensky, R, Earl, HS, Casey W, Gruchalla RS. Safety of
cephalosporin administration to patients with histories of penicillin
allergy. J Allergy Clin Immunol 2004;113:1220.
53. Fonacier L, Hirschberg R, Gerson S. Adverse drug reactions to
cephalosporins in hospitalized patients with a history of penicillin allergy.
Allergy Asthma Proc 2005;26:135.
54. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison
M, et al.; American Heart Association Rheumatic Fever, Endocarditis,
and Kawasaki Disease Committee; American Heart Association Council
on Cardiovascular Disease in the Young; American Heart Association
Council on Clinical Cardiology; American Heart Association Council on
Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes
Research Interdisciplinary Working Group. Prevention of Infective
Endocarditis: Guidelines From the American Heart Association.
Circulation 2007;116:1736–54
55. Castillo E, Magee LA, von Dadelszen P, Money D, Blonde-Hill E, van
Schalkwyk J. Our patients do not need endocarditis prophylaxis for
genitourinary tract procedures: insights fro the 2007 American Heart
Association Guidelines. J Obstet Gynaecol Can 2008;30:796–9.
56. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
APRIL JOGC AVRIL 2012 l 391
 SOGC CLINICAL PRACTICE GUIDELINE
Canadian HIV Pregnancy Planning Guidelines
These guidelines have been written and reviewed by the
Canadian HIV Pregnancy Planning Guideline Development
Team in partnership with the Society of Obstetricians
and Gynaecologists of Canada, the Canadian Fertility
and Andrology Society and the Canadian HIV/AIDS Trials
Network. They were reviewed by the Infectious Diseases
Committee and the Reproductive Endocrinology and
Infertility Committee of the Society of Obstetricians and
Gynaecologists of Canada and by the Canadian HIV
Pregnancy Planning Guideline Development Team Core
Working Group,* and endorsed by the Executive and
Council of the SOGC.
PRINCIPAL AUTHORS
Mona R. Loutfy, MD, Toronto ON
Shari Margolese, Toronto ON
Deborah M. Money, MD, Vancouver BC
Mathias Gysler, MD, Mississauga ON
Scot Hamilton, PhD, Mississauga ON
Mark H. Yudin, MD, Toronto ON
*See Appendix for a list of working group members.
Disclosure statements have been received from all authors.
Abstract
Objective: Four main clinical issues need to be considered for
HIV-positive individuals and couples with respect to pregnancy
planning and counselling: (1) pre-conceptional health;
(2) transmission from mother to infant, which has been
significantly reduced by combined antiretroviral therapy;
(3) transmission between partners during conception, which
requires different prevention and treatment strategies depending
on the status and needs of those involved; and (4) management
of infertility issues. The objective of the Canadian HIV Pregnancy
Planning Guidelines is to provide clinical information and
recommendations for health care providers to assist HIV-positive
individuals and couples with their fertility and pregnancy planning
decisions. These guidelines are evidence- and community-based
and flexible, and they take into account diverse and intersecting
local/population needs and the social determinants of health.
Key Words: HIV, pregnancy, insemination, fertility, transmission
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
No. 278, June 2012
Outcomes: Intended outcomes are (1) reduction of risk of vertical
transmission and horizontal transmission of HIV, (2) improvement
of maternal and infant health outcomes in the presence of HIV,
(3) reduction of the stigma associated with pregnancy and HIV, and
(4) increased access to pregnancy planning and fertility services.
Evidence: PubMed and Medline were searched for articles published
in English or French to December 20, 2010, using the following
terms: “HIV” and “pregnancy” or “pregnancy planning” or “fertility”
or “reproduction” or “infertility” or “parenthood” or “insemination”
or “artificial insemination” or “sperm washing” or “IVF” or “ICSI”
or “IUI.” Other search terms included “HIV” and “horizontal
transmission” or “sexual transmission” or “serodiscordant.” The
following conference databases were also searched: Conference
on Retroviruses and Opportunistic Infections, International AIDS
Conference, International AIDS Society, Interscience Conference on
Antimicrobial Agents and Chemotherapy, the Canadian Association
of HIV/AIDS Research, and the Ontario HIV Treatment Network
Research Conference. Finally, a hand search of key journals and
conferences was performed, and references of retrieved articles
were reviewed for additional citations. Subsequently, abstracts were
categorized according to their primary topic (based on an outline of
the guidelines) into table format with the following headings: author,
title, study purpose, participants, results and general comments.
Finally, experts in the field were consulted for their opinions as to
whether any articles were missed.
Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Care. Recommendations for practice were ranked according to
the method described in that report (Table) and through use of the
Appraisal of Guidelines Research and Evaluation instrument for
the development of clinical guidelines.
Sponsors: The Society of Obstetricians and Gynaecologists of
Canada, Women and HIV Research Program, Women’s College
Research Institute, Women’s College Hospital, University of
Toronto, Abbott Laboratories Canada, the Ontario HIV Treatment
Network, the Canadian Institutes of Health Research, and the
Canadian HIV Trials Network.
Key Points and Recommendations
HIV-positive people who are considering pregnancy should be
counselled on the following issues so they can make an informed
decision.
J Obstet Gynaecol Can 2012;34(6):575–590
JUNE JOGC JUIN 2012 l 575
SOGC CLINICAL PRACTICE GUIDELINE
Ensuring a Healthy Mother, Child, and Family
Recommendations
01. Reproductive health counselling, including contraception and
pregnancy planning, should be offered to all reproductive-aged
HIV-positive individuals soon after HIV diagnosis and on an
ongoing basis. (II-3A)
02. Men and women should be counselled on all relevant aspects
of pregnancy planning, such as maintaining a healthy diet and
lifestyle, the risk of genetic disease occurrence, and integrated
prenatal screening, as outlined in current Canadian practice
guidelines irrespective of their known HIV status. (III-A)
03. Women with no risk factors should start taking folic acid (in the
form of vitamin supplements) 1 mg a day for 3 months before
becoming pregnant and for at least the first 3 months of their
pregnancy. (II-3A)
04. Women should be encouraged to give up smoking, drinking
alcohol, and using recreational drugs, and should be referred for
support if required. (III-A)
05. Both prospective parents should be tested for other sexually
transmitted infections, even if they have conceived in the past
and have no symptoms of infection. (III-A)
Psychosocial/Mental Health Issues Related
to HIV Pregnancy Planning and Fertility
All individuals or couples planning pregnancy are potentially
susceptible to psychosocial and mental health problems. An
additional burden may be placed on the HIV-positive individual or
couple because of stigma associated with the condition and the risks
of HIV transmission.
Recommendations
06. Counselling should be performed by a knowledgeable health
care professional or trained peer counsellor in a supportive, non-
judgemental manner that takes into account sexual diversity and
ethnocultural or religious beliefs and practices. (III-A)
07. Counselling should include a discussion of the potential risk for
both horizontal (between partners) and vertical (from mother to
child) transmission and how that might affect the mental health
of one or both parents. (III-A)
08. HIV-positive people who intend to conceive should be made
aware of the potential stigma and discrimination they may
face from others who are less informed about how HIV is
transmitted, horizontally and vertically. In addition, HIV-positive
women who are not breastfeeding should be made aware that
they may face disapproval from people who are not aware of
their HIV status. (II-3A)
09. Further counselling may be suggested to help couples and
individuals cope more effectively with fear, stigma, and other
psychosocial issues, such as postpartum depression. (II-3A)
Legal and Ethical Issues
Recommendations
10. All HIV-positive individuals should be counselled on the possible
legal ramifications of non-disclosure of their HIV status to their
sexual partner(s). (III-A)
ABBREVIATIONS
cART combined antiretroviral therapy
ICS intracytoplasmic sperm injection  reproductive technologies if pregnancy is not achieved in 6 to 12
IUI intrauterine insemination  months. (III-A)
576 l JUNE JOGC JUIN 2012
11. HIV-positive women who are considering pregnancy should
be counselled on the possibility of legal action if they do not
permit antiretroviral therapy to be given to their baby after
birth. (III-B)
12. Ethical considerations, including those related to the health
status of HIV-positive individuals or couples, should be
discussed during pre-conception counselling. (III-B)
Antiretroviral and Other Drugs in
Pregnancy Planning
Recommendations
13. Clinicians should review all medications that HIV-positive
men and women may be using, including antidepressants,
pain medications, over-the-counter medications, and hepatitis
treatment, to ensure that they are safe during conception and
pregnancy. (II-3A)
14. All HIV-positive men and women who require combination
antiretroviral therapy for their own health during the pre-
conception period should be advised to continue their current
regimens, but women should not take any drugs that are
potentially teratogenic or considered toxic in pregnancy,
substituting other drugs when necessary or possible. The
most efficacious regimen that is safe in pregnancy should
be selected. (II-3A)
15. HIV-positive women who do not require combination
antiretroviral therapy for their own health need to consider
starting treatment before becoming pregnant or no later than late
in the first trimester of pregnancy. The most efficacious regimen
that is safe in pregnancy should be selected. (II-3A)
16. HIV-positive men and women who require treatment should be
encouraged to initiate combination antiretroviral therapy during
the pre-conception period to reduce HIV plasma viral load, which
can reduce the risk of HIV transmission to their HIV-negative
partner or reduce the risk of superinfection of their HIV-positive
partner. (II-3B)
17. All decisions about the use of combination antiretroviral
therapy and other drugs during pregnancy should be made
in consultation with experts such as HIV specialists and
pharmacists. (III-A)
Scenario-Based Recommendations for the
Prevention of Horizontal HIV Transmission
The recommended option may not always be the most practical or
preferred option for the patient, given availability of services, cost,
cultural beliefs, or personal risk evaluation. Physicians and other
health care providers should provide non-judgemental support of the
patient’s decision.
HIV-Positive Woman and HIV-Negative Man
Recommendations
18. For serodiscordant couples in which the woman is HIV positive,
it is preferable to attempt home insemination with the partner’s
sperm during ovulation for 3 to 6 months before considering
other methods. (III-A)
19. If home insemination is unsuccessful, couples should be
referred to a gynaecologist for consultation and then to a
fertility specialist for a complete fertility work-up and appropriate
treatment when necessary, including counselling on all assisted

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.80
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.80
HIV-Positive Single Woman or HIV-Positive Woman
in a Same-Sex Relationship
Recommendation
20. Single HIV-positive women or HIV-positive women in a same-
sex relationship should be referred to a fertility specialist and
should consider the option of intrauterine insemination with
HIV-negative donor sperm. This option is preferred over home
insemination with donor sperm because the cost of sperm is high
and intrauterine insemination performed in a fertility clinic has
a higher success rate than home insemination. If sperm from a
known donor is used for intrauterine insemination, regulations
applicable to the donation of sperm must be followed. (III-A)
HIV-Positive Man and HIV-Negative Woman
Recommendations
21. Serodiscordant couples in which the man is HIV positive
should be referred to a fertility specialist and should consider
the preferred option of sperm washing with intrauterine
insemination. (II-2A)
22. If intrauterine insemination is unsuccessful, couples should
consider in vitro fertilization or intracytoplasmic sperm injection
with either sperm washing or the use of donor sperm. (II-3A)
23. HIV-positive men who do not require combination
antiretroviral therapy for their own health should be
encouraged to initiate combination antiretroviral therapy
during the pre-conception period to reduce HIV plasma viral
load, which can reduce the risk of HIV transmission to their
HIV-negative partner. (II-3B)
HIV-Positive Single Man or Male Same-Sex Couple
Recommendation
24. HIV-positive single men or men in same-sex relationships who
have an HIV-negative or HIV-positive surrogate should be
referred to a fertility specialist. (III-A)
Canadian HIV Pregnancy Planning Guidelines
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
HIV-Positive Man and HIV-Positive Woman
It is common for seroconcordant couples to attempt natural conception,
especially if both partners have fully suppressed viral loads.
Seroconcordant couples may wish to consider intrauterine insemination
with sperm washing to reduce the potential risk of super-infection or
transmission of drug-resistant strains of HIV between partners.
Recommendations
25. Timed natural conception is recommended for seroconcordant
couples who are taking combination antiretroviral therapy and
who have fully suppressed HIV plasma viral loads. (II-3A)
26. Seroconcordant couples should be counselled on the risks
and benefits of timed natural conception (including HIV
superinfection and transmission of drug-resistant strains of
HIV). (II-3A)
27. If timed natural conception is unsuccessful, couples should
be referred to a gynaecologist for consultation and then to a
fertility specialist for a complete fertility work-up and appropriate
treatment when necessary, including counselling on all assisted
reproductive technologies. (III-A)
Infertility Investigations and Treatment
Historically, fertility clinics in Canada have been reluctant to provide
fertility investigation and treatment to HIV-positive people. Fertility
experts concur that this has likely been due to a lack of information
about HIV and its successful treatment coupled with a concern that
serving HIV-positive people could deter HIV-negative individuals
from accessing services. In 2010, the American Association of
Reproductive Medicine released a statement in which it endorsed the
provision of fertility services to all HIV-positive individuals.
Recommendations
28. HIV-positive people should be counselled about fertility problems
that occur in the general population, including genetic disorders
and advancing maternal age. (III-A)
29. Infertility investigations and treatment should be offered to HIV-
positive people if required. (III-A)
JUNE JOGC JUIN 2012 l 577
SOGC CLINICAL PRACTICE GUIDELINE
30. All decisions about combination antiretroviral therapy during the
pre-conception period and during pregnancy should consider
the health of the HIV-positive person and reduction of the
risk of horizontal and vertical transmission of HIV. Decisions
about combination antiretroviral therapy should be made in
consultation with an HIV specialist. (III-A)
HIV Infection Control in Fertility Clinics
Recommendations
31. Fertility laboratories should follow Canadian Standards
Association guidelines for infection control when handling HIV-
positive materials. (III-A)
32. Potentially infectious materials should be stored in segregated
containers and incubators to reduce the risk of HIV
contamination. (III-A)
33. Bio-containment straws for specimen storage should be used to
further reduce the risk of cross-contamination of samples. (III-A)
INTRODUCTION
Demand for HIV Pregnancy Planning and
Fertility Services in Canada
T
he natural history of human immunodeficiency virus
infection has changed significantly in the last decade
with advances made in medical treatment, most specifically
with the introduction of highly successful combination
antiretroviral therapy.1 As a result, individuals living with
HIV are now experiencing an improved quality of life and
a prolonged life expectancy.1–3 In countries with greater
resources, the mortality caused by HIV has significantly
decreased and approaches general population norms. A
recent study indicated that HIV-positive individuals within
7 years of their diagnosis have the same life expectancy
as the general population.2 While the overall current life
expectancy of someone infected with HIV is difficult to
predict (as successful treatment has been widely prescribed
only since 1996), present projections estimate that an
individual living with HIV today will live at least 30 to 40
years from the time of infection.3
Another significant change in the field of HIV in the past
2 decades is that the rate of HIV infection in women
has been steadily on the rise. By the end of 2007, it was
estimated that approximately 65 000 Canadians were living
with HIV and that 10 114 were women.4 This represents a
23% increase from 2002. Similarly, women now account for
more than one quarter of new positive HIV test reports.4
The use of cART, possible Caesarean section (as indicated
by current guidelines on pregnancy and HIV), and
abstaining from breastfeeding have reduced the chance
of vertical transmission of HIV to < 1%. These factors
have likely led to the increasing number of pregnancies
in HIV-positive women over the past decade.5 In Canada,
all pregnancies to HIV-positive mothers are reported
578 l JUNE JOGC JUIN 2012
through a registry created by the Canadian Perinatal
HIV Surveillance Program of the Public Health Agency
of Canada. Their 2009 annual report indicates that 180
children were born to HIV-positive women in Canada
that year. In the 4 preceding years, the number of children
born to HIV-positive women was as follows: 238 (2008),
208 (2007), 194 (2006), and 189 (2005).5 Furthermore,
pregnancy planning has been identified as a key area of
importance to people with HIV in Canada.6 Nevertheless,
the reproductive health concerns and services available and
provided to people living with HIV have received minimal
attention.
A gap exists between the desires and intentions of people
living with HIV to have children and their need for support
in doing so and the resources, relevant research, and
support networks necessary for them to do so successfully
and in a medically safe manner. Issues to consider in
pregnancy planning when at least one partner has HIV
are not just the prevention of vertical transmission but
also the prevention of horizontal transmission and the
management of potential infertility issues. In 2006,
Ogilvie et al.7 conducted a research study to examine the
fertility intentions of women living with HIV in British
Columbia. Of the 182 women analyzed in the study, 25.8%
expressed intentions to have children regardless of their
clinical HIV status.7 Most recently, Loutfy et al.8 completed
a cross-sectional study designed to assess fertility desires,
intentions, and actions. This study surveyed 490 HIV-
positive women of reproductive age (18 to 52) living in
Ontario. Sixty-one percent were born outside Canada, 52%
lived in Toronto, 47% were of African ethnicity, 74% were
currently on cART, and the median age was 38. Sixty-nine
percent wanted to give birth, and 57% intended to give
birth in the future. This study found that the significant
predictors of fertility intentions were younger age (age
< 40), African ethnicity, living in Toronto, and a lower
number of lifetime births (P = 0.02).8 In 2005, Oladapo et
al. conducted a study determining the fertility desires and
intentions of people living with HIV who were receiving
care at a suburban specialist clinic in Sagamu, Nigeria.9
Of the 147 participants, 63.3% expressed a desire for
child-bearing, even though 50.4% of them already had 2
or more children. Of those who wanted to have children,
71.5% of men and 93.8% of women intended to have 2
or more children in the near future.9 In 2009, Nattabi et
al. conducted a systematic review of 29 studies of factors
influencing fertility desires and intentions among people
living with HIV and found that fertility desires were
influenced by a variety of demographic, health, stigma-
associated, cultural, and psychosocial factors.10

In all of the aforementioned studies, it was concluded that
the desire and intention of HIV-positive individuals to
have children were high and that clinical HIV status did not
seem to be a predictor of fertility intentions. Specialized
counselling, services, and support will be required to meet
the needs of this group.
Access to HIV Pregnancy Planning and
Fertility Services in Canada
Despite the fact that many HIV-positive individuals and
couples wish to have children, there is a scarcity of HIV or
fertility clinics in North America offering advice to HIV-
positive individuals and couples on the management of
HIV during pregnancy planning, timing of ovulation to
allow fertilization, sperm washing (a procedure designed to
remove viral particles from the sperm, reducing the chance
of horizontal transmission), management of individuals or
couples affected by infertility issues, and fertility treatments
including intrauterine insemination and in vitro fertilization.
In Europe, HIV-positive couples have had access to
reproductive assistance since the 1980s, and at least 5
European countries have national programs to assist people
living with HIV in their pregnancy planning.11 As of 2003,
less than 5% of fertility clinics in the United States offered
reproductive care to HIV-serodiscordant couples.12 In
Canada, services and treatment protocols differ depending
on the clinic or centre, and therefore so do the costs. It
is important to note that in most jurisdictions in Canada
sperm washing, IUI, IVF, and ICSI are not covered by
provincial medical services plans, so costs are charged
directly to the patient.
A 2010 study by Yudin et al. showed that while over 70% of
clinics surveyed were willing to see people living with HIV
in consultation, substantially fewer had actually seen any
people living with HIV within the previous 12 months.13
Services offered also varied by region, with clinics located
in only 5 provinces offering fertility treatments to people
living with HIV. Some important procedures were also less
commonly available to people living with HIV. In particular,
sperm washing was available in only 26% of clinics in
4 provinces, a service gap noted in the Newmeyer et al.
study that described the barriers to services experienced by
people living with HIV.14
In addition to a deficiency in assisted reproductive services,
there remains a scarcity of pregnancy planning, prenatal
and postnatal care, and counselling programs for HIV-
positive individuals and couples in Canada.
Unintended Pregnancy
As is the case in the general population, many pregnancies
in people with HIV are unintended. An Ontario study of
Canadian HIV Pregnancy Planning Guidelines
HIV-positive women of reproductive age found that 56%
of their most recent pregnancies were unintended.15 One
of the goals of these guidelines is to encourage health
care providers to discuss pregnancy planning, including
contraception, with their patients as early as possible after
diagnosis to reduce the incidence of unintended pregnancy
and to reduce the risk of both vertical and horizontal
transmission of HIV.
HIV/AIDS AND HUMAN RIGHTS
The World Health Organization states that “all couples
and individuals have the right to decide freely and
responsibly the number and spacing of their children and
to have access to the information, education and means to
do so.”16 This includes people living with HIV or AIDS.
The human rights of those infected with and affected
by HIV are frequently violated, and this can affect their
intentions and desires with respect to having children.
There is a need to integrate these guiding principles into
all aspects of HIV pregnancy planning, fertility care,
treatment and support for people living with HIV in
Canada. Recommendations for care must be evidence-
based, and their implementation must be flexible and
ethnoculturally sensitive, and must also take into account
diverse and intersecting local/population needs and the
social determinants of health.17
SCOPE OF DOCUMENT
This guideline does not address the management of HIV
during pregnancy or HIV testing during pregnancy, because
this information is available elsewhere.18 Similarly, as there
are guidelines dealing with fertility and infertility issues in
the general population, these issues are not addressed in
this document.19 The postpartum period and infant feeding
options for people with HIV are outside of the scope of
this document.
ENSURING A HEALTHY MOTHER,
CHILD, AND FAMILY
Although management of HIV in pregnancy planning entails
many special considerations, it is important to remember
that most general recommendations for pregnancy planning
also apply to HIV-positive individuals and couples.
The Public Health Agency of Canada is an important
source of information to ensure a healthy mother, child,
and family. Eating Well with Canada’s Food Guide provides
women with the information they need to eat well during
pregnancy and includes specific advice for all women
JUNE JOGC JUIN 2012 l 579
SOGC CLINICAL PRACTICE GUIDELINE
of child-bearing age. Detailed recommendations for
pregnancy and breastfeeding are available for health
professionals. The Public Health Agency of Canada has
described alcohol use in pregnancy as “an important public
health and social issue for Canadians,” recognizing the
increasing societal awareness of the significant personal
and social costs associated with fetal alcohol spectrum
disorder.20 In addition to specific guidelines for alcohol use
and nutrition during pregnancy, the agency has produced
The Sensible Guide to a Healthy Pregnancy, which includes
guidance on general nutrition, folic acid, alcohol, physical
activity, smoking and oral health.21
In addition, SOGC has published numerous guidelines
addressing most of these topics.22
Recommendations
1. Reproductive health counselling, including
contraception and pregnancy planning, should
be offered to all reproductive-aged HIV-positive
individuals soon after HIV diagnosis and on an
ongoing basis. (II-3A)
2. Men and women should be counselled on all
relevant aspects of pregnancy planning, such as
maintaining a healthy diet and lifestyle, the risk
of genetic disease occurrence, and integrated
prenatal screening, as outlined in current Canadian
practice guidelines irrespective of their known
HIV status. (III-A)
3. Women with no risk factors should start taking
folic acid (in the form of vitamin supplements)
1 mg a day for 3 months before becoming
pregnant and for at least the first 3 months of their
pregnancy. (II-3A)
4. Women should be encouraged to give up smoking,
drinking alcohol, and using recreational drugs, and
should be referred for support if required. (III-A)
5. Both prospective parents should be tested for other
sexually transmitted infections, even if they have
conceived in the past and have no symptoms of
infection. (III-A)
PSYCHOSOCIAL/MENTAL HEALTH
ISSUES RELATED TO HIV PREGNANCY
PLANNING AND FERTILITY
All individuals or couples planning pregnancy must consider
the implications of psychosocial and mental health issues. An
additional burden is placed on the HIV-positive individual or
couple because of the stigma and discrimination associated
with the condition and the risks of transmission. People
living with HIV considering pregnancy may be concerned
that they will experience stigma and discrimination simply
580 l JUNE JOGC JUIN 2012
for choosing to become parents and may worry that they
will feel guilty about conceiving or breastfeeding, or that
family members, friends, or community members may
disapprove and withdraw support. As with legal and ethical
issues, little information is available on this subject, and
recommendations for psychosocial counselling have been
based on expert consensus.
The transition to parenthood is often a time of great joy,
but it is also life-altering and can result in considerable stress
and anxiety.23–25 When one or both prospective parents have
HIV, the stress can be greatly increased. Even in 2009, the
stigma and marginalization associated with HIV continued
to place a significant psychological burden on those who
were affected.26,27 A 2007 study showed that health care
professionals play a large role in the systemic discrimination
against people living with HIV who wish to have children.28
Thus the environment in which HIV-positive parents live is
one that can easily cause psychological distress.
Although the mental health needs of pregnant women
have been studied,29–31 less is known about the specific
mental health needs of HIV-positive pregnant women. A
large 2004 American study examined minority women who
were pregnant and HIV- positive in 4 regions of the United
States.32 They found that depressive symptoms were severe
and that social isolation, perceived stress, and ineffective
coping strategies were among the factors associated with
depression. On the other hand, the presence of a supportive
partner was associated with fewer depressive symptoms.
This type of research might enable the development of
appropriate interventions that will decrease the risk of
psychological morbidity for HIV-positive women during
the pregnancy planning and antenatal periods.
An earlier, longitudinal study by Larrabee et al.,33 in Texas
followed 21 HIV-positive and 21 HIV-negative women
from the antenatal period until 6 months postpartum using
the Medical Outcome Survey–Short Form to assess overall
quality of life. Overall, HIV-positive women reported
increased health distress and a more difficult transition during
the antenatal period than did HIV-negative control subjects. A
similar difference was found at 6 months postpartum, but not
during the perinatal period. Once again, seropositivity appears
to be associated with poorer mental health during pregnancy.
There are few published studies about the mental health
concerns of fathers, and even fewer about the mental
health of HIV-positive fathers.34,35 However, it is known
that a father’s behaviour during the early postnatal
weeks can significantly affect the mental health status of
new mothers,35 particularly with respect to postpartum
depression, which has a prevalence rate of about 10%.36,37
As more and more people with HIV are living longer,
healthier lives when they have access to medication, this
will become an increasingly important area of research.

Recommendations
6. Counselling should be performed by a
knowledgeable health care professional or
trained peer counsellor in a supportive,
non-judgemental manner that takes into account
sexual diversity and ethnocultural or religious
beliefs and practices. (III-A)
7. Counselling should include a discussion of
the potential risk for both horizontal (between
partners) and vertical (from mother to child)
transmission and how that might affect the mental
health of one or both parents. (III-A)
8. HIV-positive people who intend to conceive
should be made aware of the potential stigma and
discrimination they may face from others who
are less informed about how HIV is transmitted,
horizontally and vertically. In addition, HIV-positive
women who are not breastfeeding should be made
aware that they may face disapproval from people
who are not aware of their HIV status. (II-3A)
9. Further counselling may be suggested to help
couples and individuals cope more effectively with
fear, stigma, and other psychosocial issues, such as
postpartum depression. (II-3A)
LEGAL AND ETHICAL ISSUES
Legal, ethical, and policy issues related to pregnancy and
HIV remain challenging, and guidelines are still evolving
because of the absence of policies and the inconsistencies
in case law pertaining to the criminalization of HIV non-
disclosure in cases of otherwise consensual sex. This section
of the guidelines is therefore based on expert consensus
and on the premise that people living with HIV are entitled
to reproductive freedom without discrimination.
HIV-positive people who are planning pregnancy must
access health services to assist them in dealing with medical
and psychosocial issues, but this typically requires them to
disclose their HIV status to partners and others. A 2004
report by the World Health Organization summarizing
barriers to HIV serostatus disclosure by women in
resource-poor countries indicates that the most common
reasons for failure to disclose to partners included fear of
accusations of infidelity, abandonment, discrimination,
and violence.38
Fear of disclosing HIV status can also create difficulties
in resource-rich countries. A recent case report suggested
that cultural and family pressure contributed to the
mother’s inability to adhere to antiretroviral therapy
during pregnancy and breastfeeding with consequent
Canadian HIV Pregnancy Planning Guidelines
vertical transmission.17 Canadian laws with respect to the
criminal non-disclosure of HIV-positive status related to
sexual activity continue to evolve on the basis of case law.
In 1998 (R. v. Cuerrier,39) the Supreme Court of Canada
ruled that people living with HIV could be found guilty of
serious charges, such as aggravated assault, if they failed
to disclose their HIV status to sexual partners when there
was a significant risk of HIV transmission. According to
the Canadian HIV/AIDS Legal Network, charges in these
cases are becoming more serious: aggravated sexual assault,
(which carries a maximum penalty of life imprisonment),
and even murder.40
The Swiss have taken a different approach to criminalization
of HIV transmission. In a public statement published in
the Bulletin des Médecins Suisses41 Dr Pietro Vernazza and
colleagues argued that HIV-positive individuals on effective
antiretroviral treatment cannot transmit HIV through sexual
contact as long as the following criteria are met: the HIV-
positive person is adhering to cART under the supervision
of a medical doctor, his or her viral load has remained
undetectable in the previous 6 months, and the person
does not have another sexually transmitted infection. The
report concludes that unprotected sex between an HIV-
positive and an HIV-negative person does not constitute
criminal negligence if the above-mentioned criteria have
been met. This is in keeping with a UNAIDS policy brief42
stating that criminal charges against HIV-positive individuals
who transmit the virus through sexual contact cannot be
justified if the accused individual “took reasonable measures
to reduce risk of transmission.” In this case, reasonable
measures would include adherence to cART.
There is little information available on the effects of HIV
criminalization laws on pregnancy planning, but legal cases
do exist. In 2006, an HIV-positive woman in Hamilton,
Ontario, was convicted of failing to provide the necessities
of life for hiding her HIV-positive status from doctors,
preventing them from administering antiretroviral therapy
to her baby immediately after birth, which would have
significantly reduced the child’s risk of becoming infected.
The child tested HIV positive at 2 months of age, and the
mother was sentenced to a conditional 6-month sentence
to be served in the community.43
The imposition of criminal penalties for not disclosing
HIV-positive status before having otherwise consensual
sex will no doubt discourage HIV-positive people who are
thinking about starting a family. Although it is not illegal in
Canada for an HIV-positive man or woman to have children,
criminalization of non-disclosure might deter disclosure of
HIV status to health care providers and partners, and this
could result in unplanned pregnancies and limit access to
JUNE JOGC JUIN 2012 l 581
SOGC CLINICAL PRACTICE GUIDELINE
prenatal care and conception counselling. Ideally, doctors
and other health care providers should be involved from
pre-conception when women are HIV-positive, so routine
prevention measures can be planned in addition to cART
to decrease transmission rates.
A 1996 paper published by Williams et al. reviewed the
modest data available on reproductive decision-making in
HIV-positive women and found that awareness of their HIV
infection was not associated with pregnancy termination
or subsequent pregnancy prevention.44 This confirms the
fact that HIV-positive women are having and will continue
to have children, so health professionals must be prepared
to guide them in this process. There are ethical concerns
associated with all pregnancies and with conception and
assisted reproductive interventions, and these are addressed
in SOGC guidelines.22 Ethical considerations common
in HIV infection, such as the health of the prospective
parents and their financial ability to care for a child, are
reasonable and should be discussed with HIV-positive
individuals and couples. Many health care providers cite
“ethical” considerations when refusing to provide care.
These are often “perceived” ethical considerations, such as
concern that a child or partner will be infected with HIV,
or they are based on stereotypes associated with a history
of drug use. These perceptions generally arise from lack
of information or failure to review and/or accept current
scientific evidence on HIV transmission risk reduction.
Refusal to provide HIV transmission risk-reduction
services for people planning pregnancy is itself unethical
and contrary to the human right to non-discrimination and
the right to choose the number and spacing of children.45
Recommendations
10. All HIV-positive individuals should be counselled
on the possible legal ramifications of non-
disclosure of their HIV status to their sexual
partner(s). (III-A)
11. HIV-positive women who are considering
pregnancy should be counselled on the possibility
of legal action if they do not permit antiretroviral
therapy to be given to their baby after birth. (III-B)
12. Ethical considerations, including those related to
the health status of HIV-positive individuals or
couples, should be discussed during pre-conception
counselling. (III-B)
COMBINATION ANTIRETROVIRAL AND
OTHER DRUGS IN PREGNANCY PLANNING
A substantial body of evidence has shown that potent
cART not only prolongs the lives of people living with HIV
but also significantly reduces the risk of both horizontal
582 l JUNE JOGC JUIN 2012
and vertical HIV transmission, thus leading to a greater
number of people living with HIV having or planning to
have children.1–5,7–10 These breakthroughs affect both men
and women by reducing viral load to decrease the risk of
horizontal HIV transmission and, for women, the risk of
vertical transmission. It is well accepted that cART during
pregnancy should take into consideration the health of
both mother and child and that, with some exceptions,
cART is generally safe in pregnancy. The selection of
cART in pregnancy should consider drugs that are
effective in and tolerable to the mother and that are of
least toxicity to the fetus and newborn. Specifically, the
mother should be treated not only to prevent vertical HIV
transmission but also to ensure optimal therapy for herself.
Both the Canadian consensus guidelines for the care of
HIV-positive pregnant women, Putting Recommendations
into Practice, and the United States Department of Health
and Human Services guidelines recommend that women
who are not already on cART for their own health before
becoming pregnant can delay the initiation of therapy until
after the first trimester. Delaying treatment until the second
trimester is intended to reduce any theoretic teratogenic
effects of cART, which may be greater in the first trimester.
Fertility clinics generally require an HIV-positive woman to
be on a successful cART regimen before she seeks fertility
services, regardless of whether or not she requires cART
for her own health. This is supported by recently presented
conference abstract findings of the French cohort, which
show that initiation of cART before conception or early
in the first trimester led to the lowest vertical transmission
rate of 0% to 0.6 %.46
There is seldom discussion about the benefit of starting
cART during the pre-conception period for men and
women who do not require cART for their own health.
Treatment before conception is a horizontal risk-reduction
issue—as reduction in viral plasma load often correlates
to reduction of viral load in semen and vaginal fluid—and
should be discussed with the patient in all scenarios to
reduce risk to his or her HIV-negative partner or reduce
the risk of superinfection to his or her HIV-positive
partner.47–49
There are currently several ongoing studies looking
at the efficacy of HIV pre-exposure prophylaxis in
preventing HIV transmission to a non-infected partner in
a serodiscordant couple during conception. The United
States Centers for Disease Control and Prevention
published an interim guidance document for the use of
pre-exposure prophylaxis in men who have sex with men.50
This document is primarily based on the results of the
investigators for the Pre-Exposure Prophylaxis Initiative

study,51 which has shown pre-exposure prophylaxis to be
efficacious in this population. Currently, the Centers for
Disease Control and Prevention cautions against the use of
pre-exposure prophylaxis by women for HIV prevention,
as the FEM-PrEP Project (a study of pre-exposure
prophylaxis for HIV prevention among heterosexual
women)52 was stopped early because it was highly unlikely
to be able to demonstrate the effectiveness of Truvada
(emtricitabine and tenofovir disoproxil fumarate) in
preventing HIV infection in women.
There are many non-cART medications that people living
with HIV may be using to treat concurrent conditions,
including but not limited to hepatitis C and depression,
and adverse events from cART. Clinicians should review
all prescribed, over-the-counter, and complementary
therapies, as well as street drugs used by HIV-positive
individuals before conception. Most notably, treatment
for hepatitis C is considered to be teratogenic when used
by either male or female partners. Hepatitis C treatment
should be stopped at least 6 months before couples
attempt to conceive.
Recommendations
13. Clinicians should review all medications that
HIV-positive men and women may be using,
including antidepressants, pain medications, over-
the-counter medications, and hepatitis treatment,
to ensure that they are safe during conception and
pregnancy. (II-3A)
14. All HIV-positive men and women who require
combination antiretroviral therapy for their own
health during the pre-conception period should
be advised to continue their current regimens, but
women should not take any drugs that are potentially
teratogenic or considered toxic in pregnancy,
substituting other drugs when necessary or possible.
The most efficacious regimen that is safe in
pregnancy should be selected. (II-3A)
15. HIV-positive women who do not require combina­
tion antiretroviral therapy for their own health need
to consider starting treatment before becoming
pregnant or no later than late in the first trimester of
pregnancy. The most efficacious regimen that is safe
in pregnancy should be selected. (II-3A)
16. HIV-positive men and women who require
treatment should be encouraged to initiate
combination antiretroviral therapy during the pre-
conception period to reduce HIV plasma viral load,
which can reduce the risk of HIV transmission to
their HIV-negative partner or reduce the risk of
superinfection of their HIV-positive partner. (II-3B)
Canadian HIV Pregnancy Planning Guidelines
17. All decisions about the use of combination anti­
retroviral therapy and other drugs during pregnancy
should be made in consultation with experts such as
HIV specialists and pharmacists. (III-A)
OPTIONS FOR REDUCING RISK OF HORIZONTAL
HIV TRANSMISSION DURING CONCEPTION
HIV-positive couples and individuals who wish to conceive
a child need to consider the risk of horizontal HIV
transmission during conception. That risk depends on
a number of variables, including the HIV serostatus of
each partner (i.e., HIV-positive woman and HIV-negative
man or HIV-positive man and HIV-negative woman) and
the plasma viral load and level of drug-resistant virus of
each prospective parent. Couples and individuals should be
counselled thoroughly about all horizontal HIV transmission
risk-reduction methods before conception so they can make
an informed choice about which conception method is
most appropriate to their particular situation. Furthermore,
prospective parents should be informed about the rate of
success, availability, and cost of each conception option.
Timed Natural Conception
Natural conception has only recently been seen as an option
for people living with HIV. Although not for everyone,
natural conception is suitable in some circumstances,
and the nature of each individual case must be evaluated.
Prospective parents must have a frank discussion about
the risks of horizontal HIV transmission to make an
informed decision about this option. The relative risk of
horizontal HIV transmission involved in natural conception
is dependent on the plasma viral load of the HIV-positive
partner, the frequency of intercourse, the presence of
concurrent sexually transmitted infections, and which
partner is infected.41,52,53 People living with HIV who do not
have access to or who cannot afford assisted conception
services may be more likely to attempt natural conception.
Additionally, people living with HIV who fear stigma will be
associated with the use of assisted conception services may
be more likely to consider natural conception. More research
is needed to determine the factors considered when couples
decide to conceive naturally. In the case of an HIV-positive
man who is not taking cART, the risk of HIV transmission
to his uninfected female partner is quoted as 0.1% to 0.3%
per act of intercourse.54 This assumes that the couple is in a
stable relationship and that they are not participating in any
other form of high-risk activity.54 Without the intervention
of cART, the risk of transmission from an HIV-positive
woman to her uninfected male partner is reported to
be 0.03% to 0.09%.54 In general, plasma viral load may
be concordant with the viral load of genital secretions.
JUNE JOGC JUIN 2012 l 583
SOGC CLINICAL PRACTICE GUIDELINE
However, people living with HIV and their uninfected
partners should be counselled that this is not always the
case. cART further reduces the risk when long-term viral
suppression is achieved. Normally, the viral load in semen is
lower than that in blood; however, this is greatly influenced
by the use of cART, known to have optimal penetration of
the genital tract, as well as the absence of coexisting sexually
transmitted infections and the absence of drug resistance.55–57
It is possible to achieve an undetectable viral load in genital
secretions with the long-term use of cART; however, assays
to detect genital fluid viral load are not readily available.58
In early 2008, the Swiss Federal Commission for HIV/AIDS
issued a controversial statement authored by Vernazza et
al.,41 known as the Swiss Statement, claiming that an HIV-
infected person on antiretroviral therapy with completely
suppressed viremia (effective ART) is not sexually infectious
and cannot transmit HIV through sexual contact provided
that “the HIV-positive individual takes anti-retroviral therapy
consistently and as prescribed and is regularly followed by his/
her doctor; viral load is undetectable (i.e., < 40 copies/mL)
and has been so for at least 6 months; and the
HIV-positive individual does not have any sexually
transmitted infections.” Thus, although there remains a slight
risk of transmisson,59,60 some serodiscordant couples opt to
proceed with timed unprotected intercourse—only during
ovulation—to reduce the number of exposures to HIV
by the uninfected partner and to increase the probability
of conception. Women should be directed to health care
providers and the websites of relevant health care agencies
for information about timing ovulation. Ovulation timing
kits are available over the counter at most pharmacies.
Home Insemination
Home insemination is a particularly popular option for
conception for HIV-positive women with HIV-negative
partners and for same-sex female couples and single
HIV-positive women with access to donor sperm. The
procedure involves collecting sperm from a partner or
donor in a sterile container or a condom. The sperm is
drawn into a needle-less syringe and then inserted into the
vagina as close to the cervix as possible. Optimal results
are achieved when insemination is done during ovulation.
This is a particularly attractive method, as it is very low
cost and does not require the assistance of a fertility
specialist. If home insemination is unsuccessful after 3 to
6 months, HIV-positive women should be advised to seek
the assistance of a fertility specialist.
Sperm Washing
Sperm washing is a well-established, effective, and safe
risk-reduction fertility option for serodiscordant couples
in which the man is HIV-positive and the woman is
584 l JUNE JOGC JUIN 2012
HIV-negative and for seroconcordant couples when
superinfection is a concern. Semen is centrifuged to
separate live sperm (which do not carry HIV) from seminal
plasma and non-germinal cells (which may carry HIV) and
then inseminated into the female partner at the time of
ovulation. This practice is well supported by the literature,
which is extensive.12,61–75 In technical terms, sperm washing
involves centrifuging ejaculated semen in a 40% to 80%
colloidal silica density gradient to separate progressively
motile HIV-free sperm from non-sperm components
and seminal plasma, which remain in the supernatant.
The sperm pellet at the bottom is re-suspended in a fresh
medium and centrifuged twice before the preparation of
a final swim-up. There is no consensus among researchers
about the need to test washed sperm for detectable HIV
RNA before the sample is used. A nucleic-acid-based
sequence amplification (NASBA; Biomerieux, Basingstoke,
UK) or similar commercial assay can be used; however,
these assays are not commercially available in Canada. The
risk of the sample having detectable HIV is 3% to 6%. This
is because centrifugation fails to remove all of the seminal
plasma and leukocytes in a small proportion of cases. The
number of washes is limited because repeated centrifuging
leads to loss of sperm quality and quantity. A double-tube
technique has been proposed to increase yield and reduce
the need for post-wash HIV testing. Unfortunately, this
technique has not been adopted by the majority of centres
offering sperm washing, because it is not currently available
commercially. According to studies published to date, there
have been no reported cases of infection of the female
partner when sperm washing is carried out following the
reported published protocols in more than 3000 cycles of
sperm washing combined with intrauterine insemination,
in vitro fertilization and intracytoplasmic sperm injection.12
The results of a multicentre retrospective analysis of 1036
serodiscordant couples from 8 European centres offering
sperm washing reported 2840 IUI cycles, 107 IVF cycles,
394 ICSI cycles, and 49 frozen embryo transfers. At least
6 months post-treatment there was careful HIV follow-
up of the HIV-negative women. All tests recorded on the
women were negative (7.1% lost to follow-up), giving a
calculated probability of contamination equal to zero
(95% CI 0 to 0.09). Clinical pregnancy rates recorded with
all forms of treatment were comparable to those found in
cycles carried out in HIV-negative couples.76
IUI, IVF, and ICSI
IUI, IVF, and ICSI are fertility techniques that can reduce
the risk of HIV transmission to the uninfected partner.
IUI is most commonly used and is combined with sperm
washing if the male partner is HIV positive. This process
involves placing prepared sperm directly into the uterus

during ovulation. For couples who wish to further reduce
the risk of horizontal HIV transmission or for those who
have infertility issues, sperm washing can be combined
with ovulation induction, IVF, or ICSI.
IVF refers to the procedure whereby oocytes are exposed
to spermatozoa outside the uterus, and a fertilized embryo
is returned to the uterus for the gestation period.
Some studies have shown that because ICSI involves
fertilization with only one sperm, the risk of possible HIV
transmission in serodiscordant couples should be lower
than with traditional assisted reproductive technology
methods. This is because in traditional IUI women receive
millions of spermatozoa, and in classic IVF the oocytes
are exposed to thousands of spermatozoa.77
Both IVF and ICSI are very expensive, costing up to
$15 000 per cycle, making these procedures inaccessible to
many people living with HIV.
A 2003 meta-analysis assessing the efficacy of assisted
reproductive technologies in serodiscordant couples
found they were less successful in the group in which the
female partner was infected, with an overall pregnancy rate
per assisted reproductive technology attempt of 6.7%.
No pregnancies resulted from the IUI attempts, while 2
pregnancies resulted from the IVF and ICSI attempts.66
A 2007 study examining the safety and effectiveness of
assisted reproduction (IUI, IVF, and ICSI) using sperm
washing for HIV-1 serodiscordant couples in which the
male partner was infected showed pregnancy resulting in
580 of 3315 cycles. Throughout the period of treatment, all
couples were required to use condoms during intercourse.
IUI was the most frequently used procedure, representing
84% of procedure use. Out of the 580 pregnancies, there
were 112 miscarriages, 8 extra-uterine pregnancies, 2
pregnancy terminations and 1 intrauterine death. Overall,
no transmission of HIV to the female partner was
observed with complete follow-up information in 967 out
of 1036 cases.67
Sperm Donation, Egg Donation, and Surrogacy
Sperm donation, egg donation, and surrogacy are
discussed in depth in a joint policy statement on ethical
issues in assisted reproduction prepared by the Society
of Obstetricians and Gynaecologists of Canada and the
Canadian Fertility and Andrology Society.19 However, these
policies do not directly address the issues of people living
with HIV.78 Sperm donation is available to the uninfected
partners of HIV-positive men and to HIV-positive women.
Surrogacy is not currently an option in Canada for HIV-
positive single men or HIV-positive men in a same-sex
Canadian HIV Pregnancy Planning Guidelines
couple. Sperm donation by HIV-positive men is restricted
by Canadian law; however, it may be possible through the
Donor Semen Special Access Program when the recipient
is known to the donor. Further information is available
from Assisted Human Reproduction Canada and fertility
specialists. HIV-positive individuals and couples who
require sperm donation, egg donation, or a surrogate are
likely to require legal advice and contracts.
Adoption
Adoption is a legal and social process. It involves the
transferring of rights over a child from birth parents
to adoptive parents. In Canada, adoption is regulated
provincially, so requirements vary depending upon
geographical location. They may also differ depending
upon whether the adoption is undertaken privately or
through the public system, or is international.79 No current
data are available on the success rate of adoption in Canada
if one or both prospective parents are HIV positive. In
the United States, Lambda Legal has successfully assisted
same-sex couples and people living with HIV to adopt
children.
SCENARIO-BASED RECOMMENDATIONS FOR THE
PREVENTION OF HORIZONTAL HIV TRANSMISSION
The scenario-based recommendations are intended to
guide health care providers during the pre-conception
counselling process. All options, including risks and
benefits, should be presented to prospective parents
to facilitate informed decision making. Although the
recommendations are based on expert opinion of the
safest and most practical option for most individuals
and couples, they may not always be the most practical
or preferred option for some patients, depending on
availability of services, cost, cultural beliefs, and personal
preference. In these cases, physicians and other health care
providers should provide non-judgemental support of the
decision of the patient(s) involved.
HIV-Positive Woman and HIV-Negative Man
HIV serodiscordant couples in which the woman is HIV
positive and the man is HIV negative should be counselled
on the risks and benefits of timed natural conception, home
insemination, IUI, IVF, ICSI, the option of a gestational
carrier or true surrogate, and adoption.
Recommendations
18. For serodiscordant couples in which the woman
is HIV positive, it is preferable to attempt home
insemination with the partner’s sperm during
ovulation for 3 to 6 months before considering
other methods. (III-A)
JUNE JOGC JUIN 2012 l 585
SOGC CLINICAL PRACTICE GUIDELINE
19. If home insemination is unsuccessful, couples
should be referred to a gynaecologist for
consultation and then to a fertility specialist for
a complete fertility work-up and appropriate
treatment when necessary, including counselling on
all assisted reproductive technologies if pregnancy
is not achieved in 6 to 12 months. (III-A)
HIV-Positive Single Woman or HIV-Positive
Woman in a Same-Sex Relationship
HIV-positive single women or HIV-positive women in a
same-sex relationship should be counselled on the risks
and benefits of home insemination with donor sperm
(known donor or purchased sperm), IUI with donor
sperm, IVF with donor sperm, ICSI with donor sperm,
and the option of a gestational carrier or true surrogate
with donor sperm, and adoption.
Recommendation
20. Single HIV-positive women or HIV-positive
women in a same-sex relationship should be
referred to a fertility specialist and should
consider the option of intrauterine insemination
with HIV-negative donor sperm. This option is
preferred over home insemination with donor
sperm because the cost of sperm is high and
intrauterine insemination performed in a fertility
clinic has a higher success rate than home
insemination. If sperm from a known donor is
used for intrauterine insemination, regulations
applicable to the donation of sperm must be
followed. (III-A)
HIV-Positive Man and HIV-Negative Woman
HIV serodiscordant couples in which the male partner
is HIV positive should be counselled on the risks and
benefits of timed natural conception, home insemination,
IUI with sperm washing or donor sperm, IVF with sperm
washing or donor sperm, ICSI with sperm washing or
donor sperm, and adoption.
Recommendations
21. Serodiscordant couples in which the man is
HIV positive should be referred to a fertility
specialist and should consider the preferred
option of sperm washing with intrauterine
insemination. (II-2A)
22. If intrauterine insemination is unsuccessful,
couples should consider in vitro fertilization or
intracytoplasmic sperm injection with either sperm
washing or the use of donor sperm. (II-3A)
586 l JUNE JOGC JUIN 2012
23. HIV-positive men who do not require combination
antiretroviral therapy for their own health
should be encouraged to initiate combination
antiretroviral therapy during the pre-conception
period to reduce HIV plasma viral load, which
can reduce the risk of HIV transmission to their
HIV-negative partner. (II-3B)
HIV-Positive Single Man or Male Same-Sex Couple
Recommendation
24. HIV-positive single men or men in same-sex
relationships who have an HIV-negative or
HIV-positive surrogate should be referred to a
fertility specialist. (III-A)
HIV-Positive Man and HIV-Positive Woman
Heterosexual couples in which both partners are HIV
positive should be counselled on the risks and benefits
of timed natural conception, IUI with sperm washing,
IVF with sperm washing, ICSI with sperm washing, and
adoption.
Recommendations
25. Timed natural conception is recommended
for seroconcordant couples who are taking
combination antiretroviral therapy and who have
fully suppressed HIV plasma viral loads. (II-3A)
26. Seroconcordant couples should be counselled on
the risks and benefits of timed natural conception
(including HIV superinfection and transmission of
drug-resistant strains of HIV). (II-3A)
27. If timed natural conception is unsuccessful,
couples should be referred to a gynaecologist
for consultation and then to a fertility specialist
for a complete fertility work-up and appropriate
treatment when necessary, including counselling on
all assisted reproductive technologies. (III-A)
FERTILITY ISSUES IN THE CONTEXT OF HIV AND
HIV INFECTION CONTROL IN FERTILITY CLINICS
Infertility Investigations and Treatment
Historically, fertility clinics in Canada have been reluctant
to provide fertility investigation and treatment to people
living with HIV. Fertility experts concur that this has likely
been due to lack of information about HIV and concern
that serving people living with HIV could deter HIV-
negative individuals from accessing services. However, it
is common practice in many fertility clinics across Canada
to offer investigation, treatment, and storage of potentially
infected specimens to people with other infectious diseases

such as hepatitis B and C, and similar practices can be
applied to the handling of HIV-infected materials.
As all fertility clinics should be operating using Canadian
Standards Association procedures for universal
precautions and infection control, there are no scientific
grounds on which to refuse services to people living with HIV.
Recommendations
28. HIV-positive people should be counselled about
fertility problems that occur in the general
population, including genetic disorders and
advancing maternal age. (III-A)
29. Infertility investigations and treatment should be
offered to HIV- positive people if required. (III-A)
30. All decisions about combination antiretroviral
therapy during the pre-conception period and
during pregnancy should consider the health of
the HIV-positive person and reduction of the risk
of horizontal and vertical transmission of HIV.
Decisions about combination antiretroviral therapy
should be made in consultation with an HIV
specialist. (III-A)
HIV Infection Control in Fertility Clinics
Fertility laboratories routinely treat all samples as potentially
infectious, in accordance with the Canadian Standards
Association guidelines, for the protection of both health
care workers and patients. Storage of potentially infectious
materials in segregated containers and incubators may
slightly decrease the risk of HIV contamination.
Recommendations
31. Fertility laboratories should follow Canadian
Standards Association guidelines for infection control
when handling HIV-positive materials. (III-A)
32. Potentially infectious materials should be stored in
segregated containers and incubators to reduce the
risk of HIV contamination. (III-A)
33. Bio-containment straws for specimen storage
should be used to further reduce the risk of cross-
contamination of samples. (III-A)
APPLICABILITY
There are potential barriers to applying the recommendations
outlined in these guidelines. Fertility services are not available
to HIV-positive individuals and couples in all provinces.13
Additionally, many of the fertility services recommended
in these guidelines are expensive and not covered by most
provincial or private health insurance coverage and are
therefore inaccessible to many people living with HIV.
Canadian HIV Pregnancy Planning Guidelines
SUMMARY
The implementation of these guidelines will assist HIV-
positive individuals and couples with their fertility and
pregnancy planning needs through the provision of clinical
information and recommendations. It will also reduce
the risk of transmission of HIV between partners and
transmission from mother to child and will increase the
rate of pregnancy planning in the HIV-positive population
by providing safer options for conception, reducing the
stigma associated with pregnancy and HIV, and improving
access to pregnancy planning and fertility services.
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Appendix. Canadian HIV Pregnancy Planning Guideline Development Team Core
Working Group
William Cameron, MD, Ottawa ON
Adriana Carvalhal, MD, Hamilton ON
Sandra Ka Hon Chu, LLM, Toronto ON
Anthony Cheung, MD, Vancouver BC
Michael Dahan, MD, Montreal QC
Alexandra de Pokomandy, MD, Montreal QC
Believe Dhliwayo, Toronto ON
Mathias Gysler, MD, Mississauga ON
David Haase, MBBS, Halifax NS
Scot Hamilton, PhD, Mississauga ON
Precious Hove, Toronto ON
Denise Jaworsky, MD, Toronto ON
Marina Klein, MD, Montreal QC
Julie LaPrise, Mississauga ON
Marc LaPrise, Mississauga ON
Kecia Larkin, Vancouver BC
Clifford Librach, MD, Toronto ON
590 l JUNE JOGC JUIN 2012
Mona R. Loutfy, MD, Toronto ON
Julie Maggi, MD, Toronto ON
Shari Margolese, Toronto ON
John Maxwell, BA, Toronto ON
Jay MacGillivray, RM, Toronto ON
David McLay, PhD, Toronto ON
Shauna McQuarrie, MD, Winnipeg MB
Deborah M. Money, MD, Vancouver BC
Marvelous Muchenje, Toronto ON
Tamer Said, MD, Toronto ON
Robyn Salter, MSW, Toronto ON
Vyta Senikas, MD, Ottawa ON
Heather Shapiro, MD, Toronto ON
Sharon Walmsley, MD, Toronto ON
Joanna Wong, Toronto ON
Mark H. Yudin, MD, Toronto ON
 SOGC COMMITTEE OPINION

No. 281, October 2012

Classification of Caesarean Sections in Canada:

The Modified Robson Criteria
Abstract
This committee opinion has been prepared by the Maternal
Fetal Medicine Committee, reviewed by the Clinical Practice Objective: To advocate for the use of a common classification
Obstetrics Committee, and approved by the Executive and system for Caesarean section across Canada.
Council of the Society of Obstetricians and Gynaecologists
of Canada. Options: A variety of clinical parameters for classification were
considered.
PRINCIPAL AUTHORS
Outcomes: Consideration of a common system for classifying
Dan Farine, MD, Toronto ON Caesarean section.
Debra Shepherd, MD, Regina SK
Evidence: Studies published in English from 1976 to December 2011
SPECIAL CONTRIBUTOR were retrieved through searches of Medline and PubMed, using
appropriate controlled vocabulary and key words (Caesarean
Michael Robson, MD, Dublin, Ireland
section, vaginal birth after Caesarean, classification). Results
MATERNAL FETAL MEDICINE COMMITTEE were restricted to systematic reviews, randomized control
Robert Gagnon, MD (Chair), Montreal QC trials/controlled clinical trials, and observational studies. Grey
(unpublished) literature was identified through searching the web
Lynda Hudon, MD (Co-Chair), Montreal QC sites of health technology assessment and health technology
Melanie Basso, RN, Vancouver BC assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and the web sites of national
Hayley Bos, MD, London ON and international medical specialty societies.
Gregory Davies, MD, Kingston ON
Values: The studies reviewed were classified according to criteria
Marie-France Delisle, MD, Vancouver BC described by the Canadian Task Force on Preventive Health Care,
and the recommendation for practice ranked according to this
Dan Farine, MD, Toronto ON
classification (Table 1).
Savas Menticoglou, MD, Winnipeg MB
Sponsors: The Society of Obstetricians and Gynaecologists of
William Mundle, MD, Windsor ON Canada.
Lynn Murphy-Kaulbeck, MD, Allison NB
Annie Ouellet, MD, Sherbrooke QC Recommendation

Tracy Pressey, MD, Vancouver BC Modified Robson criteria should be used to enable comparison of
Caesarean section rates and indications. (III-B)
Anne Roggensack, MD, Calgary AB
Frank Sanderson, MD, Saint John NB
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all authors and
members of the committee.

Key Words: Caesarean section, vaginal birth after Caesarean,

VBAC, classification
J Obstet Gynaecol Can 2012;34(10):976–979

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

976 l OCTOBER JOGC OCTOBRE 2012

 Classification of Caesarean Sections in Canada: The Modified Robson Criteria
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.14
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.14
TRENDS IN CAESAREAN SECTION RATES
T he Caesarean section rate has been increasing during
the last 50 years.1 The rate was 5% in the 1940s and
1950s and remained unchanged for 10 to 15 years. In the
late 1970s, the rate rose to 15% and remained unchanged
for the next 10 years. In the last decade there has been a
dramatic increase in the Caesarean section rate worldwide,
which now exceeds 30% in some regions.1 The latest
Statistics Canada Caesarean section rate published in 2009
is 26.8%, with provincial rates ranging from 20.2% in
Manitoba to 31.5% in Newfoundland and Labrador.2
Although several guidelines, including those issued by the
World Health Organization3 and the United States Healthy
People 2000 initiative,4 suggest that the optimal Caesarean
section rate is 15%, there seems to be little effect on the
current Caesarean section rate.
THE CURRENT METHODS OF
ASSESSING CAESAREAN SECTION RATES
Currently the heterogeneity of Caesarean section
classification does not allow valid comparisons. Specifically,
there is a lack of clarity regarding operative indications and
relevant obstetric history.
The classification of Caesarean sections should
1. Be relevant to obstetric care providers.
2. Include all Caesarean sections.
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
3. Be easily derived from current obstetric databases.
4. Have mutually exclusive criteria so each Caesarean
section falls into a single class.
5. Allow detailed analysis without excessive complexity.
6. Be applicable for local, regional, national, and
international use.
A common classification system allows reflection and
research at the local, regional, and national levels to
better guide future care. Michael Robson, MD, has
developed such a classification system.5,6 This system’s
criteria are widely used in the United Kingdom, Ireland,
and Scandinavia and in many centres worldwide,7–10
and this classification system has already been used in
Canada.11,12 A recent meta-analysis comparing different
classifications of Caesarean section concluded that
the 10-group Robson classification was optimal.13 A
modification to the Robson criteria is proposed for
Canadian use (Table 2). This modification includes sub-
classification of women having Caesarean section after
spontaneous onset of labour, after induction of labour,
and before labour.
Recommendation
Modified Robson criteria should be used to
enable comparison of Caesarean section rates and
indications. (III-B)
OCTOBER JOGC OCTOBRE 2012 l 977
SOGC COMMITTEE OPINION

Table 2. The modified Robson criteria

Group Description
1 Nullipara, singleton cephalic, ≥ 37 weeks, spontaneous labour
2 Nullipara, singleton cephalic, ≥ 37 weeks
A: Induced
B: Caesarean section before labour

3 Multipara, singleton cephalic, ≥ 37 weeks, spontaneous labour

4 Multipara, singleton cephalic, ≥ 37 weeks
A: Induced
B: Caesarean section before labour
5 Previous Caesarean section, singleton cephalic, ≥ 37 weeks
A: Spontaneous labour
B: Induced labour
C: Caesarean section before labour

6 All nulliparous breeches

A: Spontaneous labour
B: Induced labour
C: Caesarean section before labour
7 All multiparous breeches
(including previous Caesarean section)
A: Spontaneous labour
B: Induced labour
C: Caesarean section before labour

8 All multiple pregnancies

(including previous Caesarean section)
A: Spontaneous labour
B: Induced labour
C: Caesarean section before labour
9 All abnormal lies
(including previous Caesarean section but excluding breech)
A: Spontaneous labour
B: Induced labour
C: Caesarean Section before labour
10 All singleton cephalic, ≤ 36 weeks
(including previous Caesarean section)
A: Spontaneous labour
B: Induced labour
C: Caesarean section before labour

SUMMARY 3. [No authors listed]. Appropriate technology for birth. Lancet

A common classification of Caesarean section rates and
indications allows evaluation and comparison of the
contributors to the Caesarean section rate and their impact.
It also allows comparison between institutions, regions,
and countries that adopt this classification.
REFERENCES
1. National Institutes of Health state-of-the-science conference statement.
Cesarean delivery on maternal request. Obstet Gynecol 2006;107:1386–97.
1985;2:436–7.
4. Department of Health and Human Services; Centers for Disease Control
and Prevention; National Center for Health Statistics. Healthy People
2000: national health promotion and disease prevention objectives: Full
report, with commentary (DHHS publication no. (PHS) 91–50212).
Washington: Government Printing Office; 1990:378.
5. Robson MS. Classification of caesarean sections. Fetal and Maternal
Medicine Review 2001;12(1):23–39.
6. Robson MS, Scudamore IW, Walsh SM. Using the medical audit
cycle to reduce caesarean section rates. Am J Obstet Gynecol
1996;174(1):199–205.

2. Canadian Institute for Health Information. Health indicators interactive 7. Brennan DJ, Robson MS. Murphy M, O’Herlihy C. Comparative analysis
tool: Caesarean section rates; 1997–2009. Ottawa: CIHI. Available at: of international cesarean delivery rates using 10-group classification
http://www.cihi.ca/hirpt/?language=en&healthIndicatorSelection=Csec. identifies significant variation in spontaneous labor. Am J Obstet Gynecol
Accessed August 8, 2012. 2009;201(3):308.e1–8.

978 l OCTOBER JOGC OCTOBRE 2012

 Classification of Caesarean Sections in Canada: The Modified Robson Criteria

8. McCarthy FP, Rigg L, Cady L, Cullinane F. A new way of looking at
Caesarean section births. Aust N Z J Obstet Gynaecol 2007;47(4):316–20.
9. Nesheim BI, Eskild A, Gjessing L. Does allocation of low risk parturient
women to a separate maternity unit decrease the risk of emergency
cesarean section? Acta Obstet Gynecol Scand 2010;89(6):813–6.
10. Betrán AP, Gulmezoglu AM, Robson M, Merialdi M, Souza JP, Wojdyla D,
et al. WHO global survey on maternal and perinatal health in Latin
America: classifying caesarean sections. Reprod Health 2009;6:18.
11. The Maternal Newborn Services Task Force, Child Health Network
for the Greater Toronto Area. The birthing review project. Application of
the Robson classification of cesarean sections. In focus: Robson groups
1 & 2. Toronto: Child Health Network for the Greater Toronto Area; April
2010. Available at: http://www.childhealthnetwork.com/documents/
CHN-BirthingReview-Phase1-Apri12010.pdf. Accessed August 8, 2012.
12. Perinatal Services BC. Examining cesarean delivery rates in
British Columbia using the Robson ten classification. Part
1: understanding the ten groups. A Perinatal Services BC
surveillance special report. Perinatal Services BC: December
2011;1(4). Available at: http://www.perinatalservicesbc.ca/NR/
rdonlyres/3CE464BF-3538–4A78-BA51–451987FDD2EF/0/
SurveillanceSpecialReportRobsonTenClassificationDec2011.pdf.
Accessed August 8, 2012.
13. Torloni MR, Betran AP, Souza JP, Widmer M, Allen T, Gulmezoglu M,
et al. Classifications for cesarean section: a systematic review. PLoS One.
2011;6(1):e14566.
14. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for
recommendations from the Canadian Task Force on Preventive Health
Care. CMAJ 2003;169:207–8.

Limitations of the Modified Robson Criteria

1. This classification does not allow the analysis of Caesarean section

by demand and indicated Caesarean section for specific conditions
(e.g., placenta previa).
2. This classification does not account for pre-existing medical, surgical
or fetal disease; indications for and methods used for induction of
labour; and degrees of prematurity, all of which may influence the
rate of Caesarean section.
3. Group 5 includes 2 quite different groups: (1) those who planned or
needed a repeat Caesarean section, and (2) those who attempted
VBAC and required Caesarean section.
This classification system should be considered flexible. Interested parties
may choose to further sub-classify the major categories to address specific
research and clinical issues.

OCTOBER JOGC OCTOBRE 2012 l 979

 SOGC Committee Opinion
Delayed Child-Bearing
This Committee Opinion has been prepared by the Genetics
Committee, reviewed by the Reproductive Endocrinology
and Infertility Committee, and approved by the Executive
and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHOR
Jo-Ann Johnson, MD, Calgary AB
Suzanne Tough, PhD, Calgary AB
SOGC GENETICS COMMITTEE
R. Douglas Wilson, MD (Chair), Calgary AB
François Audibert, MD, Montreal QC
Claire Blight, RN, Dartmouth NS
Jo-Ann Brock, MD, Halifax NS
Lola Cartier, MSc, CCGC, Montreal QC
Valérie A. Désilets, MD, Montreal QC
Alain Gagnon, MD, Vancouver BC
Sylvie Langlois, MD, Vancouver BC
Lynn Murphy-Kaulbeck, MD, Moncton NB
Nanette Okun, MD, Toronto ON
The literature searches and bibliographic support for this
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
Disclosure statements have been received from all members of
the committee.
J Obstet Gynaecol Can 2012;34(1):80–93
Key Words: Maternal age, delayed child-bearing, reproductive
technology, oocyte donation, late maternal age
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
80 l JANUARY JOGC JANVIER 2012
No. 271, January 2012
Abstract
Objective: To provide an overview of delayed child-bearing and to
describe the implications for women and health care providers.
Options: Delayed child-bearing, which has increased greatly in
recent decades, is associated with an increased risk of infertility,
pregnancy complications, and adverse pregnancy outcome. This
guideline provides information that will optimize the counselling and
care of Canadian women with respect to their reproductive choices.
Outcomes: Maternal age is the most important determinant of fertility,
and obstetric and perinatal risks increase with maternal age.
Many women are unaware of the success rates or limitations of
assisted reproductive technology and of the increased medical
risks of delayed child-bearing, including multiple births, preterm
delivery, stillbirth, and Caesarean section. This guideline provides
a framework to address these issues.
Evidence: Studies published between 2000 and August 2010 were
retrieved through searches of PubMed and the Cochrane Library
using appropriate key words (delayed child-bearing, deferred
pregnancy, maternal age, assisted reproductive technology,
infertility, and multiple births) and MeSH terms (maternal age,
reproductive behaviour, fertility). The Internet was also searched
using similar key words, and national and international medical
specialty societies were searched for clinical practice guidelines
and position statements. Data were extracted based on the aims,
sample, authors, year, and results.
Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Care (Table 1).
Sponsor: The Society of Obstetricians and Gynaecologists of
Canada.
Recommendations
1. Women who delay child-bearing are at increased risk of infertility.
Prospective parents, especially women, should know that their
fecundity and fertility begin to decline significantly after 32 years of
age. Prospective parents should know that assisted reproductive
technologies cannot guarantee a live birth or completely
compensate for age-related decline in fertility. (II-2A)
2. A fertility evaluation should be initiated after 6 months of
unprotected intercourse without conception in women 35 to 37
years of age, and earlier in women > 37 years of age. (II-2A)
3. Prospective parents should be informed that semen quality and
male fertility deteriorate with advancing age and that the risk of
genetic disorders in offspring increases. (II-2A)

4. Women ≥ 35 years of age should be offered screening for fetal
aneuploidy and undergo a detailed second trimester ultrasound
examination to look for significant fetal birth defects (particularly
cardiac defects). (II-1A)
5. Delayed child-bearing is associated with increased obstetrical and
perinatal complications. Care providers need to be aware of these
complications and adjust obstetrical management protocols to
ensure optimal maternal and perinatal outcomes. (II-2A)
6. All adults of reproductive age should be aware of the obstetrical
and perinatal risks of advanced maternal age so they can make
informed decisions about the timing of child-bearing. (II-2A)
7. Strategies to improve informed decision-making by prospective
parents should be designed, implemented, and evaluated. These
strategies should provide opportunity for adults to understand the
potential medical, social, and economic consequences of child-
bearing throughout the reproductive years. (III-B)
8. Barriers to healthy reproduction, including workplace policies,
should be reviewed to optimize the likelihood of healthy
pregnancies. (III-C)
INTRODUCTION
T here is a growing trend in Canada for child-bearing
to occur later in women’s lives. Not only are more
women aged > 30 years giving birth, but the proportion of
first births occurring among women aged > 30 has been
increasing steadily over the past 20 years.1 Currently, 11%
of first births occur in women aged ≥ 35 years.1 This trend
towards delayed child-bearing is also occurring in Western
Europe, Australia, New Zealand, and the United States.2
Many of the reasons why women are choosing to postpone
child-bearing reflect the availability of safe, effective, and
reversible contraception, which has allowed women the
reproductive autonomy to decide if and when they will
have children. Biologically, the optimum period for child-
bearing is between 20 and 35 years of age. After 35 years
of age, fecundity decreases, and the chance of miscarriage,
spontaneous abortion, pregnancy complications, and
adverse pregnancy outcomes (including PTD and multiple
birth) increases.3 As women age, many opt for fertility
treatment to improve their chance of conception. The
effectiveness of various reproductive technologies declines
steadily after the age of 35, while the risk of pregnancy
complications and adverse outcome increases with both
ABBREVIATIONS
ART assisted reproductive technology
OR odds ratio
ICSI intracytoplasmic sperm injection
IUI intrauterine insemination
LBW low birth weight
PTD preterm delivery
SGA small for gestational age
Delayed Child-Bearing
maternal age and the use of reproductive assistance.4,5
These pregnancy complications include ectopic pregnancy,
spontaneous abortion, fetal chromosomal abnormalities,
certain congenital anomalies, placenta previa, gestational
diabetes, preeclampsia, multiple births, PTD, and Caesarean
section. These in turn are associated with an increased risk
of preterm birth and perinatal and maternal mortality and
morbidity.6–10 Infants born preterm, especially multiples,
are at increased risk of morbidity, mortality, and long-term
disability.
If the trend towards delayed child-bearing continues, society
can anticipate increased demand for reproductive assistance
and associated increases in the need for more sophisticated
prenatal, postpartum, and early development care. While a
short delay in age at parenting poses little absolute risk for
the individual woman, small shifts in population distribution
curves affect large numbers of women, which has important
implications for the health care system.
The SOGC hopes to alert care providers to the implications
of this emerging public health issue and supports the
urgent need for better public information to enable more
informed reproductive choices.
DEFINITION OF DELAYED CHILD-BEARING
Fertility declines with increasing maternal age, especially
after the mid-30s. For this reason, delayed child-bearing
is traditionally defined as pregnancy occurring in women
aged ≥ 35 years. This population has been referred to
as advanced maternal age or late maternal age. In recent
years, advances in ART have challenged the traditional
age-related boundaries of reproduction, enabling even
postmenopausal women to conceive and give birth.11
Before ART, the oldest naturally conceived pregnancy
was in a 57-year-old woman.12 With use of ART and
donor oocytes, the birth rate in older mothers has risen
dramatically, and in one case, a 70-year-old woman has
given birth. These women are defined as “very advanced
maternal age” (44 years of age or older), “mature” gravida,
or “extremely elderly” gravida.
INCIDENCE OF DELAYED CHILD-BEARING
Currently, the average age of a woman giving birth in Canada is
29 years, which represents a significant increase from previous
decades.7 The proportion of first births occurring among
women aged ≥ 35 has also increased from 4% in 1987 to
11% in 2005. At the same time, the proportion of first births
occurring among women between 30 and 34 years increased
from 18.9% in 1982 to 31.4% in 2006, and for the first time,
JANUARY JOGC JANVIER 2012 l 81
SOGC Committee Opinion
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.101
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.101
the fertility rate of 30- to 34-year-old women exceeded the
rate for women aged 25 to 29 years.13 Over the same time
period, the proportion of live births to women between the
ages of 35 to 39 and 40 to 44 years also increased, from 4.7%
to 14.8%, and from 0.6% to 2.8% respectively.14
As women delay child-bearing and age at first birth
increases, the total number of births to each woman
decreases, and the size, composition, and future growth
of the population is affected. The postponement of first
births has been associated with smaller family sizes and
increased childlessness, all of which contribute to the overall
decline in fertility rate as experienced in Canada and other
countries, including Spain, Sweden, the United Kingdom,
and Australia. In Canada the fertility rate (average number
of children per woman) of 1.66 (2007) is well below the
replacement level of 2.1 children per woman.15
CAUSES OF DELAYED CHILD-BEARING
A number of factors have been proposed in the demographic
and sociological literature to explain the phenomenon of
delayed child-bearing, including safe, effective contraception,
changes in societal expectations of women in post-secondary
education and the workforce, and an increased population
of women 35 to 44 years of age.12
Indeed, maternal education has been identified as one of
the strongest predictors of use of contraception, timing of
child-bearing, and the total number of children a woman
will bear. In a study by Tough et al., financial security and
82 l JANUARY JOGC JANVIER 2012
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
relationship factors (e.g., partner’s interest in and suitability
for parenting) ranked as the 2 most important factors
influencing readiness for child-bearing.16
A false sense of security is associated with advances in
ART, and most women are unaware that technology cannot
compensate completely for the effects of reproductive
aging, except potentially through oocyte donation. A recent
survey of 360 Canadian undergraduate women assessing
their understanding of reproductive aging found that while
most were aware of the drop in fertility with age, they
significantly overestimated the likelihood of pregnancy at
all ages and were not aware of the steep rate of fertility
decline with age. These women also overestimated the
chance of pregnancy loss at all ages, but they did not
identify a woman’s age as the strongest risk factor for this
event.17
CONSEQUENCES OF DELAYED CHILD-BEARING
Delayed child-bearing is associated with an increased risk
of infertility, maternal comorbidity, pregnancy and birth
complications, and increased maternal and fetal morbidity
and mortality. Women who start their families in their 20s
and complete them by age 35 face significantly reduced risks.
MATERNAL AGE-RELATED SUBFERTILITY
Advancing maternal age is associated with a longer
average time to achieve conception.18 Fecundability (i.e.,
the probability of achieving a pregnancy in one menstrual

Figure 1. Natural conception: schematic demonstrating trends in
pregnancy and miscarriage rates according to age
35
30
Percentage Pregnancy per Month
25
20
15
10
5 10
0 0
22 24
Reproductive Ageing: Guidelines for First Line Physicians for Investigation of Infertility Problems
(Canadian Fertility and Andrology Society;2004). Used with permission.
cycle) begins to decline significantly in the early 30s (about
age 32), and typically subfecundability becomes more
evident by age 37.19
The influence of female age on fertility has been clearly
established by a number of observational studies that have
consistently demonstrated a decline in pregnancy rates
with advancing maternal age (Figure 1).7,20–22 Furthermore,
cycles that result in pregnancy are less likely to progress
to live births because of higher rates of aneuploidy and
spontaneous abortion among older women.19
The progressive decrease in the number and quality of
oocytes from fetal life until menopause is the cause of the
age-related decline in female fertility. The oocyte pool peaks
while the female fetus is in utero, reaching approximately
6 to 7 million at 20 weeks of gestation.23 Subsequently,
progressive atresia occurs so that the number of remaining
oocytes is approximately 1 to 2 million at birth and
250 000 at the onset of puberty. During the reproductive
years, there is continued atresia, which occurs at an
accelerated rate after the age of 37 in the average woman.18
The average age of menopause is 51, at which time
approximately 1000 oocytes remain.
As the number of oocytes declines, so too does the quality,
eventually reaching a threshold below which pregnancy is no
longer possible. The decrease in quality is primarily due to
an increased prevalence of aneuploid oocytes.18 Autosomal
trisomy is the most frequent finding and is thought to be
associated with age-related changes in the meiotic spindle that
predispose to non-disjunction.24 Chromosomally abnormal
embryos account for the lower chances of pregnancy and
the higher rates of spontaneous abortion.
Delayed Child-Bearing
70
60
50
Percentage Pregnancies that Miscarry
40
30
20
26 28 30 32 34 36 38 40 42 44 46
Age of Woman
In addition to ovarian factors, older women have an
increased probability of underlying medical pathology that
adversely affects fertility, such as endometriosis, fibroids,
tubal disease, and polyps. These and other pathologies
increase the likelihood of a history of ovarian surgery,
radiation, or chemotherapy, which are threats to fertility.
Older women are more likely to be obese, to have a chronic
medical condition, and to have lifestyle issues, including
decreased coital frequency, all of which may affect fertility.
INCREASED USE OF
REPRODUCTIVE TECHNOLOGY
Women who delay child-bearing fall into 3 broad categories:
(1) those who conceive without intervention, (2) those who
still have fertilizable oocytes and conceive through use
of ART, and (3) those who conceive after egg donation.
Women who are < 37 years of age should be supported
with expectant management for up to 6 months, after which
a referral should be offered. For women aged ≥ 37, referral
to a specialist is recommended without waiting 6 months
for “spontaneous” conception, because ovarian reserve
can further deplete during the waiting period. For women
in categories 2 and 3, active treatment options may be
initiated after appropriate investigations (which are beyond
the scope of this guideline); these include controlled
ovarian hyperstimulation with IUI, in vitro fertilization,
and oocyte donation. While IUI and IVF can accelerate
the time to conception, they cannot compensate for the
natural decline of fertility due to age. With increasing
maternal age, the chance of a woman progressing from
the beginning of ART treatment to pregnancy and live
birth using her own eggs decreases at every stage of ART
JANUARY JOGC JANVIER 2012 l 83
SOGC Committee Opinion

Figure 2. Percentages of transfers that resulted in live births for ART cycles
using fresh embryos from own and donor eggs, by ART patient’s age, 2006

70

60 Donor eggs

Live births per transfer, percent

50

40

30
Own eggs
20

10

0
<25 26 28 30 32 34 36 38 40 42 44 46 >47

Reproduced from: Assisted Reproductive Technology Success Rates: National Summary

Reproduced from Assisted Reproductive Technology Success Rates: National Summary and Fertility
and Fertility Clinic Reports Atlanta: Centers for Disease Control and Prevention 2006.
Clinic Reports. Atlanta: Centers for Disease Control and Prevention;2006.

treatment (Figure 2).3 The live birth rate per cycle of IVF
for example has been shown to drop from approximately
31% at age 35 to < 5% at age 42.25
The only effective option for older women (> 40) with
decreased ovarian reserve is oocyte donation.25 In contrast
to IVF with non-donor eggs, the success of IVF with
donor eggs does not vary significantly according to the
recipient’s age up to age 50, after which declining rates of
implantation, clinical pregnancy, and delivery are seen.26,27
In the largest study of delivery outcomes among recipients
of donated eggs, (17 339 ART recipient cycles) no effect of
recipient age was observed between ages 25 and 45 years;
however, older recipient age was associated with statistically
reduced rates of implantation, clinical pregnancy, and
delivery.27 This effect first appeared when women were in
their late 40s and became more pronounced at age 50.27
Pregnancy loss rates among recipients ≥ 45 years versus
younger recipients were also slightly higher (3%).27 Age-
related uterine factors are proposed to play a role in these
outcomes, with reduced uterine blood flow affecting
uterine receptivity to both implantation and pregnancy
maintenance.27–30
The risk of multiple births is substantially elevated in
ART pregnancies. In Canada, the incidence of twin
births increased by 35%, and triplets and higher order
multiple births by over 250%, between 1974 and 1990.31
Multiple gestations are at greater risk of pregnancy loss,
preterm birth, and maternal complications than singleton
pregnancies. Children of a multiple birth are at increased
risk of neonatal mortality, developmental disabilities, and
significant and lifelong special needs. Since the majority
of multiple births are premature and consequently require
additional medical attention before discharge, the effect
on obstetric and neonatal intensive care resources and
the health care system has been dramatic. Caring for
multiples rather than singletons, has been associated with
significant physical, economic, and psychological stress for
families.7,32–37
Recommendations
1. Women who delay child-bearing are at increased
risk of infertility. Prospective parents, especially
women, should know that their fecundity and
fertility begin to decline significantly after 32 years
of age. Prospective parents should know that
assisted reproductive technologies cannot guarantee
a live birth or completely compensate for age-
related decline in fertility. (II-2A)
2. A fertility evaluation should be initiated after
6 months of unprotected intercourse without
conception in women 35 to 37 years of age, and
earlier in women > 37 years of age. (II-2A)
ADVANCED PATERNAL AGE
While the reproductive consequences of advanced paternal
age (≥ 40 years of age at the time of conception)38 are not
as well-defined as the risks of advanced maternal age, the

84 l JANUARY JOGC JANVIER 2012

 Delayed Child-Bearing

Table 2. Risk of Down syndrome and other chromosome abnormalities in live births by maternal age
Risk Risk Risk
Maternal Total Maternal Total Maternal Total
age Down chromosome age Down chromosome age Down chromosome
(at term) syndrome abnormalities (at term) syndrome abnormalities (at term) syndrome abnormalities
25 1 in 1250 1 in 476 32 1 in 637 1 in 323 39 1 in 125 1 in 81
26 1 in 1190 1 in 476 33 1 in 535 1 in 286 40 1 in 94 1 in 63
27 1 in 1111 1 in 455 34 1 in 441 1 in 224 41 1 in 70 1 in 49
28 1 in 1031 1 in 435 35 1 in 356 1 in 179 42 1 in 52 1 in 39
29 1 in 935 1 in 417 36 1 in 281 1 in 149 43 1 in 40 1 in 31
30 1 in 840 1 in 385 37 1 in 217 1 in 123 44 1 in 30 1 in 21
31 1 in 741 1 in 385 38 1 in 166 1 in 105 ≥ 45 ≥ 1 in 24 ≥ 1 in 19
Source: Hecht CA, Hook EB.1996
Reproduced from BC Prenatal Genetic Screening Program, Provincial Health Services Authority.

data suggest a decrease in fertility and an increase in genetic Recommendation

disorders in the offspring of older fathers.
The decreased fertility associated with advanced paternal
age is related to a number of factors. These include
decreased coital frequency, reduced sexual function, and
poorer semen quality (decreased volume, sperm motility,
and percent normal sperm). It is important to note,
however, that standard sperm parameters do not necessarily
correlate with fertilizing capacity and pregnancy rate.39,40
Advanced paternal age is associated with an increased risk
of new gene mutations.41–43 During spermatogenesis, the
male germ cells pass through more mitotic replications than
female germ cells, creating greater opportunity for errors,
which increase with paternal age. The conditions most
strongly associated with advanced paternal age are those
caused by single base substitutions resulting in autosomal
dominant conditions such as, in decreasing order of
frequency, achondroplasia, thanatophoric dysplasia, Apert
syndrome, Pfeiffer syndrome, Crouzon syndrome, and
multiple endocrine neoplasia 2A and multiple endocrine
neoplasia 2B.44 There is also evidence that advanced paternal
age is associated with an increased risk of some congenital
anomalies, schizophrenia, autism spectrum disorders,
and some forms of cancer. For most of these conditions,
the relative risk is ≤ 2, and the mechanism is unknown.38
There is no evidence that advanced paternal age is associated
with increased risk of chromosomal abnormalities with the
possible exception of trisomy 21 and Klinefelter syndrome.38
Presently, there are no specific screening tests to target
conditions related to advanced paternal age. When the male
partner is aged ≥ 40, the couple should be treated as any
other couple and offered prenatal screening and diagnosis
according to SOCG guidelines.
3. Prospective parents should be informed that semen
quality and male fertility deteriorate with advancing
age and that the risk of genetic disorders in
offspring increases. (II-2A)
Maternal age-related risk of Genetic
Conditions and Congenital Anomalies
Chromosomal Aneuploidy
The risk of fetal chromosome aneuploidy, primarily
trisomies, increases with maternal age (Table 2).6 The
biological basis for this observation is that oocytes reach
metaphase I during the fetal period (5 months post-
fertilization), and chromosomes remain aligned on the
metaphase plate until the oocyte divides prior to ovulation.
Age-related errors, largely due to dysfunction of the
meiotic spindle, increase the risk of non-disjunction, which
leads to unequal chromosome products at completion of
division. This results in higher rates of aneuploid embryos,
higher rates of spontaneous abortion, and lower chances
of successful pregnancy outcome. It is estimated that after
the age of 45, the majority of oocytes may be aneuploid.6
It is standard of care to offer all pregnant women,
regardless of age, non-invasive screening for chromosomal
aneuploidy using various combinations of ultrasound
and maternal serum markers to adjust the mother’s age-
related risk.45 Women whose screening tests suggest a high
risk of aneuploidy are offered diagnostic invasive testing
(amniocentesis, chorionic villus sampling).
With the exception of pregnancies conceived though the
use of ICSI, the rate of chromosome abnormalities in
couples undergoing ART treatment is similar to the rate in

JANUARY JOGC JANVIER 2012 l 85

SOGC Committee Opinion
spontaneously conceived pregnancies. The use of sperm
from subfertile men and the ICSI procedure itself are
thought to increase the risk of chromosomal abnormalities
in children conceived using this method.46,47 Couples
undergoing IVF-ICSI for male-factor infertility should
receive information and be offered genetic counselling about
the increased risk of de novo chromosomal abnormalities
(mainly sex chromosomal anomalies) associated with their
condition. Prenatal diagnosis by chorionic villus sampling
or amniocentesis should be offered to these couples if they
conceive.47
Preimplantation genetic diagnosis with transfer of
chromosomally normal embryos has been suggested as
a way to increase rates of implantation and reduce risks
of spontaneous abortion in older women and to avoid
chromosomally abnormal births. However, despite the
high number of aneuploid embryos that are selected out
using this procedure, preimplantation genetic diagnosis
for aneuploidy screening selection has not been found to
be effective in improving pregnancy outcomes for women
35 to 41 years of age, and it is currently not recommended
solely for advanced maternal age.48,49
Gene Abnormalities  Perinatal and neonatal death and stillbirth also increase
The effect of advanced maternal age on single gene disorders
and epigenetic events, other than in the clinical area of
assisted reproduction, is not well known. Epidemiologic
studies have suggested a correlation between autism and
advanced maternal and paternal age, but larger studies are
needed to understand this association.50
Congenital Malformations 
The risk of certain non-chromosomal birth defects has
been shown to increase with maternal age. In a study of
> 1 million singleton infants born after 20 weeks of
gestation who did not have a chromosomal abnormality,
advanced maternal age (35 to 40 years) was associated
with an increased risk for all types of heart defects
(OR 1.12; 95% CI 1.03 to 1.22), tricuspid atresia (OR 1.24;
95% CI 1.02 to 1.50), right outflow tract defects
(OR 1.28; 95% CI 1.10 to 1.49), hypospadias second degree
or higher (OR 1.85; 95% CI 1.33 to 2.58), male genital
defects excluding hypospadias (OR 1.25; 95% CI 1.08 to
1.45), and craniosynostosis (OR 1.65; 95% CI 1.18 to 2.30).51
Hollier et al., prospectively catalogued malformations
detected at birth or in the newborn nursery over a 6-year
period for 102 728 pregnancies, including abortions,
stillbirths, and live births.46 After excluding infants with
chromosomal abnormalities, the incidence of structurally
malformed infants increased progressively with maternal age.
The OR for cardiac defects was 3.95 in infants of women
86 l JANUARY JOGC JANVIER 2012
≥ 40 years of age compared with women 20 to 24 years of
age.52 The risks of clubfoot and diaphragmatic hernia also
increased as maternal age increased. Overall, the additional
age-related risk of non-chromosomal malformations was
approximately 1% in women ≥ 35 years of age.
Recommendation
4. Women ≥ 35 years of age should be offered
screening for fetal aneuploidy and undergo a
detailed second trimester ultrasound examination to
look for significant fetal birth defects (particularly
cardiac defects). (II-1A)
IMPACT OF MATERNAL AGE
ON PREGNANCY OUTCOME
A large body of literature exists describing the impact
of advanced maternal age on pregnancy outcome. When
compared with younger women, women > 35 years
are at increased risk of spontaneous abortion, ectopic
pregnancy, placenta previa,8,52,53 pre-gestational diabetes,
eclampsia,8,53,54 and pregnancy-induced hypertension,8 as
well as Caesarean section8,52,55 and induction of labour. 8,55,56
with increasing maternal age.55 Some of these obstetrical
complications appear to be related to the aging process
alone, while others are related to coexisting factors such
as multiple gestation, higher parity, and underlying chronic
medical conditions (hypertension, diabetes mellitus and
other chronic diseases) that become more prevalent with
increasing age.8,52,55,56
In September 2011, the Canadian Institute of Health
Information published the results of a 3-year study (2006 to
2009)57 which determined that advanced maternal age was
associated with an increased risk of pregnancy complications
and other adverse outcomes. The study linked the birth
records and mothers’ hospital records of > 1 million
hospital live births. Findings included the following:
• Women > 40 were at least 3 times more likely to
develop gestational diabetes and placenta previa than
younger women
• More than 50% of first time mothers > 40 years of
age were delivered by Caesarean section compared
with 25% of women 20 to 24 years
• The incidence of chromosome disorders was 4-fold
higher, and the rates of preterm birth and SGA were
20% and 7% higher in women ≥ 35 years than in
women 20 to 34 years.

These data are consistent with the literature reviewed
in these guidelines and provide additional support to
the recommendations. They also further highlight the
importance of increasing public awareness of this
potentially preventable cause of maternal and neonatal
morbidity.
The paper also suggests that the additional cost to the system
associated with in-hospital births among older women (≥ 35
years) compared with younger women was $ 61.1 million
over the 3 years. The main cost drivers of maternity care
are labour and delivery complications and/or interventions,
Caesarean section, PTD, and length of hospital stay, all of
which were higher in older than in younger women. This
costing information has important implications for policy,
planning, and provision of care in Canada.
Spontaneous Abortion
Older women have a higher rate of spontaneous abortion.
These losses are both aneuploid and euploid, and most
occur between 6 and 14 weeks’ gestation. In a large study
from Denmark, the calculated risk of spontaneous loss in
women > 35 years of age was more than double that in
women < 30 years of age (25% vs. 12%), and was > 90%
in women ≥ 45 years of age.58 The influence of maternal
age on the spontaneous abortion rate was independent of
parity and history of previous abortion, although these
characteristics were also risk factors for pregnancy loss.
Chromosomally abnormal embryos (mainly autosomal
trisomies) account for the majority of spontaneous
abortions in older women. In a recent study of over
2000 IVF pregnancies in which fetal cardiac activity was
documented by transvaginal ultrasound, the pregnancy loss
rate was significantly higher in older women, increasing
from 5% in women < 30 years of age to 13% and 22% in
women aged 35 to 39, and ≥ 40 years, respectively.59,60
Ectopic Pregnancy
Ectopic pregnancy is a major source of maternal mortality
and morbidity in early pregnancy. Maternal age ≥ 35 years
is associated with a risk of ectopic pregnancy 4- to 8-fold
greater than that of younger women.60 This is due to an
accumulation of risk factors over time, such as multiple
sexual partners, pelvic infection, and tubal pathology.
Coexisting Medical Conditions
The 2 most common medical problems complicating
pregnancy are hypertension (pre-existing and gestational)
and diabetes mellitus (pre-gestational and gestational),
and the risk of both of these complications increases
with maternal age. The prevalence of medical and surgical
illnesses, such as cancer and cardiovascular, renal, and
autoimmune disease, increases with advancing age. As a
Delayed Child-Bearing
result, pregnant women ≥ 35 years of age have 2-to 3-fold
higher rates of hospitalization, Caesarean section, and
pregnancy-related complications than younger women.61–67
Lifestyle factors, such as smoking and alcohol use during
pregnancy have been associated with an increased risk of
LBW, perinatal morbidity, and stillbirth in all age groups,
and the risks are further elevated in older women.68–70
Hypertension
Although the maternal and fetal morbidity and mortality
related to hypertensive disorders during pregnancy can be
reduced with careful monitoring and timely intervention,
these disorders are associated with an increased incidence
of preterm birth, SGA infants, and Caesarean section. The
incidence of chronic hypertension is 2- to 4-fold greater in
women ≥ 35 years of age than in women 30 to 34 years of
age.71 Rates of preeclampsia in the general obstetric population
are 3% to 4%. They increase to 5% to 10% in women over 40,
and up to 35 % percent in women > 50 years of age.72
Diabetes
Pre-existing diabetes is associated with increased risks of
congenital anomalies and perinatal morbidity and mortality,
while the major complication of gestational diabetes is fetal
macrosomia and its sequelae.73 The prevalence of diabetes
increases with maternal age. The incidence of both pre-
existing diabetes mellitus and gestational diabetes is 3- to
6-fold higher in women ≥ 40 years of age than in women
aged 20 to 29.53,65,73 The incidence of gestational diabetes
is also 3- to 4-fold higher in older women (7% to 12 % in
women > 40; 20% in women > 50) compared with the 3%
incidence in the general obstetric population.
Placental Abnormalities
The prevalence of placental problems, such as placental
abruption, placenta previa, and placenta accreta, is higher
among older women.12,74 Multiparity accounts for a significant
proportion of the excess risk in these disorders. For example,
there is no significant correlation between maternal age
and abruption when parity and hypertension are taken into
account. Maternal age is, however, an independent risk factor
for placenta previa. Nulliparous women ≥ 40 years of age
have a 10-fold increased risk of placenta previa compared
with nulliparous women aged 20 to 29 years, although the
absolute risk is small (0.25% vs. 0.03%).74
Placenta accreta occurs in approximately 1 of 2500
deliveries, and the incidence is as high as 10% in women
with placenta previa. Advanced maternal age and previous
Caesarean section are independent risk factors for placenta
accreta.74
JANUARY JOGC JANVIER 2012 l 87
SOGC Committee Opinion

Figure 3. Hazard (risk) of stillbirth for singleton births without congenital anomalies by gestational
age, 2001–2002

<20 years
2.50 20-24 years
25-29 years
2.25
30-34 years
35-39 years
2.00
≥40 years
Hazard of fetal death per 1,000 ongoing pregnancies

1.75

1.50

1.25

1.00

0.75

0.50

0.25

0.00
20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Gestation (Weeks)

Reprinted from Am J Obstet Gynecol 2006;195(3), Reddy UM, Ko CW, Willinger M., Maternal age and the risk of stillbirth throughout
pregnancy in the United States, 764–70, Copyright 2006, with permission from Elsevier.

Perinatal Morbidity  diseases, the rates of PTD < 32 weeks for women 20 to
Preterm and LBW infants are at increased risk of death, 29, 40 to 44, and ≥ 45 years of age were 1.01, 1.80, and
morbidity, and long-term disability. These disabilities include 2.24%, respectively.
developmental disorders (e.g., cerebral palsy and blindness),
respiratory problems, learning problems (e.g., lower IQ and Tough et al. compared birth weight and PTD rates in
lower academic achievement), and behavioural problems women aged ≥ 35 with those < 35 years.72 Among older
(e.g., attention deficit hyperactivity disorder).75–77 mothers, the risk of LBW delivery was significantly higher
in every weight category (< 2500 g, < 1500 g, < 1250 g,
Advanced maternal age has been associated with an < 1000 g) (OR 1.1 to 1.6), as was the rate of PTD (< 37,
increased risk of LBW (< 2500 g) and PTD. A large < 35, < 32, and < 30 weeks of gestation) (OR 1.1 to 1.3).
prospective study from Sweden compared birth outcomes During the study period, delayed child-bearing accounted
in healthy nulliparous women delivering singletons at 35
for 78% of the increase in the rate of LBW and 36% of
to 40 years of age with those in women who were 20 to
the increase in the rate of PTD in the population. Maternal
24 years of age.78 After adjusting for smoking, history of
age was not related to changes in SGA, suggesting that the
infertility, and other medical conditions, older maternal
age was associated with a significantly higher risk of age effect was through pregnancy complications that led to
LBW and PTD: very LBW, < 1500 g (OR 1.9); moderate PTD and LBW.
LBW, 1500 to 2499 g) (OR 1.7); very preterm birth ≤ 32 In 2005, Joseph et al.56 published the results of a large
weeks (OR 1.7); moderately preterm birth 33 to 36 weeks population-based study of all singleton births (n = 157
(OR 1.2); and SGA infant < 2 SD for GA (OR 1.7).
445) in the province of Nova Scotia during 1988 to 1995.
A subsequent prospective population-based study, also The risk of very preterm (< 32 weeks) and preterm
from Sweden, evaluated pregnancy outcome in over 32 000 (< 37 weeks) birth and SGA (3rd and 10th percentile)
women ≥ 40 years of age and confirmed an increased increased with advanced maternal age, showing a statistically
risk of PTD.51 After adjustment for confounders such as significant excess risk for women ≥ 35 compared with 20
multiple gestation, smoking, parity, and maternal medical to 24 year olds.56

88 l JANUARY JOGC JANVIER 2012


Perinatal Mortality
Most large studies worldwide have reported that women
≥ 35 years of age are at greater risk of perinatal mortality
than younger women, with relative risks of 1.2 to 4.5.79
This excess perinatal mortality in older women is present
even after controlling for risk factors such as hypertension,
diabetes, antepartum bleeding, smoking, and multiple
gestation, and is mostly due to unexplained stillbirths.47,79–85
In a study of over 5 million singleton pregnancies in the
United States, Reddy et al. reported the risk of stillbirth
was 3.73, 6.41, and 8.65 per 1000 ongoing pregnancies in
women < age 35, 35 to 39 years, and ≥ 40 years of age
respectively, with the risk increasing sharply at 40 weeks of
gestation (Figure 3).83
Bahtiyar et al.85 analyzed > 6 million singleton pregnancies
in the United States to determine the influence of maternal
age on stillbirth risk. After women with congenital anomalies
and medical complications were excluded, older women
were compared with a group of 25- to 29-year-old women
with the lowest stillbirth risk. The odds of stillbirth at term
increased significantly with advancing maternal age: 30 to
34 years, OR 1.24, (95% CI 1.13 to 1.36), 35 to 39 years,
OR 1.45, (95% CI 1.21 to 1.74), and 40 to 44 years, OR 3.04
(95% CI 1.58 to 5.86).85 Of note, the risk of stillbirth for
women 40 to 44 years of age at 39 weeks was comparable to
the risk for women 25 to 29 years old at 42 weeks. The authors
concluded that advanced maternal age is an independent
predictor of stillbirth and that antenatal testing in women
≥ 40 years of age should begin at 38 weeks’ gestation. They
also suggested delivery by 39 weeks in women > 40 years of
age, since the cumulative risk of stillbirth in women 40 to 44
years of age at 39 weeks is the same as the risk in a 25- to
29-year-old at 42 weeks’ gestation.85
These data suggest that women ≥ 40 years of age should be
considered biologically “post-term” at 39 weeks’ gestation,
and fetal monitoring (twice-weekly fetal assessment)
should be initiated at 38 weeks in this age group.
Multiple Pregnancy
Advancing maternal age is associated with an increased
prevalence of twin pregnancy, related to both a higher rate
of naturally conceived twins and a higher use of ART in
older women.86 Data from the Centers for Disease Control
and Prevention87 show that between 1980 and 2006, twin
birth rates rose 27% for mothers < age 20 years compared
with 80% for women aged 30 to 39, and 190% for mothers
aged ≥ 40 years. In 2006, 20% of births to women aged
45 to 54 years were twins, compared with about 2% of
births to women aged 20 to 24 years. These data mainly
reflect the increased use of ART in older women.86 The
Delayed Child-Bearing
overall twin birth rate increased 70% between 1980 and
2004, from 18.9 per 1000 to 32.1 per 1000 births, but it was
essentially unchanged between 2004 and 2006, indicating a
possible slowing of the upward trend. The rate of triplet
and higher order multiple births (quadruplets, quintuplets
and other higher order multiples per 100 000 live births),
which climbed more than 400% during the 1980s and
1990s, also declined (by 21%) over the same period from
the all-time high in 1998 (193.5 per 100 000 total births).87
This is likely due in part to changes in practices in IVF
clinics across the country.
There is a high risk of an adverse outcome for multiple
births, and > 12% of twins and 30% of triplets are born
at < 32 weeks, compared with 2% of singletons. The
perinatal mortality rate is significantly higher among twins
(29.8 per 1000) and triplets (59.6 per 1000) than among
singletons (6.0 per 1000).86,87
Caesarean Section
Women ≥ 35 years of age are more likely than younger
women to be delivered by Caesarean section.25,50 The
Caesarean section rate in women 40 to 45 approximates
50%, and this increases to approximately 80% in women
aged 50 to 63 years, although the rate in the general
obstetric population is about 25%.55,68,87
The reasons for the high rate of Caesarean section
in older women include an increased prevalence of
medical complications, fetal malposition, cephalopelvic
disproportion, induction of labour, a failed trial of labour,
and uterine rupture.88–93
In a study by Smith et al., a linear increase in ORs for
Caesarean section with advancing maternal age (≥ 16 years)
was demonstrated (adjusted OR for a 5-year increase in age:
1.49; 95% CI 1.48 to 1.50).91 During the study period (1980
to 2005), the proportion of women aged 30 to 34 years
increased 3-fold, the proportion of women aged 35 to 40 years
increased 7-fold, and the proportion of women aged > 40
years increased more than 10-fold. The authors used these
data in a calculation model to determine the contribution
of advanced maternal age to the overall Caesarean section
rate and concluded that if the maternal age distribution had
stayed at the 1980 level, 38% of the additional Caesarean
sections would not have been performed.
There is also a lower threshold among both women and
physicians for performing a Caesarean section in older
women, and maternal request for Caesarean section is more
common among older women.88 There is a continuous
negative relationship between age and uterine function
throughout the child-bearing years.90
JANUARY JOGC JANVIER 2012 l 89
SOGC Committee Opinion
Maternal Mortality
Maternal mortality increases with maternal age94–96
however, the risk of dying during childbirth is very low
in developed countries (total maternal mortality rate in
Canada 6.1 per 100 000 live births).97 As the proportion
of women who are delaying child-bearing to later in life
continues to increase, age-specific increases in mortality
may be observed.98,99
Recommendations
5. Delayed child-bearing is associated with increased
obstetrical and perinatal complications. Care providers
need to be aware of these complications and adjust
obstetrical management protocols to ensure optimal
maternal and perinatal outcomes. (II-2A)
6. All adults of reproductive age should be aware
of the obstetrical and perinatal risks of advanced
maternal age so they can make informed decisions
about the timing of child-bearing. (II-2A)
Benefits of Delayed Child-Bearing
There are advantages and disadvantages to parenting when
older: there is more anxiety during pregnancy, but parents
are more mature and likely to be more financially secure and
to have higher levels of education. Multiple pregnancies
have a slightly more favourable outcome in older women.
Overall, if older women can sustain a pregnancy, the
pregnancy outcomes can be positive, and parents may be
well prepared to cope with the physical and emotional
stresses of pregnancy and parenting.57 Older parents can
bring experience, knowledge, and economic resources
to the task of child raising, which may suggest a social
advantage to delayed parenting.100
SUMMARY
The proportion of women who delay child-bearing beyond
the age of 35 years has increased greatly in recent decades.
Pregnancy after 35 years has been associated with increased
likelihood of infertility, miscarriage, spontaneous abortion,
stillbirth, medical risks, operative delivery, and pregnancy
complications. Advanced maternal age increases the risk
for multiple births, PTD and/or LBW, each of which
increases the potential need for additional medical care,
and poses lifelong threats to development.
While most women have some awareness of the “biological
clock” and realize that conception difficulties increase with
age, many are unaware of the limitations of ART or the
increased risk of adverse influences on child development
associated with PTD and multiple birth. Given these gaps
in reproductive knowledge and awareness, widespread
pre-conception counselling and education are needed and
90 l JANUARY JOGC JANVIER 2012
must be implemented so that the 95% of Canadians who
anticipate parenting at some point can make informed
decisions. Women (and men) need to be informed that age
is the single most important determinant of female fertility,
either natural or treated, and that ART cannot compensate
for age-related decline in fertility.
There is an opportunity for SOGC to lead this initiative
through the development and distribution of high-quality,
respected, educational and public health materials.
In addition, communication strategies may be most effective
if they align with the needs of government, policy makers,
and employers who are vested in the development of a
healthy, competent workforce, which may be threatened
by delayed child-bearing and its consequences. There is
an opportunity to improve public understanding about
reproductive health and child-bearing between 25 and 35
years, the limits of ART, and the limitations of science to
predict which families will be at risk when child-bearing
is delayed. The influences of maternity leave, child care,
work environments and relationship security on child-
bearing decisions require further understanding (beyond
the scope of this paper).
Recommendations
7. Strategies to improve informed decision-
making by prospective parents should be
designed, implemented, and evaluated. These
strategies should provide opportunity for adults
to understand the potential medical, social,
and economic consequences of child-bearing
throughout the reproductive years. (III-B)
8. Barriers to healthy reproduction, including
workplace policies, should be reviewed to optimize
the likelihood of healthy pregnancies. (III-C)
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94. Shipp TD, Zelop C, Repke JT, Cohen A, Caughey AB, Lieberman E.
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 Delayed Child-Bearing

Appendix. Delayed Child-Bearing Facts

Advanced maternal age (≥ 35 years) is associated with

• Decreased fertility and fecundity
• Increased risk of miscarriage
• Increased risk of ectopic pregnancy
• Increased risk of chromosomal aberrations and birth defects
• Increased risk of multiple pregnancy

Advanced paternal age (≥ 40 years) is associated with

• Decreased fertility and semen quality
• Increased risk of certain genetic disorders

Practice Points
• Pre-conceptional counselling is recommended for all couples when one or both partners are of advanced reproductive age.
• Pre-conceptional counselling and education at a government and public health level are required in order to inform younger women and men
about the possible consequences of delaying child-bearing before they make the decision whether or not to do so.
• When women ≥ 35 years become pregnant, an early ultrasound to document location, number, and viability of the pregnancy should be
undertaken.
• Prenatal screening for chromosome abnormalities and a second trimester ultrasound should be offered as is standard of care for all women.

Pregnancy in women of ≥ 35 years is associated with

• Increased risk of coexisting medical disorders
• Hypertensive disorders of pregnancy and preeclampsia
• Preexisting diabetes and gestational diabetes
• Increased risk of placenta previa
• Increased risk of LBW and PTD
• Increased risk of stillbirth
• Increased rate of Caesarean section

Practice Points
Women ≥ 35 years should
• Have a thorough history and physical examination.
• Have prenatal bloodwork that includes baseline liver and kidney function, as well as mammogram (> 40 years) and cardiology consultation >
45 years.
• Be monitored closely for hypertensive disorders of pregnancy and preeclampsia, and all should undergo screening for gestational diabetes.
• Have careful placental localization with ultrasound at the time of the second trimester scan, to be followed up at 28 weeks’ gestation if low
lying or previa.
A third trimester scan to document fetal growth and placental location should be considered.
The cumulative risk of stillbirth in women of 40 to 44 years of age at 39 weeks’ gestation is nearly identical to the risk in those of 25 to 29 years of
age at 42 weeks’ gestation.
Therefore, a strategy of antenatal testing beginning at 38 gestational weeks with delivery by the completion of the 39th week for women > 40
years of age should be considered.

JANUARY JOGC JANVIER 2012 l 93

 SOGC COMMITTEE OPINION

No. 277, May 2012

Counselling Considerations for Prenatal

Genetic Screening
INTRODUCTION
This committee opinion has been prepared by the Genetics

T
Committee and approved by the Executive of the Society of
risomies 21, 18, and 13 are the most frequently
Obstetricians and Gynaecologists of Canada.
occurring fetal aneuploidies, although all have been
PRINCIPAL AUTHORS
observed at term. Eighty percent of fetuses with trisomy
Lola Cartier, MSc, CCGC, Montreal QC
18 or 13 and 30% with trisomy 21 die in utero between 12
Lynn Murphy-Kaulbeck, MD, Moncton NB and 40 weeks of gestation.
GENETics COMMITTEE
R. Douglas Wilson, MD (Chair), Calgary AB Trisomy 21, or Down syndrome, is the most common
François Audibert, MD, Montreal QC viable chromosomal anomaly, with an incidence of
Jo-Ann Brock, MD, Halifax NS
1/770 live births. Individuals with trisomy 21 may have
physical abnormalities such as a cardiac defect, early onset
June Carroll, MD, Toronto ON
Alzheimer disease, and/or increased rates of leukemia, and
Lola Cartier, MSc, CCGC, Montreal QC
all will have some degree of developmental delay. The 18-
Alain Gagnon, MD, Vancouver BC
to 20-week ultrasound examination will show no abnormal
Jo-Ann Johnson, MD, Calgary AB findings in 50% of fetuses with trisomy 21.
Sylvie Langlois, MD, Vancouver BC
Lynn Murphy-Kaulbeck, MD, Moncton NB The risk of having an affected fetus increases with maternal
Nanette Okun, MD, Toronto ON
age. However, as most pregnancies occur in young women,
Melanie Pastuck, RN, Cochrane AB
most fetuses with trisomy 21 occur in younger mothers.
Disclosure statements have been received from all members of
the committee. SCREENING

Prenatal screening for fetal aneuploidy is a rapidly changing

field, and there are variations in screening protocols both
Abstract
provincially and regionally. Clinicians should be aware
This document has been developed to aid clinicians in counselling of the availability of and protocols for screening in their
patients about prenatal screening and to provide assistance in
counselling about both positive and negative screening results.
geographical area.

Biochemical and ultrasound screening tests are now

J Obstet Gynaecol Can 2012;34(5):489–493
Key Words: Aneuploidy, prenatal screening, chromosomal
anomalies, trisomy
available during pregnancy to assess the risk of having a
fetus with trisomy 21. If the risk of trisomy 21 is higher
than a specified risk cut-off as determined by the screening
program, a diagnostic test (e.g., amniocentesis) is offered to
confirm or exclude the presence of trisomy 21 (and some
other chromosome abnormalities).

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

MAY JOGC MAI 2012 l 489

SOGC COMMITTEE OPINION
It is important to ensure that these screening tests are
offered within the context of an organized program,
ensuring laboratory tests and ultrasound operators have
appropriate validation to meet quality assurance standards.
Screening is intended to identify women in the general
pregnancy population who are at increased risk of having
a child with an anomaly. Health care professionals should
discuss the screening tests with all pregnant women.
Information pamphlets can also be helpful in explaining the
purpose and limitations of screening tests, but health care
providers should be aware that some women may not have
sufficient English or French to understand them. Health
care providers must be satisfied that patients understand the
screening available and that screening is entirely voluntary,
and that they are making an informed decision about whether
to have testing. The decision should be documented.
Screening Methods
Screening can be divided into two broad categories:
1. Maternal serum sampling: measure of maternal
biochemical markers in the first and/or second
trimester of pregnancy. This can be done with or
without ultrasound screening.
2. Ultrasound screening: measure of first trimester nuchal
translucency and other ultrasound markers in the first
and/or second trimester of pregnancy.
Their performance, in terms of sensitivity and specificity,
varies according to the approach, but the results are
improved by using a combination of these methods. For
example, an ultrasound examination is performed in the
first trimester, and blood tests in the first and second
trimester to provide a single assessment of risk. It is not
appropriate to use one method to assess risk and then use
another method to give a separate risk assessment. When
multiple screening options are available, factors to consider
include the detection rate and false-positive rate of the
screening test, and the gestational age at the time testing
is considered.
Screen Positive Rate
•• This is the proportion of the screened population who
test positive. It includes both true positives and false
positives. Women who screen positive are eligible for
and are offered counselling and invasive testing. Most
women who screen positive will not have a fetus with
trisomy 21; that is, they will have a false-positive result.
Sensitivity (Detection Rate)
•• Sensitivity refers to the test’s ability to detect all
individuals who have the condition.
490 l MAY JOGC MAI 2012
•• The higher the sensitivity of the screening test, the more
likely it is to identify individuals with the condition.
•• Sensitivity is the probability that an individual who has
the condition will test positive; it is not the risk for
trisomy 21 after a positive screening test result.
Specificity
•• Specificity refers to the probability that an individual
who does not have the condition will test negative.
•• The higher the specificity of the screening test, the
more likely it is to correctly identify individuals who do
not have the condition.
•• Specificity measures the test’s ability to identify only
individuals who have the condition.
Positive Predictive Value
•• Positive predictive value is the probability that an
individual has the condition given a positive screening
result.
•• Positive predictive value is determined/assessed on
the basis of test sensitivity and specificity, and the
prevalence of the condition.
Negative Predictive Value
•• Negative predictive value is the probability that an
individual does not have the condition given a negative
screening result.
TIPS FOR PRE-SCREENING COUNSELLING
•• Counsel your patient that all pregnant women have some
risk of having a fetus affected by trisomy 21, 18, or 13.
•• Tell your patient that prenatal screening will use
specific maternal and pregnancy factors (e.g., age,
ethnicity) to assess her individual risk of having an
affected fetus.
•• Discuss the following points with your patient.
–– Maternal age is one factor used in the assessment
of risk, and the screening result is more likely to be
positive with increasing age.
–– A positive screening result may provide an older
woman with a risk assessment/adjustment lower
than the risk associated with her age alone.
–– The screening may assess a younger woman’s risk
as greater than that indicated by her age alone, but
it may not be high enough to result in a positive
screening test result.
 Counselling Considerations for Prenatal Genetic Screening

Current available screening options and their screening performance*

Term risk DR, FPR,
Screening option Markers Trimester cut-off % % OAPR
Options that meet the minimum standard
FTS1,2 NT, free β-hCG, PAPP-A, MA First 1 in 325 83 5.0 1:27
Quad screening3 AFP, uE3, free β-hCG, inhibin A, MA Second 1 in 385 77 5.2 1:50
IPS 1,2
NT, PAPP-A, AFP, uE3, free β-hCG/ First and second 1 in 200 87 1.9 1:10
total hCG, inhibin A, MA
IPS without inhibin A1 NT, PAPP-A, AFP, uE3, total hCG, MA First and second 1 in 200 88 3.0 1:20
Serum IPS 1,2
PAPP-A, AFP, uE3, free β-hCG/ First and second 1 in 200 85 4.4 1:26
total hCG, inhibin A
Options that do not meet the minimum standard
Maternal age4 MA First and second 1 in 385 44 16 1:218
Triple screening 4
AFP, uE3, total hCG, MA Second 1 in 385 71 7.2 1:59
*Some centres in Canada may offer variation on IPS (sequential screening or contingent screening) with cut-offs set that achieve at least the minimum standard.
DR: detection rate; FPR: false positive rate; OAPR: odds of an affected pregnancy result; FTS: first trimester combined screening; NT: nuchal translucency;
hCG: human chorionic gonadotropin; PAPP-A: pregnancy associated plasma protein A; MA: maternal age; IPS: integrated prenatal screening;
AFP: alpha fetaprotein; uE3: unconjugated estriol.
1
Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM. First and second trimester antenatal screening for Down’s syndrome: the results of the
Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen 2003;10:56–104.
2
Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, et al. First- and Second-Trimester Evaluation of Risk (FASTER) Research
Consortium. First-trimester or second-trimester screening, or both, for Down’s syndrome. N Engl J Med 2005;353:2001–11.
3
Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down’s syndrome. J Med Screen 1997;4:181–246.
4
Summers AM, Farrell SA, Huang T, Meier C, Wyatt PR. Maternal serum screening in Ontario using the triple marker test. J Med Screen 2003;10:107–11.

•• Counsel your patient that a positive screen will
mean that her risk is above a pre-determined cut-
off (set by regional programs), not that her fetus is
necessarily affected. Some patients may have difficulty
understanding the difference between a screening test
and a diagnostic test.
•• Counsel your patient that her risk is specific and
personalized. For example, a risk of 1:100 means that
for one woman carrying an affected fetus, there are 99
women carrying a fetus that is not affected. Prenatal
aneuploidy screening using age and nuchal translucency
measurement in the first trimester is appropriate
for screening in multiple gestations. For multiple
gestations, it is important to check with the screening
centre close to you, as availability of maternal serum
screening varies from centre to centre.
•• When screening is offered, discuss options and
the invasive prenatal testing that may need to be
considered after screening.
•• Tell your patient that if screening is negative, no
further testing is indicated other than routine second
trimester ultrasound. Remind her that there is a risk to
invasive procedures. Inform the patient that negative
screening does not guarantee the birth of a healthy
baby and that her child could still be born with an
aneuploidy or another genetic or developmental
condition not detected through screening. Inform your
patient that if the screening test is positive she is eligible
for diagnostic testing.
–– This testing would be done by amniocentesis, which
carries a procedural risk of 1/100 to 1/175 for loss
of the pregnancy or by chorionic villus sampling,
which carries a procedural risk of 1/100 for loss of
the pregnancy.2,3
–– Ensure your patient is aware that diagnostic testing
is entirely voluntary.
–– Ensure your patient knows that she has the option
of continuing or terminating the pregnancy if
the test shows that her fetus has an aneuploidy or
another significant chromosomal anomaly. It is a
common misconception that screening is offered
only to patients who would terminate a pregnancy
if an anomaly were found. It is important to tell
patients who may choose to continue the pregnancy
that their fetus will be given the best care possible.
In the case of chromosomal anomalies that have an
extremely poor prognosis, this may include referring
the patient to a neonatologist to discuss palliative

MAY JOGC MAI 2012 l 491

SOGC COMMITTEE OPINION
care. For the care of a fetus with Down syndrome
this should include
○ Ensuring that the fetus receives necessary testing
and monitoring, such as fetal echocardiogram
and increased surveillance.
○ Informing the patient of the support available
for parents choosing to raise a child with Down
syndrome, including the Canadian Down
Syndrome Society.
–– Be aware that undecided patients may pursue or
decline screening and testing at any point in the
screening process.
POST-SCREENING COUNSELLING
A screening program should include a reliable laboratory
that can provide a report of results within a working week.
Screening results should be reported to the patient as
soon as possible after results have been reported to the
practitioner. Ideally, screening results should be discussed
in person.
Negative Screen
For women with a negative screen, as defined by a
predetermined cut-off, counselling should include the risk
for trisomy 21 determined by screening rather than by pre-
screening risk determined by age. As part of counselling,
the patient should be informed that a negative screen does
not guarantee that her fetus does not have one of the
conditions screened for; however, the risk is low enough
that invasive testing will not offered. Routine second
trimester ultrasound will still be carried out. In younger
women, the assessment may indicate that their risk is
greater than the risk that would have been determined by
age alone but may result in a negative screen. Counselling
may be needed to help some women understand that
although the risk is increased, the result is still negative,
and invasive diagnostic testing is not required.
As regions differ with respect to the use of ultrasound
markers, regional protocols will guide any further
adjustment of risk. If one or more ultrasound markers are
present at the time of the anatomical survey, the risk for
trisomy 21, as determined by screening, will be adjusted by
the likelihood ratio assigned to the specific marker(s).
The risk for other genetic conditions is not assessed
through screening.
492 l MAY JOGC MAI 2012
Positive Screen
A positive screen for trisomy 21 is anxiety provoking and
needs to be discussed with the patient in an environment
that allows proper explanation and discussion of options.
Allow sufficient time for the woman and her partner to ask
questions.
The first point of counselling should be that there are a
number of reasons why a screen may be positive. A positive
screen is not a diagnosis of a chromosome anomaly: it is a
positive screen as established by a predetermined cut-off,
and further investigation and possibly invasive testing will
be required. It may be necessary to discuss with the patient
the false-positive rate of the tests used.
Counselling should include a discussion of risk. Patients
often find it easier to understand risks when they are
explained as percentages. For example, a risk of 1/100 is
a 1% risk of the fetus having the condition whereas a risk
of 1/200 is a risk of 0.5%. Stated another way, a risk of
1/200 means that there is a 99.5% chance that the fetus
does not have trisomy 21 or that if 200 women have this
same result, 1 of them will have a fetus with trisomy 21 and
199 will not. An explanation of a negative screen and the
percentage of risk may also be helpful.
For women of advanced maternal age (≥ 35 years of age),
screening may result in a woman’s risk for aneuploidy being
lowered but still result in a positive screen. This lowered
risk may be acceptable to some women, but counselling is
required to help women understand their risk and that they
are eligible for invasive testing.
Counselling for a positive screen should review the
patient’s options and should include a discussion about
invasive testing, what the test will diagnose, the risk of the
procedure, and why she may or may not wish to have the
test(s). In the vast majority of cases, amniocentesis will
provide a definitive answer as to whether or not the fetus
has a chromosomal anomaly. Chorionic villus sampling is
available in some centres in Canada and may be available
for women who screen positive after first trimester
biochemistry and/or nuchal translucency measurement.
In some centres in Canada, women with positive screens
are referred for further ultrasound assessment, and the
risk determined by serum screening is adjusted depending
on the presence or absence of fetal soft markers. If a
soft marker or markers are present, the risk is increased
as determined by the likelihood ratio for the marker or
markers present. The absence of any markers or anomalies
may result in a lowering of the risk. Regardless of the risk
adjustment from the ultrasound, women may still choose
to have amniocentesis for a definitive diagnosis.

Counselling should include the information that if invasive
testing does reveal a fetus has trisomy 21 or any other
chromosomal anomaly, pregnancy termination may be one
option. It should be made clear to the patient that the offer
of invasive testing is not contingent upon her terminating
the pregnancy if her baby has a chromosomal anomaly. It
is important for women to understand that if a diagnosis
of Down syndrome or other anomaly is made, further
consultation and support will be available to help her decide
whether to continue or terminate the pregnancy. Women
and families may require more information about what
trisomy 21 is and about the possible health implications
and long-term outcomes for people with this condition.
A request for consultation at a genetics service can be
helpful. Also, diagnosing trisomy 21 or other non-lethal
chromosomal anomaly prenatally ensures that the fetus
receives the most appropriate prenatal and neonatal care,
including testing and monitoring that may be necessary,
such as fetal echocardiogram and increased antenatal and
intrapartum surveillance.
Women should be made aware that although invasive
testing is being offered, it is not mandatory following a
positive screen. They should be reassured that they will still
receive the best possible care they if they choose not to
have diagnostic testing.
TIPS FOR COUNSELLING PATIENTS
WITH A POSITIVE SCREENING RESULT
Tell your patient that
•• A positive screen does not mean her baby is affected.
•• Her risk for having an affected fetus has been adjusted
from her age-only related risk and that her risk is higher
than the pre-determined cut-off, which results in a
positive screen.
•• False positives do occur.
•• She is eligible for diagnostic invasive testing, but this is
her choice, and she can decline the procedure.
•• If she has diagnostic testing following a positive
screening result, it will diagnose Down syndrome and
that other chromosome anomalies may be diagnosed.
•• The identification of a chromosomal anomaly
may require further investigation of the parents’
chromosomes before a firm diagnosis can be made.
Counselling Considerations for Prenatal Genetic Screening
•• A positive screen does not warrant further genetic
testing other than amniocentesis or chorionic villus
sampling unless there are other indications for more in-
depth testing on the basis of previous pregnancy history
or family history.
•• Chromosome analysis is specific; no other genetic testing
is done unless indicated.
•• The pregnancy loss risk associated with amniocentesis is
1:175 to 1:100.
•• If she has a fetus diagnosed with a chromosomal
anomaly, she has the option of continuing or
terminating the pregnancy.
•• If she chooses to continue her pregnancy, special tests,
such as a fetal echocardiogram, will be performed as
necessary, and routine obstetrical care will be adjusted
because there is an increased risk for adverse outcome
with a trisomy 21 affected pregnancy.
•• This is a difficult and very personal decision and she will
be supported whatever she chooses to do. Acknowledge
that a positive screen is anxiety provoking and support
the woman in her decision making.
BIBLIOGRAPHY
Chitayat D, Langlois S, Wilson RD; SOGC Genetics Committee; CCMG
Prenatal Diagnosis Committee. Prenatal screening for fetal aneuploidy in
singleton pregnancies. SOGC Clinical Practice Guideline no. 261, July 2011.
J Obstet Gynaecol Can 2011;33:736–50.
Audibert F, Gagnon A. SOGC Genetics Committee; CCMG Prenatal Diagnosis
Committee. Prenatal screening for fetal aneuploidy in twin pregnancies.
SOGC Clinical Practice Guideline no. 262, July 2011. J Obstet Gynaecol Can
2011;33:754–67.
Chodirker BN, Cadrin C, Davies GAL, Summers AM, Wilson RD, Winsor EJT,
et al.; SOGC Genetics Committee; CCMG Prenatal Diagnosis Committee.
Canadian guidelines for prenatal diagnosis: techniques of prenatal diagnosis.
SOGC Clinical Practice Guideline, no. 105, July 2001. J Obstet Gynaecol Can
2001;23:616–24.
Summers AM, Langlois S, Wyatt P, Wilson RD; SOGC Genetics Committee;
CCMG Committee on Prenatal Diagnosis; SOGC Diagnostic Imaging
Committee. Prenatal screening for fetal aneuploidy. Joint SOGC-CCMG
Clinical Practice Guideline no. 187, February 2007. J Obstet Gynaecol Can
2007;29:146–61.
Van den Hof MC, Wilson DR; SOGC Diagnostic Imaging Committee;
SOGC Genetics Committee. Fetal soft markers in obstetric ultrasound.
SOGC Clinical Practice Guideline no. 162, June 2005. J Obstet Gynaecol Can
2005;27:592–612.
Wilson RD, Langlois S, Johnson J; SOGC Genetics Committee; CCMG
Prenatal Diagnosis Committee. Mid-trimester amniocentesis fetal loss rate.
SOGC Committee Opinion, No. 194, July 2007. J Obstet Gynaecol Can
2007;29:586–90.
MAY JOGC MAI 2012 l 493
 SOGC CLINICAL PRACTICE GUIDELINE
Treatments for Overactive Bladder:
Focus on Pharmacotherapy
This clinical practice guideline has been prepared by the
Urogynaecology Committee, reviewed by Family Practice
Advisory Committee, and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists
of Canada.
PRINCIPAL AUTHOR
Roxana Geoffrion, MD, Vancouver BC
UROGYNAECOLOGY COMMITTEE
Danny Lovatsis, MD (Co-Chair), Toronto ON
Jens-Erik Walter, MD (Co-Chair), Montreal QC
Queena Chou, MD, London ON
William Easton, MD, Scarborough ON
Annette Epp, MD, Saskatoon SK
Roxana Geoffrion, MD, Vancouver BC
Marie-Andrée Harvey, MD, Kingston ON
Annick Larochelle, MD, St-Lambert QC
Kenny Maslow, MD, Winnipeg MB
Grace Neustaedter, RN, Calgary AB
Dante Pascali, MD, Ottawa ON
Marianne Pierce, MD, Halifax NS
Jane A. Schulz, MD, Edmonton AB
Vyta Senikas, MD, Ottawa ON
David Wilkie, MD, Vancouver BC
Disclosure statements have been received from all members of
the committee.
Abstract
Objective: To provide guidelines for pharmacotherapy to treat
overactive bladder syndrome (OAB).
Options: Pharmacotherapy for OAB includes anticholinergic
(antimuscarinic) drugs and vaginal estrogen. Both oral and
transdermal anticholinergic preparations are available.
Key Words: Anticholinergic, overactive bladder, urinary
incontinence
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
1092 l NOVEMBER JOGC NOVEMBRE 2012
No. 283, November 2012
Outcomes: To provide understanding of current available evidence
concerning safety and clinical efficacy of pharmacotherapy for
OAB; to guide selection of anticholinergic therapy based on
individual patient characteristics.
Evidence: The Cochrane Library and Medline were searched for
articles published from 1950 to the present related to individual
anticholinergic drugs. Review articles on management of
refractory OAB were also examined. Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. There were no date or language
restrictions. Searches were updated on a regular basis and
incorporated in the guideline to 2010.
Values: The quality of evidence is rated and recommendations are
made using the criteria described by the Canadian Task Force on
Preventive Health Care (Table 1).
Benefits, harms, and costs: Anticholinergics are the mainstay
of pharmacotherapy for OAB. Evidence for their efficacy is
mostly derived from short-term phase III randomized drug trials.
Placebo response is strong, and long-term follow-up and patient
subjective outcome data are lacking. Care providers need to be
well acquainted with the side effects of anticholinergics and select
therapy based on individual patient parameters.
Recommendations
01. Behavioural management protocols and functional electrical
stimulation should be offered in the spectrum of effective primary
treatments for overactive bladder syndrome. (I-A)
02. Oral oxybutynin, immediate and extended release, as well
as transdermal oxybutynin, may be offered as treatment for
overactive bladder syndrome, as they are associated with
significant objective clinical improvement at 12 weeks. (I-A)
Oxybutynin immediate release has superior cost-effectiveness
but more side effects than other anticholinergics. (I-A) Adverse
events associated with transdermal oxybutynin are fewer than
with oral oxybutynin. (I-A)
03. Tolterodine, immediate and extended release, may be offered as
treatment for overactive bladder syndrome, as it is associated
with significant objective clinical improvement at 12 weeks. (I-A)
J Obstet Gynaecol Can 2012;34(11):1092–1101

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.82
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.82
04. Trospium, immediate and extended release, may be offered as
treatment for overactive bladder syndrome as it is associated
with significant clinical improvement at 12 weeks. (I-A) Trospium
is an adequate anticholinergic choice for overactive bladder
syndrome patients with pre-existing cognitive impairment (II-B)
and for overactive bladder syndrome patients taking concurrent
CYP450 inhibitors. (III-B)
05. Solifenacin may be offered as treatment for overactive bladder
syndrome, as it is associated with significant objective clinical
improvement at 12 weeks. (I-A) Solifenacin may be an
adequate anticholinergic choice for elderly overactive bladder
syndrome patients or patients with pre-existing cognitive
dysfunction. (I-B)
06. Darifenacin may be offered as treatment for overactive bladder
syndrome, as it is associated with significant objective clinical
improvement at 12 weeks. (I-A) Darifenacin is an adequate
anticholinergic choice for overactive bladder syndrome patients
with pre-existing cardiac concerns or cognitive dysfunction. (I-B)
07. Overactive bladder syndrome patients should be offered a
choice between bladder training, functional electric stimulation,
and anticholinergic therapy, as there is no difference in cure
rates. Combination therapy does not have a clear advantage
over one therapy alone. (I-A)
08. The choice of anticholinergic therapy should be guided by
individual patient comorbidities, as objective efficacy of
anticholinergic drugs is similar. (I-A) Dose escalation does not
improve objective parameters and causes more anticholinergic
ABBREVIATIONS
CNS central nervous system
CYP450 cytochrome p450
ER extended release
IR immediate release
OAB overactive bladder syndrome
XR extended release
Treatments for Overactive Bladder: Focus on Pharmacotherapy
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
adverse effects. It is, however, associated with improved
subjective outcomes. (I-A) To decrease side effects, switching
to a lower dose or using an extended release formulation or a
transdermal delivery mechanism should be considered. (I-A)
09. Education on treatment efficacy, realistic expectations,
and length of treatment should be offered to patients upon
initiation of anticholinergic therapy, as continuation rates for
anticholinergic therapy are low. (III-B)
10. Oral or transdermal estrogen supplementation should not be
recommended for treatment of overactive bladder syndrome as
its effects are comparable to placebo. (I-E) Vaginal estrogen can
be suggested for subjective improvements in overactive bladder
syndrome symptoms. (III-B)
11. Intravesical botulinum toxin injection and sacral nerve
and posterior tibial nerve stimulation are clinically effective
options for patients with overactive bladder syndrome
unresponsive to conservative options, anticholinergics, or
vaginal estrogen. (I-A)
INTRODUCTION
O
veractive bladder syndrome comprises symptoms
related to abnormal urinary bladder storage. It is
defined as urinary urgency, usually accompanied by frequency
and nocturia, with or without urgency urinary incontinence,
in the absence of urinary tract infection or other obvious
pathology.1 It can be associated with detrusor overactivity
on urodynamic studies.1 The prevalence of OAB is reported
at 11.8% to 17% in women and significantly increases with
age.2–5 Most women with OAB (96%) report leakage of
urine with an overall prevalence of urgency incontinence of
12%.2 OAB has a greater impact on quality of life than stress
urinary incontinence6,7 and is responsible for several medical
comorbidities. Up to 67% of women with OAB report a
NOVEMBER JOGC NOVEMBRE 2012 l 1093
SOGC CLINICAL PRACTICE GUIDELINE

Table 2. Anticholinergic drugs and properties

Receptor CNS
Drug Route Dose selectivity Main metabolism penetration
Oxybutynin Oral IR 5 mg bid-tid Non-selective Hepatic; patch and High
gel avoid first pass
ER 5 or 10 mg qd
Transdermal, patch 3.9 mg/day; apply
twice weekly
Transdermal, gel 10% 1 g (1 sachet) qd
Tolterodine Oral IR 2 mg bid Non-selective Hepatic High
ER (LA) 4 mg qd
Trospium Oral IR 20 mg bid Non-selective Renal Low
Age > 75:20 mg qd
ER (XR) 60 mg qd
Solifenacin Oral 5 to 10 mg qd M3 M1 selective Hepatic High
Darifenacin Oral 7.5 to 15 mg qd M3 selective Hepatic Low
Fesoterodine Oral ER 4 mg Non-selective Hepatic High
8 mg
LA: long acting.
Tolterodine, solifenacin, darifenacin—use ½ dose in hepatic insufficiency; avoid use in severe hepatic insufficiency
Tolterodine, trospium, solifenacin—use ½ dose when creatinine clearance < 30 mL/min
All anticholinergics should be prescribed with caution if CYP inhibitors are used concurrently (typical examples are antifungals, antiretrovirals and
macrolide antibiotics)

negative effect on daily living.4 Significant comorbidities (Detrol or Detrol LA), trospium chloride (Trosec IR and
associated with OAB include depression,8 falls and fractures,9 XR), solifenacin (VESIcare), darifenacin (Enablex), and
and increased admissions to hospitals and nursing homes.10 fesoterodine (Toviaz).

Conservative, pharmacotherapeutic, and surgical Mechanism of Action and Drug Properties

interventions are available. This consensus guideline reviews
these interventions, focusing mainly on pharmacotherapy.
CONSERVATIVE INTERVENTIONS
Conservative management of urinary incontinence has been
reviewed in a previous consensus guideline.11 Many inter­
ventions have been described. They include Kegel exercises,
functional electrical stimulation, continence pessaries,
behavioural management, and bladder training programs.
Recommendation
1. Behavioural management protocols and functional
electrical stimulation should be offered in the
spectrum of effective primary treatments for
overactive bladder syndrome. (I-A)
PHARMACOTHERAPEUTIC
INTERVENTIONS: ANTICHOLINERGICS
There are currently six approved medications for OAB
(Table 2). These are oxybutynin (Ditropan, Ditropan XL,
Oxytrol patch, Gelnique gel 10%), tolterodine tartrate
Normal human bladder contractions are initiated via
muscarinic (cholinergic) receptors in the detrusor muscle.12
These receptors are of the M2 and M3 subtypes in the
bladder.12 Normal voiding occurs via parasympathetic
activation of the M2 or M3 receptors, while the M2
receptors also inhibit sympathetically mediated bladder
relaxation.12,13 Anticholinergic drugs competitively block
acetylcholine and increase bladder storage capacity.14,15
Furthermore, the urothelium also expresses muscarinic
receptors and consequently may be the site of action of
anti-muscarinics.16 The release of other substances, such as
adenosine triphosphate, may be affected by anticholinergic
drugs blocking these urothelial receptors.17
Muscarinic receptors are widely distributed throughout
the body, and therefore anticholinergic drugs often have
undesirable systemic side effects.14
Anticholinergics have certain characteristics accounting for
slight differences in efficacy and side-effect profiles (Table
3).18 Most United States Food and Drug Administration-
approved agents are tertiary amines with the exception
of trospium, a quaternary amine with greater polarity and

1094 l NOVEMBER JOGC NOVEMBRE 2012

 Treatments for Overactive Bladder: Focus on Pharmacotherapy

Table 3. Published short-term safety of anticholinergics in different populations at

time of manuscript preparation
Elderly and/ Concomitant use Concomitant use
or cognitively of cholinesterase of CYP450
impaired inhibitors Cardiac inhibitors
Oxybutynin – – – –
Tolterodine  
IA IA
Trospium   
IIB IIB IIIB
Solifenacin 
IB
Darifenacin  
IB IB
NOTE: A checkmark indicates “safe to use.” The corresponding level of evidence is indicated. A dash means the drug
is not necessarily unsafe but indicates that safety studies specific to each concern are lacking.

hydrophilic properties.18 Smaller molecules, neutral in charge
and lipophilic, are more likely to cross the blood–brain barrier
and cause central nervous system side effects. These can be
immediate (confusion, delirium, headache, blurred vision,
dizziness and hallucinations) or delayed (memory loss).19,20
Specific patient factors such as increased permeability of the
blood–brain barrier in older adults, and comorbid diseases
predisposing to adverse CNS effects, as well as the intake of
other drugs with anticholinergic effects may render individual
patients particularly susceptible to antimuscarinic adverse
CNS events.20 Non-selective molecules with some M2
receptor affinity may lead to an increase in heart rate.19 Some
molecules acting on potassium channels within the heart
may cause small increases in the QT interval.19 Tolterodine
and solifenacin have led to small increases in the QT interval;
on the other hand, darifenacin, fesoterodine, and trospium
have not.19 These small recordable changes in heart function
do not seem to cause clinically adverse outcomes.19 Most
anticholinergics are metabolized by the CYP450 system in
the liver with the exception of trospium, which undergoes
minimal hepatic metabolism. Therefore, other medications
or dietary components affecting the CYP450 mechanism
may interact with anticholinergic drugs.19
Clinical Efficacy: Anticholinergics
Compared With Placebo
A Cochrane Review of 5 of 6 anticholinergic drugs currently
on the market concluded that anticholinergics lead to
statistically significant improvements in OAB symptoms.20
The number needed to treat for clinical improvement or
cure was 7. On average, patients on anticholinergics had 4
fewer leakage episodes and 5 fewer voids per week when
compared with patients on placebo. As anticholinergics are
not curative in most instances, clinical success depends on
ongoing use; thus a recommendation was made for future
trials to include long-term, patient-centred outcomes.
Oxybutynin (Ditropan, Ditropan XL)
Oxybutynin oral preparations have established clinical
efficacy when compared with placebo.20 Oxybutynin IR is
also more cost-effective.21 However, it is associated with
significant anticholinergic adverse events in up to 80% of
patients22 and with discontinuation rates of up to 33%.23
Shortly after treatment initiation, oxybutynin may cause
cognitive impairment, and long-term trials of cognitive
function while on this anticholinergic are lacking.24–26
Two transdermal preparations, a patch (Oxytrol) and a gel
(Gelnique 10%), have been developed to improve on the side-
effect profile of oral oxybutynin.27–29 Both preparations have
superior clinical efficacy to placebo, with fewer side effects
than oral oxybutynin.27–30 Application site reactions (pruritus
and erythema) are more common with the transdermal
preparations (14% for the patch and 5% for the gel).27–29
Recommendation
2. Oral oxybutynin, immediate and extended release,
as well as transdermal oxybutynin, may be offered
as treatment for overactive bladder syndrome, as
they are associated with significant objective
clinical improvement at 12 weeks. (I-A)
Oxybutynin immediate release has superior cost-
effectiveness but more side effects than other
anticholinergics. (I-A) Adverse events associated
with transdermal oxybutynin are fewer than with oral
oxybutynin. (I-A)
Tolterodine (Detrol, Detrol LA,)
Both IR and ER tolterodine are associated with
improvements in health-related quality of life and objective
OAB parameters in the results of several randomized
placebo controlled trials with 12-week duration of follow-
up.30–32 Greater effects are noted in patients with moderate

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SOGC CLINICAL PRACTICE GUIDELINE
to severe OAB symptoms at baseline.33 Dry mouth is a
common side effect that occurs in one third of patients
on tolterodine,34 but it does not increase the number of
treatment discontinuations.35 Tolterodine does not seem to
cause any cardiovascular or CNS adverse effects.35
Recommendation
3. Tolterodine, immediate and extended release, may
be offered as treatment for overactive bladder
syndrome, as it is associated with significant
objective clinical improvement at 12 weeks. (I-A)
Trospium (Trosec IR and XR)
Trospium, both IR and XR, was associated with improved
OAB symptoms in reports from several randomized
placebo controlled trials with 12-week duration of follow-
up.20,36,37 Adverse effects are more common than with
placebo but do not affect discontinuation rates. The XR
formulation significantly improves OAB symptoms and
condition-specific quality of life.38,39
Trospium has low penetration into the CNS and thus fewer
CNS side effects.36,37,40 In addition, it offers benefits for the
bladder and does not affect cognitive function even when
used concurrently with a cholinesterase inhibitor for the
treatment of Alzheimer’s disease.41 Trospium undergoes
minimal hepatic metabolism. Therefore patients who
receive concurrent medications that inhibit the CYP450
hepatic metabolism are good candidates for therapy with
trospium.40 Trospium is primarily excreted intact in the urine;
however, medications competing for renal elimination, such
as digoxin, have not shown significant interactions.42
Recommendation
4. Trospium, immediate and extended release, may
be offered as treatment for overactive bladder
syndrome as it is associated with significant clinical
improvement at 12 weeks. (I-A) Trospium is an
adequate anticholinergic choice for overactive
bladder syndrome patients with pre-existing
cognitive impairment (II-B) and for overactive
bladder syndrome patients taking concurrent
CYP450 inhibitors. (III-B)
Solifenacin (VESIcare)
Several double-blind placebo-controlled randomized
controlled trials with 12-week follow-up support the
safety and clinical efficacy of solifenacin compared with
placebo.43–46 Solifenacin also significantly improves the quality
of life in patients with OAB symptoms up to 1 year.46–48
At 1 year, discontinuation rates are low.46 The incidence of
dry mouth in patients on solifenacin is significantly lower
than in patients on oxybutynin (35 vs. 83%, P < 0. 001).49
1096 l NOVEMBER JOGC NOVEMBRE 2012
The incidence of constipation is 7% to 8%.43 Solifenacin
does not appear to affect cognitive function, as shown in a
pilot randomized trial of healthy elderly volunteers.50
Recommendation
5. Solifenacin may be offered as treatment for
overactive bladder syndrome, as it is associated
with significant objective clinical improvement at
12 weeks. (I-A) Solifenacin may be an adequate
anticholinergic choice for elderly overactive bladder
syndrome patients or patients with pre-existing
cognitive dysfunction. (I-B)
Darifenacin (Enablex)
The safety and clinical efficacy of darifenacin compared with
placebo is shown by three randomized double-blind placebo-
controlled multicentre phase III trials with 12-week duration
of follow-up.51–53 The most common side effects are dry
mouth and constipation, but discontinuations are rare (0.6%
to 2.1% vs. 0.3% in the placebo group).54 Specifically, women
over 65 have a significant improvement in condition-specific
quality of life compared with those on placebo.55
Because of its M3 receptor selectivity, darifenacin does not
affect heart rate.56 Moreover, darifenacin does not affect
memory or other cognitive functions.57
Recommendation
6. Darifenacin may be offered as treatment for
overactive bladder syndrome, as it is associated
with significant objective clinical improvement
at 12 weeks. (I-A) Darifenacin is an adequate
anticholinergic choice for overactive bladder
syndrome patients with pre-existing cardiac
concerns or cognitive dysfunction. (I-B)
Clinical Efficacy: Anticholinergics
Compared With Non-Drug Therapies
A Cochrane Review compared the effects of various
anticholinergic drugs with those of non-pharmacologic
therapies, consisting mainly of bladder training, pelvic
floor muscle exercises, and electrostimulation.58 Thirteen
trials, with a total of 1770 participants, were analyzed.
Follow-up was up to 24 weeks after initiation of treatment.
Tolterodine and oxybutynin had similar cure rates and
subjective improvement for OAB when compared with
bladder training alone. Objective improvement was better in
the anticholinergic group than in the bladder training group.
When oxybutynin was compared with a more comprehensive
behavioural intervention consisting of pelvic floor muscle
exercises, biofeedback, and bladder training, the overall
effect subjectively and objectively favoured the behavioural
intervention (RR 2.42; 95% CI 1.00 to 5.85).

Oxybutynin or trospium compared with functional
electrostimulation yielded no statistically significant
difference in cure rates or subjective or objective measures
of improvement.58,59
Oxybutynin or tolterodine and bladder training compared
with bladder training alone showed a subjective advantage
of the combination treatment. Tolterodine and bladder
training or pelvic floor muscle exercises compared with
tolterodine alone did not show any statistically significant
difference in subjective improvement.58
Since the most recent Cochrane update of this review,
an additional randomized controlled trial was published
comparing darifenacin with darifenacin and a behavioural
modification program consisting of patient education
given in a primary physician’s office (timed voiding, dietary
modifications, Kegel exercises).60 There were no significant
differences between treatment groups in efficacy or health-
related quality of life variables.60
Recommendation
7. Overactive bladder syndrome patients should
be offered a choice between bladder training,
functional electric stimulation, and anticholinergic
therapy, as there is no difference in cure rates.
Combination therapy does not have a clear
advantage over one therapy alone. (I-A)
Choice of Anticholinergic Drug and Dose
A Cochrane Review analyzed 49 parallel trials comparing
different anticholinergics and commonly used doses.61
Follow-up was mostly 2 weeks to 3 months, except for 2
trials with treatment periods of 1 year or more.
Comparing oxybutynin with tolterodine, there were no
differences in subjective or objective cure. There were fewer
withdrawals among those taking tolterodine (7% vs. 12%,
RR 0.57; 95% CI 0.43 to 0.75), mainly because there were
fewer side effects.61 There were no statistically significant
differences in outcomes when oxybutynin and trospium
were compared. When several doses of tolterodine were
studied, ranging from 0.5 mg twice daily to 4 mg twice daily,
there were no statistically significant differences in objective
improvement or withdrawals because of side effects.
Subjective cure was more likely with the higher doses,
but these higher doses were more commonly associated
with high post-void residuals and dry mouth. Subjective
cure was also more likely with higher doses of extended
release oxybutynin (10 mg vs. 5 mg daily). Oxybutynin, 2.5
mg 3 times daily and 2.5 mg used as needed were equally
effective in terms of objective measures of improvement.
Trospium 40 mg daily and twice daily dosing had similar
Treatments for Overactive Bladder: Focus on Pharmacotherapy
effects in terms of objective measures of improvement.
Extended release preparations of both oxybutynin and
tolterodine, including the extended release oxybutynin
patch, were associated with less dry mouth than immediate
release preparations.61
Several other comparative randomized controlled trials
comparing anticholinergics have been published since the
most recent Cochrane Review update. One trial compared
solifenacin 5 mg and 10 mg daily with tolterodine extended
release 4 mg daily.62 Subjective cure was significantly more
common in the solifenacin group (59% vs. 49%, P = 0.006).
Objective measures of improvement and withdrawals
because of side effects were not significantly different
between the groups. Another trial comparing darifenacin
15 mg and 30 mg daily with oxybutynin 5 mg 3 times daily
showed comparable efficacy and improved tolerability
of darifenacin.63 The other trials compared fesoterodine
4 mg and 8 mg daily with tolterodine extended release 4
mg daily.64,65 Fesoterodine was superior to tolterodine on
several objective measures of improvement such as urge
incontinence episodes, severe urgency with incontinence,
mean voided volume, and number of continent days
per week. Diary dry rates were significantly better in the
fesoterodine group than in the tolterodine group (64% vs.
57%; P = 0.015).64,65
Recommendation
8. The choice of anticholinergic therapy should
be guided by individual patient comorbidities,
as objective efficacy of anticholinergic drugs is
similar. (I-A) Dose escalation does not improve
objective parameters and causes more
anticholinergic adverse effects. It is,
however, associated with improved subjective
outcomes. (I-A) To decrease side effects,
switching to a lower dose or using an extended
release formulation or a transdermal delivery
mechanism should be considered. (I-A)
Contraindications
Absolute contraindications to anticholinergic use include
urinary retention, gastric retention, uncontrolled narrow-
angle glaucoma, and known hypersensitivity to the
individual drugs or any of their ingredients.
Relative contraindications that warrant cautious use include
partial bladder outlet obstruction (borderline or high
post-void residuals), controlled narrow-angle glaucoma,
impaired cognitive function, reduced renal or hepatic
function, concomitant excessive alcohol use (added sedating
effects), decreased gastrointestinal motility, constipation,
and myasthenia gravis. Elderly patients in particular should
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SOGC CLINICAL PRACTICE GUIDELINE
be monitored for drug interactions or polypharmacy of
drugs with anticholinergic effect (e.g., antidepressants,
antipsychotics, anxiolytics), as the overall anticholinergic
load is associated with confusion, falls, and fractures.66
Anticholinergics are category C drugs in pregnancy, to be
used only if the benefits clearly outweigh the risk.
Adherence and Continuation Rates
Patient adherence to a prescribed anticholinergic treatment
plan has been shown to be low. In a study of oxybutynin
and tolterodine ER and IR prescriptions in 1117 adult
patients, only 13.2% persisted with treatment for at least
1 year, with a median time to discontinuation of 31 days.67
Adherence was significantly better but still suboptimal for
the extended release formulations.67 In another trial of
patients on immediate release oxybutynin, at 2-year follow-
up, 67% of respondents had stopped drug therapy, most
within 2 months of initiation.68 Reasons for discontinuation
were adverse effects (24%) and symptomatic improvement
or cure (53%).68 White ethnicity, previous hospitalization
length, starting with tolterodine or oxybutynin extended-
release, and previous use of topical drugs or antipsychotics
were associated with increased adherence to anticholinergics
during a 6-month period.69 Previous depression or
urinary tract infection diagnosis and polypharmacy
significantly increased the odds of early discontinuation.69
Patient counselling about efficacy of treatment, realistic
expectations, and length of treatment was recommended to
improve long-term adherence to anticholinergic therapy.70
Recommendation
9. Education on treatment efficacy, realistic
expectations, and length of treatment should be
offered to patients upon initiation of anticholinergic
therapy, as continuation rates for anticholinergic
therapy are low. (III-B)
PHARMACOTHERAPEUTIC
INTERVENTIONS: ESTROGENS
The lower urinary tract (urethra and trigone) derives from
the cloaca, which shares an embryological origin with the
lower vaginal canal. Therefore, the trigonal squamous
epithelium differs from the transitional epithelium and
undergoes squamous metaplasia. The urethral mucosa is
continuous with the squamous epithelium of the vestibule.
Both areas are hormonally sensitive.71 A Cochrane Review
examined the effect of estrogen supplementation on urinary
incontinence in postmenopausal women.72 Heterogeneous
evidence derived from trials investigating other conditions
such as stress urinary incontinence and using greater than
low dose vaginal estrogen of different types, showed that
there were 1 to 2 fewer voids in 24 hours and nocturnal
1098 l NOVEMBER JOGC NOVEMBRE 2012
voids amongst women treated with local estrogen.72 A small
trial showed modest benefit from vaginal estriol ovules in
prevention of symptoms of urgency and frequency after
tension-free vaginal tape placement.72
Oral estriol or a subcutaneous estradiol implant were not
significantly better than placebo for OAB symptoms.73,74
Recommendation
10. Oral or transdermal estrogen supplementation
should not be recommended for treatment of
overactive bladder syndrome as its effects are
comparable to placebo. (I-E) Vaginal estrogen
can be suggested for subjective improvements in
overactive bladder syndrome symptoms. (III-B)
PHARMACOTHERAPEUTIC
INTERVENTIONS: OTHER DRUG OPTIONS
There is a long list of medications with anticholinergic
effects, few of which have been studied as treatment
specifically for overactive bladder. Tricyclic antidepressants
such as imipramine and amitryptyline have been used for
overactive bladder. With a dual activity as an anticholinergic
(to relax the detrusor) and an alpha agonist (to contract
the urethral sphincter), they have adequate biologic
plausibility for the treatment of urinary urge incontinence.
Unfortunately, their anticholinergic activity is weaker
than that of modern bladder anticholinergics.75 There
is minimal evidence to support the use of imipramine
for urinary incontinence in the elderly.75 There are no
randomized controlled trials to compare tricyclics with
modern anticholinergics used to treat overactive bladder.75
REFRACTORY OAB
Options for OAB symptoms resistant to anticholinergic
therapy are limited and costly. These options include but
are not limited to local bladder therapies such as botulinum
toxin type A detrusor injections, central neurostimulation,
and peripheral neurostimulation (e.g., tibial nerve).
Botulinum toxin for OAB (100 to 300 units injected into the
detrusor muscle) has been shown, in several randomized
controlled trials, to reduce number of voids and urgency
and incontinence episodes per day and to improve
maximum cystometric capacity and condition-specific
quality of life.76 Generally, around 80% of patients treated
with botulinum toxin experienced improvement, with
some patients requiring reinjection for recurrence of OAB
symptoms.76 Overall patient satisfaction with botulinum
toxin was high.76 The most common complication related
to intravesical botulinum toxin was transient urinary

retention. Up to 43% of patients needed clean intermittent
self-catheterization, and the incidence of retention was
reported to be dose-dependent.76
There are also data from randomized controlled trials to
support the use of sacral nerve stimulation. Good clinical
response, with improvement on several objective measures
of OAB severity, was reported in 64% 88% of patients,
and clinical success seems to persist in the long term.
Subjective outcomes are also favourable.76 However, lead
migration, pain, and infection result in a 33% reoperation
rate to treat these complications.77
Another form of neurostimulation, tibial nerve
stimulation, is gaining acceptance. Two double-blind
randomized sham-controlled trials showed significant
objective and subjective improvements in OAB when
compared with placebo.78,79 Treatment benefit was
sustained at 12 months.80 A randomized controlled trial
of tibial nerve stimulation versus tolterodine showed
similar objective improvement and superior subjective
improvement or cure at 12 weeks.81
Recommendation
11. Intravesical botulinum toxin injection and sacral
nerve and posterior tibial nerve stimulation
are clinically effective options for patients with
overactive bladder syndrome unresponsive to
conservative options, anticholinergics, or vaginal
estrogen. (I-A)
CONCLUSION
Overactive bladder syndrome is a common bothersome
condition. Options for therapy include behavioural,
pharmacologic, and surgical interventions. Pharmacotherapy
for OAB includes anticholinergics and local vaginal estrogen.
Anticholinergics have been shown to offer some symptomatic
improvement over placebo, with a strong placebo therapeutic
effect noted. Anticholinergics are similar to behavioural
therapy and electrical stimulation in clinical efficacy. They
have significant side effects that need to be carefully
considered along with individual patient comorbidities.
Newer formulations, particularly those administered
transdermally, have been shown to have a better side-effect
profile. Long-term effects of anticholinergics and patient-
centred outcomes should be the focus of future studies.
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stimulation versus extended-release tolterodine: results from the
overactive bladder innovative therapy trial. J Urol 2009;182(3):1055–61.
82. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for
recommendations from the Canadian Task Force on Preventive Health
Care. CMAJ 2003;169:207–8.
NOVEMBER JOGC NOVEMBRE 2012 l 1101
 SOGC clinical practice guideline

No. 274, March 2012

Management of Varicella Infection

(Chickenpox) in Pregnancy

This Clinical Practice Guideline has been prepared by the Abstract

Maternal Fetal Medicine Committee, reviewed by the Infectious
Diseases Committee and the Family Physician Advisory
Committee, and approved by the Executive and Council of the
Society of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHORS
Objective: To review the existing data regarding varicella zoster
virus infection (chickenpox) in pregnancy, interventions to reduce
maternal complications and fetal infection, and antepartum and
peripartum management.

Alon Shrim, MD, Montreal QC Methods: The maternal and fetal outcomes in varicella zoster
infection were reviewed, as well as the benefit of the different
Gideon Koren, MD, Toronto ON treatment modalities in altering maternal and fetal sequelae.
Mark H. Yudin, MD, Toronto ON Evidence: Medline was searched for articles and clinical guidelines
Dan Farine, MD, Toronto ON published in English between January 1970 and November 2010.
MATERNAL FETAL MEDICINE COMMITTEE Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Robert Gagnon, MD (Co-Chair), Verdun QC
Care. Recommendations for practice were ranked according to
Lynda Hudon, MD (Co-Chair), Montreal QC the method described in that report (Table).
Melanie Basso, RN, Vancouver BC
Recommendations
Hayley Bos, MD, London ON
1. Varicella immunization is recommended for all non-immune
Joan Crane, MD, St. John’s NL women as part of pre-pregnancy and postpartum care. (II-3B)
Gregory Davies, MD, Kingston ON 2. Varicella vaccination should not be administered in pregnancy.
Marie-France Delisle, MD, Vancouver BC However, termination of pregnancy should not be advised
because of inadvertent vaccination during pregnancy. (II-3D)
Savas Menticoglou, MD, Winnipeg MB
William Mundle, MD, Windsor ON 3. The antenatal varicella immunity status of all pregnant women
should be documented by history of previous infection, varicella
Annie Ouellet, MD, Sherbrooke QC vaccination, or varicella zoster immunoglobulin G serology. (III-C)
Tracy Pressey, MD, Vancouver BC 4. All non-immune pregnant women should be informed of the risk
Christy Pylypjuk, MD, Saskatoon SK of varicella infection to themselves and their fetuses. They should
be instructed to seek medical help following any contact with a
Anne Roggensack, MD, Calgary AB
person who may have been contagious. (II-3B)
Frank Sanderson, MD, Saint John NB
5. In the case of a possible exposure to varicella in a pregnant
Vyta Senikas, MD, Ottawa ON woman with unknown immune status, serum testing should be
Disclosure statements have been received from all members of performed. If the serum results are negative or unavailable within
the committee. 96 hours from exposure, varicella zoster immunoglobulin should
be administered. (III-C)
6. Women who develop varicella infection in pregnancy need to be
made aware of the potential adverse maternal and fetal sequelae,
J Obstet Gynaecol Can 2012;34(3):287–292 the risk of transmission to the fetus, and the options available for
prenatal diagnosis. (II-3C)
7. Detailed ultrasound and appropriate follow-up is recommended for
Key Words: Chickenpox, varicella, diagnosis, pregnancy all women who develop varicella in pregnancy to screen for fetal
consequences of infection. (III-B)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

MARCH JOGC MARS 2012 l 287

SOGC clinical practice guideline
8. Women with significant (e.g., pneumonitis) varicella infection
in pregnancy should be treated with oral antiviral agents (e.g.,
acyclovir 800 mg 5 times daily). In cases of progression to varicella
pneumonitis, maternal admission to hospital should be seriously
considered. Intravenous acyclovir can be considered for severe
complications in pregnancy (oral forms have poor bioavailability).
The dose is usually 10 to 15 mg/kg of BW or 500 mg/m2 IV every
8 h for 5 to 10 days for varicella pneumonitis, and it should be
started within 24 to 72 h of the onset of rash. (III-C)
9. Neonatal health care providers should be informed of peripartum
varicella exposure in order to optimize early neonatal care with
varicella zoster immunoglobulin and immunization. (III-C) Varicella
zoster immunoglobulin should be administered to neonates
whenever the onset of maternal disease is between 5 days before
and 2 days after delivery. (III-C)
INTRODUCTION
V
aricella zoster virus is a highly contagious DNA virus
of the herpes family. It is transmitted by respiratory
droplets and by direct personal contact with vesicular fluid.
The primary infection is characterized by fever, malaise, and
a pruritic rash that develops into crops of maculopapules,
which become vesicular and crust over before healing. The
incubation period lasts 10 to 21 days, and the disease is
infectious 48 hours before the rash appears and continues
to be infectious until the vesicles crust over.1
Chickenpox (or primary VZV infection) is a common
childhood disease. In this population it usually causes
mild infection, and mortality rates in the United States
are as low as 0.4 per 1 million population.2 It is estimated
that > 90% of the antenatal population are seropositive
for VZV IgG antibody3 and therefore almost invariably
immune to infection. Because of this high frequency
of immunity, contact with chickenpox among pregnant
women rarely results in primary maternal VZV infection,
which is estimated to complicate up to 2 to 3 of every 1000
pregnancies.4 Therefore in Canada, with about 350 000
pregnancies per year,5 700 to 1050 cases of chickenpox in
pregnant women are expected to occur annually.
Following the primary infection, the virus may remain
dormant in sensory nerve root ganglia but can be
reactivated to cause a vesicular erythematous skin rash
in a dermatomal distribution known as herpes zoster or
shingles. As shingles in pregnancy is not associated with
viremia and does not appear to cause fetal sequelae, it is
not discussed in these guidelines.
ABBREVIATIONS
IgG immunoglobulin G
VZIG varicella zoster immunoglobulin
VZV varicella zoster virus
288 l MARCH JOGC MARS 2012
POSSIBLE SEQUELAE OF VARICELLA
INFECTION IN PREGNANCY: MATERNAL
The mortality rate for chickenpox increases with age. Thus in
early adulthood it is associated with mortality rate that is 15
times higher than the childhood mortality rate.6 According
to the Centers for Disease Control and Prevention, the case
fatality rate increases from 2.7 per 100 000 persons aged
15 to 19 years, to 25.2 per 100 000 persons aged 30 to 39.7
Mortality rates are higher in pregnant women than in non-
pregnant adults, and death usually results from respiratory
disease. It is estimated that 5% to 10% of pregnant women
with varicella infection develop pneumonitis.8 Risk factors
for the development of varicella pneumonitis in pregnancy
include cigarette smoking and > 100 skin lesions.9 Most of
the complications of adult chickenpox, such as pneumonitis
occur on day 4 or later.10 In one prospective study,11 12 out
21 pregnant patients who were diagnosed with varicella
pneumonitis and treated with acyclovir in the second or third
trimester of pregnancy required intubation and mechanical
ventilation. The strongest correlate with maternal death was
onset of disease in the third trimester, with no deaths among
the second-trimester subjects.
POSSIBLE SEQUELAE OF VARICELLA
INFECTION IN PREGNANCY: FETAL
Fetal effects of varicella can manifest as either congenital
varicella syndrome (embryopathy) or neonatal varicella (no
embryopathy, but chickenpox infection within the first 10
days of life). Since the first described cases in 1947, the
overall number of neonates that have been reported to
have congenital varicella syndrome is as low as 41 per year
in the United States, 4 per year in Canada, and 7 per year
in the United Kingdom and Germany.12,13 Maternal varicella
during the first half of pregnancy may cause congenital
malformations or deformations by transplacental infection.
Some of these manifestations include chorioretinitis, cerebral
cortical atrophy, hydronephrosis, and cutaneous and bony
leg defects, often presenting as a partial limb reduction.14
Rates of infection are approximately 0.4% before 13 weeks
and 2% between 13 and 20 weeks.4,15 In a systematic review
by the Motherisk program (Canadian data), with all available
cohort studies, the risk was 0.7% in the first trimester, 2%
in the second, and 0% in the third trimester.16 In most of
the cohorts, there was no clinical evidence of congenital
varicella embryopathy after 20 weeks’ gestation.17 Yet, Tan
and Koren reviewed the literature and identified 9 case
reports of fetal varicella syndrome occurring in weeks 21 to
28 of gestation.12 In 8 out of these 9 cases there were serious
adverse effects in the central nervous system, an incidence
as high as the rates of central nervous system involvement
in earlier trimesters.13

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.36
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.36
Findings that can be seen on ultrasound include
musculoskeletal abnormalities seen as asymmetric limb
shortening or malformations, chest wall malformations,
intestinal and hepatic echogenic foci, intrauterine growth
restriction, polyhydramnios, fetal hydrops, or fetal demise.
Cerebral anomalies documented with ultrasound include
ventriculomegaly, hydrocephalus, microcephaly with
polymicrogyria, and porencephaly. Congenital cataract
and microphthalmos are the most common ocular lesions
but are not readily visible on ultrasound.18 In most of
the relevant studies, ultrasound findings suggestive of
congenital varicella syndrome were detected in the majority
of the affected fetuses.19,20
PERIPARTUM EXPOSURE
Exposure of the baby to the virus just before or during
delivery poses a serious threat to the neonate, which may
develop a fulminant neonatal infection (neonatal varicella).
Rarely, these neonates can develop disseminated visceral
and central nervous system disease, which is commonly
fatal. Neonatal infection occurs primarily when symptoms
of maternal infection occur less than 5 days before
delivery to 2 days after.21 This period correlates with the
development of maternal IgG and is therefore too short
to provide transplacental passive immunization to the fetus
and neonate. When varicella zoster immune globulin is
administered to the mother, 30% to 40% of newborns still
develop infection; however, the number of complications
is reduced.22
Management of Varicella Infection (Chickenpox) in Pregnancy
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
PREVENTION OF MATERNAL COMPLICATIONS
The efficacy of antiviral therapy in treating varicella
pneumonia in adults has not been uniformly established
through randomized clinical trials, and its efficacy has
been debated.23 However, in one study, oral acyclovir was
shown to be more effective than placebo in reducing the
duration of fever and symptoms of varicella infection in
immunocompromised children and immunocompetent
adults if commenced within 24 hours of development of
the rash.24,25 As a result it is generally recommended that
children at high risk and adults with a substantive varicella
infection (> 100 lesions) and/or respiratory co-factors
should be treated with oral antivirals. Pregnant women
with varicella pneumonitis should definitely be treated
with oral antivirals and, if level of illness warrants, with
IV antivirals.
PREVENTION OF INTRAUTERINE INFECTION
Definition of Significant Exposure
Direct contact exposure is defined as direct contact
that lasts an hour or longer with an infectious person
while indoors. Substantial exposure for hospital
contacts consists of sharing the same hospital room
with an infectious patient or prolonged, direct, face-
to-face contact with an infectious person (e.g., health
care workers). Brief contacts with an infectious person
(e.g., contact with X-ray technicians or housekeeping
personnel) are less likely than more prolonged contacts
to result in VZV transmission.
MARCH JOGC MARS 2012 l 289
SOGC clinical practice guideline
Persons with continuous exposure to household members
who have varicella are at greatest risk for infection.7
Vaccine
An attenuated live-virus vaccine (Varivax) was approved
for use in 1995.26 Two doses, given 4 to 8 weeks apart,
are recommended for adolescents ≥ 13 years of age
and for adults with no history of varicella. This results
in 97% seroconversion.27 The vaccine, however, is not
recommended for pregnant women or for those within a
month of pregnancy. Nevertheless, a pregnancy registry
listing 362 vaccine-exposed pregnancies has reported no
case of congenital varicella syndrome or other congenital
malformation.28 Therefore, termination of pregnancy
should not be recommended because of inadvertent
vaccination during pregnancy.
Varicella Zoster Immunoglobulin
As prevention is the most effective strategy for the
reduction of maternal complications associated with
varicella infections, immunoglobulin prophylaxis is an
important objective for susceptible, exposed pregnant
women.23
VZIG has been shown to lower varicella infection rates
if administered within 72 to 96 hours after exposure.4
The effectiveness of VZIG when given beyond the
96 hours after initial exposure has not been evaluated.
Protection is estimated to extend through 3 weeks, which
corresponds with the half-life of the immunoglobulin.
The principal indication for the use of VZIG in
pregnant women is reduction of the maternal risks of
varicella infection-related complications associated with
adult disease.4 If the mother does not acquire varicella
infection, this eliminates risk for the neonate, but this
has not been studied as an end point because of the
low frequency of cases. The dose is 125 units per
10 kg given intramuscularly, with a maximum dose of
625 units. VZIG is recommended7 for all susceptible
pregnant women.29
To determine if an exposed pregnant woman is susceptible,
a history of varicella infection should be taken, and, if this
is positive, the woman can be assumed to be immune. If
the history is negative and no varicella antibody testing was
done in early pregnancy, antibody testing with enzyme-
linked immunosorbent assay or fluorescent antibody to
membrane antigen should, if possible, precede use of
VZIG. However, in settings where pregnant women might
be tested too late and/or results may not be available
quickly, using VZIG before antibody testing results are
available might be practical.
290 l MARCH JOGC MARS 2012
The value of VZIG in averting fetal varicella is primarily
in its ability to prevent maternal infection, but it may have
some effect in decreasing the risk of fetal infection even
in those women who go on to develop varicella. In a
study of 1373 women who had varicella during pregnancy,
9 cases of congenital varicella syndrome were identified, all
occurring after maternal varicella during the first 20 weeks
of gestation. However, no cases of congenital varicella
syndrome were reported in any of the 97 women in whom
varicella occurred after post-exposure prophylaxis with
anti-VZIG.4,30,31
The most frequent adverse reaction following VZIG
administration is local discomfort at the injection site, with
pain, redness, and swelling occurring in approximately
1% of people.32 Less frequent adverse events include
gastrointestinal symptoms, malaise, headache, rash, and
respiratory symptoms, which occur in approximately 0.2%
of recipients. Severe events, such as angioneurotic edema
and anaphylactic shock, are rare (occurring in < 0.1% of
recipients). Obstetrical care providers need to be aware
of the availability of testing and therapy in their local
environment. As both testing and therapy are time sensitive,
it is important to know the turnover time for the test in local
laboratories, and how to arrange VZIG administration. As
VZIG is a blood product, patient consent is required.
TREATMENT
Acyclovir
Acyclovir is a synthetic nucleoside analogue that inhibits
replication of human herpes viruses, including VZV.
Acyclovir crosses the placenta readily and can be found
in fetal tissues, cord blood as well as in the amniotic fluid.
It may inhibit viral replication during maternal viremia,
limiting transplacental passage of the virus.33,34
Safety
Data published since acyclovir became available do not
indicate increased adverse effects related to its use in
pregnancy.35
Efficacy
When compared with placebo, oral acyclovir reduces the
duration of fever and symptoms of varicella infection in
immunocompromised children and immunocompetent
adults if commenced within 24 hours of development
of the rash.24,25 In instances of serious, viral-mediated
complications (e.g., pneumonitis), the American Academy
of Pediatrics states that intravenous acyclovir should be
considered.7 It is not given as prophylaxis to exposed
women during pregnancy.

Recommendations
1. Varicella immunization is recommended for all
non-immune women as part of pre-pregnancy and
postpartum care. (II-3B)
2. Varicella vaccination should not be administered
in pregnancy. However, termination of pregnancy
should not be advised because of inadvertent
vaccination during pregnancy. (II-3D)
3. The antenatal varicella immunity status of all
pregnant women should be documented by history
of previous infection, varicella vaccination, or
varicella zoster immunoglobulin G serology. (III-C)
4. All non-immune pregnant women should be
informed of the risk of varicella infection to
themselves and their fetuses. They should be
instructed to seek medical help following any
contact with a person who may have been
contagious. (II-3B)
5. In the case of a possible exposure to varicella in
a pregnant woman with unknown immune status,
serum testing should be performed. If the serum
results are negative or unavailable within 96 hours
from exposure, varicella zoster immunoglobulin
should be administered. (III-C)
6. Women who develop varicella infection in
pregnancy need to be made aware of the potential
adverse maternal and fetal sequelae, the risk of
transmission to the fetus, and the options available
for prenatal diagnosis. (II-3C)
7. Detailed ultrasound and appropriate follow-up is
recommended to all women who develop varicella
in pregnancy to screen for fetal consequences for
infection. (III-B)
8. Women with significant (e.g., pneumonitis) varicella
infection in pregnancy should be treated with oral
antiviral agents (e.g., acyclovir 800 mg 5 times daily).
In cases of progression to varicella pneumonitis,
maternal admission to hospital should be seriously
considered. Intravenous acyclovir can be considered
for severe complications in pregnancy (oral forms
have poor bioavailability). The dose is usually 10 to
15 mg/kg of BW or 500 mg/m2 IV every 8 h for 5 to
10 days for varicella pneumonitis, and it should be
started within 24 to 72 h of the onset of rash. (III-C)
9. Neonatal health care providers should be informed
of peripartum varicella exposure in order to
optimize early neonatal care with varicella zoster
immunoglobulin and immunization. (III-C) Varicella
zoster immunoglobulin should be administered to
neonates whenever the onset of maternal disease is
between 5 days before and 2 days after delivery. (III-C)
Management of Varicella Infection (Chickenpox) in Pregnancy
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2. Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella
after implementation of varicella vaccination in the United States. N Engl
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11. Smego RA Jr, Asperilla MO. Use of acyclovir for varicella pneumonia
during pregnancy. Obstet Gynecol 1991;78:1112–6.
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2006;21:410–20.
13. Koren G. Congenital varicella syndrome in the third trimester. Lancet
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14. Andrews JI. Diagnosis of fetal infections. Curr Opin Obstet Gynecol
2004;16:163–6.
15. Pastuszak AL, Levy M, Schick B, Zuber C, Feldkamp M, Gladstone J,
et al. Outcome after maternal varicella infection in the first 20 weeks of
pregnancy. N Engl J Med 1994;330(13):901–5.
16. Koren G. Risk of varicella infection during late pregnancy. Can Fam
Physician 2003;49:1445–6.
17. Chiang CP, Chiu CH, Huang YC, Lin TY. Two cases of disseminated
cutaneous herpes zoster in infants after intrauterine exposure to varicella-
zoster virus. Pediatr Infect Dis J 1995;14:395–7.
18. Degani S. Sonographic findings in fetal viral infections: a systematic
review. Obstet Gynecol Surv 2006;61:329–36.
19. Skibsted L. Abnormal fetal ultrasound findings after maternal chickenpox
infection [article in Danish]. Ugeskr Laeger 2000;162(18):2546–9.
20. Pretorius DH, Hayward I, Jones KL, Stamm E. Sonographic evaluation
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21. Meyers JD. Congenital varicella in term infants: risk reconsidered. J Infect
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Accessed December 26, 2011.
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23. Maupin RT. Obstetric infectious disease emergencies. Clin Obstet Gynecol
2002;45(2):393–404.
24. Wallace MR, Bowler WA, Murray NB, Brodine SK, Oldfield EC III.
Treatment of adult varicella with oral acyclovir. A randomized, placebo-
controlled trial. Ann Intern Med 1992;117:358–63.
25. Nyerges G, Meszner Z, Gyarmati E, Kerpel-Fronius S. Acyclovir prevents
dissemination of varicella in immunocompromised children. J Infect Dis
1988;157:309–13.
26. ACOG practice bulletin. Perinatal viral and parasitic infections. Number
20, September 2000. (Replaces educational bulletin number 177, February
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Obstet 2002;76:95–107.
27. ACOG Committee Opinion. Immunization during pregnancy. Obstet
Gynecol 2003;101:207–12.
28. Shields KE, Galil K, Seward J, Sharrar RG, Cordero JF, Slater E. Varicella
vaccine exposure during pregnancy: data from the first 5 years of the
pregnancy registry. Obstet Gynecol 2001;98:14–9.
29. Gruslin A, Steben M, Halperin S, Money DM, Yudin MH; SOGC
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al. Serum concentrations, efficacy, and safety of a new, intravenously
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33. Henderson GI, Hu ZQ, Johnson RF, Perez AB, Yang Y, Schenker
S. Acyclovir transport by the human placenta. J Lab Clin Med
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34. Landsberger EJ, Hager WD, Grossman JH III. Successful management
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Reprod Med 1986;31:311–4.
35. Spangler JG, Kirk JK, Knudson MP. Uses and safety of acyclovir in
pregnancy. J Fam Pract 1994;38:186–91
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 SOGC Clinical Practice Guideline

No. 269, November 2011

Advanced Reproductive Age and Fertility

Abstract
This clinical practice guideline has been prepared by the
Reproductive Endocrinology and Infertility Committee, Objective: To improve awareness of the natural age-related
reviewed by the Family Physicians Advisory Committee and decline in female and male fertility with respect to natural
the Maternal-Fetal Medicine Committee, and approved by fertility and assisted reproductive technologies (ART) and
the Executive and Council of the Society of Obstetricians provide recommendations for their management, and to review
and Gynaecologists of Canada. investigations in the assessment of ovarian aging.
PRINCIPAL AUTHORS Options: This guideline reviews options for the assessment of
Kimberly Liu, MD, Toronto ON ovarian reserve and fertility treatments using ART with women of
advanced reproductive age presenting with infertility.
Allison Case, MD, Saskatoon SK
Reproductive Endocrinology and Infertility Outcomes: The outcomes measured are the predictive value of
COMMITTEE ovarian reserve testing and pregnancy rates with natural and
assisted fertility.
Anthony P. Cheung, MD (Co-Chair), Vancouver BC
Evidence: Published literature was retrieved through searches
Sony Sierra, MD (Co-Chair), Toronto ON
of PubMed or Medline, CINAHL, and The Cochrane Library in
Saleh AlAsiri, MD, Vancouver BC June 2010, using appropriate key words (ovarian aging, ovarian
Belina Carranza-Mamane, MD, Sherbrooke QC reserve, advanced maternal age, advanced paternal age, ART).
Results were restricted to systematic reviews, randomized
Allison Case, MD, Saskatoon SK controlled trials/controlled clinical trials, and observational studies.
Cathie Dwyer, RN, Toronto ON There were no date or language restrictions. Searches were
updated on a regular basis and incorporated into the guideline to
James Graham, MD, Calgary AB
December 2010.
Jon Havelock, MD, Burnaby BC
Values: The quality of evidence was rated using the criteria described
Robert Hemmings, MD, Montreal QC in the Report of the Canadian Task Force on Preventive Health
Francis Lee, MD, Winnipeg MB Care. Recommendations for practice were ranked according to
the method described in that report (Table).
Kimberly Liu, MD, Toronto ON
Benefits, harms, and costs: Primary and specialist health care
Ward Murdock, MD, Fredericton NB providers and women will be better informed about ovarian aging
Vyta Senikas, MD, Ottawa ON and the age-related decline in natural fertility and about options for
assisted reproductive technology.
Tannys D.R. Vause, MD, Ottawa ON
Benjamin Chee-Man Wong, MD, Calgary AB
Recommendations
Disclosure statements have been received from all members of
the committee. 1. Women in their 20s and 30s should be counselled about the age-
related risk of infertility when other reproductive health issues,
such as sexual health or contraception, are addressed as part of
their primary well-woman care. Reproductive-age women should
be aware that natural fertility and assisted reproductive technology
success (except with egg donation) is significantly lower for
women in their late 30s and 40s. (II-2A)
2. Because of the decline in fertility and the increased time to
Key Words: Ovarian aging, advanced reproductive age, assisted conception that occurs after the age of 35, women > 35 years
reproductive technology of age should be referred for infertility work-up after 6 months of
trying to conceive. (III-B)

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

NOVEMBER JOGC NOVEMBRE 2011 l 1165

SOGC Clinical Practice Guideline

3. Ovarian reserve testing may be considered for women ≥ 35
years of age or for women < 35 years of age with risk factors
for decreased ovarian reserve, such as a single ovary, previous
ovarian surgery, poor response to follicle-stimulating hormone,
previous exposure to chemotherapy or radiation, or unexplained
infertility. (III-B)
4. Ovarian reserve testing prior to assisted reproductive technology
treatment may be used for counselling but has a poor predictive
value for non-pregnancy and should be used to exclude women
from treatment only if levels are significantly abnormal. (II-2A)
5. Pregnancy rates for controlled ovarian hyperstimulation are low for
women > 40 years of age. Women > 40 years should consider IVF
if they do not conceive within 1 to 2 cycles of controlled ovarian
hyperstimulation. (II-2B)
6. The only effective treatment for ovarian aging is oocyte donation.
A woman with decreased ovarian reserve should be offered
oocyte donation as an option, as pregnancy rates associated with
this treatment are significantly higher than those associated with
controlled ovarian hyperstimulation or in vitro fertilization with a
woman’s own eggs. (II-2B)
7. Women should be informed that the risk of spontaneous
pregnancy loss and chromosomal abnormalities increases with
age. Women should be counselled about and offered appropriate
prenatal screening once pregnancy is established. (II-2A)
8. Pre-conception counselling regarding the risks of pregnancy
with advanced maternal age, promotion of optimal health and
weight, and screening for concurrent medical conditions such as
hypertension and diabetes should be considered for women
> age 40. (III-B)
9. Advanced paternal age appears to be associated with an
increased risk of spontaneous abortion and increased frequency
of some autosomal dominant conditions, autism spectrum
disorders, and schizophrenia. Men > age 40 and their partners
should be counselled about these potential risks when they are
seeking pregnancy, although the risks remain small. (II-2C)
J Obstet Gynaecol Can 2011;33(11):1165–1175
INTRODUCTION
first-time mothers who are > 30 years of age increased
steadily from 11% in 1987 to 26% in 2005.1 During the
same period, there was a significant rise in first-time
mothers > 35 years of age, from 4% in 1987 to 11% in
2005, and a corresponding decrease in the group who are
< 25 years.1 Similar trends have been seen in other parts
of the world.3
Ovarian function declines as women approach their later
reproductive years until menopause, and increasing age is
associated with lowered fecundity and infertility. Women
experience a decline in natural fertility that begins in the
mid-30s, and they will often reach sterility many years
before the complete cessation of menses.4 Although ART
may aid some couples who present with fertility issues, it
will not compensate for the decline in natural fertility that
occurs with delayed child-bearing.5 ART is also invasive,
expensive, and not covered by most provincial health
plans for this indication. In addition, complications of
pregnancy increase for both the mother and the offspring
with advanced maternal age.6
Women and their health care providers should be aware of
the effects of age on reproductive potential.
OVARIAN AGING
The loss of oocytes from the ovaries is a continual process
that begins in utero. The ovaries in the female fetus contain
6 to 7 million oocytes at approximately 20 weeks’ gestation.
At birth, 1 to 2 million oocytes remain, and only 300 000 to
500 000 are present at the onset of puberty.7 This process
continues until menopause, when only a few hundred
oocytes remain.8 During the reproductive years, 400 to
500 oocytes will be ovulated; the majority of oocytes are

S
lost through apoptosis, or programmed cell death. Earlier
ocial trends in Canada and around the world have led
research suggested that a more accelerated process of
to women delaying child-bearing into their 30s and, in
decline occurs in the last 10 to 15 years before menopause,
some cases, their 40s. The average age of women giving
beginning around the age of 38 years.9 However, more
birth has increased from 27 to 29.3 over the last 20 years.1
recent data suggest that oocyte loss occurs at the same
In 2006, the fertility rate for women aged 30 to 34 was the
rate through the reproductive lifetime, with the slope of
highest of any age group, surpassing that of the previous
decline remaining fairly consistent until menopause.10
highest group, women aged 25 to 29.2 The percentage of
As the ovarian follicular pool decreases, women will
experience infertility, sterility, cycle shortening, menstrual
irregularity, and finally menopause (Figure 1).10 In
ABBREVIATIONS
Western countries, the mean age of menopause is 51, and
AFC antral follicle count
1% will experience premature ovarian failure before age
AMH antimüllerian hormone
40.11 There appears to be a fixed interval through these
ART assisted reproductive technology
stages of ovarian function. Women who experience an
COH controlled ovarian hyperstimulation earlier menopause will have an earlier loss of fertility12;
FSH follicle-stimulating hormone therefore, approximately 10% of women will have
IUI intrauterine insemination decreased ovarian function in their early to mid-30s.13

1166 l NOVEMBER JOGC NOVEMBRE 2011


Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force on
Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.95
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.95
Child-bearing usually ends 10 years before menopause,
and this time period is consistent regardless of the age
of menopause.14,15 Cycle irregularity will usually occur
6 to 7 years before menopause,14 regardless of the age
of menopause, coinciding with approximately 10 000
follicles remaining.8
As the total number of remaining follicles decreases, there is
a corresponding decrease in the available follicular cohort.
As a consequence of a smaller follicular cohort, there is a
decline in inhibin-B, which is produced by the granulosa
cells in the early follicular phase.16 There is an inverse
correlation between FSH and inhibin-B, which is likely due
to a loss in negative feedback; the rise in FSH during the
early follicular phase is one of the earliest signs of ovarian
aging.17 This initial stage may not be clinically apparent,
or present only as infertility, because ovarian hormone
production remains constant, and women continue to
ovulate and have regular cycles. The first clinical signs of
ovarian aging may be shortening of menstrual cycles, which
is due to a shorter follicular phase. More rapid follicular
development leads to earlier recruitment of a dominant
follicle.18 As this transition continues, women will notice
that their cycles lengthen and become more irregular as
they enter the menopause transition and ovulation is less
consistent.8 Once women start to notice clinical signs of
ovarian aging such as cycle shortening or irregularity, their
fertility may already be greatly diminished. One review
article found that women who were sterile after age 35 had
already demonstrated lower fecundity before the age of
Advanced Reproductive Age and Fertility
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
30.12 Markers of ovarian reserve may be useful to predict
an earlier menopause or menopause transition for women
who do not yet have clinical signs or symptoms of ovarian
aging but who may already have decreased fertility.
When menopause occurs, there are often a few hundred
follicles remaining. There is still ovarian activity and
estrogen production during the first year after menopause.14
Although the mean age of menopause in Western countries
is 51, there is a significant range, from 40 to 60 years of
age. Sibling and twin studies have shown a significant
genetic component to the age of menopause.19 Smoking
has been associated with a decreased follicular pool and
earlier menopause.14
Oocyte quality also appears to be affected by age. Studies on
IVF oocytes have shown that the rate of oocyte aneuploidy
increases with age.20 The rate is low in women < age 35
(10%), but increases to 30% at the age of 40, to 40% at the
age of 43, and to 100% in women > age 45.20 These were
gonadotropin stimulated oocytes, and therefore may not
reflect the rate of aneuploidy in oocytes from a dominant
follicle recruited during a non-stimulated or natural cycle;
however, this correlates with the increase in chromosomally
abnormal pregnancies and spontaneous abortions with age.
The decline in oocyte quality may be in the formation and
function of the spindles, which appear to be more diffuse.21
This may result in chromosomes being less tightly arranged
and may therefore lead to meiotic errors. Data also suggest
that the selection process may deteriorate with age, allowing
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SOGC Clinical Practice Guideline

Figure 1. Schematic representation of the number of primordial follicles

present in the ovaries and the chromosomal quality of oocytes in relation to
female age and corresponding reproductive events.

Number of follicles

Proportion of poor quality oocytes

Proportion of poor quality oocytes (%)

10T
Optimal
fertility Declining
10 6 fertility End of
Number of follicles

fertility Menopause

105 Irregular
cycles

100
104
75
103 50
25
10 2

0 10 20 30 40 50 60
Age (years)

Graph was drawn after Hansen et al. and de Bruin et al.

Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr
Rev 2009;30:465–93.12 Copyright 2009, The Endocrine Society. Reproduced with permission.

Figure 2. Natural fertility by age poorer quality oocytes the opportunity to develop into the
dominant follicle, or to be selected during an IVF cycle.
600 The selection of the available follicular cohort may be less
discriminating, allowing follicles to mature which should
500 have undergone atresia.22 Other proposed mechanisms
include cumulative damage to the oocyte with age and
400 decreasing quality of granulosa cells.23
Rate per 1000 wives

300
FEMALE ADVANCED REPRODUCTIVE
AGE AND INFERTILITY
200
Population studies have consistently noted that the decline
100 in birth rates begins when women reach the age of 35
(Figure 2).4 On average, women will deliver their last child at
0
20 25 30 35 40 45 50 age 41, with a range of 23 to 51.24 Natural population studies
Age of wife may not take into account non-reproductive factors, such as
The ten populations (in descending order at age 20 to 24) are desire to prevent pregnancy, coital frequency, aging partners,
Hutterites, marriages 1921–30 ( ); Geneva bourgeoisie, husbands and other medical conditions that may affect live birth rates.
born 1600–49 ( ); Canada, marriages 1700–30 ( ); Normandy,
marriages 1760–90 ( ); Hutterites, marriages before 1921 ( ); In addition, conditions such as fibroids and endometriosis
Tunis, marriages of Europeans 1840-59 ( ); Normandy, marriages are more frequent in later reproductive years. These studies
1674–1742 ( ); Norway, marriages 1874–76 ( ); Iran, village therefore may not offer a full reflection of a woman’s
marriages, 1940–50 ( ); Geneva bourgeoisie, husbands born
before 1600 ( ). maximum fertility potential. Natural fertility studies of
patients who had recently discontinued contraception have
Menken J, Trussell J, Larsen U. Age and infertility. Science 1986;
shown that younger women have a higher fecundity rate,
233(4771):1389–1394.4 Reprinted with permission from AAAS. and therefore conceive sooner than older women.25

1168 l NOVEMBER JOGC NOVEMBRE 2011


The incidence of infertility and sterility increases as the
age of the female partner increases. Although the true
incidence of sterility is difficult to determine because of
non-reproductive factors such as voluntary childlessness,
population studies can provide some insight. In one study
of 7 populations in which contraception use is rare and in
which there is a low incidence of premarital conceptions,
the percentage of women who remained childless was
higher in those who married later.4 Only 6% of women
who married in their early 20s remained childless, while
64% of women who were not married until their 40s
remained childless. Studies in the Hutterite population
confirm an increase in infertility with age, escalating from
11% after age 34 to 33% by age 40 and to 87% by age 45.26
Although social changes have led to women delaying
their reproduction, concomitant advances in reproductive
sciences have led to increased options for fertility treatment
and ART. Unfortunately, this may give women false optimism
that they can delay pregnancy while pursing their education
and careers with the expectation that ART will help them to
conceive if they have difficulty conceiving later. However,
success rates for ART treatment for women using their own
eggs are directly linked to the age of the women,27 and many
women may not realize that older women are successful
using ART to achieve pregnancy later in life only with donor
eggs. Computer models have demonstrated that the current
ART success rates cannot compensate for the loss in natural
fertility that occurs in a women who has delayed child-
bearing from 30 to 35 years of age.5
Studies on donor insemination confirm an age-related
decline in pregnancy rates. Most of the earlier donor
insemination studies were performed in couples with severe
male factor infertility. These studies are thought to be a
good reflection of female fertility because non-reproductive
factors such as coital frequency are removed. A negative
effect on pregnancy rates is seen in women > age 30, and
is even more pronounced for women > age 35.28–31 One
study of almost 3000 cycles showed cumulative pregnancy
rates of 62% for women < 30 years of age, and 44% for
women aged ≥ 30 years after 12 cycles. Younger women
often conceive quickly, and more cycles of treatment were
often needed for women aged ≥ 35 years.29,31
Pregnancy rates collected from ART treatment cycles show
the significant impact of female age on success. The 2007
Canadian live birth rate after IVF was 37.4% for women
< 35 years of age, 26.5% for women aged 35 to 39 years, and
11.4% for women aged ≥ 40 years.32 ART reports from the
United States show similar age-related success rates.33 Age is
the most significant prognostic factor for IVF success.
Advanced Reproductive Age and Fertility
Age-associated infertility appears to be primarily related
to ovarian aging and the diminishing ovarian follicle
count. The uterine endometrium has the capacity to
maintain a pregnancy throughout a woman’s reproductive
years and, with newer technologies such as egg donation,
even beyond the natural reproductive years. Age does
not affect the endometrium’s response to hormonal
stimulation.34 Pregnancy rates from donor egg cycles
also confirm that the age of the recipient does not affect
pregnancy rates.33
Recommendations
1. Women in their 20s and 30s should be counselled
about the age-related risk of infertility when other
reproductive health issues, such as sexual health
or contraception, are addressed as part of their
primary well-woman care. Reproductive-age women
should be aware that natural fertility and assisted
reproductive technology success (except with egg
donation) is significantly lower for women in their
late 30s and 40s. (II-2A)
2. Because of the decline in fertility and the increased
time to conception that occurs after the age of
35, women > 35 years of age should be referred
for infertility work-up after 6 months of trying to
conceive. (III-B)
ASSESSMENT OF OVARIAN AGING
Ovarian aging will have begun before women notice any
clinical changes to their menstrual cycles; therefore, they are
often unaware that they may be at greater risk of infertility.
Ovarian reserve testing has been explored as a means to
determine a woman’s fertility potential and provide an
assessment of ovarian aging. Although chronological age
alone serves as a good marker of ovarian reserve, some
women will experience a decline in their natural fertility
sooner than average, while some older women may
maintain above average ovarian function. Identification of
these two groups, in which ovarian reserve is inconsistent
with chronological age, may be useful for counselling and
planning treatment.35
Many tests of ovarian reserve have been tried. However,
testing has mainly been performed on infertile populations,
with little data on the distribution in the normal fertile
population. Ovarian reserve testing cannot be used to
predict infertility or time to infertility; therefore, its
application to the general population as a screening tool
is untested. Most studies have used these tests to try to
predict a woman’s ovarian response and prognosis with
fertility treatment and IVF. Overall, markers of ovarian
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SOGC Clinical Practice Guideline
reserve have been shown to correlate with egg quantity and
response to ovarian stimulation, but not with egg quality.
The most commonly used test of ovarian reserve is the
cycle day 3 or basal FSH level. An elevated basal FSH level
(> 14 IU/L) is the first sign of ovarian aging that can be
detected in women, and usually occurs in women aged
35 to 40.36 Physiologically, the follicular pool is reduced
to approximately 10% of the levels present at puberty.9
The rise in basal FSH is due to a loss in ovarian feedback
(inhibin-A and B) as the available follicular cohort
diminishes. Basal FSH levels are easy to obtain, and no
special skills are required to perform the test or interpret
the results; therefore, it is easily accessible. However, basal
FSH levels have been shown to be predictive for poor
response to ovarian stimulation and for non-pregnancy
only when the levels are extremely elevated.35 Although
a high threshold may improve the usefulness of the test
in predicting a poorer prognosis, only a small number
of women will have abnormal tests at this threshold. In
addition, it has been associated with a false positive rate of
5%.35 Elevated basal FSH levels are also less predictive of
pregnancy for women < age 35.37,38
An ovarian antral follicle count can be performed early
in the menstrual cycle. Antral follicles between 2 mm and
10 mm can be identified by transvaginal ultrasound
performed by an experienced sonographer using a vaginal
transducer with a minimum frequency of 7 MHz.39 Antral
follicles are sensitive to FSH and are considered to be
representative of the available follicle pool. The number
of antral follicles seems to correlate with the number
of primordial follicles in the ovary, with a decline in
primordial follicles being reflected in a lower number of
antral follicles.24 In later reproductive years, the proportion
of antral follicles to total follicles may increase as the
ovary allows a higher proportion of follicles to be selected.
This may reflect a loosening of the selection process.14
The decline in AFC may not be as steep as the decline
in fertility. Although decline in AFC is correlated with
both the menopause transition and ovarian response to
stimulation, it is not a good predictor of pregnancy.35
Antimüllerian hormone is produced by the granulosa cells
of pre-antral and small antral follicles but not dominant
follicles.12 AMH levels decrease with decreasing AFC,
which in turn is a marker of the primordial follicle count.
Levels remain consistent throughout the menstrual cycle40
and become undetectable in women after menopause.41
Although AMH provides moderate value in prediction
of ovarian response in IVF, it is a poor predictor of
pregnancy.35 Currently, AMH testing is not widely available
across Canada.
1170 l NOVEMBER JOGC NOVEMBRE 2011
The clomiphene challenge test is performed by
administering 100 mg of clomiphene daily from day 5 to day
9 of the cycle. FSH is measured on day 3 and on day 10. If
an adequate response to clomiphene is generated, the rise
in FSH will be suppressed by the release of estradiol and
inhibin-B by developing follicles. Systematic reviews have
not shown a benefit to the clomiphene challenge test over
basal FSH or AFC.35 Inhibin-B and basal estradiol have not
been shown to be more useful predictors of poor response
or pregnancy than basal FSH.35 However, basal estradiol
levels are often screened in conjunction with FSH and can
confirm correct timing in the menstrual cycle. An elevated
estradiol level may also falsely suppress FSH levels.
Ovarian reserve tests performed before ART treatment is
begun may be useful for counselling, but they have a poor
predictive power for pregnancy.12 AFC and AMH have been
shown to be useful for prediction of poor ovarian response
with IVF.12 Although significantly abnormal results are
associated with lower pregnancy rates (< 5%), only about
3% of women will have results in this category.35 In general,
ovarian reserve testing is useful for predicting egg quantity
and ovarian response to stimulation but has little value for
the prediction of egg quality. Therefore, although these tests
may be useful for counselling before ART treatment, testing
should not be used to exclude women from ART treatment,
and abnormal tests do not preclude the possibility of
pregnancy. These test results can be used to obtain individual
prognostic information to help to guide the choice of
treatment and best use of resources.
Ovarian reserve testing may be considered in women > age
35 to screen for age-related infertility, although its results
may be useful only for counselling and to aid women in
their decision-making process. Testing in women < 35
years may be considered if they have risk factors for
decreased ovarian reserve, such as a single ovary, previous
ovarian surgery, poor response to FSH, previous exposure
to chemotherapy or radiation, or unexplained infertility.42
Although markers of ovarian reserve are not good
predictors of pregnancy rate with ART for women < 35,38
identification of these women may prompt shorter delay
to infertility investigations and treatment.
Recommendations
3. Ovarian reserve testing may be considered for
women ≥ 35 years of age or for women < 35 years
of age with risk factors for decreased ovarian reserve,
such as a single ovary, previous ovarian surgery,
poor response to follicle-stimulating hormone,
previous exposure to chemotherapy or radiation,
or unexplained infertility. (III-B)

4. Ovarian reserve testing prior to assisted
reproductive technology treatment may be used for
counselling but has a poor predictive value for non-
pregnancy and should be used to exclude women
from treatment only if levels are significantly
abnormal. (II-2A)
TREATMENT OF AGE-RELATED INFERTILITY
Fertility treatment for age-related infertility is aimed at
increasing monthly fecundity and decreasing the time to
conception. Women may be offered controlled ovarian
hyperstimulation with clomiphene citrate or gonadotropins,
or IVF to improve their chances of pregnancy and
decrease time to pregnancy. Both treatments are intended
to increase the number of mature oocytes each month to
balance decreasing oocyte quality, but they do not address
the underlying issue of oocyte quantity or quality. The only
effective treatment for age-related infertility and declining
oocyte quality is oocyte donation.
In reality, pregnancy and live birth rates with COH in
older women are low. In one retrospective review of more
than 4000 treatment cycles using clomiphene citrate and
intrauterine insemination, pregnancy rates were 7% for
women aged 38 to 40, 4% for women 41 to 42, and 1% for
women > 42.43 A small study of 130 cycles of COH with
gonadotropins and IUI found a live birth rate of 6% for
women aged 38 to 39, and 2% for women > 40.44 All live
births happened within the first or second cycles. Older
women may consider 1 to 2 cycles of COH if they do not
want to try IVF as a first-line treatment, but they should
move on to IVF quickly if they are unsuccessful within the
first couple of cycles.45
Although chance of success diminishes with age, IVF
still offers higher pregnancy and live birth rates than
COH, although significantly lower rates than oocyte
donation. In 2007, live birth rates were 11.4% per cycle
for women aged > 40 in Canada.32 One study of women
aged > 40 undergoing IVF, showed that for women aged
≥ 42, live birth rates drop to below 5%.46 In this study,
no live births were reported in 54 cycles for women
aged ≥ 45. A separate study found a significant drop in
IVF live birth rates in women aged ≥ 43 and over. Live
birth rates were 7.4% for women 40 to 42 years of age,
and only 1.1% for women ≥ 43 years. Miscarriage rates
were 43.1% in the younger age group and 65.2% in the
older age group.47
Oocyte donation offers women with an intact uterus
the opportunity to carry a pregnancy despite declining
ovarian function or menopause. In Canada, the 2004
Advanced Reproductive Age and Fertility
Assisted Human Reproduction Act regulates all reproductive
technologies, including the use of donor gametes.
Specifically, the Act prohibits the sale of eggs, sperm,
or surrogacy services.48 Compensation to donors for
receiptable expenses such as medications and parking are
allowed,49 although the specific regulations are not yet
available. Many countries, including the United States,
rely on paid, often anonymous, egg donors to ensure an
adequate supply to meet the significant demand for this
treatment option. However, as this practice is prohibited
in Canada, Canadian women must rely on altruistic
egg donors, usually family members, close friends, or
colleagues. Unfortunately, many women will not know an
appropriate donor, so egg donation may not be an option
for them. Other women turn to reproductive tourism and
seek treatment in the United States or Europe.
Pregnancy rates with oocyte donation are based on the
age of the donor, not the recipient.33,50 Pregnancies and
live births have been reported in women into their 60s51;
however, the use of donor eggs for women after the age of
50 is controversial. There are increased rates of obstetrical
and maternal complications with increasing maternal age,
including maternal death, hypertension, prematurity, fetal
and neonatal death, and operative delivery.52–55 At least one
death immediately after delivery has been reported in a
50-year-old woman who conceived with oocyte donation.56
However, many of these studies show these risks are
already increased in women > age 40, and treatment is
offered to women between the ages of 40 and 50 without
significant debate. Many clinicians feel the natural age of
menopause is an appropriate maximum age for offering
oocyte donation, although others argue this is an arbitrary
cut-off point.57 In Canada, there are no regulations that
set an age limit for oocyte donation, although many clinics
have set the age of menopause as the maximum age for
this treatment.
Recommendations
5. Pregnancy rates for controlled ovarian
hyperstimulation are low for women > 40 years
of age. Women > 40 should consider IVF if they
do not conceive within 1 to 2 cycles of controlled
ovarian hyperstimulation. (II-2B)
6. The only effective treatment for ovarian aging
is oocyte donation. A woman with decreased
ovarian reserve should be offered oocyte donation
as an option, as pregnancy rates associated
with this treatment are significantly higher
than those associated with controlled ovarian
hyperstimulation or in vitro fertilization with a
woman’s own eggs. (II-2B)
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SOGC Clinical Practice Guideline
EARLY PREGNANCY AND
MATERNAL COMPLICATIONS
Advanced reproductive age is associated with early and later
pregnancy complications in addition to infertility. Age is a
recognized risk factor for spontaneous abortion. Although
the risk of clinical pregnancy loss is low in women < 30
years of age (7% to 15%), it begins to rise for women aged
30 to 34 (8% to 21%) and women aged 35 to 39 (17% to
28%), and it increases dramatically for women aged ≥ 40
(34% to 52%).15 Data from the Canadian ART clinics also
show an increase in spontaneous pregnancy loss after ART
treatment. Pregnancy loss rates after clinical intrauterine
pregnancy ranged from 10.4% for women aged < 35 to
16.4% for women aged 35 to 39, and increased to 33% for
women aged ≥ 40.27
An increased risk of chromosomal abnormalities also occurs
with age. Much of the increased risk of early pregnancy
loss may be due to the increased rate of chromosomally
abnormal conceptions. The previously discussed underlying
mechanisms for ovarian aging and declining egg quality
leading to increased oocyte aneuploidy may lead to an
increased rate of chromosomal abnormalities in resultant
embryos and pregnancies. The age-related risks for Down
syndrome increase from 1 in 1477 for women at age 20 to
1 in 939 at age 30, 1 in 353 at age 35, 1 in 85 at age 40, and
1 in 39 at age 44. The age-related risk for all chromosomal
abnormalities rises from 1 in 526 for women at age 20 to
1 in 384 at age 30, 1 in 204 at age 35, 1 in 65 at age 40, and
1 in 2 at age 45.58
Pregnancy in women > 40 years of age is also associated
with a higher risk of obstetrical complications, including
operative delivery, gestational diabetes, preeclampsia,
IUGR, and low birth weight.6 Pre-conception screening
for significant medical conditions such as hypertension
or diabetes should be considered for women at high risk
before fertility treatment is begun.
Recommendations
7. Women should be informed that the risk of
spontaneous pregnancy loss and chromosomal
abnormalities increases with age. Women should be
counselled about and offered appropriate prenatal
screening once pregnancy is established. (II-2A)
8. Pre-conception counselling regarding the risks of
pregnancy with advanced maternal age, promotion
of optimal health and weight, and screening for
concurrent medical conditions such as hypertension
and diabetes should be considered for women
> age 40. (III-B)
1172 l NOVEMBER JOGC NOVEMBRE 2011
ADVANCED PATERNAL AGE
Although significant focus has been placed on female
reproductive aging, there is also an age-related decline in
sperm function and male fertility. Although “andropause”
is not a clearly defined event for men as menopause
is for women, there is a decline in testicular function,
which includes declining testosterone levels each year.59
Sperm parameters including semen volume, motility, and
morphology decrease with age, although a decline in sperm
concentration has not been shown.60
Studies trying to delineate the effects of male age on
natural fertility often have not accounted for female age.
One study has suggested that the odds of conception
decrease 3% per year, while other studies have shown that
the effect of male age alone on natural monthly conception
is small.61,62 Similarly, studies in ART treatment have often
not controlled adequately for maternal age.63,64 One study
suggested that male age > 35 years may have an effect on
IUI, but most studies suggest that male age does not affect
IVF/ intracytoplasmic sperm injection pregnancy rates
despite lower motility and fertilization rates.65,66 There
was also no difference seen in egg donation cycles.67,68 In
couples undergoing ART treatment, it appears that the
effect of paternal age on the number of cleavage-stage
embryos is small.69 However, a significant decrease in the
rate of blastocyst embryo formation on day 5 and in the
number of cryopreservable embryos has been noted.70,71
Paternal age > 40 years does appear to be associated
with risk of spontaneous abortion, even when maternal
age is controlled for.72,73 For chromosomal abnormalities,
the effect of maternal age is such a significant factor, the
paternal age effect is small in comparison and is not found
at all in many studies after maternal age is controlled for.74–77
However, recent studies suggest that, either alone or in
combination with a maternal effect, paternal effect may
increase the risk of Down syndrome.78 Although there has
been conflicting evidence for an association with pre-term
birth and low birth weight, a study conducted in the United
States and a population study undertaken in Alberta did not
find this association after multiple and logistic regression
analysis.79–81 Advanced paternal age has been associated with
autosomal dominant disorders such as Alport syndrome,
achondroplasia, and neurofibromatosis.82–87 The estimated
risk for autosomal dominant disorders in offspring of
fathers ≥ 40 years of age is thought to be < 0.5%.78
Autism spectrum disorders and schizophrenia have been
associated with advanced paternal age through larger
cohort and population database studies. A large Danish
prospective study on autism with one million children

found a relative risk 1.6 for fathers > 40 to 44 years of age,
and an Israeli cohort study found an OR 5.75 for fathers
aged 40 to 49.88,89 A large US study found an association
between autism and both maternal and paternal age, with
a relative risk of 1.3 for every 10-year increase in paternal
age.90 The link between paternal age and schizophrenia was
initially felt to be constitutional: people with this condition
tend to marry and reproduce later in life. A cohort of
almost 90 000 children in Jerusalem was linked to the
Israeli Psychiatric Registry. The relative risk for offspring
with schizophrenia was 2.0 for fathers aged 45 to 49, and
3.0 for fathers > age 50.91 This finding has been seen
across other studies in other ethnic populations, including
populations in Denmark, Sweden, and Japan.92–94
The American College of Medical Genetics does not
recommend additional prenatal testing solely on the basis
of advanced paternal age (defined as ≥ 40), although
prenatal counselling about the potential risks of advanced
paternal age should be undertaken.78
Recommendation
9. Advanced paternal age appears to be associated
with an increased risk of spontaneous abortion
and increased frequency of some autosomal
dominant conditions, autism spectrum disorders,
and schizophrenia. Men > age 40 and their partners
should be counselled about these potential risks
when they are seeking pregnancy, although the risks
remain small. (II-2C)
CONCLUSIONS
Female reproductive aging is a common cause of infertility
in women in their late 30s and 40s. Health care providers
should counsel women about the realities of the biological
clock and ensure they have realistic expectations about
natural and assisted fertility rates if they choose to delay
child-bearing into their later reproductive years.
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 SOGC CLINICAL PRACTICE GUIDELINE

SOGC Clinical Practice Guideline No. 249, October 2010

Asymptomatic Endometrial Thickening

Abstract
This Clinical Practice Guideline has been prepared by the Clinical Objective: To formulate clinical recommendations for the assessment
Practice Gynaecology Committee and approved by the Executive of endometrial thickening when it is found on ultrasound in a
and Council of the Society of Obstetricians and Gynaecologists of postmenopausal patient without bleeding.
Canada.
Outcomes: Ensure that women with asymptomatic thickening and
PRINCIPAL AUTHOR
endometrial polyps found on ultrasound are managed appropriately.
Wendy Wolfman, MD, Toronto ON
Evidence: Published literature was retrieved through searches of
CLINICAL PRACTICE GYNAECOLOGY COMMITTEE English language articles from the EMBASE, Cochrane, and PubMed
Nicholas Leyland, MD (Chair), North York ON databases for relevant peer-reviewed articles dating from 1970 to
2009, using appropriate controlled vocabulary (e.g., “asymptomatic
Wendy Wolfman, MD, Toronto ON
endometrial thickness,” “endometrial cancer,” “postmenopausal
Mark Heywood, MD, Vancouver BC bleeding,” “transvaginal ultrasonography,” “endometrial biopsy”
Sukhbir S. Singh, MD, Ottawa ON and “endometrial polyp”). Results were restricted to systematic
reviews, randomized control trials/controlled clinical trials, and
David Allan Rittenberg, MD, Halifax NS observational studies. Searches were updated on a regular basis
Renée Soucy, MD, Chandler QC and incorporated in the guideline to April 2010. Grey (unpublished)
literature was identified through searching the websites of health
Catherine Allaire, MD, Vancouver BC technology assessment and health technology assessment-related
Alaa Awadalla, MD, Winnipeg MB agencies, clinical practice guideline collections, clinical trial registries,
and national and international medical specialty societies.
Carolyn Best, MD, Toronto ON
Sheila Dunn, MD, Toronto ON Values: The level of evidence was determined according to the criteria
established by the Canadian Task Force on Preventative Health Care
Nathalie Leroux, MD, Montreal QC (Table). Recommendations are ranked according to this method.
Frank Potestio, MD, Thunder Bay, ON Benefits, harms, and costs: It is anticipated that the adoption of
Vyta Senikas, MD, Ottawa ON these recommendations would save postmenopausal women
unnecessary anxiety, pain, and risk of procedural complication. It
Disclosure statements have been received from all members of the
is also expected to decrease the cost to the health system by
committee.
eliminating unnecessary interventions.
SPECIAL CONTRIBUTORS
Key Words: Asymptomatic endometrial thickening, asymptomatic
Sarah Wallace, MD, Sudbury ON endometrial polyp, endometrial cancer, transvaginal ultrasonography,
Rebecca Menzies, MSc, Toronto ON hysteroscopy, endometrial biopsy tamoxifen, postmenopausal polyps
The literature searches and bibliographic support for this guideline Recommendations
were undertaken by Becky Skidmore, Medical Research Analyst,
1. Transvaginal ultrasound should not be used as screening for
Society of Obstetricians and Gynaecologists of Canada.
endometrial cancer. (II-1E)
2. Endometrial sampling in a postmenopausal woman without
bleeding should not be routinely performed. (II-1E)
3. Indications for tissue sampling of the endometrium in bleeding
postmenopausal women with an endometrial thickness of greater
than 4 to 5 mm should not be extrapolated to asymptomatic
women. (II-2E)
4. A woman who has endometrial thickening and other positive
findings on ultrasound, such as increased vascularity, inhomogeneity
of endometrium, particulate fluid, or thickened endometrium over
11 mm, should be referred to a gynaecologist for further
Key Words: Asymptomatic endometrial thickening, asymptomatic investigations. (II-1A)
endometrial polyp, endometrial cancer, transvaginal ultrasonography,
hysteroscopy, endometrial biopsy tamoxifen, postmenopausal polyps 5. Decisions about further investigations should be made on a
case-by-case basis in asymptomatic women with increased

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

990 l OCTOBER JOGC OCTOBRE 2010


Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.71
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.71
endometrial thickening and risk factors for endometrial cancer
such as obesity, hypertension, and late menopause. (II-1B)
6. In asymptomatic women on tamoxifen, a routine ultrasound for
endometrial thickening should not be performed. (II-2E)
7. Not all postmenopausal women who have asymptomatic
endometrial polyps require surgery. Women found to have
asymptomatic polyps on ultrasound should be triaged for
intervention according to size of the polyp, age, and other risk
factors. (II-1A)
J Obstet Gynaecol Can 2010;32(10):990–999
INTRODUCTION
n this guideline, asymptomatic endometrial thickening is
I defined as an endometrium of > 5 mm discovered on
ultrasound in a postmenopausal woman who is not bleed-
ing.1–3 Current ultrasound literature suggests that asymp-
tomatic endometrial thickness of 8 to 11 mm in a
postmenopausal women is not abnormal.4–8 The measure-
ment of the endometrium is made at its maximal thickness
on a midline sagittal image of the uterus obtained by
transvaginal ultrasound. It is a bilayer measurement com-
bining the width of both the anterior and the posterior layers
of the endometrium. It has been suggested that the normal
endometrial thickness in a postmenopausal woman is 5 mm.
There is controversy about the normal measurement in
ABBREVIATIONS
HT hormone therapy
TVUS transvaginal ultrasound
Asymptomatic Endometrial Thickening
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
women on hormone therapy. Studies have shown a normal
range from 5.4 to 10.8 mm.4–6,9 An endometrium 2 mm
thicker in women who use sequential therapy may be normal.10
The endometrium may normally be thicker in the first year
after the last menstrual period, reflecting some residual hor-
monal activity.11
The finding of asymptomatic endometrial thickening on
ultrasound presents a clinical management dilemma and is a
frequent reason for referral by family physicians. Concern is
raised when an endometrium of > 5 mm is discovered during
an ultrasound examination, often one that is undertaken for
non-gynaecologic reasons. Subsequent radiologic reports
prompt interventions that can be invasive and involve risk.
The incidence of endometrial thickening (³ 4.5 mm) in
postmenopausal women ranges from 3% to 17%,1–3 while
the incidence of endometrial cancer in an unselected
postmenopausal population is 1.3 to 1.7/1000.12–14
The American Cancer Society does not recommend routine
screening of asymptomatic patients for endometrial can-
cer.15 The Canadian Cancer Society reports that there is
inadequate evidence that screening by ultrasonography or
endometrial sampling would reduce the mortality from
endometrial cancer.16 The 2001 consensus statement on
bleeding published by the Society of Radiologists in Ultra-
sound included a caveat that the 5 mm threshold does not
apply to asymptomatic women with incidentally observed
thickened endometrium.17 In 2009, the American College
of Obstetricians and Gynecologists stated that there was
OCTOBER JOGC OCTOBRE 2010 l 991
SOGC Clinical Practice Guideline
no evidence to recommend routine investigations for
asymptomatic endometrial thickening.18 Despite this
recommendation, clinicians are concerned when the
ultrasound report states that endometrial cancer cannot be
ruled out because of endometrial thickening found in an
asymptomatic postmenopausal woman. Goldstein, in
2010,19 recommended postmenopausal asymptomatic
endometrial thickening be evaluated on a case-by-case
basis. The clinician must consider risk factors for
endometrial cancer including obesity, polycystic ovary
syndrome, and diabetes mellitus in their decision making.
Goldstein19 emphasized that it is inappropriate to
investigate every asymptomatic patient with thickened
endometrium > 5 mm.
ENDOMETRIAL CANCER AND RISK FACTORS
Endometrial cancer is the most common gynaecologic
malignancy.20 The incidence in Canada is 19/100 000 women.
The Canadian Cancer Society estimated that in 2009 there
would be 4400 cases of endometrial cancer and 720 deaths
due to the disease in Canada.16 Approximately 80% of
endometrial cancers occur in postmenopausal women.21
Ninety percent of women with endometrial cancer present
with bleeding.22 Most women (72%) have stage I cancer
when diagnosis is made,22 and the survival rate depends on
the stage, grade, and type of cancer. Five-year survival rates
for localized, regional, and metastatic endometrial cancer
are 95%, 67%, and 23%, respectively, and the overall 5-year
survival rate is 86%.20
Individual risk factors are obesity, high-fat diet, reproductive
factors such as nulliparity and polycystic ovary syndrome,
early menarche, and late menopause.23 Tamoxifen use also
increases the risk of developing endometrial cancer by
2.3 per 1000 women.24
Women with hereditary nonpolyposis colorectal cancer
syndrome have an estimated cumulative incidence of
endometrial cancer ranging from 20% to 60% by the age of
70 years. The mean age of developing cancer is 47 in carriers
versus 60 years in those with non-inherited endometrial
cancer.25 No studies have yet shown the benefit of screening
for endometrial cancer in female carriers of hereditary
nonpolyposis colorectal cancer syndrome.26
The incidence of endometrial cancer is lower in Black
women. However, the overall mortality due to the disease is
higher among this group.27
A Swedish longitudinal evaluation of postmenopausal
women found that a history of bleeding incurs a 64-fold
increased risk of endometrial cancer.28,29 For any woman
presenting with postmenopausal bleeding there is approxi-
mately a 10% risk of endometrial carcinoma.29 If the
woman is on hormone therapy and bleeds, the risk is 1%.29
992 l OCTOBER JOGC OCTOBRE 2010
It is unknown how many women who have endometrial
cancer are diagnosed in the absence of bleeding. Diagnosis of
cancer in asymptomatic women has been estimated by
Smith-Bindman to be 5% to 10% of all cases.30 It is also
unknown if diagnosing endometrial cancer before a woman
bleeds would improve overall survival.
In 1981 Koss et al.2 initiated a screening study of 1280
asymptomatic women aged 45 and older via endometrial
sampling in a New York Medical Center. Carcinoma was
found in only 8 patients (6/1000).
In 1997 Korhonen et al.31 published their results of patho-
logic findings for endometrial biopsy in 2964
perimenopausal and postmenopausal women who were
candidates for hormone therapy. Endometrial biopsy
findings were 68.7% atrophic, 23.5% proliferative, 0.5%
secretory, 0% hyperplastic, and < 0.07% malignant. Of the
biopsy samples, 6.6 % were insufficient for classification,
reflecting the low incidence of pathology in the general
population.
A necropsy study found an occult incidence of endometrial
cancer of 22 to 31/10 000 women (0.22% to 0.31%).32
These studies indicate a background incidence of endometrial
cancer of 0.6 to 6/1000 women (0.2% to 0.6%).2,32
SIGNIFICANCE OF ASYMPTOMATIC
ENDOMETRIAL THICKENING
In a menstruating woman the endometrium changes with
the phase of the menstrual cycle. It ranges from 3 mm after
menses to a thickness of 15 mm in the luteal phase. In the
first year after the last menstrual period the normal
endometrium is often thicker than it will be several years
after menopause, reflecting fluctuating levels of estrogen.
Descriptions of the endometrium on ultrasound examination
include global thickening, heterogeneity, thickening, focal
areas of thickening, fluid collections, increased vascularity,
and myometrial associated findings such as myometrial
cysts, and submucosal fibroids. After menopause, endometrial
thickening may reflect proliferative endometrium, cystic
hyperplasia, complex hyperplasia, atypical hyperplasia, or
carcinoma of the endometrium. Ultrasound evidence of
thickened endometrium may also indicate structural
abnormalities such as a uterine septum, submucous myomas,
polyps, or adenomyosis. Ultrasound technology, by identi-
fying vascular flow, now allows differentiation of polyps
from other abnormalities.33 Increased vascularity and fluid
accumulation in association with endometrial thickening
are cause for greater concern than other findings.34

SCREENING STUDIES OF ASYMPTOMATIC WOMEN
The purpose of performing ultrasound in non-bleeding
postmenopausal women may be to investigate abdominal
pain or masses or to delineate the adnexae when pelvic
examination is inadequate. Screening studies have been
undertaken to assess whether ultrasound can detect
endometrial cancer in large populations of asymptomatic
women.3,35,36
The American Cancer Society concluded that there was
insufficient evidence to recommend any routine screening
for endometrial cancer with TVUS or endometrial biopsy.37
Screening asymptomatic women will result in unnecessary
additional examinations because of low specificity. Most
cases of endometrial cancer are diagnosed as a result of
symptoms reported by patients, and a high proportion
of these cases are diagnosed at an early stage, with high rates
of survival.
In 1995, Ciatto and colleagues35 performed TVUS on
2025 women to evaluate the feasibility of using this modality
to screen for endometrial carcinoma solely on the basis of
endometrial thickness. In this study, 117 women (5.8%)
showed abnormal thickness of > 4 mm. Of these, 98 underwent
endometrial biopsy, but 32 had impassable cervical stenosis.
It was decided that evaluation of the endometrium by dila-
tation and curettage was not warranted. These women
underwent repeat transvaginal ultrasound examination.
The positive predictive value was 3.3%, with 3 endometrial
carcinomas found out of 66 biopsies.
A 1999 study by Vuento et al.3 focused on the feasibility of
TVUS to screen for endometrial cancer in asymptomatic
postmenopausal women using multiple criteria, one of
which was endometrial thickness. In this study, 291 of 1074
women (29%) had an abnormal thickness > 4 mm, uterine
artery pulsatility index < 1.0, or fluid accumulation in the
endometrial cavity. However, after biopsy, only 23 women
were found to have endometrial pathology, and only 3 were
found to have endometrial cancer. Endometrial fluid was
found in 12%. Another case of carcinoma was found
2.5 years later in a patient who had refused biopsy. The
authors concluded that TVUS, while sensitive for detecting
early endometrial cancer, has a low specificity that precludes
its utility as a screening modality. Doppler ultrasound did
not improve detection of abnormal endometrial pathology.
A study by Fleischer et al.36 of 1926 women who underwent
ultrasound examination as part of the workup for an osteo-
porosis prevention trial found that 93 women had an
endometrium > 6 mm. When endometrial aspiration of
42 of these women was undertaken, there were abnormal
findings in only 1 case. A further 1750 of 1833 women with
endometrial thickness of < 6 mm underwent sampling,
Asymptomatic Endometrial Thickening
yielding 5 abnormal results (1 endometrial cancer). The
sensitivity was 17% for 6 mm and 33% using 5 mm as a
threshold. The positive predictive value was 2%. The nega-
tive predictive value at < 6 mm was 99%.
Smith-Bindman et al.30 calculated a 6.7% risk of
endometrial cancer if the endometrium was > 11 mm, and a
0.002 % risk if the endometrium was thin (< 11 mm). This
theoretical risk was calculated on the basis of a review of
published and unpublished data and an estimate of 15% of
total cases of endometrial cancer occurring in women who
have no bleeding. The risk is also related to age, with
women > 70 years, with a thicker endometrium having a
higher risk (9.3% with 11 mm endometrium).
Gambacciani et al.1 undertook a retrospective review of
850 postmenopausal women who were investigated with
outpatient hysteroscopy for various causes of thickening.
The authors focused on the 148 asymptomatic postmenopausal
women with endometrium > 4 to 5 mm, and found 1 case
of adenocarcinoma (0.7%) (endometrium 16 mm) and
9 cases of hyperplasia (6.1%). In this study 24/27 cases of
adenocarcinoma presented with bleeding, 2/27 had an
abnormal Papanicolaou smear, and 1/27 (3.7%) had thickened
endometrium. One hundred forty-seven hysteroscopies
were performed for benign pathology; the false positive rate
was 93.2%.
Gerber et al.38 in a retrospective analysis discovered
16 patients (13%) had endometrial cancer when an
endometrial thickening of 10 mm was used as a cut-off in
the investigation of 123 asymptomatic women; 21 of the
women (17%) had hyperplasia. Asymptomatic women
without symptoms had no prognostic advantage over the
symptomatic women if bleeding had occurred for < 8 weeks.
Duration of postmenopausal bleeding was correlated with
increasing tumour stage and reduced survival time.
Endometrial screening often resulted in unnecessary opera-
tions with increased morbidity and cost.
Archer et al.12 attempted to obtain endometrial samples in
801 asymptomatic perimenopausal and postmenopausal
women prior to enrolment in a multicentre hormone
replacement therapy study. Of the samples, 75% contained
sufficient tissue for diagnosis. One endometrial cancer was
diagnosed, illustrating the low incidence of disease in
asymptomatic women and the low incidence of disease in
asymptomatic women. The endometrium was atrophic in
46.9%, proliferative in 16.7%, secretory in 6.8%, and
hyperplastic in 5.2%.
Tsuda et al.39 screened 1400 asymptomatic postmenopausal
Japanese women and found a prevalence of endometrial
disease of 2.3% in asymptomatic and 21% in symptomatic
women. At a cut-off of 3 mm in non-bleeding women,
sensitivity was 90%, specificity 84%, and positive predictive
OCTOBER JOGC OCTOBRE 2010 l 993
SOGC Clinical Practice Guideline
value 12%. With an endometrial thickness < 3 mm, the
probability that endometrial disease would be missed was
0.003.
A review of the literature therefore does not indicate that
routine screening via transvaginal ultrasound for endometrial
cancer is recommended. There is a baseline incidence of
thickening (³ 4.5 mm) of up to 17%, with a low incidence
of cancer < 1%.1,12,36–38
WOMEN WITH RISK FACTORS
Increased lifetime estrogen exposure has been associated
with an increased risk of endometrial cancer. Early menarche,
late menopause, obesity, and unopposed estrogen use have
been linked to an increased risk. Should endometrial thick-
ening on ultrasound be more aggressively investigated in
women with risk factors?
A regression analysis by Maatela et al.40 of endometrial
thickening in asymptomatic postmenopausal women found
an increased risk of pathological findings in the presence of
obesity (BMI > 26) and late menopause.
In a 1993 study of ultrasonic thickness of the endometrium in
300 asymptomatic postmenopausal women, Andolf et al.41
found that endometrial thickness correlated significantly
with BMI. In the same study, Andolf and colleagues found a
non-significant trend towards a higher prevalence of predis-
posing factors (hypertension, nulliparity, diabetes) in women
with a thick endometrium.
The Women’s Health Initiative data, however, showed that
the interactions of age, race/ethnicity, BMI, hypertension,
smoking status, pack-years of smoking, prior use of unopposed
estrogen, or prior use of estrogen and progesterone had no
significant effect on the observed incidence rate of endometrial
cancer.42 There was a insignificant decrease in the number
of endometrial cancer cases in women taking HT rather
than placebo (13 fewer cases per 10 000).
Martinez-Rubio and Alcazar43 prospectively compared the
prevalence of abnormal endometrium in 187 postmenopausal
asymptomatic, normotensive women and 182 asymptomatic
postmenopausal women receiving anti-hypertensive drugs.
The endometrium was assessed via office endometrial
biopsy and TVUS when the definition of abnormal
ultrasound was > 5 mm. Women taking antihypertensive
medications were significantly more likely than
normotensive women to have endometrial thickness > 5 mm
(26.9% vs. 12.8%; P 0.001), heterogeneous endometrial
polyps (23.1 vs. 12.8%; P < 0.001), and endometrial polyps
(17.6 vs. 9.6%; P < 0.001). These results were independent
of body mass index.
Sit et al.44 evaluated asymptomatic thickening as an estrogen
biomarker as a part of the Prostate, Lung, Colorectal and
994 l OCTOBER JOGC OCTOBRE 2010
Ovarian Cancer Screening Trial in 1271 women. Thickness
ranged from 1 to 32 mm (median 3 mm). Frequency of
thicker endometrium was independently associated with
increasing BMI and current use of HT.
The time from menopause is a factor in investigating the
significance of the findings. Tsuda et al.11 found histologic
findings of a proliferative endometrium in 28% of women
< 5 years post-menopause and in 4.8% in women ³ 5 years
post-menopause. Andolf and colleagues41 found only an
insignificant trend towards decreasing endometrial thickness
with time after menopause.
ENDOMETRIAL THICKENING IN WOMEN ON HT
Hänggi et al.10 compared TVUS with histological findings
in endometrial evaluation of postmenopausal women
using hormone therapy to evaluate the safety of 3 hormone
therapy regimens versus no therapy. Patients on oral
micronized 17b-estradiol/oral sequential dydrogesterone
were compared with those using transdermal
17b-estradiol/oral sequential dydrogesterone, or oral
tibolone. If endometrial thickness was < 5 mm, endometrial
biopsy sample was either inactive/atrophic or insufficient
for diagnosis. Hyperplastic or malignant change was not
reported. After 24 months, endometrial thickness was
increased both in the oral and the transdermal
17b-estradiol/dydrogesterone groups. The tibolone group
showed no difference from the control group.
In the Postmenopausal Estrogen and Progestin Interven-
tions Trial, 448 participants underwent both TVUS and
endometrial biopsy over 4 years.45 They were randomized
to placebo or to cyclic or sequential HT. Langer et al.45
found that at a threshold value of 5 mm for endometrial
thickness, TVUS had 90% sensitivity and 48% specificity.
No cancer or atypical hyperplasia was found in 261 women
with endometrial thickness of < 5 mm. Two cases of atypical
hyperplasia and 1 case of cancer were found in 307 women
with endometrial thickness ³ 5 mm. The majority of serious
disease cases were found in women with endometrial
thickness > 10 mm. Eight cases of complex hyperplasia,
3 cases of atypical hyperplasia, and 1 case of adenocarcinoma
were found in the study population. Using this threshold,
more than one half of the women would undergo a biopsy,
while only 4% had serious disease.
Gull et al.46 evaluated a random sample of 1000 women
between the ages of 45 and 80 who underwent screening
ultrasound in Sweden; 559 were postmenopausal. The cur-
rent use of HT was associated with increasing endometrial
thickness.
Kurtay et al.47 assessed the effects of hormone therapy on
endometrial thickness in asymptomatic postmenopausal

women between 1997 and 2001. Three hundred seven
women received oral equine HT, oral equine estrogen, oral
17b-estradiol, or oral tibolone. All women on estrogen also
received a progestin. Patients with endometrial thickness
> 7 mm underwent a biopsy. Patients taking tibolone did
not have a statistically significant increased thickness of
endometrium compared with those in the other arms of the
study. The authors suggested that tibolone closely mimics
the natural atrophic state of the postmenopausal
endometrium and could be considered as an alternative to
HT.
In a 10-year (1991 to 2001) study undertaken in by Mossa et al.,48
the threshold of endometrial thickness was investigated in
587 women on HT. An increased endometrial thickness
and increased incidence of bleeding was found in the HT
group. However, no difference in the prevalence of
endometrial cancer was found between the HT and control
groups. The authors recommended that women with bleeding
on HT undergo hysteroscopy and biopsy only if
endometrial thickness is > 8 mm.
STUDIES IN WOMEN WITH ENDOMETRIAL POLYPS
The estimated prevalence of polyps in women with
postmenopausal bleeding ranges from 13% to 50%.49 Several
studies have also shown that polyps are highly prevalent in
asymptomatic postmenopausal women.49–52 The molecular
and pathological etiology of endometrial polyps is evolving.
Most lesions are benign, but some may be pre-malignant
(simple or complex hyperplasia with cytological atypia) or
malignant.53 Malignant pathology is identified in 0.5% to
4.8% of polyps found in postmenopausal women.53,54 How-
ever, polyps are a known risk factor for the subsequent
development of endometrial cancer.49–53
Fernández-Parra et al.55 conducted a retrospective chart
review to determine the incidence of malignant polyps in
postmenopausal women. Of 1870 hysteroscopies conducted at
the study centre, 653 had confirmed polyps. The majority of
women had postmenopausal bleeding, and only 117 women
were asymptomatic. No cases of cancer in a polyp were
found in asymptomatic women.
In a Norwegian study of 411 pre- and postmenopausal
patients, pathological analysis of hysteroscopically resected
endometrial polyps was conducted.49 Thirty-one percent of
study participants were symptomatic in postmenopause,
and 18.5% were asymptomatic in postmenopause. In the
group of postmenopausal women with symptoms, 5.5% of
polyps were malignant or had atypical hyperplasia com-
pared with 2.6% in women with no symptoms. The authors
concluded that hysteroscopic resection of both symptom-
atic and asymptomatic polyps should be performed since
the natural course of malignant polyps is still unknown.
Asymptomatic Endometrial Thickening
Antunes et al.53 sought to determine factors associated with
malignancy in endometrial polyps in their 2007 study. A
retrospective chart review of 475 surgical patients of any
age who underwent hysteroscopy for endometrial polyp
removal were included in the study. Overall, 78.53% of the
polyps were benign, 13.47% had simple or complex hyper-
plasia, and 2.74% were malignant. Statistical subanalysis
showed that women over 60 years of age were 3.28 times
more likely than their younger counterparts to have malig-
nant endometrial polyps. Women over 60 with
postmenopausal bleeding were 5.31 times more likely than
asymptomatic younger women to have malignant polyps.
The authors did not find a significant difference in the
prevalence of malignant polyps associated with arterial
hypertension, diabetes mellitus, obesity, HT, or tamoxifen
use. Antunes et al.53 concluded that older women with
postmenopausal bleeding are at greatest risk for malignancy
and should have hysteroscopic resection of the polyps.
In 2009, Ferrazzi et al.54 sought to elucidate the risk of
malignancy in endometrial polyps in a large sample of
asymptomatic and symptomatic postmenopausal women.
A total of 1155 asymptomatic women and 770 bleeding
women who had undergone polypectomy were included in
the retrospective clinical chart review study. The authors
found only one case of a cancerous polyp in the asymptomatic
group. The polyp in this case was large, with a mean diameter
of 40 mm. There was a significantly (P < 0. 001) higher
prevalence of malignant polyps in the symptomatic group.
The authors concluded that women with incidentally found
polyps do not require polypectomy unless the polyps have a
large diameter.
In 2009, Gregoriou et al.56 published a retrospective analysis of
516 cases of women who underwent hysteroscopic
polypectomy to determine risk factors for malignancy. The
final pathology report after polyp resection was compared
with each patient chart. The majority of polyps were benign
(96.9%), and a small percentage were premalignant (1.2%)
or malignant (1.9%). Obesity (BMI > 30) (P = 0.001),
diabetes mellitus (P = 0.04), menopause (P = 0.005), and
age > 60 years (P = 0.001) were all significant risk factors
for the development of malignant polyps. Gregoriou et al.56
suggested that all clinical parameters must be considered to
assess the risk of the malignancy potential of a polyp in a
postmenopausal woman.
Baiocchi et al.57 also conducted a large-scale retrospective
study to determine the clinical factors associated with
malignant polyps. Inclusion criteria for this study were
diagnosis of an endometrial polyp or endometrial
postmenopausal thickening of ³ 5 mm. In total, 1242 cases
were included in this study run from January 1995 to
December 2006. The majority of patients (95.2%) had
OCTOBER JOGC OCTOBRE 2010 l 995
SOGC Clinical Practice Guideline
benign polyps. Hyperplastic polyps with atypia occurred in
1.3% of patients and cancer in 3.5%. Postmenopausal status,
age > 60, and hypertension were all significantly correlated
with cancer in the polyp. Other clinical factors such as dia-
betes mellitus, HT, tamoxifen, and bleeding symptoms
were not significantly different between the benign and
cancerous polyp groups. In fact, the 2 most important factors
appear to be advanced age and postmenopausal status.
Baiocci et al.57 concluded that older menopausal patients
with hypertension are at the greatest risk of developing a
malignant polyp. However, in both the Gregoriou et al.56
and Baiocci et al.57 studies the incidence of cancer in polyps
was low (1.9% and 3.5% respectively).
IMPLICATIONS OF TAMOXIFEN
FOR ENDOMETRIAL THICKENING
Women taking tamoxifen have a greater risk of endometrial
cancer. This risk is augmented further if those women were
previously taking estrogen replacement therapy.58
Routine endometrial biopsy is not necessary in asymptomatic
women who are taking tamoxifen.24 Endometrial thickening
can be confused with stromal hypertrophy in these women.
However, any abnormal bleeding should be evaluated.
Endometrial cancers that occur in these women are similar
to endometrial cancers occurring in the general population
with respect to stage, grade, and histology. Prognosis tends
to be good. To date there have been no published studies
evaluating the effect of endometrial cancer screening
modalities on mortality among women taking tamoxifen for
the treatment or prevention of breast cancer.
Fishman et al.59 found that endometrial thickness increased
with increasing duration of tamoxifen use at a rate of
0.75 mm/yr. The mean endometrial thickness after 5 years
of tamoxifen use was 12 mm (range 6 to 21 mm). After
discontinuation of tamoxifen treatment the endometrium
decreased by 1.27 mm/yr.
Gerber et al.60 investigated the effect on the endometrium
in women with breast cancer when they switched from
tamoxifen to an aromatase inhibitor, anastrozole. A total of
226 postmenopausal women who had received tamoxifen
20 mg/d for ³ 12 months, £ 48 months and had developed
abnormal vaginal bleeding and/or asymptomatic endometrial
thickness >10 mm underwent hysteroscopy and dilatation
and curettage. One hundred seventy-one were randomized
to continue tamoxifen (88) or changed to anastrozole (83).
Patients were monitored for £ 42 months via TVUS at
6-monthly intervals. There was no difference in recurrent
vaginal bleeding between groups: 4/83 on tamoxifen and
9/88 on anastrozole. Mean endometrial thickness for
patients who switched to anastrozole was significantly less
than for those on tamoxifen. Repeat hysteroscopy and
996 l OCTOBER JOGC OCTOBRE 2010
dilatation and curettage revealed endometrial atrophy in all
4 cases in the anastrozole group, and there were 14 polyps,
8 hyperplasias, and 7 atrophies in the tamoxifen group.
Women on long-term tamoxifen therapy are thought to
have higher risk of developing endometrial cancer. Berlière
et al.61 enrolled 575 women with estrogen receptor-positive
breast cancer into a prospective study of endometrial
pathology. Prior to tamoxifen treatment, all women had
TVUS, and if endometrial thickness was > 5 mm,
hysteroscopy was performed to remove polyps or lesions.
In the study by Berlière et al.,61 women who had lesions
before initiating tamoxifen therapy were found at 2-year
follow-up to be at significantly higher risk (P < 0.001) of
developing atypical lesions. The lesions in the women who
had lesions originally were also more severe than any devel-
oped in the women who were initially lesion-free. The
authors concluded that women with initial lesions may be at
greater risk for the oncologic effects of tamoxifen on their
endometrium.
Garuti et al.62 also conducted a prospective study of estrogen-
positive breast cancer patients who were being prescribed
tamoxifen adjuvant therapy. The authors enrolled 99
asymptomatic patients and evaluated the endometrium using
hysteroscopy if their endometrial thickness was > 4 mm.
Thirty-four women had thickness > 4 mm, 10 had polyps, 4 had
simple hyperplasia, and 3 had complex hyperplasia. Thus,
18.6% of the patients had asymptomatic endometrial
pathology before tamoxifen treatment. Garuti et al.62 sug-
gested routine endometrial screening for all women before
initiation of tamoxifen therapy since subclinical
endometrial pathology is prevalent in this group of women.
The most recent American College of Obstetricians and
Gynecologists guideline for tamoxifen use and endometrial
cancer risk has several recommendations for
postmenopausal women.24 Women may be stratified into
2 risk groups based on whether they have initial endometrial
lesions. Women with initial lesions are at higher risk for
developing endometrial cancers on tamoxifen therapy.
Routine endometrial screening is not recommended for
women taking tamoxifen because of the costs incurred and
risk of unnecessary further investigation. Instead, women
should be educated regarding the symptoms of endometrial
cancer and instructed to consult their doctor if they develop
any spotting or postmenopausal bleeding. If a woman
develops endometrial hyperplasia, the use of tamoxifen
should be re-assessed.
COMPLICATIONS OF INVESTIGATION
Endometrial biopsy may result in pain, bleeding, infection,
and uterine perforation, and office-based endometrial
biopsy has false negative rates of 5% to 15%.63 Dilatation

and curettage has false negative rates of 2% to 6%.46
Endometrial sampling may be limited or impossible
because of virginal status, cervical stenosis, small introitus,
pain, or anatomical abnormalities such as fibroids
aberrating the canal. The finding of insufficient tissue in the
face of endometrial thickening prompts further investigations
such as hysterosonogram, office hysteroscopy, dilatation
and curettage, and diagnostic and therapeutic hysteroscopy
under general anaesthetic.63–66 Each of these procedures has
its own complications, including untimely hysterectomy. In
a study designed to compare blind biopsy, hysteroscopy
with biopsy, and ultrasound in 683 women who were
experiencing bleeding, discomfort and distress was
reported in 16% of women who had hysteroscopy and in
10% who had blind biopsy.67
No major complications were reported in the Shushan et al.68
study of 300 women who underwent hysteroscopic polyp
removal. Minor complications reported in the study
included bradycardia during general anaesthetic and post-
operative hemorrhage that was treated conservatively with
uterine tamponade for 8 hours. Two of the 300 patients
were readmitted to hospital with postoperative fever and
treated with antibiotic combination therapy for pelvic
inflammatory disease. Lev-Sagie et al.69 reported a compli-
cation rate of 3.6% in a retrospective study of women who
underwent hysteroscopy after incidental finding of
endometrial polyp on ultrasound examination. The
complications reported in the study were uterine perforation
in 2 women and complication of general anaesthetic due to
difficult intubation. Ferrazzi et al.54 reported a particularly
low rate of complications in the literature. Only the minor
complications of cervical tears and false passages were
reported in 0.6% and 0.3% of asymptomatic patients
respectively. False passage complications were reported in
0.8% of symptomatic patients in the Ferrazzi et al. study.54
In the 2007 Lieng et al.70 study, 92.2% of hysteroscopies
performed to remove endometrial polyps were complication-
free. The complications that did occur included uterine per-
foration, creation of false passage, moderate bleeding,
endometritis, failed procedure, and uterine perforation
including bowel injury. Thus, some of the complications of
hysteroscopy carry significant morbidity and possible
mortality.
CONCLUSION
Asymptomatic endometrial thickening found on ultrasound
examination in postmenopausal women often poses a clinical
management dilemma. Although the prevalence of endometrial
cancer is relatively low in women with no bleeding, the disease
has the best outcome when it is found at an early stage. The
disease is usually diagnosed at an early stage when
postmenopausal women present with bleeding. Routine
Asymptomatic Endometrial Thickening
ultrasound screening for asymptomatic women is not rec-
ommended. Current evidence suggests that certain subsets
of women at high risk of developing endometrial cancer
who have endometrial thickening on ultrasound and other
positive findings (increased vascularity, inhomogeneity of
endometrium, particulate fluid, excessively thickened
endometrium > 11 mm) should be referred to gynaecologists
for further investigations. Women with risk factors for
endometrial cancer and endometrial thickening such as
tamoxifen use, obesity, hypertension, and late menopause
should be triaged on an individual basis. Polyps found in
asymptomatic postmenopausal women need not be removed
routinely. However, factors such as polyp size and
histopathology, and patient age must be incorporated into
the decision for polypectomy. Investigations for asymp-
tomatic endometrial thickening are not risk free, and serious
complications such as bowel injury and uterine perforation
have been reported in the literature. Thus, adoption of these
recommendations may reduce anxiety, pain and risk of
procedural complication to the postmenopausal patient.
Recommendations
1. Transvaginal ultrasound should not be used as screening
for endometrial cancer. (II-1E)
2. Endometrial sampling in a postmenopausal woman with-
out bleeding should not be routinely performed. (II-1E)
3. Indications for tissue sampling of the endometrium in
bleeding postmenopausal women with an endometrial
thickness of greater than 4 to 5 mm should not be extrap-
olated to asymptomatic women. (II-2E)
4. A woman who has endometrial thickening and other positive
findings on ultrasound, such as increased vascularity,
inhomogeneity of endometrium, particulate fluid, or
thickened endometrium over 11 mm, should be referred
to a gynaecologist for further investigations. (II-1A)
5. Decisions about further investigations should be made
on a case-by-case basis in asymptomatic women with
increased endometrial thickening and risk factors for
endometrial cancer such as obesity, hypertension, and
late menopause. (II-1B)
6. In asymptomatic women on tamoxifen, a routine ultrasound
for endometrial thickening should not be performed. (II-2E)
7. Not all postmenopausal women who have asymptomatic
endometrial polyps require surgery. Women found to
have asymptomatic polyps on ultrasound should be
triaged for intervention according to size of the polyp,
age, and other risk factors. (II-1A)
OCTOBER JOGC OCTOBRE 2010 l 997
SOGC Clinical Practice Guideline
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30. Smith-Bindman R, Kerlikowske K, Feldstein V, Subak L, Scheidle J,
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32. Horwitz RI, Horwitz SM, Feinstein R, Robboy SJ. Necropsy diagnosis
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33. Alcazar JL, Galvan R. Three-dimensional power Doppler ultrasound
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35. Ciatto S, Cecchini S, Bonardi R, Grazzini G, Mazotta A, Zappa M.
A feasibility study of screening for endometrial carcinoma in postmenopausal
women by ultrasonography. Tumori 1995;81:334–7.
36. Fleischer AC, Wheeler JE, Lindsay I, Hendrix SL, Grabill S, Kravitz B, et al.
An assessment of the value of ultrasonographic screening for endometrial
disease in postmenopausal women without symptoms. Am J Obstet Gynecol
2001;184:70–5.
37. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United
States, 2008: a review of current American Cancer Society guidelines and
cancer screening issues, 2008. CA Cancer J Clin 2008;58:161–79.
38. Gerber B, Krause A, Mueller H, Reimer T, Kuelz T, Kundt G, et al.
Ultrasonographic detection of asymptomatic endometrial cancer in
postmenopausal patients offers no prognostic advantage over symptomatic
disease discovered by uterine bleeding. Eur J Cancer 2001;37:64–71.

39. Tsuda H, Nakamura H, Inoue T, Kawamura N, Ken-ichi A. Transvaginal
ultrasonography of the endometrium in postmenopausal Japanese women.
Gynecol Obstet Invest 2005;60:218–23.
40. Maatela J, Aromaa A, Salmi T, Pohja M, Vuento M, Gronroos M. The risk
of endometrial cancer in diabetic and hypertensive patients: a nationwide
record-linkage study in Finland. Ann Chir Gynaecol Suppl 1994;208:20–4.
41. Andolf E, Dahlander K, Aspenberg P. Ultrasound thickness of the endometrium
correlated to body weight in asymptomatic postmenopausal women. Obstet
Gynecol 1993;82:936–40.
42. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SAA,
Pettinger M, et al.; Women’s Health Initiative Investigators. Effects of estrogen
plus progestin on gynecologic cancers and associated diagnostic procedures:
The Women’s Health Initiative Randomized Trial. JAMA 2003;290:1739–48.
43. Martinez Rubio M, Alcazar J. Ultrasonographic and pathological endometrial
findings in asymptomatic postmenopausal women taking antihypertensive
drugs. Maturitas 2003;46:27–32.
44. Sit AS, Modugno F, Hill LM, Martin J, Weissfeld JL. Transvaginal ultrasound
measurement of endometrial thickness as a biomarker for estrogen exposure.
Cancer Epidemiol Biomarkers Prev 2004;13:1459–65.
45. Langer RD, Pierce JJ, O’Hanlan KA, Johnson SR, Espeland MA, Trabal JF, et al.
Transvaginal ultrasonography compared with endometrial biopsy for the
detection of endometrial disease. Postmenopausal Estrogen/Progestin
Intervention Trial. N Engl J Med 1997;337:1792–8.
46. Gull B, Karlsson B, Milsom I, Granber S. Can ultrasound replace dilation
and curettage: a longitudinal evaluation of postmenopausal bleeding and
transvaginal sonographic measurement of the endometrium as predictors
of endometrial cancer. Am J Obstet Gynecol 2003;188:401–8.
47. Kurtay G, Berker B, Demirel C. Transvaginal ultrasonographic assessment
of the endometrium in asymptomatic, postmenopausal women using
different HRT regimens containing tibolone or estrogen. J Reprod Med
2004;49:893–8.
48. Mossa B, Imperato F, Marziani R, Perniola F, Melluso J, Perniola G, et al.
Hormonal replacement therapy and evaluation of intrauterine pathology
in postmenopausal women: a ten-year study. Eur J Gynaecol Oncol
2003;24:507–12.
49. Tjarks M, Van Voorhis BJ. Treatment of endometrial polyps. Obstet Gynecol
2000; 96:886–9.
50. Bakour SH, Khan KS, Gupta JK. The risk of premalignant and malignant
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2000;79:317–20.
51. Savelli L, De Iaco P, Santini D, Rosati F, Ghi T, Pignotti E, et al.
Histopathological features and risk factors for benignity, hyperplasia and
cancer in endometrial polyps. Am J Obstet Gynecol 2003;188:927–31.
52. Domingues AP, Lopes H, Dias I, De Olivera CF. Endometrial polyps
in postmenopausal women. Acta Obstet Gynecol 2009;88:618–20.
53. Antunes A, Costa-Paiva L, Arthuso M, Costa JV, Pinto-Neto AM.
Endometrial polyps in pre- and postmenopausal women: factors
associated with malignancy. Maturitas 2007;57:415–21.
54. Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, et al.
How often are endometrial polyps malignant in asymptomatic
postmenopausal women? A multicenter study. Am J Obstet Gynecol
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Asymptomatic Endometrial Thickening
55. Fernández-Parra J, Rodríguez Oliver A, López Criado S, Parrilla Fernández
F, Montoya Ventoso F. Hysteroscopic evaluation of endometrial polyps.
Int J Gynaecol Obstet 2006;95:144–8.
56. Gregoriou O, Konidaris S, Vrachnis N, Bakalianou K, Salakos N, Papadias
K, et al. Clinical parameters linked with malignancy in endometrial polyps.
Climacteric 2009; 12:454–8.
57. Baiocchi G, Manci N, Pazzaglia M, Giannone L, Burnelli L, Giannone E, et al.
Malignancy in endometrial polyps: a 12-year experience. Am J Obstet Gynecol
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58. Bernstein L, Deapen D, Cerhan JR, Schwartz SM, Liff J, McGann-Maloney
E, et al. Tamoxifen therapy for breast cancer and endometrial cancer risk.
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59. Fishman M, Mona B, Sheiner E, Rotmensch J, Abramoxicz J. Changes in
the sonographic appearance of the uterus after discontinuation of tamoxifen
therapy. J Ultrasound Med 2006;25:469–73.
60. Gerber B, Krause A, Reimer T, Mylonas I, Makovitzky J Kundt G, et al.
Anastrozole versus tamoxifen treatment in postmenopausal women with
endocrine-responsive breast cancer and tamoxifen-induced endometrial
pathology. Clin Cancer Res 2006;12:1245–50.
61. Berlière M, Radikov G, Galant C, Piette P, Marbaix E, Donnez J.
Identification of women at high risk of developing endometrial cancer
on tamoxifen. Eur J Cancer 2000; 36:S35–36.
62. Garuti G, Cellani F, Centinaio G, Sita G, Nalli G, Luerti M. Baseline endometrial
assessment before tamoxifen for breast cancer in asymptomatic menopausal
women. Gynecol Oncol 2005; 98:63–70.
63. Gull B, Carlsson SA, Karlsson B, Ylostalo P, Milsom I, Granberg S.
Transvaginal ultrasonography of the endometrium in women with
postmenopausal bleeding: is it always necessary to perform an endometrial
biopsy? Am J Obstet Gynecol 2000; 182:509–15.
64. Goldstein S, Nachtigall M, Snyder J. Endometrial assessment by vaginal
ultrasonography before endometrial sampling in patients with postmenopausal
bleeding. Am J Obstet Gynecol 1990;163:119–23.
65. Goldstein S. The endometrial echo revisited: have we created a monster?
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67. Critchley HO, Warner P, Lee AJ, Brechin S, Guise J, Graham B. Evaluation
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69. Lev-Sagie A, Hamani Y, Imbar T, Hurwitz A, Lavy Y. The significance
of intrauterine lesions detected by ultrasound in asymptomatic
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70. Lieng M, Qvigstad E, Sandvik L, Jorgensen H, Langebrekke A, Istre O.
Hysteroscopic resection of symptomatic and asymptomatic endometrial
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OCTOBER JOGC OCTOBRE 2010 l 999
 SOGC Policy Statement

No. 263, August 2011

Maternity Leave in Normal Pregnancy

Abstract
This policy statement has been prepared by the Clinical
Practice Obstetrics Committee, reviewed by the Family Objective: To assist maternity care providers in recognizing and
Physicians Advisory Committee, and approved by discussing health- and illness-related issues in pregnancy and
the Executive of the Society of Obstetricians and their relationship to maternity benefits.
Gynaecologists of Canada.
Evidence: Published literature was retrieved through searches of
PRINCIPAL AUTHOR PubMed or Medline, CINAHL, and The Cochrane Library in 2009
Dean Leduc, MD, Ottawa ON using appropriate controlled vocabulary (e.g., maternity benefits)
and key words (e.g., maternity, benefits, pregnancy). Results
CLINICAL PRACTICE OBSTETRICS COMMITTEE were restricted to systematic reviews, randomized controlled
Dean Leduc, MD (Co-Chair), Ottawa ON trials/controlled clinical trials, and observational studies. There
were no date or language restrictions. Searches were updated
Glenn H. Gill, MD (Co-Chair), Williams Lake BC
on a regular basis and incorporated in the guideline to December
Anne Biringer, MD, Toronto ON 2009. Grey (unpublished) literature was identified through
Louise Duperron, MD, Kirkland QC searching the web sites of health technology assessment and
health technology assessment-related agencies, clinical practice
Ahmed M. Ezzat, MD, Saskatoon SK guideline collections, clinical trial registries, and national and
Donna Jones, MD, Calgary AB international medical specialty societies.
Lily Lee, MSN, Vancouver BC
Suzanne Muise, MD, St. Thomas ON
Barbara Mary Parish, MD, Halifax NS J Obstet Gynaecol Can 2011;33(8):864–866

Lexy Regush, MD, Saskatoon SK

Vyta Senikas, MD, Ottawa ON BACKGROUND

T
Kathi Wilson, RM, Ilderton ON
he role of obstetrical care providers in Canada is to
Grace Yeung, MD, London ON
promote and apply best practices in caring for the
FAMILY PHYSICIANS ADVISORY COMMITTEE
pregnant woman in order to minimize risk and maximize
William Ehman, MD (Chair), Nanaimo BC positive outcomes for both mother and infant. Pregnant
Anne Biringer, MD, Toronto ON women often seek input from their caregivers on the topic
Andrée Gagnon, MD, Blainville QC of maternity leave to plan cessation of work. In Canada, the
Lisa Graves, MD, Sudbury ON importance of child care in the first year of life is recognized
Jonathan Hey, MD, Saskatoon SK with benefit programs that provide financial support to
Jill Konkin, MD, Edmonton AB families. In addition, many employers have extended these
Francine Léger, MD, Montreal QC benefits through insurance plans or collective agreements
Cindy Marshall, MD, Lower Sackville NS to promote healthy beginnings.
Disclosure statements have been received from all members of
the committees. CESSATION OF WORK AND PARENTAL BENEFITS

The Federal Employment Insurance program1 provides

maternal benefits for up to 15 weeks. In order to qualify, a
Key Words: Pregnancy, maternity benefits woman must have worked 600 hours within the preceding
42 weeks. These benefits can be collected up to 8 weeks

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

864 l AUGUST JOGC AOÛT 2011


before the expected due date and “within 17 weeks of
the actual or expected week of birth.” 1 The employment
insurance program provides parental benefits to either
parent for up to 35 weeks. The benefits can be claimed
concurrently or consecutively but must be claimed within
the 52 weeks following the birth. In addition, many
employers will supplement benefits so that parents receive
up to 95% of their salary.
Quebec is the only province that has a program that
provides financial benefits for women with uncomplicated
pregnancies whose work or work environment may pose a
threat to them or their unborn child.2
Currently, a woman with an uncomplicated pregnancy is
deemed to be unfit for work and to qualify for benefits at
the onset of labour.
Women who experience complications of pregnancy or
other illness-related problems and who are deemed unable
to continue working are eligible for sickness benefits rather
than maternal benefits.
Healthy women with uncomplicated pregnancies often
ask their care providers to support a period of absence
from work before delivery, because they want to prepare
for labour; however, such a leave of absence would be
considered a health-related rather an illness-related leave.
There are few guidelines or standards governing the timing
or duration of health-related maternity leave. In addition,
there is no conclusive evidence for the ideal length of
health-related prenatal maternity leave, and there are no
data suggesting that such a leave of absence improves
outcomes. This leads to uncertainty for care providers,
resulting in inconsistent practices.
The timing of cessation of work before delivery is unique
for each pregnancy and should be discussed between
patient and care provider. The SOGC Clinical Practice
Obstetrics Committee has reviewed and endorses the
document published by the Alberta Perinatal Health
Program: Health-Related Maternity Leave in the Uncomplicated
Pregnancy and Birth.3 This document summarizes current
evidence regarding work-related risks and presents a
summary of current practices and recommendations for
health-related maternity leave in the antepartum and the
postpartum period. It supports the federal definition,
stating that women with uncomplicated pregnancies are
deemed unfit to work no later than at the onset of labour.
The document also expands this definition by stating that
for uncomplicated singleton pregnancies, health-related
maternity leave may be required for 2 to 6 weeks before the
estimated date of birth.
Maternity Leave in Normal Pregnancy
When complications arise in the antepartum period, physicians
can recommend a medical absence from the workplace if they
feel it is in the best interests of the patient.
Even in uncomplicated pregnancies a health-related leave may
be required to optimize maternal and fetal health, although
there is no conclusive evidence of improved outcomes.3
Health care providers should initiate a discussion early in the
pregnancy to educate women about the difference between
health-related and illness-related leaves of absence. This
provides an opportunity to advise women about the possible
medical complications that would support an illness-related
leave of absence and to inform them that issues such as
discomfort, poor sleep, fatigue, and musculoskeletal pain are
an unfortunate but normal part of a healthy pregnancy.
When a patient requests a medical leave of absence for
an uncomplicated pregnancy, the physician is not required
to support this demand. The patient should also be made
aware that it is not a recommended practice for care
providers to advocate an illness-related leave for women
with uncomplicated pregnancy without justification.
However, physicians can and should support a health-
related leave to enable a woman to prepare for the eventual
delivery, although she may not receive benefits for the
entire period of the leave. If care providers do support
a health-related leave, the woman should be advised that
it cannot be defined as an illness-related medical leave
and that she would not, therefore, be entitled to receive
any medical benefits. In effect, this health-related leave to
prepare for childbirth would be voluntary. A woman would
receive employment insurance benefits if this leave began
within 8 weeks of her expected due date.
The issue of benefits is beyond the scope of maternity
care providers. If a physician does recommend a leave of
absence, he or she should advise the patient that she may
or may not be entitled to employee benefits for the entire
period. Women should be aware of the maternity benefits
they are entitled to through their employer or government
agency, and should be advised that a recommendation to
take health-related leave in preparation for delivery does
not guarantee benefits.
RECOMMENDATIONS FOR
OBSTETRICAL CARE PROVIDERS
1. Understand the difference between a health-related and
an illness-related leave of absence.
2. Initiate a routine discussion early in pregnancy about
the issues that can present in an uncomplicated
AUGUST JOGC AOÛT 2011 l 865
SOGC Policy Statement
pregnancy (e.g., discomfort, poor sleep, fatigue, etc.) so
that women can plan their cessation of work.
3. Support women in taking health-related leave to
prepare for labour and delivery.
4. Advise women that they can begin maternity benefits
up to 8 weeks before the onset of labour.
5. Advise women that physicians cannot support an
illness-related leave in an uncomplicated pregnancy and
that this leave would be voluntary.
866 l AUGUST JOGC AOÛT 2011
REFERENCES
1. Human Resources and Skills Development Canada. Employment Insurance
(EI) and maternity, parental and sickness benefits. Available at:
http://www.servicecanada.gc.ca/eng/ei/types/special.shtml#Who.
Accessed April 29, 2011.
2. Government of Quebec. Quebec Parental Insurance Plan. Available at:
http://www.formulaire.gouv.qc.ca/cgi/affiche_doc.cgi?dossier=3967.
Accessed April 29, 2011.
3. Alberta Perinatal Health Program. Health-related maternity leave in the
uncomplicated pregnancy and birth, February 2008. Available at:
http://www.aphp.ca/publications_links_pub.html. Accessed April 29, 2011.
 SOGC CLINICAL PRACTICE GUIDELINE

No. 258, May 2011

Magnesium Sulphate for Fetal Neuroprotection

This clinical practice guideline has been prepared by MATERNAL FETAL MEDICINE COMMITTEE
the Guidelines Consensus Group, reviewed by the Robert Gagnon, MD (Co-Chair), Montreal QC
Maternal Fetal Medicine Committee, and approved by the
Executive and Council of the Society of Obstetricians Lynda Hudon, MD (Co-Chair), Montreal QC
and Gynaecologists of Canada. This document has been Melanie Basso, RN, Vancouver BC
reveiwed by the Fetus and Newborn Committee of the Hayley Bos, MD, London ON
Canadian Paediatric Society.
Joan M. Crane, MD, St. John’s NL
PRINCIPAL AUTHORS
Gregory Davies, MD, Kingston ON
Laura Magee, MD, Vancouver BC
Marie-France Delisle, MD, Vancouver BC
Diane Sawchuck, RN, PhD, Vancouver BC
Savas Menticoglou, MD, Winnipeg MB
Anne Synnes, MD, Vancouver BC
William Mundle, MD, Windsor ON
Peter von Dadelszen, MBChB, Vancouver BC
Annie Ouellet, MD, Sherbrooke QC
THE MAGNESIUM SULPHATE FOR FETAL
NEUROPROTECTION CONSENSUS COMMITTEE Tracy Pressey, MD, Vancouver BC
Melanie Basso, RN, Vancouver BC Christy Pylypjuk, MD, Saskatoon SK
Joan M. Crane, MD, St. John’s NL Anne Roggensack, MD, Calgary AB
Lex Doyle, MD, Victoria, Australia Frank L. Sanderson, MD, Saint John NB
William Ehman, MD, Nanaimo BC Disclosure statements have been received from all members of
the committees.
Robert Gagnon, MD, Montreal QC
The literature searches and bibliographic support for this
William Grobman, MD, Chicago IL
guideline were undertaken by Becky Skidmore, Medical
Michael Helewa, MD, Winnipeg MB Research Analyst, Society of Obstetricians and Gynaecologists
KS Joseph, MD, Vancouver BC of Canada.
M. Jocelyne Martel, MD, Saskatoon SK
Steven Miller, MD, Vancouver BC
Nan Okun, MD, Toronto ON Abstract
Dwight Rouse, MD, Providence RI Objective: To provide guidelines for the use of antenatal magnesium
Vyta Senikas, MD, Ottawa ON sulphate (MgSO4) for fetal neuroprotection of the preterm infant.
Rebecca Sherlock, MD, Vancouver BC Options: Antenatal MgSO4 administration should be considered for
Amanda Skoll, MD, Vancouver BC fetal neuroprotection when women present at ≤ 31+6 weeks
Graeme Smith, MD, Kingston ON with imminent preterm birth, defined as a high likelihood of birth
because of active labour with cervical dilatation ≥ 4 cm, with
Brenda Wagner, MD, Richmond BC
or without preterm pre-labour rupture of membranes, and/or
Sandrine Wavrant, MD, Montreal QC planned preterm birth for fetal or maternal indications.
R. Douglas Wilson, MD, Calgary AB There are no other known fetal neuroprotective agents.
Jennifer Hutcheon, PhD, Vancouver BC
Outcomes: The outcomes measured are the incidence of cerebral
palsy (CP) and neonatal death.
Evidence: Published literature was retrieved through searches of
PubMed or Medline, CINAHL, and the Cochrane Library in May
Key Words: Magnesium sulphate, preterm birth, cerebral palsy, 2010, using appropriate controlled vocabulary and key words
death, neuroprotection (magnesium sulphate, cerebral palsy, preterm birth). Results
were restricted to systematic reviews, randomized controlled

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

516 l MAY JOGC MAI 2011


trials, and relevant observational studies. There were no date
or language restrictions. Searches were updated on a regular
basis and incorporated in the guideline to August 2010. Grey
(unpublished) literature was identified through searching the
websites of health technology assessment and health technology
assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
medical specialty societies.
Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on Preventive Health
Care (Table 1).
Benefits, harms, and costs: Antenatal magnesium sulphate for fetal
neuroprotection reduces the risk of “death or CP” (RR 0.85;
95% CI 0.74 to 0.98; 4 trials, 4446 infants), “death or moderate-
severe CP” (RR 0.85; 95% CI 0.73 to 0.99; 3 trials, 4250 infants),
“any CP” (RR 0.71; 95% CI 0.55 to 0.91; 4, trials, 4446 infants),
“moderate-to-severe CP” (RR 0.60; 95% CI 0.43 to 0.84; 3
trials, 4250 infants), and “substantial gross motor dysfunction”
(inability to walk without assistance) (RR 0.60; 95% CI 0.43
to 0.83; 3 trials, 4287 women) at 2 years of age. Results were
consistent between trials and across the meta-analyses. There
is no anticipated significant increase in health care-related costs,
because women eligible to receive antenatal MgSO4 will be
judged to have imminent preterm birth.
Validation: Australian National Clinical Practice Guidelines were
published in March 2010 by the Antenatal Magnesium Sulphate
for Neuroprotection Guideline Development Panel. Antenatal
MgSO4 was recommended for fetal neuroprotection in the
same dosage as recommended in these guidelines. However,
MgSO4 was recommended only at < 30 weeks’ gestation, based
on 2 considerations. First, no one gestational age subgroup
was considered to show a clear benefit. Second, in the face of
uncertainty, the committee felt it was prudent to limit the impact
of their clinical practice guidelines on resource allocation. Also
in March 2010, the American College of Obstetricians and
Gynecologists issued a Committee Opinion on MgSO4 for fetal
neuroprotection. It stated that, “the available evidence suggests
that magnesium sulphate given before anticipated early preterm
birth reduces the risk of cerebral palsy in surviving infants.” No
official opinion was given on a gestational age cut-off, but it was
recommended that physicians develop specific guidelines around
the issues of inclusion criteria, dosage, concurrent tocolysis, and
monitoring in accordance with one of the larger trials.
Sponsors: Canadian Institutes of Health Research (CIHR).
ABBREVIATIONS
APH antepartum hemorrhage
CP
IQR
cerebral palsy
interquartile range
IUGR intrauterine growth restriction
NNT number needed to treat
PPROM preterm pre-labour rupture of membranes
PTL preterm labour
Magnesium Sulphate for Fetal Neuroprotection
Summary Statement
1. “Imminent preterm birth” is defined as a high likelihood of birth
due to one or both of the following conditions (II-2):
• Active labour with ≥ 4 cm of cervical dilation, with or without
PPROM.
• Planned preterm birth for fetal or maternal indications.
Recommendations
1. For women with imminent preterm birth (≤ 31+6 weeks), antenatal
magnesium sulphate administration should be considered for fetal
neuroprotection. (I-A)
2. Although there is controversy about upper gestational age,
antenatal magnesium sulphate for fetal neuroprotection should be
considered from viability to ≤ 31+6 weeks. (II-1B)
3. If antenatal magnesium sulphate has been started for fetal
neuroprotection, tocolysis should be discontinued. (III-A)
4. Magnesium sulphate should be discontinued if delivery is no
longer imminent or a maximum of 24 hours of therapy has been
administered. (II-2B)
5. For women with imminent preterm birth, antenatal magnesium
sulphate for fetal neuroprotection should be administered as
a 4g IV loading dose, over 30 minutes, followed by a 1g/hr
maintenance infusion until birth. (II-2B)
6. For planned preterm birth for fetal or maternal indications,
magnesium sulphate should be started, ideally within 4 hours
before birth, as a 4g IV loading dose, over 30 minutes, followed by
a 1g/hr maintenance infusion until birth. (II-2B)
7. There is insufficient evidence that a repeat course of antenatal
magnesium sulphate for fetal neuroprotection should be
administered. (III-L)
8. Delivery should not be delayed in order to administer antenatal
magnesium sulphate for fetal neuroprotection if there are maternal
and/or fetal indications for emergency delivery. (III-E)
9. When magnesium sulphate is given for fetal neuroprotection,
maternity care providers should use existing protocols to monitor
women who are receiving magnesium sulphate for preeclampsia/
eclampsia. (III-A)
10. Indications for fetal heart rate monitoring in women receiving
antenatal magnesium sulphate for neuroprotection should follow
the fetal surveillance recommendations of the SOGC 2007 Fetal
Health Surveillance: Antepartum and Intrapartum Consensus
Guideline. (III-A)
11. Since magnesium sulphate has the potential to alter the
neonate’s neurological evaluation, causing hypotonia or apnea,
health care providers caring for the neonate should have an
increased awareness of this effect. (III-C)
J Obstet Gynaecol Can 2011;33(5):516–529
BACKGROUND
The Importance of Preterm Birth
T he Canadian preterm birth rate overall reached
8.2 % of live births in 2004, with births at < 32 weeks
representing 1.2 % of live births in Canada.1 The survival
of infants born preterm has improved with interventions
such as antenatal corticosteroids and surfactant. However,
survival has been associated with substantial risk of medical
and neurodevelopmental impairment.
MAY JOGC MAI 2011 l 517
SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
* The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.47
† Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.47
Two identified patterns of injury appear to underlie the
central nervous system complications of preterm infants:
(1) intraventricular hemorrhage and (2) white matter injury.
Severe intraventricular hemorrhage (grades 3 and 4) is reliably
detected by ultrasound and occurs primarily among babies
who are born at or before 28 weeks’ gestation. Although the
incidence of severe intraventricular hemorrhage is highest
at 24 to 25 weeks, severe intraventricular hemorrhage is still
a relevant problem up to 28 weeks, because there are more
births at 26 to 28 weeks than at 24 to 25 weeks. MRI is
required for reliable detection of white matter injury, which
has a peak prevalence at 28 weeks. Its severity is associated
with adverse motor and cognitive outcomes.2
Clinically, the most frequent adverse neurological outcomes
associated with preterm birth are cerebral palsy and cognitive
impairment. Other adverse outcomes include blindness,
deafness, developmental delay, and/or other neurological
impairment. More than 50% of very preterm babies suffer
from learning or motor disabilities or school difficulties,
compared with about 20% of normal birthweight controls.3
The Importance of Cerebral Palsy
Cerebral palsy is a symptom complex of non-progressive
motor impairment syndromes secondary to brain injury or
anomalies arising in early development.4 The typical signs of
CP include spasticity, movement disorders, muscle weakness,
ataxia, and rigidity. There are 4 main types of cerebral palsy:
1. Spastic (increased muscle tone)
2. Athetoid or dyskinetic (slow, uncontrolled movements)
518 l MAY JOGC MAI 2011
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
3. Ataxic (problems with balance and depth perception)
4. Mixed
The most common pattern is spasticity plus athetoid move-
ments.5 CP can be reliably diagnosed by the age of 2 years.
The prevalence of CP is 2 to 2.5 per 1000 live births.6 The risk
of CP is highest at earlier gestational ages. Compared with
infants born at term, infants born preterm have a CP risk
that is approximately 3-fold higher at 34 to 36 weeks,7 8-fold7
to 14-fold8 higher at 30 to 33 weeks, 46-fold higher at 28 to
30 weeks,8 and as high as 30-fold4 to 80-fold8 higher at < 28
weeks.9 The gestational age-related risk is associated, in part,
with very low birth weight (i.e., < 1500 g) and intraventricular
hemorrhage.10–12 Multiples are also at heightened CP risk.13
Temporal trends in the prevalence of CP among infants
born very preterm are a matter of controversy. Rates have
been reported to be both falling14,15 and rising,10,16 possibly
because perinatal mortality rates are decreasing, so that the
rate of “death or CP” among infants born at < 30 weeks
has appeared to be stable.6
What is agreed upon, however, is that the economic
burden associated with CP is enormous. The US Centers
for Disease Control and Prevention estimate that lifetime
health care, productivity, and social costs for a person with
CP are US$921 000 (2003).17
There is no known cure for CP, which makes effective
preventive measures of primary importance. To date, no
 Magnesium Sulphate for Fetal Neuroprotection

Table 2. Inclusion criteria in the randomized controlled trials of magnesium sulphate for fetal neuroprotection
Inclusion criteria*
Multiple Delivery
Women, pregnancy, Gestational likely within PTL, Chorioam- Pre- Severe
Study n % age, weeks 24 hours % PPROM nionitis eclampsia IUGR APH
Neuroprotective intent
ACTOMgSO4 1062 17 < 30 Yes 63 9% 14% 15% 9% 14%
Crowther et al.
200335
PREMAG Marrett 564 22 < 33 Yes 85 61% 11% Excluded Excluded 19%
et al. 200636
MAGnet 57 4 25 to 33+6 NA 100† If Excluded Excluded NA NA
Mittendorf et al. associated
2002— with PTL
neuroprotective
intent arm37
BEAM Rouse 2241 9 24 to 31+6 NA 10 87% NA Excluded Included NA
et al. 200838 by % NA
Other primary intent
MAGnet Mittendorf 92 15 25to 33+6 NA 100 If Yes‡ Excluded NA Yes‡
et al. 2002, tocolytic associated
arm37 with PTL
MAGPIE 200641 10 4 < 37 NA NA NA NA 100% NA NA
141 (but subgroup analyses
were possible for lower
gestational age categories)
LD: loading dose; NA: not available
* indications for at least 90% of study population listed.
† With cervical dilatation > 4 cm and therefore not eligible for tocolysis.
‡ 71.1% had PPROM and 50.8% had chorioamnionitis, but the results were not presented according to whether women were in the tocolytic or neuroprotective intent arms.

antenatal interventions have been identified that effectively
decrease CP risk among preterm infants.
Magnesium Sulphate for Neuroprotection
In two studies published in the 1980s, preterm infants
born to women with preeclampsia had a lower incidence
of adverse CNS outcomes than gestational age-matched
neonates born to mothers without preeclampsia.18,19 In
1995, a seminal case–control study20 was conducted with
data derived from the California Cerebral Palsy project.21
It demonstrated an association between antenatal
magnesium sulphate administration prior to preterm
birth and fewer cases of CP among infants born < 1500
g.20 It has been proposed that use of magnesium sulphate
for eclampsia treatment and prophylaxis may underlie the
potential association between antenatal administration
of magnesium sulphate and CP,20,22 but the findings
of subsequent observational studies investigating the
association have been inconsistent.23–25 Although the
effectiveness of magnesium sulphate for prevention and
treatment of maternal eclampsia is well proven, there
remains a lack of understanding of how it may act as
a neuroprotective agent.26,27 Magnesium acts in many
intracellular processes, and its actions include cerebral
vasodilation, reduction in inflammatory cytokines and/or
oxygen free radicals, and/or inhibition of calcium influx
into cells.28,29 Animal studies have shown a neuroprotective
effect.30,31
From 2002 to 2008, 5 randomized controlled trials (6145
babies) studied magnesium sulphate for fetal neuroprotection
(Table 2). In 2009, a milestone was reached with the
publication of 3 meta-analyses, all of which concluded that
magnesium sulphate for fetal neuroprotection decreases
the risk of childhood CP.32–34 Four trials used magnesium
sulphate specifically for fetal neuroprotection among women
likely to deliver within 24 hours.35–38 The fifth trial26 evaluated
the effectiveness of magnesium sulphate for eclampsia
prevention in women with preeclampsia. Of the 4 trials
with neuroprotective intent, one also included a tocolytic
arm.37 Three of these 4 trials enrolled primarily women with
preterm labour (with or without PPROM),35–37 whereas the
fourth focused on women with PPROM.38 Children were
followed-up to the age of 2 years for CP assessment, and 3
trials undertook cognitive testing.26,35,38
Study quality was good.32 Importantly, 4 of the 5 trials
(and all neuroprotective intent trials) described an adequate

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SOGC CLINICAL PRACTICE GUIDELINE

Table 3a. Magnesium sulphate versus placebo: perinatal outcomes in neuroprotection trials only
RR (95%CI) Trials, n, Infants, n
Costantine Conde-Agudelo Costantine Conde-Agudelo
Doyle et al.34 and Weiner33 and Romero32 Doyle et al.34 and Weiner33 and Romero32
Primary outcomes
Death or CP 0.85 0.86 Not presented 4 trials, 4 trials, Not presented
(0.74 to 0.98) (0.75 to 0.99) 4446 infants 4314 infants
Death or moderate- 0.85 Not presented Not presented 3 trials, Not presented
severe CP (0.73 to 0.99) 4250 infants
Death or substantial 0.84 Not presented Not presented 3 trials, Not presented Not presented
gross motor dysfunction (0.71 to 1.00) 4387 infants
Death 0.95 0.95 0.95 4 trials, 4 trials, 4 trials,
(0.80 to 1.12) (0.80 to 1.13) (0.80 to 1.12) 4446 infants 4324 infants 4446 infants
CP 0.71 0.71 0.71 4 trials, 4 trials, 4 trials,
(0.55 to 0.91) (0.55 to 0.91) (0.55 to 0.91) 4446 infants 4314 infants 4446 infants
Moderate-severe CP Not presented 0.60 Not presented Not presented 3 trials, Not presented
(0.43 to 0.84) 4250 infants
Substantial gross motor 0.60 Not presented Not presented 3 trials; Not presented Not presented
dysfunction (0.43 to 0.83) 4387 infants
Any neurological 1.03 Not presented Not presented 1 trial, Not presented Not presented
impairment (0.87 to 1.21) 1255 infants
Other neonatal CNS outcomes
IVH 0.96 Not presented Not presented 4 trials to Not presented Not presented
(0.86 to 1.07) 4446 infants
Severe IVH 0.83 Not presented Not presented 2 trials; Not presented Not presented
(grade 3 or 4) (0.62 to 1.13) 3699 infants
PVL 0.93 Not presented Not presented 4 trials to Not presented Not presented
(0.68 to 1.28) 4446 infants
Other infant/child neurodevelopmental outcomes
Developmental delay or 1.00 Not presented Not presented 3 trials, Not presented Not presented
intellectual impairment (0.91 to 1.09) 4387 infants
Major neurological 1.14 Not presented 1.09 1 trial, Not presented 2 trials,
disability (0.86 to 1.51) (0.83 to 1.43) 1255 infants 2060 infants
Blindness 0.97 Not presented 0.97 2 trials, Not presented 2 trials,
(0.14 to 6.90) (0.14 to 6.90) 1943 infants 1943 infants
Deafness 0.51 Not presented 0.51 2 trials, Not presented 2 trials,
(0.05 to 4.96) (0.05 to 4.96) 1943 infants 1943 infants
CNS: central nervous system; IVH: intraventricular hemorrhage; PVL: periventricular leukomalacia.

method of allocation concealment.26,35,36,38 All but the
tocolytic arm of Mittendorf et al.37 described double-
masking of outcome assessment.
Magnesium Sulphate Use in Obstetrics
Magnesium sulphate is widely available and commonly used
in Canadian obstetric practice for eclampsia prophylaxis
and treatment.26,27,39 Magnesium sulphate is no longer
recommended for tocolysis, because it is ineffective.34
This document summarizes the relevant evidence and
provides practice recommendations related to the use of
antenatal magnesium sulphate for fetal neuroprotection
among women with imminent preterm birth.
Summary Statement
1. “Imminent preterm birth” is defined as a high
likelihood of birth due to one or both of the
following conditions (II-2):
• Active labour with ≥ 4 cm of cervical dilation,
• with or without PPROM.
• Planned preterm birth for fetal or maternal
• indications.
Recommendation
1. For women with imminent preterm birth
(≤ 31+6 weeks), antenatal magnesium sulphate
administration should be considered for fetal
neuroprotection. (I-A)
Table 3a presents the results of the 3 relevant meta-
analyses of neuroprotective trials,32–34 and shows that
antenatal magnesi um sulphate reduced the risk of
“death or CP,” “death or moderate-severe CP,” “any CP,”

520 l MAY JOGC MAI 2011

 Magnesium Sulphate for Fetal Neuroprotection

Table 3b. Magnesium sulphate versus placebo: perinatal outcomes in all trials of antenatal magnesium sulphate
Doyle et al.34 Costantine and Weiner33 Conde-Agudelo and Romero32
Trials, n Trials, n Trials, n
RR (95% CI) Infants, n RR (95% CI) Infants n RR (95% CI) Infants n
Primary outcomes
Death or CP 0.94 5 trials, 0.92 5 trials, 0.92 5 trials,
(0.78 to 1.12) 6145 infants (0.83 to 1.03) 5225 infants (0.83 to 1.02) 5357 infants
Death or moderate- Not presented Not presented 0.85 3 trials, Not presented Not presented
severe CP (0.73 to 0.99) 4250 infants
Death or substantial 0.92 4 trials, Not presented Not presented Not presented Not presented
gross motor dysfunction (0.75 to 1.12) 5980 infants
Death 1.01 5 trials, 0.95 4 trials, 1.01 5 trials,
(0.82 to 1.23) 6145 infants (0.80 to 1.13) 4324 infants (0.89 to 1.14) 5357 infants
CP 0.69 5 trials, 0.71 4 trials, 0.69 5 trials,
(0.54 to 0.87) 6145 infants (0.55 to 0.91) 4314 infants (0.55 to 0.88) 5357 infants
Moderate-severe CP Not presented Not presented 0.60 3 trials, 0.64 3 trials,
(0.43 to 0.84) 4250 infants (0.44 to 0.92) 4387 infants
Substantial gross motor 0.60 4 trials, Not presented Not presented 0.60 3 trials,
dysfunction (0.43 to 0.83) 4387 infants (0.43 to 0.83) 4387 infants
Any neurological 1.01 2 trials, Not presented Not presented 1.02 2 trials,
impairment ( 0.86 to 1.19 ) 2848 infants (0.86 to 1.20) 2060 infants
Other neonatal CNS outcomes
IVH 0.96 4 trials, Not presented Not presented 0.96 5 trials,
(0.86 to 1.08) 4552 infants (0.86 to 1.08)) 4552 infants
Severe IVH (grade 3/4) 0.83 2 trials, Not presented Not presented 0.83 4 trials,
(0.62 to 1.13) 3699 infants (0.61 to 1.11) 3864 infants
PVL 0.93 4 trials, Not presented Not presented 0.93 5 trials,
(0.68 to 1.28) 4552 infants (0.68 to 1.28) 4552 infants
Other infant/child neurodevelopmental outcomes
Developmental delay or 0.99 4 trials, Not presented Not presented Not presented Not presented
intellectual impairment (0.91 to 1.09) 5980 infants
Major neurological 1.07 2 trials, Not presented Not presented 1.09 2 trials,
disability (0.82 to 1.40) 2848 infants (0.83 to 1.43) 2060 infants
Blindness 0.74 3 trials, Not presented Not presented 0.97 2 trials,
(0.17 to 3.30) 3536 infants (0.14 to 6.90) 1943 infants
Deafness 0.79 3 trials, Not presented Not presented 0.51 2 trials,
(0.24 to 2.56) 3536 infants (0.05 to 4.96) 1943 infants

CNS: central nervous system; IVH: intraventricular hemorrhage; PVL: periventricular leukomalacia.

“moderate-severe CP,” and “substantial gross motor
dysfunction” (inability to walk without assistance) at 2
years of age. The direction of effect was the same for
death or substantial gross motor dysfunction, but this did
not reach statistical significance. Results were consistent
between trials and across the meta-analyses. Use of
magnesium sulphate was not associated with an increase
in pediatric death. The tocolytic arm of one study37 was
stopped early because of an increase in pediatric mortality;
although this is consistent with the effects of magnesium
sulphate administered as a tocolytic in other studies,34
there were other quality issues with the Mittendorf et
al. tocolytic arm. These included the confounding effect
of multiple births (i.e., more in the magnesium sulphate
arm), the low quality score (Jahad score of 2/8 when the
other neuroprotective intent trials scored 7–8/8), the lack
of a placebo arm, that crossover was allowed, and that 3
of the 8 neonatal deaths in the magnesium sulphate arm
were related to congenital anomalies (n = 1) or twin-to-
twin transfusion (n = 2).
When the tocolytic arm of the MAGnet Trial40 and
results of the preeclampsia prophylaxis trial (MAGPIE)41
were included in the meta-analyses, antenatal magnesium
sulphate was shown to reduce the risk of death or moderate-
severe CP, any CP, moderate-severe CP, and substantial
gross motor dysfunction; the outcome of death or CP no
longer reached statistical significance (Table 3b). Although
such analyses support the use of magnesium sulphate to
decrease CP, the results of the neuroprotective intent trials
suggest a change in clinical practice.

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SOGC CLINICAL PRACTICE GUIDELINE
For antenatal magnesium sulphate given specifically for fetal
neuroprotection, the NNT to prevent one case of death or
CP is 43 (based on an event rate of 14.9% overall in the
magnesium arm of trials and 17.2% among placebo-treated
controls). The NNT to prevent one case of CP is 63 (based
on an event rate of 3.4% overall in the magnesium arm
of the trials and 5.0% among placebo-treated controls).
These compare favourably with other established obstetric
interventions, such as the NNT of 50 (95% CI 34 to 100)
for use of magnesium sulphate to prevent eclampsia among
women with severe preeclampsia.26
While the 3 meta-analyses demonstrate significant results for
antenatal magnesium sulphate reducing the risk of death or
CP, death or moderate-severe CP, any CP, moderate-severe
CP, and substantial gross motor dysfunction at 2 years of
age, it is important to note that no single trial demonstrated
a statistically significant decrease in the combined outcome
of death or CP.
Despite these favourable results, strong evidence is lacking
with respect to 4 clinical issues:
1. The gestational age below which this therapy should be
offered.
2. The optimal loading and maintenance doses.
3. Antenatal magnesium sulphate has not been
associated with a decrease in central nervous
system pathology associated with CP, cognitive
impairment (i.e., intraventricular hemorrhage or
white matter injury measured as cystic periventricular
leukomalacia), and other adverse developmental
outcomes associated with preterm birth (e.g.,
developmental delay, neurological impairment,
blindness, or deafness). However, confidence
intervals in these trials35–38 were reasonably wide and
compatible with any of the following: a protective
effect (38% reduction), harmful effect (13% increase),
or no effect at all. Further evidence is needed to
determine whether there is an association between
magnesium sulphate and decreased CNS pathology.
4. There is no information on the effect of magnesium
sulphate on learning disabilities, school difficulties, or
other common school-age disabilities, because none
of the trials reported on outcomes beyond 2 years of
age; follow-up to school-age is planned for 2 of the
trials.35,36 Neurological follow-up was conducted to the
age of 2 years in 3 trials, 2 of which undertook detailed
neurocognitive testing.35,38 However, learning disabilities
and developmental coordination disorder, which are
prevalent among extremely low birth weight babies born
preterm, cannot be reliably detected until school age.
522 l MAY JOGC MAI 2011
Recommendations
2. Although there is controversy about upper
gestational age, antenatal magnesium sulphate for
fetal neuroprotection should be considered from
viability to ≤ 31+6 weeks. (II-1B)
3. If antenatal magnesium sulphate has been started
for fetal neuroprotection, tocolysis should be
discontinued. (III-A)
There is some uncertainty about the gestational age at
which magnesium sulphate should be administered.
A lower gestational age limit for viability has not been
specified in these studies35,37 so that clinical decisions
can take into consideration both parental preference and
institutionally defined thresholds. Each of the trials in the
meta-analyses32–34 had a different upper gestational age
limit for study eligibility, ranging from < 30 weeks35 to
≤ 33+6,37 making it challenging to recommend an upper
age limit.
It is uncertain whether the neuroprotective effect of
magnesium sulphate depends on gestational age at birth.
Table 4a presents the results of trials with neuroprotective
intent. The outcome of death or CP was significantly
decreased by magnesium sulphate when therapy was
administered at < 34 weeks. The outcome of CP was
significantly decreased at all gestational ages. Results for
all trials are shown in Table 4b; the < 30 week and < 28
week analyses include post hoc analyses of the MAGPIE
and BEAM trials, as randomization was not stratified by
these gestational age groupings. No effect of magnesium
sulphate was seen on the outcome of death or CP, but CP
was significantly decreased at all gestational ages.
There are 2 key considerations when determining a
gestational cut-off: (1) the potential for effect modification
by gestational age (i.e., the potential for magnesium sulphate
to have a different effect at different gestational ages), and
(2) the baseline prevalence of CP at different gestational
ages (since the NNT will be lower with a higher baseline
prevalence of a disease). Table 4a (neuroprotective intent
trials) and Table 4b (all relevant trials) both show that the
point estimate for the effect of magnesium sulphate on CP
risk reduction appears to be lower at < 28 weeks. Since the
prevalence of CP is also higher at < 28 weeks, the NNT to
prevent one case of CP is lowest at < 28 weeks. The NNT
appears to fall for administration of magnesium at earlier
gestational ages, with a more obvious trend among all trials
rather than among only neuroprotective trials. Regardless,
the NNT to prevent one case of CP is low at all gestational
ages at < 34 weeks.
 Magnesium Sulphate for Fetal Neuroprotection

Table 4a. Subgroup analyses by gestational age at randomization: neuroprotective trials only35–38
RR (95% CI) NNT to prevent harm
Weeks Death or CP CP Death or CP CP Trials, n, infants, n
< 34 0.85 (0.74 to 0.98) 0.71 (0.55 to 0.91) 43 53 5 trials, 6145 infants
< 32 0.86 (0.74 to 1.00) 0.68 (0.52 to 0.91) 43 50 3 trials, 3981 infants
< 30* 0.87 (0.74 to 1.03) 0.69 (0.48 to 0.99) 36 53† 3 trials, 2475 infants
< 28* 0.95 (0.74 to 1.22) 0.45 (0.23 to 0.87) 91 30 1 trial, 938 infants
* Includes the < 28 week subgroup of Rouse et al.38 which had women as the denominator.
† Inclusion of only the Crowther et al.35 trial and exclusion of the BEAM data (Rouse et al.38) give an NNT of 24.

Table 4b. Subgroup analyses by gestational age at randomization: all trials26,35-38,41

RR (95% CI) NNT to prevent harm
Weeks Death or CP CP Death or CP CP Trials, n, infants, n
< 34 0.94 (0.78 to 1.12) 0.68 (0.54 to 0.87) 105 63 5 trials, 6145 infants
< 32 0.95 (0.76 to 1.18) 0.69 (0.52 to 0.91) 71 56 3 trials, 3981 infants
< 30* 0.97 (0.78 to 1.21) 0.70 (0.49 to 0.99) 71 56† 3 trials, 2475 infants
< 28* 0.95 (0.74 to 1.22) 0.45 (0.23 to 0.87) 91 30 1 trial, 938 infants
* Includes the < 28 week subgroup of Rouse et al., which had women as the denominator.
38

This also includes the < 30 week subgroup data provided by the MAGPIE trial.
† In the Cochrane review,34 the < 30 week subgroup did not include the BEAM trial data for < 28 week38 and the NNT was 50.

A more useful post hoc analysis would be to examine CP risk
reduction within gestational age strata (32 to 33 weeks, 30
to 31 weeks, 28 to 29 weeks, and < 28 weeks) to identify the
gestational age at which babies may be most likely to benefit.
In the BEAM trial,38 analyses were stratified by gestational
age (< 28 vs. 28 to 31 weeks). Although it appeared as if
the decrease in CP was confined to the < 28-week subgroup,
the test for interaction by gestational age was actually not
significant. This should be interpreted as revealing no
difference in magnesium effect on CP rate by gestational
age up to 31+6 weeks. In MAGPIE,41 which was not a
neuroprotective intent trial and which underreported CP,
CP risk was similar at < 30 weeks (RR 1.04; 95% CI 0.06 to
16.06) and at 30 to 33 weeks (RR 0.95; 95% CI 0.71 to 1.27).
In summary, CP risk is highest at earlier gestational ages,
but these very preterm infants are fewer in number. Use
of magnesium sulphate at gestational ages closer to 34
weeks has the potential to substantially increase overuse of
magnesium sulphate for women with threatened preterm
birth who do not deliver in the subsequent 24 to 48 hours.
Therefore, consensus was reached to recommend an upper
gestational age cut-off of < 32 weeks (i.e., ≤ 31+6 weeks)
to strike a balance between appropriate use of magnesium
sulphate at earlier gestational ages and potential overuse
of magnesium sulphate at later gestational ages, when
neurological morbidity is lower. Institutions may choose
different thresholds (< 34 weeks) according to other
considerations, including the accuracy of gestational age
determination and resource allocation.
Table 2 presents the baseline characteristics of women who
were enrolled in the relevant randomized controlled trials.
In 3 of the 4 neuroprotective intent trials, most women
had preterm labour with anticipated delivery within 24
hours. This is not equivalent to threatened preterm labour
for which tocolysis is an option in the hope/expectation
of being able to arrest labour; this must be emphasized
to prevent potential overuse of magnesium sulphate for
neuroprotection in patients who are not truly in labour. The
other major indications for very preterm delivery (APH or
IUGR) were present in a minority of women enrolled in the
relevant trials. Although many women also had PPROM,
only the BEAM trial38 enrolled women with PPROM
without associated preterm labour. In this guideline,
these women are not included as eligible for magnesium
sulphate for neuroprotection. First, in the BEAM trial, re-
treatment with magnesium was administered for 59.1%
of women. Second, women with PPROM who are not in
labour are not necessarily in a delivery suite and receiving
one-to-one nursing care; administration of magnesium
for neuroprotective intent could have significant hospital
resource implications for these women.
All trials excluded women with the usual contraindications to
magnesium sulphate (i.e., hypersensitivity to the drug, hepatic

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SOGC CLINICAL PRACTICE GUIDELINE
Table 5. Inclusion and exclusion criteria for antenatal
magnesium sulphate administration in randomized
controlled trials
Inclusion criteria Exclusion criteria
Singleton and multiple Magnesium sulphate already
pregnancies administered for preeclampsia/
eclampsia
Nulliparous and parous < 12 hours since discontinuation
of previous magnesium sulphate
infusion
Anticipated vaginal or Magnesium sulphate
Caesarean delivery contraindicated
Any reason for anticipated Fetus unlikely to benefit
preterm birth
coma, myasthenia gravis) and those whose fetus was unlikely
to benefit from potential neuroprotection (i.e., severe fetal
malformations or chromosomal abnormalities). Antenatal
magnesium sulphate for fetal neuroprotection should be
used with caution in women who have renal impairment, and
serum magnesium levels should be monitored.
Magnesium sulphate for neuroprotection should be
administered regardless of singleton or multiple gestation, as
women with multiple pregnancies were enrolled in all trials.
The inclusion and exclusion criteria from the published
trials are summarized in Table 5.
Recommendations
4. Magnesium sulphate should be discontinued if
delivery is no longer imminent or a maximum of 24
hours of therapy has been administered. (II-2B)
5. For women with imminent preterm birth, antenatal
magnesium sulphate for fetal neuroprotection
should be administered as a 4g IV loading dose,
over 30 minutes, followed by a 1g/hr maintenance
infusion until birth. (II-2B)
6. For planned preterm birth for fetal or maternal
indications, magnesium sulphate should be started,
ideally within 4 hours before birth, as a 4g IV
loading dose, over 30 minutes, followed by a 1g/hr
maintenance infusion until birth. (II-2B)
As shown in Table 6, 4 trials of magnesium sulphate
administered a 4 g IV loading dose over 20 to 30 min35–37,41
Maintenance dosing varied from none36,37 to 1 g/hr35,41 or
2 g/hr38 for 12 hr38 or 24 hr.35,41 The median dose received
was as high as 31.5 g (IQR of 29.0 to 44.6), but this was the
trial primarily of women who had PPROM without labour,
and 59.1% of women were re-treated when delivery was
again considered to be imminent.38 The median dose was
524 l MAY JOGC MAI 2011
much lower, at 6.5 g (IQR of 4.5 to 14.0 g),35 when women
were enrolled primarily for preterm labour, reflecting a very
short median time from enrolment to delivery.
There have been no direct comparisons of different dosing
regimens of magnesium sulphate for neuroprotection.
A loading dose of 4 g IV with a maintenance infusion of
1 g/hr has been recommended to (1) resemble current
clinical practice and hospital protocols for magnesium
sulphate for eclampsia prophylaxis and treatment, and
(2) minimize concerns about maternal safety, particularly as
higher dosing regimens have not been associated with greater
neuroprotection. Trials that administered maintenance
infusions treated for a maximum of 24 hours antenatally.
For women with planned preterm birth, for fetal or
maternal indications, it is recommended that magnesium
sulphate be started as close as possible to 4 hours before
birth, as this was the mean time from randomization to
birth in subgroup analysis.35 No trials randomized women
with planned preterm birth to different durations of
magnesium sulphate therapy.
Risk of medication errors may be decreased if magnesium
sulphate is prepared in the central pharmacy rather than in
the labour and delivery suite.
Magnesium sulphate for fetal neuroprotection should be
discontinued at delivery.
The one trial (Rouse et al.38) in which re-treatment was
performed enrolled primarily women who had PPROM
without labour, and 59.1% of women were re-treated when
delivery was again considered to be imminent.38
Magnesium sulphate was infused for neuroprotective intent
as quickly as 20 minutes before delivery.
Recommendations
7. There is insufficient evidence that a repeat
course of antenatal magnesium sulphate for fetal
neuroprotection should be administered. (III-L)
8. Delivery should not be delayed in order to
administer antenatal magnesium sulphate for fetal
neuroprotection if there are maternal and/or fetal
indications for emergency delivery. (III-E)
9. When magnesium sulphate is given for fetal
neuroprotection, maternity care providers should
use existing protocols to monitor women who are
receiving magnesium sulphate for preeclampsia/
eclampsia. (III-A)
Existing protocols developed for eclampsia prophylaxis
and treatment may be used for women given magnesium
sulphate for fetal neuroprotection. Close monitoring of
 Magnesium Sulphate for Fetal Neuroprotection

Magnesium sulphate for fetal neuroprotection in imminent preterm birth

(≤ 31+6 weeks)

Woman ≤ 31+6 weeks gestation AND imminent

preterm birth
• Active labour with ≥ 4 cm cervical dilation with either failure or
contraindication to tocolysis
• ≥ 4 cm dilation with documented progressive change in cervical
dilation
• PPROM with active labour
• Planned delivery for fetal or maternal indications

YES NO

• Administer MgSO4 loading dose, Woman currently not eligible for

4g IV over 30 minutes MgSO4 for neuroprotection
• Follow with MgSO4 maintenance
infusion of 1g/hour IV until birth or a
maximum of 24 hours of therapy
• Administer corticosteroids for fetal
lung maturation (if not already given)
• Monitor maternal vital signs as per
existing MgSO4 protocols
• Provide continuous fetal heart
surveillance

CLINICAL TIPS
• MgSO4 may be administered before tocolytic drugs have been cleared from the maternal
circulation. If nifedipine has been used for tocolysis or hypertension, there is NO
contraindication to the use of MgSO4 for fetal neuroprotection.
• Delivery should NOT be delayed in order to administer antenatal MgSO4 for fetal
neuroprotection if there are maternal and/or fetal indications for urgent delivery.
• Monitoring of serum Mg levels is NOT required.

“Imminent preterm birth” is defined as a high likelihood of birth, due to one or both of the following conditions: active
labour with ≥4 cm of cervical dilation, with or without PPROM; planned preterm birth for fetal or maternal indications.

maternal urine output should not be required to the same
degree (i.e., no requirement for Foley catheter) when
magnesium sulphate is given with neuroprotective intent.
Magnesium sulphate produces peripheral vasodilation
when infused intravenously. In neuroprotective intent
trials, dose-related effects were common, particularly
flushing, problems at the injection site, sweating, and
nausea and vomiting (Table 7). Serious maternal side effects
were uncommon, with only maternal hypotension and
tachycardia reaching statistical significance. Few women
discontinued magnesium sulphate because of side effects.
Neither maternal death nor cardiorespiratory arrest was
reported in the magnesium sulphate arm of these trials.
Monitoring of maternal serum magnesium levels is not
required when magnesium sulphate is administered solely
for fetal neuroprotection. Maternal adverse effects are
dose-related, with respiratory or cardiac arrest associated
with levels in excess of 5 mmol/L. Levels of this magnitude
are not anticipated when magnesium contraindications are
observed but are more frequent when magnesium sulphate
is prepared in the delivery suite rather than by a central
pharmacy.
Because of their underlying condition, women with
imminent preterm birth require continuous fetal heart rate
monitoring, in accordance with the SOGC fetal health
surveillance guidelines.42
   Recommendations
  10. Indications for fetal heart rate monitoring in
women receiving antenatal magnesium sulphate for
neuroprotection should follow the fetal surveillance
recommendations of the SOGC’s 2007 Fetal Health
Surveillance: Antepartum and Intrapartum Consensus
Guideline. (III-A)
  11. Since magnesium sulphate has the potential to
alter the neonate’s neurological evaluation, causing
hypotonia or apnea, health care providers caring for
the neonate should have an increased awareness of
this effect. (III-C)

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Table 6. Magnesium sulphate dosing in the randomized controlled trials of magnesium sulphate for fetal
neuroprotection
Intervention: MgSO4
Women who Median (IQR) dose
Study Women, n Loading dose received the LD, % Maintenance dose received (g)
Neuroprotective intent
ACTOMgSO4 1062 4g IV over 20 mins 90% 1g/hr IV for 24 hr or 6.5 (4.5, 14)
Crowther et al. 200335 until delivery, whichever
comes first
PREMAG Marrett et al. 564 4g IV over 30 mins 99% None given 4 g IV over 30 mins
200636
MAGnet Mittendorf et al. 57 4g IV bolus Not reported Neuroprotective arm: Not reported
2002—neuroprotective none
intent arm37 (Tocolysis arm: 2–3g/hr)
BEAM Rouse et al. 200838 2241 6g IV over > 90%† 2 g/hr IV for a maximum 31.5 (29.0, 44.6)
20–30 mins* of 12 hr or until delivery†
Other primary intent
MAGnet Mittendorf et al. 92 4g IV “bolus” Not known 2–3 g/hr Not reported
2002—tocolytic arm37
MAGPIE 200641 10 141 4g IV over 96% 1g/hr IV (or 5g/4hrs IM) 18 (9, 29)‡
10 to15 mins for 24 hours
LD: loading dose; NA: not available.
* 71.5% of women were eligible for re-treatment. 59.1% of women were re-treated and were on magnesium sulphate at delivery.
† Based on the fact that 91% of women were on magnesium sulphate for at least three hours.
‡ Estimated as value uncertain from published data.33

The relevant randomized controlled trials34 raise no concerns
about short-term neonatal adverse effects of antenatal
exposure, and no additional neonatal assessment or care
is required. Neonates with hypermagnesemia may present
with symptoms of apnea or hypoventilation, weakness,
hypotonia, absent or reduced deep tendon reflexes, and
stupor or coma. This symptom complex has been described
in the neonates of mothers administered large doses of IV
magnesium sulphate for eclampsia with neonatal serum
levels > 4.5 mEq/L.43 However, antenatal magnesium sul-
phate administered specifically for fetal neuroprotection did
not affect the incidence of Apgar score < 7 at 5 minutes
(RR 1.03; 95% CI 0.90 to 1.18; 3 trials, 4387 infants),
neonatal hypotonia (RR 1.02; 95% CI 0.77 to 1.36; 1 trial,
2444 infants), or the need for ongoing ventilatory support
(RR 0.94; 95% CI 0.89 to 1.00; 3 trials; 4387 women). None
of the main trial publications reported on the need for active
resuscitation at birth,34 but a subanalysis of the BEAM trial
found no correlation between cord blood magnesium levels
and the need for bag-mask ventilation, intubation, or chest
compressions.44 It is unknown whether magnesium sulphate
exposure would affect the need for ventilation in neonatal
intensive care units using protocols to minimize ventilation.
The relevant randomized controlled trials35–38 demonstrated
no other differences in neonatal morbidity, including
seizures, respiratory distress syndrome, bronchopulmonary
dysplasia, or necrotizing enterocolitis.
Few newborn subjects with in utero exposure to magnesium
sulphate remote from delivery were included in the
relevant trials. There is no clear rationale for any additional
assessment of these newborns.
There should be an ongoing registry of children exposed
to antenatal magnesium sulphate for neuroprotection. This
would allow evaluation of the following:
1. Effects on delivery room resuscitation, especially in
units with ventilation-avoidance protocols
2. Anticipated reduction in CP
3. Effect on the high prevalence of school age morbidities
among infants born preterm.
SPECIAL CONSIDERATIONS REGARDING
THE USE OF MAGNESIUM SULPHATE
FOR FETAL NEUROPROTECTION
Transport
When maternal transport is being considered, magnesium
administration should be decided on in consultation with
the receiving centre, on a case-by-case basis.
Drug Interactions
Antenatal corticosteroids should be administered for fetal
lung maturation.
When tocolysis has been employed to attempt to arrest
preterm labour, magnesium sulphate can be used once

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 Magnesium Sulphate for Fetal Neuroprotection

Table 7. Maternal outcomes in trials of magnesium sulphate for fetal neuroprotection in

neuroprotective intent trials (adapted from Conde-Agudelo and Romero32)
MgSO4 Placebo Trials
n (%) n (%) RR (95% CI) n
Clinical and self-assessed maternal side effects
Any side effect 1356/1917 (70.7) 343/1950 (17.6) 5.05 (2.06 to 12.39) 3
Minor side effects
Flushing 1119/1917 (58.4) 162/1950 (8.3) 7.56 (3.39 to 16.88) 3
Problems at injection site 614/1631 (37.6) 68/1672 (4.1) 9.12 (7.19 to 11.57) 2
Sweating 411/1631 (25.2) 57/1672 (3.4) 6.37 (1.96 to 20.68) 2
Nausea or vomiting 312/1917 (16.3) 76/1950 (3.9) 4.60 (1.54 to 13.75) 3
Serious side effects
Hypotension 80/821 (9.7) 52/805 (6.5) 1.51 (1.09 to 2.09) 2
Tachycardia 56/535 (10.5) 36/527 (6.8) 1.53 (1.03 to 2.29) 1
Respiratory depression 41/1631 (2.5) 31/1672 (1.9) 1.31 (0.83 to 2.07) 2
Pulmonary edema 8/1096 (0.7) 3/1145 (0.3) 2.79 (0.74 to 10.47) 1
Infusion stopped due to adverse effects 123/1631 (7.5) 44/1672 (2.6) 2.81 (2.01 to 3.93) 2
Serious maternal adverse effects
Death 0/1917 1/1950 0.32 (0.01 to 7.92) 3
Cardiac or respiratory arrest 0/1917 0/1950 —* 3
* Not estimable.

tocolysis has been discontinued because delivery is
considered imminent. If nifedipine has been used for
tocolysis or hypertension, there is no contraindication to
the use of magnesium sulphate for fetal neuroprotection.
Although case reports have described neuromuscular
blockade with concomitant use of magnesium sulphate and
nifedipine or other calcium channel blockers, a controlled
study and synthesis of the literature failed to demonstrate
an increased risk.42
Potential Obstetrical Adverse Outcomes
In the Conde-Agudelo and Romero meta-analysis,32 mag-
nesium sulphate given with neuroprotective intent was not
associated with a difference in Caesarean section (822 [42.9%]
in the magnesium arm vs. 834 [42.8%] for placebo; RR 1.0;
95% CI 0.9 to 1.1; 3 trials, 3867 women) or severe
postpartum hemorrhage (28 [3.4%] in the magnesium
arm vs. 26 [3.2%] for placebo; RR 1.1; 95% CI 0.6 to 1.8;
2 trials, 1626 women). None of the trials reported on length
of labour or augmentation of labour.
CLINICAL PRACTICE GUIDELINES
AND COMMITTEE OPINION
Australian National Clinical Practice Guidelines45 were
published in March 2010 by the Antenatal Magnesium
Sulphate for Neuroprotection Guideline Development
Panel. They recommended antenatal magnesium sulphate
for fetal neuroprotection (excellent evidence) in the same
dosage as recommended in these guidelines. However,
magnesium was recommended only at < 30 weeks’ gestation
(good evidence) on the basis of two considerations. First,
no one gestational age subgroup (of the < 34, < 33, < 32,
and < 30 week categories considered) was considered to
show a clear benefit, although the < 28 week subgroup of
Rouse et al.38 was not included, because the committee felt
that the predominance of PPROM in that study population
limited generalizability to the target population of women
with imminent preterm labour (which the committee
defined as planned or definitely expected within 24 hours).
Second, in the face of uncertainty, the committee felt it
was prudent to limit the impact of their clinical practice
guidelines on resource allocation.
Also in March 2010, the American College of Obstetricians
and Gynecologists issued a committee opinion on magnesium
sulphate for fetal neuroprotection. It stated that “the
available evidence suggests that magnesium sulphate given
before anticipated early preterm birth reduces the risk of
cerebral palsy in surviving infants.” No official opinion was
given on a gestational age cut-off, but it was recommended
that physicians develop specific guidelines around the issues
of inclusion criteria, dosage, concurrent tocolysis, and
monitoring in accordance with one of the larger trials.46

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2003;169:207–8.
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 SOGC CLINICAL PRACTICE GUIDELINE

SOGC CLINICAL PRACTICE GUIDELINE No. 256, April 2011

Substance Use in Pregnancy

This clinical practice guideline has been prepared by the Jonathan Hey, MD, Saskatoon SK
Working Group on Problematic Substance Use in Pregnancy,
Jill Konkin, MD, Edmonton AB
reviewed by the Maternal Fetal Medicine Committee, the
Family Physicians Advisory Committee and the Medico-Legal Francine Léger, MD, Montreal QC
Committee, and approved by the Executive and Council of
Cindy Marshall, MD, Lower Sackville NS
the Society of Obstetricians and Gynaecologists of Canada.
MEDICO-LEGAL COMMITTEE
PRINCIPAL AUTHORS
Deborah Robertson, MD (Chair), Toronto ON
Suzanne Wong, MD, Toronto ON
Douglas Bell, MD, Ottawa ON
Alice Ordean, MD, Toronto ON
George Carson, MD, Regina SK
Meldon Kahan, MD, Toronto ON
Donna Gilmour, MD, Halifax NS
MATERNAL FETAL MEDICINE COMMITTEE
Owen Hughes, MD, Ottawa ON
Robert Gagnon, MD (Chair), Montreal QC
Caroline Le Jour, MD, Calgary AB
Lynda Hudon, MD (Co-Chair), Montreal QC
Dean Leduc, MD, Orleans ON
Melanie Basso, RN, Vancouver BC
Nicholas Leyland, MD, Hamilton ON
Hayley Bos, MD, London ON
Paul Martyn, MD, Calgary AB
Joan Crane, MD, St. John’s NL
André Masse, MD, Montreal QC
Gregory Davies, MD, Kingston ON
AD HOC REVIEWERS
Marie-France Delisle, MD, Vancouver BC
Ron Abrahams, MD, Vancouver BC
Dan Farine, MD, Toronto ON
Sanja Avdic, MD, Toronto ON
Savas Menticoglou, MD, Winnipeg MB
Howard Berger, MD, Toronto ON
William Mundle, MD, Windsor ON
Mike Franklyn, MD, Sudbury ON
Lynn Murphy-Kaulbeck, MD, Allison NB
Samuel Harper MD, Montreal QC
Annie Ouellet, MD, Sherbrooke QC
Georgia Hunt, MD, Vancouver BC
Tracy Pressey, MD, Vancouver BC
Patricia Mousmanis, MD, Richmond Hill ON
Anne Roggensack, MD, Calgary AB
Kellie Murphy, MD, Toronto ON
Frank Sanderson, MD, Saint John NB
Sarah Payne, MA, Vancouver BC
FAMILY PHYSICIANS ADVISORY COMMITTEE
SPECIAL CONTRIBUTORS
William Ehman, MD (Chair), Nanaimo BC
Deana Midmer, EdD, Toronto ON
Anne Biringer, MD, Toronto ON
Sandra de la Ronde, MD, Calgary AB
Andrée Gagnon, MD, Blainville QC
The literature searches and bibliographic support for this
Lisa Graves, MD, Sudbury ON
guideline were undertaken by Becky Skidmore, Medical
Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
J Obstet Gynaecol Can 2011;33(4):367–384 Disclosure statements have been received from all members of
the committees.
Key Words: Pregnancy, substance-related disorders, substance use, Dr Alice Ordean received funding from National Institute on Drug
neonatal abstinence syndrome Abuse grant R01 DA015741.

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

APRIL JOGC AVRIL 2011 l 367

SOGC CLINICAL PRACTICE GUIDELINE
Abstract
Objective: To improve awareness and knowledge of problematic
substance use in pregnancy and to provide evidence-based
recommendations for the management of this challenging clinical
issue for all health care providers.
Options: This guideline reviews the use of screening tools, general
approach to care, and recommendations for clinical management
of problematic substance use in pregnancy.
Outcomes: Evidence-based recommendations for screening and
management of problematic substance use during pregnancy
and lactation.
Evidence: Medline, PubMed, CINAHL, and The Cochrane Library
were searched for articles published from 1950 using the
following key words: substance-related disorders, mass
screening, pregnancy complications, pregnancy, prenatal
care, cocaine, cannabis, methadone, opioid, tobacco, nicotine,
solvents, hallucinogens, and amphetamines. Results were
initially restricted to systematic reviews and randomized
control trials/controlled clinical trials. A subsequent search for
observational studies was also conducted because there are
few RCTs in this field of study. Articles were restricted to human
studies published in English. Additional articles were located by
hand searching through article reference lists. Searches were
updated on a regular basis and incorporated in the guideline
up to December 2009. Grey (unpublished) literature was also
identified through searching the websites of health technology
assessment and health technology assessment-related agencies,
clinical practice guideline collections, clinical trial registries, and
national and international medical specialty societies.
Values: The quality of evidence was rated using the criteria described
in the Report of the Canadian Task Force on the Preventive
Health Care. Recommendations for practice were ranked
according to the method described in that report (Table 1).
Benefits, harms, and costs: This guideline is intended to increase
the knowledge and comfort level of health care providers
caring for pregnant women who have substance use disorders.
Improved access to health care and assistance with appropriate
addiction care leads to reduced health care costs and decreased
maternal and neonatal morbidity and mortality.
Recommendations
1. All pregnant women and women of childbearing age should be
screened periodically for alcohol, tobacco, and prescription and
illicit drug use. (III-A)
2. When testing for substance use is clinically indicated, urine drug
screening is the preferred method. (II-2A) Informed consent
should be obtained from the woman before maternal drug
toxicology testing is ordered. (III-B)
3. Policies and legal requirements with respect to drug testing of
newborns may vary by jurisdiction, and caregivers should be
familiar with the regulations in their region. (III-A)
ABBREVIATIONS
HCV hepatitis C virus
MMT methadone maintenance therapy
NAS neonatal abstinence syndrome
NRT nicotine replacement therapy
UDS urine drug screening
368 l APRIL JOGC AVRIL 2011
4. Health care providers should employ a flexible approach to the
care of women who have substance use problems, and they
should encourage the use of all available community resources. (II-2B)
5. Women should be counselled about the risks of periconception,
antepartum, and postpartum drug use. (III-B)
6. Smoking cessation counselling should be considered as a
first-line intervention for pregnant smokers. (I-A) Nicotine
replacement therapy and/or pharmacotherapy can be considered
if counselling is not successful. (I-A)
7. Methadone maintenance treatment should be standard of
care for opioid-dependent women during pregnancy. (II-IA)
Other slow-release opioid preparations may be considered if
methadone is not available. (II-2B)
8. Opioid detoxification should be reserved for selected women
because of the high risk of relapse to opioids. (II-2B)
9. Opiate-dependent women should be informed that neonates
exposed to heroin, prescription opioids, methadone, or
buprenorphine during pregnancy are monitored closely for
symptoms and signs of neonatal withdrawal (neonatal abstinence
syndrome). (II-2B) Hospitals providing obstetric care should
develop a protocol for assessment and management of neonates
exposed to opiates during pregnancy. (III-B)
10. Antenatal planning for intrapartum and postpartum analgesia
may be offered for all women in consultation with appropriate
health care providers. (III-B)
11. The risks and benefits of breastfeeding should be weighed on an
individual basis because methadone maintenance therapy is not
a contraindication to breastfeeding. (II-3B)
Introduction
S
ubstance use during pregnancy is common. In national
prevalence surveys, 14% of Canadian women reported
using alcohol during their last pregnancy, and 17% reported
smoking during pregnancy.1,2 The prevalence of illicit drug
use among Canadian women of childbearing age is less but
not insignificant. In United States population surveys ~5%
of pregnant women reported illicit drug use during the
preceding month.3 Marijuana remains the most commonly
used illegal drug, followed by cocaine. Women report
higher rates than men of prescription drug use, including
pain relievers (23.1%), opioid analgesics (2.1%), sleeping
pills (1.7%), tranquilizers (1.1%), and antidepressants
(2.1%).2
The use of alcohol and drugs by pregnant women can result
in significant maternal, fetal, and neonatal morbidity.4–17 In
general, pregnant women with substance use disorders are
less likely to seek prenatal care, and they have higher rates
of infectious diseases such as HIV, hepatitis, and other
sexually transmitted infections.17–19
There are numerous direct and indirect costs of perinatal
substance exposure. In 2002, the overall social cost of
substance abuse in Canada, including burden on health
care, law enforcement, and loss of productivity due to
premature death and ill health, totalled ~$40 billion.20 Data

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.161
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.161
from American studies have indicated that the increase
in cost of neonatal care for infants born to mothers who
smoke cigarettes is ~$700, and the increase in cost for
those exposed to cocaine is $5110 per patient.21–23
Because of the prevalence of substance use and its clinical
and economic impact, health care providers need to know
how to identify and care for the affected patient population.
Management of substance use disorders is complicated
because of the associated comorbid conditions and
psychosocial and socioeconomic factors, such as mental
health problems, poor housing, financial stressors, and lack
of supports. Canadian physicians have identified a lack
of knowledge and training regarding the effects of and
treatments for substance use during pregnancy as another
barrier to providing care for these patients.24 Perinatal care
providers have several opportunities during pregnancy to
identify and assist women who have substance use problems.
Although most physicians enquire routinely about alcohol,
tobacco, and other drug use during pregnancy, many
do not use a specific screening tool and are not making
referrals to other treatment resources.25–28 As motivation to
change unhealthy or harmful behaviours is increased during
pregnancy, it is an ideal time to intervene with women who
have substance use problems.
This guideline provides a unified approach to care for
perinatal substance use disorders.
Substance Use in Pregnancy
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
DEFINITIONS
Substance abuse and dependence have well-defined
criteria based on the DSM-IV guide (Table 2).29 Substance
dependence is characterized by compulsive drug use, loss
of control over use, and physical, social, and psychological
consequences.30 Physical dependence is characterized
by tolerance and withdrawal; however, it is not in itself
sufficient to make a diagnosis of substance dependence.
Substance withdrawal consists of a combination of drug-
specific symptoms and signs that occur within hours to
days of stopping drug use (Table 3).
identification of substance-related
disorders in pregnancy
Screening and Assessment
All pregnant women regardless of socioeconomic status
should be asked about past and current alcohol, nicotine,
and illicit and prescribed drug use. A high index of suspicion
for potential substance use during pregnancy is required in
various clinical situations.31 There is no optimal screening
tool for identifying substance use in pregnancy. Maternal
interview using open-ended, non-judgemental questioning
is more likely to elicit disclosure of perinatal substance
use.31,32 Health care providers should develop their own
level of comfort and style in asking their patients about this
sensitive topic. The T-ACE and TWEAK questionnaires
were developed for screening at-risk perinatal alcohol use
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SOGC CLINICAL PRACTICE GUIDELINE
(Figure 1).33,34 The ALPHA tool incorporates the CAGE
questionnaire to screen for maternal recreational drug
use, as well as validated questions to identify associated
psychosocial risk factors such as family violence or
postpartum depression (Appendix).35,36 If the woman
acknowledges substance use, a more complete assessment
is then recommended to determine if there is a history of
substance abuse or dependence (Figure 2).
Role of Toxicology Testing
Drug toxicology testing is not recommended for universal
screening (i.e., routine testing of all women) because it has
numerous limitations (Figure 3), and it should be considered
only after a comprehensive assessment if there is a clinical
indication.37 If a woman is concerned about providing
a sample or is reluctant to do so, clinicians should focus
on developing a trusting relationship before suggesting
toxicology testing. Vulnerable women may feel threatened
if clinicians wish to gather detailed information through
drug testing and psychosocial histories.
Urine, hair, and meconium samples are sensitive biological
markers of substance use. Urine drug screening can detect
only recent substance exposure, while neonatal hair and
meconium testing can document intrauterine use because
meconium and hair form in the second and third trimester,
respectively.38–41 By itself, a single positive test result cannot
be used to diagnose substance dependence. Although
child protection agencies sometimes request hair analyses,
neither hair nor meconium is appropriate for routine
clinical use because of the high costs and propensity for
false positive results.
UDS has several clinical indications. Evidence shows that
the addition of urine drug testing to the structured maternal
interview can increase the detection of problematic
substance use in pregnancy.42,43 Detection can facilitate
early intervention, including treatment of maternal and
neonatal withdrawal and counselling and referral for long-
term outpatient treatment. For example, an unexpected
positive UDS result for opioids may prompt an assessment
for opioid dependence and observation of the neonate for
signs of withdrawal. Ongoing outpatient monitoring with
UDS is also used to advocate on behalf of patients with
child protection services and to monitor compliance with
prescribed medications (e.g., opioids).34,38 In addition, it can
be performed on maternal request.
Informed consent must be obtained and documented in
the medical record before any maternal drug testing is
performed (except in life-threatening situations where
informed consent is impossible).44 If the mother refuses,
370 l APRIL JOGC AVRIL 2011
Table 2. Definitions of substance-related disorders
Substance
use disorder Definition
Substance A pattern of substance use, leading to
dependence clinically significant impairment or distress, as
manifested by ≥ 3 of the following, occurring at
any time in the same 12-month period:
1. tolerance
2. withdrawal
3. substance taken in larger amounts or over a
longer period than was intended
4. persistent desire or unsuccessful efforts to
cut down or control substance use
5. a great deal of time spent in activities
necessary to obtain the substance (e.g.,
visiting multiple doctors or driving long
distances), use the substance (e.g., chain-
smoking), or recover from its effects
6. important social, occupational, or
recreational activities given up or reduced
because of substance use
7. continued use despite knowledge of harm
Substance abuse A pattern of substance use leading to
clinically significant impairment or distress, as
manifested by ≥ 1 of the following, occurring
within a 12-month period:
1. recurrent substance use resulting in a
failure to fulfill major role obligations at work,
school, or home
2. recurrent substance use in situations in
which it is physically hazardous
3. recurrent substance-related legal problems
4. persistent or recurrent social or interpersonal
problems caused or exacerbated by the
effects of the substance
Tolerance Characterized by a need for markedly
increased amounts of the substance to
achieve desired effect or diminished effect with
continued use of the same amount of
the substance
this should be documented, and testing should not be
performed. Neonatal toxicology testing may be performed
without consent of the parent(s) if the person requesting
this testing has a legislative right to make decisions for
the infant to be tested. However, the mother should be
informed that the neonate is being tested.34 Once consent
is obtained, any drug toxicology testing to be performed
must be ordered by the physician responsible for maternal
and/or neonatal care.
Recommendations
1. All pregnant women and women of childbearing age
should be screened periodically for alcohol, tobacco,
and prescription and illicit drug use. (III-A)
 Substance Use in Pregnancy

Table 3. Withdrawal syndromes

Substance Withdrawal symptoms and signs
Nicotine Irritability, restlessness, anxiety, insomnia, fatigue, poor concentration
Marijuana Irritability, insomnia, anorexia, anxiety
Opioids Influenza-like symptoms: myalgias, rhinorrhea, goosebumps, diaphoresis, nausea,
vomiting, diarrhea
Psychological symptoms: insomnia, anxiety, strong cravings, dysphoria
Obstetrical symptoms: abdominal cramping, uterine irritability
Benzodiazepines Seizures (high dose), anxiety, panic attacks, insomnia, emotional lability
Cocaine/amphetamines Crash phase: fatigue, increased appetite
Withdrawal dysphoria phase: dysphoria, irritability, insomnia, strong cravings
Inhalants Similar to alcohol withdrawal: tremor, malaise, gastrointestinal symptom

2. When testing for substance use is clinically indicated,
urine drug screening is the preferred method. (II-2A)
Informed consent should be obtained from the woman
before maternal drug toxicology testing is ordered.
(III-B)
3. Policies and legal requirements with respect to drug
testing of newborns may vary by jurisdiction, and
caregivers should be familiar with the regulations in
their region. (III-A)
Components of office management
Obstetrical care providers need to establish rapport
with substance-using pregnant women through good
communication and a willingness to be flexible in providing
prenatal care and ongoing support. These women face a
number of barriers to receiving optimal prenatal care
(Figure 4).45–48 Flexibility with respect to patient scheduling
and understanding late arrivals and missed appointments
are key to engaging these women for prenatal care. Women
are likely to seek and commit to prenatal care if health care
providers are welcoming and non-judgemental, and if they
acknowledge the women’s courage and persistence in the
face of very difficult personal circumstances. Studies have
shown that comprehensive care provided at one site is cost-
effective and produces better outcomes for both mother
and child.9,19,49–58
It is also important to address women’s substance use
because pregnancy is an ideal time for women to make a
change. Harm reduction is defined as a program or policy
designed to reduce the drug-related harm without requiring
the cessation of drug use.30 The philosophy of care for
women with problematic substance use in pregnancy is
harm reduction. Components of this philosophy include
encouragement of abstinence or reduction of use, safe
use, treatment of withdrawal symptoms, counselling and/
or pharmacotherapy. Pregnancy may motivate women to
abstain from or reduce drug use, given the potential effects
on fetal outcomes.
Pregnant substance-using women are also at increased
risk of infectious diseases. Injection drug use remains the
most dominant mode of hepatitis C virus acquisition.
Approximately, 70% to 80% of HCV-infected patients
report a history of current or past injection drug use.59
HCV-negative women should be advised about ways to
prevent exposure to HCV. Women should be told not to
share materials to prepare, inject, or inhale drugs, and that
they should not engage in higher risk sexual behaviours
(e.g., unprotected sex with multiple sexual partners or
unprotected sex with HCV-positive partners). Pregnant
HCV-infected women have a 5% chance of transmitting
the virus to their infants.60 There are no ways to decrease
the risk of vertical transmission. Furthermore, mode of
delivery and breastfeeding do not affect mother-to-infant
transmission. Procedures that promote mixing of maternal
and fetal blood, such as use of scalp electrodes, should be
avoided, if possible. Serology testing of infants at 12 to 18
months of age is recommended to determine HCV status.
The prevalence of sexually transmitted infections is also
higher among pregnant women with a history of substance
abuse related to high-risk sexual behaviours.61,62 Screening
for Chlamydia, gonorrhea, syphilis, hepatitis, and HIV
should be repeated throughout pregnancy if historical
factors warrant it.63
There are numerous adverse effects associated with
prenatal drug exposure (Table 4). These effects may also
be linked to other factors such as inadequate prenatal care,
poor social circumstances, and concomitant use of other
substances.64,65 Therefore, long-term studies are difficult to

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Figure 1. T-ACE and TWEAK for problematic alcohol use

T-ACE
T How many drinks does it take to make you feel high? (Tolerance)
A Have people annoyed you by criticizing your drinking?
C Have you felt you ought to cut down on your drinking?
E Have you ever had a drink first thing in the morning to steady your nerves or get rid
of a hangover? (Eye-opener)
Scoring: T: 2 points if > 3 drinks; A,C,E: 1 point for each yes answer
A total of 2 or more points indicates patient is likely to have an alcohol problem.
TWEAK
T Tolerance
W Have friends or relatives complained about your drinking? (Worried)
E Eye-opener
A Has a friend or family member ever told you about things you said or did while you
were drinking that you could not remember? (Amnesia or black-out)
K Cut-down
Scoring: T: 2 points if > 3 drinks; W, E, A, K: 1 point for each yes answer
A total of score of 3 or more points indicates patient is at-risk drinking

Figure 2. Assessment for substance-related disorders

Complete drug history: name of drug, amount, frequency, duration, route(s), last use,
injection drug use, sharing needles/paraphernalia, withdrawal symptoms
Stage of change with respect to substance use
• Consequences of drug use: medical, social, personal
• Previous treatment programs, mutual aid groups (e.g., AA)
Medical history: HIV, Hepatitis B and C, STIs
• Chronic medical conditions (e.g., chronic pain), medications
Psychiatric history: eating disorders, sexual/physical abuse, mood and
anxiety disorders
Obstetrical history: cycle regularity, LMP, past obstetrical outcomes and
complications
Social history: family situation (partner and number of children), custody status,
housing situation, legal status (current charges and court dates), finances, nutrition,
child protection agency involvement, child safety concerns
FIFE: feelings, impressions/ideas, functioning, expectations about pregnancy
and drug use

interpret because effects may be due to these confounders
and environmental deprivation rather than the drug itself.
In addition to routine care, patients should be given
counselling regarding the drug-specific fetal, neonatal, and
maternal effects of substance use.
Antenatal fetal surveillance should be based on obstetrical
indications rather than solely on substance use. Substance
use during pregnancy has been associated with obstetrical
complications such as preterm labour, placental abruption,
and intrauterine growth restriction (Table 4), and these
adverse effects may lead to an increased risk of perinatal
morbidity and mortality. Therefore, the method and
frequency of antenatal testing will be determined by the
presence or absence of these complications.66
There are two phases to the management of substance
use disorders. The first addresses treatment of withdrawal
syndromes. Pregnant women who are dependent on alcohol,
opioids, or high-dose benzodiazepines (> 50 mg daily
diazepam equivalent) may require medical detoxification
under the supervision of a physician (Table 5).30 Women
who are in withdrawal from other substances, such as
cocaine or marijuana, may also benefit from a supportive
admission to a non-medical withdrawal management
centre, if available.

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 Substance Use in Pregnancy

Figure 3. Limitations of drug toxicology

• Women can avoid detection of substances in urine samples through simple measures such as abstaining
for 1–3 days before testing, drinking lots of water to lower the concentration of the drug in the urine, or
substituting samples of another person’s urine for their own
• Alcohol is very hard to detect with laboratory testing (blood and urine sampling) because of its short half-life
• The amount of drug in a hair sample correlates with degree of drug use (which is not the case with urine
drug testing); however, a positive finding is not diagnostic of addiction
• Hair analysis can have false-positive results due to passive exposure to smoked drugs in environment
• A false positive result can have serious legal and emotional consequences for the mother

Figure 4. Barriers to prenatal care for pregnant substance-using women

• Personal factors: shame, stigma, guilt, lack of family support, substance using male partner, fear of losing
children, concomitant psychosocial issues (e.g., transportation, child care)
• Systemic factors: lack of appropriate treatment services for pregnant women, negative attitudes of health
care providers

The second phase focuses on relapse prevention by
encouraging substance abuse treatment and development
of a supportive network. Brief interventions can range
from simple physician advice to motivation counselling
sessions consisting of goal setting, problem solving with
respect to triggers, and information on potential harms.
These interventions are effective in reducing alcohol
use among pregnant women.67,68 Currently, there are no
research data on the effectiveness of similar interventions
for illicit substance use in pregnancy. However, systematic
reviews have shown that outpatient psychotherapy for
cannabis dependence is moderately effective at reducing
substance use in non-pregnant patients.69,70 Therefore,
physician counselling may also be of benefit to pregnant
women. Pharmacological maintenance options are available
for management of nicotine and opioid dependence.
Evidence suggests that enhanced treatment programs for
opioid dependence that combine methadone maintenance
therapy, group psychotherapy, and obstetrical care result
in less overall illicit substance use, improved prenatal care,
and lower rates of obstetrical complications.19,52,71–73 Evaluation
of comorbid conditions should include screening for
depression, anxiety, and other mental health disorders,
domestic violence and abuse, and psychosocial support
system. Most women in substance abuse treatment
programs report a past history of trauma (including physical
and sexual abuse), and approximately 25% have been
diagnosed with posttraumatic stress disorder.74–76 Partner
involvement in prenatal care and addiction treatment
is critical to recovery.56 A partner’s active drug use has
been linked to delayed treatment time for women seeking
care.77,78 Similarly, women with fewer social supports are less
likely to seek and to remain in treatment.79,80 Appropriate
referrals may include counselling to deal with pre-existing
trauma and assistance with other social determinants of
health (e.g., food and housing). The cornerstone of care
of problematic substance use in pregnant women is harm
reduction. Components of this include encouragement
of abstinence or reduction of use, safe use, treatment of
withdrawal, counselling, and/or pharmacotherapy.
Any health care provider who has a clinical suspicion based
on history and/or physical examination that a child is or
may be in need of protection because of abuse or neglect
must make a report to child protection services.81 Health
care professionals should be aware of province-specific
legislation with respect to child welfare and reporting
responsibilities. Clinicians are not required to report until
birth, because unborn babies do not have any legal rights,
but antenatal self-reporting is encouraged to increase
maternal self-determination, dignity, and stability and
the establishment of a treatment plan. However, if other
children present in the home are deemed to be at risk,
earlier referral to child protection is indicated to ensure
the safety of these children. Health care professionals
should advocate on behalf of women involved with
child protection agencies and should encourage a positive
relationship between mothers and workers. A history of
substance dependence is not incompatible with ability to
parent.
Recommendations
4. Health care providers should employ a flexible
approach to the care of women who have substance
use problems, and they should encourage the use of
all available community resources. (II-2B)
5. Women should be counselled about the risks of
periconception, antepartum, and postpartum drug
use. (III-B)

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Table 4. Effects of antenatal substance use

Drug Antenatal complications Neonatal effects Long-term effects
Nicotine • SA • Increased perinatal mortality • Childhood asthma
• PTL, PROM • SIDS • Behavioural problems
• Placenta previa and • ADHD
placental abruption
• IUGR, LBW
Marijuana • Inconsistent effects • • Neurobehavioural effects: decreased • Disturbed nocturnal sleep
self-quieting ability, increased fine tremors • Behaviour problems: inattention,
and startles, increased hand-to-mouth impulsivity and hyperactivity,
activity, sleep pattern changes delinquency and externalizing
problems self-reported depressive and
anxiety symptoms
Heroin • Premature labour • Increased perinatal mortality rate • Increased inattention, hyperactivity
• IUGR, LBW and behavioural problems
• Toxemia • Difficulty in physical, social, and self-
• Antepartum and adjustment and learning processes
postpartum hemorrhage
Methadone • NAS
• Strabismus
Cocaine • Spontaneous abortion • Congenital anomalies: genitourinary • Expressive language delays
• PROM, PTL malformations
• IUGR • Transient increase in central and
• Placental abruption autonomic nervous system symptoms and
signs
• Lower birth weight, length and head
circumference (dose-dependent)
Amphetamines • Maternal hypertension • Congenital anomalies:central nervous • Behavioural problems
• Fetal demise (at any system, cardiovascular, oral clefts, limbs
gestational age) • Neurobehavioural effects: decreased
• IUGR arousal, increased stress and poor quality
of movement (dose-response relationship)
Hallucinogens • Congenital anomalies: cardiovascular,
(MDMA, LSD) MSK defects
ADHD: attention-deficit hyperactivity disorder; IUGR: intrauterine growth restriction; LBW: low birth weight; LSD: lysergic acid diethylamide;
MDMA: 3,4-methylenedioxymethamphetamine; MSK: medullary sponge kidney; PTL: preterm labour; PROM: premature rupture of membranes;
SA: spontaneous abortion; SIDS: sudden infant death syndrome.

nicotine DEPENDENCE
Smoking Cessation Counselling
Smoking cessation interventions are effective in reducing the
number of women smoking during pregnancy regardless of
intensity or provider delivering the intervention.82–87 Lower
rates of preterm delivery and low birth weight infants are
additional benefits of smoking cessation interventions.
A variety of interventions have been studied ranging
from simple advice to cognitive behavioural strategies for
quitting smoking. Women also often received pregnancy-
specific self-help materials and telephone counselling to
support smoking cessation.
These interventions are estimated to be highly cost-effective
with savings of US$3 in health-related costs for every
US$1 spent on smoking cessation for pregnant women.88
However, brief interventions are ineffective in preventing
postpartum relapse to smoking.89
Pharmacotherapy
Controlled trials have failed to demonstrate that nicotine
replacement therapy increases smoking cessation
rates, although it may reduce the number of cigarettes
smoked.90,91 NRT (gum, lozenge, or patch), combined
with cognitive behavioural therapy, results in higher quit
rates during pregnancy than counselling alone.92 The
safety of NRT is unknown since the link between NRT
and congenital anomalies and poor perinatal outcomes is
uncertain.90,92–96 However, women may be offered NRT if
they continue to smoke despite counselling and after an
informed discussion regarding the benefits and risks during
pregnancy.82,83,97,98 Intermittent dosage NRT preparations
such as nicotine gum or nasal spray may be preferable to
the patch, which gives a continuous dose of nicotine. The
lowest effective dose of NRT is advised. If the patch is
used, the patient may consider removing it at night. NRT
should be discontinued if the woman continues to smoke
at the same rate.

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 Substance Use in Pregnancy

Table 5. Management of withdrawal

Substance Management recommendation
Alcohol • Thiamine 100 mg po od × 3 days, folic acid 5 mg po od
• Diazepam 20 mg po q1–2h until minimal symptoms
• Use lorazepam 2–4 mg sl/po q2–4h prn during labour
• Monitor hydration status and electrolyte levels
High-dose benzodiazepines • Start at 2/3–3/4 of diazepam equivalent dose
• Taper by 10% per day
Opioids • Offer symptomatic therapy including gravol for nausea and vomiting, acetaminophen/
NSAIDs for myalgias
• Consider methadone or buprenorphine initiation
• Can use morphine 5–10 mg po q4–6h prn if methadone is not available
NSAIDs: non-steroidal anti-inflammatories

Buproprion and varenicline are effective in non-pregnant
populations. There are limited safety data on the use
of these medications during pregnancy.82,83,97 To date,
bupropion has not been associated with malformations
during pregnancy.83,97,99 Preliminary evidence from a small
study suggests that bupropion is effective for smoking
cessation during pregnancy.100 Further research is needed on
the safety and efficacy of bupropion and varenicline before
they can be recommended for routine use in pregnancy.
Recommendation
6. Smoking cessation counselling should be considered
as a first-line intervention for pregnant smokers. (I-A)
Nicotine replacement therapy and/or pharmacotherapy
can be considered if counselling is not successful. (I-A)
OPIOID DEPENDENCE
Opioid Detoxification
Opioid detoxification is defined as medication-assisted
withdrawal for opioid-dependent patients. There is good
evidence that detoxification in the second and third trimesters
of pregnancy is not linked to increased adverse perinatal
events. Recent studies have failed to show any significant
increased rates of obstetrical complications following opioid
detoxification.91,93,94,101 Regardless, opioid detoxification is
not advisable during pregnancy primarily because of the
high rate of relapse.102–106 Opioid detoxification should be
performed only after the first trimester and with informed
consent based on a discussion of the potential risks and bene-
fits. Methadone maintenance treatment is associated with
longer adherence to treatment and decreased risk of relapse
to opioid use; therefore, the standard of care for pregnant
opioid-dependent women is opiate substitution therapy.
Methadone Maintenance Treatment
Currently, methadone maintenance treatment is the standard
of care for opioid dependence in pregnancy. Methadone is
a full opioid agonist that has an increasing effect with higher
doses. There are numerous benefits of methadone use
during pregnancy, including improved prenatal care,12,107–109
longer gestation,50,110 higher birth weight,111,112 and increased
rates of infants discharged home in the care of their
mothers.4,12,18,49,101,108,113–118 Although infants of methadone-
treated women tend to be smaller (lower birth weight,
length, and head circumference) than drug-free controls,
studies have shown a catch-up of growth by 12 months of
age.118,119 Urgent consultation with an addiction medicine
specialist should be sought to facilitate rapid access to MMT
during pregnancy. Close monitoring of methadone dosing
during pregnancy is recommended, especially during the
third trimester when methadone metabolism and clearance
are increased and dose augmentation is required.120,121
Pregnant women should receive the methadone dose
that is required for their opioid dependence, because
the literature reports inconsistent results regarding the
association between maternal methadone dose and severity
of neonatal withdrawal. Prenatal discussion with the
methadone prescribing physician is recommended to plan
for intrapartum methadone dosing.
Any regular, daily antenatal opioid exposure (e.g., morphine,
codeine, oxycodone, methadone, or buprenorphine) can
produce neonatal withdrawal, also known as neonatal
abstinence syndrome. Estimates show that up to 96%
of infants display withdrawal symptoms, and a smaller
proportion require pharmacotherapy.4,68,116,117,120,121 NAS
is characterized by respiratory, gastrointestinal, central
nervous system, and autonomic symptoms (Table 6). Onset
of withdrawal symptoms is dependent on the opiate’s half-
life; the longer the half-life, the later the onset of withdrawal.
Heroin-exposed infants may demonstrate symptoms within
24 hours of birth. In comparison, methadone-maintained
infants have a delayed presentation at more than 24 hours,
usually within 48 to 72 hours after birth and at up to
4 weeks of age.122 The length of monitoring is based on

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SOGC CLINICAL PRACTICE GUIDELINE
the specific drug exposure. Treated neonatal withdrawal
has not been associated with any long-term complications.
A variety of standards of practice have been documented
in Canadian hospitals with variability by region and
practitioner. Little research is available to validate current
practices. Several scoring scales have been developed
for evaluation of NAS and response to therapy. The
Finnegan scoring tool (also known as the Finnegan
Neonatal Abstinence Scoring System) is the method
most commonly used by Canadian hospitals.123 Non-
pharmacologic therapy is the standard of care for all
opioid-exposed infants.124 For a smaller subset of infants,
pharmacotherapy may be needed to treat severe symptoms.
Opioid agonist medications are the most effective agents
for treatment of NAS.122,125 Options include morphine,
methadone, and diluted tincture of opium (contains small
amount of alcohol). Morphine is the most frequently used
medication.122,123 Phenobarbital may be used as an adjunct
to treat infants who are not well-controlled using an opioid
alone. One half of Canadian hospitals care for substance-
exposed infants in the neonatal care unit or special care
nursery. The other half provide care for asymptomatic
infants with the mother as part of rooming-in. One
retrospective cohort study demonstrated that rooming-
in, under the care of supportive nursing and medical
staff, was associated with decreased rates and length of
morphine treatment, decreased need for admission to an
NICU, decreased mean neonatal length of stay in hospital,
and increased likelihood of discharge in the custody of
the mother.126 Additional large-scale prospective studies
are required to determine the optimal management of
neonatal withdrawal.
Buprenorphine
Buprenorphine represents an alternative opioid replacement
treatment. Buprenorphine is a partial agonist with a ceiling
effect. It has typical opioid effects with less sedation than
methadone and a threshold after which a higher dose has no
further effect, thereby reducing the risk of overdose on this
medication.127 The main rationale for buprenorphine use
for treating opioid dependence during pregnancy is reports
of reduced incidence and severity of NAS128–131; however,
there are limited data regarding the long-term effects of
in utero exposure to buprenorphine.132,133 Buprenorphine
should be prescribed by a physician who has experience with
substitution treatment for opioid dependence. The only
preparation of buprenorphine readily available in Canada
is Suboxone, which is a combination of buprenorphine
and naloxone. There is limited information on the safety
of this medication in pregnancy; therefore, the use of
buprenorphine as a single agent (Subutex) is recommended
376 l APRIL JOGC AVRIL 2011
Table 6. Neonatal abstinence syndrome
System Symptoms and signs
Respiratory Respiratory distress
Central nervous system Increased tone, tremors, seizure
Gastrointestinal Poor feeding, vomiting, regurgitation,
diarrhea
Autonomic Sweating
during pregnancy. The availability of buprenorphine during
pregnancy is limited through Health Canada’s Special
Access Program.
OPIOIDS FOR CHRONIC NON-CANCER PAIN
Pregnant women with a history of chronic pain need to be
managed according to evidence-based recommendations
for chronic non-cancer pain.134,135 The goal of therapy is
to use the lowest effective dose of scheduled controlled-
release opioids.134 Most women who use opioids for chronic
non-cancer pain are not psychologically dependent on these
medications. Risk factors for dependence on prescription
opioids include past history of drug dependence and
psychiatric comorbid conditions such as posttraumatic
stress disorder and eating disorders. Regular opioid use
for pain management during pregnancy is associated
with neonatal withdrawal.136,137 Methadone is the first-line
treatment for chronic non-cancer pain and concurrent
opioid dependence.
Recommendations
7. Methadone maintenance treatment should be standard
of care for opioid-dependent women during pregnancy.
(II-IA) Other slow-release opioid preparations may be
considered if methadone is not available. (II-2B)
8. Opioid detoxification should be reserved for selected
women because of the high risk of relapse to opioids.
(II-2B)
9. Opiate-dependent women should be informed that
neonates exposed to heroin, prescription opioids,
methadone, or buprenorphine during pregnancy are
monitored closely for symptoms and signs of neonatal
withdrawal (neonatal abstinence syndrome). (II-2B)
Hospitals providing obstetric care should develop a
protocol for assessment and management of neonates
exposed to opiates during pregnancy. (III-B)

PERIPARTUM PAIN MANAGEMENT
Women with substance use disorders, especially those
with opioid dependence, face numerous peripartum
pain management challenges, including increased pain
sensitivity, inadequate analgesia, difficult intravenous
access, and anxiety about suffering pain due to their history
of addiction.138–142 Inappropriate pain management is more
likely than provision of opioid analgesics for treatment of
acute pain to lead to a relapse. Women on MMT should
be continued on the same dose of methadone, although
this is ineffective for acute pain management.138,142 Opioids
have been found to be safe and effective even in opioid-
dependent women; however, these women may require
higher doses and more frequent analgesics for pain
relief.138,142,143 Epidural analgesia is an ideal choice for pain
management for opioid-dependent women. Agonist-
antagonist medications (e.g., butorphanol, nalbuphine,
and pentazocine) should not be used in opioid-dependent
individuals because of the risk of precipitating acute
withdrawal. For more complicated cases (e.g., poor venous
access, contraindications to epidural), referral to an
anaesthesiologist should be arranged antenatally to discuss,
in advance, alternatives for pain management.
Recommendation
10. Antenatal planning for intrapartum and postpartum
analgesia may be offered for all women in consultation
with appropriate health care providers. (III-B)
MANAGEMENT OF OPIOID OVERDOSE
Education about prevention of opioid overdose should
also be provided routinely. This includes advising patients
that they could overdose if they suddenly stop or markedly
reduce their opioid medication and then resume their usual
dose. They are also at risk of overdose if they combine
opioids with other sedatives, such as benzodiazepines.
They should be warned never to give or sell their opioid
medication to anyone else, because others may lack
tolerance to opioids. Finally, they should be advised
to contact a physician immediately at the first signs of
overdose (“nodding off,” slurred speech, drowsiness).
Acute opioid overdose during pregnancy can be managed
with respiratory support and the use of naloxone, a short-
acting opioid antagonist, as a last resort after an airway has
been established. The dose of naloxone should be based on
response to treatment and duration of action of ingested
opioid. Naloxone may be required on a continuous basis
until the effects of the opioid have diminished. Care should
be taken to prevent acute withdrawal symptoms, which
Substance Use in Pregnancy
can cause fetal distress.144 On the basis of gestational age
and viability, the fetus should be monitored throughout
treatment. Similarly, during neonatal resuscitation, naloxone
should not be administered to a newborn of an opioid-
dependent mother because of the risk of precipitating
acute withdrawal and seizures.
POSTPARTUM CARE
Substance-using women require additional supports from
health care professionals in the postpartum period. More
frequents visits may be required to deal with their complex
medical and psychosocial needs. Areas to review include
the following:
• Support of breastfeeding, as appropriate (see
paragraph below for more details)
• Follow-up of other medical problems such as liver
disease and sexually transmitted infections
• Discussion of contraceptive needs
• Surveillance and appropriate referral for treatment of
postpartum mood and anxiety disorders
• Assessment of substance use and encouragement to
continue attending drug treatment programs
• Support with child protection services involvement
• Assistance with referrals for ongoing primary care and
social services
BREASTFEEDING
Although there are numerous benefits of breastfeeding,
alcohol and illicit substances that are commonly abused
(e.g., marijuana, cocaine, amphetamines) have been detected
in breast milk.145–148 There have been reports documenting
neonatal effects due to breast milk exposure; therefore, the
decision to breastfeed should be made on an individual basis
after discussing the potential risks and benefits.146,147149,150
Breastfeeding may be delayed after maternal use of any of
these agents and any neonatal exposure to any fumes in
the environment. Women who are regular substance users
should be encouraged to remain abstinent while nursing
and counselled regarding the increased risks for neonatal effects.
All opiates have been documented in breast milk in
small amounts and are unlikely to be of any clinical
significance.106,121,151–157 Specifically, the presentation
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SOGC CLINICAL PRACTICE GUIDELINE
and treatment of neonatal withdrawal is not affected by
exposure to methadone or buprenorphine in breast milk.
Therefore, maternal opiate use is considered compatible
with breastfeeding.
Codeine should be used with caution by women who
are breastfeeding. Neonatal toxicity symptoms and signs
such as drowsiness, apnea, and bradycardia have been
demonstrated in women who have been prescribed codeine
and who have a genetic predisposition to convert codeine
to morphine at a faster rate (i.e., CYP2D6 ultrarapid
metabolizers).158,159 Symptoms and signs worsen after 4 days
of codeine use, and alternate pain management should be
considered after that time.160
Recommendation
11. The risks and benefits of breastfeeding should be
weighed on an individual basis because methadone
maintenance therapy is not a contraindication to
breastfeeding. (II-3B)
CONCLUSION
Problematic substance use in pregnancy is prevalent in
the Canadian population. Perinatal health care providers
can make a significant impact on improving pregnancy
outcomes by providing non-judgemental supportive care
within a harm reduction model to address substance
use issues and social determinants of health. Ongoing
education in this area and development of comprehensive
care models are essential for the optimal care of patients in
these challenging circumstances.
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 Substance Use in Pregnancy

Appendix

Antenatal Psychosocial Addressograph

Health Assessment (ALPHA)

Antenatal psychosocial problems may be associated with unfavorable
postpartum outcomes. The questions on this form are suggested ways
of inquiring about psychosocial health. Issues of high concern to the
woman, her family or the caregiver usually indicate a need for
additional supports or services. When some concerns are identified,
follow-up and/or referral should be considered. Additional
information can be obtained from the ALPHA Guide. *Please consider
the sensitivity of this information before sharing it with other caregivers.

ANTENATAL FACTORS CONCERN COMMENTS / PLAN

FAMILY FACTORS
Social support (CA, WA, PD) Low
How does your partner/family feel about your pregnancy? Some
Who will be helping you when you go home with your baby? High
Recent stressful life events (CA, WA, PD, PI) Low
What life changes have you experienced this year? Some
What changes are you planning during this pregnancy? High
Couple’s relationship (CD, PD, WA, CA) Low
How would you describe your relationship with your partner? Some
What do you think your relationship will be like after the birth?
High

MATERNAL FACTORS
Prenatal care (late onset) (WA) Low
First prenatal visit in third trimester? (check records) Some
High
Prenatal education (refusal or quit) (CA) Low
What are your plans for prenatal classes? Some
High
Feelings toward pregnancy after 20 weeks (CA, WA) Low
How did you feel when you just found out you were pregnant? Some
How do you feel about it now? High
Relationship with parents in childhood (CA) Low
How did you get along with your parents? Some
Did you feel loved by your parents? High
Self esteem (CA, WA) Low
What concerns do you have about becoming/being a mother? Some
High
History of psychiatric/emotional problems (CA, WA, PD) Low
Have you ever had emotional problems? Some
Have you ever seen a psychiatrist or therapist? High
Depression in this pregnancy (PD) Low
How has your mood been during this pregnancy? Some
High

ASSOCIATED POSTPARTUM OUTCOMES

The antenatal factors in the left column have been shown to be associated with the postpartum outcomes listed
below. Bold, Italics indicates good evidence of association. Regular text indicates fair evidence of association.
CA – Child Abuse CD – Couple Dysfunction PI – Physical Illness
PD – Postpartum Depression WA – Woman Abuse

APRIL JOGC AVRIL 2011 l 383

SOGC CLINICAL PRACTICE GUIDELINE

ANTENATAL FACTORS CONCERN COMMENTS / PLAN

SUBSTANCE USE
Alcohol/drug abuse (WA, CA) (1 drink=11/2 oz liquor, 12 oz beer, 5 oz wine)
How many drinks of alcohol do you have per week?
Are there times when you drink more than that? Low
Do you or your partner use recreational drugs? Some
Do you or your partner have a problem with alcohol or drugs? High
Consider CAGE (Cut down, Annoyed, Guilty, Eye opener)

FAMILY VIOLENCE
Woman or partner experienced or witnessed abuse
(physical, emotional, sexual) (CA, WA)
What was your parents’ relationship like? Low
Did your father ever scare or hurt your mother? Some
Did your parents ever scare or hurt you? High
Were you ever sexually abused as a child?

Current or past woman abuse (WA, CA, PD)

How do you and your partner solve arguments?
Do you ever feel frightened by what your partner says or does? Low
Have you ever been hit/pushed/slapped by a partner? Some
Has your partner ever humiliated you or psychologically abused you in High
other ways?
Have you ever been forced to have sex against your will?

Previous child abuse by woman or partner (CA)

Do you/your partner have children not living with you? Low
If so, why? Some
Have you ever had involvement with a child protection agency High
(ie. Children’s Aid Society)?

Child discipline (CA)

Low
How were you disciplined as a child?
Some
How do you think you will discipline your child?
High
How do you deal with your kids at home when they misbehave?

FOLLOW UP PLAN
 Supportive counselling by provider  Homecare  Legal advice
 Additional prenatal appointments  Parenting classes / parents’ support group  Children’s Aid Society
 Additional postpartum appointments  Addiction treatment programs  Other:
 Additional well baby visits  Smoking cessation resources  Other:
 Public Health referral  Social Worker  Other:
 Prenatal education services  Psychologist / Psychiatrist  Other:
 Nutritionist  Psychotherapist / marital / family therapist
 Community resources / mothers’ group  Assaulted women’s helpline / shelter / counseling

COMMENTS:

Date Completed Signature

© ALPHA Group, April, 2005; Department of Family & Community Medicine, University of Toronto
http://dfcm19.med.utoronto.ca/research/alpha
Used with permission.

384 l APRIL JOGC AVRIL 2011

 SOGC TECHNICAL UPDATE

SOGC TECHNICAL UPDATE No. 254, February 2011

Transvaginal Mesh Procedures for

Pelvic Organ Prolapse
Abstract
This technical update has been prepared by the
Objective: To provide an update on transvaginal mesh procedures,
Urogynaecology Committee and approved by the Executive
newly available minimally invasive surgical techniques for pelvic
of the Society of Obstetricians and Gynaecologists of
floor repair.
Canada.
Options: The discussion is limited to minimally invasive transvaginal
PRINCIPAL AUTHOR
mesh procedures.
Jens-Erik Walter, MD, Montreal QC
Evidence: PubMed and Medline were searched for articles published
UROGYNAECOLOGY COMMITTEE in English, using the key words “pelvic organ prolapse,”
transvaginal mesh,” and “minimally invasive surgery.” Results
Danny Lovatsis, MD (Chair), Toronto ON
were restricted to systematic reviews, randomized control trials/
Jens-Erik Walter, MD (Co-Chair), Montreal QC controlled clinical trials, and observational studies. Searches
were updated on a regular basis, and articles were incorporated
William Easton, MD, Scarborough ON
in the guideline to May 2010. Grey (unpublished) literature was
Annette Epp, MD, Saskatoon SK identified through searching the websites of health technology
Scott A. Farrell, MD, Halifax NS assessment and health technology assessment-related agencies,
clinical practice guideline collections, clinical trial registries, and
Lise Girouard, RN, Winnipeg MB national and international medical specialty societies.
Chander K. Gupta, MD, Winnipeg MB Values: The quality of evidence was rated using the criteria described
Marie-Andrée Harvey, MD, Kingston ON in the Report of the Canadian Task Force on the Preventive
Health Care. Recommendations for practice were ranked
Annick Larochelle, MD, St-Lambert QC according to the method described in that report (Table 1).
Magali Robert, MD, Calgary AB Benefits, harms, and costs: Counselling for the surgical treatment of pelvic
Sue Ross, PhD, Calgary AB organ prolapse should consider all benefits, harms, and costs of the
surgical procedure, with particular emphasis on the use of mesh.
Joyce Schachter, MD, Ottawa ON
Recommendations
Jane A. Schulz, MD, Edmonton AB
1. Patients should be counselled that transvaginal mesh procedures
David H.L. Wilkie, MD, Vancouver BC are considered novel techniques for pelvic floor repair that
Disclosure statements have been received from all members demonstrate high rates of anatomical cure in uncontrolled short-
of the committee. term case series. (II-2B)
2. Patients should be informed of the range of success rates until
stronger evidence of superiority is published. (II-2B)
3. Training specific to transvaginal mesh procedures should be
undertaken before procedures are performed. (III-C)
4. Patients should undergo thorough preoperative counselling
regarding (a) the potential serious adverse sequelae of
J Obstet Gynaecol Can 2011;33(2):168-174 transvaginal mesh repairs, including mesh exposure, pain,
and dyspareunia; and (b) the limited data available comparing
transvaginal mesh systems with traditional vaginal prolapse
repairs or with traditional use of graft material in the form of
Key Words: Pelvic organ prolapse, transvaginal mesh, augmented colporrhaphy and sacral colpopexy. (III-C)
minimally invasive surgery 5. Until appropriate supportive data are available, new trocarless
kits should be considered investigative. (III-C)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

168 l FEBRUARY JOGC FÉVRIER 2011


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.36
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.36
INTRODUCTION
T he prevalence of pelvic organ prolapse increases with
age and is approximately 31% across all age groups.1
The likelihood of requiring surgical repair by age 80 is
approximately 11%,2 and 29% to 40% undergo reoperation
within 3 years following traditional surgery.2,3 Traditional
non-augmented vaginal techniques include, but are not
limited to, anterior and posterior colporrhaphy, McCall
culdoplasty, and sacrospinous and uterosacral ligament
apical vault suspensions. Persistently high failure rates
have led to graft use,4 but non-standardized techniques
have resulted in varied outcomes and complication rates.5
Graft use for pelvic floor surgery is commonly accepted,
mainly in the form of sacral colpopexy and tension-free
vaginal tape, both of which demonstrate longevity of
successful repair.6,7 However, sacral colpopexy can carry
significant morbidity that may be increased if performed
by laparotomy.6 Its laparoscopic counterpart may provide
comparable success rates and expedite convalescence.8
This technical update does not focus on the specific issue
of graft use, because its use in sacral colpopexy is already
accepted in general practice and because grafts may be
of various types: synthetic (polypropylene), xenografts
(porcine dermis or porcine small intestinal submucosa), or
allografts (cadaveric). This update focuses on the rapidly
expanding area of transvaginal mesh (TVM) systems that
employ graft material, usually polypropylene mesh, placed
vaginally, using trocars.
Transvaginal Mesh Procedures for Pelvic Organ Prolapse
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
The novel TVM procedures have been part of a surgical
evolution attempting to maintain durability of repair,
minimize morbidity and invasiveness, allow regional
anaesthesia, and address appropriate anatomical defects of
pelvic floor dysfunction.9 They are intended to be minimally
invasive surgical techniques for pelvic organ prolapse
repair that facilitate a tension-free placement of a broad
coverage polypropylene implant without trimming of the
vagina or suturing of the mesh to the vagina. The involved
“systems” allow selective application of anterior, posterior,
or total vaginal implants, and the need for hysterectomy is
potentially eliminated. The mesh implants have arms that
are delivered with trocars through anatomical landmarks
via the obturator membrane or the ischiorectal fossa. The
currently available commercial kits are listed in Table 2.
Early literature with short-term follow-up has shown
the TVM systems to be relatively effective, but there is
limited long-term follow-up to demonstrate their potential
longevity or safety profile.9-17 The issues of mesh erosion,
dyspareunia, pelvic pain, mesh shrinkage, and de novo
stress incontinence have been introduced in early studies.
Modifications of the TVM procedure were carried out
(elimination of hysterectomy and creating only longitudinal
incisions) upon review of initial case series in attempts to
reduce rates of vaginal mesh exposure.15
Even newer technology has allowed the development of
single-incision trocarless TVM systems. These include the
FEBRUARY JOGC FÉVRIER 2011 l 169
SOGC TECHNICAL UPDATE
Elevate system from AMS and the Pinnaclesystem from
Boston Scientific (both approved by the FDA). Their intent
is to lower rates of nerve and vascular injury associated
with trocar placement, expedite operating time, and
potentially reduce rates of pelvic pain and dyspareunia. As
no literature yet exists on their risks and effectiveness, they
are not discussed in this update.
TVM PROCEDURE
The TVM procedure addresses midline, paravaginal,
and apical defects through placement of a macroporous
monofilament polypropylene implant. Characteristics of
the available TVM systems are listed in Table 3. Typically
hydrodissection guides creation of a full-thickness
longitudinal vaginal incision through which the paravesical
and/or pararectal spaces are then accessed. Arms of
the mesh implant are delivered through the obturator
membrane and/or ischiorectal fossa via trocars. Positioning
of the mesh is performed, and the vaginal epithelium is
closed without trimming. A mid-urethral sling can then be
carried out through a separate incision. There are variations
of this procedural technique.
TVM OUTCOMES
Currently the vast majority of the published studies are
limited to short-term follow-up (typically 3 to 12 months)
through either observational or retrospective studies.11-15,17-25
Initial rates of anatomical cure (typically defined as less
than POP-Q stage II) in all compartments combined range
from 79% to 100%.11-15,17-23,26 These results are comparable
to subjective satisfaction rates from the procedure.
The only published randomized clinical trial in this area
compared the Perigee system from AMS with traditional
anterior colporrhaphy for anterior compartmental
prolapse.27 Seventy-five patients were randomized to
either traditional anterior colporrhaphy (n = 38) or a
Perigee procedure (n = 37). Anatomic failure was defined
as recurrent POP-Q stage II prolapse or greater. Optimal
repair was achieved in 55% of the colporrhaphy group and
87% of the Perigee group (P = 0.005). Rates of dyspareunia
and voiding symptoms were not different. Mesh exposure
rate was 5% in the Perigee group, and all were managed as
outpatients. Number needed to treat analysis was carried
out and determined that 9 anterior colporrhaphy patients
would have recurrent anterior vaginal wall prolapse to
prevent 1 mesh erosion. A summary of outcomes is shown
in Table 4.
170 l FEBRUARY JOGC FÉVRIER 2011
Table 2. Commercial TVM kits available
Company Device Implant material
American Medical Systems Apogee/ Intepro
Inc., Minnetonka, MN Perigee polypropylene
InteXen porcine
dermis
Gynecare/Ethicon, Johnson & Prolift Gynemesh-PS
Johnson, Somerville, NJ polypropylene
CR Bard Inc., Murray Hill, NJ Avaulta- Polypropylene
Plus +Porcine collagen
*Trocarless not included: see Recommendation 5.
TVM COMPLICATIONS
TVM procedures have introduced postoperative
complications that initially received little attention.
These include higher rates of mesh exposure than
previous procedures (4.7%), mesh shrinkage (≤ 17%),
and dyspareunia (≤ 13%).21,22 The TVM procedures have
relatively low rates of intraoperative complication. A
summary of perioperative complications is shown in
Table 5. The following factors may increase the incidence of
mesh exposure: lack of full-thickness dissection, improper
mesh placement, estrogen status, patient nutritional
status, BMI, age, smoking, inadequate hemostasis, and
immunosuppression.12,28,29 Although visceral mesh erosion
is possible, there is little evidence of it to date. Significant
complications should be managed by a subspecialist.
In October 2008, the FDA released a statement regarding
potential serious complications associated with transvaginal
placement of surgical mesh in pelvic floor surgery.30
On February 4, 2010, Health Canada issued important
safety information on surgical mesh for stress urinary
incontinence and pelvic organ prolapse.31 It outlined the
serious potential adverse events associated with transvaginal
meshes placed for pelvic organ prolapse or incontinence,
using minimally invasive procedures information from over
1000 reports from 9 urogynaecologic surgical companies.
These included vaginal mesh exposure, infection, pain,
voiding dysfunction, pelvic floor dysfunction recurrence,
and visceral or vascular perforation. The Health Canada
document31 made recommendations for obtaining
specialized training to carry out these procedures, being
vigilant for adverse events associated with the trocars
and the mesh, obtaining informed consent for surgery by
advising the patient of potentially uncorrectable sequelae
of mesh placement including pelvic pain and dyspareunia,
and reporting complications to appropriate bodies.
Relatively new long-term sequelae of pelvic floor
reconstruction—vaginal scarring and mesh exposure—
were also addressed in this notification. These may reduce
 Transvaginal Mesh Procedures for Pelvic Organ Prolapse

Table 3. Characteristics of TVM systems

Anterior Posterior Retrieval
Device Trocar attachment attachment device Mesh material
Prolift Straight + Proximal & Sacrospinous Y Type I polypropylene;
cannula distal ATFP ligament Anterior/posterior/total
Apogee Straight Ileococcygeus N Type I polypropylene
muscle or porcine dermis
Perigee Helical Proximal & N Type I polypropylene
distal ATFP or porcine dermis
Avaulta- Straight Proximal & Ileococcygeus + Y Type I polypropylene coated
Plus & helical distal ATFP perineal body (InSnare) with porcine collagen;
anterior/posterior
ATFP: arcus tendineus fascia pelvis

Table 4. Outcomes of TVM procedures

Follow-up, Anatomic cure,
Author Design N Device months %

Gauruder-Burmester et al.22 Retrospective 120 AMS 12 93

Fatton et al. 21
Retrospective 110 Prolift 6 95.3
Altman et al.10 Prospective cohort 123 Prolift 2 87 to 91
Abdel-Fattah and Retrospective cohort 289 Prolift/AMS 3 94 to 100
Ramsay14
Shek et al.23 Retrospective 46 Perigee 10 87
Van Raalte et al. 12
Observational 350 Prolift 6 90
Hinoul 19
Observational 48 Prolift 95.2
Lucioni 20
Observational 12 Prolift 10 92
Gabriel et al.11 Case series 73 Avaulta 4 100
Nguyen and Burchette27 RCT vs. AR 75 Perigee 12 87 vs. 55
Retrospective cohort
Murphy18 cf colpocleisis 90 Prolift 24 97.8 vs. 93.3

Elmer et al.26 Prospective cohort 261 Prolift 12 79 to 86

Cosson et al.4 Retrospective 687 Prolift 3 94
Kdous et al. 16
Observational 45 Prolift 24 93
Davila 13
Observational 55 Apogee 3 91
Rane et al.17 Observational 70 Perigee 36 95.7
Moore et al.24 Observational 42 Perigee 12 93
Davila 25
Observational 298 AMS 9 96

patients’ quality of life through debilitating discomfort and
dyspareunia. Several studies have investigated this issue
with conflicting results.12,13,19,27,32-34
DISCUSSION
While numerous short-term observational and
retrospective studies are emerging that demonstrate the
potential effectiveness of the TVM systems, there is a
need to demonstrate their longevity and safety profiles,
particularly in comparison with traditional and established
procedures for pelvic floor repair. Appropriately designed
and adequately powered prospective and randomized
trials with sufficient long-term follow-up comparing
TVM with accepted “gold-standard” procedures such
as sacral colpopexy would allow accurate assessment of
success with appropriate subjective and objective outcome
measures and complication rates. TVM procedures must
be more thoroughly evaluated before it is assumed they
offer benefits over traditional repairs. The ethical issues
associated with the introduction of new surgical devices
are discussed in a commentary by Ross et al.35
The purported intent of the TVM systems is to further
reduce the invasiveness and potential morbidity of the

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SOGC TECHNICAL UPDATE

Table 5. Complications of TVM procedures

Follow-up,
Author Device N months Intraoperative, % Postoperative, % Exposure rate, %
Cosson et al.4 Prolift 687 3 6.7 6.7 6.7

Gauruder-Burmester et al.22 AMS 120 12 – 2.8 hematoma 8 to 11

Fatton et al.21 Prolift 110 3 1 cystotomy 6 4.7
2 hematoma 2.8 granuloma
Altman et al.34 Prolift 248 6 4 viscus injury 14.5 total 2
0.4 EBL >1L (UTI, retention, fever)

Abdel-Fattah and Ramsay14 Prolift 76% 289 3 1.6 cystotomy 5.2 buttock pain 10 vaginal
AMS 24% 1.1 rectal injury 0.07 sepsis 0.06 bladder
0.06 vascular
Van Raalte et al.12 Prolift 350 6 – 6 dyspareunia 1
2 de novo SUI

Davila13 Apogee 55 3 – 4 granulation 11

4 dyspareunia
Rane et al.17 Perigee 70 36 – 1.4 pain 7.1

Moore et al.24 Perigee 42 12 – 11 de novo SUI 7

Davila 25
AMS 298 9 – 1 pain 12

Hinoul19 Prolift 48 – 13 de novo SUI 10.4

15 dyspareunia

Gabriel et al.11 Avaulta 73 4 2.7 EBL > 500 mL – 3.1

1.4 cystotomy
Shek et al.23 Perigee 46 10 – 10.9 mesh arm 6.5
dislodgement

laparoscopic sacral colpopexy by delivering the mesh
vaginally as opposed to using an intraperitoneal approach
and to eliminate the need for general anaesthesia and
concurrent hysterectomy. Comparison of these procedures
with traditional techniques by adequately trained pelvic
floor surgeons is the first step towards elucidating the
effectiveness and appropriateness of the use of these
novel surgical techniques in our common urogynaecologic
practices. The evolution of graft materials with interwoven
absorbable mesh, such as monocryl, addition of barrier
layers, such as bovine collagen, and xenografts, such as
porcine dermis or small intestinal submucosa further
complicates the challenge of determining the best
materials and techniques for pelvic floor surgery. These
graft materials mimic to a certain extent the anatomical
considerations of the transvaginal mesh systems and
warrant further evaluation and comparison with TVM
systems as an alternate minimally invasive novel vaginal
approach to pelvic floor repair.
The more than 1000 reports of mesh complication
referenced in the FDA notification30 raise concerns about
adequacy of training and ability to prevent complications.
Traditionally, advanced pelvic floor reconstructive surgery
(such as laparoscopic sacral colpopexy, pubovaginal
slings, vaginal paravaginal repairs, and to a lesser extent
colpocleisis) has been the domain of the trained pelvic
floor reconstructive surgeon and, less commonly, the
general gynaecologist who feels competent to carry out
these procedures from experience or extra training. The
role of the subspecialist has included mentoring and
training of generalists interested in novel techniques. The
TVM systems assume familiarity with pelvic floor anatomy
and surgical techniques not typically known to most
generalists. Familiarity with these procedures does require
surgical expertise, knowledge of pertinent anatomy, and
experience with the procedure itself. These elements would
facilitate the trained pelvic floor surgeon’s dissemination of
his or her knowledge and skill to the interested generalist.
Adequate training programs would ensure that trainees
could perform competently and safely. Until adequate
effectiveness and safety evidence is available, the use of
new TVM devices for prolapse repair should be considered
experimental and restricted to use in investigative trials.

172 l FEBRUARY JOGC FÉVRIER 2011


Recommendations
1. Patients should be counselled that transvaginal
mesh procedures are considered novel techniques
for pelvic floor repair that demonstrate high rates
of anatomical cure in uncontrolled short-term case
series. (II-2B)
2. Patients should be informed of the range of
success rates until stronger evidence of superiority is
published. (II-2B)
3. Training specific to transvaginal mesh procedures
should be undertaken before procedures are
performed. (III-C)
4. Patients should undergo thorough preoperative
counselling regarding (a) the potential serious adverse
sequelae of transvaginal mesh repairs, including
mesh exposure, pain, and dyspareunia; and (b) the
limited data available comparing transvaginal mesh
systems with traditional vaginal prolapse repairs or
with traditional use of graft material in the form
of augmented colporrhaphy and sacral colpopexy.
(III-C)
5. Until appropriate supportive data are available, new
trocarless kits should be considered investigative. (III-C)
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15. Cosson M, Caquant F, Collinet P, Rosenthal C, Clave H, Debodinance P,
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Sexual dysfunction after trocar-guided transvaginal mesh repair of pelvic
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 257, May 2011

Ultrasonographic Cervical Length

Assessment in Predicting Preterm Birth
in Singleton Pregnancies
This clinical practice guideline has been prepared by the MATERNAL FETAL MEDICINE COMMITTEE
Diagnostic Imaging Committee, reviewed by the Family Robert Gagnon, MD (Chair), Verdun QC
Physicians Advisory Committee and the Maternal Fetal
Medicine Committee, and approved by the Executive and Lynda Hudon, MD (Co-Chair), Montreal QC
Council of the Society of Obstetricians and Gynaecologists Melanie Basso, RN, Vancouver BC
of Canada. Hayley Bos, MD, London ON
PRINCIPAL AUTHORS
Joan M. Crane, MD, St. John’s NL
Kenneth Lim, MD, Vancouver BC
Gregory Davies, MD, Kingston ON
Kimberly Butt, MD, Fredericton NB
Marie-France Delisle, MD, Vancouver BC
Joan M. Crane, MD, St. John’s NL
Savas Menticoglou, MD, Winnipeg MB
DIAGNOSTIC IMAGING COMMITTEE
William Mundle, MD, Windsor ON
Lucie Morin, MD (Chair), Montreal QC
Stephen Bly, PhD, Ottawa ON Annie Ouellet, MD, Sherbrooke QC
Kimberly Butt, MD, Fredericton NB Tracy Pressey, MD, Vancouver BC
Yvonne Cargill, MD, Ottawa ON Christy Pylypjuk, MD, Saskatoon SK
Gregory Davies, MD, Kingston ON Anne Roggensack, MD, Calgary AB
Nanette Denis, RDMS, CRGS, Saskatoon SK Frank Sanderson, MD, Saint John NB
Kenneth Lim, MD, Vancouver BC Disclosure statements have been received from all members of
Annie Ouellet, MD, Sherbrooke QC the committees.
Shia Salem, MD, Toronto ON The literature searches and bibliographic support for this
Vyta Senikas, MD, Ottawa ON guideline were undertaken by Becky Skidmore, Medical
FAMILY PHYSICIANS ADVISORY COMMITTEE Research Analyst, Society of Obstetricians and Gynaecologists
of Canada.
William Ehman, MD (Chair), Nanaimo BC
Anne Biringer, MD, Toronto ON
Andrée Gagnon, MD, Blainville QC
Lisa Graves, MD, Sudbury ON
Jonathan Hey, MD, Saskatoon SK Abstract
Jill Konkin, MD, Edmonton AB
Francine Léger, MD, Montreal QC Objectives: To review (1) the use of ultrasonographic-derived cervical
length measurement in predicting preterm birth and
Cindy Marshall, MD, Lower Sackville NS
(2) interventions associated with a short cervical length.
Outcomes: Reduction in rates of prematurity and/or better
identification of those at risk, as well as possible prevention of
unnecessary interventions.
Key Words: Preterm birth, prediction, ultrasonography, transvaginal, Evidence: Published literature was retrieved through searches of
cervical cerclage PubMed and The Cochrane Library up to December 2009,
using appropriate controlled vocabulary and key words (preterm

These guidelines reflect emerging clinical and scientific advances as of the date issued and are subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of the contents may be
reproduced in any form without prior written permission of SOGC.

486 l MAY JOGC MAI 2011

 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies
labour, ultrasound, cervix, incompetent cervix, transvaginal,
transperineal, cervical length, fibronectin). Results were
restricted to general and systematic reviews, randomized
controlled trials/controlled clinical trials, and observational
studies. There were no date or language restrictions. Grey
(unpublished) literature was identified through searching
the websites of health technology assessment and health
technology assessment-related agencies, clinical practice
guideline collections, clinical trial registries, and national and
international medical specialty societies.
Values: The evidence and this guideline were reviewed by the
Diagnostic Imaging Committee and the Maternal Fetal Medicine
Committee of the Society of Obstetricians and Gynaecologists of
Canada, and the recommendations were made according to the
guidelines developed by The Canadian Task Force on Preventive
Health Care (Table 1).
Benefits, harms, and costs: Preterm birth is a leading cause of
perinatal morbidity and mortality. Use of the ultrasonographic
technique reviewed in this guideline may help identify women
at risk of preterm birth and, in some circumstances, lead to
interventions that may reduce the rate of preterm birth.
Sponsors: The Society of Obstetricians and Gynaecologists of
Canada
Summary Statements
1. Cervical length in the general obstetrical population is relatively
stable over the first 2 trimesters. The natural history of cervical
length change may be useful in identifying women at increased
risk of spontaneous preterm birth. Because there may be
different patterns or a delay in cervical length shortening, repeat
assessment of cervical length may be useful. (II-2)
2. There is no consensus on the optimal timing or frequency of
serial evaluations of cervical length. If repeat measurements are
performed, they should be done at suitable intervals to minimize
the likelihood of observation error. (II-2)
3. Transvaginal sonography can be used to assess the risk of
preterm birth in women with a history of spontaneous preterm
birth and to differentiate those at higher and lower risk of preterm
delivery. The gestational age of a prior preterm birth affects the
cervical length in a future pregnancy. (II–2)
4. Cervical length measurement can be used to identify increased
risk of preterm birth in asymptomatic women at < 24 weeks who
have other risk factors for preterm birth (previous excisional
treatment for cervical dysplasia, uterine anomaly, or prior
multiple dilatation and evacuation procedures beyond 13 weeks’
gestation). However, there is insufficient evidence to recommend
specific management strategies, such as cerclage, in these
women. (II-2)
5. No specific randomized trials have evaluated any interventions
in asymptomatic women at > 24 weeks’ gestation who are at
increased risk of preterm birth (e.g., those who have a history of
prior spontaneous preterm birth, previous excisional treatment
for cervical dysplasia, uterine anomaly, or prior multiple dilatation
and evacuation procedures beyond 13 weeks’ gestation) and
who have a short cervical length. This information may help with
ABBREVIATIONS
LEEP loop electrical excision procedure
TP transperineal
TV transvaginal
empiric management of these women, including reduction of
activity level, work, or travel, relocation, increased surveillance,
and administration of corticosteroids. (III)
6. Transvaginal ultrasound appears to be safe in preterm premature
rupture of membranes, but its clinical predictive value is uncertain
in this context. (II-2)
7. It is unclear whether ultrasonographic cervical length assessment
has significant advantages over clinical examination alone after
elective or emergency cervical cerclage placement, although
some signs, such as funnelling to the stitch, are associated with a
high risk of preterm premature rupture of membranes. There is no
consensus on the frequency or timing of ultrasonographic cervical
length assessment post cerclage. (II-2)
8. It is unclear whether a policy of cervical length surveillance is
equivalent to clinical assessment of the need for elective cerclage
in those at risk of preterm delivery. (I)
9. Ultrasonographic cervical length assessment and fetal fibronectin
appear to be similar in predictive ability, and the combination of
both in a high-risk population may be of value. However, further
research is needed in this area. (II-2)
Recommendations
1. Transabdominal ultrasonography should not be used for cervical
length assessment to predict preterm birth. (II-2D)
2. Transvaginal ultrasonography is the preferred route for cervical
assessment to identify women at increased risk of spontaneous
preterm birth and may be offered to women at increased risk of
preterm birth. (II-2B)
3. Transperineal ultrasonography may be offered to women at
increased risk of preterm birth if transvaginal ultrasonography is
either unacceptable or unavailable. (II-2B)
4. Because of poor positive predictive values and sensitivities and lack
of proven effective interventions, routine transvaginal cervical length
assessment is not recommended in women at low risk. (II-2E)
5. In women presenting with suspected preterm labour, transvaginal
sonographic assessment of cervical length may be used to help
in determining who is at high risk of preterm delivery and may
be helpful in preventing unnecessary intervention. It is unclear
whether this information results in a reduced risk of preterm birth.
(II-2B)
6. In asymptomatic women with a history of spontaneous preterm
birth and an ultrasonographically diagnosed short cervical length
(< 25 mm) prior to 24 weeks of gestation, cervical cerclage should
be considered to reduce the risk of preterm birth. (I-B)
7. In all asymptomatic women who present with membranes at or
protruding past the external cervical os, an emergency cerclage
should be considered to reduce the risk of preterm delivery. (I-B)
J Obstet Gynaecol Can 2011;33(5):486–499
INTRODUCTION
P reterm birth is the leading cause of perinatal morbidity
and mortality.1–5 Despite advances in perinatal care,
the incidence of preterm birth continues to rise, primarily
because of the increased multiple pregnancies resulting
from assisted reproduction.6–9 Tocolytics prolong pregnancy
minimally once preterm labour has begun, and they can
be associated with significant undesirable maternal, fetal,
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Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
* The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.141
† Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.141

and neonatal consequences.10–19 In order to address the demographic factors, but these have not been fully validated
prematurity problem, it is important to identify those at in large scale studies.30–42 Other screening strategies that have
increased risk. been suggested include measuring biochemical markers
such as fetal fibronectin and screening for infections.27,43–46
The following are risk factors for spontaneous preterm
birth: In the 1980s, an objective, ultrasound-based measurement
was developed to identify women at increased risk of preterm
• Reproductive history (previous spontaneous
birth. The risk of preterm birth was inversely correlated to
preterm birth and use of assisted reproductive
the length of the cervix as measured by ultrasound. This
technologies)8,20–22
observation has been confirmed in multiple studies using
• Antepartum bleeding, rupture of membranes,
different techniques; however, the most widely accepted and
cervical/uterine factors (cervical insufficiency, uterine
used technique is transvaginal ultrasound.34,47–57 A number of
anomalies,22 fibroids, and excisional cervical treatment
interventions based on this observation have been studied in
for cervical intraepithelial neoplasia)23–25
randomized trials. A recent meta-analysis58 has looked at its
• Fetal/intrauterine factors (multifetal gestation, fetal
efficacy in preventing preterm birth. Since the publication
anomaly, and polyhydramnios)
of the 2001 SOGC guideline,36 there have been numerous
• Infection (chorioamnionitis, bacteruria, periodontal
studies on imaging, natural history, and use of transvaginal
disease,26 current bacterial vaginosis with a prior
ultrasound in common clinical scenarios, as well as a number
preterm birth27)
of randomized trials looking at interventions for a short
• Demographic factors (low socioeconomic status, single
cervix. This updated guideline provides a comprehensive
marital status, low level of education, First Nations
review of studies of shortened cervical length diagnosed
ethnicity, or maternal age < 18 years or > 35 years)
on transvaginal ultrasound and is broader in scope than the
• Lifestyle issues (cigarette smoking, illicit drug use,
2001 guideline.36
stress, physical abuse28)
• Inadequate prenatal care, low pre-pregnancy weight
and poor weight gain in pregnancy.29 ULTRASONOGRAPHY COMPARED WITH DIGITAL
ASSESSMENT OF CERVICAL LENGTH
However, many women who deliver preterm do not have
any known risk factors.8,22 Digital assessment of the cervix has been commonly
used to diagnose premature labour or to evaluate women
Research has focused on combined risk scoring systems perceived to be at increased risk of preterm labour. Digital
that use multiple serum markers, ultrasound, and maternal assessment of cervical length is subjective, varies between

488 l MAY JOGC MAI 2011

 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies
examiners, and underestimates true anatomic length.
In one study, digital examinations before hysterectomy
underestimated cervical length by approximately 14 mm,
whereas ultrasonography measured length accurately.59
Investigations using transvaginal ultrasound measurement
as the standard confirmed that digital examination
underestimates cervical length.57,60 This underestimation
may result from an inability to assess the cervix length
digitally beyond the vaginal fornices unless there is 2 cm
or more of dilatation and the entire intracervical canal
is examined. The majority of studies have found that
ultrasound assessment of cervical length is superior to
clinical examination for the prediction of preterm birth.61–64
Therefore, ultrasound assessment of cervical length is more
reliable and more clinically predictive of preterm birth than
manual examination of the cervix.
COMPARISON OF TRANSVAGINAL,
TRANSABDOMINAL, AND TRANSPERINEAL
ULTRASONOGRAPHIC CERVICAL
LENGTH ASSESSMENT
Ultrasound assessment of the cervix was initially performed
transabdominally, but specific disadvantages led to a
preference for transvaginal ultrasound assessment. Both
TP and TV cervical assessments have been studied, with
most studies evaluating TV assessment.65,66
The patient’s bladder must be full for transabdominal
ultrasonography to assess the cervix adequately, but
this may spuriously lengthen the cervix by opposing
the anterior and posterior lower uterine segments65 and
concealing cervical shortening or funnelling. In contrast,
TV ultrasound is performed with the bladder empty.66
Transabdominal ultrasound is significantly less likely
than the other 2 methods to provide adequate imaging
and measurements.67 Visualization of the cervix by
transabdominal ultrasonography is hampered significantly
by maternal obesity, shadowing from fetal parts, and the
need for lower frequency transducers.
Recommendations
1. Transabdominal ultrasonography should
not be used for cervical length assessment
to predict preterm birth. (II-2D)
TP ultrasonography has been found to be as accurate as
transabdominal ultrasound for examining the cervix, and
one study found it was more acceptable to women than
TV scanning.55,67 Other studies, however, have found both
TV and TP techniques acceptable to women.55,68–70 TP
assessment is more accurate than digital examination for
predicting preterm birth, and, when adequate images can
be obtained, TP ultrasonography can predict preterm birth
as accurately as TV ultrasonography.56,63 However, most
authors suggest that adequate images can be obtained more
frequently with TV than with TP technique,55,67,71,72 that TV
assessment is easier to obtain and more reproducible, and
that TV correlates better with true cervical length than TP
assessment.69,71,72 Since the TV technique is more studied
and more likely to be obtainable, TP ultrasonography
should be reserved for women at increased risk of preterm
birth for whom vaginal assessment is unavailable or
unacceptably invasive or uncomfortable.
Recommendations
2. Transvaginal ultrasonography is the preferred
route for cervical assessment to identify
women at increased risk of spontaneous
preterm birth and may be offered to women
at increased risk of preterm birth. (II-2B)
3. Transperineal ultrasonography may be offered
to women at increased risk of preterm birth
if transvaginal ultrasonography is either
unacceptable or unavailable. (II-2B)
NORMAL CERVICAL LENGTH
Cervical length is normally distributed and remains
relatively constant in pregnancy until the third trimester.73–75
If there is any statistically significant reduction in length,
it is not clinically significant (< 0.5 mm /week).73–77 Heath
et al.52 found a mean length of 38 mm at 23 weeks. Iams
et al.34 found a mean length of 35 mm at 24 weeks and of
34 mm at 28 weeks. If funnelling is present, measurement
should exclude the funnel and be taken from the funnel tip
to the external os.47
CERVICAL CHANGE IN WOMEN WHO
DELIVER PRETERM
In women who deliver preterm or require cerclage, the rate
of cervical length change may be predictive of preterm
birth. The rate of cervical shortening is faster in women
who deliver preterm than in those who deliver at term;
however, the difference can be quite small.76–80 The range
of cervical length decline in those who go on to preterm
delivery, preterm labour, or pregnancy intervention varies
from 0.5 mm/week to 8 mm/week.76–80 In a cross-sectional,
longitudinal study, Yoshizato et al.81 examined cervical
change in women whose cervix became short (< 25 mm)
in either the early (< 26 weeks) or the late preterm period
(26 to 30 weeks). They found that “rapid CL shortening
occurred between 16–20 and 21–25 weeks in the early
group and between 21–25 and 26–30 weeks in the late
group”81 Intervention in terms of tocolytics or cerclage was
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SOGC CLINICAL PRACTICE GUIDELINE
used in 19 of 20 in the early group, and 10 of 19 in the late
group. More interesting was that the longitudinal cervical
length change (mm/week) in the late group was statistically
the same as in controls between 16 and 25 weeks, and then
accelerated 3-fold in the next observation period. This study
suggests that cervical length may be stable for a period of
time and then undergo a phase of rapid decline prior to
the onset of symptoms.81 Hence, repeat evaluation of the
cervical length may be reasonable to screen for those who
may be at increased risk of late preterm delivery.
Summary Statement
1. Cervical length in the general obstetrical population
is relatively stable over the first 2 trimesters.
The natural history of cervical length change
may be useful in identifying women at increased
risk of spontaneous preterm birth. Because
there may be different patterns or a delay in
cervical length shortening, repeat assessment
of cervical length may be useful. (II-2)
FREQUENCY OF CERVICAL
LENGTH MEASUREMENT
The natural history of cervical shortening in women
who will deliver preterm may be used to determine when
serial measurements should be performed. These studies
may make it possible to time reassessment and perhaps
stratify follow-up according to length of measurement
and the desired target threshold for intervention. Studies
report thresholds for intervention ranging from 15 mm to
25 mm.82–87 Thus depending on the initial cervical length,
the chosen threshold for intervention, and knowledge of
natural history, it is possible to estimate when the next
measurement should be performed. For example, if the
measured cervical length is 36 mm and the threshold for
intervention is 20 mm, then it is reasonable to wait 2 weeks
to reassess cervical length, assuming the greatest velocity of
cervical decline (8 mm/week). Using a mid-range estimate
of cervical decline (5 mm/week), it would be reasonable
to wait at least 3 weeks between ultrasound assessments.
If the initial cervical length is greater than that, the interval
between assessments could be longer.
Minimum Interval of Time Between Cervical
Assessments
Since the published rates of cervical decline in those
destined to deliver preterm are quite small (1 to
8 mm/week)76–80 and fall within the 95% CI of
interobserver and intraobserver variability (intraobserver
repeatability coefficient of approximately ± 6 mm and
the interobserver limits of agreement of approximately
± 10 mm),88 the interval should be at least 1 week, and
490 l MAY JOGC MAI 2011
perhaps even 2, to avoid observation error. The shorter
the interval of time between measurements, the higher
the rate of observation error: either not enough time
has elapsed between assessments to detect change in
the cervical length, or a small observed change is really
observational error. The current evidence and the regional
differences in resources, access, and practice across the
country do not allow the development of a national
consensus surveillance protocol.
Summary Statement
2. There is no consensus on the optimal timing or
frequency of serial evaluations of cervical length.
If repeat measurements are performed, they
should be done at suitable intervals to minimize
the likelihood of observation error. (II-2)
TRANSVAGINAL SONOGRAPHIC
CERVICAL LENGTH ASSESSMENT IN
ASYMPTOMATIC WOMEN AT LOW RISK
Cervical length is inversely related to the risk of preterm
birth in asymptomatic women.34,47–49,52,54,57 The largest
study of this relationship34 noted that when compared
with women who had values above the 75th percentile
of cervical length, those with a shorter cervix at
24 weeks had the following relative risks: approximately
4 if length was < 30 mm (25th percentile), 6 if < 26 mm
(10th percentile), 9 if < 22 mm (5th percentile), and 14 if
< 13 mm (1st percentile). However, the positive predictive
values (6 to 44%) and sensitivities (47%) were poor in
this low-risk population. Davies et al.,89 in a Canadian,
prospective, blinded observational trial of 964 women
(general obstetrical population), found a sensitivity of 57%
and a specificity of 82% for preterm birth, using a 30 mm
cut-off at 24 to 28 weeks. The positive predictive value
for preterm birth (< 35 weeks) was only 4.5%, because
preterm birth was infrequent. The authors concluded
that using TV ultrasonographic cervical length to screen
for preterm birth in a general obstetrical population was
unwarranted. Also, no studies have shown that cervical
cerclage is beneficial in women at low risk who have a short
cervix.87,89,90 Because of the low incidence of preterm birth
in this low-risk population34 routine screening of cervical
length as a predictor of preterm birth in this population is
not recommended.35
Recommendation
4.  Because of poor positive predictive values and
sensitivities and lack of proven effective interventions,
routine transvaginal cervical length assessment is
not recommended in women at low risk. (II-2E)
 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies
TRANSVAGINAL SONOGRAPHIC
CERVICAL LENGTH ASSESSMENT IN
ASYMPTOMATIC WOMEN WITH A
HISTORY OF SPONTANEOUS PRETERM BIRTH
Cervical length is a better predictor of preterm birth in
women at increased risk, such as those with a history of
spontaneous preterm birth, than in asymptomatic women
at low risk.35,49,87,91–95 In studies of women with a history of
preterm birth, using a cervical length cut-off of 25 to 30 mm
to predict preterm birth < 37 weeks of gestation, sensitivity
is 60% to 80%, positive predictive value is 55% to 70%,
and negative predictive value is 89% to 94%. Thus, a long
cervix (at least 25 to 30 mm) is reassuring and can help to
reduce unnecessary and costly interventions, such as activity
restriction, maternal transfer, steroids, and tocolytics.
A study published in 2009 found that the gestational age
at which the prior preterm delivery occurred affects the
frequency and rate of cervical shortening in the current
pregnancy. A prior spontaneous early preterm birth (< 24
weeks) puts women at a higher risk of cervical shortening.
Women in this group also have a higher rate of cervical
decline that begins at an earlier gestational age than women
with a history of a later preterm birth (24 to 32 weeks).96
Summary Statement
3. Transvaginal sonography can be used to assess the
risk of preterm birth in women with a history of
spontaneous preterm birth and to differentiate
those at higher and lower risk of preterm delivery.
The gestational age of a prior preterm birth affects
the cervical length in a future pregnancy. (II–2)
TRANSVAGINAL SONOGRAPHIC
CERVICAL LENGTH ASSESSMENT IN
OTHER ASYMPTOMATIC WOMEN AT HIGH RISK
Transvaginal cervical length assessment has been found to
be effective in predicting preterm birth in asymptomatic
high-risk groups, including those with uterine anomalies,97
excisional cervical treatment for cervical intraepithelial
neoplasia (LEEP and cone biopsy),23,98 and prior multiple
dilatation and evacuation procedures (beyond 13 weeks
of gestation).23,51,92,97–100 There is no evidence that cervical
cerclage placement is beneficial in these women if they are
found to have a short cervix on transvaginal ultrasound.
Summary Statement
4. Cervical length measurement can be used to identify
increased risk of preterm birth in asymptomatic
women at < 24 weeks who have other risk factors
for preterm birth (previous excisional treatment for
cervical dysplasia, uterine anomaly, or prior multiple
dilatation and evacuation procedures beyond 13
weeks’ gestation). However, there is insufficient
evidence to recommend specific management
strategies, such as cerclage, in these women. (II-2)
DIAGNOSIS OF SHORT CERVIX BEYOND
24 WEEKS’ GESTATION IN ASYMPTOMATIC
WOMEN AT HIGH RISK
The finding of a short cervix in asymptomatic women
at increased risk of preterm birth can be divided into 2
categories according to when the diagnosis is made: < 24
weeks of gestation and ≥ 24 weeks of gestation. No
randomized trials have evaluated specific management
strategies for women at > 24 weeks with a short cervix;
however, having this information may help with empiric
management of these women. This may include altering
activity level, work, and travel, increased surveillance,
relocation close to a tertiary care centre, and administration
of corticosteroids.
Summary Statement
5. No specific randomized trials have evaluated any
interventions in asymptomatic women at > 24 weeks’
gestation who are at increased risk of preterm birth
(e.g., those who have a history of prior spontaneous
preterm birth, previous excisional treatment for
cervical dysplasia, uterine anomaly, or prior multiple
dilatation and evacuation procedures beyond 13 weeks’
gestation) and who have a short cervical length. This
information may help with empiric management of
these women, including reduction of activity level,
work, or travel, relocation, increased surveillance,
and administration of corticosteroids. (III)
ULTRASONOGRAPHIC CERVICAL LENGTH
ASSESSMENT IN CLINICAL MANAGEMENT
Ultrasonographic Cervical Assessment in Women
Suspected of Being in Preterm Labour
The use of cervical length measurement has been studied
in women presenting with suspected preterm labour. The
goal of these studies was to attempt to differentiate between
women who were likely to deliver preterm and those who were
not. This information may help women avoid unnecessary
interventions of limited or unproven value, such as tocolysis,
hospitalization, and activity restriction. Spontaneous preterm
birth is unlikely if the cervical length is ≥ 30 mm.39,101–103
Fuchs et al.104 showed that a cervical length of < 15 mm
in a population presenting with painful contractions (< 32
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SOGC CLINICAL PRACTICE GUIDELINE
weeks) had a 5.5-fold increased risk (44%) of delivery within
a week, and those with a cervical length of ≥ 15 mm had a
2% risk.104 In other studies, delivery occurred within 7 days
of presentation in 37% of 43 women with cervical length
< 15 mm,102 and a cervical length of < 20 mm had a 93.7%
and 87.5% positive predictive value for preterm birth in
primiparous and multiparous women respectively.105 In all
these studies, the cervical length was an independent predictor
of preterm delivery.102–105 In 2010, Sotiriadis et al.106 published
a meta-analysis on the use of cervical length measurements in
patients presenting with symptoms of preterm labour. They
included prospective cohort and/or case–control studies
that evaluated transvaginal ultrasonographic assessment of
cervical length for the prediction of preterm birth in women
with a singleton pregnancy and intact membranes (studies
with < 20% premature rupture of membranes and multiples
were included, however). Studies involving the use of
tocolytics and/or prophylactic steroid administration were
also included. They used a weighted analysis to determine test
performance. The cumulative data suggest that the cervical
length measurement in symptomatic women can be used
to discriminate between those at higher and those at lower
risk of preterm delivery, which may help to rationalize their
management; however, there was considerable heterogeneity
across the studies. Table 2 presents data from the study by
Sotiriadis et al.106
On the basis of the weighted estimates, and using a
pooled prevalence of 11.1% for birth within 1 week of
presentation, Sotiriadis et al.106 calculated that the negative
predictive values of 15 mm, 20 mm, and 25 mm would be
94.8%, 96.3%, and 95.8%, respectively.
Use of Transvaginal Ultrasound to Stratify
Women Presenting With Preterm Labour
In a prospective cohort study among several hospitals using
different protocols for threatened preterm labour, the use
of ultrasound assessment of cervical length appeared to
shorten hospital stay without compromising patient care.107
In a small (N = 41) trial,108 women with threatened preterm
labour were randomized to a control group, who received
tocolytics and steroids in keeping with the hospital’s
protocol, or to an assessment group who had cervical
length measured by transvaginal ultrasound. Women in the
assessment group who were found to have a cervical length
of < 15 mm were given tocolytics and steroids. Those with
cervical length of ≥15 mm were not given tocolytics and
steroids. No babies in the group considered to be at low
risk of preterm birth were born prematurely without a
full course of antenatal corticosteroid therapy, and babies
in this group had significantly lower rates of exposure to
steroids and tocolytics.
492 l MAY JOGC MAI 2011
The results suggest that it may be safe to use ultrasonographic
cervical length assessment to prevent unnecessary use of
tocolytics and steroids.108 However, the small sample size
of this study does not provide adequate power to assess
uncommon outcomes such as preterm birth at < 34 weeks
and to determine whether this approach could cause harm.
A meta-analysis by Berghella et al.58 evaluated the efficacy
of cervical length measurements to prevent preterm birth
by asking whether the knowledge of ultrasonographic
cervical length affected the rate of preterm birth.58 This
was studied in 2 groups: those that presented in preterm
labour and those with preterm rupture of membranes.
Knowledge of TV ultrasonographic cervical length results
was associated with a non-significant decrease in preterm
birth at < 37 weeks (22.3% and 34.7%, respectively;
RR 0.59; 95% CI 0.26 to 1.32). Delivery occurred at a later
gestational age in the knowledge than in the no-knowledge
group (mean difference 0.64 weeks; 95% CI 0.03 to 1.25).
The authors concluded that there was insufficient evidence
to recommend routine screening of asymptomatic
or symptomatic pregnant women with transvaginal
ultrasound. However, it should be noted that the total
number of women in the study was small (total N = 290
in preterm labour, n = 92 in premature preterm rupture of
membranes). Also, the study did not determine whether
progesterone or cerclage was used, and it included clinical
presentations in which neither of those interventions
would likely be used.
In summary, it appears that TV ultrasonography can be
used to stratify risk in women presenting with preterm
labour, and there is some evidence that suggests this can be
done safely and with some benefit.
Recommendation
5. In women presenting with suspected preterm
labour, transvaginal sonographic assessment of
cervical length may be used to help in determining
who is at high risk of preterm delivery and may
be helpful in preventing unnecessary intervention.
It is unclear whether this information results
in a reduced risk of preterm birth. (II-2B)
Ultrasonographic Cervical Assessment in
Women With Suspected Preterm Premature
Rupture of Membranes
Preterm premature rupture of membranes conveys an
increased risk of chorioamnionitis and preterm birth.27,28
In such circumstances, uterine contractions causing
cervical change are difficult to assess because the digital
cervical examination is associated with an increased risk
 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies

Table 2. Meta-analysis of the use of cervical length measurements (Sotiriadis et al.106)

Performance based on a 15 mm threshold
Outcome Studies n Prevalence Sens Spec LR+ LR− PPV NPV
< 48 hours 3 1266 7.1 71.1 86.6 5.92 0.35 28.8* 97.5*
< 7 days 6 1781 11.1 59.9 90.5 5.71 0.51 44.03* 94.7*
< 34 wks 4 429 18.18 46.2 93.7 4.31 0.63 62.2* 88.7*
Performance based on a 20 mm threshold
Outcome Studies n Prevalence Sens Spec LR+ LR− PPV NPV
< 7 days 4 1263 9.3 75.4 79.6 3.74 0.33 27.6* 96.9*
< 34 wks 2 385 20.5 49.4 93.1 n/a n/a 65* 88.5*
Performance based on a 25 mm threshold
Outcome Studies n Prevalence Sens Spec LR+ LR− PPV NPV
< 7 days 4 856 9.7 78.3 70.8 2.81 0.36 22.3* 96.8*
< 34 wks 5 735 11.40 64.3 68.4 n/a n/a 20.8* 93.7*
* Extrapolations based on unweighted data presented for each horizontal category
Sens: sensitivity; Spec: specificity; LR: likelihood ratio; PPV: positive predictive value; NPV: negative predictive value.

of infection and should be postponed until labour is
established. Several cohort studies have shown that the
cervical length measured by TV predicts latency to delivery
in preterm premature rupture of membranes.109,110 In
a much smaller study, cervical length measurements by
TP ultrasound did not correlate with latency duration to
delivery.111 Transvaginal cervical length measurement in
a randomized trial was not found to increase the risk of
infection in patients with preterm premature rupture of
membranes. This study did not find that cervical length had
predictive value for latency. This is not consistent with the
findings of another study.112
Summary Statement
6. Transvaginal ultrasound appears to be safe in preterm
premature rupture of membranes, but its clinical
predictive value is uncertain in this context. (II-2)
The Use of Progesterone in Women With a Short
Cervical Length by Ultrasonographic Assessment
Recent studies have evaluated the use of progesterone in
patients with a short cervix to prevent preterm delivery.
In a study by Fonseca et al.,83 250 women (24 to 34 weeks’
gestation) who were determined to have a cervical length of
< 15 mm were randomized to either vaginal progesterone
(200 mg each night) or placebo. The primary outcome was
spontaneous delivery before 34 weeks. Delivery before 34
weeks of gestation was less frequent in the progesterone
group than in the placebo group (19.2% vs. 34.4%; RR 0.56;
95% CI 0.36 to 0.86). However, there was no statistically
significant reduction in neonatal morbidity (8.1% vs.
13.8%; RR 0.59; 95% CI 0.26 to 1.25; P = 0.17). There
were no serious adverse events associated with the use of
progesterone.83 In a secondary analysis of a randomized,
double-blind, placebo-controlled trial of progesterone to
prevent preterm birth in patients with a history of preterm
birth,113 the use of progesterone when cervical length was
< 28 mm was associated with a reduction in preterm birth
prior to 32 weeks (0% vs. 29.6%, P = 0.014), fewer NICU
admissions (15.8% vs. 51.9%, P = 0.016), and shorter NICU
stays (1.1 vs. 16.5 days, P = 0.013). A recent randomized trial
compared cerclage and 17 α-hydroxyprogesterone for short
cervix (< 25 mm) in a high-risk population and showed no
difference in rates of preterm birth; however, this study
was small (N = 79) and underpowered, because recruitment
was halted at the midpoint of the study. In a sub-analysis
of that data set, it was shown that cerclage may be better if
the cervix is < 15 mm.114 In 2009, the  United States Food
and Drug Administration declined approval of this use of
progesterone, because of concerns about possible adverse
effects, but in February 2011, intramuscular progesterone was
approved for the prevention of preterm birth.115 Although
progesterone supplementation in women  with a previous
preterm birth  and a  short cervix appears promising,  more
data are needed to better demonstrate benefit and a number
of studies are in progress.116 A committee consensus could
not be reached to recommend its use in this population.
Ultrasonographic Cervical Length Assessment
and Cervical Cerclage
Several studies have evaluated the value of cervical cerclage
in women with ultrasonographically diagnosed short cervix.
A prospective cohort study was the first to show benefits
in those who had a cerclage versus those who had usual
care, with significantly lower rates of prematurity and
no fetal losses.84 Subsequently, 3 randomized trials had
disparate findings, although their patient populations were
different.87,90,117 A meta-analysis of patient level data of

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those 3 studies showed that in women with a history of
spontaneous preterm birth and a cervical length < 25 mm
before 24 weeks’ gestation, placement of a cervical cerclage
was associated with a significant decrease in preterm birth
< 35 weeks of gestation (from 39% to 23%).86 A recent
National Institutes of Health-sponsored multicentre trial
confirmed these findings, noting a significant reduction
in preterm birth < 35 weeks and/or previable delivery in
women with a prior spontaneous preterm birth and mid-
trimester transvaginal cervical length < 25 mm, with findings
most pronounced when cervical length was < 15mm.118
In patients with membrane prolapse at or beyond the
external os of the cervix, there may be benefit to emergency
cerclage compared with conservative management. Several
retrospective studies119–122 suggest that pregnancy outcomes
are better with emergency cerclage, and a small randomized
trial82 also showed significant prolongation of pregnancy
and reduced preterm delivery rates.
Recommendations
6. In asymptomatic women with a history of
spontaneous preterm birth and an ultrasonographi-
cally diagnosed short cervical length (< 25 mm) prior
to 24 weeks of gestation, cervical cerclage should be
considered to reduce the risk of preterm birth. (I-B)
7. In all asymptomatic women who present with
membranes at or protruding past the external
cervical os, an emergency cerclage should be con-
sidered to reduce the risk of preterm delivery. (I-B)
Ultrasonographic Cervical Length Assessment
After Cervical Cerclage Placement
There is limited information on the use of ultrasonographic
cervical length assessment after cervical cerclage placement.
Studies involve a combination of both elective and
emergency cerclage, which can confuse the results. It is
unclear whether ultrasound assessment is superior to clinical
examination in determining the need for cerclage.123 Cervical
length significantly increases post cerclage,124–126 but the
overall length post cerclage does not seem to predict preterm
birth.124,126 There is some evidence that absent or short
cervical length above the cerclage123,125 or the appearance of
funnelling to the level of the cerclage123,126 (at 24 to 28 weeks)
increases the risk of preterm delivery. In particular, 2 studies
have shown that funnelling down to the cerclage has a 50%
risk of preterm premature rupture of membranes.123,126
Progressive shortening may also indicate an increased risk
of preterm birth, but the difference between women who
deliver preterm and those who deliver at term, is slight.123–126
There is considerable disagreement about when to initiate,
how frequently to reassess, and when to stop performing
transvaginal cervical length assessments after cerclage, and its
494 l MAY JOGC MAI 2011
value is therefore in doubt.123,124 O’Brien et al.126 empirically
suggest every 2 to 4 weeks post cerclage placement until
28 weeks of gestation, whereas other authors suggest that
cervical length shortening after 28 weeks is most diagnostic
of preterm delivery.123,124 Although the assessment of the
cervix may help identify those at increased risk of preterm
birth, it cannot predict when it will occur.
Summary Statement
7. It is unclear whether ultrasonographic cervical
length assessment has significant advantages
over clinical examination alone after elective or
emergency cervical cerclage placement, although
some signs, such as funnelling to the stitch, are
associated with a high risk of preterm premature
rupture of membranes. There is no consensus
on the frequency or timing of ultrasonographic
cervical length assessment post cerclage. (II-2)
Serial Ultrasonographic Cervical Length
Assessment Compared With Clinical Assessment
of Need for Elective Cerclage Placement
Several authors have noted that if a policy of surveillance
is used in women at high risk, with urgent or emergency
cerclage for those who develop a short cervix, approximately
60% of those patients would not have required cerclage. In
small studies, this approach of using cervical cerclage in
only women with a short cervix had perinatal outcomes
equivalent to those in women who had elective cerclage.117,127
The CIRCLE trial128 was a randomized trial of either serial
TV ultrasound measurements with cerclage when cervical
length was < 20 mm or clinician-based assessment of
need for elective cerclage. Its findings, published in 2009,
were not consistent with those of earlier studies: the TV
ultrasound group was found to have significantly more
interventions, including cerclage, hospitalization, and
progesterone use with no difference in outcomes.128
Summary Statement
8. It is unclear whether a policy of cervical length surveillance
is equivalent to clinical assessment of the need for
elective cerclage in those at risk of preterm delivery. (I)
ULTRASONOGRAPHIC CERVICAL LENGTH
COMBINED WITH FETAL FIBRONECTIN IN THE
PREDICTION OF PRETERM BIRTH
Multiple studies have considered association between
ultrasonographic assessment of cervical length and
the presence of fetal fibronectin. It appears they are
independently associated with an increased risk of preterm
birth although there is some overlap.42,50,129–132 Direct
comparison of these tests can be difficult. Depending
 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies
on the threshold of cervical length or fetal fibronectin
concentration used, the sensitivities and specificities will
vary. The definitions of preterm birth and/or the outcome
of interest (delivery within a certain interval of time) differ
from study to study. These tests have a low sensitivity in a
low-risk population and should be used in women at high
risk rather than for general screening.133 Study findings vary,
so it is unclear whether one is more predictive than the
other.129,134,135 The combination of both (sequentially or
in tandem) may be more effective than using one alone,
but again conflicting results have been found.31,50,129,133–137
Whether these screening strategies result in reduced
interventions and use of resources remains uncertain.138–140
Summary Statement
9. Ultrasonographic cervical length assessment
and fetal fibronectin appear to be similar in
predictive ability, and the combination of both in
a high-risk population may be of value. However,
further research is needed in this area. (II-2)
CONCLUSION
Ultrasonographic cervical measurement is a safe and
effective technique to predict increased risk of preterm
delivery in selected women. The transvaginal route appears
to be the most well studied and is acceptable to women;
however, the transperineal route can also be used if the
patient declines the transvaginal route. It can also be used
to prevent unnecessary interventions in women at increased
risk of preterm delivery if the result is reassuring. In
contrast, routine prenatal transvaginal ultrasound screening
of cervical length in low-risk populations is not supported
by available evidence. Evidence from randomized trials
supports the recommendation of cerclage in patients with
a prior preterm birth and a short cervix. The thresholds
proposed vary from 15 mm to 28 mm. The use of
progesterone in patients with a short cervix appears
promising, but consensus recommendation awaits further
evidence and/or analysis. Further evidence is also needed
with respect to the utility of measuring fetal fibronectin in
conjunction with measurements of cervical length.
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102. Tsoi E, Akmal S, Rane S, Otigbah C, Nicolaides KH. Ultrasound
assessment of cervical length in threatened preterm labor. Ultrasound
Obstet Gynecol 2003;21:552–5.
103. Tsoi E, Fuchs IB, Rane S, Geerts L, Nicolaides KH. Sonographic
measurement of cervical length in threatened preterm labor in singleton
pregnancies with intact membranes. Ultrasound Obstet Gynecol
2005;25:353–6.
104. Fuchs IB, Henrich W, Osthues K, Dudenhausen JW. Sonographic cervical
length in singleton pregnancies with intact membranes presenting with
threatened preterm labor. Ultrasound Obstet Gynecol 2004;24:554–7.
105. Daskalakis G, Thomakos N, Hatziioannou L, Mesogitis S, Papantoniou N,
Antsaklis A. Cervical assessment in women with threatened preterm labor.
J Matern Fetal Neonatal Med 2005;17:309–12.
106. Sotiriadis A, Papatheodorou S, Kavvadias A, Makrydimas G. Transvaginal
cervical length measurement for prediction of preterm birth in women
with threatened preterm labor: a meta-analysis. Ultrasound Obstet
Gynecol 2010;35:54–64.
107. Sanin-Blair J, Palacio M, Delgado J, Figueras F, Coll O, Cabero L, et al.
Impact of ultrasound cervical length assessment on duration of hospital
stay in the clinical management of threatened preterm labor. Ultrasound
Obstet Gynecol 2004;24:756–60.
108. Alfirevic Z, len-Coward H, Molina F, Vinuesa CP, Nicolaides K. Targeted
therapy for threatened preterm labor based on sonographic measurement
of the cervical length: a randomized controlled trial. Ultrasound Obstet
Gynecol 2007;29:47–50.
109. Rizzo G, Capponi A, Angelini E, Vlachopoulou A, Grassi C, Romanini
C. The value of transvaginal ultrasonographic examination of the uterine
cervix in predicting preterm delivery in patients with preterm premature
rupture of membranes. Ultrasound Obstet Gynecol 1998;11:23–9.
110. Tsoi E, Fuchs I, Henrich W, Dudenhausen JW, Nicolaides KH.
Sonographic measurement of cervical length in preterm prelabor
amniorrhexis. Ultrasound Obstet Gynecol 2004;24:550–3.
111. Fischer RL, Austin JD. Cervical length measurement by translabial
sonography in women with preterm premature rupture of membranes: can
it be used to predict the latency period or peripartum maternal infection?
J Matern Fetal Neonatal Med 2008;21:105–9.
112. Carlan SJ, Richmond LB, O’Brien WF. Randomized trial of endovaginal
ultrasound in preterm premature rupture of membranes. Obstet Gynecol
1997;89:458–61.
113. Defranco EA, O’Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, et al.
Vaginal progesterone is associated with a decrease in risk for early preterm
birth and improved neonatal outcome in women with a short cervix:
a secondary analysis from a randomized, double-blind, placebo-controlled
trial. Ultrasound Obstet Gynecol 2007;30:697–705.
114. Keeler SM, Kiefer D, Rochon M, Quinones JN, Novetsky AP, Rust O.
A randomized trial of cerclage vs. 17 alpha-hydroxyprogesterone caproate
for treatment of short cervix. J Perinat Med 2009;37:473–9.
115. FDA approves drug to reduce risk of preterm birth in at-risk pregnant
women [press release]. United States Food and Drug Administration;
February 4, 2011.
116. Lee HJ, Park TC, Norwitz ER. Management of pregnancies with cervical
shortening: a very short cervix is a very big problem. Rev Obstet Gynecol
2009;2:107–15.
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117. Althuisius SM, Dekker GA, Hummel P, Bekedam DJ, van Geijn HP. Final
results of the Cervical Incompetence Prevention Randomized Cerclage
Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.
Am J Obstet Gynecol 2001;185:1106–12.
118. Owen J, Hankins G, Iams JD, Berghella V, Sheffield JS, Perez-Delboy A,
et al. Multicenter randomized trial of cerclage for preterm birth prevention
in high-risk women with shortened midtrimester cervical length. Am J
Obstet Gynecol 2009;201:375–8.
119. Stupin JH, David M, Siedentopf JP, Dudenhausen JW. Emergency cerclage
versus bed rest for amniotic sac prolapse before 27 gestational weeks.
A retrospective, comparative study of 161 women. Eur J Obstet Gynecol
Reprod Biol 2008;139:32–7.
120. Wong GP, Farquharson DF, Dansereau J. Emergency cervical cerclage:
a retrospective review of 51 cases. Am J Perinatol 1993;10:341–47.
121. Daskalakis G, Papantoniou N, Mesogitis S, Antsaklis A. Management
of cervical insufficiency and bulging fetal membranes. Obstet Gynecol
2006;107:221–6.
122. Olatunbosun OA, al-Nuaim L, Turnell RW. Emergency cerclage compared
with bed rest for advanced cervical dilatation in pregnancy. Int Surg
1995;80:170–4.
123. Hedriana HL, Lanouette JM, Haesslein HC, McLean LK. Is there value for
serial ultrasonographic assessment of cervical lengths after a cerclage? Am
J Obstet Gynecol 2008;198:705–6.
124. Dijkstra K, Funai EF, O’Neill L, Rebarber A, Paidas MJ, Young BK.
Change in cervical length after cerclage as a predictor of preterm delivery.
Obstet Gynecol 2000;96:346–50.
125. Groom KM, Shennan AH, Bennett PR. Ultrasound-indicated cervical
cerclage: outcome depends on preoperative cervical length and presence
of visible membranes at time of cerclage. Am J Obstet Gynecol
2002;187:445–9.
126. O’Brien JM, Hill AL, Barton JR. Funneling to the stitch: an informative
ultrasonographic finding after cervical cerclage. Ultrasound Obstet
Gynecol 2002;20:252–5.
127. Groom KM, Bennett PR, Golara M, Thalon A, Shennan AH. Elective
cervical cerclage versus serial ultrasound surveillance of cervical length
in a population at high risk for preterm delivery. Eur J Obstet Gynecol
Reprod Biol 2004;112:158–61.
128. Simcox R, Seed PT, Bennett P, Teoh TG, Poston L, Shennan AH.
A randomized controlled trial of cervical scanning vs history to determine
cerclage in women at high risk of preterm birth (CIRCLE trial). Am J
Obstet Gynecol 2009;200:623.e1–6.
129. Heath VC, Daskalakis G, Zagaliki A, Carvalho M, Nicolaides KH.
Cervicovaginal fibronectin and cervical length at 23 weeks of gestation:
relative risk of early preterm delivery. BJOG 2000;107:1276–81.
130. Iams JD, Goldenberg RL, Mercer BM, Moawad A, Thom E, Meis PJ,
et al. The Preterm Prediction Study: recurrence risk of spontaneous
preterm birth. National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. Am J Obstet
Gynecol 1998;178:1035–40.
131. Goldenberg RL, Iams JD, Mercer BM, Meis P, Moawad A, Das A,
et al. What we have learned about the predictors of preterm birth. Semin
Perinatol 2003;27:185–93.
132. Hincz P, Wilczynski J, Kozarzewski M, Szaflik K. Two-step test: the
combined use of fetal fibronectin and sonographic examination of the
uterine cervix for prediction of preterm delivery in symptomatic patients.
Acta Obstet Gynecol Scand 2002;81:58–63.
133. Iams JD, Goldenberg RL, Mercer BM, Moawad AH, Meis PJ, Das
AF, et al. The preterm prediction study: can low-risk women destined
for spontaneous preterm birth be identified? Am J Obstet Gynecol
2001;184:652–5.
 Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies
134. Rizzo G, Capponi A, Arduini D, Lorido C, Romanini C. The value of
fetal fibronectin in cervical and vaginal secretions and of ultrasonographic
examination of the uterine cervix in predicting premature delivery for
patients with preterm labor and intact membranes. Am J Obstet Gynecol
1996;175:1146–51.
135. Rozenberg P, Goffinet F, Malagrida L, Giudicelli Y, Perdu M, Houssin
I, et al. Evaluating the risk of preterm delivery: a comparison of fetal
fibronectin and transvaginal ultrasonographic measurement of cervical
length. Am J Obstet Gynecol 1997;176:196–9.
136. Schmitz T, Maillard F, Bessard-Bacquaert S, Kayem G, Fulla Y, Cabrol
D, et al. Selective use of fetal fibronectin detection after cervical length
measurement to predict spontaneous preterm delivery in women with
preterm labor. Am J Obstet Gynecol 2006;194:138–43.
137. Tsoi E, Akmal S, Geerts L, Jeffery B, Nicolaides KH. Sonographic
measurement of cervical length and fetal fibronectin testing in threatened
preterm labor. Ultrasound Obstet Gynecol 2006;27:368–72.
138. Grobman WA, Welshman EE, Calhoun EA. Does fetal fibronectin
use in the diagnosis of preterm labor affect physician behavior and
health care costs? A randomized trial. Am J Obstet Gynecol
2004;191:235–40.
139. Mozurkewich EL, Naglie G, Krahn MD, Hayashi RH. Predicting
preterm birth: a cost-effectiveness analysis. Am J Obstet Gynecol
2000;182:1589–98.
140. Ness A, Visintine J, Ricci E, Berghella V. Does knowledge of cervical
length and fetal fibronectin affect management of women with
threatened preterm labor? A randomized trial. Am J Obstet Gynecol
2007;197:426–7.
141. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
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 SOGC CLINICAL PRACTICE GUIDELINE

No. 260, June 2011

Ultrasound in Twin Pregnancies

This Clinical Practice Guideline has been prepared by the Jo-Ann Johnson, MD, Calgary AB
Diagnostic Imaging Committee, reviewed by the Genetics
Sylvie Langlois, MD, Vancouver BC
Committee and the Maternal Fetal Medicine Committee, and
approved by the Executive and Council of the Society of Lynn Murphy-Kaulbeck, MD, Moncton NB
Obstetricians and Gynaecologists of Canada. Nanette Okun, MD, Toronto ON
PRINCIPAL AUTHORS Melanie Pastuck, RN, Cochrane AB
Lucie Morin, MD, Outremont QC MATERNAL FETAL MEDICINE COMMITTEE
Kenneth Lim, MD, Vancouver BC Robert Gagnon, MD, Montreal QC
DIAGNOSTIC IMAGING COMMITTEE Lynda Hudon, MD (Co-Chair), Montreal QC
Lucie Morin, MD (Chair), Outremont QC Melanie Basso, RN, Vancouver BC
Kenneth Lim, MD (Co-Chair), Vancouver BC Hayley Bos, MD, London ON
Stephen Bly, MD, Ottawa ON Joan M. Crane, MD, St. John’s NL
Kimberly Butt, MD, Fredericton NB Gregory Davies, MD, Kingston ON
Yvonne M. Cargill, MD, Ottawa ON Marie-France Delisle, MD, Vancouver BC
Gregory Davies, MD, Kingston ON Savas Menticoglou, MD, Winnipeg MB
Nanette Denis, CRGS, Saskatoon SK William Mundle, MD, Windsor ON
Robert Gagnon, MD, Montreal QC Annie Ouellet, MD, Sherbrooke QC
Marja Anne Hietala-Coyle, RN, Halifax NS Tracy Pressey, MD, Vancouver BC
Annie Ouellet, MD, Sherbrooke QC Christy Pylypjuk, MD, Saskatoon SK
Shia Salem, MD, Toronto ON Anne Roggensack, MD, Calgary AB
Vyta Senikas, MD, Ottawa ON Frank Sanderson, MD, Saint John NB
SPECIAL CONTRIBUTOR Disclosure statements have been received from all members of
Jon Barrett, MD, Toronto ON the committees.
GENETICS COMMITTEE
R. Douglas Wilson, MD (Chair), Calgary AB
François Audibert, MD, Montreal QC
Abstract
Jo-Ann Brock, MD, Halifax NS
June Carroll, MD, Toronto ON Objective: To review the literature with respect to the use of
diagnostic ultrasound in the management of twin pregnancies.
Lola Cartier, MSc, Montreal QC
To make recommendations for the best use of ultrasound in twin
Alain Gagnon, MD, Vancouver BC pregnancies.
Outcomes: Reduction in perinatal mortality and morbidity and
short- and long-term neonatal morbidity in twin pregnancies.
Optimization of ultrasound use in twin pregnancies.

Key Words: Ultrasound, twins, antenatal, prematurity, cervix,

amniotic fluid
J Obstet Gynaecol Can 2011;33(6):643–656

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

JUNE JOGC JUIN 2011 l 643

SOGC CLINICAL PRACTICE GUIDELINE
Evidence: Published literature was retrieved through searches of
PubMed and the Cochrane Library in 2008 and 2009 using
appropriate controlled vocabulary (e.g., twin, ultrasound, cervix,
prematurity) and key words (e.g., acardiac, twin, reversed
arterial perfusion, twin-to-twin transfusion syndrome, amniotic
fluid). Results were restricted to systematic reviews, randomized
control trials/controlled clinical trials, and observational studies.
There were no date restrictions. Studies were restricted to those
with available English or French abstracts or text. Searches were
updated on a regular basis and incorporated into the guideline
to September 2009. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: The evidence collected was reviewed by the Diagnostic
Imaging Committee of the Society of Obstetricians and
Gynaecologists of Canada, with input from members of the
Maternal Fetal Medicine Committee and the Genetics Committee
of the SOGC. The recommendations were made according to the
guidelines developed by The Canadian Task Force on Preventive
Health Care (Table 1).
Benefits, harms, and costs: The benefit expected from this guideline
is facilitation and optimization of the use of ultrasound in twin
pregnancy.
Summary Statements
1. There are insufficient data to make recommendations on repeat
anatomical assessments in twin pregnancies. Therefore, a
complete anatomical survey at each scan may not be needed
following a complete and normal assessment. (III)
2. There are insufficient data to recommend a routine preterm labour
surveillance protocol in terms of frequency, timing, and optimal
cervical length thresholds. (II-2)
3. Singleton growth curves currently provide the best predictors of
adverse outcome in twins and may be used for evaluating growth
abnormalities. (III)
4. It is suggested that growth discordance be defined using either
a difference (20 mm) in absolute measurement in abdominal
circumference or a difference of 20% in ultrasound-derived
estimated fetal weight. (II-2)
5. Although there is insufficient evidence to recommend a specific
schedule for ultrasound assessment of twin gestation, most
experts recommend serial ultrasound assessment every 2 to
3 weeks, starting at 16 weeks of gestation for monochorionic
pregnancies and every 3 to 4 weeks, starting from the anatomy
scan (18 to 22 weeks) for dichorionic pregnancies. (II-1)
6. Umbilical artery Doppler may be useful in the surveillance of twin
gestations when there are complications involving the placental
circulation or fetal hemodynamic physiology. (II-2)
ABBREVIATIONS
AC abdominal circumference
CL cervical length
EFW estimated fetal weight
IUGR intrauterine growth restriction
NPV negative predictive value
NT nuchal translucency
PPV positive predictive value
TTTS twin-to-twin transfusion syndrome
644 l JUNE JOGC JUIN 2011
7. Although many methods of evaluating the level of amniotic fluid in
twins (deepest vertical pocket, single pocket, amniotic fluid index)
have been described, there is not enough evidence to suggest
that one method is more predictive than the others of adverse
pregnancy outcome. (II-3)
8. Referral to an appropriate high-risk pregnancy centre is indicated
when complications unique to twins are suspected on ultrasound.
(II-2) These complications include:
1.  Twin-to-twin transfusion syndrome
2.  Monoamniotic twins gestation
3.  Conjoined twins
4.  Twin reversed arterial perfusion sequence
5.  Single fetal death in the second or third trimester
6.  Growth discordance in monochorionic twins.
Recommendations
1. All patients who are suspected to have a twin pregnancy on first
trimester physical examination or who are at risk (e.g., pregnancies
resulting from assisted reproductive technologies) should have first
trimester ultrasound performed. (II-2A)
2. Every attempt should be made to determine and report amnionicity
and chorionicity when a twin pregnancy is identified. (II-2A)
3. Although the accuracy in confirmation of gestational age at the first
and second trimester is comparable, dating should be done with
first trimester ultrasound. (II-2A)
4. Beyond the first trimester, it is suggested that a combination of
parameters rather than a single parameter should be used to
confirm gestational age. (II-2C)
5. When twin pregnancy is the result of in vitro fertilization, accurate
determination of gestational age should be made from the date of
embryo transfer. (II-1A)
6. There is insufficient evidence to make a recommendation of which
fetus (when discordant for size) to use to date a twin pregnancy.
However, to avoid missing a situation of early intrauterine growth
restriction in one twin, most experts agree that the clinician may
consider dating pregnancy using the larger fetus. (III-C)
7. In twin pregnancies, aneuploidy screening using nuchal
transluscency measurements should be offered. (II-2B)
8. Detailed ultrasound examination to screen for fetal anomalies
should be offered, preferably between 18 and 22 weeks’ gestation,
in all twin pregnancies. (II-2B)
9. When ultrasound is used to screen for preterm birth in a twin
gestation, endovaginal ultrasound measurement of the cervical
length should be performed. (II-2A)
10. Increased fetal surveillance should be considered when there is
either growth restriction diagnosed in one twin or significant growth
discordance. (II-2A)
11. Umbilical artery Doppler should not be routinely offered in
uncomplicated twin pregnancies. (I-E)
12. For defining oligohydramnios and polyhydramnios, the
ultrasonographer should use the deepest vertical pocket in either
sac: oligohydramnios when < 2 cm and polyhydramnios when
> 8 cm. (II-2B)

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
* The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.100
† Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.100
INTRODUCTION
T his document was originally to be written for multiple
pregnancy: twins and higher order multiples. However,
since twins make up > 98% of all multiple pregnancies,
and most published studies in the areas covered by this
document are of twins and not higher order multiples,
this guideline discusses only twins. As twins and higher
order multiples were included in some studies, areas of
this document are applicable to higher order multiples (e.g.,
determination of chorionicity and amnionicity), but others
are applicable only to twin pregnancy.
From the first trimester until delivery of the second fetus,
the use of ultrasound in the management of twins is both
ubiquitous and indispensable. Some of the most common
clinical uses are determination of chorionicity, confirmation
of gestational age, diagnosis of anomalies and complications,
measurement of cervical length, and assessment of growth
and amniotic fluid, placental localization, and fetal position
for intrapartum management.
Ultrasound is the only safe and reliable method for the
diagnosis and assessment of twins, although improved
detection of twins by routine sonographic examination
has not led to a significant reduction in perinatal mortality.
This may be due to lack of standardized protocols for the
management of twins rather than the technology itself.1
In addition, protocols for increased surveillance in twins
have not been investigated in a prospective, randomized
Ultrasound in Twin Pregnancies
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
fashion or stratified according to chorionicity. Established
guidelines for the type and frequency of testing are neither
evidence-based nor uniformly followed. Nevertheless,
despite the lack of level I evidence, virtually all twins are
followed routinely with greater fetal surveillance than low-
risk singleton fetuses.2
SONOGRAPHIC DETERMINATION OF
CHORIONICITY AND AMNIONICITY
Early and accurate determination of amnionicity and
chorionicity is critical in the antenatal management of
twins. Ideally, determination of chorionicity should be
done in the first trimester. The management of structural
anomalies, screening for and identification of aneuploidy,
determination of the etiology of fetal growth and/or fluid
discordance, early diagnosis of twin-to-twin transfusion
syndrome, and the management of a surviving twin
following intrauterine demise are examples of clinical
management depending on chorionicity. The high mortality
and morbidity of monoamniotic twins is well-documented,
and early and intensive monitoring and intervention may
improve outcomes.3–5
Before 10 weeks’ gestation, several sonographic findings
can help determine chorionicity. These are (1) the number
of observable gestational sacs, (2) the number of amniotic
sacs within the chorionic cavity, and (3) the number of yolk
sacs.
JUNE JOGC JUIN 2011 l 645
SOGC CLINICAL PRACTICE GUIDELINE
1. Number of Gestational Sacs
The relationship between the number of gestational sacs
and the number of embryonic heartbeats gives strong
evidence of chorionicity. Each gestational sac forms
its own placenta and chorion. Thus, the presence of
2 gestational sacs implies a dichorionic pregnancy, while a
single gestational sac with 2 identified heartbeats implies a
monochorionic twin pregnancy.6
2. Number of Amniotic Sacs Within the
Chorionic Cavity
When diamniotic twins are identified before 10 weeks’
gestation, separate and distinct amnions may be visible on
ultrasound. The amnion grows outward from the embryonic
disk, and before 10 weeks the separate amnions of a
diamniotic pregnancy will not have enlarged sufficiently to
contact each other and create the inter-twin septum. Each
single amnion is extremely thin and delicate and may be
very difficult to see on transabdominal scanning; however,
endovaginal imaging is often successful in differentiating
separate amnions.
3. Number of Yolk Sacs
The number of yolk sacs may help diagnose the amnionicity.7
When 2 yolk sacs are seen in the extra-embryonal coeloma,
the pregnancy will be diamniotic, while a single yolk sac
will in most cases indicate monoamniotic twins. A single
yolk sac seen when there are dual embryos should prompt
a follow-up first trimester scan to definitively assign
amnionicity.
After 10 weeks, these sonographic signs are no longer
present: gestational sacs are no longer distinctly separable,
and the inter-twin membrane is formed. At this stage, a
new set of sonographic findings will help determine
amnionicity/chorionicity. These findings are (1) fetal
genitalia, (2) placental number, (3) chorionic peak sign, and
(4) membrane characteristics.
The following order provides a logical sequence to
determine chorionicity after 10 weeks of gestation. Of
note, step 1 is not routinely used at the 10- to 14-week scan.
1. Sex Discordance
Phenotypic discordance identifies dichorionicity in all but
the rarest cases. Concordance of phenotype does not rule
out dichorionicity.
2. Number of Distinct Placentas
A single placental mass likely indicates monochorionicity,
whereas the presence of 2 distinct, separate placentas
identifies dichorionicity. Careful sonographic examination
may help distinguish a single placenta from 2 placentas in
abutment.
646 l JUNE JOGC JUIN 2011
3. Presence or Absence of the Chorionic Peak
(also called the twin peak or lambda sign)
This represents a projecting zone of tissue of similar
echotexture to the placenta, triangular in cross-section
and wider at the chorionic surface of the placenta,
extending into, and tapering to a point within, the inter-
twin membrane. The twin peak sign most often identifies
dichorionicity.8,9 Monochorionicity can be determined by
absence of the twin peak sign.
4. Inter-Twin Membrane Characteristics
The membrane of a dichorionic pregnancy consists of
2 layers of amnion and 2 layers of chorion. It is thicker
and more reflective than the monochorionic diamniotic
membrane. A membrane thickness of > 2 mm identifies
dichorionicity with a positive predictive value of 95%
and monochorionicity with a positive predictive value of
90% for a membrane thickness ≤ 2 mm.10 In the second
trimester, the number of membranes may be counted, and
if there are > 2, then dichorionicity is strongly suggested.11
If a membrane is not detected, careful evaluation to
diagnose or exclude the possibility of monochorionic
monoamniotic twinning is warranted. When an inter-
twin membrane is not visualized, possibilities include
monoamniotic twinning, presence of a twin with
complete oligohydramnios (stuck twin), or a diamniotic
twin pregnancy in which the membrane is present but
not seen owing to its thinness and orientation to the
transducer. The most definitive sonographic finding in the
diagnosis of monoamniotic twins is the demonstration
of cord entanglement from the placental or umbilical
origin. Colour Doppler may facilitate identification of
this finding. Entanglement of limbs or observation
of a limb circumscribing the other is suggestive of
monoamnionicity. Failure to find the membrane between
the 2 cord insertions in the placenta strongly supports
monoamnionicity. The use of transvaginal ultrasound is
often a helpful adjunct to transabdominal scanning in
identifying the membrane.
Accuracy is improved when the assessment of chorionicity
is undertaken before 14 weeks’ gestation rather than
after 14 weeks. Stenhouse et al.8 in a study of 131 twin
pregnancies found the sensitivity after 14 weeks was 77%
for monochorionicity (10/13) and 90% for dichorionicity
(26/29); before 14 weeks, accuracy was 99% for both
groups (98/99 overall, 21 of 22 for monochorionics)
combined.
The twin peak sign alone in the second trimester can
accurately identify the chorionicity in many cases, but that
may not be sufficient to guide clinical management in

all cases.9,12 Scardo et al.12 in their second trimester study
found that the twin peak alone may not be sufficiently
accurate. With a composite of second trimester ultrasound
markers (number of placentas, fetal phenotype, membrane
thickness, and twin peak sign), the sensitivity for correct
identification of monochorionic pregnancies is reported
at 91.7% with 97.3% specificity.12 In the second trimester,
the twin peak sign becomes more difficult to visualize,
and it disappears in about 7% of dichorionic pregnancies
at 16 to 20 weeks. Therefore, the absence of the twin
peak sign in the second or third trimester cannot exclude
dichorionicity.12,13
Recommendations
1. All patients who are suspected to have a twin
pregnancy on first trimester physical examination
or who are at risk (e.g., pregnancies resulting from
assisted reproductive technologies) should have first
trimester ultrasound performed. (II-2A)
2. Every attempt should be made to determine and
report amnionicity and chorionicity when a twin
pregnancy is identified. (II-2A)
DETERMINING GESTATIONAL
AGE IN TWIN PREGNANCIES
The accurate confirmation of gestational age using
ultrasound is essential to pregnancy management. It
necessitates determining whether there is a high probability
that the measurements of the fetus are appropriate for the
estimated gestational age. Early studies of the reliability
of ultrasound to confirm gestational age used menstrual
dating in women with regular cycles; however, menstrual
dating is fraught with biological variability. More recently,
studies of this nature were done in IVF pregnancies, for
which conception date is known precisely, but it is unclear
whether this will work as well with natural conceptions.
The literature on gestational age confirmation is also not
specific to multiple pregnancies, and in general these studies
were a mixture of singletons, twins, and triplets, with
the vast majority of subjects being singleton.14–17 Studies
assessing the benefits of confirmation of gestational age
by ultrasound have been published,18 but with singleton not
twin pregnancies. A comprehensive and critical review of
this topic is well beyond the scope of this document.
The first trimester is generally considered to be the ideal time
to confirm or establish accurate gestational age dating, and it
is statistically superior to second trimester dating. However,
in 2 dating studies using twins, the difference in accuracy
compared with IVF could be considered clinically insignificant
Ultrasound in Twin Pregnancies
(underestimate 1 day from IVF dating) with both first (11 to
14 weeks) and second (18 to 22 weeks) trimester ultrasound
estimates being very accurate in relation to conceptual age by
IVF.15,19 Hence, in twins, although there is expert consensus
that first trimester ultrasound dating is preferable, second
trimester dating is also acceptable and accurate.
The best parameter or parameters to use for the most
accurate dating vary according to the gestational age. Many
studies show that singleton dating formulas work equally well
with twins, hence studies in this area are usually a mixture of
singletons and multiples.14–17 In the first trimester, crown–
rump length provides appropriate gestational dating within
5 to 7 days.15–17 First trimester crown–rump length and
second trimester biparietal diameter provide gestational age
with an error of plus or minus 7 days and are very similar in
accuracy.16 In the second trimester, different combinations
of each parameter demonstrate slight differences in
accuracy, with the best estimate using a combination of
head circumference, abdominal circumference, and femur
length.14 Some centres use an average of all parameters,
equally weighted, or use mathematical formulas that give
different significance to each parameter used. There are
more than 30 different formulas in the literature, using
different combinations of parameters.14 In general, about
95% of gestational age estimates in the first and second
trimester will be within 5 to 7 days of the “true” gestational
age, regardless of the parameter or parameters used.14,16,17
In twin pregnancies, modest size discordance is common.
Several studies have cited the need to use the larger twin for
dating purposes to minimize the chance of missing a fetus
that might present with IUGR.16,19 Some studies have based
the estimated gestational age on the mean of the fetuses.14
Salomon et al.20 recently suggested that if the inter-twin
crown–rump length discrepancy was less than the 95th
percentile, according to their charts, the biometry of the
smaller fetus was the more correlative with the conception
date of IVF pregnancies.20 However, the majority of
centres, largely on the basis of expert opinion, use the
larger of the 2 fetuses to date a pregnancy, erring on the
side of overestimation of gestational age and lessening the
chance of missing IUGR in the smaller twin.
Therefore, there is no absolute consensus on the optimal
method to determine gestational age in twin pregnancies.
Most academic centres use the estimated gestational age
based on a known last menstrual period, corrected for a
regular cycle length if the initial ultrasound falls within
an accepted range of days. If the fetal biometry does not
agree, new gestational age estimates can be established with
an anticipated accuracy of 5 to 7 days. Further study in this
area appears to be warranted.
JUNE JOGC JUIN 2011 l 647
SOGC CLINICAL PRACTICE GUIDELINE
Recommendations
3. Although the accuracy in confirmation of
gestational age at the first and second trimester
is comparable, dating should be done with first
trimester ultrasound. (II-2A)
4. Beyond the first trimester, it is suggested that a
combination of parameters rather than a single
parameter should be used to confirm gestational
age. (II-2C)
5. When twin pregnancy is the result of in vitro
fertilization, accurate determination of gestational
age should be made from the date of embryo
transfer. (II-1A)
6. There is insufficient evidence to make
recommendation of which fetus (when discordant
for size) to use to date a twin pregnancy. However,
to avoid missing a situation of early intrauterine
growth restriction in one twin, most experts agree
that the clinician may consider dating pregnancy
using the larger fetus. (III-C)
SCREENING FOR ANOMALIES
IN TWIN PREGNANCIES
Aneuploidy Screening in First Trimester
The literature on aneuploidy screening in twins is relatively
scant, consisting of small studies with < 10 abnormal
fetuses.21–24 Conclusions are inconsistent, and much larger
studies are required to provide definitive answers.
Nuchal transluscency and maternal age in twins
In 1996, Sebire and colleagues22 evaluated NT in 448
twin pregnancies (both dichorionic and monochorionic).
A total of 7.3% of fetuses had an elevated NT above
the 95th percentile. In 88.4% of twin pregnancies, both
fetuses had a normal NT. An elevated NT was seen in
one fetus in 8.7% and in both fetuses in 2.9%. Seven of
8 Down syndrome fetuses were detected with an overall
sensitivity of 88%, which is comparable with the singleton
detection rate. The screen positive rate was higher in
monochorionic twins at 8.4% than in dichorionic twins
at 5.4%.22 In a small study of monochorionic twins,
Vandecruys et al.24 suggested that the best performance
was achieved using the average NT, rather than the larger
or smaller NT measured within a twin pair. Using the
average NT resulted in an estimated 100% sensitivity for
a 4.2% false-positive rate. It would appear that NT in
conjunction with maternal age has the potential to reach
the standard of 75% sensitivity for a 5% screen positive
rate proposed by the SOGC in 200725; however, larger
studies are needed to verify this.
648 l JUNE JOGC JUIN 2011
NT may also be useful in the early detection or prediction
of TTTS. One study suggests that an increased NT in
monochorionic twins may be an early manifestation
of TTTS. An NT threshold at the 95th percentile had a
positive and negative predictive value of 43% and 91%,
respectively.26
Recommendation
7. In twin pregnancies, aneuploidy screening using
nuchal transluscency measurements should be
offered. (II-2B)
Aneuploidy Screening in the Second Trimester
The use of genetic sonograms to detect Down syndrome
in the second trimester has been well studied in singleton
pregnancies. A detailed scan is performed with a number of
soft markers of Down syndrome, and if there are abnormal
findings, a fetus-specific risk is calculated according to
the soft marker detected. In twins, the singleton genetic
sonogram principles are applied to individual fetuses,
and prenatal diagnosis is offered if sufficient risk exists.27
However, there is very little, if any, information to
estimate the efficacy of this approach in twins. Typically,
in mixed population studies, the data in twin pregnancies
are combined with the singleton data, and abstraction of
efficacy specific to twins is impossible.28 In one study, soft
marker discordance was sought for in twin sets discordant
for Down syndrome. Of the markers studied, nuchal
translucency thickness was found to correctly identify
5 of 9 Down syndrome cases, with the other markers
being significantly less efficacious.29 Therefore, although
there may be some utility of second trimester ultrasound
in screening for Down syndrome in twins, its efficacy is
uncertain.
Congenital Malformations
Congenital anomalies are 1.2 to 2 times more common
in twin gestation.30 In dizygotic twins the rate per fetus
is the same as in singletons, whereas in monozygotic
twins the rate is 2 to 3 times higher.31 The most common
structural abnormalities are cardiac anomalies, neural tube
and brain defects, facial clefts, and gastrointestinal and
anterior abdominal wall defects. Apart from structural
defects, which also occur in singletons, there are 3 types of
congenital anomalies unique to twin pregnancies.30
1. Midline structural defects, believed to be a consequence
of the twinning process, exemplified by conjoined
twins.
2. Malformations resulting from vascular events as a
consequence of placental anastomoses, leading to
hypotension and/or ischemia. This can happen to
 Ultrasound in Twin Pregnancies

Table 2. Risk of spontaneous preterm birth (< 32 to 33 weeks) given various CL thresholds
Author Prevalence N CL (mm) GA (weeks) Sensitivity Specitivity % PPV % NPV %
Goldenberg et al. 34
8.8% 147 ≤ 25 24 53.8 85.8 26.9 95.0
Skentou et al.35 7.8% 434 ≤ 25 22 to 24 35.3 91.8 26.7 94.3
Vayssiere et al.36
5.4% 251 ≤ 25 21 to 23 38 97 38 96
Sperling et al.37 6.0% 383 ≤ 20 23 21.4 96.4 27.8 95.4
Guzman et al.38 9.2% 131 ≤ 20 21 to 24 42.0 85 22.0 94

a surviving twin after the demise of the other twin.
Anomalies seen as consequence of such events
include microcephaly, periventricular leukomalacia,
hydrocephalus, intestinal atresia, renal dysplasia, and
limb amputation.
3. Defects or deformities from intrauterine crowding:
foot deformities, hip dislocation, and skull
asymmetry
Edwards et al.32 evaluated the accuracy of antenatal
ultrasound in the detection of fetal anomalies in 245 twins
managed in a specialized multiples clinic. The prevalence of
anomalies was 4.9%. In this study, antepartum ultrasound
detected 88% of anomalies; ultrasound for the detection
of congenital anomalies in twins therefore appears to be
effective.32
Twin pregnancies will be scanned multiple times during
pregnancy, predominantly to assess fetal growth. There
are no data to determine whether formal reassessment of
fetal anatomy at each scan is of significant value in anomaly
detection in twins. Only one study of singleton pregnancies33
found that routine repeat anatomy scanning in the early
third trimester resulted in further diagnosis of anomalies.
In the second trimester, a major anomaly was detected in
0.36% of scanned fetuses, and anatomical reassessment in
the third trimester resulted in further diagnosis in 0.22% of
the fetuses previous assessed as “normal.” The anomalies
detected were predominantly lesions that may develop
late in pregnancy and that would not be detectable in the
mid-second trimester. Given the number of ultrasound
examinations per twin pregnancy and the rising rates of
multiple gestations, the resource implications of a policy
of repeated anatomical evaluation are significant. There
are insufficient data to make a recommendation on how
often repeat anatomical survey should be done in twin
pregnancies.
Ultrasound scanning for fetal anomalies in twins is clearly
justifiable and best performed between 18 and 22 weeks’
gestation. A management plan necessitates knowledge of
chorionicity and consideration of the risk to the unaffected
fetus.
Summary Statement
1. There are insufficient data to make recommendations
on repeat anatomical assessments in twin pregnancies.
Therefore, a complete anatomical survey at each scan
may not be needed following a complete and normal
assessment. (III)
Recommendation
8. Detailed ultrasound examination to screen for
fetal anomalies should be offered, preferably
between 18 and 22 weeks’ gestation, in all twin
pregnancies. (II-2B)
SCREENING FOR PRETERM BIRTH
Preterm birth is a major cause of mortality and morbidity in
twin pregnancies. Sonographic assessment of the cervical
length can identify twins at significantly elevated risk of preterm
delivery. A number of studies have shown that cervical length
can help identify those twins that may be at either increased or
reduced risk of early delivery. Most of these studies include both
monochorionic and dichorionic pregnancies, and differentiation
on that basis is not known. Studies varied with respect to the
cervical length threshold chosen, the gestational age at which the
cervical length assessment was performed, and the definition of
preterm birth. Tables 2 and 3 show information from studies
that were similar with respect to these 3 variables. None of the
studies included patients who had a cerclage, and all studies
employed transvaginal ultrasound.
The studies listed in Table 2 show that a finding of a
certain cervical length measured between 21 and 24 weeks
 
correlates highly with preterm birth at < 32 to 33 weeks.
The results are fairly consistent in that the risk of preterm
birth is increased 3- to 5-fold from baseline prevalence.
The absolute PPV ranges from 22% to 38 %. Notably, the
negative predictive values are quite high and consistent
across these studies: 94% to 96%.
Table 3 shows studies that attempted to define a threshold
at which the likelihood of delivery prior to 34 to 35 weeks
is low. The results are more variable than those shown in

JUNE JOGC JUIN 2011 l 649

SOGC CLINICAL PRACTICE GUIDELINE
Table 3. Probability of exceeding 34 to 35 weeks given CL > 35 mm
Definition threshold Prevalence of
Author weeks threshold %
Soriano et al.39 > 35 79.5
Sperling et al. 37
> 34 87
Yang et al.40 > 35 76.9
Vayssiere et al. 36
> 35 85.3
GA: gestational age
Table 2. Given a CL > 35 mm measured around the mid-
second trimester, the probability of reaching 34 to 35
weeks is quite high (88% to 98%).
Cervical length decreases with increasing gestational age,
and those who deliver preterm have a cervical shortening
rate greater than those who do not. Fujita et al.,41 in a
study of 144 twin pregnancies delivering after 34 weeks,
demonstrated a cervical length decrease of 0.8 mm/week.
Bergelin et al.42 found that the median rate of cervical
shortening in women who delivered at term was 1.8 mm
per week compared with a rate of 2.9 mm/week for those
who delivered preterm. Gibson et al.43 found that a rate
of cervical shortening > 2.5 mm/week predicted preterm
delivery (positive likelihood ratio of 10.8). Thus, it is clear
that progressive shortening greater than expected may
indicate a higher risk of preterm labour.
However, application to clinical practice is less clear.
The 95% confidence interval of inter- and intraobserver
variability (intraobserver repeatability coefficient of
approximately ± 6 mm and the interobserver limits of
agreement was approximately ±10 mm)44 is quite large
relative to the reported rates of cervical change. Observed
changes may simply be observer variability unless the
interobservation interval is quite long. There is also no
proven intervention in this scenario. Thus, the optimal
protocol for serial CL evaluation in twins is unclear.
In women with signs and symptoms of preterm labour
between 23 and 33 weeks, CL was a better predictor of
preterm delivery than funnelling and digital examination.45
Fuchs et al.46 found that among twin pregnancies that
presented in preterm labour, the longer the CL, the less
likely it was that delivery would occur within 1 week. At a
cervical length of > 25 mm, there were no deliveries (0/21)
that occurred within a week, whereas when cervical lengths
were ≤ 15 mm, the rate of delivery was 44% (18 of 32).
Summary Statement
2. There are insufficient data to recommend a routine
preterm labour surveillance protocol in terms
of frequency, timing, and optimal cervical length
thresholds. (II-2)
650 l JUNE JOGC JUIN 2011
GA at scan Sensitivity Specificity
N CL (mm) weeks % % PPV %
44 > 35 18 to 24 88.5 88.9 96.7
383 > 35 23 62.8 54 90.1
65 > 35 18 to 26 90 93.3 97.6
225 > 30 21 to 23 90 27.3 87.8
Recommendation
9. When ultrasound is used to screen for preterm
birth in a twin gestation, endovaginal ultrasound
measurement of the cervical length should be
performed. (II-2A)
ASSESSMENT OF FETAL GROWTH
The growth of twins is not significantly different from the
growth of singletons in the first and second trimesters.
However, there is disagreement regarding the rate of
fetal growth in the third trimester in uncomplicated twin
pregnancies. Most studies have described slower fetal growth
after 30 to 32 weeks’ gestation.47–50 The slower growth rate
in twins has been attributed to placental crowding and more
frequent anomalous umbilical cord insertion.
The American Congress of Obstetricians and Gynecologists
technical bulletin on assessment of growth51 suggests
that centres should use growth tables derived from twin
gestations. However, most studies of twin growth curves are
derived from a small sample size that includes pregnancies
with adverse outcomes and do not take into account
chorionicity, race, or gender. The argument in favour of using
twin growth charts is that it likely prevents the over-diagnosis
of IUGR in normally grown twins (which would result in
an increase in iatrogenic preterm delivery). A large cohort
study52 comparing the outcome of twins and singletons,
taking into account chorionicity and fetal growth centiles,
demonstrated that twins with growth restriction (defined
using singleton growth curves) were not protected from
perinatal loss; growth restricted monochorionic twins were,
in fact, at increased risk of perinatal mortality. Therefore,
although it is suggested that the twin growth curve pattern
starts to decelerate from 32 weeks’ gestation, IUGR twins
defined according to the singleton growth curve have worse
outcomes than those defined as appropriately grown using
the same curve. Thus, the literature still suggests that the
use of biometry charts from singletons in the follow-up of
twin pregnancy provide good predictors of adverse perinatal
outcome.52 Further investigation in this area using twin
growth charts is warranted.

Determination of fetal growth discordance is important,
because studies have shown an association with increased
mortality and morbidity when there are significant
differences in birthweight.53–58 Therefore, detection of
antenatal growth discordance by ultrasound is useful in
identifying twins that may require increased surveillance to
prevent higher fetal/neonatal complications. Confounding
factors in studies of twin growth discordance include
chorionicity, gestational age at delivery, and growth
restriction relative to expected birth weight, as well as
suboptimal sample size. Growth discordance has been
defined in several ways, with the most common being the
difference in estimated fetal weight derived by ultrasound
biometry.59 Another method uses absolute differences
in abdominal circumference.59 Both methods have their
strengths and weaknesses.
Birthweight discordance is defined by the following
formula, using the larger of the twins as the denominator.
EFW larger twin − EFW smaller twin
× 100%
EFW largest twin
00000000
There is no single definition of growth discordance in twins.
Clinically significant birthweight threshold definitions
in the literature (based on morbidity and mortality in the
postnatal population) range from 15%54 to 30%.57,60 The
largest (more than 250 000 cases) and most recent postnatal
study55 (which also corrected for IUGR) found statistically
significant odds ratios of neonatal mortality for the smaller
fetus at 25% birthweight discordance and for the larger
fetus at 30% birth weight discordance.
Study findings have not been consistent with respect to
the accuracy of ultrasound to diagnose discordance.61–69
This may be due to the error associated with all of the
ultrasound-derived estimated fetal weight formulas. The
SOGC consensus statement on twin gestations59 suggests
using an EFW discordance of > 20%. Given the relative
imprecision of EFW formulas (none of which were
determined from pure twin populations) and the desire to
have a high index of suspicion, adopting a 20% threshold
is a reasonable option.
Another definition of significant growth discordance
includes abdominal circumference measurement
differences of > 20 mm. A large study by Caravello et al.66
compared the use of AC difference and ultrasound EFW
difference to predict true birthweight discordance. This
study was of twins delivered between the mid-second
trimester and term. Other studies were not all concordant
in term of definitions. The range of sensitivities for IUGR
was 43% to 83% and 33% to 93% for AC and EFW,
Ultrasound in Twin Pregnancies
respectively. The range of specificities for appropriate for
gestational age was 68% to 91% versus 81% to 98% for AC
and EFW, respectively.66 Studies that directly compared the
2, showed them to be equally efficacious compared with
estimated fetal weight formulas.66,67 Regardless of growth
curves used, increased fetal surveillance is indicated when
abdominal circumference and/or EFW of one or both
twins is < 10th percentile or when growth discordance is
identified.19,70–72
Summary Statements
3. Singleton growth curves currently provide the best
predictors of adverse outcome in twins and may be
used for evaluating growth abnormalities. (III)
4. It is suggested that growth discordance be defined
using either a difference (20 mm) in absolute
measurement in abdominal circumference or a
difference of 20% in ultrasound derived estimated
fetal weight. (II-2)
FETAL SURVEILLANCE
There are few published studies indicating how frequently
routine reassessment should be done in twin pregnancies.
Giles et al.73 in a secondary analysis of their randomized
trial (all twins) reported fewer fetal deaths than expected
in their routine surveillance group: 11.4/1000 live births
(9/1000 live births in the Doppler group) compared with
historical control subjects (85.7/1000). In that study, twins
had repeat biometry scans at 30 and 35 weeks after a normal
25-week scan. Thus routine surveillance of twin pregnancies
every 5 weeks appears to be beneficial. Whether more
frequent surveillance would improve the results further
remains to be seen; however, it is suggested that more
frequent surveillance will result in significantly higher false-
positive rates for IUGR.74
In current practice, the frequency of ultrasound evaluation
in twin pregnancies is determined according to chorionicity
and growth pattern. In general, when monochorionic twin
pregnancies are identified, ultrasound scans are scheduled
every 2 to 3 weeks, starting at 16 to 18 weeks, to better
ascertain early evidence of TTTS.59 For all twin pregnancies,
the anomaly screening scan should be scheduled at 18 to
22 weeks. Most tertiary care centres routinely assess fetal
growth every 2 to 4 weeks, depending on chorionicity, largely
on the basis of expert opinion.59 Monochorionic twins are
scanned more frequently to allow for earlier diagnosis of
TTTS and/or growth restriction or discordance, which have
greater implications for the non-affected twin than they do
in dichorionic pregnancies. Some specialized centres or
clinics perform growth scans more frequently than every
JUNE JOGC JUIN 2011 l 651
SOGC CLINICAL PRACTICE GUIDELINE
2 weeks in uncomplicated monochorionic twin pregnancies,
but there is little evidence beyond expert opinion to support
this practice. Some centres advocate scanning dichorionic
twins every 3 weeks in the third trimester, since the growth
rate slows down after 30 to 32 weeks.
Grobman and Parilla75 found that in twins (of all types)
the positive predictive value of a sonogram for a growth
abnormality at birth significantly decreased if the 20- to
24-week sonogram was normal. Furthermore, in gestations
with normal growth at 20 to 24 weeks a mean of 10.3 (± 3.9)
weeks elapsed before a growth abnormality was subsequently
detected.75 This suggests that some routine growth scans
may be of very limited benefit while increasing the false
positive rate. Increased surveillance is warranted when one
or both fetuses show growth restriction or discordance. In
these circumstances, serial growth scans every 2 to 3 weeks
(or more frequently in monochorionic twins) and fetal
surveillance testing are indicated as for singleton (Doppler,
non-stress test, and/or biophysical profile).
Summary Statements
5. Although there is insufficient evidence to recommend
a specific schedule for ultrasound assessment of twin
gestation, most experts recommend serial ultrasound
assessment every 2 to 3 weeks, starting at 16 weeks of
gestation for monochorionic pregnancies and every
3 to 4 weeks, starting from the anatomy scan
(18 to 22 weeks) for dichorionic pregnancies. (II-1)
Recommendation
10. Increased fetal surveillance should be considered
when there is either growth restriction diagnosed in
one twin or significant growth discordance. (II-2A)
USE OF UMBILICAL ARTERY
DOPPLER VELOCIMETRY IN TWINS
Because inequality of the 2 fetal-placental circulations can
cause inter-twin differences in growth, umbilical artery
Doppler velocimetry may improve the detection of IUGR
or fetal growth discordance.65 The largest trial of Doppler
assessment of twin pregnancy (n = 526) compared
routine biometric ultrasound assessment to routine
assessment plus umbilical artery Doppler velocimetry in
a randomized fashion at 25, 30, and 35 weeks’ gestation.73
There were no differences between groups in any
antenatal, intrapartum, or neonatal outcome; there were
fewer unexplained fetal deaths in the Doppler group,
but this was not statistically significant. Unfortunately,
this study was limited by insufficient power and because
monochorionic pregnancies were not analyzed separately.
The available data do not show a clear benefit of Doppler
652 l JUNE JOGC JUIN 2011
velocimetry over the use of ultrasound alone; therefore,
routine use of Doppler velocimetry in twin gestations
cannot be recommended at this time.
Of note, in uncomplicated monochorionic twins, uterine
artery waveform abnormalities may be common, and
they reflect retrograde transmission of arterio-arterial
interference patterns in the presence of large arterio-
arterial anastomosis rather than fetal compromise.76,77
Summary Statement
6. Umbilical artery Doppler may be useful in the
surveillance of twin gestations when there are
complications involving the placental circulation
or fetal hemodynamic physiology. (II-2)
Recommendation
11. Umbilical artery Doppler should not be routinely
offered in uncomplicated twin pregnancies. (I-E)
ASSESSMENT OF AMNIOTIC FLUID
Currently available evidence78–81 is insufficient to make a
formal recommendation on the best method of amniotic
fluid assessment in twins. Outcome-based studies are
lacking. Identification of the inter-twin membrane is vital
in order to determine the fluid space around each fetus.
Accepted methods for fluid estimation include subjective
assessment, deepest vertical pocket, modified amniotic
fluid index and 2-dimensional pockets. Another method
is to ascertain the presence of fluid, caudal and rostral,
and determine to which fetus it belongs and subjectively
estimate if normal. When amniotic fluid volume appears
reduced or increased, the vertical measurement of the
largest pocket in each sac is taken. The condition is
defined as oligohydramnios when the deepest vertical
pocket < 2 cm and as polyhydramnios when the deepest
vertical pocket is > 8 cm. These definitions correspond
approximately to the 2.5th percentile and 95th percentile
across all gestational ages.82 This is also a common
criterion used in defining TTTS, and for these reasons,
this may be the clinically useful method for assessing
amniotic fluid in twins.83
Summary Statements
7. Although many methods of evaluating the level of
amniotic fluid in twins (deepest vertical pocket, single
pocket, amniotic fluid index) have been described,
there is not enough evidence to suggest that one
method is more predictive than the others of adverse
pregnancy outcome. (II-3)

Recommendation
12. For defining oligohydramnios and polyhydramnios,
the ultrasonographer should use the deepest vertical
pocket in either sac: oligohydramnios when < 2 cm
and polyhydramnios when > 8 cm. (II-2B)
Diagnosis of Twin-To-Twin Transfusion Syndrome
Prenatal diagnosis of twin-to-twin transfusion syndrome
is made on the basis of specific ultrasound criteria.
Monochorionic twins with an oligohydramnios-
polyhydramnios sequence and the presence of a large fetal
bladder in the polyhydramnios twin and a small or absent
fetal bladder in the oligohydramnios twin are consistent
with TTTS. Discordance in fetal size with the larger twin
in the polyhydramnios sac is often seen but is not essential
to the diagnosis. A pathognomonic sign for the diagnosis
of TTTS is the appearance of the donor as the stuck twin
contained within the collapsed inter-twin membrane because
of anhydramnios. Doppler studies are also part of the
diagnostic evaluation. Absent or low end diastolic flow in
the umbilical artery of the donor and decreased ventricular
function depicted by tricuspid regurgitation, reversal of A
wave in ductus venosus, and/or cardiac chamber enlargement
in the recipient are seen in more advanced stages of TTTS.
Currently, the Quintero classification method83 is used to
stage and determine the management plan for TTTS.
Stage 1 oligo-polyhydramnios sequence
Stage 2 absent bladder in the donor
Stage 3 abnormal fetal vascular Doppler studies
Stage 4 hydrops of one fetus
Stage 5 death of one fetus
In the absence of oligo-polyhydramnios sequence, the
diagnosis of TTTS should be entertained with caution
when fetal growth discordance is seen in the presence
of velamentous cord insertion, 2 vessel cord, or unequal
placental partition.
DIAGNOSIS OF RARE OBSTETRICAL
COMPLICATIONS UNIQUE TO TWINS
Monoamnionicity
This occurs in approximately 1% of all monozygotic twin
pregnancies. These pregnancies are at elevated risk of fetal death
because of cord entanglement. Early series reported double
survival in only 46% to 65% until 30 to 32 weeks’ gestation.84,85
More recent series reported improved double perinatal survival
of 92% when accurate prenatal diagnosis, serial sonography,
and antenatal testing were done.86 Thus early identification is
important in the management of these pregnancies.
Ultrasound in Twin Pregnancies
First trimester ultrasound can predict virtually all cases of
monoamniotic twins. Other sonographic indicators include
the presence of a single yolk sac and detection of cord
entanglement.87 In the second trimester, the diagnosis of
monoamnionicity is made on the basis of the following
second trimester ultrasound criteria: (1) single shared
placenta, (2) fetal phenotype concordance, (3) absence
of inter-twin membrane, (4) adequate amniotic fluid
surrounding both fetuses, and (5) free movement of both
twins within the uterine cavity.
Twin Reversed Arterial Perfusion Syndrome
Also known as acardiac twinning, twin reversed arterial
perfusion syndrome occurs in 1 in 35 000 deliveries, 1 in
100 monozyotic twins, and 1 in 30 monozygotic triplets.88
These pregnancies have a 90% risk of preterm birth and
a 30% risk of congestive heart failure in the normal twin
(also called pump twin).89 Diagnosis of acardiac twins is
made when one monochorionic twin has the absence of
cardiac pulsation along with poor definition of fetal parts.
Definitive diagnosis is established with colour Doppler
demonstrating reversal of blood flow within the abnormal
fetus. Blood-flow pattern reveals a paradoxical direction of
arterial flow towards rather than away from the acardiac twin
and retrograde flow in the acardiac twin’s abdominal aorta.
Differential diagnosis includes intrauterine fetal demise or an
abnormal monochorionic twin, or placental tumours.
After the diagnosis of twin reversed arterial perfusion
syndrome sequence is made, fetal hemodynamic function
should be assessed by fetal echocardiography; hydrops in
the pump twin being a poor prognostic feature. In addition,
estimation of the weight ratio of the acardiac to the pump
twin should be established. In a 1990 study, Moore et al.89
found that when the weight of the acardiac twin was ≥ 70%
of the weight of the normal pump twin, the incidence of
preterm birth, polyhydramnios, and fetal hydrops was 90%,
40%, and 30%, respectively. When the ratio was < 70%, the
rates were 70%, 30%, and 10%.89 When the weight ratio
was < 50% the complication rates were 18%, 0%, and 35%
compared with 44%, 25%, and 94% when > 50%.92 The
overall perinatal mortality was 55% in this untreated cohort.89
A multitude of treatment options have been described in the
literature, and the optimal method depends on gestational
age and centre experience. In a review of all reported cases of
minimally invasive therapies, Tan et al.88 reported an overall
pump twin survival of 74%. Two recent series reviewed the
use of radio frequency ablation and reported pump twin
survival rate of around 90%.90,91 However, in one small case
series of untreated, antenatally diagnosed acardiac twins,
the perinatal survival of the pump twin was 90%, with 40%
demonstrating spontaneous cessation of flow in the acardiac
JUNE JOGC JUIN 2011 l 653
SOGC CLINICAL PRACTICE GUIDELINE
twin over time.92 Because of the complexity of these cases
and the possible management options, including expectant
management,92,93 referral to a tertiary care unit is indicated.
Conjoined Twins
The incidence of conjoined twins varies between 1 in 50 000
and 1 in 100 000 births.94,95 The diagnosis can be made by
ultrasound examination in the first trimester. If the embryo
appears bifid, follow-up imaging should be performed to
confirm the diagnosis. Other clues to the diagnosis include
the inability to separate the fetal bodies and skin contours, lack
of a separating membrane between the twins, the presence
of more than 3 vessels in the umbilical cord, heads remaining
at the same level and body plane, extremities in unusual
proximity, and failure of the fetuses to change their relative
positions over time. Of all conjoined twins, only those who
are omphalopagus have a reasonable chance of survival.96
Single Fetal Death
It is estimated that only 50% of twin pregnancies identified
in the first trimester will result in 2 live born infants.97 When
the demise occurs early in pregnancy, the prognosis for the
surviving fetus is excellent.98,99
Demise of one fetus occurs in 2% to 5% of twin
pregnancies during the second and third trimesters. The
occurrence of single fetal death is 3-fold to 4-fold higher
in monochorionic twins than in dichorionic twins. It is
also more common in high-order multiples, complicating
14% to 17% of triplet pregnancies. The loss of a fetus in a
twin gestation has been associated with adverse outcomes
for the surviving fetus. The greatest risk to the surviving
fetus, regardless of chorionicity, is preterm delivery and
the associated complications of prematurity. Overall,
50% to 80% of surviving twins are born preterm, most
often because of preterm labour. In monochorionic twins,
multi-organ damage in the surviving twin can occur.
Ischemic injury, which is thought to occur at the time of
the demise, has been documented in the spleen, kidney,
gastrointestinal tract, skin, and brain of the surviving
twin. Up to 20% of surviving fetuses in monochorionic
twin pregnancies may experience neurologic injury, such as
multicystic encephalomalacia. These abnormalities may not
be diagnosed by ultrasound until much later in pregnancy,
far removed from the ischemic event. Immediate delivery
may not prevent the development of such complications.
In dichorionic twin pregnancies, the risk of major perinatal
morbidity or mortality to the surviving twin appears to be
negligible, apart from the risk related to preterm delivery.
654 l JUNE JOGC JUIN 2011
Summary Statement
8. Referral to an appropriate high-risk pregnancy centre
is indicated when complications unique to twins are
suspected on ultrasound. (II-2) These complications
include:
1. Twin-to-twin transfusion syndrome
2. Monoamniotic twins gestations
3. Conjoined twins
4. Twin reversed arterial perfusion sequence
5. Single fetal death in the second or third trimester
6. Growth discordance in monochorionic twins.
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 SOGC CLINICAL PRACTICE GUIDELINE
SOGC CLINICAL PRACTICE GUIDELINENo.243, June 2010
Adhesion Prevention in Gynaecological Surgery
This clinical practice guideline has been reviewed and approved
by the Clinical Practice Gynaecology Committee and by the
Executive and Council of the Society of Obstetricians and
Gynaecologists of Canada.
PRINCIPAL AUTHORS
Deborah Robertson, MD, Toronto ON
Guylaine Lefebvre, MD, Toronto ON
CLINICAL PRACTICE GYNAECOLOGY COMMITTEE
Nicholas Leyland, MD (Co-Chair), Toronto ON
Wendy Wolfman, MD (Co-Chair), Toronto ON
Catherine Allaire, MD, Vancouver BC
Alaa Awadalla, MD, Winnipeg MB
Carolyn Best, MD, Hamilton ON
Elizabeth Contestabile, RN, Ottawa ON
Sheila Dunn, MD, Toronto ON
Mark Heywood, MD, Vancouver BC
Nathalie Leroux, MD, Outremont QC
Frank Potestio, MD, Thunder Bay ON
David Rittenberg, MD, Halifax NS
Vyta Senikas, MD, Ottawa ON
Renéee Soucy, MD, Chandler QC
Sukhbir Singh, MD, Ottawa ON
Disclosure statements have been received from the primary
authors and all committee members.
Abstracts
Objectives: To review the etiology and incidence of and associative
factors in the formation of adhesions following gynaecological
surgery. To review evidence for the use of available means of
adhesion prevention following gynaecological surgery.
Options: Women undergoing pelvic surgery are at risk of developing
abdominal and/or pelvic adhesive disease postoperatively.
Surgical technique and commercial adhesion prevention systems
may decrease the risk of postoperative adhesion formation.
Key Words: Hysterectomy, postoperative adhesions, adhesion barriers
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
598 l JUNE JOGC JUIN 2010
Outcomes: The outcomes measured are the incidence of
postoperative adhesions, complications related to the formation of
adhesions, and further intervention relative to adhesive disease.
Evidence: Medline, EMBASE, and The Cochrane Library were
searched for articles published in English from 1990 to March
2009, using appropriate controlled vocabulary and key words.
Results were restricted to systematic reviews, randomized control
trials/controlled clinical trials, cohort studies, and meta-analyses
specifically addressing postoperative adhesions, adhesion
prevention, and adhesive barriers. Searches were updated on a
regular basis and incorporated in the guideline to March 2009.
Grey (unpublished) literature was identified through searching the
websites of health technology assessment and health technology
assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
medical specialty societies.
Values: The quality of evidence was rated using the criteria
described in the Report of the Canadian Task Force on Preventive
Health Care
Summary Statements
1. Meticulous surgical technique is a means of preventing adhesions.
This includes minimizing tissue trauma, achieving optimal
hemostasis, minimizing the risk of infection, and avoiding
contaminants (e.g., fecal matter) and the use of foreign materials
(e.g., talcum powder) when possible. (II-2)
2. The risk of adhesions increases with the total number of abdominal
and pelvic surgeries performed on one patient; every surgery
needs to be carefully considered in this context. (II-2)
3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than
no barrier or oxidized regenerated cellulose in preventing
adhesion formation. (I)
4. Oxidized regenerated cellulose (Interceed) adhesion barrier is
associated with a reduced incidence of pelvic adhesion formation
at both laparoscopy and laparotomy when complete hemostasis is
achieved. Oxidized regenerated cellulose may increase the risk of
adhesions if optimal hemostasis is not achieved. (II-2)
5. Chemically modified sodium hyaluronate/carboxymethylcellulose
(Seprafilm) is effective in preventing adhesion formation, especially
following myomectomies. There is insufficient evidence on the effect
of sodium hyaluronate/carboxymethylcellulose on long-term clinical
outcomes such as fertility, chronic pelvic pain or small bowel
obstruction. (II-2)
6. No adverse effects have been reported with the use of oxidized
regenerated cellulose, polytetrafluoroethylene, or sodium
hyaluronate/carboxymethylcellulose. (II-1)
7. Various pharmacological agents have been marketed as a means
of preventing adhesions. None of these agents are presently
available in Canada. There is insufficient evidence for the use of
pharmacological agents in preventing adhesions. (III-C)

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.1
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.1
Recommendations
1. Surgeons should attempt to perform surgical procedures using the
least invasive method possible in order to decrease the risk of
adhesion formation. (II-1B ) When feasible, for example, a
laparoscopic surgical approach is preferable to an abdominal
approach, and a vaginal or laparoscopic hysterectomy is
preferable to an abdominal hysterectomy.
2. Precautions should be taken at surgery to minimize tissue trauma
in order to decrease the risk of postoperative adhesions. These
precautions include limiting packing, crushing, and manipulating of
tissues to what is strictly required for safe completion of the
procedure. (III-B)
3. Surgeons could consider using an adhesion barrier for patients
who are at high risk of forming clinically significant adhesions (i.e.,
patients who have endometriosis or pelvic inflammatory disease or
who are undergoing a myomectomy). If there is a risk of ongoing
bleeding from the surgical site, oxidized regenerated cellulose
(Interceed) should not be used as it may increase the risk of
adhesions in this situation. (II-2B)
J Obstet Gynaecol Can 2010;32(6) 598–602
INTRODUCTION
dhesions have a variety of causes, including surgical
A procedures. Pelvic and abdominal adhesions have been
associated with significant gynaecological morbidity,
including infertility, chronic pelvic pain, small bowel
obstruction, and difficulty with surgical access or surgical
complications in the future. It is therefore important to
minimize adhesions at the time of surgery. Traditionally,
techniques such as meticulous hemostasis have been advo-
cated as a means of minimizing adhesion formation. Many
new products have recently been marketed to further
Adhesion Prevention in Gynaecological Surgery
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
reduce the formation of adhesions, but the evidence for
adhesion barriers is limited by the difficulty in assessing the
impact of postoperative adhesion formation in patients.
Recommendations for the prevention of adhesion formation
in gynaecological surgery are quantified according to the
evaluation of evidence guidelines developed by the Canadian
Task Force on Preventive Health Care (Table).1
INCIDENCE OF ADHESIONS
It has been estimated that 90% of patients undergoing
major abdominal surgery and 55% to 100% of women
undergoing pelvic surgery develop adhesions.2 It would
therefore seem that adhesions are an inevitable conse-
quence of abdominal and pelvic surgery. Fortunately, the
majority of patients with intra-abdominal adhesions are
asymptomatic.3 As surgeons we are faced with the difficult
task of trying to predict which patients are predisposed to
symptomatic adhesion formation on the basis of the type of
surgery performed and the patients’ underlying pathology.
CAUSES AND ASSOCIATIONS OF ADHESIONS
Within hours of surgery, fibrin is deposited in the area of
surgery.4 This fibrin is either then resorbed or becomes
organized into fibrous adhesions.4 It is unclear why some
patients experience resorption, while others have further
formation of these adhesions. Two specific risk factors for
the further organization of fibrin into adhesions have been
identified: tissue injury and an inflammatory response.4
JUNE JOGC JUIN 2010 l 599
SOGC CLINICAL PRACTICE GUIDELINE
Ischemic Injury
When tissue damage is associated with vascular insuffi-
ciency, adhesions form as a means of preventing ischemic
injury.4 Therefore, following operations during which the
tissues are crushed, sutured, or ligated, adhesions typically
form in the area of injury to provide new blood supply to
the devascularized organ.
Inflammatory Response
Contamination of the peritoneal cavity by foreign material
(e.g., talcum powder, sutures, fecal material) has also been
associated with the formation of adhesions because it pro-
duces an inflammatory response.4,5 Bacterial infection
causes a similar inflammatory reaction.6 Averting bowel
injury, preventing postoperative infections, and precluding
the use of foreign materials are advocated as means of
preventing inflammation but cannot always be achieved.
CONSEQUENCE OF ADHESIONS
The majority of patients who develop postoperative adhe-
sions are asymptomatic. Clinically significant outcomes associ-
ated with adhesions include chronic pelvic and abdominal
pain, bowel obstruction, infertility due to the formation of
adnexal adhesions, and complications at subsequent surgeries,
such as difficult dissection and visceral injury.3
METHODS OF ADHESION PREVENTION
Meticulous Surgical Technique
Meticulous surgical technique has long been advocated in
the prevention of adhesions.4 Avoidance of tissue trauma
with gentle tissue handling and prevention of thermal injury,
meticulous hemostasis, prevention of bacterial infection or
fecal contamination, use of copious irrigation, and avoidance
of foreign objects intuitively make sense as intraoperative
means of preventing postoperative adhesions.3 When possible,
the omentum can be placed such that bowel is shielded from
the abdominal wall before closure of the laparotomy incision.4
With every surgery, a certain amount of tissue injury inevitably
occurs.7 With increasing number of surgeries there is an
increased risk of adhesion formation.8 It is therefore important
to attempt to minimize the total number of surgeries per-
formed on one patient.
Laparoscopic surgical procedures have been associated with
fewer postoperative adhesions than open surgeries.7,9–11
Patients requiring a hysterectomy should be offered a vagi-
nal or laparoscopic approach rather than an abdominal
approach when feasible.12 Surgeons should attempt to per-
form surgical procedures using the least invasive method
possible, while respecting the limitations of the individual
patient characteristics, anticipated pathology, and their own
level of skill.
600 l JUNE JOGC JUIN 2010
Adhesions are not always preventable despite meticulous
surgical technique. Some conditions may increase the likeli-
hood of forming adhesions, such as endometriosis or
chronic pelvic inflammatory disease.13 Patients undergoing
myomectomy are also at increased risk of adhesions, and in
those women who are hoping to preserve fertility adhesions
add an element of risk of interrupting tubal patency.14 When
patients are at particular risk of postoperative adhesions, the
use of adjuvant measures of adhesion prevention could be
considered.
Summary Statements
1. Meticulous surgical technique is a means of preventing
adhesions. This includes mirnimizing tissue trauma,
achieving optimal hemostasis, minimizing the risk of
infection, and avoiding contaminants (e.g., fecal matter)
and the use of foreign materials (e.g., talcum powder)
when possible. (II-2)
2. The risk of adhesions increases with the total number of
abdominal and pelvic surgeries performed on one
patient; every surgery needs to be carefully considered in
this context. (II-2)
Recommendations
1. Surgeons should attempt to perform surgical procedures
using the least invasive method possible in order to decrease
the risk of adhesion formation. (II-1B ) When feasible, for
example, a laparoscopic surgical approach is preferable to an
abdominal approach, and a vaginal or laparoscopic hysterec-
tomy is preferable to an abdominal hysterectomy.
2. Precautions should be taken at surgery to minimize tissue
trauma in order to decrease the risk of postoperative
adhesions. These precautions include limiting packing,
crushing, and manipulating of tissues to what is strictly
required for safe completion of the procedure. (III-B)
Two systematic reviews have considered whether barrier
agents and pharmacological agents are clinically effective in
preventing the formation of postoperative adhesions in
patients who have undergone pelvic surgery.15,16
Barrier Agents
Barrier agents were devised to create a synthetic barrier
agent between opposing pelvic structures during tissue
healing that would prevent the formation of adhesions. The
main theoretical concern with the use of these agents is that
they could cause a foreign material reaction, thus contributing
to adhesion formation. There is insufficient evidence of the
effect of barrier agents on long-term clinical outcomes such
as fertility, chronic pelvic pain, or small bowel obstruction.
Oxidized regenerated cellulose (Interceed)
Interceed is an absorbable synthetic mechanical barrier
made of oxidized regenerated cellulose. When applied on

damaged peritoneum, Interceed transforms into a gel that
covers the area and is postulated to prevent adhesion for-
mation.17 The membrane may be cut as necessary, which
may allow for its use in both open and laparoscopic surgeries;
however, the product monograph specifies that it has been
approved only for use at laparotomy. It should be applied in
a single layer between two adjacent tissues. Interceed is
completely absorbed within two weeks. Meticulous
hemostasis must be achieved before Interceed is applied;
when mixed with blood Interceed increases fibrin deposition
and may increase the formation of adhesions.18
There have been numerous studies evaluating the use of
Interceed versus no treatment.19-28 When compared with no
treatment, Interceed was associated with a reduced
incicence of pelvic adhesion (OD 0.39; 95% CI 0.28 to
0.55) following laparotomy.15 Similar results were noted
following laparoscopy, with a reduction noted in new
formation (OD 0.31; 95% CI 0.23 to 0.79) and in
reformation (OR 0.19; 95% CI 0.09 to 0.42) of adhesions.15
There are no data on its effects on the incidence of small
bowel obstruction, chronic pelvic pain, or pregnancy rates.
Polytetrafluoroethylene (Gore-Tex)
Gore-Tex is a permanent, nonabsorbable membrane that
must be sutured into place. Particularly at laparoscopy, the
need to stabilize the membrane with sutures may result in
surgical delays.
There is evidence to suggest that, compared with no treat-
ment, Gore-Tex results in a reduction in the formation of
new adhesions in patients undergoing a myomectomy (OR
0.21; 95% CI 0.05 to 0.87).29 Gore-Tex has been reported to
have less adhesion reformation than Interceed in women
undergoing adhesiolysis (OR 0.16; 95% CI 0.03 to 0.80).15,30
Results should be interpreted with caution, as it is unclear if
the surgeon was unblinded at the time of second look lapa-
roscopy.15 Again, no studies have evaluated the incidence of
small bowel obstruction and chronic pelvic pain or preg-
nancy rates following the use of Gore-Tex.
Chemically modified sodium hyaluronate/
carboxymethylcellulose (Seprafilm)
Seprafilm is an absorbable synthetic membrane made up of
two polysaccharides: sodium hyaluronate and
carboxymethylcellulose. Seprafilm is supplied within a
plastic sleeve which must be removed before the Seprafilm
is placed on the tissues. Within 24 to 48 hours, the mem-
brane becomes gelatinous, and it is absorbed within one
week. At the present time, Seprafilm is indicated only for
use at laparotomy.
Some surgeons use Seprafilm at laparoscopy by creating a
“slurry” (i.e., a thin mixture of Seprafilm mixed with normal
saline) and then flushing this preparation via a catheter
Adhesion Prevention in Gynaecological Surgery
through one of the laparoscopic ports. The slurry produces
a gelatinous membrane coating on any surface on which it is
deposited, and it is postulated that its adhesion-preventing
effects may be similar to those produced when Seprafilm is
used at laparotomy. Although this slurry is being used by
Canadian and international surgical experts, there is insuffi-
cient evidence to support its use in preventing adhesions,
and this constitutes an off-label use of the product. Trials
of benefits are presently underway.
The only study to examine the use of Seprafilm at
laparotomy versus no treatment31 concluded that it reduced
the incidence, extent, and severity of postoperative
adhesions. However, the Cochrane database found that
suboptimal statistical analyses were used in this study, and
the results should therefore be interpreted with caution.15
No studies have yet evaluated the incidence of small bowel
obstruction or chronic pelvic pain or pregnancy rates fol-
lowing the use of Seprafilm.
Summary Statements
3. Polytetrafluoroethylene (Gore-Tex) barrier is more
effective than no barrier or oxidized regenerated
cellulose in preventing adhesion formation. (I)
4. Oxidized regenerated cellulose (Interceed) adhesion
barrier is associated with a reduced incidence of
pelvic adhesion formation at both laparoscopy and
laparotomy when complete hemostasis is achieved.
Oxidized regenerated cellulose may increase the risk
of adhesions if optimal hemostasis is not achieved. (II-2)
5. Chemically modified sodium hyaluronate/
carboxymethylcellulose (Seprafilm) is effective in
preventing adhesion formation, especially following
myomectomies. There is insufficient evidence on the
effect of sodium hyaluronate/carboxymethylcellulose
on long-term clinical outcomes such as fertility,
chronic pelvic pain, or small bowel obstruction. (II-2)
6. No adverse effects have been reported with the use
of oxidized regenerated cellulose,
polytetrafluoroethylene, or sodium
hyaluronate/carboxymethylcellulose. (II-1)
Recommendation
3. Surgeons could consider using an adhesion barrier for
patients who are at high risk of forming clinically
significant adhesions (i.e., patients who have
endometriosis or pelvic inflammatory disease or who are
undergoing a myomectomy). If there is a risk of ongoing
bleeding from the surgical site, oxidized regenerated
cellulose (Interceed) should not be used as it may
increase the risk of adhesions in this situation. (II-2B)
JUNE JOGC JUIN 2010 l 601
SOGC CLINICAL PRACTICE GUIDELINE
Pharmacological Agents
The use of various pharmacological agents has been proposed
to prevent the formation of adhesions. None of these agents
have been approved for use in Canada. There is insufficient
evidence for the use of pharmacological agents in preventing
adhesions.
Summary Statement
7. Various pharmacological agents have been marketed
as means of preventing adhesions. None of these
agents are presently available in Canada. There is
insufficient evidence for the use of pharmacological
agents in preventing adhesions. (III-C)
SUMMARY
Meticulous surgical technique is an inexpensive and
risk-free practice that may decrease likelihood of adhesion
formation. Studies involving the use of commercial
adhesion prevention and barrier methods such as Interceed,
Gore-Tex, and Seprafilm revealed that these agents appear
safe for use in gynaecological surgery. However, there is
limited evidence for the long-term benefits of adhesion
prevention agents in gynaecological surgery. Previous
studies typically assessed only the rate of adhesion forma-
tion and did not evaluate long-term, clinically relevant out-
comes such as fertility rates or abdominal or pelvic pain.
Further studies of commercial adhesion prevention and
barrier methods that evaluate these long-term clinical out-
comes are needed.
REFERENCES
1. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on Preventive Health Care. New grades for recommendations from
the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
2. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal
adhesions: etiology, pathophysiology, and clinical significance. Recent
advances in prevention and management. Dig Surg 2001;18:260–73.
3. Monk BJ, Berman ML, Montz FJ. Adhesions after extensive gynecologic
surgery: clinical significance, etiology, and prevention. Am J Obstet
Gynecol 1994;170(5 Pt 1):1396.
4. Ellis H. The causes and prevention of intestinal adhesions. Br J Surg
1982;69:241–3.
5. Luijendijk R, de Lange D, Wauters C, Hop WC, Duron JJ, Pailler JL, et al.
Foreign material in postoperative adhesions. Ann Surg 1996;223:242–8.
6. Thompson JN, Whawell SA. Pathogenesis and prevention of adhesion
formation. Br J Surg 1995;82:3–5.
7. Schäfer M, Krähenbühl L, Büchler MW. Comparison of adhesion
formation in open and laparoscopic surgery. Dig Surg 1998;15:148–52.
8. Weibel M. Peritoneal adhesions and their relation to abdominal surgery.
Am J Surg 1973;126:354–3.
9. Levrant SG, Bieber EJ, Barnes RB. Anterior abdominal wall adhesions after
laparotomy or laparoscopy. Am Assoc Gyn Laparosc 1997;4:353–6.
10. Bulletti C, Polli V, Negrini V, Giacomucci E, Flamigni C. Adhesion
formation after laparoscopic myomectomy. J Am Assoc Gynecol Laparosc
1996;3:533–6.
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11. Polymeneas G, Theodosopoulos T, Stamatiadis A, Kourias E.
A comparative study of postoperative adhesion formation after
laparoscopic vs open cholecystectomy. Surg Endosc 2001;15:41–3.
12. Lefebvre G, Allaire C, Jeffrey J, Vilos G; SOGC Clinical Practice
Gynaecology Committee. Hysterectomy. SOGC Clinical Practice Guideline
No. 109, January 2002. J Obstet Gynaecol Can 2002;24:37–48.
13. Diamond MP, Freeman ML. Clinical implications of postsurgical adhesions.
Hum Reprod Update 2001;7:567–76.
14. Tulandi T, Murray C, Guralnick M. Adhesion formation and reproductive
outcome after myomectomy and second-look laparoscopy. Obstet Gynecol
1993;82:213–5.
15. Ahmad G, Duffy J, Farquhar C, Vail A, Vandekerckhove P, Watson A, et al.
Barrier agents for adhesion prevention after gynaecological surgery.
Cochrane Database Syst Rev 2008;2:1–40.
16. Metwally M, Watson A, Lilford R, Vandekerckhove P. Fluid and
pharmacological agents for adhesion prevention after gynaecological
surgery. Cochrane Database Syst Rev 2006;2:1–52.
17. Al-Jaroudi D, Tulandi T. Adhesion prevention in gynecologic surgery.
Obstet Gynecol Surv 2004;59:360–7.
18. DeCherney AH, diZerega GS. Clinical problem of intraperitoneal
postsurgical adhesion formation following general surgery and the use of
adhesion prevention barriers. Surg Clin North Am 1997;77:671–88.
19. Mais V, Ajossa S, Marongiu D, Peiretti RF, Guerriero S, Melis GB.
Reduction of adhesion reformation after laparoscopic endometriosis
surgery: a randomized trial with an oxidized regenerated cellulose
absorbable barrier. Obstet Gynecol 1995;86:512–5.
20. Mais V, Ajossa S, Piras B, Guerriero S, Marongiu D, Melis GB. Prevention
of de-novo adhesion formation after laparoscopic myomectomy: a randomized
trial to evaluate the effectiveness of an oxidized regenerated cellulose
absorbable barrier. Hum Reprod 1995;10:3133–5.
21. Saravelos H, Li TC. Post-operative adhesions after laparoscopic
electrosurgical treatment for polycystic ovarian syndrome with the
application of Interceed to one ovary: a prospective randomized controlled
study. Hum Reprod 1996;11:992–7.
22. Keckstein J, Ulrich U, Sasse V, Roth A, Tuttlies F, Karageorgieva E.
Reduction of postoperative adhesion formation after laparoscopic ovarian
cystectomy. Hum Reprod 1996;11:579–82.
23. Azziz R. Microsurgery alone or with INTERCEED absorbable adhesion
barrier for pelvic sidewall adhesion re-formation. The INTERCEED (TC7)
Adhesion Barrier Study Group II. Surg Gynecol Obstet 1993;177:135–9.
24. Li TC, Cooke ID. The value of an absorbable adhesion barrier, Interceed®,
in the prevention of adhesion reformation following microsurgical
adhesiolysis. Br J Obstet Gynaecol 1994;101:335–9.
25. The efficacy of Interceed (TC7) for prevention of reformation of
postoperative adhesions on ovaries, fallopian tubes, and fimbriae in
microsurgical operations for fertility: a multicenter study. Nordic Adhesion
Prevention Study Group. Fertil Steril 1995;63:709–14.
26. Franklin RR. Reduction of ovarian adhesions by the use of Interceed.
Ovarian Adhesion Study Group. Obstet Gynecol 1995;86:335–40.
27. Sekiba K. Use of Interceed (TC7) absorbable adhesion barrier to reduce
postoperative adhesion reformation in infertility and endometriosis surgery.
The Obstetrics and Gynecology Adhesion Prevention Committee. Obstet
Gynecol 1992;79:518–22.
28. Van Geldorp H. Interceed absorbable adhesion barrier reduces the
formation
of postsurgical adhesions after ovarian surgery. Fertil Steril
1994;62(Suppl):273.
29. An expanded polytetrafluoroethylene barrier (Gore-Tex surgical membrane)
reduces post-myomectomy adhesion formation. Myomectomy Adhesion
Multicenter Study Group. Fertil Steril 1995;63:491–3.
30. Haney AF, Hesla J, Hurst BS, Kettel LM, Murphy AA, Rock JA, et al.
Expanded polytetrafluoroethylene (Gore-Tex Surgical Membrane) is
superior to oxidized regenerated cellulose (Interceed TC7+) in preventing
adhesions. Fertil Steril 1995;63:1021–6.
31. Diamond MP. Reduction of adhesions after uterine myomectomy by
Seprafilm membrane (HAL-F): a blinded, prospective, randomized,
multicenter clinical study. Seprafilm Adhesion Study Group. Fertil Steril
1996;66:904–10.
 SOGC CLINICAL PRACTICE GUIDELINE
SOGC Clinical Practice Guideline
Antibiotic Prophylaxis in Obstetric Procedures
This Clinical Practice Guideline has been prepared by the
Infectious Diseases Committee and approved by the Executive
and Council of the Society of Obstetricians and Gynaecologists of
Canada.
PRINCIPAL AUTHORS
Julie van Schalkwyk, MD, Vancouver BC
Nancy Van Eyk, MD, Halifax NS
INFECTIOUS DISEASES COMMITTEE
Mark H. Yudin, MD (Chair), Toronto ON
Marc Boucher, MD, Montreal QC
Beatrice Cormier, MD, Montreal QC
Andrée Gruslin, MD, Ottawa ON
Deborah M. Money, MD, Vancouver BC
Gina Ogilvie, MD, Vancouver BC
Eliana Castillo, MD, Vancouver BC
Caroline Paquet RM, Trois-Rivières QC
Audrey Steenbeek, RN, Halifax NS
Nancy Van Eyk, MD, Halifax NS
Julie van Schalkwyk, MD, Vancouver BC
Thomas Wong, MD, Ottawa ON
Disclosure statements have been received from all members of
the committee.
The literature searches and bibliographic support for this guideline
were undertaken by Becky Skidmore, Medical Research Analyst,
Society of Obstetricians and Gynaecologists of Canada.
Abstract
Objective: To review the evidence and provide recommendations
on antibiotic prophylaxis for obstetrical procedures.
Outcomes: Outcomes evaluated include need and effectiveness
of antibiotics to prevent infections in obstetrical procedures.
Evidence: Published literature was retrieved through searches
of Medline and The Cochrane Library on the topic of antibiotic
prophylaxis in obstetrical procedures. Results were restricted
to systematic reviews, randomized controlled trials/controlled
clinical trials, and observational studies. Searches were updated
on a regular basis and articles published from January 1978 to June
Key Words: Antibiotic prophylaxis, surgical prophylaxis, obstetrical
procedures, surgical site infection, SSI, endometritis, endocarditis
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
879 l SEPTEMBER JOGC SEPTEMBRE 2010
No. 247, September 2010
2009 were incorporated in the guideline. Current guidelines
published by the American College of Obstetrics and Gynecology
were also incorporated. Grey (unpublished) literature was identified
through searching the websites of health technology assessment
and health technology assessment-related agencies, clinical
practice guideline collections, clinical trial registries, and national
and international medical specialty societies.
Values: The evidence obtained was reviewed and evaluated by the
Infectious Diseases Committee of the Society of Obstetricians and
Gynaecologists of Canada under the leadership of the principal
authors, and recommendations were made according to guidelines
developed by the Canadian Task Force on Preventive Health Care
(Table 1).
Benefits, Harms, and Costs: Implementation of this guideline should
reduce the cost and harm resulting from the administration of
antibiotics when they are not required and the harm resulting from
failure to administer antibiotics when they would be beneficial.
Summary Statements
1. Available evidence does not support the use of prophylactic
antibiotics to reduce infectious morbidity following operative
vaginal delivery. (II-1)
2. There is insufficient evidence to argue for or against the use of
prophylactic antibiotics to reduce infectious morbidity for manual
removal of the placenta. (III)
3. There is insufficient evidence to argue for or against the use of
prophylactic antibiotics at the time of postpartum dilatation and
curettage for retained products of conception. (III)
4. Available evidence does not support the use of prophylactic
antibiotics to reduce infectious morbidity following elective or
emergency cerclage. (II-3)
Recommendations
1. All women undergoing elective or emergency Caesarean section
should receive antibiotic prophylaxis. (I-A)
2. The choice of antibiotic for Caesarean section should be a single
dose of a first-generation cephalosporin. If the patient has a
penicillin allergy, clindamycin or erythromycin can be used. (I-A)
3. The timing of prophylactic antibiotics for Caesarean section should
be 15 to 60 minutes prior to skin incision. No additional doses are
recommended. (I-A)
4. If an open abdominal procedure is lengthy (> 3 hours) or estimated
blood loss is greater than 1500 mL, an additional dose of the
prophylactic antibiotic may be given 3 to 4 hours after the
initial dose. (III-L)
5. Prophylactic antibiotics may be considered for the reduction of
infectious morbidity associated with repair of third and fourth degree
perineal injury. (I-B)
SOGC Clinical Practice Guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.40
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.40
6. In patients with morbid obesity (BMI > 35), doubling the antibiotic
dose may be considered. (III-B)
7. Antibiotics should not be administered solely to prevent
endocarditis for patients who undergo an obstetrical procedure
of any kind. (III-E)
J Obstet Gynaecol Can 2010;32(9):878–884
INTRODUCTION
nfectious complications following obstetric surgical
I procedures are a significant source of morbidity and
potential mortality. They include urinary tract infection,
endometritis, wound infection, perineal infection, and sepsis,
which lead to prolonged hospital stays and increased health
care costs. Much work has been done to study the effect of
prophylactic antibiotics in reducing infectious morbidity. A
plethora of antibiotic types, dosing schedules, and routes of
administration have been investigated. There is evidence to
support the use of prophylactic antibiotics for a number of
procedures in obstetrics. Unfortunately, few comparative
trials have been conducted, leaving the clinician with uncer-
tainty as to which regimen is superior.
The presence of antibiotic resistant organisms is a reality in
Canadian health care facilities.1 These organisms include
ABBREVIATIONS
CDC Centers for Disease Control and Prevention
IE infective endocarditis
SSI surgical site infection
880 l SEPTEMBER JOGC SEPTEMBRE 2010
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
methicillin resistant Staphylococcus aureus, vancomycin resistant
Enterococcus, and extended-spectrum beta-lactamase-producing
organisms.
Both morbidity and mortality are increased in infections
caused by these organisms, as they may be more virulent
and are more difficult to treat because therapeutic options
are limited. Antibiotic resistance development results
mainly from the inappropriate use of antibiotics. Incomplete
courses of antibiotic therapies and the unnecessary use of
broader spectrum regimens play a role.2 Adherence to both
treatment and prophylaxis guidelines likely assists in reducing
infection and antibiotic resistance. Physician adherence to
antibiotic prophylaxis guidelines is variable and usually at
odds with published guidelines.3,4
In addition to antibiotic prophylaxis, it is essential to review
all factors that affect infectious risk reduction in obstetrical
care.5 Adherence to appropriate skin preparation procedure,
including hair clipping as opposed to shaving, and effective
antisepsis of both patient and staff are required.6 Sterile
surgical fields must be ensured, and ongoing quality assess-
ment of sterilization technique, air ventilation, and postop-
erative wound care is needed. Consistent infection control
surveillance and reporting of infectious complications track
ability to minimize these morbidities and possibly to
identify clusters of infection and the emergence of antibiotic
resistant organisms. This will dictate changes to operative
routines to respond to evolving microbial diversity that
seems inevitable.

PRINCIPLES OF ANTIBIOTIC PROPHYLAXIS
The purpose of antibiotic prophylaxis in surgical procedures
is not to sterilize tissues but to reduce the colonization pres-
sure of microorganisms introduced at the time of operation
to a level that the patient’s immune system is able to over-
come.7 Prophylaxis does not prevent infection caused by
postoperative contamination. Prophylactic antibiotic use
differs from treatment with antibiotics5 in that the former is
intended to prevent infection, whereas the latter is intended
to resolve an established infection, typically requiring a longer
course of therapy. Prophylaxis is intended for elective pro-
cedures when the incision will be closed in the operating
room.
Before an agent can be considered for use as a prophylactic
antibiotic, there must be evidence that it reduces postoperative
infection. It must also be safe and inexpensive, and it must
be effective against organisms likely to be encountered in
the surgical procedure.
The agent must be administered in a way that ensures that
serum and tissue levels are adequate before an incision is made
and that therapeutic levels of the agent can be maintained in
serum and tissue during surgery and for a few hours (at most)
after the incision is closed.7
Wound infections—surgical site infections—in the form of
cellulitis, abscess, or dehiscence can occur following
laparotomy. Pelvic infections, such as an abscess or infected
hematoma, are a risk with any surgical procedure that enters
the abdominal cavity. Cuff cellulitis is a specific risk for hys-
terectomy. Endometritis can result from Caesarean section
or surgical abortion. Urinary tract infections can occur as a
result of any procedure that involves catheterization of the
bladder.
A 1999 guideline published by the US Centers for Disease
Control and Prevention lists the specific and stringent criteria
that must be met for diagnosis of a surgical site infection.7
Accurate surveillance for SSI monitoring requires follow-
up for 30 days postoperatively, and the trend towards early
discharge from hospital makes surveillance a challenge. It is
estimated that up to 84% of surgical site infections occur
following discharge from hospital.7
If prophylactic antibiotics are to be given, they should be
administered shortly prior to or at bacterial inoculation.8,9
The majority of studies suggest that a single dose is effective,
but for lengthy procedures (> 3 hours) the dose should be
repeated at intervals 1or 2 times the half-life of the drug. It
has also been suggested that with large blood loss (> 1500 mL),
a second dose should be given.10
USE OF ANTIBIOTIC PROPHYLAXIS IN OBSTETRICS
Procedures reviewed in this section include Caesarean section,
operative vaginal delivery, manual removal of placenta,
Antibiotic Prophylaxis in Obstetric Procedures
repair of third or fourth degree perineal laceration, cervical
cerclage, and postpartum dilatation and curettage. Recent
changes to endocarditis prophylaxis guidelines are also be
reviewed.
Caesarean Section
The single most important risk factor for postpartum maternal
infection is Caesarean section.11 Women having Caesarean
section have a 5- to 20-fold greater risk of infection than
women having vaginal delivery. Rates of wound infection
and serious infectious complications can be as high as
25%.12 There is no consistent application of definitions for
SSI, and the practice of post-discharge surveillance varies
widely.13 A recent prospective study with proper application
of CDC definitions for surgical site infection with follow-
up to 30 days post-Caesarean section identified a wound
infection rate of 8.9%.14 It is likely that post- Caesarean
wound infection rates are inaccurate, because up to 84% of
infections occur after discharge,7 when surveillance may be
lacking.
Endomyometritis, urinary tract infection, wound infection,
and sepsis may occur following Caesarean section. Numerous
studies have investigated the use of prophylactic antibiotics
to reduce these complications, the rates of which are all
higher in the case of emergency Caesarean section, with or
without the presence of maternal fever and/or chorioamnionitis.
A Cochrane review published in 2002 included 81 randomized
trials assessing antibiotic prophylaxis versus placebo or no
treatment for both elective and emergency Caesarean sections.
The review included just over 2000 women in each arm.
When antibiotics were given rather than placebo or no
treatment, the relative risk of endometritis in both elec-
tive and emergency Caesarean sections was reduced
(RR 0.38; 95% CI 0.22 to 0.64 and RR 0.39; 95% CI 0.34 to 0.46),
as was the risk of wound infection (RR 0.36; 95% CI 0.26 to
0.51 and RR 0.73; 95% CI 0.53 to 0.99).15
There has been debate about the benefit of prophylactic
antibiotics for a woman who has an elective Caesarean section
with intact membranes and without labour. A meta-analysis
of 4 studies found that antibiotic prophylaxis resulted in a
decrease in postoperative fever (RR 0.25; 95% CI 0.14 to 0.44)
and endometritis (RR 0.05; 95% CI 0.01 to 0.38).16
Taken together, these data support the recommendation to
use prophylactic antibiotics for all women undergoing
Caesarean section.
Controversy also exists about whether prophylactic antibiotics
in Caesarean section should be given prior to skin incision
or at the time of the umbilical cord clamping. Traditionally,
prophylaxis has been delayed in an effort to avoid masking a
neonatal infection and to prevent an unnecessary septic
work-up. However, recent evidence may change this practice.
A randomized trial compared maternal infectious and
SEPTEMBER JOGC SEPTEMBRE 2010 l 881
SOGC Clinical Practice Guideline
neonatal outcomes in women randomized to receive
cefazolin 15 to 60 minutes before incision versus at cord
clamp. Three hundred fifty-seven women were enrolled.
Overall maternal infectious morbidity was reduced in the
pre-treatment group (RR 0.4; 95% CI 0.18 to 0.87); in
particular, endometritis was reduced (RR 0.2; 95% CI 0.15 to 0.94).
No increase in neonatal sepsis, investigation, or length of
stay was observed.17 A recent meta-analysis supports the
use of prophylactic antibiotics prior to Caesarean incision
to prevent total infectious morbidity (RR 50; 95% CI 0.33
to 0.78, P = 0.002). Neonatal outcomes were not affected.18
The most widely studied antibiotics for surgical prophylaxis
are cephalosporins. Cefazolin is a first-generation cephalosporin
and is a Pregnancy Category B drug. When given intrave-
nously, its half-life is 1.8 hours. It provides good coverage
for gram positive organisms and has modest gram negative
coverage. In a 1999 guideline, the US Centers for Disease
Control and Prevention recommended its use at Caesarean
section.7 It is recommended that 1 to 2 grams should be
administered intravenously not more than 30 minutes before
the skin is cut. An additional dose can be considered if
blood loss exceeds 1500 mL or at 4 hours if the procedure
lasts more than 4 hours (i.e., up to 2 half-lives of the drug).19
Trials have shown that broader spectrum antibiotics for
Caesarean section do reduce infectious morbidity. Superi-
ority trials with cefazolin have not been conducted. Given
the potential for antibiotic resistance in both mother and
neonate, recommendations for the use of broader spectrum
antibiotics require further study.20
Operative Vaginal Delivery
A 2004 Cochrane review investigated the use of prophylactic
antibiotics for operative vaginal delivery, with either forceps
or vacuum assisted deliveries, to determine if prophylaxis
reduces the incidence of postpartum infections.21 The
review identified only one trial of 393 women, and only 2 of
9 outcomes deemed appropriate by the reviewers were
assessed in this study: endometritis and length of hospital
stay. These did not differ between those who received
prophylaxis and those who received no treatment. The
review concluded there were insufficient data on which to
base recommendations for practice and that further
research is needed. No additional studies addressing this
issue have been published to date.
Manual Removal of Placenta
There is limited information regarding the use of prophy-
lactic antibiotics to reduce the development of postpartum
endometritis following manual removal of the placenta.
A Cochrane review, updated in April 2009, did not identify
any randomized controlled trials.22 The World Health
Organization suggests that prophylaxis should be offered
but recognizes that there is no direct evidence of the value
882 l SEPTEMBER JOGC SEPTEMBRE 2010
of antibiotic prophylaxis after manual removal of the pla-
centa and bases the recommendation on studies involving
Caesarean section and abortion and on observational
studies of other intrauterine manipulations.23
The effect of operator glove change before manual removal
of the placenta at Caesarean section was studied in a group
of 228 women, with operators changing gloves in one half
of the cases. No difference in post-Caesarean endometritis
was noted between the 2 groups.24 However, the incidence
of endometritis was decreased when the placenta delivered
spontaneously rather than being manually removed at Cae-
sarean section in a study of 333 women, all of whom
received prophylactic antibiotics (15% vs. 26%, RR 0.6;
P = 0.01).25
Third or Fourth Degree Perineal Laceration
A 2005 Cochrane review26 on this subject found there were
no randomized trials comparing prophylactic antibiotics
with placebo or no treatment in fourth degree perineal tears
during vaginal birth. A well-designed randomized trial was
recommended. This was undertaken by Duggal et al.27 and
published in 2008. This prospective trial followed 107 women
post third or fourth degree laceration repair for 2 weeks; the
women had been randomly assigned to receive a single
intravenous dose of cefotetan, cefoxitin, or placebo. Four
of 49 (8%) who received antibiotics and 14 of 58 (24%) who
received placebo developed perineal wound complication
(P = 0.037). This suggests a benefit to using prophylactic
antibiotics to reduce morbidity following significant perineal
laceration.27
Elective and Emergency Cerclage, With or
Without Exposed Membranes
There is insufficient evidence to support the use of prophy-
lactic antibiotics with the placement of cervical cerclage in
any clinical setting. One study28 investigated the use of
continuous low-dose antibiotics in women with a history
of second trimester pregnancy loss with the placement
of cerclage at 14 to 24 weeks’ gestation on the basis of
transvaginal sonographic findings of cervical funnelling.
Each of the 10 patients had a live birth, and pregnancy was
prolonged by a mean of 13.4 ± 4.2 weeks beyond the
previous pregnancy. There was no control group.28 In a second
retrospective study of 116 mid-trimester cerclage place-
ments, antibiotic use was not associated with a decreased
risk of delivery before 28 weeks’ gestation.29 Randomized
clinical trials are needed to confirm the role of antibiotics in
these high-risk pregnancies.
Postpartum Dilatation and Curettage
No studies were identified that investigated the use of
prophylactic antibiotics for postpartum dilatation and curettage.
 Antibiotic Prophylaxis in Obstetric Procedures

Table 2. Cardiac conditions associated with the highest risk of adverse outcome from endocarditis

Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous infective endocarditis
Congenital heart disease (CHD)
Unrepaired cyanotic CHD (including palliative shunts and conduits)
Completely repaired CHD with prosthetic material < 6 months after procedure
Repaired CHD with residual defects at/near site of prosthetic material
Cardiac transplant recipient with cardiac valvulopathy

Adapted from Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al. 38

Table 3. Prophylactic antibiotic recommendations for obstetrical procedures

Procedure Antibiotic Dosage Level of evidence

Emergency or elective caesarean section Cefazolin IV 15–60 mins prior to skin incision 1–2 g IV I-A
(no labour, no rupture of membranes)
If penicillin allergic
Clindamycin OR 600 mg IV
erythromycin 500 mg IV
Operative vaginal delivery None recommended N/A II-1C
Manual removal placenta None recommended N/A III-L
Repair third or fourth degree laceration Cefotetan 1 g IV I-B
Cefoxitin 1 g IV I-B
Postpartum dilatation and curettage None recommended N/A No evidence
Cerclage None recommended N/A II-3C

Dosage of Antibiotic Prophylaxis in Obesity PREVENTION OF INFECTIVE ENDOCARDITIS

Increased BMI is associated with higher rates of both
obstetric and infectious complications.30 Controlled trials
assessing the required dosage for antibiotic prophylaxis
based on patient BMI have not been assessed in our
specialty. Expert opinion recommends twice the normal
dose of prophylaxis for morbidly obese patients, who have
a BMI > 35.19 Future research in this area is needed.
RECOMMENDATIONS FOR PENICILLIN /
CEPHALOSPORIN ALLERGY
Penicillin allergy is self-reported by up to 10 % of patients,
yet only 10 % of those are actually allergic when skin testing
is performed.31–33 True anaphylactic response to penicillin is
rare, occurring in 1 to 4 of 10 000 administrations.34 An
allergic reaction to cephalosporins in those with a penicillin
allergy occurs at rates of 0.17% to 8.4%.35–37 An alternative
to cephalosporins should be given only to individuals with a
history of penicillin anaphylaxis (shortness of breath or
evidence of airway edema rather than just rash or other
allergic reaction) or cephalosporin allergy. Alternative
prophylactic antibiotics include clindamycin 600 mg IV or
erythromycin 500 mg IV.
An American Heart Association guideline38 published in
2007 found no evidence that genitourinary procedures cause
IE or that administration of antibiotics prevents IE following
such procedures. The American Heart Association
therefore does not recommend prophylactic antibiotics for
patients undergoing genitourinary procedures; this is a change
from their 1997 guideline. They identified 4 conditions that
are at highest risk of adverse outcome (Table 2). For
patients with the conditions listed in Table 2 who have an
established gastrointestinal or genitourinary tract infection
or for those who receive antibiotic therapy for another reason
(e.g., to prevent wound infection), they suggest it may be rea-
sonable that the choice of antibiotic also be active against
enterococci (i.e., ampicillin, piperacillin, or vancomycin).
They also suggest that it may be reasonable for patients at
high risk of IE who have a known enterococcal urinary tract
infection or colonization to receive antibiotic treatment
prior to any urinary tract manipulation. A review on this
recommendation change has been recently published.39

SEPTEMBER JOGC SEPTEMBRE 2010 l 883

SOGC Clinical Practice Guideline
SUMMARY
For a number of procedures in obstetrics and gynaecology,
the use of prophylactic antibiotics has been shown to
reduce infectious morbidity in a safe and cost-effective
manner (Table 3).
There remain a number of procedures where the utility of
prophylactic antibiotics is either unclear or not well studied.
Appropriate antibiotics used at the correct dose and time
and with the appropriate frequency will reduce infectious
postoperative complications and minimize the development
of antibiotic resistant organisms.
Summary Statements
1. Available evidence does not support the use of
prophylactic antibiotics to reduce infectious morbidity
following operative vaginal delivery. (II-1)
2. There is insufficient evidence to argue for or against
the use of prophylactic antibiotics to reduce infectious
morbidity for manual removal of the placenta. (III)
3. There is insufficient evidence to argue for or against
the use of prophylactic antibiotics at the time of
postpartum dilatation and curettage for retained
products of conception. (III)
4. Available evidence does not support the use of
prophylactic antibiotics to reduce infectious morbidity
following elective or emergency cerclage. (II-3)
Recommendations
1. All women undergoing elective or emergency Caesarean
section should receive antibiotic prophylaxis. (I-A)
2. The choice of antibiotic for Caesarean section should be
a single dose of a first-generation cephalosporin.
If the patient has a penicillin allergy, clindamycin or
erythromycin can be used. (I-A)
3. The timing of prophylactic antibiotics for Caesarean
section should be 15 to 60 minutes prior to skin incision.
No additional doses are recommended. (I-A)
4. If an open abdominal procedure is lengthy (> 3 hours)
or estimated blood loss is greater than 1500 mL,
an additional dose of the prophylactic antibiotic may be
given 3 to 4 hours after the initial dose. (III-L)
5. Prophylactic antibiotics may be considered for the reduction
of infectious morbidity associated with repair of third
and fourth degree perineal injury. (I-B)
6. In patients with morbid obesity (BMI > 35), doubling the
antibiotic dose may be considered. (III-B)
7. Antibiotics should not be administered solely to prevent
endocarditis for patients who undergo an obstetrical pro-
cedure of any kind. (III-E)
884 l SEPTEMBER JOGC SEPTEMBRE 2010
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11. Gibbs RS. Clinical risk factors for puerperal infection. Obstet Gynecol
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14. Opoein HK, Valbo A, Grinde-Andersen Q, Qalberg M. Post-cesarean
surgical site infections according to CDC standards: rates and risk factors.
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17. Sullivan SA, Smith T, Chang E, Hulsey T, Vandorsten JP, Soper D.
Administration of cefazolin prior to skin incision is superior to cefazolin
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Timing of perioperative antibiotics for cesarean delivery: a metaanalysis.
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20. Tita AT, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW.
Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic
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22. Chongsomchai C, Lumbiaganon P, Laopaiboon M. Prophylactic antibiotics
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of postpartum hemorrhage and retained placenta. Geneva: WHO; 2009.
Available at: http://whqlibdoc.who.int/publications/2009/
9789241598514_eng.pdf. Accessed May 23, 2010.
24. Turrentine MA, Banks TA. Effect of changing gloves before placental
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Gynecol 1996;4:16–9.
25. Lasley DS, Eblen A, Yancey MK, Duff P. The effect of placental removal
method on the incidence of postcesarean infections. Am J Obstet Gynecol
1997;176:1250–4.
26. Buppasiri P, Lumbiganon P, Thinkhamrop J, Thinkhamrop B. Antibiotic
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Antibiotic prophylaxis for prevention of postpartum perineal wound
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2008;111:1268–73.
28. Shiffman RL. Continuous low-dose antibiotics and cerclage for recurrent
second-trimester pregnancy loss. J Reprod Med 2000;45:323–6.
29. Terkildsen MF, Parilla BV, Kumar P, Grobman WA. Factors associated
with success of emergent second-trimester cerclage. Obstet Gynecol
2003;101:565–9.
30. Heslehurst N, Simpson H, Ells LJ, Rankin J, Wilkinson J, Lang R, et al.
The impact of maternal BMI status on pregnancy outcomes with
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immediate short-term obstetric resource implications: a meta-analysis.
Obes Rev 2008;9635–83.
31. Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA,
Peterson LR, et al. The incidence of antimicrobial allergies in hospitalized
patients: implications regarding prescribing patterns and emerging bacterial
resistance. Arch Intern Med 2000;160:2819–22.
32. Sogn DD, Evans R 3rd, Shepherd GM, Casale TB, Condemi J,
Greenberger PA, et al. Results of the National Institute of Allergy and
Infectious Diseases collaborative clinical trial to test the predictive value
of skin testing with major and minor penicillin derivatives in hospitalized
adults. Arch Intern Med 1992;152:1025.
33. del Real GA, Rose ME, Ramirez-Atamoros MT, Hammel J, Gordon SM,
Arroliga AC, Arroliga ME. Penicillin skin testing in patients with a history
of beta-lactam allergy. Ann Allergy Asthma Immunol 2007;98:355–9.
34. International Rheumatic Fever Study Group. Allergic reactions to
long-term benzathine penicillin propylaxis for rheumatic fever.
Lancet 1991;337(8753):1308–10.
35. Dash, CH. Penicillin allergy and the cephalosporins. J Antimicrob Chemother
1975;1:107.
36. Daulat, S, Solensky, R, Earl, HS, Casey W, Gruchalla RS. Safety of
cephalosporin administration to patients with histories of penicillin allergy.
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37. Fonacier L, Hirschberg R, Gerson S. Adverse drug reactions to a cephalosporins
in hospitalized patients with a history of penicillin allergy. Allergy Asthma
Proc 2005;26:135.
38. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, et al.;
American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki
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39. Castillo E, Magee LA, von Dadelszen P, Money D, Blondel-Hill E,
van Schalkwyk J. Our patients do not need endocarditis prophylaxis
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SEPTEMBER JOGC SEPTEMBRE 2010 l 885
 SOGC CLINICAL PRACTICE GUIDELINE

SOGC CLINICAL PRACTICE GUIDELINENo. 240, April 2010

Cytomegalovirus Infection in Pregnancy

Abstract
This guideline has been reviewed by the Maternal Fetal Medicine
Committee and approved by Executive and Council of the Society Objectives: To review the principles of prenatal diagnosis of
of Obstetricians and Gynaecologists of Canada congenital cytomegalovirus (CMV) infection and to describe the
outcomes of the affected pregnancies.
PRINCIPAL AUTHORS
Outcomes: Effective management of fetal infection following primary
Yoav Yinon, MD, Toronto ON
and secondary maternal CMV infection during pregnancy.
Dan Farine, MD, Toronto ON Neonatal signs include intrauterine growth restriction (IUGR),
Mark H. Yudin, MD, Toronto ON microcephaly, hepatosplenomegaly, petechiae, jaundice,
chorioretinitis, thrombocytopenia and anemia, and long-term
MATERNAL FETAL MEDICINE COMMITTEE sequelae consist of sensorineural hearing loss, mental retardation,
Robert Gagnon, MD (Chair), Montreal QC delay of psychomotor development, and visual impairment. These
guidelines provide a framework for diagnosis and management of
Lynda Hudon, MD (Co-Chair), Montreal QC suspected CMV infections.
Melanie Basso, RN, Vancouver BC Evidence: Medline was searched for articles published in English
Hayley Bos, MD, London ON from 1966 to 2009, using appropriate controlled vocabulary
(congenital CMV infection) and key words (intrauterine growth
Marie-France Delisle, MD, Vancouver BC
restriction, microcephaly). Results were restricted to systematic
Dan Farine, MD, Toronto ON reviews, randomized controlled trials/controlled clinical trials, and
Savas Menticoglou, MD, Winnipeg MB observational studies. Searches were updated on a regular basis
and incorporated into the guideline. Grey (unpublished) literature
William Mundle, MD, Windsor ON was identified through searching the websites of health technology
Annie Ouellet, MD, Sherbrooke QC assessment and health technology assessment-related agencies,
clinical practice guideline collections, clinical trial registries, and
Tracy Pressey, MD, Vancouver BC national and international medical specialty societies.
Anne Roggensack, MD, Calgary AB Recommendations
INFECTIOUS DISEASES COMMITTEE The quality of evidence reported in this document has been
Mark H. Yudin, MD (Chair), Toronto ON assessed using the evaluation of evidence criteria in the Report of
the Canadian Task Force on Preventive Health Care (Table 1).
Marc Boucher, MD, Montreal QC
1. Diagnosis of primary maternal cytomegalovirus (CMV) infection in
Eliana Castillo, MD, Vancouver BC
pregnancy should be based on de-novo appearance of
Andrée Gruslin, MD, Ottawa ON virus-specific IgG in the serum of a pregnant woman who was
Deborah M. Money, MD, Vancouver BC previously seronegative, or on detection of specific IgM antibody
associated with low IgG avidity. (II-2A)
Kellie Murphy, MD, Toronto ON
2. In case of primary maternal infection, parents should be informed
Gina Ogilvie, MD, Vancouver BC about a 30% to 40% risk for intrauterine transmission and fetal
Caroline Paquet, RM, Trois-Rivières QC infection, and a risk of 20% to 25% for development of sequelae
postnatally if the fetus is infected. (II-2A)
Nancy Van Eyk, MD, Halifax NS
3. The prenatal diagnosis of fetal CMV infection should be based on
Julie van Schalkwyk, MD, Vancouver BC amniocentesis, which should be done at least 7 weeks after
Disclosure statements have been received from all members of presumed time of maternal infection and after 21 weeks of
the committees. gestation. This interval is important because it takes 5 to 7 weeks
following fetal infection and subsequent replication of the virus in
the kidney for a detectable quantity of the virus to be secreted to
the amniotic fluid. (II-2A)
Key Words: Congenital infection, cytomegalovirus, CMV, prenatal 4. The diagnosis of secondary infection should be based on a
diagnosis, intrauterine growth restriction, IUGR, microcephaly significant rise of IgG antibody titre with or without the presence of
IgM and high IgG avidity. In cases of proven secondary infection,
amniocentesis may be considered, but the risk–benefit ratio is
different because of the low transmission rate. (III-C)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

348 l APRIL JOGC AVRIL 2010


5. Following a diagnosis of fetal CMV infection, serial ultrasound
examinations should be performed every 2 to 4 weeks to detect
sonographic abnormalities, which may aid in determining the prognosis
of the fetus, although it is important to be aware that the absence of
sonographic findings does not guarantee a normal outcome. (II-2B)
6. Quantitative determination of CMV DNA in the amniotic fluid may
assist in predicting the fetal outcome. (II-3B)
7. Routine screening of pregnant women for CMV by serology testing
is currently not recommended. (III-B)
8. Serologic testing for CMV may be considered for women who develop
influenza-like illness during pregnancy or following detection of
sonographic findings suggestive of CMV infection. (III-B)
9. Seronegative health care and child care workers may be offered
serologic monitoring during pregnancy. Monitoring may also be
considered for seronegative pregnant women who have a young
child in day care. (III-B)
J Obstet Gynaecol Can 2010;32(4):348–354
INTRODUCTION
C ytomegalovirus is the most common cause of intrauterine
infection, occurring in 0.2% to 2.2% of all live births, and is
a common cause of sensorineural hearing loss and mental
retardation.1,2
Most healthy people who acquire CMV after birth experience
few or no symptoms and no long-term sequelae. Some
experience a mononucleosis-like syndrome with symptoms
including malaise, persistent fever, myalgia, cervical
lymphadenopathy, and, less commonly, pneumonia and
hepatitis.3 After the primary infection, defined as CMV
infection in a previously seronegative person, the virus
becomes dormant and exists in a latent state, from which it
can be reactivated. This is designated as recurrent (secondary)
infection.4 In addition, there seem to be several strains of
CMV that infect humans, so reinfection can occur, even in
immunocompetent individuals. Therefore, secondary
infection, defined as intermittent excretion of the virus in
the presence of host immunity, may be due to either reacti-
vation of an endogenous virus or exposure to a new virus
strain from an exogenous source. Differentiation between
these two kinds of secondary infection is not possible by
serology but only by molecular analysis of virus isolates.3–5
Seroconversion occurs in 1% to 4% of all pregnancies and
is higher in women who are of low socioeconomic status or
who have poor personal hygiene.6,7
Congenital infections are the result of transplacental
transmission of CMV. Transmission to the fetus may occur
because of primary or secondary maternal infection. The
ABBREVIATIONS
CMV cytomegalovirus
PCR polymerase chain reaction
IUGR intrauterine growth restriction
Cytomegalovirus Infection in Pregnancy
probability of intrauterine transmission following primary
infection during pregnancy is 30% to 40%,1,8 compared
with only 1% following secondary infection. 1,8 Ten to
fifteen percent of congenitally infected infants will have
symptoms at birth including intrauterine growth restriction,
microcephaly, hepatosplenomegaly, petechiae, jaundice,
chorioretinitis, thrombocytopenia, and anemia, and 20% to 30%
of them will die, mostly of disseminated intravascular coag-
ulation, hepatic dysfunction, or bacterial superinfection.8–10
Most of the congenitally infected infants (85–90%) have no
signs or symptoms at birth, but 5% to 15% of them will
develop sequelae such as sensorineural hearing loss, delay of
psychomotor development, and visual impairment.11,12
PRENATAL DIAGNOSIS
The first step in the prenatal diagnosis of congenital CMV
infection is determination of maternal primary and secondary
infection by serological testing.12 In women with proven
CMV infection, the second step is to identify fetal infection
by non-invasive (ultrasound examination) and invasive
(amniocentesis) prenatal tests12 (Figure).
Diagnosis of Maternal Infection
Revello and Gerna13 state:
The diagnosis of primary CMV infection is ascer-
tained when seroconversion is documented, i.e., the
de novo appearance of virus-specific IgG in the serum
of a pregnant woman who was previously
seronegative. However, such an approach is feasible
only when a screening program is adopted and
seronegative women are identified and prospec-
tively monitored13 [or when maternal serum speci-
mens are saved].
When the immune status before pregnancy is unknown,
determination of primary CMV infection should be based
on detection of specific IgM antibody. However, IgM can
also be detected in 10% of recurrent infections14 and can be
detected for months after primary infection.15 Therefore,
the group of women designated CMV-IgM positive could
include women with primary infection acquired before
pregnancy and a few women with recurrent infections.16
The IgG avidity assay can help distinguish primary infec-
tion from past or recurrent infection and can assist in deter-
mining when infection occurred.13,17
This assay is based on the observation that
virus-specific IgG of low avidity is produced during
the first months after onset of infection, whereas
subsequently a maturation process occurs by
which IgG antibody of increasingly higher avidity is
generated. IgG antibody of high avidity is detected
only in subjects with remote or recurrent CMV
APRIL JOGC AVRIL 2010 l 349
SOGC CLINICAL PRACTICE GUIDELINE
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.38
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.38
infection. Avidity levels are reported as the avidity
index, expressing the percentage of IgG bound to
the antigen following treatment with denaturing
agents.13
An avidity index > 60% is highly suggestive of past or
secondary infection, while an avidity index < 30% is
highly suggestive of a recent primary infection (duration
< 3 months).17 Hence, serologic diagnosis of primary CMV
infection during pregnancy is documented by either
seroconversion (the appearance of CMV-specific IgG
antibody in a previously seronegative woman) or detection
of specific IgM antibody associated with low IgG avidity.
Women who have detectable specific IgG antibodies with-
out IgM antibodies before pregnancy and a significant rise
of IgG antibody titre with or without the presence of spe-
cific IgM antibodies and with high IgG avidity can be classi-
fied as having recurrent infection.18
Diagnosis of Fetal Infection
Since intrauterine transmission of the virus occurs in only
30% to 40% of pregnancies in women with primary infection
and at a significantly lower rate in women with secondary
infection, it is important in cases of proven maternal infection
to find out if the fetus is infected.
Ultrasonographic findings are helpful but not diagnostic
because CMV has features in common with other
intrauterine infections and with other fetal diseases. Moreover,
these abnormalities are observed in less than 25% of
infected fetuses.19 The most frequently reported
350 l APRIL JOGC AVRIL 2010
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
Table 2. Congenital CMV infection-sonographic finding
IUGR
Cerebral ventriculomegaly
Microcephaly
Intracranial calcifications
Ascites/pleural effusion
Hydrop fetalis
Oligohydramnios/polyhydramnios
Hyperechogenic bowel
Liver calcifications
sonographic findings of fetal CMV infection include fetal
growth restriction, cerebral ventriculomegaly, ascites,
intracranial calcifications, abnormality of amniotic fluid volume
(usually oligohydramnios), microcephaly, hyperechogenic
bowel, hydrops fetalis, pleural effusion, and liver
calcifications19–21 (Table 2).
Because of its high sensitivity and specificity, CMV isolation
from amniotic fluid has been recognized as the gold standard
for prenatal diagnosis of fetal CMV infection.9,13,22 To achieve
the highest sensitivity, the amniocentesis should be per-
formed until at least 7 weeks after the onset of maternal
infection and after 21 weeks of gestation because a detectable
quantity of the virus is not secreted to the amniotic fluid
until 5 to 7 weeks after fetal infection and replication of the
virus in the kidney.9,16,23 It has been repeatedly reported that

Algorithm for prenatal diagnosis of congenital CMV
prenatal diagnosis procedures performed too close to the
onset of maternal infection carry a substantial risk of false
negative results.24–26 The diagnosis of fetal CMV infection
should be based on the results of culture and PCR testing of
amniotic fluid samples. CMV isolation can be done by con-
ventional culture on fibroblasts or by the shell vial tech-
nique, which uses monoclonal antibodies to the major
immediate early protein p72 and enables detection of the
virus 16 to 24 hours after amniotic fluid collection.23,27,28
Diagnosis of fetal infection by testing for fetal IgM is not
recommended not only because of the risk associated with
cordocentesis but also because many fetuses infected by
CMV do not develop specific IgM until late in pregnancy,
resulting in poor sensitivity.5,25
Although it is accepted that amniocentesis in primary
maternal CMV infection is warranted because of the high
risk of fetal infection, there is no consensus on whether to
perform amniotic fluid viral studies in cases of secondary
infection, when the risk of fetal infection is low. However,
there are several cases of secondary infection with severe
sequelae described in the literature; therefore, amniocente-
sis for prenatal diagnosis of fetal infection may be consid-
ered even in cases of secondary infection.3,29
Cytomegalovirus Infection in Pregnancy
Prognostic Markers of CMV Disease
One of the major limitations of prenatal diagnosis of CMV
is that positive results of amniotic fluid tests such as viral
isolation and PCR do not discriminate between infants who
will have symptoms at birth and those who will not.
The severity of the sonographically detected abnormalities
may aid in determining the prognosis of the fetus, but the
absence of sonographic findings does not guarantee a normal
outcome. Once fetal infection is diagnosed, serial ultra-
sound examinations should be done every 2 to 4 weeks to
look for signs of CMV infection (Table 2) that might help in
predicting the outcome. The ultrasound follow-ups should
be performed in a laboratory that is capable of diagnosing
the abnormalities outlined in Table 2, and preferably in a
referral centre.
Fetal MRI may improve the prognostic evaluation, espe-
cially when brain abnormalities are detected by ultrasound.
However, the role of fetal MRI in providing useful information
in fetuses with CMV still needs to be determined.30,31
The clinical significance of the viral load in amniotic fluid as
a prognostic factor has been investigated by several studies,
which showed that the CMV DNA load values in amniotic
fluid samples were significantly higher in the group of
APRIL JOGC AVRIL 2010 l 351
SOGC CLINICAL PRACTICE GUIDELINE
symptomatic than in the group of asymptomatic fetuses.32
However, a great number of values were found to overlap
between the two groups33,34; thus the role of quantitative
determination of CMV DNA in the amniotic fluid as a
prognostic factor of CMV disease still awaits confirmation.
PRENATAL TREATMENT AND PREVENTION OF
CONGENITAL CMV INFECTION
Despite advances in the diagnosis of fetal CMV infection,
there is no effective therapy, and the option of pregnancy
termination is often raised once fetal infection is detected by
ultrasound or amniocentesis or once a fetus is determined or
suspected to be affected.
A recent multicentre prospective cohort study of 157 preg-
nant women with confirmed primary CMV infection evalu-
ated the use of CMV-specific hyperimmune globulin for the
treatment and prevention of fetal CMV infection.32
Forty-five women had a primary infection more than 6 weeks
before enrolment, underwent amniocentesis, and had CMV
detected in the amniotic fluid. Thirty-one of these women
elected to receive intravenous treatment with
CMV-hyperimmune globulin (200 U/kg of the mother’s
body weight). Fourteen women declined treatment with
hyperimmune globulin, and 7 of them had infants who were
symptomatic at delivery. In contrast, only 1 of the 31 treated
women had an infant with clinical CMV disease at birth
although 15 of them were carrying fetuses with
ultrasonographic evidence of CMV disease.32 In the preven-
tion group, 37 received hyperimmune globulin, 6 (16%) of
whom had infants with congenital CMV infection, com-
pared with 19 of 47 women (40%) who did not receive
hyperimmune globulin. No adverse effects of
hyperimmune globulin were observed.32 These results offer
a potential measure to treat and prevent congenital CMV
infection. However, this was not a randomized controlled
trial, and further study is necessary prior to widespread
adoption of this strategy.
Regarding postnatal therapy, there is some evidence sug-
gesting a limited beneficial role for ganciclovir treatment of
neonates with symptomatic congenital CMV infection. A
few studies have demonstrated some hearing improvement
and less hearing deterioration in infants treated with
ganciclovir.33–35
The ultimate goal in prevention of congenital CMV infection
is to develop a vaccine, which would be administered to
seronegative women of childbearing age to prevent the
occurrence of primary CMV infection during pregnancy.
Until an effective vaccine is available, recommendations for
seronegative pregnant women with respect to CMV infection
include practising good personal hygiene such as avoiding
intimate contact with salivary secretions and urine from
352 l APRIL JOGC AVRIL 2010
young children and careful hand washing after changing
diapers and wiping secretions.33 Despite our assumption
that changing protective behaviours prevents child to
mother transmission of CMV during pregnancy, Adler et al.
did not show any benefit for such intervention.34 However,
their data also demonstrated that intervention is more effective
during pregnancy than before pregnancy, because pregnant
women are more motivated to adhere to recommendations
than non-pregnant women.35
The Question of Screening
Screening for CMV by serology has been and still is a
debated issue. Routine serologic screening for pregnant
women has never been recommended by any public health
authority.13 The screening, if done, should be performed at
the beginning of pregnancy or even prior to a planned
pregnancy. If a woman is seronegative, repeated examinations
during pregnancy should be done when there is clinical
suspicion. However, screening is usually done before
pregnancy for diseases such as rubella and varicella against
which immunization can be provided, whereas there is
currently no effective and safe immunization against CMV.
Moreover, because effective prenatal treatment options are
not yet available, the choices when a women is carrying a
baby with CMV infection or disease are limited to elective
termination of the pregnancy or expectant observation until
delivery. Prenatal testing, however, offers an opportunity to
educate women about behaviours, and precautionary measures
can be suggested to seronegative women.36 Moreover, routine
antibody testing, especially if done before pregnancy, may
help to differentiate between primary and secondary infection
in cases of suspected CMV infection during pregnancy.29
Naessens et al. evaluated a screening program for CMV in
which serological testing was performed at the first prenatal
visit; they showed that such screening allows the detection
of 82% of all congenital CMV infections.37 Nevertheless,
routine serologic testing of all pregnant women for CMV to
identify those who have acquired primary infection during
pregnancy is not currently recommended. Therefore,
serological testing for CMV should be used only in women
who develop influenza-like symptoms during pregnancy or
following detection of sonographic findings that are suggestive
of CMV infection and that cannot be explained by another
cause (placental insufficiency in case of IUGR and
oligohydramnios and fetal anemia in case of ascites etc.).
SUMMARY
Congenital CMV infection is the leading infectious cause of
mental retardation and sensorineural deafness. Once pri-
mary maternal CMV infection has been diagnosed, fetal
infection can be accurately determined by amniocentesis.
Prenatal counselling in case of fetal infection is difficult

because of our limited ability to predict outcome. Because
20% to 25% of infected fetuses will develop sequelae, ter-
mination of pregnancy should be discussed as one of the
management options. Currently, routine serologic testing of
all pregnant women is not recommended, and use of sero-
logic testing should be used only in pregnant women who
develop influenza-like illness or following detection of
sonographic findings suggestive of CMV infection.
RECOMMENDATIONS
The quality of evidence reported in this document has been
assessed using the evaluation of evidence criteria in the
Report of the Canadian Task Force on Preventive Health
Care (Table 1).
1. Diagnosis of primary maternal cytomegalovirus (CMV)
infection in pregnancy should be based on de-novo
appearance of virus-specific IgG in the serum of a preg-
nant woman who was previously seronegative, or on
detection of specific IgM antibody associated with low
IgG avidity. (II-2A)
2. In case of primary maternal infection, parents should be
informed about a 30% to 40% risk for intrauterine trans-
mission and fetal infection, and a risk of 20% to 25% for
development of sequelae postnatally if the fetus is
infected. (II-2A)
3. The prenatal diagnosis of fetal CMV infection should be
based on amniocentesis, which should be done at least
7 weeks after presumed time of maternal infection and
after 21 weeks of gestation. This interval is important
because it takes 5 to 7 weeks following fetal infection and
subsequent replication of the virus in the kidney for a
detectable quantity of the virus to be secreted to the
amniotic fluid. (II-2A)
4. The diagnosis of secondary infection should be based on
a significant rise of IgG antibody titre with or without the
presence of IgM and high IgG avidity. In cases of proven
secondary infection, amniocentesis may be considered,
but the risk–benefit ratio is different because of the low
transmission rate. (III-C)
5. Following a diagnosis of fetal CMV infection, serial ultra-
sound examinations should be performed every 2 to
4 weeks to detect sonographic abnormalities, which may
aid in determining the prognosis of the fetus, although it
is important to be aware that the absence of sonographic
findings does not guarantee a normal outcome. (II-2B)
6. Quantitative determination of CMV DNA in the
amniotic fluid may assist in predicting the fetal outcome.
(II-3B)
7. Routine screening of pregnant women for CMV by serol-
ogy testing is currently not recommended. (III-B)
Cytomegalovirus Infection in Pregnancy
8. Serologic testing for CMV may be considered for women
who develop influenza-like illness during pregnancy or
following detection of sonographic findings suggestive
of CMV infection. (III-B)
9. Seronegative health care and child care workers may be
offered serologic monitoring during pregnancy. Moni-
toring may also be considered for seronegative pregnant
women who have a young child in day care. (III-B)
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 SOGC CLINICAL PRACTICE GUIDELINE

SOGC CLINICAL PRACTICE GUIDELINENo. 239, February 2010

Obesity in Pregnancy
Abstract
This Clinical Practice Guideline has been prepared by the Objective: To review the evidence and provide recommendations for
Maternal Fetal Medicine Committee, reviewed by the Clinical the counselling and management of obese parturients.
Practice Obstetrics Committee, and approved by the Executive
and Council of the Society of Obstetricians and Gynaecologists of Outcomes: Outcomes evaluated include the impact of maternal
Canada obesity on the provision of antenatal and intrapartum care,
maternal morbidity and mortality, and perinatal morbidity and
PRINCIPAL AUTHORS mortality.
Gregory A.L. Davies, MD, Kingston ON Evidence: Literature was retrieved through searches of Statistics
Cynthia Maxwell, MD, Toronto ON Canada, Medline, and The Cochrane Library on the impact of
obesity in pregnancy on antepartum and intrapartum care,
Lynne McLeod, MD, Halifax NS maternal morbidity and mortality, obstetrical anaesthesia, and
MATERNAL FETAL MEDICINE COMMITTEE perinatal morbidity and mortality. Results were restricted to
systematic reviews, randomized controlled trials/controlled clinical
Robert Gagnon, MD (Chair), Montreal QC
trials, and observational studies. There were no date or language
Melanie Basso, RN, Vancouver BC restrictions. Searches were updated on a regular basis and
Hayley Bos, MD, London ON incorporated in the guideline to April 2009. Grey (unpublished)
literature was identified through searching the websites of health
Marie-France Delisle, MD, Vancouver BC technology assessment and health technology
Dan Farine, MD, Toronto ON assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
Lynda Hudon, MD, Montreal QC medical specialty societies.
Savas Menticoglou, MD, Winnipeg MB Values: The evidence obtained was reviewed and evaluated by the
William Mundle, MD, Windsor ON Maternal Fetal Medicine and Clinical Practice Obstetric
Committees of the SOGC under the leadership of the principal
Lynn Murphy-Kaulbeck, MD, Allison NB
authors, and recommendations were made according to
Annie Ouellet, MD, Sherbrooke QC guidelines developed by the Canadian Task Force on Preventive
Tracy Pressey, MD, Vancouver BC Health Care.

Anne Roggensack, MD, Calgary AB Benefits, Harms, and Costs: Implementation of the
recommendations in this guideline should increase recognition of
CLINICAL PRACTICE OBSTETRICS the issues clinicians need to be aware of when managing obese
Dean Leduc, MD (Chair), Ottawa ON women in pregnancy, improve communication and consultation
amongst the obstetrical care team, and encourage federal and
Charlotte Ballerman, MD, Edmonton AB provincial agencies to educate Canadians about the values of
Anne Biringer, MD, Toronto ON entering pregnancy with as healthy a weight as possible.
Louise Duperron, MD, Montreal QC Recommendations
Donna Jones, MD, Calgary AB 1. Periodic health examinations and other appointments for
gynaecologic care prior to pregnancy offer ideal opportunities to
Lily Shek-Yun Lee, MSN, Vancouver BC
raise the issue of weight loss before conception. Women should
Debra Shepherd, MD, Regina SK 2
be encouraged to enter pregnancy with a BMI < 30 kg/m , and
2
Kathleen Wilson, RM, Ilderton ON ideally < 25 kg/m . (III-B)

Disclosure statements have been received from all members of
the committees.
Key Words: Obesity, pregnancy, obstetric anaesthesia, Caesarean
section, body mass index, ultrasound, decision to delivery interval
2. BMI should be calculated from pre-pregnancy height and weight.
2
Those with a pre-pregnancy BMI > 30 kg/m are considered
obese. This information can be helpful in counselling women
about pregnancy risks associated with obesity. (II-2B)
3. Obese pregnant women should receive counselling about weight
gain, nutrition, and food choices. (II-2B)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

FEBRUARY JOGC FÉVRIER 2010 l 165

SOGC CLINICAL PRACTICE GUIDELINE
Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.79
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
Task Force on Preventive Health Care.79
4. Obese women should be advised that they are at risk for medical
complications such as cardiac disease, pulmonary disease,
gestational hypertension, gestational diabetes, and obstructive
sleep apnea. Regular exercise during pregnancy may help to
reduce some of these risks. (II-2B)
5. Obese women should be advised that their fetus is at an increased
risk of congenital abnormalities, and appropriate screening should
be done. (II-2B)
6. Obstetric care providers should take BMI into consideration when
arranging for fetal anatomic assessment in the second trimester.
Anatomic assessment at 20 to 22 weeks may be a better choice
for the obese pregnant patient. (II-2B)
7. Obese pregnant women have an increased risk of Caesarean
section, and the success of vaginal birth after Caesarean section
is decreased. (II-2B)
8. Antenatal consultation with an anaesthesiologist should be
considered to review analgesic options and to ensure a plan is in
place should a regional anaesthetic be chosen. (III-B)
9. The risk of venous thromboembolism for each obese woman
should be evaluated. In some clinical situations, consideration for
thromboprophylaxis should be individualized. (III-B)
J Obstet Gynaecol Can 2010;32(2):165–173
INTRODUCTION
T he people of industrialized nations, including Canada,
have experienced a dramatic increase in obesity in
recent times1 The proportion of overweight and obese
women in Canada rose from 34% in 1978 to 40% in 1992,
and in 2004 it was 53%.2,3 Of particular concern is the rapid
increase in overweight and obesity in Canada’s adolescents,
in whom rates have risen 100% since 1978.4 Rising rates of
obesity are associated with increasing time spent in front of
166 l FEBRUARY JOGC FÉVRIER 2010
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
the television and computer, a sedentary lifestyle, and poor
nutrition.4 The lifestyle that leads to obesity has a direct
effect on indicators of health. Women who are overweight
or obese are significantly more likely to suffer from high
blood pressure, diabetes, and heart disease.3 Concordantly,
rates of obesity in pregnancy are increasing.5 This guideline
examines the impact of obesity on maternal, fetal, and neo-
natal outcomes. Recommendations for the management of
obese patients in pregnancy are quantified according to the
evaluation of evidence guidelines developed by the
Canadian Task Force on Preventive Health Care (Table 1).
DEFINING OBESITY
The most clinically relevant definition of obesity is the body
mass index. BMI is weight in kilograms divided by height in
meters squared (kg/m2).6 Canadian guidelines for appropri-
ate BMI are aligned with those of the World Health Organi-
zation and separated into six categories (Table 2).3
Studies of the non-pregnant population show that increas-
ing values of BMI are associated with an increased risk for
cardiovascular disease, diabetes, osteoarthritis, and cancer.3
The definition of obesity in pregnancy varies by author and
includes women who are 110% to 120% of their ideal body
weight or > 91 kg (200 lbs) or who have a BMI > 30 kg/m2.
There is a paucity of information describing the prevalence
of overweight and obesity specifically in the pregnant popu-
lation. However, BMI data from the 2004 Canadian
 Obesity in Pregnancy

Community Health Survey estimate rates of obesity

Table 2. BMI classification
between 11% and 21% for women of child-bearing age.3
Women who were more active and had higher fruit and veg- Risk of developing
etable consumption had lower rates of obesity.3 Obesity in BMI range health problems

pregnancy is increasing. According to Nova Scotia’s Atlee Underweight < 18.5 Increased
perinatal database, using a definition of obesity as > 90 kg, Normal weight 18.5 to 24.9 Least
the rate of obesity rose from 3.2% in 1988 to 10.2% Overweight 25.0 to 29.9 Increased
in 2002.7 Obese Class I 30.0 to 34.9 High

Most obstetrical caregivers in Canada record pre- Obese Class II 35.0 to 39.9 Very high
pregnancy weight in the antenatal record, although docu- Obese Class III ³ 40.0 Extremely high
mentation of maternal height is inconsistent.7 Recent
evidence from the United States suggests that many
obstetrician- gynaecologists use BMI data to screen for obe-
sity.8 The identification of women at risk is not routinely Table 3. Pregnancy weight gain based on BMI
followed by interventions. Suggested strategies include
behavioural weight loss treatments and specific counselling BMI range Suggested weight gain (kg)

regarding exercise, diet, and pregnancy weight gain.8 Underweight < 18.5 12.5 to 18
Normal weight 18.5 to 24.9 11.5 to 16
WEIGHT GAIN IN PREGNANCY Overweight 25.0 to 29.9 7 to 11.5

Women should set pregnancy weight gain goals based on
their pre-pregnancy BMI as shown in Table 3.9
To achieve these goals women should be at the healthiest
weight possible when they enter pregnancy. During
well-woman checks and other health care interactions,
non-pregnant women of child-bearing age can be advised
of their BMI. An evaluation of dietary intake and exercise
habits can provide insight into women at risk.10 According
to the joint guidelines on exercise in pregnancy by the
SOGC and the Canadian Society for Exercise Physiology,
all pregnant women without contraindications should par-
ticipate in regular exercise.11 During prenatal visits women
can be questioned and advised about their diet and exercise
habits. Where available, nutritional counselling can be a
helpful adjunct for women not meeting the weight gain
guidelines in Table 3.12 Pregnancy outcomes are related to
maternal weight gain.13 Fifty-two percent of a Canadian
cohort of women gained more than the recommended
weight in pregnancy. Depending on pre-pregnancy BMI,
these pregnancies were at increased risk of macrosomia
> 4000 g, augmentation of labour, gestational hypertension,
and neonatal metabolic abnormalities. Regardless of BMI,
those women who gained the recommended amount of
weight in pregnancy had fewer adverse outcomes (Caesar-
ean section, gestational hypertension, birth weight < 2500 g
or ³ 4000 g).13
IMPACT OF OBESITY ON OBSTETRIC OUTCOMES
Ultrasound
With the exception of women who are underweight, most
women are best assessed at 18 to 22 weeks to allow better
Obese Class I 30.0 to 34.9 7
Obese Class II 35.0 to 39.9 7
Obese Class III ³ 40.0 7
evaluation of fetal structures.14,15 The sonographer’s ability
to evaluate fetal structures is largely dependent on maternal
size. Approximately 15% of normally visible structures will
be suboptimally seen in women with a BMI above the 90th
percentile.15 In women with a BMI above the 97.5th percen-
tile, only 63% of structures are well visualized. The ana-
tomic structures commonly less well seen with increasing
BMI include the fetal heart, spine, kidneys, diaphragm, and
umbilical cord.16 Repeat examinations 2 to 4 weeks later to
assess the fetal cardiac anatomy will reduce the number of
suboptimally viewed fetuses; however, 12% to 20%
(depending on BMI class) will remain poorly visualized.15
Obstetric care providers should take BMI into consider-
ation when arranging for fetal anatomic assessment in the
second trimester. Anatomic assessment at 20 to 22 weeks
may be a better choice for the obese pregnant patient.
The challenge of fetal ultrasound in obese mothers is
further complicated by evidence suggesting an increased
rate of fetal anomalies. Nuthalapaty and Rouse17 reviewed
17 studies published between 1978 and 2003 associating
maternal pre-pregnancy BMI with congenital anomalies.
They reported a two-fold increase in neural tube defects in
the offspring of obese women. A dose-response was noted,
with heavier women having an even higher risk. Their
report is supported by the findings of Anderson et al.18
Alarmingly, the protective effects of periconceptional folic

FEBRUARY JOGC FÉVRIER 2010 l 167

SOGC CLINICAL PRACTICE GUIDELINE
acid do not appear to benefit the obese woman.19 It is
unknown whether an increased dose of folic acid would
reduce the risk to that of a lean woman. In their review,
Nuthalapaty and Rouse17 also found associations between
obesity and risk of other congenital malformations such as
heart defects, ventral wall defects, and orofacial clefts but
commented that these data were less consistent.
Ultrasound estimation of fetal weight is not superior to
clinical estimation in the obese population.20 Although both
methods have an associated error of approximately 10%, in
the series reported by Field et al.,20 30% of obese women
had an ultrasound estimated fetal weight within 5 days of
delivery that was > 10% different from the actual birth
weight.
PREGNANCY COMPLICATIONS
Spontaneous Abortion
The risk of spontaneous abortion is increased in obese
women. Using a retrospective case–control model and a
sample size of 4932, Lashen et al.21 identified an odds ratio
for spontaneous abortion of 1.2 (95% CI 1.01 to 1.46) for
obese women (BMI > 30 kg/m2). The authors also identi-
fied an increased risk of recurrent early miscarriages (more
than 3 successive miscarriages < 12 weeks’ gestation) in the
obese population, odds ratio 3.5 (95% CI 1.03 to 12.01).21
Similar risks have been identified in obese women undergo-
ing in vitro fertilization therapy.22
Hypertensive Disorders of Pregnancy
Robinson et al.7 reviewed pregnancy outcomes stratified by
maternal pre-pregnancy weight, comparing women whose
weight was 55 to 75 kg with those whose weight was > 90 kg.7
In this 15-year retrospective review (1988–2002), there were
79 005 women between 55 and 75 kg, 9355 women between
90 and 120 kg (moderate obesity) and a further 779 women
> 120 kg (severe obesity). Compared with the normal
weight group, the odds ratio of pregnancy induced hyper-
tension for the moderate obesity group was 2.38 (95% CI
2.24 to 2.52). The odds ratio for the severe obesity group
was 3.00 (95% CI 2.49 to 3.62). Obesity also increased the
likelihood that women would experience more severe
forms of hypertensive complications. For the moderate
obesity group the odds ratio of severe pregnancy induced
hypertension, including HELLP syndrome, was 1.56 (95%
CI 1.35 to 1.80) and for the severe obesity group was 2.34
(95% CI 1.59 to 3.46). Relative to non-obese women there
was 1 excess case of pregnancy induced hypertension for
every 10 moderately obese women and every 7 severely
obese women.7 These findings have been confirmed by oth-
ers.23 In contrast, retrospective cohorts show a 24% to 60%
reduction in preeclampsia in nulliparous women who had
168 l FEBRUARY JOGC FÉVRIER 2010
increasing levels of exercise both during the pregnancy and
in the year prior to conception.24,25 Postulations on the pro-
tective mechanisms of exercise against preeclampsia
include enhanced placental growth and vascularity, preven-
tion and reduction of oxidative stress, and correction of
vascular endothelial dysfunction.26
Gestational Diabetes
It is well documented that rising rates of obesity in North
America are responsible for the concordant rise in type 2
diabetes in the general population.27 Pre-gestational diabe-
tes is more prevalent in obese women. Therefore, testing in
women with risk factors early in pregnancy is recom-
mended.28 Obese women are also at increased risk of
developing gestational diabetes.29 In a cohort of 16 102
women, Weiss et al.23 found that in contrast to control sub-
jects (BMI < 30 kg/m2), the odds ratio for obese women
(BMI 30 to 34.9 kg/m2) to develop gestational diabetes is
2.6 (95% CI 2.1 to 3.4) and for morbidly obese women
(BMI ³ 35 kg/m2) is 4.0 (95% CI 3.1 to 5.2). Not surpris-
ingly, obese women are also at increased risk of having a
macrosomic child. The likelihood of delivering an infant
weighing more than 4000 g was 1.7 times (95% CI 1.4 to
2.0) greater for obese and 2.0 times (95% CI 1.5 to 2.3)
greater for morbidly obese patients. The odds of delivering
an infant weighing more than 4500 g was 2.0 times (95% CI
1.4 to 3.0) and 2.4 times (95% CI 1.5 to 3.8) greater for
obese and morbidly obese patients, respectively.22 Physical
activity is inexpensive and can significantly reduce the risk
of gestational diabetes. Zhang et al.29 reported a significant
inverse relationship between the amount of weekly vigor-
ous activity and the risk for gestational diabetes. More rele-
vant to the obese population, they also reported a 34%
reduction in the development of gestational diabetes in
women who did not participate in vigorous exercise but
who did participate in brisk walking compared with those
who participated in easy pace walking.28 At a Canadian cen-
tre, regular walking has been used in addition to diet and
insulin as part of therapy for gestational diabetes. Com-
pared with a non-exercising matched control group, those
who included walking 25 to 40 minutes 3 to 4 times per
week were able to significantly reduce fasting and 1-hour
postprandial glucose levels using less insulin over fewer
injections. The study design did not permit comment on
perinatal outcomes.30
INTRAPARTUM COMPLICATIONS AND MANAGEMENT
Macrosomia and Shoulder Dystocia
Sheiner et al.31 analyzed pregnancy outcomes in a cohort of
126 080 deliveries. Patients with hypertension and diabetes
were excluded. Obese women (BMI > 30 kg/m2) had an

increased risk of fetal macrosomia with an odds ratio of 1.4
(95% CI 1.2 to 1.7). Sheiner et al.31 did not find an increased
risk for shoulder dystocia in the obese population. Jensen et
al.32 found similar results in their cohort. The use of antena-
tal ultrasound to detect fetal macrosomia is associated with
increased obstetric interventions such as induction of
labour and Caesarean section.33 Delpapa and
Mueller-Heubach33 reported 86 women with an estimated
fetal weight > 4000 g within 3 days of delivery. In 77%, the
ultrasound estimate was greater than the actual birth
weight.33 The rate of Caesarean section is affected when
sonographic examination indicates a macrosomic fetus.34
Parry et al.34 compared the rate of Caesarean section when
fetal macrosomia was incorrectly predicted by antenatal
ultrasound with the rate of Caesarean section in pregnancies
when antenatal ultrasound correctly predicted the fetal
weight not to be macrosomic. The estimated fetal weight
for the predicted macrosomic group was significantly
greater than that of the non-macrosomic group: 42.3% ver-
sus 24.3%, RR 1.74, (95% CI, 1.09 to 2.78).34 Although fetal
macrosomia is a risk factor for shoulder dystocia, the abso-
lute risk of a severe shoulder dystocia associated with
permanent impairment, or death, remains low.35 When the
sensitivity and specificity of ultrasound to predict a birth
weight > 4500 g are included, it is estimated that 3695
non-diabetic women would require Caesarean section to
prevent a single case of permanent brachial plexus injury
due to shoulder dystocia.35
Fetal Monitoring
External fetal monitoring is at times more difficult in the
presence of maternal obesity given the challenge of trans-
ducing the fetal heart through the maternal pannus. There is
no evidence to support the routine use of internal fetal
monitoring in this population, but it may be more effective
in some women.
Uterine Monitoring
There is increasing evidence that uterine contractility in
obese women, compared with normal weight women, may
be altered or impaired.36,37 It is unclear whether these alter-
ations in myometrial response may lead to abnormal labour
and the observed increase in risk of Caesarean delivery.
Monitoring contractions and ensuring adequate labour in
obese women poses a special challenge. Although most
obstetric care providers rely on manual palpation and/or
external tocometry, the use of an intrauterine pressure cath-
eter may be advantageous in some cases. Newer techniques,
such as electrohysterography, may prove superior to both
tocodynometry and intrauterine pressure assessment for
labour monitoring in this population.38
Obesity in Pregnancy
Caesarean Section
The risk of Caesarean section is increased in the obese
parturient. Dietz et al.39 analyzed 24 423 nulliparous women
stratified by pre-pregnancy BMI and pregnancy complica-
tions. The Caesarean section rate was 14.3% for lean
women (BMI < 19.8 kg/m2) and 42.6% for very obese
women (BMI ³ 35 kg/m2). Among women without any
complications, the relative risk of Caesarean section was 1.4
(95% CI 1.0 to 1.8) for overweight women (BMI 25 to
29.9 kg/m2), 1.5 (95% CI 1.1 to 2.1) for obese women (BMI
30 to 34.9 kg/m2), and 3.1 (95% CI 2.3 to 4.8) for very
obese women (BMI ³ 35 kg/m2).39 Large cohorts from dif-
fering jurisdictions show similar findings.22,40 The increase
in the rate of Caesarean section may be due, in part, to the
fact that overweight and obese nulliparous women progress
more slowly through the first stage of labour.41 When faced
with lack of descent in the second stage of labour, some
practitioners may opt for Caesarean section rather than
operative vaginal delivery because of concerns about fetal
macrosomia and shoulder dystocia. This may explain the
decreased operative vaginal delivery rate in some series.42
Obese women undergoing Caesarean section experience
more complications, including blood loss > 1000 mL,
increased operative time, increased postoperative wound
infection and endometritis, and need for vertical skin inci-
sion.43,44 Those obese women with diabetes who undergo
Caesarean section have an odds ratio for postoperative
wound infection of 9.3 (95% CI 4.5 to 19.2), and those who
require a vertical skin incision have a 12% rate of wound
complication serious enough to require opening the inci-
sion.43,45 Postoperative infections are even increased in
those obese women who have elective Caesarean section
with prophylactic antibiotics.46
Hospitals should ensure that there is an operating room
table that can accommodate morbidly obese parturients.
Similarly, hospitals and obstetrical caregivers should ensure
there are appropriate surgical instruments to adequately
visualize and operate on obese patients who require
Caesarean section.
Vaginal Birth After Caesarean Section
In the absence of contraindications, women who have had
their first child by Caesarean section are asked to consider
vaginal birth in subsequent pregnancies.47 The success of
vaginal birth after Caesarean section is commonly quoted at
80%.48 Obese women are less likely than their lean peers to
be successful in delivering vaginally after previous Caesar-
ean section. In women with a BMI > 29 kg/m2 the success
rate is 54% to 68%.49,50 The rate of success is further
reduced in even heavier women. Chauhan et al.51 found a
13% VBAC success rate in women > 300 lbs (136 kg). When
FEBRUARY JOGC FÉVRIER 2010 l 169
SOGC CLINICAL PRACTICE GUIDELINE
discussing VBAC, obstetric care providers should consider
the longer time required to prepare for and commence Cae-
sarean section in obese patients. This includes longer time
for patient transport and set-up in an operating room, lon-
ger time for establishment of anaesthesia, and longer time
from incision to delivery of the fetus. Obese women would
benefit from knowing the success rates for women in their
BMI group when they make a decision about vaginal birth
after Caesarean section.
Obstetric Anaesthesia
Rates of difficult or failed tracheal intubations are increased
in obese parturients.52 A 6-year review of failed intubations
in obstetric patients in a United Kingdom region reported
36 cases of failed intubation; the average BMI of these
women was found to be 33.53 The equipment and expertise
required to manage a difficult intubation should be readily
available. In obese patients the risk of epidural failure is
increased. The initial failure rate for epidural catheter place-
ment can be very high (42%),54 and multiple attempts at
catheter placement may be required. More than a single
attempt is necessary for successful epidural placement in
approximately 75% of morbidly obese parturients. and
more than three attempts are needed in 14%.55 The use of
regional anaesthesia may require significant time and staff
resources, which may limit its use in some health care set-
tings. Techniques to improve the success of regional anaes-
thesia in obese pregnant women, such as ultrasound guid-
ance, will require further investigation in obstetrics.56 Given
the increased risks of regional anaesthesia in this popula-
tion, and dependent on the wishes of the patient, consider-
ation should be given to early epidural in labour. Obese
women have an increased risk for sleep apnea, which may
influence the choice of location for postoperative care for
obese parturients.
Caesarean Section and Decision to Delivery Interval
The decision to delivery interval may be longer when an
emergent or urgent Caesarean section is required for an
obese parturient. Causes for this delay may include patient
transport and bed transfer, the establishment of adequate
analgesia, and the operative time from incision to delivery.
The performance of emergent Caesarean section within
30 minutes is an arbitrary threshold rather than an evi-
dence-based standard. Thomas et al.57 reviewed 17 780
emergency Caesarean sections performed in 2000 in Eng-
land and Wales. Only 22% of women were delivered within
30 minutes. Of the 4622 Caesarean sections performed for
immediate threat to the life of the mother or fetus only 46%
were achieved within 30 minutes. There was no difference
noted in the rate of 5-minute Apgar scores < 4 or < 7, or the
rate of stillbirth between those delivered less than 15
170 l FEBRUARY JOGC FÉVRIER 2010
minutes and those delivered between 16 and 75 minutes
after the decision to proceed to Caesarean section.57 There
are no published data from Canadian centres that indicate
whether obstetric providers can reliably meet this arbitrary
standard. There are no published data that address decision
to delivery interval in obese patients.
Thromboembolism
The risk of thromboembolism is increased in obese
parturients. Edwards et al.58 reported 683 obese women
(BMI > 29 kg/m2) who were matched to 660 women of
normal weight (BMI 19.8 to 26.0 kg/m2). The incidence of
thromboembolism was 2.5% in the obese women, and only
0.6% in the control subjects.58 The Royal College of Obste-
tricians and Gynaecologists (RCOG) in the United King-
dom recommends thromboprophylaxis for 3 to 5 days,
using low molecular weight heparin after vaginal delivery
for women who are over age 35 and have a pre-pregnancy
or early pregnancy BMI > 30 kg/m2 or weight > 90 kg.59 In
addition, the RCOG recommends thromboprophylaxis
before and for 3 to 5 days following Caesarean section for
women with a pre-pregnancy or early pregnancy BMI > 30
kg/m2 or with a current weight > 80 kg. The RCOG also
recommends considering thromboprophylaxis in
“extremely obese” women who are hospitalized
antenatally.59,60 However, the Pregnancy and Thrombosis
Working Group in the United States does not concur with
the RCOG guidelines. This group recommends consider-
ation of thromboprophylaxis for patients who are obese, on
bed rest, or having surgery.61 There have been no random-
ized controlled trials regarding thromboprophylaxis when
there are additional factors to consider in the obese
parturient. Therefore, the risk of venous thromboembolism
for each obese woman should be evaluated. Depending on
the clinical situation, consideration for thromboprophylaxis
should be individualized.
PERINATAL OUTCOMES
The most prevalent risk factor for unexplained stillbirth is
pre-pregnancy obesity.62 The odds ratio for stillbirth is 2.79
(95% CI 1.94 to 4.02) for morbidly obese women (BMI ³
35 kg/m2).63 The mechanisms suggested for increased still-
birth risk in the obese woman include a decreased ability to
perceive a reduction in fetal movement, hyperlipidemia
leading to atherosclerosis affecting placental blood flow,
and increased snoring and sleep apnea associated with oxy-
gen desaturation and hypoxia.57
There is a growing body of literature demonstrating the in
utero environment is a predictor of future neonatal, child,
and adult health.64 In the Growing Up Today Study, a
cohort of over 14 000 adolescents in the United States, a
1 kg increment in birth weight in full-term infants was

associated with an approximately 50% increase in the risk of
being overweight at ages 9 to 14 years.65 This is especially
true for the offspring of women who experienced gesta-
tional diabetes during the pregnancy.63 In the Hypertension
in Pregnancy Offspring Study, Himmelmann et al.66
reported that neonates born to women who were hyperten-
sive during pregnancy appear to have a propensity to
impaired glucose tolerance in later childhood.66 Taittonen et
al.67 have also reported an increased risk of hypertension in
the children of women who are hypertensive during pregnancy .
THERAPY AND MANAGEMENT
All women should be encouraged to participate in regular
physical exercise during their pregnancy.11 Joint recommen-
dations by the SOGC and the Canadian Society for Exercise
Physiology were published in 2003.11 It is recommended
that women exercise four times weekly at moderate inten-
sity. The actual effect of these recommendations is hard to
measure because of the difficulty of behavioural change
assessment; however, the rising obesity rate in the Canadian
pregnant population and the maternal and neonatal
sequelae described above are most disturbing. Heart rate
target zones for previously sedentary obese pregnant
women have recently been developed, using a Canadian
population. Davenport et al. recommend target heart rate
zones of 102 to 124 beats per minute in obese women
aged 20 to 29, and 101 to 120 beats per minute in those aged
30 to 39.68
Nutritional counselling and dietary records may be helpful
in guiding overweight and obese women with respect to
adequate weight gain during pregnancy. Ideally these should
be offered prior to pregnancy so that health status can be
optimized before conception.69 The role of behavioural
therapy and caloric restriction in obese women to prevent
excess weight gain has not been established. Randomized
controlled studies using behavioural intervention in normal
weight and obese women with the goal of preventing excess
weight gain have been inconclusive.70 A systematic review
examining energy and protein restriction as preventive
strategies to avoid adverse perinatal outcomes concluded
these measures are unlikely to be beneficial and may pose
harm to the developing fetus.71
The rate of unintended pregnancy increases following
bariatric or gastric bypass surgery in morbidly obese
women. Although this therapy is not recommended during
pregnancy, it may arise as a discussion point during
pre-pregnancy or postpartum visits. New evidence and sys-
tematic reviews suggest that weight loss surgery is more
effective than conventional treatments in morbid obesity
(Table 2). Thus, women who meet the criteria may benefit
from counselling and consultation with obesity surgery
Obesity in Pregnancy
specialists.72 A limited but growing body of literature
regarding pregnancy outcomes in women who have
undergone obesity surgery suggests reassuring outcomes;
however, there are reports of significant complications such
as nutrient deficiency, severe fetal growth restriction, and
maternal bowel obstruction.73–78
SUMMARY
It is critical that women be informed prior to pregnancy
about the need to be as healthy as possible before becoming
pregnant, which includes having a normal BMI, eating a bal-
anced diet, and participating in regular exercise. It is also
critical that provincial and federal authorities recognize the
impact on future populations and health care costs of preg-
nancies complicated by obesity. A long-term national infor-
mation campaign is required to exploit women’s interest in
having as healthy a pregnancy as possible by giving them the
information they need to become fit and have a normal
BMI before they consider pregnancy. Only a national strat-
egy can change the complacency about pre-pregnancy
weight and inform women about the significant increase in
risks for themselves and their children.
Recommendations
1. Periodic health examinations and other appointments for
gynaecologic care prior to pregnancy offer ideal oppor-
tunities to raise the issue of weight loss before concep-
tion. Women should be encouraged to enter pregnancy
with a BMI < 30 kg/m2, and ideally < 25 kg/m2. (III-B)
2. BMI should be calculated from pre-pregnancy height and
weight. Those with a pre-pregnancy BMI > 30 kg/m2 are
considered obese. This information can be helpful in
counselling women about pregnancy risks associated
with obesity. (II-2B)
3. Obese pregnant women should receive counselling about
weight gain, nutrition, and food choices. (II-2B)
4. Obese women should be advised that they are at risk for
medical complications such as cardiac disease, pulmo-
nary disease, gestational hypertension, gestational
diabetes, and obstructive sleep apnea. Regular exercise
during pregnancy may help to reduce some of these
risks. (II-2B)
5. Obese women should be advised that their fetus is at an
increased risk of congenital abnormalities, and appropri-
ate screening should be done. (II-2B)
6. Obstetric care providers should take BMI into consider-
ation when arranging for fetal anatomic assessment in
the second trimester. Anatomic assessment at 20 to
22 weeks may be a better choice for the obese pregnant
patient. (II-2B)
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SOGC CLINICAL PRACTICE GUIDELINE
7. Obese pregnant women have an increased risk of Caesar-
ean section, and the success of vaginal birth after Caesar-
ean section is decreased. (II-2B)
8. Antenatal consultation with an anaesthesiologist should
be considered to review analgesic options and to ensure a
plan is in place should a regional anaesthetic be
chosen. (III-B)
9. The risk of venous thromboembolism for each obese
woman should be evaluated. In some clinical situations,
consideration for thromboprophylaxis should be indi-
vidualized. (III-B)
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FEBRUARY JOGC FÉVRIER 2010 l 173
 SOGC CLINICAL PRACTICE GUIDELINE
SOGC CLINICAL PRACTICE GUIDELINE
Oral Contraceptives and the Risk of Venous
Thromboembolism: An Update
This clinical practice guideline has been reviewed by the Clinical
Practice Gynaecology Committee and approved by the Executive
and Council of the Society of Obstetricians and Gynaecologists
of Canada.
PRINCIPAL AUTHOR
Robert Reid, MD, Kingston, ON
CLINICAL PRACTICE GYNAECOLOGY COMMITTEE
Nicholas Leyland, MD (Co-Chair), North York ON
Wendy Wolfman, MD (Co-Chair), Toronto ON
Catherine Allaire, MD, Vancouver BC
Alaa Awadalla, MD, Winnipeg MB
Carolyn Best, MD, Toronto ON
Sheila Dunn, MD, Toronto ON
Madeleine Lemyre, MD, Quebec QC
Violaine Marcoux, MD, Ville Mont-Royal QC
Chantal Menard, RN, Ottawa ON
Frank Potestio, MD, Thunder Bay ON
David Rittenberg, MD, Halifax NS
Sukhbir Singh, MD, Ottawa ON
Vyta Senikas, MD, Ottawa ON
Disclosure statements have been received from all members of
the committee.
The literature searches and bibliographic support for this guideline
were undertaken by Becky Skidmore, Medical Research Analyst,
Society of Obstetricians and Gynaecologists of Canada.
Abstract
Objective: To provide current and emerging evidence on oral
contraceptives and the risk of venous thromboembolism.
Evidence: Articles published in English from 2005 were retrieved
through searches of PubMed and Medline, using the following
terms: venous thromboembolism, VTE, contraception, oral
Key Words: Venous thromboembolism, VTE, contraception,
oral contraceptives, hormonal contraception
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should
not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
1192 l DECEMBER JOGC DÉCEMBRE 2010
No. 252, December 2010
contraceptives, hormonal contraception. Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. Searches were updated on a
regular basis and incorporated in the guideline to May 2010. Grey
(unpublished) literature was identified through searching the
websites of health technology assessment and health technology
assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
medical specialty societies.
Values: The quality of evidence was rated using the criteria described
by the Canadian Task Force on Preventive Health Care (Table).
Summary Statements
1. Modern oral contraceptives offer highly effective contraception and
a range of non-contraceptive benefits. (I)
2. Venous thromboembolism, although rare, remains one of the
serious adverse consequences of hormonal contraception. Best
evidence indicates that venous thromboembolism rates in
non-users of reproductive age approximate 4–5/10 000 women
per year; rates in oral contraceptive users are in the range of
9–10/10 000 women per year. For comparison, venous
thromboembolism rates in pregnancy approach 29/10 000 overall
and may reach 300–400/10 000 in the immediate postpartum
period. (II-1)
3. Research demonstrates that oral contraceptives with £ 35 µg
of ethinyl estradiol carry a lower risk of venous thromboembolism
than oral contraceptives with 50 µg. (II-2) Although preliminary
data suggest a possible further reduction in venous
thromboembolism with oral contraceptives with < 35 µg ethinyl
estradiol, robust data to support this conclusion are presently
lacking.
4. Recent contradictory evidence and the ensuing media coverage
of the venous thromboembolism risk attributed to the progestin
component of certain newer oral contraceptive products have led
to fear and confusion about the safety of oral contraceptives in
general and drospirenone-containing oral contraceptives in
particular. “Pill scares” of this nature have occurred in the past,
with panic stopping of the pill, increased rates of unplanned
pregnancy, and no subsequent decrease in venous
thromboembolism rates. (II-3)
5. Two high quality research studies that addressed the venous
thromboembolism risk associated with various oral contraceptives
found comparable venous thromboembolism rates with
drospirenone-containing oral contraceptives and other approved
products. (II-1)
6. Two reports suggesting an increased risk of venous thromboembolism
with drospirenone-containing oral contraceptives have significant
 Oral Contraceptives and the Risk of Venous Thromboembolism: An Update
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.35
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.35
methodological flaws that render their conclusions suspect. It seems
likely that residual confounding could have distorted both the
results and the conclusions of these reports. (II-3)
J Obstet Gynaecol Can 2010;32(12):1192–1197
INTRODUCTION
odern oral contraceptives afford not only excellent
M contraception but also a variety of non-contraceptive
benefits, ranging from regulation and reduction of both
menstrual bleeding and dysmenorrhea to treatment of
premenstrual syndrome, menstrual migraines, acne, and
hirsutism. Long-term benefits include reduced rates of
endometrial, ovarian, and colorectal cancer.1 Modern OCs
are well tolerated (serious side effects are rare), and adherence
to prescribed regimens is generally excellent. As a result,
OC users are able to prevent pregnancy and the considerable
risks associated with being pregnant while enjoying the
non-contraceptive benefits of hormonal contraception.
ABBREVIATIONS
FDA US Food and Drug Administration
OC oral contraceptives
VTE venous thromboembolism
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
VENOUS THROMBOEMBOLISM
Risk Factors
Venous thromboembolism is a rare but potentially serious
condition, usually involving a blood clot in the deep veins of
the legs or pelvis. If the clot breaks away into the circulation
it may block blood flow to the lungs (pulmonary embolism)
with potentially fatal consequences. Known risk factors for
VTE include advancing age,2 cigarette smoking,3 immobility
(such as that associated with travel or hospitalization),4
obesity,5 and pregnancy and the peripartum period.6,7
Hormonal Effects on Venous
Thromboembolism
Hormonal contraceptives increase the risk of VTE above
the background rate (from 5/10 000 woman years in non-
users8 to 9–10/10 000 woman years in OC users9).
To keep the risks of VTE for OC users in perspective, it is
important to remember that the risk of VTE in pregnancy
may reach 29/10 000,9,10 and in the peripartum period the
risk has been reported to be as high as 300–400/10 000.6,7
Among the most widely used and effective contraceptive
methods, OCs reduce rates of unplanned pregnancies and
actually decrease the overall rate of VTE in the population
compared with rates in populations without access to effec-
tive contraception.11
Older OCs, which contained higher levels of estrogen, carried
a slightly greater risk than currently available OCs, most of
DECEMBER JOGC DÉCEMBRE 2010 l 1193
SOGC CLINICAL PRACTICE GUIDELINE
which contain < 50 µg of ethinyl estradiol. Sub-50 µg pills
have a lower risk of VTE than pills with ³ 50 µg.12 Although,
in theory, greater reductions in the dosage of estrogen
might further decrease the risk of VTE, this benefit has not
been clearly established. A non-significant decrease in VTE
was noted in the European Active Surveillance Study when
OCs containing 30µg ethinyl estradiol were compared with
those containing 20µg.9 Lidegaard et al.13 also reported that
“a reduction in estrogen dose from 30–40 µg to 20 µg for
OCs containing desogestrel or gestodene reduced the risk
of venous thromboembolism by 18%”; however, the valid-
ity of the VTE diagnoses in the Danish National Patient
Registry (1 of 4 registries used by the Lidegaard et al. study)
has been questioned.14
Many pills with ethinyl estradiol levels lower than 35 µg are
currently on the market, and although they may be associated
with fewer estrogen-related nuisance side effects (such as
nausea or breast tenderness) in the first months of use, no
conclusive data exist to establish that they result in a lower
risk of VTE. Pills with £ 20 µg of ethinyl estradiol have the
potential to cause more breakthrough (unscheduled) bleeding,
and this may be a deterrent to consistent use for some
women.15
Innovations in hormonal contraception in recent years have
largely involved the use of new progestins, and this has
brought the progestin component of the OC under increasing
scrutiny. New progestins are, in part, responsible for some
of the most desired non-contraceptive benefits, while main-
taining a low risk of serious side effects.
Third generation pills have been promoted as being less
androgenic and as possibly having fewer adverse effects on
cardiovascular and metabolic parameters and therefore as
being safer than existing pills. Shortly after the introduction
of these third generation pills, reports of a possible increased
risk of VTE began to appear, bringing the progestin com-
ponent of these pills under scrutiny. A phenomenon called
“stimulated reporting” occurred: physicians with patients
on these new pills were more likely to send their patients for
assessment of any leg pain and more likely to report any
VTE episodes to regulatory authorities because of height-
ened awareness of the possible risk. What followed was the
“pill scare” in 1995, when regulatory authorities issued an
alert about the possible increased risk of VTE with third
generation pills. The abrupt rise in births and abortions16,17
(each associated with an increased risk of VTE) that resulted
from unplanned pregnancies indicated that many women
stopped taking OCs because of this scare. The history of
this unfortunate episode is well-documented.18,19 Subsequent
analysis and/or replication has shown systematic error in the
epidemiological studies that examined VTE risks. The precise
effects of different hormonal contraceptives on the hemostatic
1194 l DECEMBER JOGC DÉCEMBRE 2010
system continue to be studied and debated,20 but because
there were no compelling data demonstrating an increased
risk, third generation pills remain on the market and are
widely prescribed.21
Assessing Venous Thromboembolism Risks
of Oral Contraceptives
VTE remains one of the few serious side effects of OC use.
Because VTE is so rare, valid information about the risks
associated with a given pill cannot be adequately gleaned
from pre-marketing research, which may involve only 1000
to 3000 women. Information on serious but rare side effects
like VTE must come from post-marketing surveillance.
The current Canadian system requires that health care pro-
viders voluntarily report unexpected or severe adverse
reactions to drugs to Health Canada. Although such a system
can alert regulatory authorities to rare unexpected side
effects of a medication, it cannot provide valid information
about the rates of complications or inform consumers
about the comparative risks of available products. This is
because newer products tend to be prescribed for women
who already have risk factors. For example, drospirenone-
containing pills, which are effective in reducing acne and
hair growth, tend to be prescribed for women who are
obese and who therefore already have an independent risk
factor for a blood clot. Isolated reports of serious side
effects of a specific OC may motivate health care providers
to be more vigilant in looking for and reporting similar
cases (stimulated reporting). Numerators in adverse event
reporting are therefore selectively biased towards certain
products, which may give a misleading impression of risk.
Since denominators (the number of women using a particular
product) and risk factors in the entire population of women
prescribed a specific type of OC are unknown, voluntary
reports of individual cases cannot provide valid information
on comparative risks for rare but serious side effects.
Another suggested methodology is to try to obtain more
comprehensive data by retrospectively searching large
databases for use of specific products and establish links between
their use and complications like VTE. These techniques
may be useful if the original data set includes information
on age, weight, duration of use, etc., which are important
independent risk factors that might influence risks for VTE.
In the absence of quality data on such variables, it is possible
that a risk apparently associated with a specific OC is
actually associated with the characteristics of the women
who were taking that OC. Databases, especially those
developed for administrative purposes, may lack adequate
validation of discharge diagnoses. A 2010 study has shown
that conditions signed out as VTEs in an administrative
database are often found to be something else when testing
is completed.14 A valid comparison of VTE risk with
 Oral Contraceptives and the Risk of Venous Thromboembolism: An Update
different OCs must consider the fact that the risk for VTE
is greatest in the first months of use and declines thereaf-
ter.9,22–24 This same effect was noted in the largest random-
ized clinical trial to examine VTE in menopausal women
receiving hormone therapy at the time of menopause.25
Comparisons of the VTE risks for different OCs must
account for duration of use and ensure that new users of
one pill are truly being compared with new users of the
other pill.
RECENT RESEARCH
Legitimate information on these rare risks is most likely to
come from research that uses a prospective approach with
subjects who are all new users of various OCs. Careful follow-
up by active surveillance (regular patient contact) and
validation of all suspected cases (through examination of
the medical records) is critical.
The European Active Surveillance Study was conducted
by the manufacturer of a new drospirenone-containing
OC with an independent advisory board and after approval
by European regulatory authorities. This prospective non-
interventional active surveillance study followed 59 674 new
users of different OCs for a total of 142 475 woman years,
with a loss to follow-up of only 2.4%. The study demonstrated
that drospirenone-containing OCs were prescribed more
often to heavier women and that despite this there was no
difference in VTE rates between users of this new
drospirenone- containing OC and other OCs.
Another large prospective study used a propensity (risk factor)
scoring system to match new users of different pills according
to baseline VTE risk.26,27 This study matched new OC pre-
scriptions (drospirenone-containing OCs vs. other OCs in a
2:1 ratio) and evaluated the medical records of all potential
VTE episodes. No differences in VTE rates were found
between drospirenone-containing OCs and other OCs.
Recent publicity about class action litigation in the US and
Canada over complications related to drospirenone-
containing OCs has again raised questions about whether
VTE rates are higher with drospirenone-containing OCs.
Critical analysis of the 2 studies responsible for this adverse
publicity,13,28 however, suggests that the conclusions could
have resulted from methodologic flaws and/or misinterpre-
tation of findings, a view shared by the FDA.29
The Dutch Mega Study,28 a retrospective case-control study,
was designed to evaluate environmental and genetic factors
influencing VTE and the effects of different OCs on VTE.
Controls were found in an unusual way: many were the
partners of men who were seen in a thrombosis clinic, and
the remainder were recruited through random-digit dialling.
The authors showed hazard ratios for various OCs with
wide and overlapping 95% confidence intervals indicating
no statistically significant differences between drospirenone
and so-called second generation progestins. Duration of use
information was not available on all women, so it is not
clear that all were new users. In addition, the risk estimates
were not adjusted for important risk factors (such as obesity).
Despite this the authors concluded that second generation
OCs were safer than third generation as far as VTE was
concerned. The FDA has recently revised the product labelling
for a drospirenone-containing OC, and with respect to the
Dutch Mega Study notes that “The number of [drospirenone-
containing OC] cases (in the Dutch Mega Study) was very
small (1.2% of all cases) making the risk estimates
unreliable.”29
The other study reporting increased rates of VTE with
drospirenone-containing and other third generation OCs
was a large Danish national cohort study.13 It consisted of a
retrospective examination of Danish women who had
prescriptions for hormonal contraception and subsequent
hospital diagnostic codes for deep vein thrombosis between
1995 and 2005 in a number of interrelated databases
maintained by the Danish national health service. This com-
prehensive data set included 3.4 million woman years of
hormonal contraceptive use. The investigators identified
2045 hormonal contraceptive-related VTEs during this
time period. In keeping with prior reports, they found that
the risk of VTE decreased with duration of use and with
pills containing lower estrogen dosages. In contrast to the
prospective studies reported above, they found that
drospirenone-containing OCs and other third generation
OCs (those containing desogestrel, gestodene) carried an
increased risk of VTE compared with levonorgestrel-
containing OCs. Several significant methodological weak-
nesses have been identified since the publication of that
report.13 First, detailed information on confounders such as
obesity was not available for the analysis. This is important:
obesity rates in the Danish population have almost tripled
in the past decade, and evidence from other research
suggests that obese women are more likely to be prescribed
drospirenone-containing OCs because of the perceived
beneficial effects on androgenic symptoms that affect many
obese women and on body weight (diuretic effect). In
addition, the investigators had no information on OC use
before 1995. Therefore, they classified all levonorgestrel use
in 1995 as short-term use, but others have estimated that
60% of those levonorgestrel users should have been
classified as long-term users.30 Supporting this premise was
the finding that the expected first year elevation of VTE risk
was seen with all OCs except the levonorgestrel products.
More importantly, the incidence of VTE could not reliably
be assessed in the Danish registry.14 Severinsen et al.14
examined the medical records of patients with a diagnosis of
DECEMBER JOGC DÉCEMBRE 2010 l 1195
SOGC CLINICAL PRACTICE GUIDELINE
VTE in the same Danish registry used for the Lidegaard et al.13
study and could confirm only 31% of diagnoses made
through emergency room visits and only 71% of those
made in women admitted to the ward for diagnostic testing.
The Danish database was designed as an administrative
database rather than as a medical research database, and the
diagnostic codes were primarily intended to capture costs
related to hospitalization. Many physicians were incorrectly
entering a diagnostic code for VTE rather than the intended
code of “admitted for evaluation of possible VTE.”14
The increased rate ratio of VTEs with drospirenone-
containing OCs compared with levonorgestrel containing
OCs was 1.64 (95% CI 1.27 to 2.10). With the potential
methodological issues identified above and with rate ratios
that in epidemiological terms are very small (relative risks of
£ 2), it is extremely difficult to exclude bias or residual con-
founding as the explanation for the findings.30–33 Despite
the recent serious allegations about the validity of the VTE
diagnostic codes in the Danish database, the authors of this
research have yet to acknowledge the possibility that their
data were invalid and their conclusions incorrect.34 The new
FDA-endorsed product labelling for a drospirenone-
containing OC addresses the Lidegaard et al. study and
concludes, “The risk estimates may not be reliable because
the analysis may include women of varying risk levels.”29
CONCLUSION
The highest quality scientific studies evaluating the risk of
VTE in OC users show a baseline risk of approximately
4–5/10 000 woman years in women who do not use
hormonal contraception. In the absence of reliable contra-
ception, women of reproductive age face risks of VTE
associated with pregnancy of up to 29/10 000 woman years,
and in the immediate postpartum period this risk is as high
as 300–400/10 000 woman years. Prospective observa-
tional studies have shown that all currently available OCs
increase the risk of VTE to the range of 9–10/10 000
woman years of use and that this risk is highest in the first
months of use, with a fall towards baseline risk thereafter.
Modern OCs offer excellent contraceptive efficacy, and
adherence is good because of their many non-contraceptive
benefits. The occurrence of serious risks such as VTE,
including pulmonary embolism, are rare with contemporary
OCs, but individualized risk assessment should always be
unertaken to identify women who would be better advised
to use other forms of contraception. For most healthy
women of reproductive age, the benefits of OCs will
outweigh the risks.
1196 l DECEMBER JOGC DÉCEMBRE 2010
Summary Statements
1. Modern oral contraceptives offer highly effective
contraception and a range of non-contraceptive
benefits. (I)
2. Venous thromboembolism, although rare, remains one
of the serious adverse consequences of hormonal
contraception. Best evidence indicates that venous
thromboembolism rates in non-users of reproductive
age approximate 4–5/10 000 women per year; rates
in oral contraceptive users are in the range of
9–10/10 000 women per year. For comparison,
venous thromboembolism rates in pregnancy approach
29/10 000 overall and may reach 300–400/10 000
in the immediate postpartum period. (II-1)
3. Research demonstrates that oral contraceptives with
£ 35 µg of ethinyl estradiol carry a lower risk of venous
thromboembolism than oral contraceptives with 50 µg.
(II-2) Although preliminary data suggest a possible
further reduction in venous thromboembolism with
oral contraceptives with < 35 µg ethinyl estradiol,
robust data to support this conclusion are presently
lacking.
4. Recent contradictory evidence and the ensuing media
coverage of the venous thromboembolism risk
attributed to the progestin component of certain
newer oral contraceptive products have led to fear
and confusion about the safety of oral contraceptives
in general and drospirenone-containing oral
contraceptives in particular. “Pill scares” of this
nature have occurred in the past, with panic stopping
of the pill, increased rates of unplanned pregnancy,
and no subsequent decrease in venous
thromboembolism rates. (II-3)
5. Two high quality research studies that addressed the
venous thromboembolism risk associated with
various oral contraceptives found comparable venous
thromboembolism rates with
drospirenone-containing oral contraceptives and
other approved products. (II-1)
6. Two reports suggesting an increased risk of venous
thromboembolism with drospirenone-containing oral
contraceptives have significant methodological flaws
that render their conclusions suspect. It seems likely
that residual confounding could have distorted both
the results and the conclusions of these reports. (II-3)
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2. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton
L J 3rd. Trends in the incidence of deep vein thrombosis and pulmonary
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1998;158:585–93.
3. Pomp ER, Rosendaal FR, Doggen CJM. Smoking increases the risk
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4. Cannegieter SC, Doggen CMJ, van Houwelingen HC, Rosendaal FR.
Travel-related venous thrombosis: results from a large population-based
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5. Pomp ER, le Cessie S, Rosendaal FR, Doggen CJR. Risk of venous
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6. Ros HS, Lichtenstein P, Belloco R, Petersson G, Cnattingius S. Increased
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Epidemiology 2001;12:456–60.
7. Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJM. Pregnancy, the
postpartum period and prothrombotic defects: risk of venous thrombosis
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8. Heinemann LAJ, Dinger JC. Range of published estimates of venous
thromboembolism incidence in young women. Contraception
2007;75:328–36.
9. Dinger JC, Heinemann LAJ, Kuhl-Habich D. The safety of a
drospirenone-containing oral contraceptive: final results from the European
Active Surveillance study on Oral Contraceptives based on 142,475
women-years of observation. Contraception 2007;75:344–54.
10. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd.
Trends in the incidence of venous thromboembolism during pregnancy
or postpartum: a 30-year population-based study. Ann Intern Med
2005;143:697–706.
11. Ory HW. Mortality associated with fertility and fertility control: 1983.
Fam Plann Perspect 1983;15:57–63.
12. Gerstman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Lundin FE.
Oral contraceptive estrogen dose and the risk of deep venous thromboembolic
disease. Am J Epidemiol 1991;133:32–7.
13. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Hormonal contraception
and risk of venous thromboembolism: national follow-up study. BMJ
2009;339: b2890.
14. Severinsen MT, Kristensen SR, Overvad K, Dethlefsen C, Tjønneland A,
Johnsen SP. Venous thromboembolism discharge diagnoses in the Danish
National Patient Registry should be used with caution. J Clin Epidemiol
2010;63:223–8.
15. Gallo MF, Nanda K, Grimes DA, Schulz KF. Twenty micrograms vs.
> 20 microg estrogen oral contraceptives for contraception: systematic
review of randomized controlled trials. Contraception 2005;71:162–9.
16. Mills A. Combined oral contraception and the risk of venous thromboembolism.
Hum Reprod 1997;12:2595–8.
17. Goodyear-Smith A, Arroll B. Termination of pregnancy following panic-stopping
of oral contraceptives. Contraception 2002;66:163–7.
18. Spitzer WO. The aftermath of a pill scare: regression to reassurance.
Hum Reprod Update 1999;5:736–45.
19. Lewis MA, MacRae KD, Kuhl-Habichl D, Bruppacher R, Heinemann LA,
Spitzer WO. The differential risk of oral contraceptives: the impact of full
exposure history. Hum Reprod 1999;14:1493–9.
20. Hennessy S, Berlin JA, Kinman JL, Margolis DJ, Marcus SM, Strom BL.
Risk of venous thromboembolism from oral contraceptives containing
gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal
sensitivity analysis. Contraception 2001;64:125–33.
21. Spitzer WO. The 1995 pill scare revisited: anatomy of a non-epidemic.
Hum Reprod 1997;12:2347–57.
22. Suissa S, Blais L, Spitzer WO, Cusson J, Lewis M, Heineman L. First time
use of newer oral contraceptives and the risk of venous thromboembolism.
Contraception 1997;56:141–6.
23. Herings RM, Urquhart J, Leufkens HG. Venous thromboembolism among
new users of different oral contraceptives. Lancet 1999;354:127–8.
24. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP.
Higher risk of venous thrombosis during early use of oral contraceptives in
women with inherited clotting defects. Arch Intern Med 2000;160:49–52.
25. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al.;
for the WHI Investigators. Estrogen plus progestin and the risk of venous
thrombosis. JAMA 2004;292:1573–80.
26. Seeger JD, Loughlin J, Eng PM, Clifford CR, Cutone J, Walker AM. Risk
of thromboembolism in women taking ethinyl estradiol/drospirenone and
other oral contraceptives. Obstet Gynecol 2007;110:587–93.
27. Eng PM, Seeger JD, Loughlin J, Clifford CR, Mentor S, Walker AM.
Supplementary data collection with case-cohort analysis to address potential
confounding in a cohort study of thromboembolism in oral contraceptive
initiators matched on claims-based propensity scores. Pharmacoepidemiol
Drug Saf 2008;17:297–305.
28. Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJM,
Rosendaal FR. Effects of oestrogen dose and progestogen type on venous
thrombotic risk associated with oral contraceptives: results of the MEGA
case-control study. BMJ 2009;339:b2921.
29. Yasmin physician labeling. Available at:
http://www.yasmin-us.com/index.html. Accessed September 29, 2010.
30. Shapiro S, Dinger J. Risk of VTE among users of oral contraceptives
[reply to letter to editor]. J Fam Plann Reprod Health Care 2010:36:104–5.
31. Spitzer WO. Bias or causality: Interpreting recent evidence of oral
contraceptive studies. Am J Obstet Gynecol 1998;179:S43–S50.
32. Dinger J. Oral contraceptives and venous thromboembolism: old questions
revisited. J Fam Plann Reprod Health Care 2009;35:211–3.
33. Shapiro S. Causation, bias and confounding: a hitchhiker’s guide to the
epidemiological galaxy. Part 3: principles of causality in epidemiological
research: statistical stability, dose- and duration-response effects, internal
and external consistency, analogy and biological plausibility. J Fam Plann
Reprod Health Care 2008:34:261–4.
34. Lidegaard O. Risk of venous thromboembolism among users of oral
contraceptives: a review of two recently published studies. J Fam Plann
Reprod Health Care 2010;36:103–4.
35. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on Preventive Health Care. New grades for recommendations from
the Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.
DECEMBER JOGC DÉCEMBRE 2010 l 1197
 SOGC CLINICAL PRACTICE GUIDELINE

SOGC Clinical Practice Guideline No. 242, May 2010

Ovulation Induction in Polycystic Ovary

Syndrome
Options: This guideline reviews the evidence for the various options
This Clinical Practice Guideline has been prepared by the for ovulation induction in PCOS.
Reproductive Endocrinology and Infertility Committee and
Outcomes: Ovulation, pregnancy and live birth rates, risks, and side
approved by Executive and Council of the Society of Obstetricians
effects are the outcomes of interest.
and Gynaecologists of Canada.
Evidence: Published literature was retrieved through searches of
PRINCIPAL AUTHORS
Medline using appropriate controlled vocabulary and key words.
Tannys D.R. Vause, MD, Ottawa ON Results were restricted to systematic reviews, randomized control
Anthony P. Cheung, MD, Vancouver BC trials/controlled clinical trials, and observational studies. Grey
(unpublished) literature was identified through searching the
REPRODUCTIVE ENDOCRINOLOGY AND websites of health technology assessment and of health
INFERTILITY COMMITTEE technology assessment-related agencies, clinical practice
Anthony P. Cheung, MD (Chair), Vancouver BC guideline collections, clinical trial registries, and national and
international medical specialty societies.
Sony Sierra, MD (Co-Chair), Toronto ON
Values: The evidence gathered was reviewed and evaluated by the
Paul Claman, MD, Ottawa ON Reproductive Endocrinology and Infertility Committee of the
James Graham, MD, Calgary AB Society of Obstetricians and Gynaecologists of Canada. The
quality of evidence was quantified using the Canadian Task Force
Jo-Anne Guillemin, RN, Regina SK
on Preventive Health Care.
Louise Lapensée, MD, Outremont QC
Benefits, Harms, and Costs: Benefits include weight reduction and
Sabrina Stewart, MD, Saskatoon SK improvements in ovulation, pregnancy, and live birth rates. Potential
Tannys D.R.Vause, MD, Ottawa ON harms include medication side effects and multiple pregnancies.

Benjamin Chee-Man Wong, MD, Calgary AB
CANADIAN FERTILITY AND ANDROLOGY SOCIETY
Jason Min, MD (président), Ottawa (Ont.)
Ken Cadesky, MD, Toronto (Ont.)
Ellen Greenblatt, MD, Toronto (Ont.)
Jon Havelock, MD, Burnaby (C.-B.)
Jeff Roberts, MD, Burnaby (C.-B.)
Disclosure statements have been received from all members of
the committee.
Abstract
Objective: To review current non-pharmacologic and pharmacologic
options for ovulation induction in women with polycystic ovary
syndrome (PCOS).
Key Words: Polycystic ovary syndrome, ovulation induction,
infertility
Validation: These guidelines have been reviewed and approved by
the Reproductive Endocrinology and Infertility Committee of the
SOGC.
Sponsor: The Society of Obstetricians and Gynaecologists of Canada.
Recommendations
1. Weight loss, exercise, and lifestyle modifications have been
proven effective in restoring ovulatory cycles and achieving
pregnancy in overweight women with PCOS and should be the
first-line option for these women. (II-3A) Morbidly obese women
should seek expert advice about pregnancy risk. (III-A)
2. Clomiphene citrate has been proven effective in ovulation
induction for women with PCOS and should be considered the
first-line therapy. Patients should be informed that there is an
increased risk of multiple pregnancy with ovulation induction
using clomiphene citrate. (I-A)
3. Metformin combined with clomiphene citrate may increase
ovulation rates and pregnancy rates but does not significantly
improve the live birth rate over that of clomiphene citrate
alone.(I-A) Metformin may be added to clomiphene citrate in
women with clomiphene resistance who are older and who have
visceral obesity. (I-A)
4. Gonadotropin should be considered second-line therapy for fertility
in anovulatory women with PCOS. The treatment requires
ultrasound and laboratory monitoring. High costs and the risk of
multiple pregnancy and ovarian hyperstimulation syndrome are
drawbacks of the treatment. (II-2A)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

MAY JOGC MAI 2010 l 495

SOGC Clinical Practice Guideline

Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care

Quality of evidence assessment* Classification of recommendations†

I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making

*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preven-
tive Health Care.69
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.69

5. Laparoscopic ovarian drilling may be considered in women with

clomiphene-resistant PCOS, particularly when there are other
indications for laparoscopy. (I-A) Surgical risks need to be
considered in these patients. (III-A)
6. In vitro fertilization should be reserved for women with PCOS who
fail gonadotropin therapy or who have other indications for IVF
treatment. (II-2A)
J Obstet Gynaecol Can 2010;32(5):495–502
INTRODUCTION
olycystic ovary syndrome is a heterogeneous endocrine
P condition that affects approximately 5% to 10% of
women in the reproductive age group.1–3 Depending on the
population being examined, however, prevalence rates as high
as 26% have been reported.4 Although debate on what con-
stitutes PCOS continues, the Rotterdam Consensus on
Diagnostic Criteria for PCOS published in 2003 is the most
current definition. According to this consensus, a diagnosis
of PCOS is based on at least 2 of the following 3 criteria:
oligo-ovulation or anovulation, clinical or biochemical evi-
dence of hyperandrogenism, and polycystic ovaries on
ultrasound assessment (> 12 small antral follicles in an
ovary), with the exclusion of medical conditions such as
congenital adrenal hyperplasia, androgen-secreting tumours, or
Cushing’s syndrome.5
Patients who fulfill these criteria are often plagued by infertility
secondary to both ovulatory dysfunction and the effects of
hyperandrogenism. Several methods have been effective for
ovulation induction and fertility treatment in women with PCOS:
• Weight loss, exercise, and lifestyle modifications
• Clomiphene citrate
• Metformin
• Gonadotropins
• Ovarian drilling
• IVF
This guideline addresses the sequential steps that should be
undertaken, as well as the pregnancy rates, risks, and benefits
of each method.

ABBREVIATIONS WEIGHT LOSS AND LIFESTYLE MODIFICATIONS

CC clomiphene citrate
Obesity is strongly associated with PCOS and may be present
FSH follicle stimulating hormone
in up to 50% of cases.6–10 Obese women with PCOS are
hCG human chorionic gonadotropin more likely than thin women with PCOS to suffer from
LH luteinizing hormone anovulation.6 This effect on ovulation may be secondary to
LOD laparoscopic ovarian drilling insulin resistance, which in turn results in hyperinsulinemia
PCOS polycystic ovary syndrome and stimulation of excess androgen production from the

496 l MAY JOGC MAI 2010


ovaries. Intraovarian hyperandrogenism in turn inhibits
follicular maturation.10
Weight loss through exercise and diet has been proven
effective in restoring ovulatory cycles and achieving
pregnancy for many of these patients.11–13 In obese,
anovulatory women with PCOS, weight loss of even 5% to 10%
of body weight often restores ovulatory cycles.7,9,14,15 Studies
also show that overweight women are less likely to respond
to pharmacologic ovulation induction methods.7,16
Obese women often report difficulty in achieving and
maintaining weight loss. The extent to which their obesity
reflects an inherent metabolic disturbance, making it more
challenging for them to lose weight, remains a question.
The current recommendation is to reduce weight gradually
to increase the chances of maintaining the weight loss.
Preferential diet composition has been evaluated in 2 small
studies.17,18 These studies compared a high carbohydrate
(55%), low protein (15%) hypocaloric diet with a low
carbohydrate (40%), high protein (30%) hypocaloric diet
and found similar weight loss and decrease in circulating
androgen and insulin levels. Although the patient sample
size was small, these 2 studies suggest that patients can
safely pursue either dietary composition, despite the need
for larger confirmatory studies.
Routine exercise is also very important in the reproductive
health of women with PCOS. Exercise increases insulin
sensitivity and helps achieve and maintain weight loss.19 Other
lifestyle factors such as excessive caffeine intake, alcohol
consumption, and smoking should also be addressed.8
Once patients have achieved weight loss, they should be
encouraged to maintain this in the long term and to have
normal weight gain during pregnancy. Obesity contributes
to poor obstetric outcome (increased risk of spontaneous
abortion and preterm labour) and also increases maternal
complications, including gestational hypertension, gestational
diabetes mellitus, thromboembolism, and wound infection.6
Long-term lifestyle modifications can decrease predisposition
to health conditions such as type 2 diabetes mellitus and
modify risk factors for cardiovascular disease.8
Recommendation
1. Weight loss, exercise, and lifestyle modifications have
been proven effective in restoring ovulatory cycles and
achieving pregnancy in overweight women with PCOS
and should be the first-line option for these women.
(II-3A) Morbidly obese women should seek expert
advice about pregnancy risk. (III-A)
CLOMIPHENE CITRATE
Clomiphene citrate has been used as a first-line ovulation
induction agent for over 40 years.20,21 It is a selective estrogen
Ovulation Induction in Polycystic Ovary Syndrome
receptor modulator that stimulates endogenous FSH pro-
duction and secretion by interrupting estrogen feedback to
the hypothalamus and pituitary. PCOS patients can be sensitive
to ovulation induction medications because of a large number
of antral follicles. This places some women with PCOS at risk
of overresponse with multiple follicular development and
ovarian hyperstimulation; however, other women have a
poor response without development of a dominant follicle,
despite using higher doses of CC.
The starting dose of clomiphene citrate is 50 mg per day for
5 days, commencing between day 2 and 5 of menses.22 Menses
may be induced with a progestin if required. If this dose
produces multiple follicular development, the dose can be
lowered to 25 mg. If ovulation is not achieved using 50 mg per
day, the dose can be increased in increments of 50 mg. The
manufacturer does not recommend exceeding 100 mg per
day23; however, many clinicians use doses up to 150 mg and
some even up to 250 mg per day for 5 days,24 taking into
account that alternatives treatments such as gonadotropins
are more costly and have greater risk (see below).
Cycle monitoring should be considered in at least the first
cycle and when the treatment dose has to be increased
because of failure to ovulate. Common indications of an
ovulatory response are a biphasic pattern on basal body
temperature charting and a serum progesterone measurement
in the expected luteal phase of > 10 nmol/L if tested 6 to 8 days
before the onset of menses.25 However, in some circumstances,
detection of the pre-ovulatory LH surge with urinary kits, and
ovarian follicle and endometrial assessment with transvaginal
ultrasound during the late follicular phase can be useful.
If ovulation cannot be achieved with CC, the patient should
be offered further options.
Although 60% to 85% of patients will ovulate on CC, only
about one half will conceive.26,27 Approximately 50% of
conceptions will occur on 50 mg, with another 20% to 25%
and 10% occurring on 100 mg and 150 mg, respectively.15,28
Lack of conception despite evidence of ovulation may be
due to anti-estrogenic effects of CC on the endometrium,
which may manifest as a thin endometrium on ultrasound.29
In one study, no pregnancies occurred when the
endometrium was < 6 mm at midcycle,30 but others have
not found a similar association.31 Nevertheless, alternatives for
ovulation induction should be considered if the
periovulatory endometrium is persistently thin on CC therapy.
Similarly, if pregnancy does not occur within 6 ovulatory
cycles, another ovulation induction method should be
considered.
Other drawbacks of CC include an increased rate of twin
(7% to 9%) and triplet (0.3%) pregnancy, and side effects
such as vasomotor hot flashes.32 Unusual visual symptoms
(visual blurring or persistent after-images) are also noted in
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1% to 2% of patients taking CC, which are likely due to
anti-estrogenic effects of CC on the visual cortex.33
Although more studies are required, it is best to limit a
patient’s lifetime exposure to CC to 12 treatment cycles, as
additional cycles may place the patient at increased risk of
borderline ovarian tumours.34
Recommendation
2. Clomiphene citrate has been proven effective in ovulation
induction for women with PCOS and should be considered
the first-line therapy. Patients should be informed that
there is an increased risk of multiple pregnancy with
ovulation induction using clomiphene citrate. (I-A)
INSULIN SENSITIZING AGENTS
The recognition of an association between PCOS and
hyperinsulinemia has led to the use of insulin-sensitizing
agents in ovulation induction. Metformin, the most widely
studied agent used in PCOS, is a biguanide insulin-sensitizing
agent that acts by inhibiting hepatic glucose production and
increasing peripheral glucose uptake.35 It does not stimulate
secretion of insulin or cause hypoglycemia.
Many earlier studies examining the use of metformin alone
or in conjunction with CC in ovulation induction showed
promising results,36–42 but most of these studies had relatively
small sample sizes. A meta-analysis of 13 randomized
controlled trials by Lord et al.43 in 2003 concluded that
metformin is effective in achieving ovulation in women
with PCOS, with odds ratios of 3.88 (95% CI 2.25 to 6.69)
for metformin compared with placebo and 4.41 (95% CI
2.37 to 8.22) for metformin and CC compared with CC
alone. Pregnancy rates were not significantly better with
metformin than with placebo (OR 2.76; 95% CI 0.85 to
8.98), but an improvement was seen with metformin plus
CC over CC alone (OR 4.4; CI 1.96 to 9.85).43
A more recent meta-analysis published in April 200844 com-
paring CC and metformin, both alone and in combination,
found that metformin alone increased the odds of ovulation
compared with placebo (OR 2.94; 95% CI 1.43 to 6.02) but
did not result in a statistically significant difference in preg-
nancy rates (OR 1.56; 95% CI 0.74 to 3.33). When CC and
metformin were compared with CC alone, both ovulation
and pregnancy rates were statistically increased to 4.39
(95% CI 1.94 to 9.96) and 2.67 (95% CI 1.45 to 4.94),
respectively.
This meta-analysis also included studies that reported live
birth rates. Ng et al.45 in 2001 compared metformin and
placebo in 20 women and found that women who received
metformin were less likely to achieve a live birth, although
this difference did not reach statistical significance (OR 0.44;
95% CI 0.03 to 5.88). Four of the included trials examined
498 l MAY JOGC MAI 2010
live birth rates with CC and metformin versus CC
alone.41,46–48 Collectively, the combination of CC and
metformin suggested an increase in live birth rate over CC
alone, but this increase was not statistically significant (OR
1.74; 95% CI 0.79 to 3.86). The only trial adequately pow-
ered to assess live birth rates was the large randomized-
controlled trial published by Legro et al. in 2007.46 This trial
included 626 patients and demonstrated that although the
live birth rate following up to 6 months of treatment with
metformin and CC was increased (26.8%), it was not signifi-
cantly different from that with CC alone (22.5%). Live birth
rates using CC alone or with metformin were significantly
higher than rates with metformin alone (7.2%).
The evidence supports the use of clomiphene citrate over
metformin as first-line pharmacologic therapy following
lifestyle modification in women with PCOS. However,
there may be a role for the addition of metformin to CC in
women who are clomiphene-resistant. Siebert et al.49 exam-
ined 6 trials in which metformin was randomized with
either placebo or CC in clomiphene-resistant patients and
found an overall statistically significant improvement in
ovulation with combination therapy (OR 6.82; 95% CI 3.59
to 12.96). Further, a recent study also suggested that women
with PCOS who are older and have increased visceral obe-
sity may benefit from the additional use of metformin.50
Patients on metformin often experience unpleasant side effects
of nausea, bloating, cramps, and diarrhea, and they should
be counselled to start with 250 mg to 500 mg PO daily and
increase as tolerated to the optimal daily dose of 500 mg to
750 mg 3 times daily with food. Metformin can also be
dosed 850 mg PO twice daily or a long-acting formulation
(Glumetza) can be used to improve compliance.
Although some studies have shown that continuing
metformin in pregnancy may decrease the spontaneous
abortion rate,42,51–53 none of these are prospective, random-
ized trials. Randomized controlled trials are needed in this
area before sustained metformin treatment throughout
pregnancy can be recommended.
Recommendation
3. Metformin combined with clomiphene citrate may
increase ovulation rates and pregnancy rates but does not
significantly improve the live birth rate over that of
clomiphene citrate alone.(I-A) Metformin may be added
to clomiphene citrate in women with clomiphene resis-
tance who are older and who have visceral obesity. (I-A)
GONADOTROPINS
Use of intramuscular gonadotropins began in the 1960s.
These preparations, from the purified urine of
postmenopausal women, contained both FSH and LH.

Over the last decade, recombinant human FSH has been
the main preparation, and it can be self-administered subcu-
taneously.54 Gonadotropins are used when PCOS patients
fail either to ovulate or to conceive with oral ovulation induc-
ing medications.
Daily injections of gonadotropins are combined with con-
current blood and ultrasound monitoring with the aim of
monofollicular growth and development. However,
because of the inherent nature of exogenous gonadotropin
treatment, multifollicular development is not uncommon,
despite careful dose adjustment and monitoring. Once the
dominant follicle has reached the appropriate size, hCG is
administered to trigger ovulation.
Injectable gonadotropins are very expensive and require
frequent monitoring, with serum estradiol and ultrasound
assessments to minimize the risks from excessive follicular
growth and development. Because of the high number of
antral follicles in women with PCOS, it is not uncommon
that treatment is cancelled to minimize the occurrence of
multiple pregnancy and also of ovarian hyperstimulation
syndrome.55 Pregnancy rates with gonadotropins are 20%
to 25% per cycle.54 Drawbacks to gonadotropin treatment,
as mentioned earlier, are requirements for intensive moni-
toring, cost, multiple pregnancy, and ovarian
hyperstimulation. Gonadotropins should be administered
by physicians with specific training in reproductive medi-
cine and with ready access to ultrasound monitoring and
rapid hormone testing.
Recommendation
4. Gonadotropin should be considered second-line therapy
for fertility in anovulatory women with PCOS. The treat-
ment requires ultrasound and laboratory monitoring.
High costs and the risk of multiple pregnancy and ovar-
ian hyperstimulation syndrome are drawbacks of the
treatment. (II-2A)
OVARIAN DRILLING
Surgical ovarian wedge resection by open laparotomy was
one of the first treatments for anovulation due to PCOS.56
It was thought to induce ovulation by decreasing the ovarian
theca and thus reducing androgen production. Because of
the operative morbidity of the procedure and the risk of
postoperative adhesions,57 ovarian wedge resection by
laparotomy has largely been abandoned as more effective
medical therapies for ovulation induction have become
available. With the popularity of minimally invasive surgery,
laparoscopic ovarian drilling is thought to be less destructive
to the ovary and has a lower risk of adhesion formation.
Laparoscopic ovarian drilling uses either cautery or laser to
create approximately 10 superficial perforations per ovary.58
Ovulation Induction in Polycystic Ovary Syndrome
A Cochrane review published in 2007 examined 16 random-
ized controlled trials evaluating ovulation induction in
clomiphene-resistant PCOS with LOD. The dose at which
clomiphene resistance was defined ranged from 100 mg to
200 mg in the various studies. Approximately 80% of
PCOS patients will become ovulatory after LOD. There
was no difference found in the rates of miscarriage, ongoing
pregnancy, or live birth between patients who underwent
LOD and patients treated with gonadotropins for ovulation
induction. There were significantly fewer multiple pregnancies
in the LOD than in the gonadotropin treatment groups
(1% vs. 16%; OR 0.13; 95% CI 0.03 to 0.59).58 In one of the
included trials, adjuvant therapy with CC or gonadotropins
was required to achieve equivalent pregnancy and live birth
rates in patients remaining anovulatory 8 weeks after LOD
or those who subsequently became anovulatory.59
Despite this evidence that LOD may be equivalent to gon-
adotropins in achieving ovulation, the effects of LOD on
postoperative adhesion formation remain a concern,60
although it has been shown that in women who respond to
this treatment, the rate of cessation of ovulation is low.61
Recommendation
5. Laparoscopic ovarian drilling may be considered in
women with clomiphene-resistant PCOS, particularly
when there are other indications for laparoscopy. (I-A)
Surgical risks need to be considered in these patients.
(III-A)
AROMATASE INHIBITORS
Aromatase inhibitors have been used for the last decade as
adjunctive treatments in breast cancer.62 They block the
conversion of testosterone and androstenedione to
estradiol and estrone, respectively, and hence inhibit the
estrogen-negative feedback on the hypothalamic–pituitary
axis. This leads to increased gonadotropin secretion, which in
turn leads to ovarian follicular growth and development.62
The use of aromatase inhibitors in ovulation induction was
first introduced in 2001.63 Ovulation and pregnancy rates
with aromatase inhibitors such as letrozole and anastrozole
appear to be promising, and these agents appear to have less
anti-estrogen effect on the endometrium, but the evidence
on endometrial effects is conflicting, and most studies show
equivalence with clomiphene citrate.62–65 In 2005, however,
Health Canada and the manufacturing company of
letrozole issued a “Physician Warning Letter” on the
off-label use of letrozole for fertility and the possibility of
embryotoxicity, fetotoxicity, and teratogenicity found in
rats.66 This followed preliminary research findings by Biljan
et al.67 comparing congenital malformations in babies con-
ceived with letrozole with or without gonadotropins with
those in babies born to a low-risk population of women
MAY JOGC MAI 2010 l 499
SOGC Clinical Practice Guideline
without known fertility treatments. These findings reported a
higher incidence of both cardiac and bone abnormalities in
the letrozole group.67 More recently, however, Tulandi et al.68
retrospectively evaluated 911 newborns from letrozole and
CC pregnancies. They found a 2.4% incidence of congenital
malformations and chromosomal abnormalities in the
letrozole group versus 4.8% in the CC group.68 However, until
aromatase inhibitors have been approved for ovulation
induction by Health Canada, they should be used with
caution, and patients should be carefully counselled, given
potential medico–legal implications.
IN VITRO FERTILIZATION
IVF, with or without intracytoplasmic sperm injection, is
the next treatment option for women with PCOS who fail
to conceive with gonadotropin treatment or in the presence
of other indications for advanced reproductive technologies.
In IVF, gonadotropins are administered to achieve
multifollicular development for oocyte retrieval and generation
of embryos for transfer into the uterus. Pregnancy rates can
approach 40% to 50% per cycle with IVF, but, as with fertility
in general, success is significantly influenced by the
women’s age.54 PCOS patients achieve pregnancy and live
birth rates similar to those of non-PCOS patients during
conventional IVF cycles. Side effects include multiple preg-
nancy when multiple embryos are transferred, and a higher
risk of ovarian hyperstimulation; however, the risk of multiple
pregnancy is more easily controlled with IVF than with
ovulation induction with gonadotropins, because the num-
ber of embryos transferred into the patient’s uterus can be
limited and surplus good quality embryos cryopreserved for
future transfer.
Recommendation
6. In vitro fertilization should be reserved for women with
PCOS who fail gonadotropin therapy or who have other
indications for IVF treatment. (II-2A)
SUMMARY
Patients with polycystic ovary syndrome commonly present
with a history of infertility due to oligo-ovulation or
anovulation. First-line management of infertility should
always include weight loss and exercise and lifestyle modifi-
cations in the overweight patient. This is beneficial in the
patient’s overall health, it may lead to spontaneous ovulation,
and it will improve response to ovulation-induction
medications. Clomiphene citrate has been used for many
years and remains the first-line medication despite potential
anti-estrogenic effects on the endometrium and cervical
mucous. Recent evidence indicates that insulin-sensitizing
agents should not be used as a first-line therapy, although
they may be beneficial in PCOS patients who are older and
500 l MAY JOGC MAI 2010
who have increased visceral obesity as assessed by increased
waist-to-hip ratios, and in those who have failed to ovulate
on clomiphene citrate alone. Laparoscopic ovarian drilling
should be considered in women who are resistant to
clomiphene citrate because of the lower risk of multifetal
gestation compared with gonadotropin therapy. Further trials
are needed in the area of aromatase inhibitors if they are to
be used routinely for ovulation induction.
Clinicians should always consider a patient’s age and duration of
infertility as they progress through the different treatment
options available. If a patient does not become pregnant in a
timely manner, referral to a fertility clinic and appropriate
uses of gonadotropins and IVF are effective options.
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the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
 SOGC CLINICAL PRACTICE GUIDELINE

No. 325, June 2015

Guidelines for the Management of a

Pregnant Trauma Patient
Abstract
This clinical practice guideline has been prepared by the
Maternal Fetal Medicine Committee, reviewed by the Clinical Objective: Physical trauma affects 1 in 12 pregnant women and
Practice – Obstetrics, Medico-Legal, and Family Physician has a major impact on maternal mortality and morbidity and on
Advisory Committees, and approved by Executive and pregnancy outcome. A multidisciplinary approach is warranted to
Board of the Society of Obstetricians and Gynaecologists optimize outcome for both the mother and her fetus. The aim of this
of Canada document is to provide the obstetric care provider with an evidence-
based systematic approach to the pregnant trauma patient.
PRINCIPAL AUTHORS
Outcomes: Significant health and economic outcomes considered in
Venu Jain, MD, Edmonton AB comparing alternative practices.
Radha Chari, MD, Edmonton AB Evidence: Published literature was retrieved through searches of
Sharon Maslovitz, MD, Tel Aviv, Israel Medline, CINAHL, and The Cochrane Library from October 2007
to September 2013 using appropriate controlled vocabulary (e.g.,
Dan Farine, MD, Toronto ON pregnancy, Cesarean section, hypotension, domestic violence,
shock) and key words (e.g., trauma, perimortem Cesarean,
MATERNAL FETAL MEDICINE COMMITTEE Kleihauer-Betke, supine hypotension, electrical shock). Results
Emmanuel Bujold (Co-Chair), MD, Quebec QC were restricted to systematic reviews, randomized control trials/
controlled clinical trials, and observational studies published in
Robert Gagnon (Co-Chair), MD, Montreal QC English between January 1968 and September 2013. Searches
Melanie Basso, RN, Vancouver BC were updated on a regular basis and incorporated in the guideline
to February 2014.
Hayley Bos, MD, Victoria BC
Grey (unpublished) literature was identified through searching the
Richard Brown, MD, Montreal QC
websites of health technology assessment and health technology-
Stephanie Cooper, MD, Calgary AB related agencies, clinical practice guideline collections, clinical
Katy Gouin, MD, Quebec QC trial registries, and national and international medical specialty
societies.
N. Lynne McLeod, MD, Halifax NS
Values: The quality of evidence in this document was rated using the
Savas Menticoglou, MD, Winnipeg MB criteria described in the Report of the Canadian Task Force on
William Mundle, MD, Windsor ON Preventive Health Care (Table 1).

Christy Pylypjuk, MD, Winnipeg MB Benefits, harms, and costs: This guideline is expected to facilitate
optimal and uniform care for pregnancies complicated by trauma.
Anne Roggensack, MD, Calgary, AB
Frank Sanderson, MD, Saint John, NB SUMMARY STATEMENT
Disclosure statements have been received from all contributors. Specific traumatic injuries
At this time, there is insufficient evidence to support the practice of
disabling air bags for pregnant women. (III)

J Obstet Gynaecol Can 2015;37(6):553–571 RECOMMENDATIONS

Primary survey

Key words: Abruption, electrical, fall, fetal, injury, maternal, MVC,   1. Every female of reproductive age with significant injuries should
penetrating, perimortem, pregnancy. be considered pregnant until proven otherwise by a definitive
pregnancy test or ultrasound scan. (III-C)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

JUNE JOGC JUIN 2015 l 553

SOGC clinical practice guideline
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case–control studies, preferably from
more than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with
penicillin in the 1940s) could also be included in this category
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees
*The quality of evidence reported in here has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on Preventive Health
Care.133
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.133
  2. A nasogastric tube should be inserted in a semiconscious or
unconscious injured pregnant woman to prevent aspiration of
acidic gastric content. (III-C)
  3. Oxygen supplementation should be given to maintain
maternal oxygen saturation > 95% to ensure adequate fetal
oxygenation. (II-1B)
  4. If needed, a thoracostomy tube should be inserted in an
injured pregnant woman 1 or 2 intercostal spaces higher than
usual. (III-C)
  5. Two large bore (14 to 16 gauge) intravenous lines should be
placed in a seriously injured pregnant woman. (III-C)
  6. Because of their adverse effect on uteroplacental perfusion,
vasopressors in pregnant women should be used only
for intractable hypotension that is unresponsive to fluid
resuscitation. (II-3B)
  7. After mid-pregnancy, the gravid uterus should be moved off
the inferior vena cava to increase venous return and cardiac
output in the acutely injured pregnant woman. This may be
achieved by manual displacement of the uterus or left lateral
tilt. Care should be taken to secure the spinal cord when using
left lateral tilt. (II-1B)
  8. To avoid rhesus D (Rh) alloimmunization in Rh-negative
mothers, O-negative blood should be transfused when needed
until cross-matched blood becomes available. (I-A)
  9. The abdominal portion of military anti-shock trousers should
not be inflated on a pregnant woman because this may reduce
placental perfusion. (II-3B)
Transfer to health care facility
10. Transfer or transport to a maternity facility (triage of a labour
and delivery unit) is advocated when injuries are neither life-
nor limb-threatening and the fetus is viable (≥ 23 weeks), and
to the emergency room when the fetus is under 23 weeks’
gestational age or considered to be non-viable. When the
injury is major, the patient should be transferred or transported
to the trauma unit or emergency room, regardless of
gestational age. (III-B)
554 l JUNE JOGC JUIN 2015
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive action
B. There is fair evidence to recommend the clinical preventive action
C. The existing evidence is conflicting and does not allow to make a
recommendation for or against use of the clinical preventive action;
however, other factors may influence decision-making
D. There is fair evidence to recommend against the clinical preventive action
E. There is good evidence to recommend against the clinical preventive
action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
11. When the severity of injury is undetermined or when the
gestational age is uncertain, the patient should be evaluated in the
trauma unit or emergency room to rule out major injuries. (III-C)
Evaluation of a pregnant trauma patient in the emergency room
12. In cases of major trauma, the assessment, stabilization, and
care of the pregnant women is the first priority; then, if the
fetus is viable (≥ 23 weeks), fetal heart rate auscultation and
fetal monitoring can be initiated and an obstetrical consultation
obtained as soon as feasible. (II-3B)
13. In pregnant women with a viable fetus (≥ 23 weeks) and
suspected uterine contractions, placental abruption, or
traumatic uterine rupture, urgent obstetrical consultation is
recommended. (II-3B)
14. In cases of vaginal bleeding at or after 23 weeks, speculum or
digital vaginal examination should be deferred until placenta
previa is excluded by a prior or current ultrasound scan. (III-C)
Adjunctive tests for maternal assessment
15. Radiographic studies indicated for maternal evaluation
including abdominal computed tomography should not be
deferred or delayed due to concerns regarding fetal exposure to
radiation. (II-2B)
16. Use of gadolinium-based contrast agents can be considered
when maternal benefit outweighs potential fetal risks. (III-C)
17. In addition to the routine blood tests, a pregnant trauma patient
should have a coagulation panel including fibrinogen. (III-C)
18. Focused abdominal sonography for trauma should be considered
for detection of intraperitoneal bleeding in pregnant trauma
patients. (II-3B)
19. Abdominal computed tomography may be considered as an
alternative to diagnostic peritoneal lavage or open lavage when
intra-abdominal bleeding is suspected. (III-C)
Fetal assessment
20. All pregnant trauma patients with a viable pregnancy (≥ 23 weeks)
should undergo electronic fetal monitoring for at least 4 hours. (II-3B)

21. Pregnant trauma patients (≥ 23 weeks) with adverse factors
including uterine tenderness, significant abdominal pain, vaginal
bleeding, sustained contractions (> 1/10 min), rupture of the
membranes, atypical or abnormal fetal heart rate pattern, high
risk mechanism of injury, or serum fibrinogen < 200 mg/dL should
be admitted for observation for 24 hours. (III-B)
22. Anti-D immunoglobulin should be given to all rhesus D-negative
pregnant trauma patients. (III-B)
23. In Rh-negative pregnant trauma patients, quantification of
maternal–fetal hemorrhage by tests such as Kleihauer-Betke
should be done to determine the need for additional doses of
anti-D immunoglobulin. (III-B)
24. An urgent obstetrical ultrasound scan should be undertaken
when the gestational age is undetermined and need for delivery
is anticipated. (III-C)
25. All pregnant trauma patients with a viable pregnancy who are
admitted for fetal monitoring for greater than 4 hours should have
an obstetrical ultrasound prior to discharge from hospital. (III-C)
26. Fetal well-being should be carefully documented in cases
involving violence, especially for legal purposes. (III-C)
Obstetrical complications of trauma
27. Management of suspected placental abruption should not be
delayed pending confirmation by ultrasonography as ultrasound
is not a sensitive tool for its diagnosis. (II-3D)
Specific traumatic injuries
28. Tetanus vaccination is safe in pregnancy and should be given
when indicated. (II-3B)
29. Every woman who sustains trauma should be questioned
specifically about domestic or intimate partner violence. (II-3B)
30. During prenatal visits, the caregiver should emphasize the
importance of wearing seatbelts properly at all times. (II-2B)
Perimortem Caesarean section
31. A Caesarean section should be performed for viable pregnancies
(≥ 23 weeks) no later than 4 minutes (when possible) following
maternal cardiac arrest to aid with maternal resuscitation and
fetal salvage. (III-B)
ABBREVIATIONS
CNS central nervous system
CT computerized tomography
DPL diagnostic peritoneal lavage
ECG electrocardiogram
EFM electronic fetal monitoring
ER emergency room
FAST focused abdominal sonography for trauma
ICU intensive care unit
KB Kleihauer-Betke
L&D labour and delivery
MAST military anti-shock trousers
MFH maternal-fetal hemorrhage
MVC motor vehicle collision
Rh rhesus D
Guidelines for the Management of a Pregnant Trauma Patient
INTRODUCTION
T
rauma during pregnancy is the leading cause of non-
obstetric maternal mortality, with 20% of maternal
deaths directly attributable to injuries.1 Non-lethal
injuries occur in 1 in every 12 pregnant women and are
most commonly the result of an MVC or of domestic
or intimate partner violence.1–3 Other common causes
of trauma in a pregnant patient are penetrating injuries
and falls.4–6 Health Canada reported maternal mortality
as 6.1 per 100 000 live births during 1997–2000.7
During that period 15 maternal deaths (an incidence of
1.5/100 000) were attributed to MVC. There was no other
single diagnosis (pulmonary embolism, preeclampsia,
hemorrhage, etc.) with such a high mortality rate. A
Swedish national population-based study (1991–2001)
reported an MVC incidence of 207/100 000 pregnancies
that was associated with a maternal mortality of 1.4 per
100 000 pregnancies and a perinatal mortality of 3.7 per
100 000 pregnancies (an odds ratio of 3.55 compared
with the background risk).8 There was no significant
difference in fatal injury risk among pregnant and non-
pregnant women involved in an MVC.8 A report by
the National Trauma Data Bank (2001–2005) indicated
that trauma-related mortality among pregnant women
is lower than that among non-pregnant women.9 This
difference has been attributed to protective hormonal
and physiologic effects of pregnancy as well as a higher
likelihood of hospital admission of pregnant versus non-
pregnant trauma victims.9,10
The management of a pregnant trauma patient warrants
consideration of several issues specific to pregnancy
such as alterations in maternal physiology and anatomy,
exposure to radiation and other possible teratogens,
the need to assess fetal well-being, and conditions that
are unique to pregnancy and are related to trauma (Rh
isoimmunization, placental abruption, and preterm
labour). Optimization of outcome in severe trauma
cases mandates a multidisciplinary team approach
involving trauma surgeons, emergency medicine
physicians, obstetricians, neonatologists, nursing staff,
and technicians. The obstetrician (or other obstetric care
provider) plays a major role in determining gestational
age, optimizing uteroplacental perfusion, assessing fetal
well-being, providing information about the risks of
radiation exposure and use of medications, and deciding
upon and executing an emergency Caesarean section.
A systematic, evidence-based approach to the management
of maternal trauma is hereby provided to assist and
guide physicians involved in such cases, either as primary
caregivers or consultants.
JUNE JOGC JUIN 2015 l 555
SOGC clinical practice guideline
PRIMARY SURVEY
Seriously injured trauma victims are occasionally unable to
communicate with the primary caregiver. In addition, some
women may be unaware of their pregnancy status. One
study showed that 3% of women admitted to a trauma
unit were pregnant, and of these 11% were incidental
pregnancies.11 Therefore, it is recommended that every
injured female of childbearing years should be considered
pregnant until proven otherwise. Following admission
of the patient for further care in a health care facility, a
pregnancy test should be performed.12 The confirmation
of pregnancy may have a major impact on future decisions
regarding diagnostic imaging, use of medications, and
other treatment modalities.
As with non-pregnant women, the initial assessment of an
acutely injured pregnant woman should include securing
her airway, ensuring breathing, and maintaining adequate
circulation. The most important lifesaving primary
interventions might include, for example, intubation and
controlling severe external hemorrhage.
Airway
The pregnant patient has a greater risk for airway
management problems and difficult intubation than the
non-pregnant patient.13 Weight gain, respiratory tract
mucosal edema, decreased functional residual capacity,
reduced respiratory system compliance, increased airway
resistance, and increased oxygen requirements are
pregnancy-induced changes that place the injured pregnant
woman at risk for failure to maintain a patent airway
and secured ventilation.14 An early intubation should be
considered in whenever airway problems are anticipated.
Injured pregnant women with an unsecured airway are at
increased risk for aspiration of gastric contents. Gastric
emptying is delayed in pregnancy and pregnant women
should be considered to have a full stomach for up to 24
hours after their last meal. Intubation is more difficult
in pregnant patients, with failed intubations being 8
times more likely.15 A smaller size of endotracheal tube
is recommended.15 Cricoid pressure can be considered
during intubation to decrease the risk of regurgitation of
gastric contents into the pharynx and for manipulation
of laryngoscopic view.15,16 However, adjustment of
pressure or early release may be necessary if the view is
poor. In addition, early placement of a nasogastric tube is
warranted in an unconscious or semiconscious pregnant
patient to avoid aspiration in light of decreased gastric
motility, compression of the upper gastrointestinal tract,
elevated gastric acid, decreased pH, and relaxation of the
lower esophageal sphincter.17
556 l JUNE JOGC JUIN 2015
Breathing
Marked increases in basal oxygen consumption and
extreme sensitivity of the fetus to maternal hypoxia
mandate supplemental oxygen by a nasal cannula, mask,
or endotracheal tube to all pregnant trauma patients to
maintain oxygen saturation above 95%.
Taking into account the displacement of the diaphragm
during pregnancy, it may be advisable to insert a
thoracostomy tube, when indicated, one to 2 intercostal
spaces higher than usual.18
Circulation
Administration of fluids and blood products during
resuscitation should proceed according to standard trauma
protocols.19 Nevertheless, some modifications should be
made in the pregnant trauma victim.
Insertion of 2 large bore needles (14–16 gauge) is
recommended for all seriously injured trauma patients
to facilitate initial rapid crystalloid infusion, intravascular
volume expansion, and possible further blood transfusion
as required. The uteroplacental vasculature is highly
responsive to vasopressors, and their administration
may decrease placental perfusion. In cases of maternal
hypotension vasopressors should be avoided unless the
patient is unresponsive to replenishment of intravascular
volume by fluid administration.20 Bicarbonate should be
used with caution, because rapid correction of maternal
acidosis can reduce the compensatory hyperventilation.21 To
further facilitate the evaluation of maternal hypovolemia,
the pregnant trauma patient should be undressed and a
thorough examination for sources of blood loss should be
undertaken.
Care must be taken to avoid supine hypotension in the
pregnant trauma patient after mid-pregnancy. Compression
of the vena cava by the uterus can cause up to 30%
reduction in cardiac output.22 The displacement of the
uterus off of the inferior vena cava and abdominal aorta
enhances maternal venous return and cardiac output, and
consequently improves uterine perfusion.19,23 This can
be achieved either by placing the patient in the left lateral
position or by manual displacement of the uterus while the
injured patient is secured in the supine position. The latter
may allow more effective chest compressions while cardio-
pulmonary resuscitation is in progress.24 A third option is to
use a backboard for lateral tilt with secured spine in suspected
spinal injuries. Fetal risks from maternal defibrillation are
small, especially if all fetal monitors have been removed.25
In the setting of acute blood loss necessitating immediate
administration of blood products in a pregnant trauma

patient, O-negative blood should be transfused in order to
avoid Rh sensitization in Rh-negative women until type-
specific or cross-matched donor blood becomes available.
Inflation of the abdominal portion of the MAST is
contraindicated during pregnancy as it may lead to reduced
placental perfusion and increased cardiac workload.26
Recommendations
1. Every female of reproductive age with significant
injuries should be considered pregnant until
proven otherwise by a definitive pregnancy test or
ultrasound scan. (III-C)
2. A nasogastric tube should be inserted in a
semiconscious or unconscious injured pregnant
woman to prevent aspiration of acidic gastric
content. (III-C)
3. Oxygen supplementation should be given to
maintain maternal oxygen saturation > 95% to
ensure adequate fetal oxygenation. (II-1B)
4. If needed, a thoracostomy tube should be inserted
in an injured pregnant woman 1 or 2 intercostal
spaces higher than usual. (III-C)
5. Two large bore (14 to 16 gauge) intravenous lines
should be placed in a seriously injured pregnant
woman. (III-C)
6. Because of their adverse effect on uteroplacental
perfusion, vasopressors in pregnant women should
be used only for intractable hypotension that is
unresponsive to fluid resuscitation. (II-3B)
7. After mid-pregnancy, the gravid uterus should be
moved off the inferior vena cava to increase venous
return and cardiac output in the acutely injured
pregnant woman. This may be achieved by manual
displacement of the uterus or left lateral tilt. Care
should be taken to secure the spinal cord when
using left lateral tilt. (II-1B)
8. To avoid rhesus D (Rh) alloimmunization in Rh-
negative mothers, O-negative blood should be
transfused when needed until cross-matched blood
becomes available. (I-A)
9. The abdominal portion of military anti-shock
trousers should not be inflated on a pregnant
woman because this may reduce placental
perfusion. (II-3B)
TRANSFER TO HEALTH CARE FACILITY
Following successful initial maternal stabilization,
the primary care provider should organize further
appropriate referral, consultation, and transfer of care
as required. The dilemma is not only whether and how
Guidelines for the Management of a Pregnant Trauma Patient
to transfer patient care between different health facilities,
but also where further care should be provided: in the
trauma unit, ER, or community-designated emergency
care facility/personnel unit, in an ICU, or in the
maternity/L&D unit or community-designated maternity
facility/personnel unit. Although most injuries are not
categorized as life threatening, they may still be extensive
or mandate immediate intervention to prevent long-term
consequences for the mother.
Factors that should be taken into consideration are severity
of the injuries and gestational age. Maternal health should
always take priority over interventions for the fetus. When
major maternal trauma is evident or suspected, the patient
should be transferred without delay to the trauma unit or
ER. The same applies for women with pregnancies of under
23 weeks’ gestation, when the fetus is considered non-
viable and serious obstetric complications are uncommon.
Women over 23 weeks’ gestation without life- or limb-
threatening injuries should be transported to a maternity or
L&D unit as soon as possible. However, the diagnosis of
pregnancy is not always certain or obvious. Many seriously
injured trauma victims cannot communicate, and some are
unaware of their pregnancy status. Gestational age may be
unobtainable or uncertain, complicating the process of
decision making. The primary care provider should try to
assess the gestational age by verbal communication with
the patient or her companion or through documentation
found in her possession. Fundal height may give a rough
estimate of gestational age in most cases of a singleton
gestation. Occasionally, injury-related distention of the
abdomen may interfere with the estimation of fundal
height.
Multiple systems for scoring the severity of trauma have
been proposed in the literature,27 but most of them are
cumbersome and are not applicable for on-scene decision
making. Severity assessment scoring systems frequently
used in trauma and intensive care patients to predict
outcome are often not useful in pregnant women admitted
to a general ICU.28 The standard Injury Severity Score
assessment is also not accurate in predicting placental
abruption and fetal demise. Buchsbaum described simple
and applicable criteria that essentially distinguish between
major maternal injuries that require further assessment in
a trauma centre and minor injuries for which obstetrical
surveillance takes precedence.29 Buchsbaum used criteria
such as hematuria, suspected internal bleeding, loss of
conscious, and fractures to delineate major trauma. We
suggest that these simple parameters should be considered
along with common sense when deciding upon patient
transfer and transport arrangements for a pregnant woman
after 23 weeks’ gestation.
JUNE JOGC JUIN 2015 l 557
SOGC clinical practice guideline
Recommendations
10. Transfer or transport to a maternity facility (triage
of a labour and delivery unit) is advocated when
injuries are neither life- nor limb-threatening and the
fetus is viable (≥ 23 weeks), and to the emergency
room when the fetus is under 23 weeks’ gestational
age or considered to be non-viable. When the
injury is major, the patient should be transferred or
transported to the trauma unit or emergency room,
regardless of gestational age. (III-B)
11. When the severity of injury is undetermined or
when the gestational age is uncertain, the
patient should be evaluated in the trauma
unit or emergency room to rule out major
injuries. (III-C)
EVALUATION OF A PREGNANT
TRAUMA PATIENT IN THE ER
Assessment of a pregnant trauma patient in the ER
may require the involvement of a multidisciplinary team
that may include an emergency physician or trauma
specialist (or the designated emergency care provider), an
obstetrician (or obstetrical care provider), a neonatologist,
an anaesthetist, and skilled nursing staff. The pregnant
patient should be fully assessed, as is a non-pregnant
patient, with a thorough history, examination, laboratory
tests, imaging studies, and invasive diagnostic procedures
as indicated. In addition, special attention should be given
to fetal evaluation when gestational age is ≥ 23 weeks and
to trauma complications that are unique to pregnancy
such as placental abruption. Communication between
health care providers can be facilitated by incorporating
the emergency triage protocol in the management of
pregnancy trauma patients.30
History
As in the non-pregnant trauma patient, a thorough
history is of utmost importance to delineate the
mechanism of injury and possible concealed damage
in a pregnant patient. The caregiver should also obtain
information about past obstetrical history (e.g., scarred
uterus, previous obstetrical complications) and the
course of the current pregnancy. Certain pregnancy
complications will affect the management of trauma-
related injuries. For example, patients with preeclampsia
have reduced intravascular volume and are extremely
sensitive to hypovolemia and anemia. These patients may
also have compromised renal function on the one hand
and increased capillary permeability with proneness to
pulmonary edema on the other. Awareness of these
factors may lead to modification of fluid management
558 l JUNE JOGC JUIN 2015
with regard to the method and rate of volume
replacement and the means of monitoring intravascular
volume and cardiac output.
The history should also include inquiries into specific
complications of trauma in pregnancy: leakage of fluid,
vaginal bleeding, abdominal pain or cramping, intensity
and frequency of contractions, and maternal perception
of fetal movements.
Physical Examination
The physical examination of pregnant trauma patients is
similar to that of non-pregnant patients with modifications
for pregnancy-related complications. We endorse the
recommendations proposed by the Advanced Trauma Life
Support Course of the American College of Surgeons’
Committee on Trauma.19
All body parts of the pregnant trauma patient should be
exposed and thoroughly examined. In recording vital signs
it is helpful to keep in mind that the heart rate increases by
15% during pregnancy. Tachycardia and hypotension, typical
of hypovolemic shock, may appear late in the pregnant
trauma patient because of her increased blood volume.31
During pregnancy, maternal vital signs and perfusion may
be preserved at the expense of uteroplacental perfusion,
delaying the occurrence of signs of hypovolemic shock.32
Not uncommonly, noticeable alterations in vital signs occur
only after significant blood loss that may have already
diminished uteroplacental perfusion. In these instances, an
atypical or abnormal fetal heart rate pattern, in addition to
indicating impending fetal hypoxemic injury or even death,
may be the first indicator of significant maternal hypovolemia
due to hemorrhage.32–34 Therefore, in a pregnant patient
≥ 23 weeks’ gestation, fetal heart rate monitoring should be
initiated as soon as possible. This may require having staff
from the maternity or L&D unit visit the unit where the
pregnant woman is receiving care for her injuries. For those
< 23 weeks’ gestation, a brief assessment of fetal viability
is adequate. Continuous monitoring of oxygen saturation
is advised since maternal desaturation may compromise
oxygenation of the fetus. Oxygen supplementation should
be given to increase oxygen saturation.
Special attention should be paid to the abdomen since
serious injuries may involve the gravid uterus as well as other
abdominal organs. The contour of the abdomen should be
carefully inspected for abnormal distension as a sign of intra-
abdominal hemorrhage or perforation of hollow viscus.
Meticulous documentation of the location of entrance
and exit wounds of penetrating trauma is of paramount
importance. The uterus and its contents usually cushion
the impact of penetrating trauma; therefore, in women
 Guidelines for the Management of a Pregnant Trauma Patient

after mid-pregnancy mortality and incidence of visceral Table 2. Estimated fetal radiation doses
injury with penetrating abdominal trauma are substantially during some common radio-diagnostic
lower than in the general population.35 However, injuries procedures
below the fourth intercostal space anteriorly, or the tip of Fetal dose
Examination (mrad)
the scapula posteriorly, should be carefully evaluated for
X-ray
potential thoraco-abdominal penetrating injuries. Risk factors
Upper gastrointestinal series 100
associated with maternal death include bruising injuries to
Cholecystography 100
the abdomen, pelvis, or lower back, pelvic fractures, intra-
Lumbar spine radiography 400
abdominal injuries, and penetrating trauma.34,36
Pelvic radiography 200
Clinical signs of peritoneal irritation are less evident in Hip and femur radiography 300
the pregnant woman; therefore, in cases of suspected Retrograde pyelography 600
abdominal injury, physical examination is less informative Abdominal radiography 250
in ruling out major organ damage and further Lumbar spine,
investigations should be conducted.37 The uterus should Anteroposterior 750
be assessed for fundal height, shape, hypertonus, and Lateral 91

tenderness. Tenderness over the uterus is an important Oblique 100

sign suggestive of abruption of the placenta. Irregularities Barium enema 1000

on the abdomen may represent fetal body parts in cases of Intravenous pyelogram 480

traumatic uterine rupture. In these cases, rapid response Computed tomography

of the medical team can significantly reduce maternal Head 0

and fetal risks, and urgent obstetrical consultation is Chest 16

recommended.33,38,39 In some communities, the consultant Abdomen 3000

(Adapted from Ratnapalan S, Bona N, Koren G; Motherisk
who can perform a Caesarean and other requisite surgical Team. Ionizing radiation during pregnancy. Can Fam
procedures may be a family physician or a surgeon. Physician. 2003 Jul;49:873–4. By permission of Canadian
Family Physician.)

Vaginal examination should be performed for cervical mrad: milli-rad (radiation absorbed dose)

dilatation, effacement, fetal presentation, and station.

However, in cases of vaginal bleeding after 23 weeks,
speculum or digital vaginal examination should be deferred
until placenta previa is excluded by an ultrasound scan. A
speculum examination should be performed to assess for
vaginal bleeding, pooling of amniotic fluid, cervical dilatation,
vaginal or cervical lacerations, and expulsion of gestational
tissue.
Recommendations
12. In cases of major trauma, the assessment,
stabilization, and care of the pregnant women is
the first priority; then, if the fetus is viable
(≥ 23 weeks), fetal heart rate auscultation and
fetal monitoring can be initiated and an obstetrical
consultation obtained as soon as feasible. (II-3B)
13. In pregnant women with a viable fetus (≥ 23
weeks) and suspected uterine contractions, placental
abruption, or traumatic uterine rupture, urgent
obstetrical consultation is recommended. (II-3B)
14. In cases of vaginal bleeding at or after 23 weeks,
speculum or digital vaginal examination should be
deferred until placenta previa is excluded by a prior
or current ultrasound scan. (III-C)
ADJUNCTIVE TESTS FOR
MATERNAL ASSESSMENT
Radiographic Studies
Plain radiographs of the cervical spine, chest, and pelvis are
first line radiological studies.19 Clinicians are often reluctant
to order imaging studies for pregnant patients out of concern
about fetal exposure to ionizing radiation. Patients’ attitudes
may also reflect anxieties that are disproportionate to the
actual risks. Ionizing radiation has the highest teratogenic
potential during the period of organogenesis (5–10 weeks),
with an increased risk of miscarriage before this period.40–42
After 10 weeks, radiation is more likely to produce growth
restriction or CNS effects than teratogenenic changes.40,43
Fetal exposure from the radiological examinations that
are routinely used in the evaluation of pregnant trauma
patients presents a very low risk to the developing fetus
(Table 2).40,44,45 Radiation exposure with a cumulative dose of
> 5–10 rads (50–100 mGy) is associated with an increased
risk of fetal malformation or CNS effects, limited usually
to a gestational age < 18 weeks.40,42,46–48 Concerns about
fetal exposure to radiation should not preclude or delay any
indicated radiological evaluation. CT studies are associated

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SOGC clinical practice guideline
with increased fetal radiation exposure depending on the
body part being scanned, the gestational age, the number
and thickness of slices, and the equipment used. With
abdominal CT during the third trimester the fetal exposure
is around 3.5 rads, which is still under the threshold for fetal
damage.49 Use of gadolinium-based contrast agents has
shown fetal toxicity in animal studies, though no adverse
effects have been reported in human fetuses.50 Their use
can be considered when the maternal benefit outweighs
potential fetal risks.
The carcinogenic effects of ionizing radiation exposure are
still in dispute. Some studies have suggested an increased
risk with exposure to even a low dose of ionizing radiation
in utero, especially before 8 weeks.48,51–53 However, the
lifetime cancer risk from prenatal exposure is considered
to be similar to that from exposure during childhood.48
Further, at an exposure level of < 5 rad, the additional
lifetime risk was < 2% (< 0.6% during childhood), over
and above the background lifetime risk of around 40%.46
Other studies, including a large Ontario-based cohort,
could not confirm an increased risk.54,55 Therefore, if
there is any carcinogenic potential of ionizing radiation
exposure at levels usually used in diagnostic procedure, it
is thought to be quite low. However, careful consideration
of alternative forms of evaluation, accurate completion
of ionizing studies to avoid duplication, and limitation of
the number of CT cuts or area studied may be beneficial
in limiting fetal exposure to radiation.
Laboratory Tests
In all trauma patients, laboratory tests are often ordered
by protocol, but in pregnant patients the clinician should
be aware of alterations in the normal range of a few
laboratory values. The white blood count is usually
elevated and counts up to 20 × 109/L may represent the
physiologic response to pregnancy. Leukocytosis should
be correlated with clinical findings, other lab tests, and
imaging studies to confirm the suspicion of infection
or inflammation. Fibrinogen values are often more than
4 g/L during pregnancy,56 therefore the normal values of
2.5 to 3 g/L for a non-pregnant patient may actually signify
mild hypofibrinogenemia, and levels below 2 g/L may
indicate disseminated intravascular coagulation, a frequent
comorbidity of significant placental abruption.57 D-dimer
measurement is a marker for venous thromboembolism.
However, during pregnancy, the D-dimer is often positive
and therefore is of little value in the diagnosis or exclusion
of venous thromboembolism. Normal range for the
partial pressure of CO2 is decreased during pregnancy
to 27 to 32 mmHg, thus normal non-pregnant values of
40 mmHg may result from mild hypoventilation. Serum
creatinine levels are decreased during pregnancy to 50 to
560 l JUNE JOGC JUIN 2015
60 µmol/L, and even a value as low as 90 µmol/L may
be abnormal. Alkaline phosphatase is secreted by the
placenta, thus levels that are twice the upper limit for
non-pregnant patients are within the normal range during
pregnancy (up to 140 IU/L).58,59 In addition to the routine
laboratory studies for trauma evaluation, it is advisable to
order a coagulation profile including fibrinogen.57
Additional Investigations
Abdominal ultrasound
FAST is a useful aid for the detection of intraperitoneal
fluid in pregnant trauma patients with suspected intra-
abdominal injury. The sensitivity of FAST in detecting
intraperitoneal fluid in pregnant blunt trauma patients was
83% in a study that reviewed 127 pregnant trauma patients.60
This rate is similar to that in a previously published study
of non-pregnant trauma patients.61,62 FAST is an easy and
rapid modality that has the added advantage of avoiding
fetal exposure to ionizing radiation, it should therefore
be part of the secondary survey in pregnant patients with
major trauma.
Peritoneal lavage and laparotomy
DPL is a very rapid and sensitive test with sensitivity of
96% to 100% for detection of traumatic intra-abdominal
injury.63 The main disadvantages of this low cost, easily
interpretable test are that it does not provide information
about specific organ damage, and abdominal injuries
that can be managed conservatively following CT would
require operative intervention based upon DPL. For these
reasons, CT is the most widely used screening modality
for blunt abdominal trauma. CT identifies specific organ
injury, evaluates the retroperitoneum as well and is less
invasive than DPL. Concerns over fetal exposure to
radiation during pregnancy may lead to a more frequent
use of DPL. The open lavage technique is preferable over
a blind needle insertion in the pregnant patient in order
to minimize uterine injury.64 When significant abdominal
blood is detected, an exploratory laparotomy with a
midline incision should be performed.
Recommendations
15. Radiographic studies indicated for maternal
evaluation including abdominal computed
tomography should not be deferred or delayed
due to concerns regarding fetal exposure to
radiation. (II-2B)
16. Use of gadolinium-based contrast agents can
be considered when maternal benefit outweighs
potential fetal risks. (III-C)
17. In addition to the routine blood tests, a pregnant
trauma patient should have a coagulation panel
including fibrinogen. (III-C)

18. Focused abdominal sonography for trauma should
be considered for detection of intraperitoneal
bleeding in pregnant trauma patients. (II-3B)
19. Abdominal computed tomography may be
considered as an alternative to diagnostic peritoneal
lavage or open lavage when intra-abdominal
bleeding is suspected. (III-C)
FETAL ASSESSMENT
Assessment of a viable fetus (≥ 23 weeks gestational age)
should be initiated immediately following, or in parallel
with the physical examination of the stabilized mother
since it has been shown that most placental abruptions
occur shortly after the insult.33 The objectives are:
•• identification of impending hypoxemic fetal injury
or death as a result of uteroplacental compromise or
placental abruption,
•• detection of trauma-related complications of
pregnancy such as placental abruption, preterm
delivery and spontaneous rupture of the membranes,
•• evaluation of the degree of maternal–fetal hemorrhage
and resultant fetal anemia,
•• delineation of fetal injuries, and
•• identification of compensated maternal hypovolemia
first manifested by decreased placental perfusion.
Knowledge of the estimated gestational age is essential
for appropriate interpretation of tests for fetal viability
and well-being. Along with clinical examination of fundal
height and palpation for uterine contractions and tone,
in absence of certainty regarding the gestational age, an
ultrasound examination should be undertaken. Electronic
monitoring of the fetal heart rate should be initiated on
viable fetuses (≥ 23 weeks) as soon as possible. With
a confirmed pre-viable fetus, it may be sufficient to
demonstrate the presence of fetal cardiac activity.
Monitoring of Fetal Heart Rate and Uterine Activity
EFM allows assessment of fetal well-being and uterine
activity, with abnormality of either being predictive of
potential obstetrical complications such as placental
abruption, fetal hypoxic injury or fetal death. Rothenberger
et al reported fetal loss in 61% of cases with major
maternal injuries and 27% with minor injuries, with no
effect on pregnancy outcome following insignificant
maternal injuries.39 Hospital-based studies have suggested
a 5% to 19% risk of fetal death as opposed to a 1.3% risk
in population-based studies. This difference may result
from the fact that more serious injuries are more likely
to be assessed in a hospital.8,65–67 Fetal death may be an
Guidelines for the Management of a Pregnant Trauma Patient
expected consequence of maternal death.33,38 However, a
high Injury Severity Score, serious abdominal injury and
hemorrhagic shock all increase the risk of fetal loss.33,38
Maternal trauma resulting in hypovolemic shock can
reduce uterine perfusion, a direct function of systemic
blood pressure.68 This can be further compounded by
visceral vasoconstriction. Placental abruption can further
reduce transplacental oxygenation. A combination
of these factors can lead to fetal hypoxemic injury.
Compromised fetal perfusion and oxygenation usually
presents with abnormalities in the fetal heart rate pattern.
An abnormality in the fetal heart rate pattern may also be
the first sign of maternal hemodynamic compromise.67
Occasional uterine contractions are the most common
finding with trauma during pregnancy, occurring in
40% of cases,69 and resolving in 90% of cases with no
adverse fetal outcome.70 The intensity and frequency
of contractions are predictive of complications such
as traumatic placental abruption and preterm labour.
Elevated basal uterine tone also raises the suspicions for
placental abruption.
Abnormal EFM tracings following trauma are not
reliable in predicting adverse obstetrical outcome
(sensitivity of 62% and specificity of 49%).69,71 However,
the combination of a normal tracing and physical
examination has a negative predictive value of 100% in
excluding major adverse fetal outcome.33,69,72 Atypical or
abnormal fetal heart rate patterns such as decelerations,
bradycardia, tachycardia or loss of variability mandate
further testing, in utero resuscitation with supplemental
oxygen, IV fluids and left lateral decubitus positioning
or delivery, depending on the severity of the abnormal
pattern, the presumed cause and gestational age. About
2.4% to 7.2% of maternal trauma patients require a
Caesarean delivery shortly after trauma.34,38 Need for a
Caesarean section shortly after trauma is also a risk factor
for maternal death.34
The duration of fetal monitoring following maternal
trauma remains disputed. For many years it has been
suggested that fetal monitoring should continue for at
least 24 hours following the insult33,64,73,74 and some even
suggested a 48-hour period of close fetal monitoring.75
In a prospective study of pregnant trauma patients
that had EFM for a minimum of 4 hours, the majority
demonstrated uterine activity during that period.70
Contractions then abated in most patients. Patients were
discharged home if contractions ceased or were less
frequent than once every 15 minutes. These patients
had pregnancy outcomes similar to that in an uninjured
control group. The sensitivity of predicting placental
JUNE JOGC JUIN 2015 l 561
SOGC clinical practice guideline
abruption by the frequency of uterine activity in the first
4 hours after trauma was 100%. The study suggested
that 4 hours of monitoring was a sensitive method of
predicting immediate post-traumatic adverse obstetrical
outcomes. Another retrospective study of 271 pregnant
patients, suggested monitoring for at least 24 hours
only for a selected group of patients at high risk for
fetal demise, preterm labour, and placental abruption.76
This high risk group consisted of patients involved in
motorcycle, pedestrian or high velocity collisions, those
ejected from motor vehicles and patients demonstrating
maternal tachycardia, abnormal fetal heart rate pattern,
and high injury severity scores. In a study of 317 patients
with minor trauma (48% with falls), 14% had frequent
contractions requiring observation for 24 hours.77
Delivery information was available in 80%. Only one case
of placental abruption occurred, remote from the trauma.
There were no other trauma-related adverse events.
We suggest hospitalization and intermittent fetal heart
rate and uterine activity monitoring by EFM for 24 hours
for patients with
•• uterine tenderness,
•• significant abdominal pain,
•• vaginal bleeding,
•• a contraction frequency of more than once per 10
minutes during a monitoring period of 4 hours,
•• rupture of the membranes,
•• atypical or abnormal fetal heart rate pattern (fetal
tachycardia, bradycardia or decelerations),
•• high risk mechanism of injury (motorcycle, pedestrian,
high speed crash), or
•• serum fibrinogen < 200 mg/dL
•• Monitoring for 4 hours is sufficient to rule out major
trauma-related complications in low risk patients
without the above mentioned risk factors.69,72,78
Prevention of Rh Alloimmunization and
Evaluation of Maternal-fetal Hemorrhage
Traumatic placental injury can result in MFH. MFH occurs
in 10% to 30% of pregnant trauma patients.79 Massive
MFH is a rare complication of trauma and is usually
clinically evident, with fetal demise, abnormal fetal heart
rate pattern (bradycardia or recurrent decelerations), or
abrupt fetal anemia and cardiac failure. The vast majority of
post-traumatic transplacental hemorrhages are smaller and
subclinical. The quantification of the amount of fetal blood
cells in the maternal circulation enables the obstetric care
provider to roughly estimate the degree of transplacental
hemorrhage. This may be important in prevention of Rh
562 l JUNE JOGC JUIN 2015
alloimmunization in Rh-negative mothers. It has also been
suggested that a larger MFH may be predictive of other
adverse obstetrical outcomes.80
The Rh antigen is well developed by 6 weeks gestation81 and
as little as 0.001 mL of fetal blood can cause sensitization
of the Rh-negative mother. Even minor trauma in
pregnancy may cause sensitizing MFH. Several studies
have demonstrated reduced Rh alloimmunization after
routine administration of anti-D immune globulin G (IgG)
to Rh-negative mothers.81–83 Therefore, anti-D IgG should
be given to all Rh-negative pregnant trauma patients.84 A
single dose of 300 mg, administered within 72 hours of
injury, provides protection against sensitization for up
to 30 mL of fetal blood in the maternal circulation.84–86
The feto-placental blood volume is estimated to be
120 mL/kg of fetal weight. In most cases of traumatic
maternal–fetal hemorrhage, the estimated volume of
fetal blood in the maternal circulation is less than 15 mL
and in more than 90% of cases it is less than 30 mL.70,78
Therefore, the vast majority of Rh-negative patients are
protected by one ampule.
The KB test has been used to quantify MFH, so that Rh-
negative women could receive appropriate Rh immune
prophylaxis. If the KB test indicates transplacental
hemorrhage in excess of 30 mL fetal blood, additional
doses of anti-D IgG may be required. According to
the SOGC recommendations for prevention of Rh
alloimmunization,84 KB test may be considered following
events potentially associated with placental trauma and
disruption of the maternal–fetal interface (e.g., placental
abruption, blunt trauma to the abdomen).
A novel approach for detecting MFH, using flow cytometry
as a simpler, more objective, and more precise alternative
to the KB method has been advocated.87,88 Another study
has shown that both manual KB test and flow cytometry
have good sensitivity in detecting and quantifying fetal red
cells.89 Taking into consideration that flow cytometry is not
available in most medical facilities and its added value is
still being investigated, we cannot recommend its routine
use at this time.
The universal use of KB testing for all pregnant
trauma patients, regardless of their Rh status had been
advocated by some,80,90 hypothesizing that the magnitude
of MFH reflects severity of injury and therefore would
be predictive of trauma-related obstetrical complication
such as preterm labour. In one study of maternal
trauma, of the 46 patients with a positive KB test, 44
had contractions (of which 25 had preterm labour),
and of the 25 patients with a negative KB test, none

had contractions or preterm labour.80 No information
was available in this study regarding the incidence of
preterm delivery. The authors concluded that KB test
accurately predicted the risk of preterm labour, and
clinical examination did not. However, it can be argued
that since all women with contractions had a positive
test, and those without contractions did not, presence of
uterine contractions can be used as a surrogate marker
for occurrence of MFH. Therefore the utility of KB test
in rhesus-positive women is not clear. Another review
suggested that KB test should be performed in all maternal
trauma cases, although the basis for this recommendation
for rhesus-positive women was not apparent.90 Others
have suggested the KB test is only useful in Rh-negative
women.69,91 A study comparing incidence of a positive
KB test in women with history of trauma and that in
a low risk population found no significant difference
(2.6% vs. 5.1%, respectively).92 Based on the evidence,
we suggest that KB testing should be done in all rhesus-
negative pregnant trauma patients. Though EFM is more
likely to be clinically useful in rhesus-positive women, KB
test can be considered as an optional test to determine the
need for prolonged monitoring. Given the high incidence
of a false-positive KB test, in rhesus-positive women,
assessment of MFH by flow cytometry could be a useful
adjunct in differentiating true positive KB tests from the
false-positive ones.
The Role of Ultrasound
Ultrasonography is a rapid, non-invasive, valuable tool in
the assessment of pregnant trauma patients and it does
not require transport of the patient from the trauma unit.
An obstetrical ultrasound scan should be done urgently
in cases where the gestational age cannot be determined
with certainty and need for delivery is anticipated based
on an atypical or abnormal fetal heart rate pattern or
suspicion of placental abruption. However, it is not
sensitive in diagnosing placental abruption.70,72 Between
50% and 80% of traumatic abruptions will be missed and
those detected by sonography are usually the clinically
apparent ones, which pose no diagnostic challenge.70,78
The role of the biophysical profile in predicting adverse
obstetrical outcome following trauma is yet to be studied.93
However, in the setting of trauma, EFM is a more
sensitive tool not only to rule out a placental abruption
but also for assessment of fetal well-being as compared to
ultrasound.70,74,78 Nevertheless, ultrasound is an important
adjunctive to the physical examination and fetal assessment
tests. Ultrasonography may assist in:
•• determination of gestational age
•• demonstration of fetal cardiac rate and rhythm
Guidelines for the Management of a Pregnant Trauma Patient
•• placental localization and exclusion of placenta previa
•• assessment of amniotic fluid volume
•• cervical length assessment
•• fetal well-being (biophysical profile)
•• detection of fetal anemia by peak systolic flow velocity
in the middle cerebral artery
•• delineation of possible fetal injury, and
•• confirmation of fetal demise.
Therefore, an obstetrical ultrasound examination is
recommended in all cases of significant maternal trauma
that are admitted for monitoring for more than 4 hours.
However, ultrasound should only be used to complement
EFM, the latter being more sensitive in predicting adverse
outcomes such as placental abruption or fetal hypoxic
injury.69–72 In cases where severe MFH occurred, generally
there is no time for diagnostic tests such as KB test or
middle cerebral artery Doppler. Fetal heart tracing is
usually abnormal, and prompt delivery is recommended.
Ultrasound needs to be done on an urgent basis only in
cases where fetal viability is in question, in all other cases, it
can be undertaken as a non-urgent follow-up examination
prior to discharge of the patient from the hospital. A
reassuring biophysical profile should never be used as a
surrogate for EFM. After discharge from hospital, a follow-
up obstetric ultrasound examination in 2 weeks should be
considered for all patients who needed hospital admission
for maternal or fetal factors (regardless of gestational age),
this is to document normalcy after the traumatic event,
especially of fetal intracranial anatomy and to assess fetal
growth in the interval.94
Recommendations
20. All pregnant trauma patients with a viable
pregnancy (≥ 23 weeks) should undergo electronic
fetal monitoring for at least 4 hours. (II-3B)
21. Pregnant trauma patients (≥ 23 weeks) with
adverse factors including uterine tenderness,
significant abdominal pain, vaginal bleeding,
sustained contractions (> 1/10 min), rupture of the
membranes, atypical or abnormal fetal heart rate
pattern, high risk mechanism of injury, or serum
fibrinogen < 200 mg/dL should be admitted for
observation for 24 hours. (III-B)
22. Anti-D immunoglobulin should be given to all
rhesus D-negative pregnant trauma patients. (III-B)
23. In Rh-negative pregnant trauma patients,
quantification of maternal–fetal hemorrhage by
tests such as Kleihauer-Betke should be done to
determine the need for additional doses of anti-D
immunoglobulin. (III-B)
JUNE JOGC JUIN 2015 l 563
SOGC clinical practice guideline
24. An urgent obstetrical ultrasound scan should be
undertaken when the gestational age is undetermined
and need for delivery is anticipated. (III-C)
25. All pregnant trauma patients with a viable
pregnancy who are admitted for fetal monitoring
for greater than 4 hours should have an obstetrical
ultrasound prior to discharge from hospital. (III-C)
26. It is important to have careful documentation
of fetal well-being in cases involving violence,
especially for legal purposes. (III-C)
OBSTETRICAL COMPLICATIONS OF TRAUMA
Placental Abruption
Abruption of the placenta is a major complication of
maternal trauma, occurring in 5-50% of cases, depending
on the severity of injury.70,78 It is the most common cause
of fetal death in cases of blunt trauma. Resulting from the
difference in physical properties of the relatively inelastic
placental tissue versus the elastic myometrium, significant
abruption of the highly vascular uteroplacental interface
can mediate rapid maternal and in some cases fetal
exsanguination. Most abruptions occur within 2 to 6 hours
after the injury, and almost all of them with 24 hours of
injury.33,95 Abruption may follow even minor trauma and
requires high index of suspicion to detect. The diagnosis
of abruption is based on clinical impression, laboratory
tests and fetal evaluation. Typical findings include
abdominal pain, uterine tenderness, uterine contractions
or hypertonicity, vaginal bleeding, preterm labour, or an
atypical or abnormal EFM tracing. Specific sonographic
findings are uncommon; retroplacental hematoma is
seen in 2% to 25% of abruptions. Treatment should
never be delayed for ultrasound confirmation because
ultrasonography is not reliable in diagnosing placental
abruption. In a study of 149 women with vaginal bleeding,
the sensitivity, specificity, and positive and negative
predictive values of sonography in diagnosing placental
abruption were 24%, 96%, 88%, and 53%, respectively.96
Some have suggested that traumatic abruption tends to
be occult without uterine tenderness or vaginal bleeding
but with a higher incidence of coagulopathy.97 Abruption,
occult or concealed, may lead to major maternal bleeding
and consumption coagulopathy with thrombocytopenia,
prolonged coagulation tests and hypofibrinogenemia.57
Although severe placental abruption can be lethal to the
fetus, a timely and prompt Caesarean section may result
in considerable survival rates of up to 75%.34,98 Delay in
recognition of non-reassuring fetal status, in such cases,
was accountable for 60% of potentially preventable
perinatal deaths. In cases of a non-viable fetus, vaginal
564 l JUNE JOGC JUIN 2015
birth is preferable. Although placental abruption,
particularly with greater than 50% placental separation,
increases the risk of fetal death, it more often results in
preterm labour. Placental abruption is often associated
with a rapid cervical dilation and delivery, induction or
augmentation of labour with a trial of vaginal birth may
be reasonable in a hemodynamically stable mother at or
near term with a normal fetal heart rate pattern. However,
in the presence of fetal or maternal compromise, prompt
delivery by Caesarean is often indicated. Maternal bleeding
and coagulation abnormalities should be aggressively
treated to optimize maternal and fetal outcome. Abruption
remote from term is challenging to manage. Deterioration
in fetal condition or maternal hemodynamic instability is
indications for immediate delivery, even at the expense of
prematurity.95
Uterine Rupture
Post-trauma uterine rupture is rare (0.6% of all maternal
injuries), but seen more frequently with a scarred uterus
or with direct abdominal impact during the latter half
of pregnancy.74 Most (75%) uterine ruptures involve
the fundal area. The degree of rupture may vary from
complete avulsion of the uterus to serosal hemorrhage
and abrasions. Symptoms and signs suggestive of
uterine rupture include: maternal shock, abdominal
distension, irregular uterine contour, palpable fetal parts,
sudden abnormal fetal heart rate pattern, ascent of fetal
presenting part and peritoneal irritation (abdominal
rigidity, guarding and tenderness). Maternal mortality has
been described with traumatic uterine rupture and fetal
mortality is almost universal. It is the cause of MVC-
related perinatal death in 17.5% of the cases.8 Suspected
uterine rupture with maternal and/or fetal comprise
should prompt urgent laparotomy to control bleeding
and facilitate resuscitation.
Preterm Labour
Traumatic injury during pregnancy can result in preterm
labour through several mechanisms. Placental abruption
may culminate in preterm labour in 20% of cases.99 The
extravasation of blood at the placental margin may lead
to decidual necrosis, which, in turn, could initiate the
production of prostaglandin, thereby leading to preterm
labour.99 Traumatic injury to the uterus may also result in
destabilization of lysosomal enzymes which can initiate
prostaglandin production.68 Preterm premature rupture
of membranes is also associated with preterm labour.
Regardless of the mechanism, trauma (even with minor
injuries) is associated with a 2-fold higher risk of preterm
delivery.100 The risk is higher with increasing injury severity
and among those injured early in gestation.100 Signs of

preterm labour should be sought in every patient with a
viable fetus. EFM should be used to assess regularity and
frequency of contractions. When regular contractions
are noted, the fetal fibronectin test or cervical length
assessment to determine the risk for preterm labour
should be considered. Rupture of the membranes, when
suspected, should be ruled out by a speculum examination
including assessment with nitrazine paper and the ferning
test. If risk of preterm delivery is high because of preterm
labour or preterm premature rupture of membranes,
steroids (and any other indicated medications such as
antibiotics and magnesium sulfate), transfer to a tertiary
care centre, and neonatology consultation should be
considered based on gestational age and current location
of the patient. In many cases, iatrogenic preterm delivery
may be indicated to improve fetal or maternal outcome.
Direct Fetal Injury
Direct fetal injury is seen in less than 1% of blunt maternal
trauma.101 Maternal soft tissues, uterus, and amniotic fluid
serve to diminish the force delivered to the fetus. Direct
fetal injury from blunt abdominal trauma often involves
the fetal skull and brain. One possible mechanism involves
fracture of the maternal pelvis in late gestation with an
engaged fetal head resulting in fetal skull fracture.102 A
deceleration injury of an unengaged head can also occur.103
Fetal injuries in other modes of maternal trauma are
considered in the section below.
Recommendation
27. Management of suspected placental abruption
should not be delayed pending confirmation by
ultrasonography; ultrasound is not a sensitive tool
for its diagnosis. (II-3B)
ADDITIONAL CONSIDERATIONS REGARDING
SPECIFIC TRAUMATIC INJURIES
Penetrating Trauma
Penetrating trauma during pregnancy is becoming more
common. Penetrating abdominal injuries are caused
primarily by gunshot or stab wounds. As in non-pregnant
individuals, stab wounds tend to have a better prognosis
than gunshot wounds. The maternal bowel is less likely
to be involved with penetrating injuries after the second
trimester due to the protection provided by the large uterus.
The incidence of maternal visceral injury with penetrating
abdominal trauma is only 15% to 40% compared with 80%
to 90% in non-pregnant women.35 Although the visceral
organs are displaced upwards and are less likely to be
injured, upper abdominal stab wounds can result in more
complex bowel injury. Thoraco-abdominal penetrating
injuries, below the fourth intercostal space anteriorly, or the
Guidelines for the Management of a Pregnant Trauma Patient
tip of the scapula posteriorly, may cause visceral injuries
that are easily missed. At the same time that the gravid,
abdominal uterus provides protection to the abdominal
viscera, it is susceptible, along with the fetus, to direct injury.
According to Buchsbaum, the uterine musculature absorbs
a great amount of the projectile’s velocity and diminishes
its ability to damage the viscera.29 Therefore, depending
on the gestational age and the size of the uterus, the fetus
is much more likely than the mother to sustain significant
injury (and to die) after a penetrating abdominal trauma. In
general, the fetus sustains injury in 60% to 70% of cases,
while visceral maternal injuries are seen only in 20% of
penetrating abdominal trauma.
Gunshot wounds produce transient shock waves and
cavitations in displacement of kinetic energy to body
tissue, causing more damage and thus higher mortality
for both mother and fetus than low-velocity injuries:
70% of abdominal gunshot wounds result in fetal injury,
and 40% to 65% of these fetuses die.104 Fetal mortality
generally results from premature delivery, maternal shock,
uteroplacental injury, or direct fetal injury.105 A study
of 321 pregnant trauma patients showed that 9% had
penetrating trauma, of which 73% were gunshot wounds.4
The risk of maternal death was not significantly higher
with penetrating trauma than with blunt trauma (7% vs.
2%); however, fetal mortality was significantly higher (75%
vs. 10%) with penetrating trauma.
Penetrating injuries in pregnant trauma patients are
managed in essentially the same way as in non-pregnant
patients. The standard of care is to prioritize the emergent
treatment of the gravid patient above that of her fetus.
The hemodynamically stable patient should be assessed
by non-invasive diagnostic methods such as ultrasound
and triple contrast CT scan. The same indications for
surgical exploration apply as in the non-pregnant patient
(positive findings on lavage, free air under the diaphragm
before lavage, progressive abdominal distention with
a declining hematocrit, or abdominal wall disruption
or perforation). In cases of exploration, the decision
to proceed with Caesarean section should be weighed
against the likelihood for fetal survival and long-term
complications of prematurity and should be made in
consultation with the trauma surgeon, neonatologist, and
pediatric surgeon. Factors that can influence the decision
to proceed with Caesarean section are gestational age,
extent and severity of fetal injury, degree of uteroplacental
compromise, parameters of fetal well-being, and the
need for hysterectomy with extensive uterine injury.
A dead or injured fetus is not considered an indication
for exploration, as the fetus will usually spontaneously
JUNE JOGC JUIN 2015 l 565
SOGC clinical practice guideline
abort or can be delivered vaginally. Tetanus vaccination
is safe in pregnancy and should be given, when indicated,
according to the usual protocol.106,107
Domestic or Intimate Partner Violence
The incidence of domestic or intimate partner violence
increases during pregnancy and is clustered in the third
trimester.6,108 Domestic violence was reported by 6.6%
of pregnant women in Ontario.108 The most commonly
struck body area was the abdomen (64%), a risk factor
for both maternal and fetal adverse outcome. Other
studies have reported an even higher incidence of abuse
during pregnancy (10–30%), with 5% resulting in fetal
death.109,110 Every woman who sustains trauma, particularly
penetrating abdominal trauma, should be questioned
specifically about domestic violence. Careful, detailed,
and contemporaneous documentation is essential. Such
inquiry should occur in the absence of the partner.
Motor Vehicle Collision
In the pregnant population, MVC is the leading cause
of maternal death, and after placental abruption,
maternal death is the leading cause of fetal death.111,112
Of 351 maternal deaths from non-obstetric causes in
a trauma centre registry, 72% resulted from MVC.113
Documentation of the nature of the injury and of
maternal and fetal status is important for reasons that
include evaluating whether any subsequent adverse
outcome should be attributed to the MVC.
The outcome of MVC can range from no trauma at all
to severe multi-organ damage and death. The outcome
is related to various factors including the mechanism of
the collision itself, the acceleration-deceleration velocities
of the vehicles involved, and the use of protective
mechanisms, such as seat belts, air bags, and other safety
features. Wearing a seat belt in a motor vehicle during
pregnancy is useful and effective in reducing the risk
of adverse pregnancy outcomes including maternal
death.113,114 Crosby and Costiloe reported a reduction in
the maternal death rate from 33% to 5% with the use
of a two-point seatbelt, and that finding was reproduced
by a more recent study.112,115 During prenatal visits, the
caregiver should emphasize the importance of wearing a
properly adjusted and positioned seatbelt at all times and
refute any misconception about the use of seatbelts during
pregnancy.116 Ejection from the vehicle increases the risk
to both the woman and the fetus. The lap belt should be
positioned below the abdomen and not over the uterus.
The shoulder belt should be placed between the breasts.
The belt should be comfortable, but not tight. Air bags
are a relatively newer modality in preventing and reducing
injuries in MVC. In a simulated study, a combination of
566 l JUNE JOGC JUIN 2015
seatbelts and air bag was the most beneficial, and could
be lifesaving in severe MVC.117 Deployment of airbags
has been associated with adverse events such as uterine
rupture, placental abruption, and fetal death that were
attributed to the air bags.113,118,119 However, this is more
likely a reflection of the severity of traumatic force rather
than a causal association. At this point there are not
enough data to make a recommendation about disabling
air bags during pregnancy. Furthermore, when the risk
of fetal death or injury is balanced against risks to the
mother, the latter should take precedence, recognizing
the fact that fetal well-being is dependent on maternal
well-being.
Although organ damage, fractures, and hemorrhage can
occur in MVC, the most common mechanism of injury
is blunt trauma, which can cause both maternal and fetal
morbidity and mortality. The mechanism of trauma often
involves the uterus. A force applied to the uterus can
deform the shape of the uterus due to its elasticity, but
can have a smaller deforming effect on the less elastic
placenta. This can result in a shearing force that may
separate the attached placenta from the uterus. Abrupt
changes in amniotic fluid pressure may further contribute
to placental separation. The end result of this kind of
mechanism is placental abruption. One report suggested
that up to 37% of life-threatening maternal injuries after
MVC are complicated by abruption, whereas in non–
life-threatening injuries, the incidence of abruption was
only 1.6%.120 Uterine contractions may also result from
blunt trauma and lead to preterm labour. Relatively
minor injuries may be associated with a grave pregnancy
outcome.121 Maternal–fetal hemorrhage may be a serious
complication of blunt trauma. Exsanguination into
maternal circulation can occasionally culminate in fetal
demise. Direct fetal intracranial injury is another, albeit
uncommon, mechanism of fetal injury.122 This type of
injury may be attributed to a direct trauma to the fetal
head but may also result from a massive maternal–fetal
hemorrhage and significant fetal hypotension with
subsequent hypoxic-ischemic intracranial injury.
Falls
Falls are the cause in 3% to 31% of cases of maternal
trauma.69,123 Less than 10% of falls are associated with
significant maternal or fetal complications.124 They are
more common in the latter half of pregnancy, particularly
after 32 weeks.69,74 The increase in lumbar lordosis that is
seen in pregnancy moves the centre of gravity forward
and contributes to an increased incidence of falls.123
Therefore, aggressive high-impact activity should be
avoided in advanced pregnancy. Complications associated

with falls include preterm labour, placental abruption,
uterine rupture, fetal growth restriction, and fetal death.123
Electrical Trauma
Electrical shock is the fifth leading cause of fatal
occupational injuries in the United States and most
commonly result from failure to ground appliances
properly or from using electrical devices while wet.125
The literature on maternal electrical trauma is scarce and
possibly misleading due to publication bias stemming
from the tendency to report adverse outcomes rather
than uneventful insults. Nevertheless, several case series
have emphasized poor fetal outcome of electrical trauma.
Fatovich reviewed the literature and found 15 cases
of maternal electric shock with a fetal mortality rate of
73% and only 1 normal pregnancy outcome.126 The
Motherisk Program published a prospective cohort study
of 31 pregnant women with electric shock who sought
experts’ advice via telephone127; 28 of those women
delivered healthy newborns. One spontaneous abortion
was temporally related to the insult, another was probably
unrelated to the injury, and a third baby was born with
a ventricular septal defect. Mean birth weight, gestational
age at delivery, rates of Caesarean section, and incidence of
neonatal distress were similar between electric shock and
control groups.127 Several risk factors for adverse perinatal
outcome were identified. The magnitude of the current
obviously has an impact on outcome. The pathway of the
current in the body, from entrance to exit points, is of
utmost importance. A current that travels from the hand
to the foot will probably go through the uterus, stimulating
myometrial contractions, which may culminate in preterm
labour.127 Electrical current that traverses the amniotic
fluid (an excellent conductor) may lead to spontaneous
abortion, fetal demise, or fetal burns.128 Other risk factors
include maternal body weight, blunt trauma following the
electrical insult, and being wet.
Maternal and fetal assessment is warranted in cases of
electrical injury during pregnancy.129 Electrocardiography,
urine tests for major muscle injury, X-ray imaging, and
sometimes CT are all part of the initial evaluation of the
mother. With a viable fetus, EFM is recommended for 24
hours if the injury involved loss of consciousness, abnormal
maternal ECG, or known maternal cardiovascular illness.
In most other cases, and especially if the insult involved
low voltage, immediate fetal effects are unlikely.
Summary Statement
At this time, there is insufficient evidence to
support the practice of disabling air bags for pregnant
women. (III)
Guidelines for the Management of a Pregnant Trauma Patient
Recommendations
28. Tetanus vaccination is safe in pregnancy and should
be given when indicated. (II-3B)
29. Every woman who sustains trauma should be
questioned specifically about domestic or intimate
partner violence. (II-3B)
30. During prenatal visits, the caregiver should
emphasize the importance of wearing seatbelts
properly at all times. (II-2B)
PERIMORTEM CAESAREAN SECTION
The concept of performing Caesarean section concurrent
with maternal resuscitation was introduced in 1986
when it was recommended that the procedure should be
done no later than 4 minutes following maternal cardiac
arrest.130,131 The rationale for the recommendation was
improved efficacy of maternal chest compression after
delivery by alleviating the aortocaval compression exerted
by the gravid uterus and allowing adequate venous return.
Neurologic injury in the mother begins 6 minutes after
cessation of cerebral blood flow; to obtain cardiac
return by 5 minutes and avoid neurological damage the
Caesarean section should be started 4 minutes after the
maternal pulse ceases.24,41,132 A perimortem Caesarean
section is recommended for viable pregnancies (≥ 23
weeks, or fundal height 2 or more fingerbreadths
above the umbilicus).132 In these cases, not only is the
uterus large enough to cause significant aortocaval
compression (its emptying therefore allowing improved
maternal cardiac output), the baby is also mature enough
that it may survive the event even if the mother does
not.132 Prolonged resuscitation is not recommended
if no pulse can be obtained, and the uterus should be
emptied to increase the likelihood of successful maternal
resuscitation and a healthy infant. In many trauma cases,
resuscitation will be futile because of a fatal cause. In
such cases, there is no reason to delay Caesarean section
to save a viable fetus. It should be emphasized that many
studies and case reports relate non-traumatic cardiac
arrests in which the maternal resuscitation efforts were
the major indication for delivery. Trauma patients with
cardiac arrest are less likely to respond to resuscitation; in
these cases, perimortem Caesarean is performed primarily
for fetal salvage. Delivery of a viable neonate is less likely
when no maternal vital signs have been recorded for 15
to 20 minutes.131,132 A multi-institutional retrospective
cohort study showed that of 33 fetuses delivered by
emergency Caesarean section in the setting of maternal
trauma, 13 had no fetal heart tones at the initiation of
the Caesarean section and none survived. When no fetal
JUNE JOGC JUIN 2015 l 567
SOGC clinical practice guideline
heart tones can be demonstrated at initial assessment
of a pregnant trauma patient after 23 weeks’ gestation,
Caesarean section is likely to be futile in terms of fetal
survival.34
Recommendation
31. A Caesarean section is recommended for viable
pregnancies (≥ 23 weeks) no later than 4 minutes
(when possible) following maternal cardiac
arrest to aid with maternal resuscitation and fetal
salvage. (III-B)
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North Am 2007;34:555–83.
112. Crosby WM, Costiloe JP. Safety of lap-belt restraint for pregnant victims
of automobile collisions. N Engl J Med 1971;284:632–6.
113. Brookfield KF, Gonzalez-Quintero VH, Davis JS, Schulman CI. Maternal
death in the emergency department from trauma. Arch Gynecol Obstet
2013;288:507–12.
114. Hyde KH, Cook LJ, Olson LM, Weiss HB, Dean JM. Effect of
motor vehicle crashes on adverse fetal outcomes. Obstet Gynecol
2003;102:279–86.
115. Luley T, Fitzpatrick CB, Grotegut CA, Hocker MB, Myers ER,
Brown HL. Perinatal implications of motor vehicle accident trauma
during pregnancy: identifying populations at risk. Am J Obstet Gynecol
2013;208(6):466.e1–e5.
116. Johnson HC, Pring DW. Car seatbelts in pregnancy: the practice and
knowledge of pregnant women remain causes for concern. BJOG
2000;107:644–7.
117. Moorcroft DM, Stitzel JD, Duma GG, Duma SM. Computational model
of the pregnant occupant: predicting the risk of injury in automobile
crashes. Am J Obstet Gynecol 2003;189:540–4.
118. Schultze PM, Stamm CA, Roger J. Placental abruption and fetal death
with airbag deployment in a motor vehicle accident. Obstet Gynecol
1998;92(4 Pt 2):719.
119. Fusco A, Kelly K, Winslow J. Uterine rupture in a motor vehicle crash
with airbag deployment. J Trauma 2001;51:1192–4.
120. Pearlman MD. Motor vehicle crashes, pregnancy loss and preterm labor.
Int J Gynecol Obstet 1997;57:127–32.
121. Schiff MA, Holt VL. The injury severity score in pregnant trauma
patients: predicting placental abruption and fetal death. J Trauma
2002;53:946–9.
122. Hagmann CF, Schmitt-Mechelke T, Caduff JH, Berger TM. Fetal
intracranial injuries in a preterm infant after maternal motor vehicle
accident: a case report. Pediatr Crit Care Med 2004;5:396–8.
123. Tweddale CJ. Trauma during pregnancy. Crit Care Nurs Q 2006;29:53–67.
124. Fort A, Harlin R. Pregnancy outcome after noncatastrophic maternal
trauma during pregnancy. Obstet Gynecol 1970;35:912–5.

125. Fish R. Electric shock. Part I: physics and pathophysiology. J Emerg Med
1993;11:309–12.
126. Fatovich DM. Electric shock in pregnancy. J Emerg Med 1993;11:175–7.
127. Einarson A, Bailey B, Inocencion G, Ormond K, Koren G. Accidental
electric shock in pregnancy: a prospective cohort study. Am J Obstet
Gynecol 1997;176:678–81.
128. Jaffe R, Fejgin M, Ben Aderet N. Fetal death in early pregnancy due to
electric current. Acta Obstet Gynecol Scand 1986;65:283.
129. Fish RM. Electric injury. Part III: cardiac monitoring indications, the
pregnant patient, and lightning. J Emerg Med 2000;18:181–7.
Guidelines for the Management of a Pregnant Trauma Patient
130. Katz VL, Dotters DJ, Droegemueller W. Perimortem cesarean delivery.
Obstet Gynecol 1986;68:571–6.
131. Katz V, Balderston K, DeFreest M. Perimortem cesarean delivery: were
our assumptions correct? Am J Obstet Gynecol 2005;192(6):1916–20.
132. Katz VL. Perimortem cesarean delivery: its role in maternal mortality.
Semin Perinatol 2012;36:68–72.
133. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian
Task Force on Preventive Health Care. New grades for recommendations
from the Canadian Task Force on Preventive Health Care. CMAJ
2003;169:207–8.
JUNE JOGC JUIN 2015 l 571
 JOINT SOGC-APOG POLICY STATEMENT

JOINT SOGC-APOG POLICY

No. 246,STATEMENT
September 2010 (Replaces No. 176, April 2006)

Pelvic Examinations by Medical Students

This joint policy statement has been reviewed by the Society
of Obstetricians and Gynaecologists of Canada (SOGC) Ethics
Committee, the Association of Professors of Obstetrics and
Gynaecology of Canada (APOG) Undergraduate Committee,
and the APOG Department Chairs Committee, and approved
by the Executive and Council of the SOGC and the Board of
Directors of the APOG.
PRINCIPAL AUTHORS
Kimberly E. Liu, MD, Toronto ON
Jodi Shapiro, MD, Toronto ON
Deborah Robertson, MD, Toronto ON
Susan Chamberlain, MD, Kingston ON
ETHICS COMMITTEE
Jodi Shapiro, MD (Chair), Toronto ON
Saima S. Akhtar, MD, London ON
Bruno Camire, MD, Quebec QC
Jan Christilaw, MD, Vancouver BC
Julie Corey, RM, St Jacobs ON
Erin Nelson, LLM, Edmonton AB
Marianne Pierce, MD, Halifax NS
Deborah Robertson, MD, Toronto ON
Anne H. Simmonds, MN, Halifax NS
Disclosure statements have been received from all members
of the committees.
GENERAL PRINCIPLES
nsuring the quality of medical education is important to
E ensuring that all Canadians have access to good health
care today and in the future; however, patient autonomy
should be respected in all clinical and educational interactions.
When a medical student is involved in patient care, patients
should be told what the student’s roles will be, and patients
must provide consent. Patient participation in any aspect of
medical education should be voluntary and non-discriminatory.
J Obstet Gynaecol Can 2010;32(9):872–874
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
PREAMBLE
Women’s health is an important element of the medical
school curriculum, and all physicians must be trained in the
basic knowledge and skills pertinent to the care of the
female patient. Regardless of the specialty that medical stu-
dents ultimately choose to pursue, as medical practitioners
they need to learn to perform pelvic examinations in a sensitive,
competent, and ethical manner. They need not only the
capacity to perform the examination but also the ability to
communicate with the patient and obtain consent for the
examination. Use of standardized patients and models can
be effective in teaching medical students the technique of
pelvic examinations and should allow students to feel com-
fortable with pelvic examinations prior to patient contact.1
Medical students will also have the opportunity to learn pelvic
examinations during clinical clerkship in the ambulatory
clinic setting, as well as in hospital rotations under appropriate
supervision.
Pelvic examinations are an integral component of any
gynaecologic consultation, and pelvic examinations under
anaesthesia are a fundamental part of most gynaecologic
surgery. Under anaesthesia, pelvic and abdominal muscles
are relaxed, and the patient is free from discomfort, thus
allowing the surgeon to fully appreciate the pelvic anatomy
and clinical findings in a way that may not be possible when
the patient is awake.
All surgeries require a surgical team, which, in addition to
the primary surgeon, may consist of an anaesthesiologist,
surgical assistants, and nurses, who are all present in the
operating room. Resident physicians and medical students
are also members of the surgical team and are involved in
the preoperative, intraoperative, and postoperative care of the
patient. During surgery, they are not merely observers but
often play an essential role as surgical assistants. Members
of the gynaecologic surgical team examine the patient
preoperatively in order to confirm underlying pathology,
determine the most appropriate surgical approach, and
understand the patient’s individual anatomy.2 As an educa-
tional setting, this also provides an opportunity for the

872 l SEPTEMBER JOGC SEPTEMBRE 2010


student to be guided through a pelvic examination by an
expert teacher.
If future generations of women are to have access to adequate
health care, medical students must be trained to competently
examine female patients. The teaching of these examinations,
however, can pose ethical problems.3 Many women under-
going pelvic surgery may not be aware of the role medical
students play or of the importance of performing a pelvic
examination at the time of surgery.4 The sensitivity of this
issue has been recognized within the medical community
for over 20 years,5 and medical societies have enacted
guidelines in response to these concerns.6,7 The controversy
about medical students’ performing pelvic examinations on
anaesthetized women has been well documented.2,8,9
The most important consideration in this educational setting is
the need to establish that the patient has consented to a pelvic
examination by a medical student before that examination is
performed.10 Patients have the right to refuse medical treat-
ment and participation in medical teaching exercises. In
fact, most patients are willing to participate in medical
education5,11–15 but want to be informed of medical student
involvement in their care.4,14,15 Physicians and students
must be explicit about student participation during the
consent process.16 Patient participation in medical education
in an academic or any teaching centre should be non-
discriminatory and respectful of patients’ rights and
autonomy.6 Race or socioeconomic status should not be the
basis for selection of patients for teaching. Pelvic examina-
tions under anaesthesia are not the primary means of
teaching pelvic examinations to medical students, and
students should not be brought into the operating room
solely to perform a pelvic examination on an anaesthetized
patient.
OBTAINING INFORMED CONSENT TO PELVIC
EXAMINATIONS PERFORMED BY MEDICAL STUDENTS
1. On Patients in Clinical Settings (in-patient
wards, out-patient clinics, and birth units)
Medical students must introduce themselves to patients and
identify themselves as medical students. If a student will be
performing a pelvic examination, he or she must explain the
procedure that will be performed and seek the patient’s
permission to perform the examination. Patient consent
must be voluntary and not coerced.
2. On Patients Under Anaesthesia During Surgery
All members of the gynaecologic surgical team (including
medical students, residents, and fellows) are expected to
introduce themselves to the patient before her gynaecologic
surgery. Medical students must identify themselves as
Pelvic Examinations by Medical Students
medical students, and they must explain that they will be
assisting in the surgery.
As part of the surgical consent, patients should be informed
that pelvic examinations will be performed by members of
the gynaecologic surgical team following the induction of
anaesthesia and before initiation of surgery. Verbal consent
for a medical student to be part of the surgical team and to
perform an examination under anaesthesia should be
obtained and documented. Patient consent must be volun-
tary and not coerced. When possible, a discussion about the
teaching environment in the operating room should take
place with the patient in the office when she signs consent
for surgery.
In summary, in out-patient clinics, in-patient settings, and
birth units, medical students must introduce themselves
and identify themselves as medical students to the patient.
Verbal consent from the patient is required before a pelvic
examination is performed.
When pelvic examinations are to be performed during
surgery while a patient is under anaesthesia, medical
students must introduce themselves and identify them-
selves as medical students to the patient before the surgery.
Consent for the pelvic examination under anaesthesia by
the gynaecologic surgical team, including the medical
student, must be obtained.
Pelvic examinations under anaesthesia should not be the
primary means of teaching pelvic examinations to medical
students, and students must not be brought into the operating
room solely to perform a pelvic examination on an
anaesthetized patient.
ENSURING ADEQUATE SUPERVISION
Medical students must perform pelvic examinations only
under the supervision of an appropriately qualified health
care professional (i.e., nurse, resident, midwife, or
physician). Medical students may and should decline to
participate if they do not feel comfortable with the
circumstances of the examination.
SUMMARY
The pelvic examination is an integral part of the gynaeco-
logical consultation and fundamental to planning any
gynaecological surgical intervention. Competently performing
the pelvic examination is an essential skill for all medical
professionals, but its sensitive nature makes it challenging
to teach and to learn. While educational tools such as didactic
teaching sessions and the use of standardized patients and
pelvic models have largely replaced the clinical patient as the
initial stage of teaching medical students how to perform a
pelvic examination, the best means of consolidating that
SEPTEMBER JOGC SEPTEMBRE 2010 l 873
JOINT SOGC-APOG POLICY STATEMENT
knowledge is examining a patient in a clinical setting.
Indeed, our patients are our best teachers.
In all settings, the patient’s consent must always be obtained
by the medical student or a member of the gynaecologic
surgical team before the medical student performs a pelvic
examination. Medical students must introduce themselves
to all patients in whose care they are participating and identify
their role as medical students. Specifically, patients who are
undergoing gynaecologic surgery should understand the
role of a pelvic examination during the procedure and that it
may be performed by members of the gynaecologic surgical
team, including medical students. In all settings, consent
must be given voluntarily and must not be coerced.
In order to maintain high standards of women’s health care
in Canada, all physicians must be trained to perform an
appropriate pelvic examination and to detect abnormal
pathology. Medical students are members of the medical
team, and they should be involved in the full scope of
patient care—communication, physical examination
including pelvic examinations, diagnosis, and therapy. During
their clinical rotations, medical students need to learn and
perform pelvic examinations with adequate supervision to
ensure the safety and comfort of the patient and to optimize
their learning experience.
REFERENCES
1. Siwe K, Wijma K, Stjernquist M, Wijma B. Medical students learning the
pelvic examination: comparison of outcome in terms of skills between
a professional patient and a clinical patient model. Patient Educ Couns
2007;68(3):211–7.
2. Wall LL, Brown D. Ethical issues arising from the performance of pelvic
examinations by medical students on anesthetized patients. Am J Obstet
Gynecol 2004;190(2):319–23.
874 l SEPTEMBER JOGC SEPTEMBRE 2010
3. Coldicott Y, Pope C, Roberts C. The ethics of intimate examinations-
teaching tomorrow’s doctors. BMJ 2003;326(7380):97–101.
4. Wainberg S, Wrigley H, Fair J, Ross S. Teaching pelvic examinations under
anaesthesia: what do women think? J Obstet Gynaecol Can 2010;32:49–53.
5. Bibby J, Boyd N, Redman CW, Luesley DM. Consent for vaginal examination
by students on anaesthetised patients. Lancet 1988;2(8620):1150.
6. Professional responsibilities in obstetric-gynecologic education. ACOG
Committee Opinion 2007, No. 358. American College of Obstetricians
and Gynecologists. Obstet Gynecol 2007;109:239–42. Available at:
http://www.acog.org/from_home/publications/ethics/c0358.pdf.
Accessed February 15, 2010.
7. Gynaecological examinations: guidelines for specialist practice. London:
Royal College of Obstetricians and Gynaecologists Press; 2002.
8. Ubel PA, Jepson C, Silver-Isenstadt A. Don’t ask, don’t tell: a change in
medical student attitudes after obstetrics/gynecology clerkships toward
seeking consent for pelvic examinations on an anesthetized patient.
Am J Obstet Gynecol 2003;188(2):575–9.
9. Hicks LK, Lin Y, Robertson DW, Robinson DL, Woodrow SI.
Understanding the clinical dilemmas that shape medical students’
ethical development: questionnaire survey and focus group study.
BMJ 2001;322(7288):709–10.
10. Wilson RF. Autonomy suspended: using female patients to teach intimate
exams without their knowledge or consent. J Health Care Law Policy
2005;8:240–63.
11. Lawton FG, Redman CW, Luesley DM. Patient consent for gynaecological
examination. Br J Hosp Med 1990;44(5):326,9.
12. Ubel PA, Silver-Isenstadt A. Are patients willing to participate in medical
education? J Clin Ethics 2000;11:230–5.
13. Silver-Isenstadt A, Ubel PA. Erosion in medical students’ attitudes about
telling patients they are students. J Gen Intern Med 1999;14:481–7.
14. Wilson RF. Unauthorized practice: teaching pelvic examination on women
under anesthesia. J Am Med Womens Assoc 2003;58:217–20; discussion 221–2.
15. Magrane D, Gannon J, Miller CT. Student doctors and women in labor:
attitudes and expectations. Obstet Gynecol 1996;88:298–302.
16. O’Flynn N, Rymer J. Consent for teaching: the experience of women
attending a gynaecology clinic. Med Educ 2003;37:1109–14.
 SOGC CLINICAL PRACTICE GUIDELINE

SOGC CLINICAL PRACTICE GUIDELINE No. 250, November 2010

Recurrent Urinary Tract Infection

Abstract
This Clinical Practice Guideline has been prepared by the
Urogynaecology Committee, reviewed by the Family Physicians Objective: To provide an update of the definition, epidemiology,
Advisory Committee, and approved by the Executive and Council clinical presentation, investigation, treatment, and prevention of
of the Society of Obstetricians and Gynaecologists of Canada. recurrent urinary tract infections in women.
PRINCIPAL AUTHORS Options: Continuous antibiotic prophylaxis, post-coital antibiotic
Annette Epp, MD, Saskatoon SK prophylaxis, and acute self-treatment are all efficient alternatives
to prevent recurrent urinary tract infection. Vaginal estrogen and
Annick Larochelle, MD, St. Lambert QC cranberry juice can also be effective prophylaxis alternatives.
UROGYNAECOLOGY COMMITTEE
Evidence: A search of PubMed and The Cochrane Library for
Danny Lovatsis, MD (Chair), Toronto ON articles published in English identified the most relevant literature.
Jens-Erik Walter, MD (Co-Chair), Westmount QC Results were restricted to systematic reviews, randomized control
trials/controlled clinical trials, and observational studies. There
William Easton, MD, Scarborough ON were no date restrictions.
Annette Epp, MD, Saskatoon SK
Values: This update is the consensus of the Sub-Committee on
Scott A. Farrell, MD, Halifax NS Urogynaecology of the Society of Obstetricians and
Lise Girouard, RN, Winnipeg MB Gynaecologists of Canada. Recommendations were made
according to the guidelines developed by the Canadian Task
Chander Gupta, MD, Winnipeg MB Force on Preventive Health Care (Table 1).
Marie-Andrée Harvey, MD, Kingston ON
Options: Recurrent urinary tract infections need careful investigation
Annick Larochelle, MD, St. Lambert QC and can be efficiently treated and prevented. Different prophylaxis
Magali Robert, MD, Calgary AB options can be selected according to each patient’s
characteristics.
Sue Ross, PhD, Calgary AB
Joyce Schachter, MD, Ottawa ON Recommendations

Jane A. Schulz, MD, Edmonton AB 1. Urinalysis and midstream urine culture and sensitivity should be
performed with the first presentation of symptoms in order to
David Wilkie, MD, Vancouver BC
establish a correct diagnosis of recurrent urinary tract infection.
FAMILY PHYSICIANS ADVISORY COMMITTEE (III-L)
William Ehman, MD (Chair), Naniamo BC 2. Patients with persistent hematuria or persistent growth of bacteria
Sharon Domb, MD, Toronto ON aside from Escherichia coli should undergo cystoscopy and
imaging of the upper urinary tract. (III-L)
Andrée Gagnon, MD, Blainville QC
Owen Hughes, MD, Ottawa ON 3. Sexually active women suffering from recurrent urinary tract
infections and using spermicide should be encouraged to consider
Jill Konkin, MD, Edmonton AB an alternative form of contraception. (II-2B)
Joanna Lynch, MD, Winnipeg MB
4. Prophylaxis for recurrent urinary tract infection should not be
Cindy Marshall, MD, Lower Sackville NS undertaken until a negative culture 1 to 2 weeks after treatment
Disclosure statements have been received from all members of has confirmed eradication of the urinary tract infection. (III-L)
the committees. 5. Continuous daily antibiotic prophylaxis using cotrimoxazole,
The literature searches and bibliographic support for this guideline nitrofurantoin, cephalexin, trimethoprim, trimethoprim-
were undertaken by Becky Skidmore, Medical Research Analyst, sulfamethoxazole, or a quinolone during a 6- to 12-month period
Society of Obstetricians and Gynaecologists of Canada. should be offered to women with ³ 2 urinary tract infections in
6 months or ³ 3 urinary tract infections in 12 months. (I-A)
6. Women with recurrent urinary tract infection associated with
sexual intercourse should be offered post-coital prophylaxis as
Key Words: Recurrent urinary tract infection, prophylaxis, an alternative to continuous therapy in order to minimize cost
treatment, antibiotic, prevention and side effects. (I-A)

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should
not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

1082 l NOVEMBER JOGC NOVEMBRE 2010


Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.82
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.82
7. Acute self-treatment should be restricted to compliant and
motivated patients in whom recurrent urinary tract infections have
been clearly documented. (I-B)
8. Vaginal estrogen should be offered to postmenopausal women
who experience recurrent urinary tract infections. (I-A)
9. Patients should be informed that cranberry products are effective
in reducing recurrent urinary tract infections. (I-A)
10. Acupuncture may be considered as an alternative in the prevention
of recurrent urinary tract infections in women who are unresponsive
to or intolerant of antibiotic prophylaxis. (I-B)
11. Probiotics and vaccines cannot be offered as proven therapy for
recurrent urinary tract infection. (II-2C)
12. Pregnant women at risk of recurrent urinary tract infection should
be offered continuous or post-coital prophylaxis with nitrofurantoin
or cephalexin, except during the last 4 weeks of pregnancy.
(II-1B)
J Obstet Gynaecol Can 2010;32(11):1082–1090
DEFINITION AND EPIDEMIOLOGY
rinary tract infection is one of the most common
U bacterial infections in women, and 50% to 60% of
adult women experience a UTI during their lifetime.1,2 It is
ABBREVIATIONS
E. coli Escherichia coli
HPF high-power field
TMP-SMX trimethoprim-sulfamethoxazole
UTI urinary tract infection
Recurrent Urinary Tract Infection
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
estimated that in young women there are 0.5 episodes of
acute cystitis per person per year.3 This incidence decreases
with age. In postmenopausal women, it is estimated that
there are 0.07 episodes of acute cystitis per person per year.4
Recurrent UTI is defined as 2 uncomplicated UTIs in
6 months or, more traditionally, as ³ 3 positive cultures
within the preceding 12 months.5,6 This is estimated to
affect 25% of women with a history of UTI. When there is
recurrent infection with the same organism despite ade-
quate therapy, it is considered a relapse. Reinfection is
defined as recurrent UTI caused by a different bacterial
isolate, or by the previously isolated bacteria after a negative
intervening culture or an adequate time period (³ 2 weeks)
between infections.7
Reinfection is more common than relapse.8 Most recur-
rences occur within the first 3 months after the primary
infection, and there can often be clustering of infections.9,10
When the initial infection is caused by E. coli, there is a
higher risk of reinfection within the first 6 months.11
PRESENTATION
Classic symptoms of acute lower UTI include dysuria, uri-
nary frequency, and suprapubic pain plus or minus
hematuria. Differential diagnoses include vaginitis, acute
urethritis, interstitial cystitis, and pelvic inflammatory dis-
ease. Other organisms that may be involved and mimic
acute cystitis include Chlamydia, Neisseria gonorrhea, Candida,
NOVEMBER JOGC NOVEMBRE 2010 l 1083
SOGC CLINICAL PRACTICE GUIDELINE
bacterial vaginosis, and herpes simplex virus.12 Classic
symptoms seem to be highly predictive of true disease. If
dysuria, frequency, and hematuria are present in the absence
of vaginal discharge, the probability of a positive culture is
81%.12 Women with recurrent UTI can self-diagnose on the
basis of symptoms very accurately, with an 84% positive
culture rate.13 Positive predictive factors for recurrent UTIs
in women are symptoms after intercourse, a prior history of
pyelonephritis, absence of nocturia, and prompt resolution
of symptoms (48 hours) after initiation of treatment. The
main negative predictors are the presence of nocturia and
persistence of symptoms between episodes of treated
infection.5
PATHOPHYSIOLOGY
The main causative pathogen involved in recurrent UTI in
women is E. coli, which is responsible for approximately
80% of all episodes of infection. Other significant
pathogens include Staphylococcus saprophyticus, Klebsiella
pneumoniae, and Proteus mirabilus, which each cause approxi-
mately 4% of all episodes of acute cystitis. Citrobacter and
Enterococci are less likely causes of UTI in women.14 Infec-
tion with organisms that do not usually cause UTIs may be
an indicator of underlying structural abnormalities or renal
calculi.7
Uropathogenic E. coli have virulence factors, such as the
type of fimbria, that promote binding to the epithelium of the
vagina and urethra and enhance their ability to cause cystitis.
Other factors increase resistance to serum bactericidal
activity and host defence mechanisms. Animal models
suggest that E. coli can remain dormant in large bacterial
reservoirs within the host and be reactivated to cause infection
in the future.15 In a 2007 study,16 midstream urine samples
from women with acute uncomplicated cystitis also showed
evidence of intracellular bacterial communities of
uropathogenic E. coli. These communities are relatively
protected from host immune response mechanisms and
antibiotic therapy and may reactivate, causing recurrent
UTI.16
In the classic theory for development of UTI, the
uropathogen is part of the fecal flora. It colonizes the vagina
and distal urethra. Subsequently, it ascends into the bladder
and causes infection. This model is the same for sporadic
and for recurrent UTI in women.8,17 Reservoirs of
uropathogenic bacteria can remain in the gastrointestinal
tract and vagina of the susceptible individual. The results of
one study suggest that household members, including pets,
could act as reservoirs for the recolonization of a person
with UTI.18 Lactobacilli in the vagina are protective, because
they prevent initial colonization with uropathogens.19
1084 l NOVEMBER JOGC NOVEMBRE 2010
RISK FACTORS
Premenopausal Women
In young women who suffer from recurrent UTIs there are
behavioural risk factors at play. These include increased
frequency of intercourse, use of a spermicide, and new
sexual partners.20 Intercourse and spermicide exposure
increase the rate of vaginal and periurethral colonization
with E. coli. When a first UTI is caused by E. coli, the risk of
a second infection within 6 months is greater than when a
first infection is cause by another uropathogen.11 Dysfunc-
tional voiding patterns in which there is increased tone of
the external sphincter during micturition can also be associ-
ated with recurrent UTI in otherwise urologically normal
women.21 There are also some non-behavioural risk factors
for recurrent UTI in young women. These include a history
of UTI before age 15 and a maternal history of UTI. This
suggests that there are also anatomic and genetic factors
involved.20 Most women with recurrent UTI do not have
any functional or anatomic abnormalities of the urinary
tract, and extensive radiologic and cystoscopic examination
is not indicated.8,22
Postmenopausal Women
In premenopausal women, 90% of the vaginal flora are
lactobacilli, which protects against colonization with
uropathogens such as E. coli. Estrogen loss at menopause
results in thinning of the vaginal epithelium and decreased
amounts of glycogen. The resulting environment is hostile
to lactobacilli, and the numbers decrease. The vaginal pH
increases, and there is an increased propensity for coloniza-
tion with uropathogens.10 Women who are non-secretors of
histocompatibility blood-group antigens are at increased
risk of recurrent UTI. This is thought to be a result of
attachment of P-fimbriated E. coli to glycolipids on vaginal
and uroepithelial cells.10 Non-secretor status is a more
significant risk factor in postmenopausal than in premeno-
pausal women.
Postmenopausal women who suffer from incontinence and
who have significant pelvic floor prolapse and elevated
post-void residual volumes are at increased risk for recurrent
UTI.10
Other significant factors for recurrent UTI in post-
menopausal woman are diabetes mellitus and a previous
history of UTI.3
INVESTIGATION
All women with recurrent UTI should undergo a physical
examination to evaluate urogenital anatomy and
estrogenization of vaginal tissues and to detect prolapse.
Post-void residual urine volume should be measured.
Diabetes screening is indicated in patients with other risk

factors, such as family history and obesity. Most women do
not require extensive urologic investigations.8,22 However,
women who suffer infection with organisms that are not
common causes of UTI, such as Proteus, Pseudomonas,
Enterobacter, and Klebsiella may have structural abnormalities
or renal calculi. They would benefit from imaging studies of
the upper urinary tract and cystoscopy.7 Women who have
persistent hematuria after resolution of their infection also
require a complete urologic workup.8
Although empiric therapy based on symptoms is generally
accurate and cost-effective, women who are felt to be in the
early stages of a problem with recurrent UTI should have
documented cultures.23 Urine culture not only serves as the
gold standard for diagnostic accuracy but also provides
specific information about the uropathogen and its antibi-
otic susceptibilities.6 The standard definition of a UTI on
culture is > 100 000 colony forming units per HPF. This
value has excellent specificity but a sensitivity of only 50%.7
In women with symptoms of a UTI > 1000 colony forming
units per HPF is considered sufficient to document infec-
tion without compromising specificity. The sensitivity to
detect infection is 80% and the specificity 90%.7 When a
“clean-catch” or midstream technique is used to obtain a
urine sample, the rates of contamination with vaginal flora
are approximately 30%.24 The presence of > 20 epithelial
cells per HPF on urinalysis suggests contamination by
vaginal secretions.23
Because bacteria reduce urinary nitrates to nitrites, the use
of urine dipstick analysis can be helpful. A positive result
usually indicates infection, with a specificity of 92% to
100% and a sensitivity of 19% to 48%.25 A negative result
does not rule out infection if the patient is symptomatic.
Some bacteria such as Staphylococcus saprophyticus lack the
enzymes to reduce nitrates. If urine has not been present in
the bladder for at least 4 hours, there may not have been
sufficient time for the reaction to occur.25
Leukocyte esterase is produced by neutrophils and indicates
pyuria, which is associated with UTI. Organisms other than
uropathogens can produce leukocyte esterase. Therefore, this
is a sensitive (72% to 97%) but not specific (41% to 86%)
test for UTI in women. Blood on dipstick can help to con-
firm infection, but this can be associated with other clinical
circumstances and therefore is more sensitive (68% to 92%)
than specific (42% to 46%) for UTI.25
TREATMENT OF ACUTE URINARY TRACT INFECTIONS
Ampicillin and sulfonamides generally should not be used
for empiric therapy because more than one third of isolates
demonstrate in vitro resistance.26,27 More than 15% to 20%
of E. coli strains causing uncomplicated cystitis are now
resistant to these agents in several areas of the United States
Recurrent Urinary Tract Infection
and other countries.28 The prevalence of resistance to
nitrofurantoin among E. coli is < 5%, although non-E. coli
uropathogens are often resistant. Resistance to the
fluoroquinolones remains < 5% in most studies of
uropathogenic strains.
Three-day regimens are recommended because they are
associated with better compliance, lower cost, and lower
frequency of adverse reactions than 7- to 10-day regimens.29
Several studies and clinical experience have confirmed the
effectiveness of 3-day regimens of trimethoprim, trimethoprim-
sulfamethoxazole, or a fluoroquinolone for treatment of
acute uncomplicated cystitis, and these agents are generally
recommended for empiric therapy.29 In comparison, 3-day
regimens with beta-lactams are less effective than ³ 5 days
of therapy.29 Nitrofurantoin is a safe and generally effective
agent, but it should be administered for a minimum of
7 days. Single-dose regimens are somewhat less effective
than 3- to 7-day regimens, even with fluoroquinolones.27,29
First-line treatment suggested by the Infectious Disease
Society of America in 1999 was TMP-SMX in a 3-day
regimen.29 Given the increasing prevalence of TMP-SMX
resistance among uropathogens, it is important to examine
risk factors predicting in vitro resistance. These are diabetes,
recent hospitalization, antibiotic use in the past 3 to 6 months
(for any reason), and recent TMP-SMX use.30
Fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin,
fleroxacin) are generally not recommended as first-line
treatment because of their greater expense and concerns
regarding the promotion of quinolone resistance. However,
fluoroquinolones can become a reasonable first-line treat-
ment for women who have or are suspected of having
antimicrobial resistance or of being allergic to or not tolerating
more conventional therapy, and for women in areas where
resistance to TMP-SMX is > 15% to 20%.29 Other reason-
able empiric choices for mild cystitis include a 7-day course
of nitrofurantoin or a single-dose of fosfomycin.29 In 2007,
Gupta et al. demonstrated the equivalent efficacy of a 5-day
course of nitrofurantoin and a 3-day course of TMP-SMX.31
Recurrent cystitis that occurs during or within the first week
following treatment suggests possible relapse and should be
managed with a pre-treatment urine culture, antimicrobial
susceptibility testing, and treatment with a fluoroquinolone
for 7 days.8
PREVENTION OF RECURRENT
URINARY TRACT INFECTIONS
Lifestyle Modification
Women using spermicide-containing contraception should
be offered an alternative form of contraception.27,32 Several
studies have shown that there is no association between
recurrent UTI and pre- and post-coital patterns, frequency
NOVEMBER JOGC NOVEMBRE 2010 l 1085
SOGC CLINICAL PRACTICE GUIDELINE

of urination, delayed voiding habits, douching, use of hot Table 2. Antimicrobial prophylaxis regimens for women
tubs, bubble baths, BMI, frequent use of pantyhose or with recurrent urinary tract infections
tights, use of tight clothing, type of clothing, bicycle riding,
Oral regimens
and the volume of fluid consumed.32,33 However, behavioural
approaches are unlikely to be harmful.34 Continuous prophylaxis
TMP-SMX 40/200 mg daily
Antimicrobial Strategy TMP-SMX 40/200 mg 3´/week

There are as many options for prevention and management TMP 100 mg daily

of recurrent UTI as there are studies on the issue Nitrofurantoin 50–100 mg daily
monohydrate/macrocrystals
(Table 2).8,10,33,35–39 A Cochrane review,35 of 19 trials (Macrobid)
including 1120 patients, showed that antibiotics are better Nitrofurantoin macrocrystal 50–100 mg daily
than placebo in reducing the number of clinical and (Macrodantin)
microbiological recurrences in pre- and postmenopausal Cephalexin 125–250 mg daily
women with recurrent UTI. Seven trials including 257 Cefaclor 250 mg daily
patients showed a relative risk of having a clinical UTI of Norfloxacin 200 mg daily
0.15 (95% CI 0.08 to 0.28) favouring antibiotic over pla- Ciprofloxacin 125 mg daily
cebo. The number needed to treat to prevent one symptom- Cinoxacin 250–500 mg daily
atic recurrent UTI was 2.2. Antibiotics in this review were Post-coital prophylaxis
fluoroquinolones (norfloxacin, ciprofloxacin, pefloxacin), (single dose)
cephalosporins (cephalexin, cefaclor), trimethoprim, TMP-SMX 40/200 mg
sulfamethoxazole, and nitrofurantoin. No antibiotic was TMP-SMX 80/400 mg
superior. Choice of antibiotic should rely on community Nitrofurantoin macrocrystal 50–100 mg
patterns of resistance, adverse events, and local costs. Three (Macrodantin)
main management strategies generally considered are con- Cephalexin 125–250 mg
tinuous antimicrobial prophylaxis, post-coital prophylaxis, Cinoxacin 250 mg
and patient-administered self-treatment.36 For patients with Ciprofloxacin 125 mg
£ 2 UTIs per year, the acute self-treatment may be useful. Norfloxacin 200 mg

Patients with ³ 3 infections annually should be offered a Ofloxacin 100 mg

regimen of continuous, low-dose prophylaxis or post-coital Acute self-treatment

prophylaxis.36 TMP-SMX 160/800 mg twice daily × 3 days
Ciprofloxacin 250 mg twice daily × 3 days
Continuous Prophylaxis Norfloxacin 200 mg twice daily × 3 days

Continuous prophylaxis can be given daily at bedtime.

Some authors suggest prophylaxis on alternate nights or
3 nights per week (Table 2). One study showed that weekly
prophylaxis was better than monthly prophylaxis.40 No
studies compared daily and weekly prophylaxis.35 No rec-
ommendation can be made about the optimal prophylaxis.
Post-coital Prophylaxis
Another study41 showed that sexually active women who
took post-coital ciprofloxacin had similar outcomes to
women who took ciprofloxacin daily. A causal relationship
between infections and intercourse can be suspected when
the interval is consistently between 24 and 48 hours.42 Two
studies41,43 suggest that for sexually active women with UTI
related to sexual intercourse, the post-coital approach could
be a better option. The authors of one study41 noted that a
major advantage of post-intercourse prophylaxis was that it
produced fewer side effects because women took only one
third of the amount of antibiotic used in daily prophylaxis.
Acute Self-treatment
The self-start therapy is ideal for women who are not suitable
candidates for long-term daily prophylaxis or who are
unwilling to take it. However, this strategy should be restricted
to those women who have clearly documented recurrent
infections and who are motivated, compliant with medical
instructions, and have a good relationship with a medical
provider.8 Such women should be reminded to call their
provider if the symptoms are not completely resolved within
48 hours. The patient identifies episodes of infection on the
basis of symptoms, performs her own culture, and initiates a
standard 3-day course of empiric treatment. Antimicrobial agents
with minimal side effects are recommended, because this
approach could lead to some degree of overtreatment
(Table 2).42
The efficacy of antimicrobial agents to prevent recurrent
UTIs seems to arise through 2 mechanisms. First, agents

1086 l NOVEMBER JOGC NOVEMBRE 2010


such as TMP-SMX and norfloxacin decrease the rate of
recovery of aerobic Gram-negative uropathogens such as
E. coli from the fecal reservoir.44 Nitrofurantoin in contrast,
decreases the recurrence rate by intermittently sterilizing the
urine and possibly by inhibiting bacterial attachment.36,45,46
Adverse Events
In a 2004 Cochrane Review,35 the rates of adverse events
were higher in the antibiotic group than in the placebo
group. The relative risk for severe side effects requiring
withdrawal of treatment was 1.58 (95% CI 0.47 to 5.28)
and for mild side effects the relative risk was 1.78 (95% CI
1.06 to 3.00). The most frequently reported adverse events
were nausea and vaginal and oral candidiasis. Nitrofuran-
toin required the highest number of withdrawals, followed
by cephalexin and weekly pefloxacin.35 Several adverse effects
have been described with the use of nitrofurantoin,
including aplastic anemia, polyneuritis, acute cholestatic
and hepatocellular reactions, and pulmonary toxicity.47
Chronic pulmonary toxicity is uncommon and may develop
after 1 month to 6 years of therapy. Patients who are
long-term users of nitrofurantoin should be checked
regularly for any complications.
Most authorities advocate an antibiotic prophylaxis duration
of 6 to 12 months, although in certain cases this has been
extended to 2 to 5 years.48 However, as no study has looked
at prophylaxis for more than 1 year, no conclusion can be
made about the optimal duration.
In the two studies that had a follow-up assessment at up
to 6 months after the prophylaxis period,44,49 there was
no difference in the microbiological recurrences between
the antibiotic group and the placebo group. There were
no studies that assessed clinical recurrences after prophy-
laxis. However, it appears that most women revert to the
previous pattern of recurrent infections once prophylaxis
is stopped.
Estrogen Use in Postmenopausal Women
Evidence from two small RCTs shows that in
postmenopausal women with recurrent UTI, vaginal
estrogens reduce the number of UTIs.50,51 Raz and Stamm
reported a significant reduction in UTI among
postmenopausal women using 0.5 mg of estriol cream
vaginally every night for 2-weeks and then twice a week
for 8-months compared with those using a placebo (0.5 vs.
5.9 episodes per patient-year, P < 0.001).52 Eriksen has
shown a similar beneficial prophylactic effect with the use
of an estradiol-releasing vaginal ring (Estring, Pharmacia &
Upjohn) compared with a placebo vaginal ring.53 After
36 weeks of the study, the cumulative likelihood of remaining
free of UTI was 45% in the Estring group compared with
approximately 20% in the placebo group (P < 0.008).53
Recurrent Urinary Tract Infection
The mechanism of action is thought to be the reappearance
of vaginal lactobacilli which, unlike placebo, decrease the
vaginal pH. This results from maturation and thickening of
the vaginal epithelium with increased cellular glycogen, a
main substrate for lactobacilli.52,53 This process prevents
overgrowth and colonization of Enterobacteriaceae in the
vagina.54 It can take at least 12 weeks for the vaginal ring to
be effective in reducing the occurrence of UTIs.53
Studies have provided insufficient evidence for recom-
mending a particular type or form of vaginal estrogen.50,51
Creams are cheaper and possibly more efficient but could
be more difficult to apply for some women and can produce
some adverse effects (e.g., itching, burning, occasional
spotting). Estradiol vaginal tablets may have fewer side
effects but are more expensive. The vaginal ring is also
more expensive and may require a trained professional to
place it correctly.51
A recent Cochrane review51 did not show a significant
difference in the number of women with UTI at the end of
treatment period between oral estrogens and placebo. It
seems that the route of administration may be more impor-
tant than the compound itself.50 The studies comparing
vaginal estrogens to antibiotics were inconclusive because
of their heterogeneity.51,55,56
Cranberries
Cranberries (particularly in the form of cranberry juice)
have been touted as an effective home remedy for the pre-
vention and treatment of UTIs for several decades. So far,
no definite mechanism of action has been established. The
main suggestion is that cranberries prevent bacteria
(particularly E. coli) from adhering to uroepithelial cells.57,58
Without adhesion, the bacteria cannot infect the mucosal
surface of the urinary tract.
A recent Cochrane review59 of 10 studies with a total of
1049 subjects showed some evidence that cranberry juice
and derivatives may decrease the number of symptomatic
UTIs over a period of 12 months, particularly for women
with recurrent UTIs. A meta-analysis of the results of
4 RCTs found that cranberry products significantly reduced
the incidence of UTIs (RR 0.66; 95% CI 0.47 to 0.92)
compared with placebo or control.60–63 Further, there is no
clear evidence of the amount and concentration that must
be consumed and over what period for the intervention to
be most effective. No published trials have been
undertaken that compare cranberry with established
interventions (e.g., antibacterials) for preventing UTIs.59
Other Potential Strategies
Antibiotics are usually effective in treating acute infections
and are the primary means of prophylaxis for recurrent UTI
patients; however, their value is being lessened by the
NOVEMBER JOGC NOVEMBRE 2010 l 1087
SOGC CLINICAL PRACTICE GUIDELINE
emergence of increasing numbers of drug-resistant bacte-
ria. Consequently, it is important that alternative prevention
strategies be developed.
Acupuncture
Two small RCTs evaluated the role of acupuncture
compared with sham acupuncture or no treatment in the
prophylaxis of recurrent UTIs.64,65 During a 6-month
period, both studies demonstrated that acupuncture could
play a significant role in preventing recurrent UTIs.
Authors concluded that it seems a worthwhile alternative to
antibiotic strategy.
Probiotics
The instillation of Lactobacillus into the vagina is believed to
stop the ascension of uropathogens into the bladder.
Available studies suggest that probiotics can be beneficial,
and most authors consider this approach promising, but
further research is needed before probiotics can be recom-
mended for prevention of UTI.66–70
Vaccines
An injectable vaccine developed in Switzerland was found
to be effective, with no adverse effects observed in preg-
nant women or their offspring.71 In order to obviate some
adverse reactions of the parenteral vaccine, four mucosal
vaccines were developed as a vaginal suppository or an oral
tablet, but the vaccine’s benefits seemed to decline after the
last dose.72 The only parenteral vaccine currently under
development, FimCH, has proven to be safe in a phase I
clinical trial.73 A phase II clinical trial has been completed,
but data are not yet available.34
Others
Other potential preventive strategies, which include the use
of bacterial interference (E. coli 83972)74 and topical
application of carbohydrates (hyaluronic acid),34,75–78 are still
under development.
PREGNANCY AND RECURRENT UTIs
For pregnant women with symptomatic or asymptomatic
bacteriuria, the risk of a preterm delivery and low birth
weight infant is significantly increased.79 Hooton and
Stamm recommend a follow-up culture for test of cure a
week after completion of therapy and monthly follow-up
until the completion of the pregnancy.34 Indications for
prophylaxis are (1) all women with a pre-pregnancy history
of recurrent UTIs, (2) persistent symptomatic or asymptomatic
bacteriuria after two antibiotic treatments, and (3) after only one
UTI for a woman who has other conditions that potentially
increase the risk of urinary complications during the episode
of UTI (e.g., diabetes or sickle cell trait). Both continuous
and post-coital prophylaxis regimens have been shown to
1088 l NOVEMBER JOGC NOVEMBRE 2010
be effective, and agents of choice are nitrofurantoin (50 mg)
and cephalexin (250 mg).34,36,80,81
Recommendations
Recommendations were made according to the guidelines
developed by the Canadian Task Force on Preventive
Health Care (Table 1).
1. Urinalysis and midstream urine culture and sensitivity
should be performed with the first presentation of
symptoms in order to establish a correct diagnosis of
recurrent urinary tract infection. (III-L)
2. Patients with persistent hematuria or persistent growth
of bacteria aside from Escherichia coli should undergo cystoscopy
and imaging of the upper urinary tract. (III-L)
3. Sexually active women suffering from recurrent urinary
tract infections and using spermicide should be encour-
aged to consider an alternative form of contraception.
(II-2B)
4. Prophylaxis for recurrent urinary tract infection should
not be undertaken until a negative culture 1 to 2 weeks
after treatment has confirmed eradication of the urinary
tract infection. (III-L)
5. Continuous daily antibiotic prophylaxis using cotri- moxazole,
nitrofurantoin, cephalexin, trimethoprim, trimethoprim-
sulfamethoxazole, or a quinolone during a 6- to 12-month
period should be offered to women with ³ 2 urinary
tract infections in 6 months or ³ 3 urinary tract infections
in 12 months. (I-A)
6. Women with recurrent urinary tract infection associated
with sexual intercourse should be offered post-coital
prophylaxis as an alternative to continuous therapy in
order to minimize cost and side effects. (I-A)
7. Acute self-treatment should be restricted to compliant
and motivated patients in whom recurrent urinary tract
infections have been clearly documented. (I-B)
8. Vaginal estrogen should be offered to postmenopausal
women who experience recurrent urinary tract infec-
tions. (I-A)
9. Patients should be informed that cranberry products are
effective in reducing recurrent urinary tract infections.
(I-A)
10. Acupuncture may be considered as an alternative in the
prevention of recurrent urinary tract infections in women
who are unresponsive to or intolerant of antibiotic pro-
phylaxis. (I-B)
11. Probiotics and vaccines cannot be offered as proven
therapy for recurrent urinary tract infection. (II-2C)

12. Pregnant women at risk of recurrent urinary tract infec-
tion should be offered continuous or post-coital prophy-
laxis with nitrofurantoin or cephalexin, except during the
last 4 weeks of pregnancy. (II-1B)
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58. Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of
craberry juice on adherence of type 1 and type P fimbriated Escherichia coli
to eucaryotic cells. Antimicrob Agents Chemother 1989;33:92–8.
59. Jepson JP, Craig JC. Cranberries for preventing urinary tract infections.
Cochrane Database Syst Rev 2008;(1):CD 001321.
60. Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M.
Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink
for the prevention of urinary tract infections in women. BMJ
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61. McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. Does
ingestion of cranberry juice reduce symptomatic urinary tract infections
in older people in hospital? A double-blind, placebo-controlled trial.
Age Ageing 2005;34:256–61.
62. Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness
of naturopathic cranberry products as prophylaxis against urinary tract
infection in women. Can J Urol 2002;9:1558–62.
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63. Waites KB, Canupp KC, Armstrong S, DeVivo MJ. Effect of cranberry
extract on bacteriuria and pyuria in persons with neurogenic bladder
secondary to spinal cord injury. J Spinal Cord Med 2004; 27:35–40.
64. Aune A, Alreak T, LiHua H, Baerheim A. Acupuncture in the prophylaxis
of recurrent lower urinary tract infection in adult women. Scand J Prim
Health Care 1998; 16:37–9.
65. Alraek T, Fagerheim U, Baerheim A. Acupuncture treatment in the
prevention of uncomplicated recurrent lower urinary tract infections in
adult women. Am J Public Health 2002;92:1609–11.
66. Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rational
and evidence. World J Urol 2006;24:28–32.
67. Reid G, Bruce AW, Taylor M. Instillation of Lactobacillus and stimulation
of indigenous organisms to prevent recurrence of urinary tract infections.
Microecol Ther 1995;23:32–45.
68. Uehara S, Monden K, Nomoto K, Seno Y, Kariyama R, Kumon H.
A pilot study evaluating the safety and effectiveness of Lactobacillus
vaginal suppositories in patients with recurrent urinary tract infection.
Int J Antimicrob Agents 2006;28(Suppl 1):S30–4.
69. Baerheim A, Larsen E, Digranes A. Vaginal application of lactobacilli
in the prophylaxis of recurrent urinary tract infection in women.
Scand J Prim Health Care 1994;12:239–43.
70. Falagas ME, Betsi GI, Tokas T, Athanasiou S. Probiotics for prevention
of recurrent urinary tract infections in women. Drugs 2006;66:1253–61.
71. Grischke EM, Rüttgers H. Treatment of bacterial infections of the female
urinary tract by immunization of the patiets. Urol Int 1987;42:338–41.
72. Uehling DT, Hopkins WJ, Beierle LM, Kryger JV, Heisey DM. Vaginal
mucosal immunization for recurrent urinary tract infection: extended phase II
clinical trial. J Infect Dis 2001;183 (Suppl 1): S81–3.
73. Hopkins WJ, Uehling DT. Vaccine development for the prevention
of urinary tract infections. Curr Infect Dis Rep 2002;4:509–13.
74. Sundén F, Håkansson L, Ljunggren E, Wullt B. Bacterial interference—is
deliberate colonization with Escherichia coli 83972 an alternative treatment
for patients with recurrent urinary tract infection? Int J Antimicrob Agents
2006;28(Suppl 1):S26–9.
75. Lipovac M, Kurz C, Reithmayr F, Verhoeven HC, Huber JC, Imhof M.
Prevention of recurrent bacterial urinary tract infections by intravesical
instillation of hyaluronic acid. Int J Gynaecol Obstet 2007;96:192–5.
76. Constantinides C, Manousakas T, Nikolopoulos P, Stanitsas A, Haritopoulos
K, Giannopoulos A. Prevention of recurrent bacterial cystitis by intravesical
administration of hyaluronic acid: a pilot study. BJU Int 2004;93:1262–6.
77. Eden CS, Fretr R, Hagberg L, Hull R, Hull S, Leffler H, et al. Inhibition of
experimental ascending urinary tract infection by an epithelial cell-surface
receptor analogue. Nature 1982;298(5874):560–2.
78. Zopf D, Roth S. Oligosaccharides anti-infectives agents. Lancet
1996;347(9007):1017–21.
79. Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M.
Meta-analysis of the relationship between asymptomatic bacteriuria and
preterm delivery/low birth weight. Obstet Gynecol 1989;73:576–82.
80. Pfau A, Sacks TG. Effective prophylaxis for recurrent urinary tract infections
during pregnancy. Clin Infect Dis 1992;14:810–4.
81. Ovalle A, Levancini M. Urinary tract infections in pregnancy.
Curr Opin Urol 2001:11:55–9.
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the Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.
 SOGC CLINICAL PRACTICE GUIDELINE

SOGC Clinical Practice Guideline

No. 248, September 2010 (Replaces No. 74, July 1998)

Guidelines for the Evaluation and Treatment

of Recurrent Urinary Incontinence Following
Pelvic Floor Surgery
Abstract
This clinical practice guideline has been prepared by the Objective: To provide general gynaecologists and urogynaecologists
Urogynaecology Committee and approved by the Executive and with clinical guidelines for the management of recurrent urinary
Council of the Society of Obstetricians and Gynaecologists of incontinence after pelvic floor surgery.
Canada.
Options: Evaluation includes history and physical examination,
PRINCIPAL AUTHORS multichannel urodynamics, and possibly cystourethroscopy.
Danny Lovatsis, MD, Toronto ON Management includes conservative, pharmacological, and
surgical interventions.
William Easton, MD, Scarborough ON
David Wilkie, MD, Vancouver BC Outcomes: These guidelines provide a comprehensive approach
to the complicated issue of recurrent incontinence that is based
UROGYNAECOLOGY COMMITTEE on the underlying pathophysiological mechanisms.
Danny Lovatsis, MD, (Chair), Toronto ON Evidence: Published opinions of experts, and evidence from clinical
Jens-Erik Walter, MD (Co-Chair), Montreal QC trials where available.
William Easton, MD, Scarborough ON Values: The quality of the evidence is rated using the criteria
Annette Epp, MD, Saskatoon SK described by the Canadian Task Force on Preventive Health Care
(Table).
Scott Farrell, MD, Halifax NS
Recommendations
Lise Girouard, RN, Winnipeg MB
Chander Gupta, MD, Winnipeg MB 1. Thorough evaluation of each patient should be performed to determine
the underlying etiology of recurrent urinary incontinence and to
Marie-Andrée Harvey, MD, Kingston ON guide management. (II-3B)
Annick Larochelle, MD, St-Lambert QC 2. Conservative management options should be used as the first line
Magali Robert, MD, Calgary AB of therapy. (III-C)
Sue Ross, PhD, Calgary AB 3. Patients with a hypermobile urethra, without evidence of intrinsic
Joyce Schachter, MD, Ottawa ON sphincter deficiency, may be managed with a retropubic urethropexy
(e.g., Burch procedure) or a sling procedure (e.g., mid-urethral
Jane Schulz, MD, Edmonton AB sling, pubovaginal sling). (II-2B)
David Wilkie, MD, Vancouver BC 4. Patients with evidence of intrinsic sphincter deficiency may be
Disclosure statements have been received from all members of the managed with a sling procedure (e.g., mid-urethral sling, pubovaginal
committee. sling). (II-3B)
The literature searches and bibliographic support for this guideline 5. In cases of surgical treatment of intrinsic sphincter deficiency,
were undertaken by Becky Skidmore, Medical Research Analyst, retropubic tension-free vaginal tape should be considered rather
Society of Obstetricians and Gynaecologists of Canada. than transobturator tape. (I-B)
6. Patients with significantly decreased urethral mobility may be
managed with periurethral bulking injections, a retropubic sling
procedure, use of an artificial sphincter, urinary diversion, or
chronic catheterization. (III-C)
7. Overactive bladder should be treated using medical and/or
behavioural therapy. (II-2B)
Key Words: Urinary incontinence, recurrent, surgery
8. Urinary frequency with moderate elevation of post-void residual
volume may be managed with conservative measures such as drugs

This document reflects emerging clinical and scientific advances on the date issued, and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

SEPTEMBER JOGC SEPTEMBRE 2010 l 893

SOGC Clinical Practice Guideline
Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well–designed cohort (prospective or
retrospective) or case–control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.20
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian Task
Force on Preventive Health Care.20
to relax the urethral sphincter, timed toileting, and double voiding.
Intermittent self-catheterization may also be used. (III-C)
9. Complete inability to void with or without overflow incontinence
may be managed by intermittent self-catheterization or
urethrolysis. (III-C)
10. Fistulae should be managed by an experienced physician. (III-C)
J Obstet Gynaecol Can 2010;32(9):893–898
INTRODUCTION
areful investigation and patient selection before
C primary pelvic surgery for prolapse and/or urinary
incontinence will minimize the incidence of immediate or
delayed failure.1 Conservative (i.e., non-surgical) or surgical
intervention may be required when prior surgery has failed,
although non-surgical options should first be considered.2
Patients who complain of either de novo or recurrent
urinary incontinence following reconstructive pelvic floor
or incontinence surgery must undergo a thorough evalua-
tion to identify the cause of this incontinence. The causes of
incontinence for most of these patients will fall into one
of the following categories.
Early Causes of Urinary Incontinence
1. Surgical correction of stress incontinence either
unsuccessful or not sustained.
2. Latent (occult) stress incontinence not recognized
preoperatively in a patient with pelvic organ prolapse.
894 l SEPTEMBER JOGC SEPTEMBRE 2010
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
3. An intraoperative or postoperative complication of
surgery (e.g., fistula).
4. Surgery was inappropriate therapy or an inappropriate
procedure used.
5. Pre-existing or de novo overactive bladder causing
urgency incontinence.
6. Urinary tract infection causing urgency incontinence.
7. Voiding dysfunction causing urgency/frequency or
overflow incontinence.
Long-term Progressive Causes of Urinary
Incontinence
1. Deficiency of pelvic floor support either through
genetic predisposition or other medical condition.
2. Predisposing medical conditions (e.g., chronic
obstructive pulmonary disease, obesity, chronic
constipation).
3. Urogenital aging and estrogen deficiency.
ASSESSMENT
Although some recurrent urinary incontinence may fit into
the category outlined in the 2003 SOGC guideline, “The
Evaluation of Stress Incontinence Prior to Primary
Surgery,”1 specialized evaluation, including urodynamics,
will permit accurate diagnosis and measurement of
 Guidelines for the Evaluation and Treatment of Recurrent Urinary Incontinence Following Pelvic Floor Surgery
urodynamic variables that may significantly affect the
management plan. Should a patient meet all the criteria on
the following list, then assessment may proceed as suggested
in the guideline1 without multichannel urodynamics.
• No more than one prior surgery for incontinence
• Symptoms of pure stress urinary incontinence
• No symptoms of overactive bladder
• No symptoms of voiding dysfunction such as urinary
hesitancy, slow or interrupted stream, straining to void,
or incomplete bladder emptying
• Hypermobile urethra
• Post-void residual urine volume < 100 mL
• Normal urinalysis
If any of the above requirements are not met, then a more
thorough evaluation is required, using multichannel
urodynamics, and referral to a subspecialist may be indicated.
In all cases, the assessment must be designed to identify one
or a combination of the following predisposing conditions.
1. Compromise to the urethral sphincter mechanism
2. Detrusor overactivity (overactive bladder)
3. Voiding dysfunction
4. Urogenital fistula
5. Persistent or de novo pelvic prolapse
Recommendation
1. Thorough evaluation of each patient should be per-
formed to determine the underlying etiology of recurrent
urinary incontinence and to guide management. (II-3B)
Investigation of Urethral Sphincter Function
Extrinsic support of the urethra is critical to continence, and
it is provided laterally by connective tissue attachment to
the pelvic side walls and posteriorly by the levator ani mus-
cles. Urethral mobility should be assessed to evaluate
extrinsic support. However, continence is maintained only
if extrinsic support is complemented by normal intrinsic ure-
thral function, which consists of the following:
1. Healthy urethral mucosa
2. A normal vascular plexus
3. Normal smooth muscle sphincter function
4. Normal external striated sphincter function
Such factors as lack of estrogen, aging tissues,
devascularization, denervation, or disruption of muscular
sphincters can result in marked impairment of intrinsic ure-
thral sphincter function. These problems may also arise
from prior trauma, surgery, or pelvic radiation. Some
patients may have a combination of recurrent
hypermobility and deficiency of intrinsic urethral function.
The majority of surgical procedures used to treat stress
incontinence are designed to restore normal anatomic rela-
tionships and re-establish extrinsic urethral support.
Although the exact mechanism responsible for the restora-
tion of continence that results from successful surgery is
uncertain3; the only consistent postoperative urodynamic
finding is enhanced pressure transmission to the urethra.
This urodynamic change is probably a consequence of
better transmission of intra-abdominal pressure to the
newly supported urethra. It is also speculated that support
of the mid-urethra results in some degree of kinking of the
urethra when the proximal urethra and bladder descend
during increased intra-abdominal pressure.4 Using this
model, it is evident that in order for surgery to correct stress
incontinence, it must stabilize the urethra at an appropriate
anatomic level to allow pressure transmission to the
urethra. If this stability is not established at the time of the
operation or if it cannot be maintained over time, the
surgery may fail.
Repeated surgery may cause significant trauma to the urethra
resulting in a poorly vascularized, scarred, rigid “drainpipe
urethra” that has no sphincteric function (intrinsic
sphincter deficiency).5 In this condition, the urethra is a
poorly coapted conduit through which urine may leak with
minimal increases in intra-abdominal pressure or on a
nearly continuous basis. Urethroscopy will reveal a smooth
rigid tube which does not coapt. The urethrovesical junction is
open and can be visualized from any point along the
urethra. Videocystourethrography will confirm a urethra
which is immobile and open. Intrinsic sphincter deficiency
(ISD) may result after prior retropubic urethropexy
(e.g., Burch procedure) or needle suspension (e.g., Pereyra
procedure), or less frequently after prior anterior
colporrhaphy.6 The likelihood of ISD increases as the
number of prior surgeries increases.6
Urethrovesical junction mobility can be assessed by Q-tip
test,7 inspection and palpation of the distal anterior vaginal
wall during Valsalva manoeuvre, ultrasound examination,
videocystourethrography, and urethroscopy. If recurrent
hypermobility is found, it may be assumed that surgery has
failed either to establish or to maintain urethral support. If
the urethra is maintained in an elevated retropubic position,
then it can be assumed that the goal of surgery has been
achieved and that failure is the result of ISD. A patient with
ISD will require subspecialized evaluation and manage-
ment, including multichannel urodynamics. Urodynamic
variables consistent with ISD include a maximum urethral
closure pressure less than 20 cm of water or a leak point
pressure less than 60 cm of water.6 The choice of any subse-
quent surgical procedure will be determined by the degree
of urethral fixation by scar, the patient’s medical condition,
SEPTEMBER JOGC SEPTEMBRE 2010 l 895
SOGC Clinical Practice Guideline
and the degree to which detrusor and urethral function has
been compromised by denervation caused by previous
surgical procedures.8
MANAGEMENT OF RECURRENT STRESS INCONTINENCE
Any decision to proceed with a specific treatment must
include an assessment of the severity of the patient’s
symptoms, and a trial of conservative management must
be considered (as described in the SOGC guideline
“Conservative Management of Urinary Incontinence”).2
Conventional retropubic urethropexy (Burch procedure)9
has a higher rate of failure in cases of suspected ISD where
maximum urethral closure pressure is less than 20 cm of
water. Tension-free vaginal tape has shown success rates of
74% to 82% when performed as a repeat procedure,
depending on the degree of ISD present.8 Some data indi-
cate that transobturator tape may not be as effective as
tension-free vaginal tape in cases where there is an element
of ISD,10 particularly if the maximum urethral closure
pressure is less than 40 cm of water,11 with success rates of
only approximately 50%. Patients with significant ISD,
such as a fixed drainpipe urethra, may also have persistent
incontinence even if undergoing a urethral sling as the
repeat surgical technique. Referral to a subspecialist for a
retropubic sling procedure with or without lysis of bladder
neck and paraurethral scar may provide continence under
these circumstances. The risk of failure and urinary reten-
tion may be increased. Periurethral bulking agents may also
be injected.12 Consideration may be given to other
“end-stage” options, such as placement of an artificial
sphincter, urinary diversion, or chronic catheterization.
Patients with recurrent stress incontinence who opt for
surgical treatment should be managed according to the
following recommendations.
Recommendations
2. Conservative management options should be used as the
first line of therapy. (III-C)
3. Patients with a hypermobile urethra, without evidence of
intrinsic sphincter deficiency, may be managed with a
retropubic urethropexy (e.g., Burch procedure) or a sling
procedure (e.g., mid-urethral sling, pubovaginal sling).
(II-2B)
4. Patients with evidence of intrinsic sphincter deficiency
may be managed with a sling procedure (e.g., mid-ure-
thral sling, pubovaginal sling). (II-3B)
5. In cases of surgical treatment of intrinsic sphincter defi-
ciency, retropubic tension-free vaginal tape should be
considered rather than transobturator tape. (I-B)
6. Patients with significantly decreased urethral mobility
may be managed with periurethral bulking injections, a
896 l SEPTEMBER JOGC SEPTEMBRE 2010
retropubic sling procedure, use of an artificial sphincter,
urinary diversion, or chronic catheterization. (III-C)
OVERACTIVE BLADDER
Overactive bladder, a symptom complex consisting of
urgency, frequency, nocturia, and urgency incontinence, is
caused by a failure of bladder inhibition and, if unrecog-
nized prior to surgery, may cause persistent incontinence
following surgery. De novo overactive bladder may develop
following surgery for stress incontinence,13 particularly if
extensive vaginal dissection has been performed or as a sec-
ondary result after outlet obstruction. Patients will usually
present with urinary urgency, frequency, nocturia, with or
without urge incontinence. Cystoscopy may identify blad-
der pathology responsible for the urinary symptoms, such
as suture or mesh penetrating the bladder or urethra.
Although a simple cystometrogram will identify most cases
of overactive bladder, multichannel subtracted cystometry
is indicated if the diagnosis is uncertain.
The management of overactive bladder is medical or behav-
ioural. Medical therapy typically uses anticholinergic/
antimuscarinic medications.14 Behavioural therapy includes
prompted voiding, bladder training, caffeine reduction, or
biofeedback, with or without electrostimulation.2 In some
instances, overactive bladder is a result of outlet obstruc-
tion, (discussed in the next section), and urethrolysis may
provide improvement.15
Some patients may have mixed urinary incontinence.
Although surgery is not contraindicated in cases of mixed
urinary incontinence,16 conservative management options
for both the stress and urgency incontinence should be
used, and benefits maximized before further surgery is
undertaken.
Recommendation
7. Overactive bladder should be treated using medical
and/or behavioural therapy. (II-2B)
VOIDING DYSFUNCTION
Voiding dysfunction as a consequence of pelvic surgery
may develop for several reasons. In general, voiding dys-
function is due to either urethral obstruction or detrusor
underactivity. A patient with subclinical preoperative dys-
functional voiding may not be able to empty her bladder
after surgical stabilization of the urethrovesical junction.17
Excessive elevation of the urethra in patients with a normal
preoperative voiding mechanism may partially obstruct uri-
nary outflow, causing voiding dysfunction. Mild degrees of
incomplete emptying will appear as urinary frequency, hesi-
tancy, and nocturia. More severe voiding compromise is
manifested in urinary retention, bladder distension and
 Guidelines for the Evaluation and Treatment of Recurrent Urinary Incontinence Following Pelvic Floor Surgery
overflow incontinence, recurrent urinary tract infections,
and possible upper tract decompensation. Simple
uroflowmetry including measurement of peak flow rate and
post-void residual volume is sufficient to screen for voiding
dysfunction.1 Post-void residual levels can be measured by
catheterization, ultrasound examination, or contrast radiog-
raphy. An intermittent voiding pattern on uroflowmetry, a
decreased peak flow rate (< 15 mL/second), or a high
post-void residual volume (> 150 mL) should prompt more
sophisticated voiding studies, which may include voiding
cystometry (simultaneous measurement of intravesical and
abdominal pressures during voiding), urine flow rate,
electromyogram, and urethral sphincter activity.15
Treatment should be individualized, and options include
timed toileting, double voiding, intermittent
catheterization, or urethrolysis. There are limited data on
the use of urethral relaxants (e.g., benzodiazepines, lioresal,
alpha-blockers). Detrusor stimulation using bethanecol is
typically ineffective.18 Occasionally, voiding may be
improved by use of a pessary or surgery to correct a high
cystocoele if present. If detrusor hypotonia is the cause,
then sacral nerve stimulation can be used. Additional
anti-incontinence operations for stress incontinence should
be planned cautiously in patients with marked postopera-
tive voiding dysfunction.15
Recommendations
8. Urinary frequency with moderate elevation of post-void
residual volume may be managed with conservative mea-
sures such as drugs to relax the urethral sphincter, timed
toileting, and double voiding. Intermittent
self-catheterization may also be used. (III-C)
9. Complete inability to void with or without overflow
incontinence may be managed by intermittent
self-catheterization or urethrolysis. (III-C)
UROGENITAL FISTULA
Urogenital fistula following incontinence surgery is a rare
complication. A fistula may exist between the vagina and
the urethra, the bladder, the ureter, or a combination of
these organs. Methylene blue solution may be instilled into
the bladder followed by speculum examination or place-
ment of tampons in the vagina. Direct visualization of dye
or staining of the tampon will confirm the presence of a
vesicovaginal fistula. Cystourethroscopy should permit the
identification of a fistula in either the urethra or the bladder,
as well as assessment of the precise size, location, and num-
ber of fistulae. Injection of intravenous indigo carmine fol-
lowed by speculum examination or the tampon test may
identify a ureterovaginal fistula if a vesicovaginal fistula has
been ruled out. Intravenous pyelography or computed
tomography with intravenous contrast (CT urogram) is
indicated to identify possible upper tract damage.
Urogenital fistula is a surgical problem that must be cor-
rected.19 The choice of procedure will depend on the sever-
ity and location of the fistula. Fistula and stress inconti-
nence can co-exist. If surgery is undertaken, it should cor-
rect all incontinence and pelvic floor prolapse disorders,
either concomitantly or in stages, depending on individual
circumstances.
Recommendations
10. Fistulae should be managed by an experienced physi-
cian. (III-C)
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tape, Burch, and slings: are there predictors for early postoperative voiding
dysfunction? Int Urogynecol J Pelvic Floor Dysfunct 2004;15:183–7.
20. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
18. Farrell SA, Webster RD, Higgins LM, Steeves RA. Duration of postoperative Force on Preventive Health Care. New grades for recommendations from
catheterization: a randomized, double-blind trial comparing two catheter the Canadian Task Force on Preventive Health Care. CMAJ 2003;169:207–8.

898 l SEPTEMBER JOGC SEPTEMBRE 2010

 SOGC CLINICAL PRACTICE GUIDELINE
SOGC CLINICAL PRACTICE GUIDELINENo. 238, January 2010
Supracervical Hysterectomy
This guideline has been reviewed by the Clinical Practice
Gynaecology Committee and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists of
Canada.
PRINCIPAL AUTHORS
Sari Kives MD, Toronto ON
Guylaine Lefebvre MD, Toronto ON
CLINICAL GYNAECOLOGY COMMITTEE
Wendy Wolfman (Co-Chair), MD, Toronto ON
Nicholas Leyland (Co-Chair), MD, Toronto ON
Catherine Allaire, MD, Vancouver BC
Alaa Awadalla, MD, Winnipeg MB
Carolyn Best, MD, Hamilton ON
Nathalie Leroux, MD, Montreal QC
Frank Potestio, MD, Thunder Bay ON
David Rittenberg, MD, Halifax NS
Renée Soucy, MD, Chandler QC
Sukhbir Singh, MD, Ottawa ON
Disclosure statements have been received from all members of
the committee.
Abstract
Objective: This guideline reviews the evidence relating to the
potential benefits of the vaginal hysterectomy (VH) and
supracervical hysterectomy (SCH) versus total abdominal
hysterectomy (TAH) with respect to postoperative sexual function,
urinary function, and peri- and postoperative complications.
Laparoscopic options are not included in this guideline.
Options: Women considering hysterectomy for benign disease can
be given the option of retaining the cervix or proceeding with a
total hysterectomy.
Outcomes: The outcomes measured are postoperative sexual
function and urinary function, and peri- and postoperative
complications.
Key Words: Hysterectomy, vaginal, supracervical, perioperative
complications, postoperative complications
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
62 l JANUARY JOGC JANVIER 2010
Evidence: The Cochrane Library, Medline, and Embase were
searched for articles published in English from January 1950 to
March 2008 specifically comparing VH and SCH with TAH in the
prevention of sexual dysfunction, urinary dysfunction, and peri-
and postoperative complications. Results were restricted to
systematic reviews, randomized control trials/controlled clinical
trials, and observational studies. Additional publications were
identified from the bibliographies of these articles. Randomized
controlled trials were considered evidence of the highest quality,
followed by cohort studies.
Grey (unpublished) literature was identified through searching the
websites of health technology assessment and health technology
assessment-related agencies, clinical practice guideline
collections, clinical trial registries, and national and international
medical specialty societies.
Values: The quality of evidence was rated using the criteria
described in the Report of the Canadian Task Force on Preventive
Health Care (Table).
Recommendations
1. Vaginal hysterectomy is generally considered the first choice of
surgical approach for most benign indications for hysterectomy, as
it is associated with lower rates of morbidity, fewer postoperative
complications, and a faster recovery time than abdominal
hysterectomy. (I-A)
2. Women contemplating a vaginal, laparoscopic, or abdominal
hysterectomy for the management of benign uterine disease
should be reassured that hysterectomy is usually associated with
improved quality of life, including improved sexual function,
whether or not the cervix is removed. (I-B)
3. Supracervical hysterectomy should not be recommended as a
superior technique to total abdominal hysterectomy for the
prevention of postoperative lower urinary tract symptoms. (I-B)
4. Although supracervical hysterectomy may be associated with less
blood loss and a shorter surgical time, these parameters have not
been found to be clinically significant, and supracervical
hysterectomy should not be recommended as a superior
technique to total abdominal hysterectomy for the prevention of
peri- and postoperative complications. (I-B)
5. Women considering a supracervical hysterectomy should be
counselled that they may continue experiencing cyclic vaginal
bleeding following the surgery. (I-B)
6. Women must be advised that they require routine cytological
screening following a supracervical hysterectomy. (II-B)
7. Women who require a hysterectomy and who have a current or
significant history of abnormal cervical cytological results should
be counselled on the advantages of vaginal hysterectomy or total
abdominal hysterectomy over supracervical hysterectomy. (I-B)
J Obstet Gynaecol Can 2010;32(1):62–68

Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of evidence assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.26
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
Task Force on Preventive Health Care.26
APPROACHES TO HYSTERECTOMY
ysterectomy involves the removal of the uterine body
H and cervix, referred to as total abdominal hysterec-
tomy, or the removal of the uterine body only at or below
the level of the isthmus, referred to as supracervical hyster-
ectomy. Hysterectomy may also be associated with removal
of the ovaries and fallopian tubes (bilateral salpingo-
oophorectomy). Currently, hysterectomy is one of the most
frequently performed surgical procedures in Canada.1 Since
1981, hysterectomy rates have decreased from 937 to 462
hysterectomies per year per 100 000 women ³ 20 years of
age.2 Patient satisfaction following hysterectomy has been
evaluated and is consistently high. Hysterectomy usually is
associated with improvement in lower tract urinary symp-
toms, whether or not the cervix is removed. As vaginal
hysterectomy is associated with lower rates of morbidity,
fewer postoperative complications, and a faster recovery
time than abdominal hysterectomy, it is usually the first
ABBREVIATIONS
LAVH laparoscopically assisted vaginal hysterectomy
LSCH laparoscopically assisted supracervical hysterectomy
MUI mixed urinary incontinence
RCT randomized controlled trial
SCH supracervical hysterectomy
SUI stress urinary incontinence
TAH total abdominal hysterectomy
UUI urge urinary incontinence
VH vaginal hysterectomy
Supracervical Hysterectomy
Classification of recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
choice of surgical approach when indications for hysterec-
tomy are benign.3,4
In Canada, 72% of hysterectomies are still performed
abdominally in women under 40 years of age.5 It is not clear
how many of these are supracervical hysterectomies, as this
method is not uniquely identified in the Canadian Classifi-
cation of Health Interventions, but SCH likely accounts for
10% of all hysterectomies performed in Canada.6 The
advent of minimally invasive surgeries has led to an increas-
ing number of hysterectomies being performed
laparoscopically. At present there is insufficient evidence to
compare laparoscopic subtotal with laparoscopic total hys-
terectomy; therefore, this guideline considers operations
done by laparotomy.
Recommendation
1. Vaginal hysterectomy is generally considered the first
choice of surgical approach for most benign indications
for hysterectomy, as it is associated with lower rates of
morbidity, fewer postoperative complications, and a
faster recovery time than abdominal hysterectomy. (I-A)
During the 1940s, SCH was replaced almost universally by
TAH because of the risk of cervical stump cancer and per-
sistent blood-stained discharge associated with retaining the
cervix. Surgical skills and availability of anaesthesia and anti-
biotics also allowed for longer and more complex surgeries.
More recently, there has been a re-emergence of SCH, as
some literature has suggested that retaining the cervix offers
better postoperative sexual and urinary function and may
protect the integrity of the pelvic floor.7,8 In the United
JANUARY JOGC JANVIER 2010 l 63
SOGC CLINICAL PRACTICE GUIDELINE
States, the number of SCHs appears to be increasing simul-
taneously with a decrease in TAH.9 With the advent of min-
imally invasive surgical options, the laparoscopic SCH may
be favoured over a total laparoscopic hysterectomy because
it is perceived to be technically easier laparoscopically to
leave the cervix behind. The superiority of SCH over TAH
still remains largely theoretical and is not supported by a
review of evidence.
RATIONALE FOR GUIDELINE DEVELOPMENT
This guideline provides a consolidation of a systematic
review of the evidence supporting or opposing the use of
SCH rather than TAH, and the consensus on whether or
not SCH offers our patients an advantage in the prevention
of sexual dysfunction, urinary dysfunction, and peri- and
postoperative complications.
SEXUAL FUNCTION AND QUALITY OF LIFE
Four RCTs were identified that specifically address sexual
function and/or quality of life after total versus
supracervical hysterectomy.10–13 All 4 trials used objective,
previously validated questionnaires to assess sexual func-
tion and/or quality of life,10,11 psychological well-being,11,12
and pain.12 These 4 trials included only women undergoing
a hysterectomy for benign indications. Exclusion criteria
varied, but postmenopausal women were excluded in 3 of
the 4 trials.10–12 Oophorectomy was the only concomitant
procedure permitted in all 4 trials. Thakar et al.11 also
excluded women with comorbidities, including a body
weight > 100 kg, previous pelvic surgery, and known
endometriosis. Follow-up varied, ranging from a minimum
of 7 months to a maximum of 24 months after surgery. One
study also tested subjects 2 to 3 weeks prior to surgery.12 All
trials stated the method of randomization and included an
intention-to-treat analysis. Adequate follow-up of > 80%
was obtained in all 4 trials. All 4 trials were graded as good
because either the outcome was blinded,11 or the outcome
was considered to be as objective as possible for a qualita-
tive measure.10–13
Kupperman et al.10 conducted a randomized trial of 135
women (67 TAH and 68 SCH). Each woman was followed
for 2 years. Baseline sexual functioning and quality of life
variables were measured at randomization and again, with a
telephone interview, at 1, 3, 9, and 15 months, and with
clinic-based interviews every 6 months. At 2 years, both
groups reported few problems with sexual functioning
(mean score 82, SD 26 for SCH and 80, SD 26 for TAH). In
addition, both randomization groups demonstrated
substantial improvement in most measures of sexual func-
tioning and health-related quality of life at 2 years. This
64 l JANUARY JOGC JANVIER 2010
study was significantly longer than the other 3 trials, and its
findings suggest that these results persist beyond 1 year.
The study by Thakar et al.11 of 279 women (146 TAH and
133 SCH) was the only double-blind RCT. Each woman
was followed for 1 year. A short-form, previously validated
36-question health survey (SF-36) and psychological out-
come measure (GHQ: general health questionnaire) were
used preoperatively and at 6 and 12 months postoperatively
(0–100 scale). No statistical difference was found between
TAH and SCH on the SF-36 and GHQ before and after
surgery. The frequency of intercourse, desire for inter-
course, orgasm, and initiation of intercourse did not differ
significantly between the groups. In addition, most aspects
of quality of life improved in both randomization groups.
All aspects of mental health improved following hysterec-
tomy. There was also a significant increase in the frequency
of intercourse in both groups after surgery (P = 0.01). Deep
dyspareunia was reduced significantly in both groups
(46.2% to 6.6% SCH and 39.3% to 14.3% TAH) at
12 months (P < 0.001), but there was no statistical differ-
ence between groups.
Zobbe et al.13 conducted a randomized trial of 319 women
(158 TAH and 161 SCH). Each woman was followed for 1
year. At the 12-month follow-up, there was no statistical
difference between the 2 intervention groups regarding fre-
quency of sexual desire, intercourse, masturbation, and
orgasm, as well as quality of orgasm, vaginal lubrication, or
satisfaction with sexual life (P > 0.05). Dyspareunia
decreased significantly in both groups (89 women pre sur-
gery and 22 post surgery P = 0.009). A multivariate logistic
regression analysis identified preoperative satisfaction with
sexual life, good relationship with partner, chronic disease,
and use of hormone therapy as significant predictors of
postoperative satisfaction with sexual life.
Flory et al.12 conducted a randomized trial of 63 women
(32 LAVH and 31 LSCH). Each woman was followed for
7 months. Two control groups of women who did not
undergo hysterectomy were included. There were no
differences among the 4 groups in sexual functioning over-
all (P > 0.05). There was significant improvement in sex
drive, arousal, and sexual behaviour in the LAVH group,
and significant improvement in sexual behaviour and sexual
function in the LSCH group (P < 0.01). No significant
difference in pain variables among the 4 groups was found
(P > 0.05). Chronic pain in the abdomen and intensity of
pain during gynaecologic examination was alleviated in
both hysterectomy groups (P < 0.01). An overall postopera-
tive improvement in depressive and psychological
symptoms was also demonstrated in both hysterectomy
groups (P < 0.001). Similarly, no statistical difference in
adverse psychological effects was demonstrated among the

4 groups (P > 0.05). While the laparoscopic approach to the
surgery is more modern, the findings about sexual function
specifically are consistent, regardless of the approach to
surgery.
Recommendation
2. Women contemplating a vaginal, laparoscopic, or
abdominal hysterectomy for the management of benign
uterine disease should be reassured that hysterectomy is
usually associated with improved quality of life, includ-
ing improved sexual function, whether or not the cervix
is removed. (I-B)
URINARY DYSFUNCTION
Two RCTs specifically addressed urinary dysfunction after
TAH compared with SCH.14,15 Three RCTs addressed uri-
nary dysfunction as part of a larger study that also looked at
peri- and postoperative morbidity.16–18 All of these trials
included only women undergoing a hysterectomy for
benign indications. Only 1 trial was reported as a
double-blind controlled trial.16 Two were multicentre trials,
but investigators were not blinded to the treatment assign-
ment.14,17 All 3 trials used standardized questionnaires in
addition to cystometrography to assess urinary function.14,16,17
The study by Thakar et al.11 of 279 women (146 TAH and
133 SCH) was the only double-blind RCT. Each woman
was followed for 1 year. Urinary function was assessed by
use of twin-channel subtracted cystometrography and
uroflowmetry, as well as by the women’s response to sub-
jective standardized questionnaire. Urinary frequency,
stress urinary incontinence, urgency, urgency incontinence,
poor stream, interrupted stream, and incomplete emptying
did not differ significantly between groups. (P > 0.05). In
both groups, significantly fewer women had stress inconti-
nence (subjective and by urodynamic testing), urgency,
urinary frequency, nocturia, interrupted stream, and incom-
plete emptying at 1 year after surgery (P < 0.05).
Gimbel et al.18 conducted an RCT of 319 women (158 TAH
and 161 SCH). Each woman was followed for 1 year. A
non-validated questionnaire was administered at random-
ization and at 2, 6, and 12 months after surgery. The com-
parison of the 2 hysterectomy techniques showed a lower
rate of all urinary incontinence in the TAH group (OR 0.46,
95% CI 0.23 to 0.95; P = 0.03) than in the SCH at 12
months. Although there was no significant difference
found between the method of operation, and the 3 catego-
ries of urinary incontinence were examined individually, the
TAH did show a larger reduction in SUI and MUI than the
SCH group, resulting in the demonstrated overall reduc-
tion. No other differences between the women in the TAH
and SCH groups regarding lower urinary tract symptoms
were observed at the 12-month follow-up. (P > 0.05).
Supracervical Hysterectomy
Overall urinary frequency decreased and double/triple
(repetitive emptying) voiding increased in both groups at 1
year following hysterectomy (OR not provided). A
multivariate logistic regression analysis identified preopera-
tive incontinence, duration of surgery, and size of uterus, as
the most important variables predicting urinary inconti-
nence at 1 year after surgery.
Learman et al.17 conducted a randomized trial of 135
women (67 TAH and 68 SCH). Each woman was followed
for 2 years. There was no differential improvement in uri-
nary symptoms overall according to randomization group
(P > 0.05). There was a statistically significant reduction of
urgency incontinence, urinary urgency, sensation of incom-
plete emptying, frequent urination, and stress incontinence
in the TAH group. There was a statistically significant
reduction of urinary urgency, sensation of incomplete emp-
tying, and frequent urination in the SCH group (P < 0.05).
Recommendation
3. Supracervical hysterectomy should not be recommended
as a superior technique to total abdominal hysterectomy
for the prevention of postoperative lower urinary tract
symptoms. (I-B)
PERIOPERATIVE AND POSTOPERATIVE MORBIDITY
Three RCTs specifically addressed perioperative or postop-
erative complications of TAH compared with SCH.16–18 All
3 trials used objective measures abstracted from operative
reports, pathology reports, and discharge summaries to esti-
mate the intraoperative and postoperative complication
rates. All 3 trials included only women undergoing hysterec-
tomy for benign indications. Only 1 trial was reported as a
double-blind controlled trial.16 Two were multicentre trials,
but investigators were not blinded to the treatment assign-
ment.15,17 Repeat hospitalizations were ascertained by
cross-referencing abstracted data with diagnosis- related
group codes on readmission to hospitals affiliated with each
clinical centre and by assessing patients’ reports of hospital-
ization every 3 months.17
Learman et al.17 conducted a randomized trial of 135
women (67 TAH and 68 SCH). Each woman was followed
for 2 years. There were no statistically significant differ-
ences in procedure time, estimated blood loss, febrile
events, length of stay, and surgical complications between
the 2 randomized groups (P > 0.05). The rate of hospital
readmission was somewhat greater in the SCH group, but
the difference was not statistically significant (relative haz-
ard 1.99, 95% CI 0.58 to 6.8; P > 0.5). Five percent of the
SCH group experienced postoperative cyclical vaginal
bleeding.
JANUARY JOGC JANVIER 2010 l 65
SOGC CLINICAL PRACTICE GUIDELINE
Gimbel et al.18 conducted an RCT of 318 women (158 TAH
and 161 SCH). Each woman was followed for 1 year after
hysterectomy. SCH had a shorter median operation time
(70 minutes; range 34–165 vs. 85 minutes; range 35–255, P
< 0.001 ) and women who underwent this procedure had
less median perioperative blood loss than those who under-
went TAH (250 mL, range 10–2500 vs. 400 mL, range
25–4500; P < 0.001). Postoperative complications were
grouped into 4 categories according to severity and showed
no difference between the 2 hysterectomy methods (OR
1.02, CI 0.55 to 1.88; P = 0.95). The overall complication
rate was 41%. Twenty percent of the SCH group had cycli-
cal vaginal bleeding postoperatively.
In the double-blind RCT of 279 women (146 TAH and
133 SCH) by Thakar et al.,11 each woman was followed for
1 year. SCH had a shorter duration of surgery (59 minutes,
range 39.6–80.2 vs. 71.1 minutes, range 47.7–84.5; P <
0.001), and women who underwent this procedure had less
estimated blood loss (320.1 mL, range 49.1–591.1 vs. 422.6 mL,
range 120.8–724.4; P = 0.004) and a shorter hospital stay
than those who underwent TAH (5.2 days, range 4.3–6.3 vs.
6.0 days, range 1.3–10.7; P = 0.04). Immediate postopera-
tive complications were greater in the TAH group: 9.8%
(13) versus 27.4% (40) (P < 0.001), but delayed complica-
tions after discharge were greater in the SCH group: 10.5%
(10) versus 6.2% (9) (P < 0.001). No visceral damage was
sustained in either group. The majority of the immediate
postoperative complications were pyrexia, retention of
urine, and vault hematoma. Seven percent of the SCH
group experienced cyclical vaginal bleeding.
Recommendation
4. Although supracervical hysterectomy may be associated
with less blood loss and a shorter surgical time, these
parameters have not been found to be clinically signifi-
cant, and supracervical hysterectomy should not be rec-
ommended as a superior technique to total abdominal
hysterectomy for the prevention of peri- and postopera-
tive complications. (I-B)
5. Women considering a supracervical hysterectomy should
be counselled that they may continue experiencing cyclic
vaginal bleeding following the surgery. (I-B)
ADVERSE EFFECTS
Potential Harm of Leaving the Cervix at the Time of
Hysterectomy
Cervical cancer
We identified 2 papers that specified the incidence of cervi-
cal cancer following a SCH. A case–control study of 1104
women who underwent SCH in Denmark between 1978
and 1988 revealed 2 cases of cervical cancer, for an overall
66 l JANUARY JOGC JANVIER 2010
incidence of cervical cancer of 0.3% at 10 years. Both cases
of cervical cancer occurred in women over the age of 50.19
Oats et al. looked at 1515 women treated for cervical cancer
between 1946 and 1972 and found a 3.6% incidence of cer-
vical cancer in the stump.20 The incidence of cervical cancer
is very low in both studies, but in view of the persistent risk,
all women must continue to undergo routine cytological
screening following a SCH.
Recommendation
6. Women must be advised that they require routine
cytological screening following a supracervical hysterec-
tomy. (II-B)
There are no data to suggest that screening is less adequate
or less frequent following the removal of the corpus. A ret-
rospective cohort study on cervical screening in the US
demonstrated no difference in screening between women
after SCH and women who had not undergone hysterec-
tomy.21 Women with supracervical hysterectomies had the
same rate of testing—approximately one test every 2.5
years—as their non-exposed counterparts (mean differ-
ence: –0.03 tests/year, P = 0.62). Additionally, a retrospec-
tive cohort study by Hannoun-Levi et al. identified 77
patients with an infiltrating carcinoma of the cervical stump
and demonstrated similar treatment results in patients with
carcinoma of the cervical stump and in patients with carci-
noma of the intact uterus.22 The advantages of removing the
cervix when it is potentially diseased should be presented to
patients who are having a hysterectomy and who have a cur-
rent or significant history of abnormal cervical cytological
results. In the study by Learman et al.,17 3 TAH patients had
high-grade dysplasia in the cervical specimens despite the
requirement for up-to-date Papanicolaou smears and the
exclusion from the study of women with a previous history
of cervical dysplasia. This may reflect limitations in the sen-
sitivity of cervical cancer screening tests. It is also important
to discuss the need for ongoing surveillance of the vaginal
vault in women who have a total hysterectomy performed
in the presence of cervical dysplasia.
Recommendation
7. Women who require a hysterectomy and who have a cur-
rent or significant history of abnormal cervical cytologi-
cal results should be counselled on the advantages of
vaginal hysterectomy or total abdominal hysterectomy
over supracervical hysterectomy. (I-B)
Vaginal bleeding
Most surgeons routinely attempt to ablate the endocervical
canal after removal of the corpus at the time of SCH.
Persistent cyclical vaginal bleeding still occurs in up to 25%
women with a retained cervix following SCH. In a
retrospective cohort by Van Der Stege et al., 25% of women

experienced regular vaginal bleeding following SCH.23
Three RCTs16–18 described cyclical vaginal bleeding in 5%
to 20% of women following SCH. The problem of cyclical
vaginal bleeding exceeded acceptability in 2 women in the
study by Gimbel et al.,18 and each had her cervical stump
removed at 3 months after SCH. In the study by Learman et
al.,17 persistent vaginal bleeding led to a trachelectomy in
one SCH patient 15 months after hysterectomy.
COST
The direct costs following SCH have been shown to be sim-
ilar to those following TAH. In a retrospective cohort study
of 11 Ontario hospitals, the direct costs of TAH and SCH
were comparable in community hospitals and teaching hos-
pitals. There were, however, considerable variations in the
mean direct costs for hysterectomy by surgical approach
(e.g., $955–$1831 in the community hospital and
$1665–$3190 in the teaching hospital for SCH). Addition-
ally, the overall direct cost was much greater in the teaching
hospitals for both SCH and TAH.6 A trial by Showstack et
al. that randomized 120 women to receive either TAH or
SCH found that overall resource use was similar at 12 and
24 months.24
Women who undergo SCH still require regular cervical can-
cer screening, which may mean additional expenses in the
case of abnormal Papanicolaou smears, including repeat
cytologic studies, colposcopy, and treatment not incurred
with women who have their cervix removed. Women pre-
senting for definitive management of ongoing symptoms
related to the cervical stump may choose a trachelectomy,
which is associated with significant additional costs.
SUMMARY
Using the evidence, a November 2007 ACOG Committee
Opinion states that
Recently published Level 1 evidence reveals no
advantage of the supracervical hysterectomy with
regards to surgical complications, urinary symptoms
or sexual function for women undergoing hysterec-
tomy for symptomatic uterine leiomyomata or abnor-
mal uterine bleeding. The supracervical hysterectomy
should not be recommended as a superior technique
for hysterectomy for benign disease.25
The 4 RCTs specifically addressing sexual dysfunction do
not support the suggestion that removal of the uterine cer-
vix at hysterectomy is detrimental to sexual satisfaction.10–13
In fact, regardless of operative technique used, sexual func-
tion and frequency of intercourse often improved, as did
quality of life, mental health, intensity and frequency of
pain, and frequency of dyspareunia.
Supracervical Hysterectomy
The 3 RCTs15–17 specifically addressing urinary dysfunction
do not support the suggestion that removal of the uterine
cervix at hysterectomy is more detrimental to urinary func-
tion. Overall, SCH is not associated with any significant
improvement in urinary function when compared with
TAH; rather, women in both intervention groups had an
improvement in urinary symptoms, specifically SUI and
urgency.
The 3 RCTs16–18 specifically addressing peri- and postoper-
ative complications do not suggest that removal of the uter-
ine cervix at hysterectomy is detrimental. Two studies did
demonstrate a longer operating time,16,18 greater estimated
blood loss,16,18 and length of stay16 with SCH than with
TAH. Differences in operation time and blood loss are
unlikely to be clinically significant. The variation in length
of stay was less than 1 day, which is also not considered clin-
ically relevant. Perioperative complications were greater in
the TAH group in one study,16 but the most commonly doc-
umented complication was pyrexia, which may not be
clinically significant. The other 2 studies failed to demon-
strate a difference in postoperative complications17,18 or in
readmission rates.17
Although, in the past, data from uncontrolled series may
have suggested there are benefits in preserving the cervix, a
review of the recently published level 1 evidence reveals no
advantage to the supracervical technique of hysterectomy
with respect to sexual function, urinary symptoms, and sur-
gical complications in women undergoing hysterectomy for
benign indications.
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(Statistics Canada Cat 82–003).
2. Statistics Canada, Hospital Morbidity File, 1981/82; Canadian Institute for
Health Information, 1996/97.
3. Ottosen C, Lingman G, Ottosen L. Three methods for hysterectomy:
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Gynaecol Can 2002;24(1):37–48.
5. Brown AD, Magistretti AI, Ferris L, Steward DE. Hospital Report 2001:
Preliminary study volume 2. Exploring women’s health, 2001.
6. Cohen MM, Young W. Costs of hysterectomy: does surgical approach make
a difference? J Womens Health 1998 Sep;7(7):885–92.
7. Kilkku P, Grönroos M, Hirvonen T, Rauramo L. Supravaginal uterine
amputation vs. hysterectomy. Effects on libido and orgasm. Acta Obstet
Gynecol Scand 1983;62(2):147–52.
8. Vervest HA, Kiewiet de Jonge M, Vervest TM, Barents JW, Haspels AA.
Micturition symptoms and urinary incontinence after non-radical
hysterectomy. Acta Obstet Gynecol Scand 1988;67(2):141–6.
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9. Sills ES, Saini J, Steiner CA, McGee M 3rd, Gretz HF 3rd. Abdominal
hysterectomy practice patterns in the United States. Int J Gynaecol Obstet
1998 Dec;63(3):277–83.
10. Kuppermann M, Summitt RL Jr, Varner RE, McNeeley SG,
Goodman-Gruen D, Learman LA, et al. and Total or Supracervical
Hysterectomy Research Group. Sexual functioning after total compared
with supracervical hysterectomy: a randomized trial. Obstet Gynecol 2005
Jun;105(6):1309–18.
11. Thakar R, Ayers S, Georgakapolou A, Clarkson P, Stanton S, Manyonda I.
Hysterectomy improves quality of life and decreases psychiatric symptoms:
a prospective and randomised comparison of total versus subtotal
hysterectomy. BJOG 2004 Oct;111(10):1115–20.
12. Flory N, Bissonnette F, Amsel RT, Binik YM. The psychosocial outcomes
of total and subtotal hysterectomy: a randomized controlled trial. J Sex Med
2006 May;3(3):483–91.
13. Zobbe V, Gimbel H, Andersen BM, Filtenborg T, Jakobsen K, Sørensen
HC, et al. Sexuality after total vs. subtotal hysterectomy. Acta Obstet
Gynecol Scand 2004 Feb;83(2):191–6.
14. Lalos O, Bjerle P. Bladder wall mechanics and micturition before and after
subtotal and total hysterectomy. Eur J Obstet Gynecol Reprod Biol 1986
Mar;21(3):143–50.
15. Gimbel H, Zobbe V, Andersen BJ, Sørensen HC, Toftager-Larsen K,
Sidenius K, et al. Lower urinary tract symptoms after total and subtotal
hysterectomy: results of a randomized controlled trial. Int Urogynecol J
Pelvic Floor Dysfunct 2005 Jul-Aug;16(4):257–6.
16. Thakar R, Ayers S, Clarkson P, Stanton S, Manyonda I. Outcomes after
total versus subtotal abdominal hysterectomy. N Engl J Med 2002 Oct
24;347(17):1318–25.
17. Learman LA, Summitt RL Jr, Varner RE, McNeeley SG, Goodman-Gruen
D, Richter HE, et al. and Total or Supracervical Hysterectomy (TOSH)
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Research Group. A randomized comparison of total or supracervical
hysterectomy: surgical complications and clinical outcomes. Obstet Gynecol
2003 Sep;102(3):453–62.
18. Gimbel H, Zobbe V, Andersen BM, Filtenborg T, Gluud C, Tabor A.
Randomised controlled trial of total compared with subtotal hysterectomy
with one-year follow up results. BJOG 2003 Dec;110(12):1088–98.
19. Storm HH, Clemmensen IH, Manders T, Brinton LA. Supravaginal uterine
amputation in Denmark 1978–1988 and risk of cancer. Gynecol Oncol 1992
May;45(2):198–201.
20. Oats JJ. Carcinoma of the cervical stump. Br J Obstet Gynaecol 1976
Nov;83(11):896–9.
21. Eaker ED, Vierkant RA, Konitzer KA, Remington PL. Cervical cancer
screening among women with and without hysterectomies. Obstet Gynecol
1998 Apr;91(4):551–5.
22. Hannoun-Lévi JM, Peiffert D, Hoffstetter S, Luporsi E, Bey P, Pernot M.
Carcinoma of the cervical stump: retrospective analysis of 77 cases.
Radiother Oncol 1997 May;43(2):147–53.
23. van der Stege JG, van Beek JJ. Problems related to the cervical stump at
follow-up in laparoscopic supracervical hysterectomy. JSLS 1999
Jan-Mar;3(1):5–7.
24. Showstack J, Kuppermann M, Lin F, Vittinghoff E, Varner RE, Summitt
RL Jr, et al. Resource use for total and supracervical hysterectomies: results
of a randomized trial. Obstet Gynecol 2004 May;103(5 Pt 1):834–41.
25. ACOG Committee Opinion No. 388 November 2007: supracervical
hysterectomy. Obstet Gynecol 2007 Nov;110(5):1215–7.
26. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on Preventive Health Care. New grades for recommendations from
the Canadian Task Force on Preventive Health Care. CMAJ
2003;169(3):207–8.
 SOGC CLINICAL PRACTICE GUIDELINE

SOGC CLINICAL PRACTICE GUIDELINE

No. 235 October 2009 (Replaces No. 88, April 2000)

Active Management of the Third Stage of

Labour: Prevention and Treatment of
Postpartum Hemorrhage
be relevant. Each full-text article was critically appraised with use
This Clinical Practice Guideline has been prepared by the Clinical of the Jadad Scale and the levels of evidence definitions of the
Practice Obstetrics Committee and approved by the Executive and Canadian Task Force on Preventive Health Care.
Council of the Society of Obstetricians and Gynaecologists of
Canada. Values: The quality of evidence was rated with use of the criteria
described by the Canadian Task Force on Preventive Health Care.
PRINCIPAL AUTHOR
Sponsor: The Society of Obstetricians and Gynaecologists of
Dean Leduc, MD, Ottawa ON Canada.
Vyta Senikas, MD, Ottawa ON Recommendations
André B. Lalonde, MD, Ottawa ON Prevention of Postpartum Hemorrhage
CLINICAL PRACTICE OBSTETRICS COMMITTEE 1. Active management of the third stage of labour (AMTSL) reduces
Dean Leduc (Chair), MD, Ottawa ON the risk of PPH and should be offered and recommended to all
women. (I-A)
Charlotte Ballerman, MD, Edmonton AB
2. Oxytocin (10 IU), administered intramuscularly, is the preferred
Anne Biringer, MD, Toronto ON medication and route for the prevention of PPH in low-risk vaginal
Martina Delaney, MD, St. John’s NL deliveries. Care providers should administer this medication after
delivery of the anterior shoulder. (I-A)
Louise Duperron, MD, Montreal QC
3. Intravenous infusion of oxytocin (20 to 40 IU in 1000 mL, 150 mL
Isabelle Girard, MD, Montreal QC
per hour) is an acceptable alternative for AMTSL. (I-B)
Donna Jones, MD, Calgary AB
4. An IV bolus of oxytocin, 5 to 10 IU (given over 1 to 2 minutes), can
Lily Shek-Yun Lee, MD, Vancouver BC be used for PPH prevention after vaginal birth but is not
Debra Shepherd, MD, Regina SK recommended at this time with elective Caesarean section. (II-B)

Kathleen Wilson, RM, Ilderton ON 5. Ergonovine can be used for prevention of PPH but may be
considered second choice to oxytocin owing to the greater risk of
Disclosure statements have been received from all members of the maternal adverse effects and of the need for manual removal of a
committee. retained placenta. Ergonovine is contraindicated in patients with
hypertension. (I-A)

Abstract 6. Carbetocin, 100 mg given as an IV bolus over 1 minute, should be

used instead of continuous oxytocin infusion in elective Caesarean
Objective: To review the clinical aspects of postpartum hemorrhage section for the prevention of PPH and to decrease the need for
(PPH) and provide guidelines to assist clinicians in the prevention therapeutic uterotonics. (I-B)
and management of PPH. These guidelines are an update from
7. For women delivering vaginally with 1 risk factor for PPH,
the previous Society of Obstetricians and Gynaecologists of
Canada (SOGC) clinical practice guideline on PPH, published in carbetocin 100 mg IM decreases the need for uterine massage to
April 2000. prevent PPH when compared with continuous infusion of oxytocin. (I-B)

Evidence: Medline, PubMed, the Cochrane Database of Systematic
Reviews, ACP Journal Club, and BMJ Clinical Evidence were
searched for relevant articles, with concentration on randomized
controlled trials (RCTs), systematic reviews, and clinical practice
guidelines published between 1995 and 2007. Each article was
screened for relevance and the full text acquired if determined to
Key Words: Prevention, hemorrhage, obstetrics, obstetric
hemorrhage
8. Ergonovine, 0.2 mg IM, and misoprostol, 600 to 800 mg given by
the oral, sublingual, or rectal route, may be offered as alternatives
in vaginal deliveries when oxytocin is not available. (II-1B)
9. Whenever possible, delaying cord clamping by at least 60 seconds
is preferred to clamping earlier in premature newborns (< 37 weeks’
gestation) since there is less intraventricular hemorrhage and less
need for transfusion in those with late clamping. (I-A)
10. For term newborns, the possible increased risk of neonatal
jaundice requiring phototherapy must be weighed against the

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

980 l OCTOBER JOGC OCTOBRE 2009

 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage
Table 1. Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of Evidence Assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.54
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
Task Force on Preventive Health Care.54
physiological benefit of greater hemoglobin and iron levels up to
6 months of age conferred by delayed cord clamping. (I-C)
11. There is no evidence that, in an uncomplicated delivery without
bleeding, interventions to accelerate delivery of the placenta
before the traditional 30 to 45 minutes will reduce the risk of PPH.
(II-2C)
12. Placental cord drainage cannot be recommended as a routine
practice since the evidence for a reduction in the duration of the
third stage of labour is limited to women who did not receive
oxytocin as part of the management of the third stage. There is no
evidence that this intervention prevents PPH. (II-1C)
13. Intraumbilical cord injection of misoprostol (800 mg) or oxytocin
(10 to 30 IU) can be considered as an alternative intervention
before manual removal of the placenta. (II-2C)
Treatment of PPH
14. For blood loss estimation, clinicians should use clinical markers
(signs and symptoms) rather than a visual estimation. (III-B)
15. Management of ongoing PPH requires a multidisciplinary
approach that involves maintaining hemodynamic stability while
simultaneously identifying and treating the cause of blood loss. (III-C)
16. All obstetric units should have a regularly checked PPH
emergency equipment tray containing appropriate equipment. (II-2B)
17. Evidence for the benefit of recombinant activated factor VII has
been gathered from very few cases of massive PPH. Therefore
this agent cannot be recommended as part of routine practice. (II-3L)
18. Uterine tamponade can be an efficient and effective intervention to
temporarily control active PPH due to uterine atony that has not
responded to medical therapy. (III-L)
19. Surgical techniques such as ligation of the internal iliac artery,
compression sutures, and hysterectomy should be used for the
ABBREVIATIONS
AMTSL active management of the third stage of labour
PPH postpartum hemorrhage
RCT randomized controlled trial
Classification of Recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
management of intractable PPH unresponsive to medical
therapy. (III-B)
Recommendations were quantified using the evaluation of
evidence guidelines developed by the Canadian Task Force on
Preventive Health Care (Table 1).
J Obstet Gynaecol Can 2009;31(10):980–993
INTRODUCTION
ostpartum hemorrhage is the leading cause of maternal
P death worldwide, with an estimated mortality rate of
140 000 per year, or 1 maternal death every 4 minutes.1 PPH
occurs in 5% of all deliveries and is responsible for a major
part of maternal mortality.2,3 The majority of these deaths
occur within 4 hours of delivery, which indicates that they
are a consequence of the third stage of labour.4,5 Nonfatal
PPH results in further interventions, iron deficiency ane-
mia, pituitary infarction (Sheehan’s syndrome) with associ-
ated poor lactation, exposure to blood products,
coagulopathy, and organ damage with associated
hypotension and shock.
Since all parturient women are at risk for PPH, care provid-
ers need to possess the knowledge and skills to practise
active management of the third stage of labour to prevent
PPH and to recognize, assess, and treat excessive blood
loss.
DEFINITION OF PPH
Primary PPH is defined as excessive bleeding that occurs in
the first 24 hours after delivery.
OCTOBER JOGC OCTOBRE 2009 l 981
SOGC CLINICAL PRACTICE GUIDELINE
Table 2. Signs and symptoms of shock resulting from
blood loss
Degree of shock Blood loss Signs and symptoms
Mild < 20% Diaphoresis
Increased capillary refilling
Cool extremities
Anxiety
Moderate 20% to 40% Above plus
Tachycardia
Tachypnea
Postural hypotension
Oliguria
Severe > 40% Above plus
Hypotension
Agitation/confusion
Hemodynamic instability
Traditionally the definition of PPH has been blood loss in
excess of 500 mL after vaginal delivery and in excess of
1000 mL after abdominal delivery. For clinical purposes,
any blood loss that has the potential to produce
hemodynamic instability should be considered PPH. The
amount of blood loss required to cause hemodynamic insta-
bility will depend on the pre-existing condition of the
woman. Hemodynamic compromise is more likely to occur
in conditions such as anemia (e.g., iron deficiency,
thalassemia) or volume-contracted states (e.g., dehydration,
gestational hypertension with proteinuria).
Hypovolemic Shock6
Excessive bleeding, or hemorrhage, results in net loss of
intravascular volume and decreased oxygen delivery to tis-
sues and organs. Physiological compensatory mechanisms
such as reflex tachycardia, peripheral vasoconstriction, and
increased myocardial contractility help to maintain tissue
perfusion. Increasing blood loss results in circulatory col-
lapse, end-organ damage, and eventual death.
Ideally, care providers should be able to assess the amount
of blood loss in order to estimate the volume of fluid that
needs to be replaced. However, research has shown that cli-
nicians often underestimate the actual loss.7 The signs and
symptoms listed in Table 2 should be used at the bedside to
evaluate the amount of blood loss since, in general, the
degree of shock parallels the amount of blood loss that
results in these clinical markers.6
Etiology of PPH
In regard to the underlying causes of PPH, it may be helpful
to think in terms of the 4 Ts:
• Tone: uterine atony, distended bladder
• Tissue: retained placenta and clots
• Trauma: vaginal, cervical, or uterine injury
• Thrombin: coagulopathy (pre-existing or acquired)
982 l OCTOBER JOGC OCTOBRE 2009
The most common and important cause of PPH is uterine
atony. The primary protective mechanism for immediate
hemostasis after delivery is myometrial contraction causing
occlusion of uterine blood vessels, the so-called living liga-
tures of the uterus. Thus blood flow from the vascular
space to the uterine cavity via the myometrium is impeded.
Maternity care providers should recognize the risk factors
for PPH due to the 4 Ts, as listed in Table 3, and take appro-
priate action.
PREVENTION OF PPH
AMTSL involves interventions to assist in expulsion of the
placenta with the intention to prevent or decrease blood
loss. Interventions include use of uterotonics, clamping of
the umbilical cord, and controlled traction of the cord. In
contrast, with expectant, or physiological, management,
spontaneous delivery of the placenta is allowed, with subse-
quent intervention, if necessary, that involves uterine
massage and use of uterotonics.
Prendiville and colleagues’ meta-analysis8 demonstrated the
benefits of AMTSL to prevent and reduce PPH after vagi-
nal delivery for women at low risk of PPH. Studies included
in the meta-analysis had design methods that involved rou-
tine use of uterotonics after delivery of the newborn and
before delivery of the placenta, early cord clamping, and
controlled cord traction. The primary goal of these inter-
ventions was to assist placental delivery, thereby allowing
the uterus to contract and reduce blood flow across the
myometrium.
The meta-analysis concluded that active compared with
expectant management significantly reduced the risk in all
areas, including mild PPH (estimated blood loss > 500 mL;
OR 0.38; 95% CI 0.32 to 0.46), severe PPH (estimated
blood loss > 1000 mL; OR 0.32; 95% CI 0.21 to 0.50), low
postpartum hemoglobin level (< 9 g/dL; OR 0.38; 95% CI
0.27 to 0.53), need for transfusion (OR 0.33; 95% CI 0.21 to
0.52), and need for additional uterotonic medication (OR
0.17; 95% CI 0.14 to 0.21). There was no difference in the
incidence of retained placenta or management of this
complication by manual or surgical removal. There was
significantly more nausea and hypertension in the actively
managed group given ergonovine (OR 1.83; 95% CI 1.51
to 2.23).
A review of the data resulted in a joint statement in 2004 by
the International Confederation of Midwives and Interna-
tional Federation of Gynaecologists and Obstetricians
endorsing the need for all deliveries to be attended by a
caregiver trained in AMTSL, which should include routine
use of uterotonics, controlled cord traction, and uterine
massage.9 Delaying cord clamping by 1 to 3 minutes was
 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage

Table 3. Risk factors for postpartum hemorrhage (PPH)

Etiologic category and process Clinical risk factors
Tone: abnormalities of uterine contraction
Overdistension of uterus Polyhydramnios
Multiple gestation
Macrosomia
Uterine muscle exhaustion Rapid labour
Prolonged labour
High parity
Oxytocin use
Intra-amniotic infection Fever
Prolonged rupture of membranes
Functional/anatomic distortion of uterus Fibroids
Placenta previa
Uterine-relaxing medications
Uterine anomalies
Bladder distension, which may prevent Halogenated anesthetics
uterine contraction 4 Nitroglycerin
Tissue: retained
Retained products of conception Incomplete placenta at delivery
Previous uterine surgery
Abnormal placentation
High parity
Retained cotyledon or succenturiate lobe Abnormal placenta seen on ultrasonography
Retained blood clots Atonic uterus
Trauma: of the genital tract
Lacerations of the cervix, vagina, or perineum Precipitous delivery
Operative delivery
Extensions, lacerations at cesarean section Malposition
Deep engagement
Uterine rupture Previous uterine surgery
Uterine inversion High parity
Fundal placenta
Excessive cord traction
Thrombin: abnormalities of coagulation
Pre-existing states History of hereditary coagulopathies or liver disease
Hemophilia A
Von Willebrand’s disease
History of previous PPH
Acquired in pregnancy
Idiopathic thrombocytopenic purpura Bruising, elevated blood pressure
Thrombocytopenia with preeclampsia
Disseminated intravascular coagulation
Gestational hypertensive disorder of pregnancy Elevated blood pressure
with adverse conditions
a) Dead fetus in utero Fetal demise
b) Severe infection Fever, neutrophilia/neutropenia
c) Abruption Antepartum hemorrhage
d) Amniotic fluid embolus Sudden collapse
Therapeutic anticoagulation History of thrombotic disease

favoured over early cord clamping to reduce anemia in the
newborn.
A similar review of the literature in 2006 by the World
Health Organization10 highlighted the most common cause
of PPH as uterine atony and the fact that most women with
PPH have no identifiable risk factors. The review resulted
in several recommendations to minimize maternal morbid-
ity and mortality rates.
1. Active management should be offered to all women
by skilled care providers.
2. Skilled attendants should offer uterotonics (oxytocin
preferred over ergonovine, misoprostol, and
carboprost) to prevent PPH.
3. Early cord clamping is recommended only when the
newborn needs to be resuscitated.

OCTOBER JOGC OCTOBRE 2009 l 983

SOGC CLINICAL PRACTICE GUIDELINE
4. Despite the lack of evidence to support cord traction,
this practice should be continued as part of active
management.
Uterotonics
During the third stage of labour the muscles of the uterus
contract downward, causing constriction of the blood ves-
sels that pass through the uterine wall to the placental sur-
face and stopping the flow of blood. This action also causes
the placenta to separate from the uterine wall. The absence
of uterine contractions, clinically defined as atony, may
result in excessive blood loss. Uterotonics promote uterine
contractions to prevent atony and speed delivery of the
placenta.
The uterotonic agents include oxytocin, ergonovine,
carbetocin, misoprostol, and Syntometrine (a combination
of ergonovine and oxytocin, unavailable in Canada).
Oxytocin and ergonovine
The 1997 Abu Dhabi study11 included in Prendiville and
colleagues’meta-analysis8 randomly allocated low-risk
women who delivered vaginally to receive either 10 IU of
oxytocin IM with delivery of the anterior shoulder followed
by controlled cord traction upon signs of placental separa-
tion or minimal intervention. The results revealed a benefit
for the oxytocin group: a lower incidence of blood loss
> 500 mL (OR 0.50; CI 0.34 to 0.73) and > 1000 mL (OR
0.22; CI 0.08 to 0.57), fewer retained placentas (OR 0.31; CI
0.15 to 0.63), and less need for additional uterotonics (OR
0.44; CI 0.24 to 0.78).
A 2004 Cochrane Review12 compared the efficacy of
Syntometrine and oxytocin alone, both administered IM, in
AMTSL. The results showed a small benefit for
Syntometrine in preventing blood loss > 500 mL (OR 0.82;
95% CI 0.71 to 0.95) but no difference in preventing losses
> 1000 mL. The group receiving Syntometrine were more
likely to have elevated diastolic blood pressure (OR 2.40;
95% CI 1.58 to 3.64), nausea (OR 4.07; 95% CI 3.43 to
4.84), and vomiting (OR 4.92; 95% CI 4.03 to 6.00). The
authors favoured oxytocin alone on the basis of the lower
incidence of maternal side effects.
A 2008 meta-analysis13 included 14 studies assessing the
benefits of oxytocin in AMTSL for vaginal deliveries. Seven
trials comparing oxytocin and no uterotonics found a lower
incidence of blood loss > 500 mL (RR 0.50; 95% CI 0.43 to
0.59) and less need for therapeutic oxytocin (RR 0.5; 95%
CI 0.39 to 0.64) in the groups receiving oxytocin. Six trials
found no difference between the results with oxytocin and
ergonovine except that the groups receiving oxytocin had
fewer manual removals of the placenta (RR 0.57; 95% CI
0.41 to 0.79) and a tendency to a lower incidence of raised
blood pressure (RR 0.53; 95% CI 0.19 to 1.52) than the
984 l OCTOBER JOGC OCTOBRE 2009
groups receiving ergonovine. Five trials showed little evi-
dence of a synergistic effect of adding oxytocin to
ergonovine versus ergonovine alone.
One double-blind randomized controlled trial14 compared
the efficacy of 10 IU of oxytocin in saline solution with
saline solution alone in cephalic vaginal deliveries in
low-risk women. The oxytocin group had a lower mean
blood loss (407 vs. 527 mL), a lower incidence of blood loss
> 800 mL (8.8% vs. 5.2%), and a lower rate of use of addi-
tional ergonovine (3.5% vs. 2.3%). Another double-blind
RCT15 found no difference in the incidence of PPH among
women with low-risk vaginal deliveries given an IV bolus of
oxytocin (20 IU in 500 mL of crystalloid) before or after
delivery of the placenta.
The use of a slow IV bolus in management of the third stage
of labour has been adopted as standard practice although
there is little supporting evidence in the literature. The
Dublin trial16 was the only study in Prendiville and
colleagues’meta-analysis8 in which a uterotonic
(Syntometrine) was administered IV; the result was a lower
incidence of PPH but more retained placentas.
There has been concern about the safety of such rapid
administration of oxytocin in the third stage, although
99 women given 10 IU in an IV push after vaginal delivery
did not have significant hemodynamic effects. The study,
however, was underpowered to demonstrate a reduction in
the incidence of PPH.17
For women undergoing elective Caesarean section, recent
studies have demonstrated adverse maternal effects of an
oxytocin IV bolus. One double-blind RCT found
hemodynamic changes in 30 patients given 5 IU IV over 30
seconds compared with women who received the same
dose over 5 minutes.18 In another double-blind RCT, 40
patients given 10 IU of oxytocin as an IV bolus manifested
electrocardiographic changes consistent with myocardial
ischemia when compared with pregnant women who
received 0.2 mg of ergonovine and nonpregnant women;
the effect was transient, with onset at 1 minute and resolu-
tion by 5 minutes after exposure to oxytocin.19 These stud-
ies suggest a potential maternal effect of the rapid adminis-
tration (within 30 seconds) of oxytocin, and it may be
dose-related.
Oxytocin given as part of AMTSL has been shown to
reduce the need for manual removal of a retained placenta
compared with expectant management.8,13 The greater need
for manual removal noted in the Dublin trial16 was attrib-
uted to the use of Syntometrine as an IV bolus. A 2001
Cochrane review13 of prophylactic IM oxytocin use during
the third stage of labour demonstrated a significantly
reduced need for manual removal of the placenta compared
with ergometrine use (RR 0.57; 95% CI 0.41 to 0.79).
 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage
Recommendations
Recommendations were quantified using the evaluation of
evidence guidelines developed by the Canadian Task Force
on Preventive Health Care (Table 1).
1. AMTSL reduces the risk of PPH and should be offered
and recommended to all women. (I-A)
2. Oxytocin (10 IU), administered intramuscularly, is the
preferred medication and route for the prevention of
PPH in low-risk vaginal deliveries. Care providers
should administer this medication after delivery of the
anterior shoulder. (I-A)
3. Intravenous infusion of oxytocin (20 to 40 IU in 1000 mL,
150 mL per hour) is an acceptable alternative for
AMTSL. (I-B)
4. An IV bolus of oxytocin, 5 to 10 IU (given over 1 to
2 minutes), can be used for PPH prevention after vaginal
birth but is not recommended at this time with elective
Caesarean section. (II-B)
5. Ergonovine can be used for prevention of PPH but may
be considered second choice to oxytocin owing to the
greater risk of maternal adverse effects and of the need
for manual removal of a retained placenta. Ergonovine is
contraindicated in patients with hypertension. (I-A)
Carbetocin
Carbetocin is a long-acting oxytocin studied by Dansereau
et al.,20 who performed an RCT comparing the incidence of
PPH in women undergoing elective Caesarean section who
received either carbetocin as a 100-mg IV bolus or oxytocin
as a continuous infusion for 8 hours (25 IU of oxytocin in
1000 mL of Ringer’s lactate, 125 mL per hour). The
carbetocin group had a decreased incidence of PPH and of
the need for therapeutic oxytocics (4.7% vs. 10.1%; P <
0.05). The recommended dose of carbetocin is 100 mg given
either IM or slowly (over 1 minute), the pharmacokinetics
of the 2 administration routes being almost the same.21
Boucher and colleagues’ double-blind 2003 RCT22 demon-
strated that women with at least 1 risk factor for PPH who
were given carbetocin (100 mg IM) immediately after pla-
cental delivery were less likely to required uterine massage
as a uterotonic intervention than those given a continuous
infusion of oxytocin over 2 hours: 43.4% of women in the
carbocetin group (36/83 [43.4%]; 95%CI, 32.7% to 54%
vs. 48/77 [62.3%] of women in the oxytocin group; 95%
CI, 51.5% to 73.2%) required the massage (P = 0.02). There
was no difference in the requirement for additional
uterotonic medication (i.e., oxytocin, ergonovine), esti-
mated blood loss, or difference in hemoglobin level before
and after vaginal delivery. There was no significant benefit
of carbetocin over oxytocin in the prevention of PPH. The
authors commented on the advantage of IM intervention in
a setting where IV treatment is unavailable.
A 2007 Cochrane Review23 included 4 RCTs that compared
carbetocin with oxytocin for prevention of PPH. The
results were consistent with the results of the trials con-
ducted by Dansereau and Boucher and their colleagues.20,22
Since none of the trials included low-risk women, there was
insufficient evidence that 100 mg of carbetocin given IV is
as effective as oxytocin in the prevention of PPH in low-risk
vaginal deliveries.
An RCT by Leung et al.24 compared IM administration of
carbetocin and Syntometrine in AMTSL for singleton vagi-
nal deliveries after 34 weeks. The results showed no differ-
ence in the incidence of a low hemoglobin level, blood loss
> 500 mL, retained placenta, or use of additional uterotonic
agents. Carbetocin recipients had less nausea (RR 0.18;
95%CI 0.04 to 0.78), vomiting (RR 0.1; 95% CI 0.01 to
0.74), and hypertension 30 minutes (0 vs. 8 cases, P < 0.01)
and 60 minutes (0 vs. 6 cases, P < 0.05) after delivery. There
was a higher incidence of maternal tachycardia (RR 1.68;
95% CI 1.03 to 3.57) in the carbetocin group.
We did not identify any published reports of trials compar-
ing oxytocin and carbetocin, each administered IM for
AMTSL, in low-risk term vaginal deliveries.
Recommendations
6. Carbetocin, 100 mg given as an IV bolus over 1 minute,
should be used instead of continuous oxytocin infusion
in elective Caesarean section for the prevention of PPH
and to decrease the need for therapeutic uterotonics. (I-B)
7. For women delivering vaginally with 1 risk factor for
PPH, carbetocin 100 mg IM decreases the need for uter-
ine massage to prevent PPH when compared with con-
tinuous infusion of oxytocin. (I-B)
Misoprostol
Misoprostol is a prostaglandin that has generated consider-
able interest as an effective uterotonic agent owing to its
ease of administration, safety profile, cost, and ease of stor-
age. The first study of misoprostol as a uterotonic agent was
an uncontrolled prospective study for prevention of PPH.25
A systematic review26 that analyzed the pharmacokinetics of
misoprostol concluded the following:
• There is a shorter time to peak concentration with oral
and sublingual administration than with vaginal or
rectal administration.
• Sublingual administration results in the most rapid
onset of effects and the highest peak concentration.
• The initial increase in tonus is more pronounced after
oral than after vaginal administration.
OCTOBER JOGC OCTOBRE 2009 l 985
SOGC CLINICAL PRACTICE GUIDELINE
• The effects have a slower onset but longer duration
with rectal and vaginal routes than with oral and
sublingual routes.
• Pyrexia is more common when the dose exceeds
600 mg.
There have been 3 systematic reviews of the use of
misoprostol for the prevention of PPH.27–29 The WHO
multicentre trial30 and the Cochrane review27 suggested that
the observed lesser efficacy of misoprostol compared with
injectable uterotonics may be due to the later achievement
of peak plasma levels with oral and sublingual administra-
tion of misoprostol: 30 minutes versus 1 to 2 minutes for
IM or IV administration of oxytocin. All of the reviews con-
cluded that misoprostol was not as effective as oxytocin for
the prevention of PPH and that maternal pyrexia was a sig-
nificant adverse effect.
A 2007 study comparing 800 mg of misoprostol adminis-
tered rectally with 10 IU of oxytocin administered IM in a
developing country found these 2 agents to be equally effec-
tive in minimizing blood loss during the third stage of
labour.31 There was more pyrexia in the misoprostol group,
however.
The systematic review by Joy and colleagues29 compared the
efficacy of misoprostol with that of oxytocin, other
uterotonic agents, and placebo in preventing PPH in the
third stage of labour. Compared with placebo, misoprostol
was associated with a decreased need for additional
uterotonics (OR 0.64; 95% CI 0.46 to 0.90) and an
increased risk of shivering and pyrexia. Oxytocin was supe-
rior to misoprostol in preventing blood loss and the need
for additional agents, and the patients had less shivering and
pyrexia. The authors proposed that misoprostol is a reason-
able agent for management of the third stage of labour
when other agents are not available for reasons of cost, stor-
age, or difficulty of administration.
There have been no studies to determine the benefit of a
combination of oxytocin and misoprostol compared with
either agent alone.
Recommendation
8. Ergonovine, 0.2 mg IM, and misoprostol, 600 to
800 mg given by the oral, sublingual, or rectal route,
may be offered as alternatives in vaginal deliveries
when oxytocin is not available. (II-1B)
Management of the Placenta
Timing of cord clamping
Clamping of the umbilical cord is a necessary part of the
third stage of labour. Its timing varies widely throughout
the world, early clamping being the predominant practice in
Western countries.32 Physiological studies have shown that
986 l OCTOBER JOGC OCTOBRE 2009
25% to 60% of the fetal–placental circulation is found in the
placental circulation.33,34 Early cord clamping in term new-
borns results in a decrease of 20 to 40 mL/kg of blood,
which is equivalent to 30 to 35 mg of iron. A delay in clamp-
ing, causing increased neonatal blood volume, may lead to
complications such as respiratory distress, neonatal
jaundice, and polycythemia.
Prendiville and colleagues’ meta-analysis espousing the
benefit of AMTSL8 included studies that applied early cord
clamping, controlled traction, and uterotonics before deliv-
ery of the placenta. In these studies, early cord clamping was
included as part of controlled traction and was not inde-
pendently studied to demonstrate a benefit.
A 2004 Cochrane Review by Rabe et al.35 and a prospective
study by Ibrahim et al.36 demonstrated that delaying cord
clamping by 30 to 120 seconds resulted in less need for
transfusion because of anemia (RR 2.01; 95% CI 1.24 to
3.27) and less intraventricular hemorrhage (RR 1.74; 95%
CI 1.08 to 2.81) in nonresuscitated premature infants (< 37
weeks’ gestation).
A systematic review and meta-analysis comparing cord
clamping done early (less than 1 minute after delivery of the
infant) and late (at least 2 minutes after delivery) showed
that late clamping conferred physiological benefit to the
newborn that extended up to 6 months into infancy.37
Advantages included prevention of anemia over the first 3
months of life and enhanced iron stores (weighted mean
difference 19.90; 95% CI 7.67 to 32.13) and ferritin concen-
tration (weighted mean difference 17.89; 95% CI 16.58 to
19.21) for up to 6 months. There was no increase in respira-
tory distress, defined as tachypnea or grunting. Neonates
were at increased risk of asymptomatic polycythemia (RR
3.82; 95% CI 1.11 to 13.21). There was no significant differ-
ence between the early and late groups in bilirubin levels
and proportions of infants receiving phototherapy.
A 2008 Cochrane review included 11 RCTs that compared
the effect on maternal and neonatal outcomes of cord
clamping done early (up to 60 seconds after delivery) and
late (beyond 60 seconds after delivery).38 The results
showed no difference in the incidence of PPH but an
increased incidence of neonatal jaundice requiring
phototherapy, higher newborn hemoglobin levels up to 6
months of age, and higher ferritin levels at 6 months of age
after late clamping.
Recommendations
9. Whenever possible, delaying cord clamping by at least
60 seconds is preferred to clamping earlier in premature
newborns (< 37 weeks’ gestation) since there is less
intraventricular hemorrhage and less need for transfu-
sion in those with late clamping. (I-A)
 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage
10. For term newborns, the possible increased risk of neo-
natal jaundice requiring phototherapy must be weighed
against the physiological benefit of greater hemoglobin
and iron levels up to 6 months of age conferred by
delayed cord clamping. (I-C)
Timing of placental delivery
Placental delivery is essential to allow the uterus to contract
and thus reduce blood loss in the third stage of labour. This
process is completed within 5 minutes in 50% of deliveries
and by 15 minutes in 90%. Failure of the placenta to be
delivered in such a timely manner is a well-known risk fac-
tor of PPH.39,40
The traditional definition of retained placenta includes fail-
ure of placental delivery within 30 to 45 minutes and a
requirement of intervention to assist with delivery. One
study published in 2006 concluded that the risk of PPH
increases if the placenta has not been delivered by 10 min-
utes, although research is needed to determine if the risk of
PPH can be reduced by intervening at this stage.41
Recommendation
11. There is no evidence that, in an uncomplicated delivery
without bleeding, interventions to accelerate delivery of
the placenta before the traditional 30 to 45 minutes will
reduce the risk of PPH. (II-2C)
Placental cord drainage
Drainage of cord blood has been proposed to assist with
delivery of the placenta.
A 2005 Cochrane review42 included only 2 studies address-
ing this intervention, which makes it difficult to draw con-
clusions. The selection criteria for the review were low-risk
vaginal deliveries in which a cord clamped within 30 sec-
onds of delivery and separated was unclamped, which
allowed the blood from the placenta to drain freely. The
measured outcomes included incidence of retained placenta
(at 30 to 45 minutes), manual removal of the placenta, PPH,
length of the third stage of labour, need for blood transfu-
sion, decrease in maternal hemoglobin level, and maternal
pain. The outcomes reported were a decreased incidence of
retained placenta at 30 minutes (RR 0.28; 95% CI 0.10 to
0.73) and a shorter third stage (weighted mean difference
–5.46; 95% CI –8.02 to –2.90) after cord drainage. A major
confounding factor was the lack of use of uterotonics and
the varied definition of a prolonged third stage: from 30 to
45 minutes.
Sharma et al.43 randomly assigned 958 women to either pla-
cental cord drainage or controlled traction after administra-
tion of 0.2 mg of ergonovine with delivery of the anterior
shoulder and immediate cord clamping. Measured out-
comes were PPH and length of the third stage. The third
stage had a mean duration of 3.24 and 3.20 minutes in the
drainage group versus 8.57 and 6.20 minutes in the traction
group in primigravid (P < 0.05) and multigravid (P < 0.05)
women, respectively. There was no significant difference
between the groups in the incidence of blood loss > 500 mL
and the need for transfusion (P > 0.05), and none of the
women had a retained placenta.
The limited number of studies makes it difficult to recom-
mend a change in practice to support routine cord drainage,
but this intervention does appear to reduce the length of the
third stage of labour and the risk of a retained placenta.
More research is required to determine if the length of the
third stage is reduced with routine drainage after the use of
uterotonics and if this intervention reduces the risk of PPH.
Recommendation
12. Placental cord drainage cannot be recommended as a
routine practice since the evidence for a reduction in the
duration of the third stage of labour is limited to women
who did not receive oxytocin as part of the management
of the third stage. There is no evidence that this interven-
tion prevents PPH. (II-1C)
Injection of the umbilical vein
Injection of the umbilical vein has been proposed to assist
in uterine contractions and dehiscence of the placenta from
the uterine wall to effect delivery. If successful, this inter-
vention would avoid manual removal of the placenta, an
invasive procedure with potential complications, including
hemorrhage, infection, and trauma. A 2001 Cochrane
Review44 assessed if injection of various agents would
reduce the need for manual removal of a retained placenta.
The authors derived the following conclusions.
• Saline versus expectant management: no difference
(RR 0.97; 95% CI 0.83 to 1.14).
• Saline plus oxytocin versus expectant management:
nonsignificant reduction in the incidence of manual
removal (RR 0.86; 95% CI 0.72 to 1.01) with the use of
saline plus oxytocin.
• Saline plus oxytocin versus saline: significantly lower
incidence of manual removal of the placenta (RR 0.79;
95% CI 0.69 to 0.91) (number needed to treat: 8; 95%
CI 5 to 20) with the use of saline plus oxytocin.
• Saline plus oxytocin versus plasma expander:
nonsignificantly greater incidence of manual removal of
the placenta (RR 1.34; 95% CI 0.97 to 1.85) with the
use of saline plus oxytocin.
• Saline plus prostaglandin versus saline: significantly
lower incidence of manual removal of the placenta (RR
0.05; 95% CI 0.00 to 0.73) with the use of saline plus
prostaglandin but no difference in the incidence of
blood loss, fever, pain, and oxytocin augmentation.
OCTOBER JOGC OCTOBRE 2009 l 987
SOGC CLINICAL PRACTICE GUIDELINE

Figure 1. Pipingas technique for injection of the intraumbilical vein if the placenta has not separated or
delivered within 45 minutes after delivery of the baby

• Prepare a syringe of misoprostol (800 mg) or oxytocin (50 IU) dissolved in 30 mL of normal saline.
• Insert a size 10 nasogastric suction catheter along the umbilical vein. If resistance is felt, retract the catheter 1 to 2 cm
and advance it further, if possible. If the catheter cannot be advanced further without force, inject the solution in this
position.
• If most of the catheter has been inserted when resistance is felt, indicating that it has reached the placenta, retract it 3 to
4 cm to ensure that the tip is in the umbilical vein and not in a placental branch.
• Connect the syringe to the catheter and inject the solution. Clamp the catheter in situ and record the time of the injection.
• Allow 30 minutes for the placenta to deliver before undertaking further intervention.

• Saline plus prostaglandin versus saline plus oxytocin:
no difference (RR 0.10; 95% CI 0.01 to 1.59).
This review suggests that umbilical vein injection of
uterotonics assists with the third stage of labour but pro-
vides no convincing evidence of the benefit; the last 3 con-
clusions were based on the results of a single small trial. The
authors conclude that umbilical vein injection of oxytocin
may reduce the need for manual removal of a retained pla-
centa, but further investigation is required. There is an
ongoing systematic review to determine if routine injection
of the umbilical vein with a uterotonic within 15 minutes of
birth will affect perinatal and maternal outcomes.45
An RCT compared the effect of intraumbilical vein injec-
tion of Syntocinon (synthetic oxytocin; 50 IU in 30 mL of
normal saline), misoprostol (800 mg in 30 mL of normal
saline), or normal saline (30 mL) on the need for manual
removal of the placenta in a prolonged third stage of labour
in 87 low-risk women at term.46 The Pipingas technique
(Figure 1) was used for injection. All the women had
AMTSL with either oxytocin or Syntometrine with delivery
of the anterior shoulder, early cord clamping, and cord trac-
tion when signs of placental separation were observed. The
women whose third stage exceeded 30 minutes were ran-
domly assigned to intervention at 45 minutes with 1 of the 3
injections. The trial was stopped when the misoprostol
group had many fewer instances of manual removal of the
placenta (9 of 21 women) compared with the Syntocinon
group (16 of 20 women) and the saline group (7 of 13
women).
Recommendation
13. Intraumbilical cord injection of misoprostol (800 mg) or
oxytocin (10 to 30 IU) can be considered as an alternative
intervention before manual removal of the placenta.
(II-2C)
large volume of blood.43 Clinical signs and symptoms
(Table 2) are useful bedside indicators of ongoing blood
loss and will assist clinicians in management. A previously
established plan of action is of great value when preventive
measures have failed. This plan should include aggressive
fluid resuscitation, control of bleeding to minimize loss, and
access to a surgical room and support personnel (Table 4).
The initial goal of management is to determine the cause of
blood loss while instituting resuscitative measures. Evalua-
tion of uterine tone and a complete inspection of the lower
genital tract are required. The goal of resuscitative measures
is to maintain hemodynamic stability and oxygen perfusion
of the tissues. An IV infusion of crystalloid solution should
be instituted, using large-bore tubing, along with oxygen
supplementation. The “ABCs” should be observed and
vital signs, oxygen saturation, and urinary output moni-
tored. A visual assessment of clotting can be done at the
bedside while blood is sent for analysis and matching for
transfusion.
PPH emergencies often occur unexpectedly and, depending
on the volume of deliveries in each institution, may be infre-
quent. When a situation does not resolve with the usual
interventions, there is a need for more equipment that may
not be readily available when needed. For these reasons,
every obstetric unit should have a readily available tray with
all of the necessary equipment. Since clinicians may rarely
apply these interventions, this equipment should be accom-
panied by appropriate diagrams illustrating the relevant
anatomy and technique. A previously prepared PPH tray in
a large Canadian birthing centre was used in 1 in 250 Caesarean
sections and 1 in 1000 vaginal deliveries.47
Recommendations
14. For blood loss estimation, clinicians should use clinical
markers (signs and symptoms) rather than a visual
estimation. (III-B)

TREATMENT OF ESTABLISHED PPH

15. Management of ongoing PPH requires a multidisciplinary
approach that involves maintaining hemodynamic stabil-
Research has shown that care providers poorly estimate ity while simultaneously identifying and treating the
blood loss7 and consistently underestimate the loss of a cause of blood loss. (III-C)

988 l OCTOBER JOGC OCTOBRE 2009

 Table 4. Treatment of PPH
Initial assessment and
treatment for primary PPH
Call for help
Resuscitation
• Assess the “ABC”
• Oxygen by mask
• IV line
• Crystalloid, isotonic
fluid replacement
• Monitor BP, P, R
• Empty bladder, monitor
urine output
Laboratory tests
• Complete blood count
• Coagulation screen
• Blood grouping
and cross
OCTOBER JOGC OCTOBRE 2009 l
Adapted with permission of the World Health Organization from Postpartum Hemorrhage Technical Consultation Meeting Document55
989
Assess etiology Directed therapy
Uterus soft and relaxed Uterine atony Uterine massage
Uterotonic drugs
Placenta not separated Retained Whole placenta in uterus
or partially separated placenta • Uterotonics
(with or without
hemorrhage) • Controlled cord
traction
• Intraumbilical vein
injection
Incomplete separation
• Manual vacuum
aspiration
• Manual exploration
• Gentle curettage
Excess bleeding or Low genital ® Repair tears in
shock shortly after birth, tract trauma perineum, vagina and
uterus contracted cervix
Uterine rupture ® Laparotomy:
• Primary repair
• Hysterectomy
Uterine fundus not felt Uterine ® Correct inversion in
abdominally OR visible inversion theatre under general
vaginally anaesthesia
Clotting Clotting disorder
• Treat accordingly with
blood products
If bleeding continues If bleeding continues If bleeding continues
Nonsurgical uterine Compression sutures Artery ligation
compression • B-Lynch
(uterine, hypogastric)
• Bimanual uterine
• Vertical compression
compression Hysterectomy
• Cho square
• External aortic (subtotal or total)
compression Uterine artery
embolization
• Uterine packing
• Balloon (condom)
tamponade
Placenta still retained Placenta still retained
(placenta accreta)
Manual removal
Partial or complete
removal of placenta
through laparotomy
Hysterectomy
Hysterectomy
If nonsurgical correction Surgery
fails, ensure that uterus
remains contracted by
continued oxytocin Correction via
infusion laparotomy
Hysterectomy
Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage
SOGC CLINICAL PRACTICE GUIDELINE
16. All obstetric units should have a regularly checked PPH
emergency equipment tray containing appropriate
equipment. (II-2B)
Uterine Massage and Additional Uterotonic
Administration
Since the most common cause of PPH is uterine atony, the
clinician’s initial efforts should be directed at preventing
ongoing blood loss by performing the initial basic
maneuvres of uterine massage and administering additional
uterotonics, which include the following.
1. Oxytocin
• 10 IU IM. Consider ability of the medication to
reach a uterus with poor tissue perfusion.
• 5 IU IV push
• 20 to 40 IU in 250 mL of normal saline, infused IV
at an hourly rate of 500 to 1000 mL.
2. 15-methyl prostaglandin (carboprost tromethamine
[Hemabate])
• 250 mg IM or intramyometrially
• Can be repeated every 15 minutes to a maximum of
2 mg (8 doses).
• Asthma is a relative contraindication.
3. Carbetocin
• 100 mg IM or IV over 1 minute
• Shown to reduce bleeding due to uterine atony in
Caesarean sections but not low-risk vaginal
deliveries.
4. Misoprostol (off-label use not approved for PPH by
Health Canada)
• 400 to 800 mg. Onset of effects is faster with oral or
sublingual than with rectal administration.
• 800 to 1000 mg. Effects are longer lasting with rectal
than with oral administration.
• Higher incidence of pyrexia with oral than with
rectal administration.
5. Ergonovine
• 0.25 mg IM or IV, can be repeated every 2 hours
• Contraindicated in women with hypertension and
those taking certain drugs (e.g., proteases for HIV
infection).
6. Recombinant activated factor VII
• Has been used in women with massive PPH but in a
limited number of studies, all without
randomization.
• A review by Franchini et al.48 suggests a potential
role, although further research is required to
determine this agent’s role and benefit.
990 l OCTOBER JOGC OCTOBRE 2009
Recommendation
17. Evidence for the benefit of recombinant activated fac-
tor VII has been gathered from very few cases of massive
PPH. Therefore this agent cannot be recommended as
part of routine practice. (II-3L)
Tamponade
The quickest method of tamponade is with bimanual com-
pression of the uterus. One hand is placed over the uterus
externally; the other is placed in the vagina to apply pressure
on the lower segment. Consistent compression with the 2
hands results in external compression of the uterus to
reduce blood flow. This can be continued until further mea-
sures are taken or assistance arrives.
In the case of uterine atony, the following can be placed
inside the uterus to provide direct compression of the uter-
ine wall and thus decrease blood loss.
• Bakri SOS tamponade balloon catheter
• Sengstaken Blakemore esophageal catheter
• Foley catheter filled with 60 to 80 mL of sterile
solution
• Rusch hydrostatic urologic balloon
• Hydrostatic condom catheter
• Uterine packing
All the above have been reported to be successful for the
temporary control of active bleeding. The insertion tech-
nique for a balloon device is relatively simple and requires
the operator to ensure that the entire balloon is positioned
past the cervical canal. Once inserted, the balloon is filled
with sterile solution until there is no further bleeding. After
successful tamponade, continued oxytocin infusion may be
required to maintain uterine tone. Prophylactic antibiotic
therapy should be considered. The balloon can be left in
place for 8 to 48 hours and then gradually deflated and
removed.
Uterine packing requires greater skill and experience to
properly pack the uterus with enough gauze to control
bleeding while avoiding trauma to the uterine wall. Other
disadvantages include risk of infection, unrecognized bleed-
ing with blood soaking the packing material, and the possi-
ble need for another surgical procedure to remove the
material.
Recommendation
18. Uterine tamponade can be an efficient and effective
intervention to temporarily control active PPH due to
uterine atony that has not responded to medical
therapy. (III-L)
 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage

Figure 2. B-Lynch technique for uterine compression sutures

Reproduced from B-Lynch et al52 with permission of the Royal College of Obstetricians and Gynaecologists.

Figure 3. Cho technique for uterine compression sutures

Reproduced from Cho et al53 with permission of the Royal College of Obstetricians and Gynaecologists.

OCTOBER JOGC OCTOBRE 2009 l 991

SOGC CLINICAL PRACTICE GUIDELINE
Radiologic Methods
Percutaneous transcatheter arterial embolization is an
option when there is active bleeding in a hemodynamically
stable woman and before surgical intervention.49 A review
of the literature found success rates of 100% after 49 vagi-
nal deliveries and 89% after 18 Caesarean sections. This
technique preserves the uterus and adnexa and thus fertility.
The procedure requires rapid access to imaging technology
and interventional radiologists, which is not available to all
centres.
Surgical Methods
Ligation of the internal iliac artery was used to control
intraoperative bleeding from cervical cancer before being
applied to obstetric cases.50 A retrospective study found this
technique to be useful for preventing PPH in women at
high risk of hemorrhage and for treating PPH due to uterine
atony or genital tract injury.51 The timing of this interven-
tion is important: it must be done without delay, before
excessive blood loss has occurred. Surgical skill is required
to avoid failure and complications such as damage to other
vascular structures and the ureters.
Uterine compression sutures, described by B-Lynch52 (Fig-
ure 2) and Cho53 (Figure 3), have the benefit of preserving
the uterus. Both techniques involve external compression
of the uterus to control bleeding, followed by application of
sutures into and over the uterus. The sutures are tied down
to maintain uterine compression and control further bleed-
ing. A hysterotomy at the lower segment is required to
ensure that there are no retained products that would pre-
vent compression of the uterus and subsequent failure of
pregnancy.
Peripartum hysterectomy is indicated when massive hemor-
rhage has not responded to previous interventions and
requires a surgical intervention familiar to surgeons. Indica-
tions include abnormal placentation (previa, accreta), atony,
trauma, rupture, and sepsis. The disadvantage of
peripartum hysterectomy is the loss of fertility in women
who wish to continue childbearing.
Recommendation
19. Surgical techniques such as ligation of the internal iliac
artery, compression sutures, and hysterectomy should be
used for the management of intractable PPH unrespon-
sive to medical therapy. (III-B)
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double-blind comparison of oxytocin and methylergometrine during
caesarean section. Br J Anaesth 2008;100:683–9.
20. Dansereau J, Joshi AK, Helewa ME, Doran TA, Lange IR, Luther ER, et al.
Double-blind comparison of carbetocin versus oxytocin in prevention of
uterine atony after cesarean section. Am J Obstet Gynecol 1999;180(3 Pt
1):670–6.
21. Sweeney G, Holbrook AM, Levine M, Yip M, Alfredsson K, Cappi S, et al.
Pharmacokinetics of a long-acting oxytocin analogue, in non-pregnant
women. Curr Ther Res 1990;47:528–40.
22. Boucher M, Nimrod CA, Tawagi GF, Meeker TA, Rennicks White RE,
Varin J. Comparison of carbetocin and oxytocin for the prevention of
 Active Management of the Third Stage of Labour: Prevention and Treatment of Postpartum Hemorrhage
postpartum hemorrhage following vaginal delivery: a double-blind
randomized trial. J Obstet Gynaecol Can 2004;26:481–8.
23. Su LL, Chong YS, Samuel M. Oxytocin agonists for preventing postpartum
hemorrhage. Cochrane Database Syst Rev 2007;(3):CD005457.
24. Leung SW, Ng PS, Wong WY, Cheung TH. A randomized trial of
carbetocin versus Syntometrine in the management of the third stage of
labour. BJOG 2006;113:1459–64.
25. El-Refaey H, O’Brien P, Morafa W, Walder J, Rodeck C. Misoprostol for
third stage of labour [letter]. Lancet 1996;347:1257.
26. Hofmeyr GJ, Walraven G, Gülmezoglu AM, Maholwana B, Alfirevic Z,
Villar J. Misoprostol to treat postpartum haemorrhage: a systematic review.
BJOG 2005;112:547–53.
27. Gülmezoglu AM, Forna F, Villar J, Hofmeyr GJ. Prostaglandins for
prevention of postpartum haemorrhage. Cochrane Database Syst Rev
2004;(1):CD000494.
28. Villar J, Gülmezoglu AM, Hofmeyr GJ, Forna F. Systematic review of
randomized controlled trials of misoprostol to prevent postpartum
hemorrhage. Obstet Gynecol 2002;100:1301–12.
29. Joy SD, Sanchez-Ramos L, Kaunitz AM. Misoprostol use during the third
stage of labor. Int J Gynaecol Obstet 2003;82:143–52.
30. Gülmezoglu AM, Villar J, Ngoc NT, Piaggio G, Carroli G, Adetoro L, et al.
WHO multicentre randomised trial of misoprostol in the management of
the third stage of labour. Lancet 2001;358:689–95.
31. Parsons SM, Walley RL, Crane JMG, Matthews K, Hutchens D. Rectal
misoprostol versus oxytocin in the management of the third stage of labour.
J Obstet Gynaecol Can 2007;29:711–8.
32. Morley G. Cord closure: Can hasty clamping injure the newborn? OBG
Manage 1998;July:29–36.
33. Dixon LR. The complete blood count: physiologic basis and clinical usage.
J Perinat Neonatal Nurs 1997;11:1–18.
34. Yao AC, Moinian M, Lind J. Distribution of blood between infant and
placenta after birth. Lancet 1969;2:871–3.
35. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord
clamping in preterm infants. Cochrane Database Syst Rev
2004;(4):CD003248.
36. Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Placental
transfusion: umbilical cord clamping and preterm infants. J Perinatol
2000;20:351–4.
37. Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in
full-term neonates: systematic review and meta-analysis of controlled trials.
JAMA 2007;297:1241–52.
38. McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of
term infants on maternal and neonatal outcomes. Cochrane Database Syst
Rev 2008;(2):CD004074.
39. Dombrowski MP, Bottoms SF, Saleh AA, Hurd WW, Romero R. Third
stage of labor: analysis of duration and clinical practice. Am J Obstet
Gynecol 1995;172:1279–84.
40. Combs CA, Laros RK. Prolonged third stage of labor; morbidity and risk
factors. Obstet Gynecol 1991;77:863–7.
41. Magann EF, Doherty DA, Briery CM, Niederhauser A, Morrison JC.
Timing of placental delivery to prevent post-partum haemorrhage: lessons
learned from an abandoned randomised clinical trial. Aust N Z J Obstet
Gynaecol 2006;46:549–51.
42. Soltani H, Dickinson F, Symonds I. Placental cord drainage after
spontaneous vaginal delivery as part of the management of the third stage
of labour. Cochrane Database Syst Rev 2005;(4):CD004665.
43. Sharma JB, Pundir P, Malhotra M, Arora R. Evaluation of placental drainage
as a method of placental delivery in vaginal deliveries. Arch Gynecol Obstet
2005;271:343–5.
44. Carroli G, Bergel E. Umbilical vein injection for management of retained
placenta. Cochrane Database Syst Rev 2001;(4):CD001337.
45. Nardin JM, Carroli G, Weeks a.d., Mori R. Umbilical vein injection for the
routine management of third stage of labour [Protocol]. Cochrane Database
Syst Rev 2006;(4):CD006176.
46. Rogers MS, Yuen PM, Wong S. Avoiding manual removal of placenta:
evaluation of intra-umbilical injection of uterotonics using the Pipingas
technique for management of adherent placenta. Acta Obstet Gynecol
2007;86:48–54.
47. Baskett TF. Surgical management of severe obstetrical hemorrhage:
experience with an obstetrical hemorrhage equipment tray. J Obstet
Gynaecol Can 2004;26:805–8.
48. Franchini M, Lippi G, Franchi M. The use of recombinant activated factor
VII in obstetric and gynaecological haemorrhage. BJOG 2007;114:8–15.
49. Vedantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery
embolization: an underused method of controlling pelvic hemorrhage. Am J
Obstet Gynecol 1997;176:938–48.
50. Kelly HA. Ligation of both internal iliac arteries for hemorrhage in
hysterectomy for carcinoma uteri. Bull Johns Hopkins Hosp 1984;5:53.
51. Joshi V, Otiv SR, Majumder R, Nikam YA, Shrivastava M. Internal iliac
artery ligation for arresting postpartum haemorrhage. BJOG
2007;114:356–61.
52. B-Lynch C, Coker A, Lawal AH, Abu J, Cowen MJ. The B-Lynch surgical
technique for the control of massive postpartum haemorrhage: An
alternative to hysterectomy? Five cases reported. Br J Obstet Gynaecol
1997;104:372–5.
53. Cho JH, Jun HS, Lee CN. Hemostatic suturing technique for uterine
bleeding during cesarean delivery. Obstet Gynecol 2000;96(1):129–31.
54. Woolf SH, Battista RN, Angerson GM, Logan AG, Eel W. Canadian Task
Force on Preventive Health Care. New grades for recommendations from
the Canadian Task Force on Preventive Health Care. CMAJ
2003;169(3):207–8.
55. Mathai M, Gulmezoglu AM. Postpartum haemorrhage and retained
placenta. WHO guideline. Geneva: World Health Organization;2009.
OCTOBER JOGC OCTOBRE 2009 l 993
 SOGC CLINICAL PRACTICE GUIDELINE
SOGC CLINICAL PRACTICE GUIDELINE
Guidelines for the Management of Pregnancy at
41+0 to 42+0 Weeks
This guideline was prepared by the Clinical Practice Obstetrics
Committee and reviewed by the Maternal Fetal Medicine
Committee and reviewed and approved by the Executive and
Council of the Society of Obstetricians and Gynaecologists of
Canada.
PRINCIPAL AUTHORS
Martina Delaney, MD, St. John’s NL
Anne Roggensack, MD, Toronto ON
CLINICAL PRACTICE OBSTETRICS COMMITTEE
Dean C. Leduc, MD (Chair), Ottawa ON
Charlotte Ballermann, MD, Edmonton AB
Anne Biringer, MD, Toronto ON
Martina Delaney, MD, St. John’s NL
Loraine Dontigny, MD, Lasalle QC
Thomas P. Gleason, MD, Edmonton AB
Lily Shek-Yn Lee, RN, Vancouver BC
Marie-Jocelyne Martel, MD, Saskatoon SK
Valérin Morin, MD, Cap-Rouge QC
Joshua Nathan Polsky, MD, Windsor ON
Carol Rowntree, MD, Sundre AB
Debra-Jo Shepherd, MD, Regina SK
Kathi Wilson, RM, Ilderton ON
Disclosure statements have been received from all members of the
committee.
Abstract
Objective: To provide evidence-based guidelines for the
management of pregnancy at 41+0 to 42+0 weeks.
Outcomes: Reduction of perinatal mortality associated with
Caesarean section at 41+0 to 42+0 weeks of pregnancy.
Evidence: The Medline database, the Cochrane Library, and the
American College of Obstetricians and Gynecologists and the
Royal College of Obstetricians and Gynecologists, were searched
Key Words: Labour, induction, postdates pregnancy, post-term
pregnancy
This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
800 l SEPTEMBER JOGC SEPTEMBRE 2008
No. 214, September 2008
for English language articles published between 1966 and March
2007, using the following key words: prolonged pregnancy,
post-term pregnancy, and postdates pregnancy. The quality of
evidence was evaluated and recommendations were made
according to guidelines developed by the Canadian Task Force on
Preventive Health Care.
Recommendations
1. First trimester ultrasound should be offered, ideally between 11
and 14 weeks, to all women, as it is a more accurate assessment
of gestational age than last menstrual period with fewer
pregnancies prolonged past 41+0 weeks. (I-A)
2. If there is a difference of greater than 5 days between gestational
age dated using the last menstrual period and first trimester
ultrasound, the estimated date of delivery should be adjusted as
per the first trimester ultrasound. (I-A)
3. If there is a difference of greater than 10 days between gestational
age dated using the last menstrual period and second trimester
ultrasound, the estimated date of delivery should be adjusted as
per the second trimester ultrasound. (I-A)
4. When there has been both a first and second trimester ultrasound,
gestational age should be determined by the earliest ultrasound. (I-A)
5. Women should be offered the option of membrane sweeping
commencing at 38 to 41 weeks, following a discussion of risks and
benefits. (I-A)
6. Women should be offered induction at 41+0 to 42+0 weeks, as the
present evidence reveals a decrease in perinatal mortality without
increased risk of Caesarean section. (I-A)
7. Antenatal testing used in the monitoring of the 41- to 42-week
pregnancy should include at least a non-stress test and an
assessment of amniotic fluid volume. (I-A)
8. Each obstetrical department should establish guidelines dependent
on local resources for scheduling of labour induction. (I-A)
J Obstet Gynaecol Can 2008;30(9):800–810
INTRODUCTION
he World Health Organization defines a post-term
T pregnancy as one that has extended to or beyond 42
weeks (294 days) of gestation.1 In 1997, the SOGC pub-
lished clinical practice guidelines recommending that
women with an uncomplicated pregnancy who reach 41 to
42 weeks’ gestation should be offered elective delivery.2
 Guidelines for the Management of Pregnancy at 41+0 to 42+0 Weeks
Sue-A-Quan et al. undertook a Canadian study to examine
trends over time in the rates of induction in post-term
pregnancies.3 The proportion of births occurring at 41
weeks’ gestation increased significantly from 11.9% in 1980
to 16.3% in 1995, and the proportion of births occurring at
42 weeks or more decreased significantly from 7.1% in 1980
to 2.9% in 1995. The authors reported that the rate of
labour induction increased significantly between 1980 and
1995 among women delivering at 41 or more weeks’ gesta-
tion, which indicates that the guidelines are, for the most
part, being followed. The stillbirth rate was also examined in
the study by Sue-A-Quan and colleagues. Interestingly, the
stillbirth rate among deliveries at 41 or more weeks’ gesta-
tion decreased significantly from 2.8/1000 total births in
1980 to 0.9/1000 total births in 1995 (P < 0.001).
Concern about increased risk to the post-term (³ 42 weeks)
fetus has existed since the early to mid 1900s.4 Increased
PMRs for the post-term fetus have been reported in
descriptive studies.4,5 However, these studies did not
exclude all high-risk pregnancies or fetuses with congenital
anomalies. Older descriptive studies that did correct for
congenital anomalies did not find any difference in PMRs
for post-term infants.6,7 More recent database studies have
demonstrated an increasing risk of stillbirth with advancing
gestational age.8–11 However, a Canadian database study did
not demonstrate an increased post-term PMR.12 Other
obstetrical and perinatal complications that were found to
be higher in post-term pregnancies in these non-
randomized studies include fetal distress, non-progression,
operative delivery (both operative vaginal and Caesarean),
macrosomia, shoulder dystocia, low Apgar scores, and
meconium aspiration.12–14 A linear decline of umbilical
artery pH from term has also been described.15 Kitlinski
et al.15 collected data on singleton pregnancies planned for
vaginal delivery after 37 completed weeks. They defined
acidemia as a pH < 7.10 and a gestational age-dependent
acidemia as a pH < mean-2 SDs. Their data show that the
mean umbilical cord arterial blood pH at birth decreases lin-
early with gestational age. The odds ratio trend curve for
ABBREVIATIONS
CI confidence interval
CRL crown–rump length
EDC estimated date of conception
LMP last menstrual period
NST non-stress test
OR odds ratio
PMR perinatal mortality rate
RCT randomized controlled trial
RR relative risk
low pH according to the gestational age-dependent defini-
tion of < mean-2 SDs showed no linear association with
gestational age but a significant increase after 42 weeks (OR
1.24; 95% CI 1.05–1.47). The odds ratio for pH < 7.10
among infants born after 41 weeks 3 days was also signifi-
cant at 1.48 (95% CI 1.26–1.72).
The RCT is the most reliable form of scientific evidence, as
it is the best known design for eliminating biases that can
compromise the validity of research. Controversy about the
management of and the risks associated with the post-term
pregnancy led to the performance of many RCTs designed
to determine if induction before or at the start of the
post-term period versus expectant management results in
any difference in maternal or perinatal outcomes.
This document updates the 1997 SOGC Guideline.2 Its rec-
ommendations refer only to otherwise uncomplicated preg-
nancies at 41 to 42 weeks’ gestation. This guideline reviews
the following:
1. Interventions to decrease the incidence of pregnancy
beyond 41+0 weeks.
2 . The evidence for induction of labour versus antenatal
surveillance in an uncomplicated pregnancy at 41+0 to
42+0 weeks.
3. The role of antenatal fetal surveillance in the
uncomplicated pregnancy at 41+0 to 42+0 weeks.
Sources of information include Medline, the Cochrane
Library, and guidelines from the American College of
Obstetricians and Gynecologists and the Royal College of
Obstetricians and Gynaecologists. The quality of evidence
was evaluated and recommendations were made according
to guidelines developed by the Canadian Task Force on
Preventive Health Care (Table).16
INTERVENTIONS TO REDUCE PREGNANCY
DURATION BEYOND 41+0 WEEKS
Accurate Pregnancy Dating
Error is associated with pregnancy dating by LMP alone. If
the gestational age is underestimated, prematurity may be
misdiagnosed, and unnecessary obstetric interventions per-
formed. However, overestimation of gestational age is
more likely, increasing the risks of unnecessary induction of
labour.
Dating gestational age with LMP alone assumes both accu-
rate recall of the LMP and ovulation on the 14th day of the
menstrual cycle. Error in estimating LMP is due to inaccu-
rate patient recall, maternal preference of date of LMP, and
random error.17 The duration of the follicular phase is vari-
able, ranging from 7 to 21 days. Sixty-eight percent of
women originally dated at greater than 42+0 weeks by LMP
SEPTEMBER JOGC SEPTEMBRE 2008 l 801
SOGC CLINICAL PRACTICE GUIDELINE
Key to evidence statements and grading of recommendations, using the ranking of the
Canadian Task Force on Preventive Health Care
Quality of Evidence Assessment*
I: Evidence obtained from at least one properly randomized
controlled trial
II-1: Evidence from well-designed controlled trials without
randomization
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more
than one centre or research group
II-3: Evidence obtained from comparisons between times or
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment
with penicillin in the 1940s) could also be included in this
category
III: Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force
on Preventive Health Care.16
†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The Canadian
Task Force on Preventive Health Care.16
were actually less advanced in gestational age when basal
body temperature was used to determine the ovulation
date.18
Delayed ovulation is an important cause of perceived pro-
longed pregnancy.19 Most pregnancies induced after 41+0
weeks are found not to be > 41+0 when ultrasound rather
than LMP is used to date the pregnancy.20
Ultrasound biometry in the second trimester ultrasound is
accurate for dating ± 10 days and is routinely used in the
diagnosis of congenital anomalies. Biometry is most accu-
rate if two or more parameters, such as biparietal diameter,
abdominal circumference, and femur length, are used to
estimate gestational age.21 Pregnancies noted to be term by
second trimester ultrasound dating, but pregnancies
post-term by LMP estimate do not have an increased risk of
adverse fetal outcome.22 Induction of labour for post-term
pregnancy is decreased when gestational age is estimated
using second trimester biometry versus LMP alone.23–25
When pregnancies are dated from a second trimester ultra-
sound, delivery past 41+0 weeks occurs in 16.3%, com-
pared with 6.7% dated from a first trimester ultrasound.26
Gestational age is most accurately determined by first tri-
mester CRL, with an error estimated to be ± 5 days. In addi-
tion to accurate pregnancy dating, first trimester ultrasound
allows for early diagnosis of missed abortion, ectopic preg-
nancy, multiple gestations, and limited assessment of fetal
anatomy. A study involving 44 623 births in a Canadian ter-
tiary centre demonstrated that the use of first trimester
802 l SEPTEMBER JOGC SEPTEMBRE 2008
Classification of Recommendations†
A. There is good evidence to recommend the clinical preventive
action
B. There is fair evidence to recommend the clinical preventive
action
C. The existing evidence is conflicting and does not allow to
make a recommendation for or against use of the clinical
preventive action; however, other factors may influence
decision-making
D. There is fair evidence to recommend against the clinical
preventive action
E. There is good evidence to recommend against the clinical
preventive action
L. There is insufficient evidence (in quantity or quality) to make
a recommendation; however, other factors may influence
decision-making
ultrasound for dating significantly decreases the incidence
of birth after 41+0 and 42+0 weeks of gestation. Different
algorithms for combining LMP and CRL estimates were
compared. The lowest rates for delivery at > 41+0 or
> 42+0 weeks were seen with using early ultrasound alone
for pregnancy dating (11.2% and 1.9%, respectively) and
changing the EDC if the discrepancy was > 3 days between
LMP and CRL (11.7% and 1.9%). These data are compared
with the results of using LMP alone (20.9% and 6.4%) or
changing the EDC if the discrepancy was > 14 days (16.9%
and 3.5%).27
Bukowski et al.28 studied 3588 pregnancies in women with
known LMP who had a first trimester ultrasound as part of
the FASTER trial. When pregnancies were dated by the
CRL rather than the LMP, pregnancies reaching ³ 41+0
were less frequent. The number of pregnancies at ³ 41+0
weeks (8.2% vs. 22.1%; [P < 0.001, RR 0.37; 95% CI
0.33–0.4]), and at ³ 42+0 weeks (1.6% vs. 12.7% [P <
0.001, RR 0.13; 95% CI 0.1–0.2]) at birth was significantly
reduced when gestational age was determined by CRL,
compared with determination of gestational age by LMP.28
Bennett et al.29 conducted an RCT of routine first trimester
ultrasound and the rate of post-term induction in a low-risk
obstetric population. Two hundred eighteen women were
randomized to first trimester ultrasound (EDC changed if
> 5 days different from LMP) or second trimester
ultrasound (changed if > 10 days different from LMP dates)
to determine the gestational age. Routine use of first
trimester ultrasound demonstrated a statistically and
 Guidelines for the Management of Pregnancy at 41+0 to 42+0 Weeks
clinically significant reduction in induction of labour for
pregnancy ³ 41+0 from 13% to 5% (P = 0.04, RR 0.37;
95% CI 0.14–0.96). There was no difference between the
two groups in induction of labour for other indications,
mode of delivery, or neonatal outcomes.29 There are no
studies investigating the cost-effectiveness of using first tri-
mester ultrasound to decrease induction of labour between
41+0 and 42+0 weeks.
Routine first trimester ultrasound reduces error in estimat-
ing gestational age and induction of labour between 41+0
and 42+0 weeks.30 Other benefits of early ultrasound
include measurement of nuchal translucency,31 visualiza-
tion of other markers of aneuploidy,32 and early diagnosis of
some anatomical anomalies.33
Recommendations
1. First trimester ultrasound should be offered, ideally
between 11 and 14 weeks, to all women, as it is a more
accurate assessment of gestational age than last
menstrual period with fewer pregnancies prolonged past
41+0 weeks. (I-A)
2. If there is a difference of greater than 5 days between ges-
tational age dated using the last menstrual period and
first trimester ultrasound, the estimated date of delivery
should be adjusted as per the first trimester ultrasound. (I-A)
3. If there is a difference of greater than 10 days between
gestational age dated using the last menstrual period and
second trimester ultrasound, the estimated date of deliv-
ery should be adjusted as per the second trimester ultra-
sound. (I-A)
4. When there has been both a first and second trimester
ultrasound, gestational age should be determined by the
earliest ultrasound. (I-A)
Sweeping of Fetal Membranes
Sweeping (or stripping) of membranes off the lower uterine
segment has been reported since the 19th century and is
believed to stimulate the onset of labour. During a vaginal
examination, the fetal membranes are separated from the
cervix and lower uterine segment as far as possible, sweep-
ing a finger inserted through the cervical os 360º if possible.
This procedure necessitates a sufficiently dilated cervix,
usually representing a favourable Bishop score. When the
cervix is closed, some clinicians attempt to stretch the cer-
vix open or perform cervical massage. There are no trials
comparing these different techniques. Sweeping results in
the release of endogenous prostaglandins, softening the cer-
vix and augmenting oxytocin-induced uterine contrac-
tions.34 Plasma prostaglandin concentrations after sweep-
ing are 10% of those achieved in labour, thus possibly
improving labour outcomes.35
Theoretical risks of membrane sweeping include
chorioamnionitis, premature rupture of membranes, and
bleeding from an undiagnosed placenta previa. However, in
review of clinical trials, there was no increased incidence of
fetal infection or neonatal morbidity related to the proce-
dure. A small study did not find any increased colonization
with group B streptococcus during membrane sweeping.36
Maternal morbidity is related mainly to significant discom-
fort or pain during procedure, bleeding, and contractions
not leading to labour within 24 hours.37,38
In an RCT investigating indicated induction of labour at 39
weeks in conjunction with membrane sweeping, the benefi-
cial effect of membrane sweeping was limited to nulliparous
women with unfavourable Bishop scores. In this patient
group, both the induction-to-labour interval and oxytocin
use were decreased, and there was an increased rate of nor-
mal vaginal delivery.39 Weekly membrane stripping preced-
ing induction of labour has similar effects.40 However, the
need for an intervention (sweeping membranes) at 38 weeks
to routinely shorten pregnancy has been widely questioned
in the literature. The results of membrane sweeping are not
predictable and should not be used alone for induction if
the indication for induction is urgent.
In several small trials, membrane stripping has been an
effective outpatient method to reduce the number of
patients with pregnancies exceeding 41+0.41–44 Again,
membrane sweeping is generally most efficacious in
nulliparous women with unfavourable Bishop scores. In a
study by Berghella et al.,45 patients were randomized to
weekly sweeping of membranes or gentle exams starting at
38 weeks. Time to delivery was significantly decreased with
membrane stripping, and there were fewer pregnancies
reaching past 41+0 weeks.45 Not all studies have noted a
reduction in the need for post-term induction.46 A
well-designed Canadian study enrolled patients at 38 to 40
weeks, and did not find any differences between a single
membrane sweeping and routine examination with respect
to onset of after 41 weeks or need for induction of labour.47
Multiple episodes of membrane sweeping may be more effi-
cacious. There are no trials comparing single and multiple
sweepings of the membranes.
A recently published RCT by de Miranda et al.48 random-
ized 750 low-risk pregnant women from the Netherlands at
41 weeks’ gestational age to routine monitoring or mem-
brane sweeping every two days until spontaneous labour or
42 weeks’ gestational age. Sweeping was defined as separat-
ing the lower membranes as much as possible from their
cervical attachment, with three circumferential passes of the
examining fingers. If the cervix was closed, cervical massage
was performed. Analysis was by intention-to-treat. Serial
sweeping of the membranes decreased the risk of
SEPTEMBER JOGC SEPTEMBRE 2008 l 803
SOGC CLINICAL PRACTICE GUIDELINE
pregnancy reaching 42+0 weeks (87/375 [23%] versus
149/367 [41%]); RR 0.57 [95% CI 0.46–0.71], NNT 6 [95%
CI 4–12]).48 Benefits were noted in both nulliparous and
multiparous patients. Uncomplicated vaginal bleeding was
reported more frequently in the sweeping group (111/364
vs. 16/345, RR 6.58 [95% CI 3.98–10.87]). As well, 68% of
treated women reported sweeping as “somewhat” to “very
painful.” Of note, 88% of all women randomized to sweep-
ing reported that they would chose sweeping in the next
pregnancy, despite the discomfort. Obstetric outcomes and
neonatal morbidity were similar between groups.48
A recent Cochrane review assessed 22 trials involving
sweeping membranes. Sweeping of the membranes at term
(38–41 weeks) reduced the frequency of pregnancies con-
tinuing after 41+0 weeks (RR 0.59; 95% CI 0.46–0.74) and
after 42+0 weeks (RR 0.28; 95% CI 0.15–0.50). Eight
women would need to undergo sweeping of membranes to
prevent one induction of labour.38
Recommendation
5. Women should be offered the option of membrane
sweeping commencing at 38 to 41 weeks, following a dis-
cussion of risks and benefits. (I-A)
LABOUR INDUCTION VERSUS EXPECTANT
MANAGEMENT AT 41 WEEKS
Nineteen trials randomizing women with uncomplicated
pregnancies at 41 or more weeks’ gestation to induction or
expectant management with surveillance were identi-
fied.49–67 A recently published trial randomized women at
41 weeks and two days of gestation to induction or expec-
tant management; however, the authors do not specify if the
pregnancies are uncomplicated.68 Two of these trials are
reported as abstracts only.50,66 A trial in a Spanish journal
was identified through the Cochrane Collaboration and was
not reviewed for this document.65 Nine trials began enrol-
ment at 41+0 weeks53,55,56,60–63,66,67 (two of these recruited at
41 weeks but did not randomize until 42 weeks);53,62 one
trial at 41+2 weeks68; five trials at 41+3 weeks;49,50,52,54,64
two trials at 42+0 weeks;51,57 and two trials at 42+1
weeks.58,59 Dating was by various methods (menstrual cycle
history, positive pregnancy tests, physical examination, and
ultrasound) in each of the trials. Five trials did not use ultra-
sound assessment.49,54,57,59,63 It was unclear from one of the
trials published only as an abstract if ultrasound was used.66
All trials reported perinatal mortality and delivery mode.
Perinatal morbidities and other maternal outcomes were
reported in variable detail. As the incidence of substantive
outcomes, such as perinatal mortality and morbidity associ-
ated with post-term pregnancy are low, a large sample size
would be required to detect a statistically significant differ-
ence between these two management methods. The largest
804 l SEPTEMBER JOGC SEPTEMBRE 2008
trial was a Canadian multi-centre trial enrolling 3407
women.60 The remainder of the trials had sample sizes
ranging from 22 to 440.49–59,61–64,66–68
The Canadian trial randomized women at 41 or more
weeks’ gestation to induction or to serial antenatal monitor-
ing, with delivery indicated for non-reassuring fetal status,
the development of obstetrical complications, or the attain-
ment of 44 weeks’ gestation.60 Those assigned to the induc-
tion group were to have labour induced within four days
after randomization. The primary outcome of the study was
perinatal mortality and neonatal morbidity. The sample size
was based on finding a reduction in the incidence of an
Apgar score less than 7 at five minutes. The secondary out-
come was the rate of Caesarean section. The authors con-
cluded that there was no difference in the risk of perinatal
mortality or neonatal morbidity between the two manage-
ment schemes. There were two stillbirths in the monitored
group and none in the induction group. The two groups did
not differ significantly in the rate of neonatal morbidity.
The frequency of fetal distress was lower in the induction
group (10.3% vs. 12.8%, P = 0.017). The incidence of
meconium staining of the amniotic fluid was significantly
lower in the induction group (25% vs. 28.7%, P = 0.009).
There was a statistically significant higher rate of Caesarean
section among women who were monitored than among
those induced (24.5% vs. 21.25%, P = 0.03; OR 1.22; 95%
CI 1.02–1.45), and this difference was due to a lower rate of
this procedure for fetal distress. There were limitations in
this study’s methods. Prostaglandin E2 gel was not used in
the monitoring group, as the authors felt there was insuffi-
cient evidence to use this preparation in the presence of
fetal compromise, and they speculated that most of the
women in this group requiring induction would have evi-
dence of fetal compromise. They acknowledge that this
could account for the difference in the rate of Caesarean
section. Also, this trial was not blinded, which introduces
the potential for bias toward a higher Caesarean rate, as
pregnancies are likely to be considered higher risk as they
became further post-term. The authors conclude that
labour induction in post-term pregnancies decreases the
Caesarean rate but leads to no difference in the incidence of
perinatal mortality and morbidity.
As the authors of the Canadian trial point out, the perinatal
mortality rate in their study was low at 0.6 per 1000. They
reported that to detect a reduction of 50% in the perinatal
mortality rate by inducing women with post-term preg-
nancy, approximately 30 000 women would need to be
enrolled. Such a trial does not exist and for logistical reasons
is likely not to be carried out. In the absence of such a trial,
clinical practice relies on information from smaller trials
and from systematic reviews.
 Guidelines for the Management of Pregnancy at 41+0 to 42+0 Weeks
Three meta-analyses addressing labour induction versus
expectant management of pregnancies at 41 weeks and
beyond have been published.69–71
In 1993, Hannah69 published a review of the literature on
post-term pregnancy. Included in this review was a
meta-analysis of 11 randomized or quasi randomized trials
in which a policy of routine induction at 41 weeks was com-
pared with expectant management with serial fetal surveil-
lance. A total of 5057 women were included in these trials.
Methods of fetal surveillance and induction varied between
the studies. Ten studies reported on probability of Caesar-
ean and the results showed that inducing labour at ³ 41
weeks resulted in a significantly lower Caesarean section
rate (OR 0.85; 95% CI 0.74–0.97). Inducing labour at ³ 41
weeks resulted in a lower rate of fetal distress, as defined by
different authors, than expectant management (OR 0.81;
95% CI 0.68–0.97) and a lower rate of meconium staining
of amniotic fluid (OR 0.79; 95% CI 0.69–0.90). Labour
induction at ³ 41 weeks resulted in a lower rate of
macrosomia (usually defined as birth weight < 4000 g) than
expectant management (OR 0.80; 95% CI 0.69–0.92).
Inducing labour at ³ 41 weeks resulted in a lower rate of
fetal or neonatal death (excluding lethal congenital anoma-
lies) than expectant management (OR 0.23; 95% CI
0.06–0.90). The reduction in perinatal death was largely due
to a reduction in fetal death (OR 0.14; 95% CI 0.02–0.98).
There was no difference in other measures of neonatal mor-
bidity, such as small for gestational age, Apgar score < 7 at
one minute, Apgar score < 7 at five minutes, shoulder
dystocia, cord prolapse, neonatal seizures, birth trauma,
admission to NICU, and meconium aspiration syndrome.
The author concludes that the induction of labour groups
are less likely to undergo delivery by Caesarean, to have an
operative vaginal delivery, or to have fetal distress,
macrosomic babies, or babies who die during the perinatal
period. She states that women who reach 41 weeks should
be appropriately counselled about the higher risks to them-
selves and to their babies if they pursue expectant manage-
ment, and she suggests that a policy of labour induction is to
be preferred.
A meta-analysis published in 2003 compared routine labour
induction with expectant management for patients at 41
weeks.70 Trials consisting of uncomplicated, singleton, live
pregnancies were included. The primary outcomes assessed
were perinatal mortality and Caesarean section. Sixteen tri-
als enrolling 6588 subjects were included in the review.49–64
The trials differed in methods of antenatal fetal surveillance
and means of labour induction. The meta-analysis showed
that women who underwent labour induction had a signifi-
cantly lower rate of Caesarean section (20.1% vs. 22%; OR
0.88; 95% CI 0.78–0.99). Those whose labour was induced
required Caesarean section secondary to fetal heart rate
abnormalities at a significantly lower rate than those expec-
tantly managed (6.2% vs. 8.0%; OR 0.77; 95% CI
0.61–0.96). Those whose labour was induced were less
likely to have meconium staining of amniotic fluid (22.4%
vs. 27.75; OR 0.75; 95% CI 0.66–0.84). Women whose
labour was induced had a lower rate of perinatal mortality;
however, this difference was not statistically significant
(0.09% vs. 0.33%; OR 0.41; 95% CI 0.14–1.18). Other neo-
natal outcomes showed no significant differences and
included meconium below the vocal cords, meconium aspi-
ration, NICU admissions, and Apgar scores < 7 at 5 min-
utes. The authors concluded that labour induction in
women at 41 weeks’ gestation with otherwise uncompli-
cated pregnancies lowers the Caesarean rate without com-
promising perinatal outcomes. As the authors state, none of
these 16 trials had adequate statistical power to assess the
perinatal mortality rate. Even when combined in a
meta-analysis, the statistical power for assessing this out-
come remained low. They calculated that 16 000 women
would need to be enrolled to detect a 50% reduction in the
PMR rate of 3 per 1000 with routine labour induction, com-
pared with expectant management at a power of 80% and
allowing for a type I error of 5%. To detect an even smaller
reduction in the PMR that would be clinically relevant,
would require even more participants.
The Cochrane Collaboration published a review in 2006
whose objective was to evaluate the benefits and harms of a
policy of labour induction at term or post-term, compared
with awaiting spontaneous labour or later induction of
labour.71 Eligible trials were RCTs enrolling women at low
risk. This review included three trials65–67 not in the
meta-analysis by Sanchez-Ramos et al. and excluded three
trials included in that review for methodological rea-
sons.51,52,58 The review included 19 trials involving 7984
women undergoing induction of at various times from 38 to
> 42 weeks’ gestation. The review grouped the trials by ges-
tational age of induction at (1) 37 to 40 weeks, (2) 41 com-
pleted weeks, and (3) 42 completed weeks, and compared
this with waiting until a later date for induction. Subgroup
analyses were also done according to the condition of the
cervix. In this document, results from the 41-week and the
42-week groups from 16 trials are reviewed.49,50,53–57,59–67
The primary outcome was perinatal mortality, which was
defined as intrauterine deaths plus newborn deaths in the
first week of life. Secondary infant and maternal outcomes
were also assessed. Eleven trials intervened at or during the
41st completed week49,50,54–56,60,61,63,64,66,67 and five trials at
or after 42 completed weeks.53,57,59,62,65 The relative risk of
perinatal death in the 41st week group was 0.25 with 95%
CI 0.05 to 1.18 (0/2835 vs. 6/2808), not statistically signifi-
cant. When the 41- and 42-week groups were analyzed
SEPTEMBER JOGC SEPTEMBRE 2008 l 805
SOGC CLINICAL PRACTICE GUIDELINE
together, the RR was 0.30 with 95% CI 0.09 to 0.99 (1/2986
vs. 9/2953), statistically significant. Labour induction sig-
nificantly reduced the risk of meconium aspiration syn-
drome in the 41-week group (RR 0.29; 95% CI 0.12–0.68).
In the 42-week group, fewer babies in the induction group
had meconium aspiration syndrome, but the difference was
not statistically significant (RR 0.66; 95% CI 0.24–1.81).
There was no difference in neonatal intensive care admis-
sions. There was no evidence of an increased risk of Caesar-
ean section for women induced at 41 and 42 weeks, respec-
tively (RR 0.92; 95% CI 0.76–1.12; RR 0.97; 95% CI
0.72–1.31). There was no evidence of a statistically signifi-
cant difference in the risk of assisted vaginal delivery for
women induced at 41 and 42 completed weeks, respectively
(RR 1.05; 95% CI 0.94–1.17; RR 0.95; 95% CI 0.65–1.38).
Obstetric outcomes were also analyzed according to cervi-
cal status. This subgroup analysis was limited by the small
number of trials reporting cervical status. No differences
between a policy of labour induction and expectant man-
agement were identified for Caesarean section or assisted
vaginal birth in these analyses. The reviewers did not pro-
duce a point estimate because of significant heterogeneity
for these outcomes. The authors conclude in their discus-
sion that routine labour induction at 41 completed weeks or
later, compared with waiting for the onset of labour for at
least one week is associated with fewer perinatal deaths and
meconium aspiration syndrome. The absolute number of
perinatal deaths was small in the induction group (1/3285,
0.03%) and in the expectant management group (11/3238,
0.33%). In this review, there was one stillbirth reported
among the seven trials since 1992. Excluding congenital
anomalies, there were no deaths in the labour induction
group and nine deaths in the expectant management group.
Regarding Caesarean rates, the authors acknowledge that
the data are difficult to interpret because of heterogeneity
among trials. This review also analyzed the data excluding
the multicentre trial by Hannah et al., which did not use
prostaglandins in the expectantly managed group,60 and
reported that there did not seem to be a difference in Cae-
sarean rates.” The authors state that the effect on Caesarean
section is unclear, but the rate is not increased. With respect
to fetal monitoring in the expectant arms, most trials
included twice weekly non-stress tests and amniotic fluid
index assessments, and the authors speculate that in centres
that can offer these services, expectant management could
be safely practised. In conclusion, the authors state that they
think the results are valid and indicate beneficial outcomes
with a policy of labour induction at 41 completed weeks.
They acknowledge that the risk of the primary outcome
(perinatal death) is small but that such a policy is associated
with fewer perinatal deaths. They state that labour induc-
tion should be offered to women at low risk at 41 weeks and
806 l SEPTEMBER JOGC SEPTEMBRE 2008
that the pros and cons should be discussed so that women
can make an informed decision. There does not seem to be
any increased risk of Caesarean or assisted vaginal delivery
with such a policy. The authors state that if a woman
chooses to await spontaneous labour, regular fetal
monitoring would be prudent as longitudinal
epidemiological studies suggest that there is an increased
risk of perinatal death with increasing gestational age.
The evidence suggests that the rate of Caesarean section is
either reduced or not increased when women are induced,
compared with those expectantly managed.65,30,66 The three
meta-analyses have different conclusions regarding the policy
of labour induction on PMR. The Hannah review69 demon-
strated a statistically significant lower PMR with induction
at 41 weeks or more. The meta-analysis by Sanchez-Ramos
et al. showed a lower PMR in the induced group, but it was
not statistically significant.70 The most recent Cochrane
review demonstrated a lower perinatal mortality rate for
induction at 41 weeks and beyond.71 In this review, when
the group induced at or during the 41st week was analyzed,
the induced group had a lower PMR, but it did not reach
statistical significance. However, even when these studies
are combined in a meta-analysis, there is still low statistical
power to assess this outcome. When the groups induced at
or during the 41st and at or during the 42nd week were
combined, the PMR was lower in those induced, just reach-
ing statistical significance. If anything, it appears induction
during the 41st week may decrease the PMR, but there are
inadequate numbers of enrolled women to answer this
question definitively. Given that induction does not
increase the risk of Caesarean and that uncertainty remains
regarding whether induction at 41 to 42 weeks decreases the
PMR, it would seem reasonable to offer women induction
in this gestational age range.
A 2002 commentary on routine labour induction at 41
weeks’ gestation noted that aggregate data to that point
showed that not all of the seven perinatal deaths in the
expectantly managed groups occurred in women who
received contemporary fetal testing, and it is questionable
whether all causes were related to pregnancy duration.72
The stillbirth rate within the following week for women
who remain undelivered at 41 weeks 0 days is about 0.1%
(1.04–1.27 per 1000).72 Concern has been expressed that
obstetricians have responded to the previous SOGC guide-
line by booking induction by one week past the expected
due date.72 A proportion of women will labour spontane-
ously between 41 and 42 weeks. Provided there are no indi-
cations for delivery earlier, that fetal surveillance is
employed and is reassuring, and if the patient chooses,
induction at the latter end of this gestational age spectrum
will maximize the chances of spontaneous labour. Each
 Guidelines for the Management of Pregnancy at 41+0 to 42+0 Weeks
obstetrics department should establish guidelines depend-
ent on their local resources for scheduling of labour
inductions.
Recommendation
6. Women should be offered induction at 41+0 to 42+0
weeks, as the present evidence reveals a decrease in
perinatal mortality without increased risk of Caesarean
section. (I-A)
FETAL SURVEILLANCE IN THE
41 TO 42 WEEK PREGNANCY
Options for fetal surveillance include fetal movement
counting, non-stress test, biophysical profile or modified
biophysical profile (non-stress test plus amniotic fluid vol-
ume estimation), and contraction stress test. In each of the
aforementioned randomized trials of labour induction,
compared with expectant management of the post-term
patient, some form of antenatal test of fetal well-being was
used at varying frequencies.49–64,66–68 There is a paucity of
data from randomized trials on the type and frequency of
fetal surveillance in post-term pregnancy. There has been
only one randomized trial on forms of antenatal testing in
the post-term pregnancy.73 Alfirevic et al. randomized 145
women with singleton, uncomplicated pregnancies after 42
weeks to a modified biophysical profile defined as comput-
erized cardiotocography, amniotic fluid index, and assess-
ment of fetal breathing, tone, and gross body movements or
to standard cardiotocography and maximum pool depth.
Women were monitored at randomization and then twice
weekly until 43 weeks. Outcome measures were cord pH at
delivery, number of abnormal monitoring tests,
intrapartum management, mode of delivery, and neonatal
outcome. There were significantly more abnormal monitor-
ing results in the modified biophysical group (47.2% vs.
20.5%; OR 3.5; 99% CI 1.3–9.1). Amniotic fluid volume
was more likely to be labelled abnormal with amniotic fluid
index than with maximum pool depth (44.4% vs. 15.1%;
OR 4.5; 99% CI 1.6–12.8). There were no differences in
cord blood gases, neonatal outcome, or outcomes related to
labour and delivery between the two groups. These results
suggest that monitoring pregnancies with their definition of
a modified biophysical profile after 42 weeks does not
improve pregnancy outcome as measured by cord pH; how-
ever, the number of patients included in this trial is
insufficient to reach any definitive conclusions about the
impact of fetal testing on outcomes in post-term
pregnancies.
There are no randomized trials regarding antepartum fetal
testing between 41 and 42 weeks. The commencement of
antenatal testing at 41 weeks’ gestation is supported by
case-control studies. Guidetti et al.74 reported on 293
women at low risk who began twice weekly testing at 41
weeks’ gestation with an NST and amniotic fluid volume
assessment. The control population consisted of 59 women
at low risk delivered between 39 and 41 weeks’ gestation,
who were referred for routine testing at term. The outcome
parameters studied were abnormal NST, oligohydramnios,
Caesarean section for fetal distress, Apgar score £ 6 at five
minutes, NICU admissions, and perinatal deaths. When the
study group delivering at 41 to 42 weeks were compared
with the control group, the former had a statistically signifi-
cant increase in the incidence of abnormal NSTs,
oligohydramnios, Caesarean section for fetal distress, and
admissions to the neonatal unit. When the study group who
were delivered between 41 and 42 weeks were compared
with those delivered after 42 weeks, the only significant dif-
ference was that the former had more abnormal NSTs.
Bochner et al.75 compared neonatal outcomes of patients
with antenatal fetal testing starting at 41 weeks’ gestation
with patients who delivered between 41 and 42 weeks with-
out testing and those who started testing at 42 weeks. All
patients were at low risk. The study population consisted of
1260 women. Of these, 908 started testing at 41 weeks, and
352 started at 42 weeks. The control group consisted of
1807 women who delivered between 41 and 42 weeks with-
out any antenatal testing. Antepartum testing consisted of
twice weekly amniotic fluid assessment, NST, and contrac-
tion stress test when necessary. The total number of adverse
outcomes in the untested group resulted in a significantly
increased incidence of neonatal morbidity (seizures, apnea,
pneumonia, severe meconium aspiration, or infection),
compared with the tested group. Those who delivered after
42 weeks and whose testing started at 41 weeks had signifi-
cantly fewer abnormal antepartum testing results leading to
labour induction and Caesarean sections due to fetal dis-
tress than whose testing started at 42 weeks. The group
whose testing started at 42 weeks had a significantly greater
incidence of fetal distress.
Despite the lack of evidence from RCTs that antenatal test-
ing improves perinatal outcome in uncomplicated pregnan-
cies at 41 to 42 weeks’ gestation, most practitioners utilize
some form of monitoring in this clinical situation. The ran-
domized trials comparing labour induction with expectant
management at 41 weeks and beyond have included fetal
assessment.49–64,66–68 For most trials, those women who
were randomized to induction did not undergo antenatal
surveillance. In eight trials, however, fetal assessment was
carried out before patients were eligible for study enrol-
ment, and they therefore had some type of fetal surveillance
between 41 and 42 weeks.51,53,55,56,61,62,67,68 Therefore, for
some pregnancies, fetal surveillance started at 41 weeks and
for others at 42 weeks. For some women, fetal monitoring
was started at 41 weeks but only if they were randomized to
SEPTEMBER JOGC SEPTEMBRE 2008 l 807
SOGC CLINICAL PRACTICE GUIDELINE
expectant management. Those randomized to expectant
management underwent fetal surveillance of various types
and at various intervals from randomization to delivery.
Most studies carried out fetal testing at least twice per week.
Twelve studies included assessment of amniotic fluid vol-
ume and an NST for women randomized to expectant man-
agement.50,52,55,56,60–64,66–68 The Canadian trial, which is the
largest, utilized amniotic fluid volume two to three times
per week, NST three times weekly, and daily fetal move-
ment counts.60 A reasonable approach would be at least an
NST and some type of amniotic fluid assessment twice
weekly. The American College of Obstetrician and Gyne-
cologists have a Level C recommendation (consensus and
expert opinion) for initiation of fetal surveillance between
41 and 42 weeks because of evidence that perinatal morbid-
ity and mortality increase as gestational age advances and
that a twice weekly assessment of amniotic fluid and a NST
should be adequate.76 The Royal College of Obstetricians
and Gynaecologists recommends increased antenatal sur-
veillance consisting of a twice weekly NST and an ultra-
sound estimation of maximum amniotic pool depth from
42 weeks in women who decline labour induction.77
Recommendations
7. Antenatal testing used in the monitoring of the 41- to
42-week pregnancy should include at least a non-stress
test and an assessment of amniotic fluid volume. (I-A)
8. Each obstetrical department should establish guidelines
dependent on local resources for scheduling of labour
induction. (I-A)
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method to reduce prolonged pregnancies. Obstet Gynecol 1996;87:927–31.
46. Wong SF, Hui SK, Choi H, Ho LC. Sweeping of membranes in formal
induction of labour. BJOG 2002;109:632–5.
47. Crane J, Bennett K, Young D, Windrim R, Kravitz H. The effectiveness of
sweeping membranes at term: a randomized trial. Obstet Gynecol 1997;
89:586–90.
48. de Miranda E, van der Bom JG, Bonsel GJ, Bleker OP, Rosendaal FR.
Membrane sweeping and prevention of post-term pregnancy in low-risk
pregnancies: a randomized controlled trial. BJOG 2006;113:402–8.
49. Henry GR. A controlled trial of surgical induction of labor and amnioscopy
in the management of prolonged pregnancy. J Obstet Gynaecol Br Cmwlth
1969;76:795–8.
50. Suikkari Am, Jalkanen M, Heiskala H, Koskela O. Prolonged pregnancy:
induction or observation. Acta Obstet Gynecol Scand Suppl 1983;116:58.
51. Katz Z, Yemini M, Lancet M, Mogilner BM, Ben-Hur H, Caspi B.
Non-aggressive management of post-date pregnancies. Eur J Obstet
Gynecol Reprod Biol 1983; 15:71–9.
52. Cardozo L, Fysh J, Pearce JM. Prolonged pregnancy: the management
debate. Br Med J 1986;293:1059–63.
53. Witter FR, Weitz CM. A randomized trial of induction at 42 weeks of
gestation vs. expectant management for postdates pregnancies. Am J
Perinatol 1987;4:206–11.
54. Augensen K, Bergsjo P, Eikeland T, Askvik K, Carlsen J. Randomised
comparison of early versus late induction of in post-term pregnancy.
Br Med J 1987;294:1192–5.
55. Dyson DC, Miller PD, Armstrong MA. Management of prolonged
pregnancy: Induction of labor versus antepartum testing. Am J Obstet
Gynecol 1987;156:928–34.
56. Martin JM, Sessums JK, Howard P, Martin RW, Morrison JC. Alternative
approaches to the management of gravidas with prolonged-postterm-
postdate pregnancies. J Miss State Med Assoc 1989;30:105–11.
57. Bergsjo P, Gui-dan H, Su-qin Y, Zhi-zeng G, Bakketeig LS. Comparison of
induced versus non-induced labor in post-term pregnancy. Acta Obstet
Gynecol Scand 1989; 68:683–7.
58. Heden L, Ingemarsson I, Ahlstrom H, Solum T. Induction of labor versus
conservative management in prolonged pregnancy: controlled study. Int J
Fetomaternal Med 1991;4(4):231–6.
59. Herabutya Y, Prasertsawat PO, Tongyai T, Isarangura Na Ayudthya N.
Prolonged pregnancy: the management dilemma. Int J Gynecol Obstet
1992;37:253–8.
60. Hannah ME, Hannah WJ, Hellamn J, Hewson S, Milner R, Willan and the
Canadian Multicenter post-term pregnancy trial group. Induction of labor as
compared with serial antenatal monitoring in post-term pregnancy.
A randomized controlled trial. N Engl J Med 1992;326:1587–92.
61. The national institute of child health and human development network of
maternal-fetal medicine units. A clinical trial of induction of labor versus
expectant management in postterm pregnancy. Am J Obstet Gynecol
1994;170:716–23.
62. Roach VJ, Rogers MS. Pregnancy outcome beyond 41 weeks gestation. Int J
Gynecol Obstet 1997;59:19–24.
63. James C, George SS, Guanekar N, Seshadri L. Management of prolonged
pregnancy: A randomized trial of induction and antepartum foetal
monitoring. Nat J India 2001;14:270–3.
64. Chanrachakul B, Herabutya Y. Postterm with favorable cervix: is induction
necessary? Eur J Obstet Gynecol Reprod Biol 2003;106:154–7.
65. Ocon L, Hurtado R, Coteron JJ, Zubiria A, Ramirez O, Garcia JA.
Prolonged Pregnancy: procedure guidelines. Progresos de Obstetricia y
Ginecologia 1997; 40:101–6.
66. Chakravarti S, Goenka B. Conservative policy of induction of labor in
uncomplicated postdated pregnancies. XVI FIGO World Congress of
Obstetrics and Gynecology; 2000 Sept 3–8; Washington DC, USA (Book
3). 2000:62.
67. Gelisen O, Caliskan E, Dilbaz S, Ozdas E, Dilbaz B, Ozdas E, Haberal A.
Induction of labor with three different techniques at 41 weeks of gestation
or spontaneous follow-up until 42 weeks in women with definitely
unfavorable cervical scores. Eur J Obstet Gynecol Reprod Biol
2005;120(2):164–9.
68. Heimstad R, Skogvoll E, Mattson L, Johansen OJ, Eik-Nes SH, Salvesen
KA. Induction of labor or serial antenatal fetal monitoring in postterm
pregnancy. Obstet Gynecol 2007;109:609–17.
SEPTEMBER JOGC SEPTEMBRE 2008 l 809
SOGC CLINICAL PRACTICE GUIDELINE
69. Hannah ME. Postterm pregnancy: should all women have labour induced?
A review of the literature. Fetal and Maternal Medicine Review 1993;5:3–17.
70. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz AM. Labor induction versus
expectant management for postterm pregnancies: a systematic review with
meta-analysis. Obstet Gynecol 2003;101:1312–8.
71. Gulmezoglu AM, Crowther CA, Middleton P. Induction of labour for
improving birth outcomes for women at or beyond term. Cochrane
Database Syst Rev 2006 Oct 18;(4):CD004945.
72. Menticoglou SM, Hall PH. Routine induction of labour at 41 weeks
gestation: nonsensus consensus. Br J Obstet Gynaecol 2002;109:485–91.
73. Alfirevic Z, Walkinshaw SA. A randomised controlled trial of simple
compared with complex antenatal fetal monitoring after 42 weeks of
gestation. Br J Obstet Gynaecol 1995;102:638–43.
810 l SEPTEMBER JOGC SEPTEMBRE 2008
74. Guidetti DA, Divon MY, Langer O. Postdate fetal surveillance: is 41 weeks
too early? Am J Obstet Gynecol 1989;161:91–3.
75. Bochner CJ, Williams J, Castro L, Medearis A, Hobel CJ, Wade M. The
efficacy of starting postterm antenatal testing at 41 weeks as compared with
42 weeks of gestational age. Am J Obstet Gynecol 1988;159:550–4.
76. American College of Obstetricians and Gynecologists. Practice Bulletin.
Management of postterm pregnancy. No. 55, 2004.
77. Royal College of Obstetricians and Gynecologists. Induction of labour.
Evidence based clinical Guideline No. 9, June 2001. London: RCOG Press.
Available at: http://www.rcog.org.uk/resources/public/pdf/
rcog_induction_of_labour.pdf. Accessed July 9, 2008.
 SOGC CLINICAL PRACTICE GUIDELINES
SOGC CLINICAL PRACTICE
No GUIDELINES
155 (Replaces guideline No 147), February 2005
Guidelines for Vaginal Birth After Previous
Caesarean Birth
This guideline has been prepared and reviewed by the Clinical
Practice Obstetrics Committee and approved by the Executive
and Council of the Society of Obstetricians and Gynaecologists of
Canada.
PRINCIPAL AUTHORS
Marie-Jocelyne Martel, MD, FRCSC, Saskatoon SK
Catherine Jane MacKinnon, MD, FRCSC, Brantford ON
CLINICAL PRACTICE OBSTETRICS COMMITTEE
Catherine Jane MacKinnon, MD, FRCSC, Brantford ON
Marc-Yvon Arsenault, MD, FRCSC, Montreal QC
Elias Bartellas, MD, FRCSC, St John’s NL
Yvonne M. Cargill, MD, FRCSC, Ottawa ON
Sue Daniels, RN, Dartmouth NS
Tom Gleason, MD, FRCSC, Edmonton AB
Stuart Iglesias, MD, Gibsons BC
Michael C. Klein, MD, CCFP, Vancouver BC
Marie-Jocelyne Martel, MD, FRCSC, Saskatoon SK
Ann Roggensack, MD, Kingston ON
Ann Kathleen Wilson, BHSc, RM, Ilderton ON
SPECIAL CONTRIBUTOR
Gregory A. Davies, MD, FRCSC, Kingston ON
Abstract
Objective: To provide evidence-based guidelines for the provision of
a trial of labour (TOL) after Caesarean section.
Outcome: Fetal and maternal morbidity and mortality associated with
vaginal birth after Caesarean (VBAC) and repeat Caesarean
section.
Evidence: MEDLINE database was searched for articles published
from January 1, 1995, to February 28, 2004, using the key words
“vaginal birth after Caesarean (Cesarean) section.” The quality of
evidence is described using the Evaluation of Evidence criteria
outlined in the Report of the Canadian Task Force on the Periodic
Health Exam.
Key Words: Vaginal birth after Caesarean, trial of labour, uterine
rupture, induced labour, oxytocin, prostaglandins, misoprostol
These guidelines reflect emerging clinical and scientific advances as of the date issued and are subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
164 lFEBRUARY JOGC FÉVRIER 2005
Recommendations:
1. Provided there are no contraindications, a woman with 1 previous
transverse low-segment Caesarean section should be offered a
trial of labour (TOL) with appropriate discussion of maternal and
perinatal risks and benefits. The process of informed consent with
appropriate documentation should be an important part of the birth
plan in a woman with a previous Caesarean section (II-2B).
2. The intention of a woman undergoing a TOL after Caesarean
section should be clearly stated, and documentation of the
previous uterine scar should be clearly marked on the prenatal
record (II-2B).
3. For a safe labour after Caesarean section, a woman should deliver
in a hospital where a timely Caesarean section is available. The
woman and her health care provider must be aware of the hospital
resources and the availability of obstetric, anesthetic, pediatric,
and operating-room staff (II-2A).
4. Each hospital should have a written policy in place regarding the
notification and (or) consultation for the physicians responsible for
a possible timely Caesarean section (III-B).
5. In the case of a TOL after Caesarean, an approximate time frame
of 30 minutes should be considered adequate in the set-up of an
urgent laparotomy (III-C).
6. Continuous electronic fetal monitoring of women attempting a TOL
after Caesarean section is recommended (II-2A).
7. Suspected uterine rupture requires urgent attention and expedited
laparotomy to attempt to decrease maternal and perinatal morbidity
and mortality (II-2A).
8. Oxytocin augmentation is not contraindicated in women undergoing
a TOL after Caesarean section (II-2A).
9. Medical induction of labour with oxytocin may be associated with an
increased risk of uterine rupture and should be used carefully after
appropriate counselling (II-2B).
10. Medical induction of labour with prostaglandin E2 (dinoprostone)
is associated with an increased risk of uterine rupture and should
not be used except in rare circumstances and after appropriate
counselling (II-2B).
11. Prostaglandin E1 (misoprostol) is associated with a high risk of
uterine rupture and should not be used as part of a TOL after
Caesarean section (II-2A).
12. A foley catheter may be safely used to ripen the cervix in a woman
planning a TOL after Caesarean section (II-2A).
13. The available data suggest that a trial of labour in women with
more than 1 previous Caesarean section is likely to be successful
but is associated with a higher risk of uterine rupture (II-2B).
14. Multiple gestation is not a contraindication to TOL after Caesarean
section (II-2B).

15. Diabetes mellitus is not a contraindication to TOL after Caesarean
section (II-2B).
16. Suspected fetal macrosomia is not a contraindication to TOL after
Caesarean section (II-2B).
17. Women delivering within 18 to 24 months of a Caesarean section
should be counselled about an increased risk of uterine rupture in
labour (II-2B).
18. Postdatism is not a contraindication to a TOL after Caesarean
section (II-2B).
19. Every effort should be made to obtain the previous Caesarean
section operative report to determine the type of uterine incision
used. In situations where the scar is unknown, information
concerning the circumstances of the previous delivery is helpful in
determining the likelihood of a low transverse incision. If the
likelihood of a lower transverse incision is high, a TOL after
Caesarean section can be offered (II-2B).
Validation: These guidelines were approved by the Clinical Practice
Obstetrics and Executive Committees of the Society of
Obstetricians and Gynaecologists of Canada.
J Obstet Gynaecol Can 2005;27(2):164–174
BACKGROUND
his document reviews the contraindications to and
T maternal and fetal risks of a trial of labour (TOL) after
Caesarean birth and makes recommendations for
achieving vaginal birth after Caesarean (VBAC) safely.
Delivery by Caesarean section occurs in 15% to 25% of
births.1–5 In 2000 and 2001, the Caesarean section rate in
Canada was 21.2%.6 The most frequent indications for Cae-
sarean delivery are previous Caesarean delivery, dystocia,
malpresentation, and nonreassuring fetal status.7,8 In any
given region, the rate of birth by Caesarean section and the
rate of VBAC tend to be inversely related.4 Schell first
reported VBAC in 1923, describing the successful vaginal
delivery of 34 infants in 23 mothers with previous Caesar-
ean deliveries.9
A trial of labour after Caesarean should be considered in
women who present for prenatal care with a history of pre-
vious Caesarean birth.10–12 In certain situations, a TOL after
Caesarean will be contraindicated3 and a repeat Caesarean
section will be advised, but in most cases, successful vaginal
birth can be safely achieved for both mother and infant.13–15
Women and their health care providers will need to discuss
the risks and benefits of VBAC when planning the birth.
A Canadian consensus statement on VBAC was published
in 1985, and Clinical Practice Guidelines were published by
the Society of Obstetricians and Gynaecologists of Canada
(SOGC) in 1997.3 This document updates the 1997 SOGC
Guidelines with articles published from January 1, 1995, to
February 28, 2004. Articles were obtained by searching the
MEDLINE database, using the key words “vaginal birth
after Caesarean (Cesarean) section.” The data are limited by
3 important factors: first, there are no randomized trials of
TOL versus elective repeat Cesarean section (ERCS); sec-
ond, adverse maternal or perinatal outcomes are rare, and
large study populations are necessary to observe a
Guidelines for Vaginal Birth After Previous Caesarean Birth
significant difference in maternal and perinatal outcomes;
and finally, a woman’s choice to attempt TOL after Caesar-
ean is heavily influenced by her health care provider and
local resources, often leading to selection bias in published
reports.12,16
The level of evidence and quality of the recommendations
in this guideline have been determined using the criteria
described by the Canadian Task Force on the Periodic
Health Examination (Table).17
TRIAL OF LABOUR VERSUS ELECTIVE
REPEAT CAESAREAN SECTION
The success rate of a TOL after Caesarean ranges between
50% and 85%.3,4,14,18–21 In a study examining 1776 women
undergoing TOL after Caesarean, the overall success rate
was 74%.14 A Canadian study reported similar results, quot-
ing a success rate of 76.6%.2 Predictors of successful VBAC
include nonrecurring indication for Caesarean birth, such as
malpresentation (odds ratio [OR], 1.9; 95% confidence
interval [CI], 1.0–3.7)22 or gestational hypertension (OR,
2.3; 95% CI, 1.0–5.8),22 and a previous vaginal delivery (OR,
1.8; 95% CI, 1.1–3.1),22 where success rates are as high as
82%.1,22,23 When the previous Caesarean birth was for
dystocia, failure to progress, or cephalopelvic dispropor-
tion, some studies found the rates of successful VBAC
comparable,24,25 while others reported lower-than-expected
rates.14,18,22,26
In 1996 McMahon et al. published a report of maternal mor-
bidity in TOL compared with ERCS in Nova Scotia from
1986 to 1992.1 In an examination of 3249 women undergo-
ing a TOL and 2889 women who delivered by ERCS, the
risk of major complications (for example, hysterectomy,
uterine rupture, and operative injury) was almost doubled
(1.6% vs. 0.8%) in the TOL group (OR, 1.8; 95% CI,
1.1–3.0).1 Complications like puerperal fever, transfusion,
and abdominal wound infection were comparable. When
comparing women who had a successful TOL with those
who required a repeat Caesarean section after failed TOL,
the risks were greater of operative injury (3.0% vs. 0.1%;
OR, 5.1; 95% CI, 2.5–10.7) and fever (8.0% vs. 3.5%; OR,
1.5; 95% CI, 1.3–1.8) in the failed TOL group.1 Hibbard et
al. also reported a greater rate of complication in women
who attempted a TOL and failed.27
In 1999 Rageth et al. reviewed 17 613 TOL and 11 433
ERCS deliveries.20 The rates of hysterectomy (relative risk
[RR], 0.36; 95% CI, 0.23–0.56), febrile morbidity (RR, 0.65;
95% CI, 0.55–0.77), and thromboembolic complications
(RR, 0.52; 95% CI, 0.34–0.78) were less in the TOL group
than in the ERCS group.20 There is less blood loss with a
successful VBAC (OR, 0.50; 95% CI, 0.3–0.9)27 and a
shorter hospital stay with a more rapid recovery and return
to full activity.
FEBRUARY JOGC FÉVRIER 2005 l 165
SOGC CLINICAL PRACTICE GUIDELINES
Table Criteria for quality of evidence assessment and classification of recommendations
Level of results*
I: Evidence obtained from at least one properly randomized
controlled trial.
II-1: Evidence from well-designed controlled trials without
randomization.
II-2: Evidence from well-designed cohort (prospective or
retrospective) or case-control studies, preferably from more than
one centre or research group.
II-3: Evidence obtained from comparisons between times or places
with or without intervention. Dramatic results in uncontrolled
experiments (such as the results of treatment with penicillin in
the 1940s) could also be included in this category.
III: Opinions of respected authorities, based on clinical experience,
descriptive studies, or reports of expert committees.
*The quality of evidence reported in these guidelines has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force
on the Periodic Health Exam.
†Recommendations included in these guidelines have been adapted from the ranking method described in the Classification of Recommendations found in the
Report of the Canadian Task Force on the Periodic Health Exam.
Rosen et al. also reported that the risk of febrile morbidity is
lower in women who attempt a TOL after Caesarean (OR,
0.5; 95% CI, 0.5–0.6) and is lowest in those who succeed
(OR, 0.2; 95% CI, 0.2–0.2), compared with ERCS, but is
increased in those who attempt a TOL and ultimately
deliver by Caesarean (OR, 2.0; 95% CI, 1.7–2.5).28
An examination of 16 938 Finnish women who had under-
gone a Caesarean delivery found that previous Caesarean
section is associated with an increased risk of ectopic preg-
nancy (RR, 1.28), placenta previa (RR, 3.89), and abruptio
placenta (RR, 2.41).29 A repeat Caesarean has been associ-
ated with an increase in the risk of placenta previa (OR,
1.59; 95% CI, 1.21–2.08)30 and placenta accreta in subse-
quent pregnancies.31
A meta-analysis published in 2000 demonstrated that the
overall risk of perinatal death is increased in women
attempting a TOL (OR, 1.71; 95% CI, 1.28–2.28).32 The
risks of perinatal mortality and severe morbidity are directly
related to uterine rupture as a sentinel event. If uterine rup-
ture occurs, the risks of perinatal mortality and severe mor-
bidity are increased. The risk of suspected neonatal sepsis is
greater in women attempting TOL but appears to be con-
fined to those who fail TOL and require a repeat Caesarean
section (OR, 4.8; 95% CI, 2.6–9.0).33 In women who
choose ERCS, the risk of respiratory problems in the new-
born is increased (6% vs. 3%), compared with women who
have a successful VBAC (OR, 2.3; 95% CI, 1.4–3.8).33
166 l FEBRUARY JOGC FÉVRIER 2005
Classification of recommendations†
A. There is good evidence to support the recommendation that the
condition be specifically considered in a periodic health
examination.
B. There is fair evidence to support the recommendation that the
condition be specifically considered in a periodic health
examination.
C. There is poor evidence regarding the inclusion or exclusion of
the condition in a periodic health examination, but recommenda-
tions may be made on other grounds.
D. There is fair evidence to support the recommendation that the
condition not be considered in a periodic health examination.
E. There is good evidence to support the recommendation that the
condition be excluded from consideration in a periodic health
examination.
CONTRAINDICATIONS TO VAGINAL BIRTH
AFTER CAESAREAN SECTION
The following situations are contraindications to a TOL
after Caesarean:
1. previous classical or inverted “T” uterine scar3,13;
2. previous hysterotomy or myomectomy entering the uter-
ine cavity3,19;
3. previous uterine rupture3,19;
4. presence of a contraindication to labour, such as placenta
previa or malpresentation3;
5. the woman declines a TOL after Caesarean and requests
ERCS.3,19
Recommendation
1. Provided there are no contraindications, a woman with 1
previous transverse low-segment Caesarean section should
be offered a trial of labour after Caesarean with appropriate
discussion of maternal and perinatal risks and benefits. The
process of informed consent with appropriate documenta-
tion should be an important part of the birth plan in women
with a previous Caesarean section (II-2B).
PLANNING A TRIAL OF LABOUR AFTER
CAESAREAN SECTION
A woman and her health care provider must decide together
whether an appropriate situation exists for considering
TOL after Caesarean. The evaluation and discussion should
address the issues outlined below and should be well docu-
mented in the prenatal record or chart.

Documentation of Previous Uterine Incision
Documentation of the location and type of uterine incision
used during the previous Caesarean section is ideal.3 In
most cases, this information can be obtained by reviewing
the operative record from the previous surgery. Other
information in this record, such as the indication for the
Caesarean section and the opinion of the previous surgeon,
may be helpful in counselling as well. The fact that the
record has been reviewed and that no contraindications to a
TOL after Caesarean are present should be documented
clearly on the prenatal record.34 If the operative record is
not available, the scar is considered “unknown.” Review of
the operative report from previous hysterotomy or
myomectomy should be documented in detail.
Recommendation
2. The intention of a woman undergoing a TOL after Cae-
sarean should be clearly stated, and documentation of the
previous uterine scar should be clearly marked on the pre-
natal record (II-2B).
Facilities and Resources
A trial of labour after Caesarean is always associated with a
risk of uterine rupture, however small, and a good outcome
is not guaranteed under any circumstances. Further, little
evidence exists about the exact timing of a Caesarean sec-
tion following a suspected uterine rupture, which would
prevent a poor neonatal outcome. A TOL after Caesarean
can be offered to women within any hospital setting where
there is an ability to perform a Caesarean section.13,34,35 This
document does not intend to set a standard regarding
whether staff must be “in house” or “on site” to provide
safe intrapartum care and therefore makes no statements on
such attendance. Facilities providing TOL after Caesarean
should have a policy in place to manage such parturients, so
that all resources are mobilized promptly if an intrapartum
emergency occurs.23 The SOGC recognizes that in such
cases of maternal fetal compromise, necessitating timely
Caesarean section, an approximate time frame of 30 min-
utes may be required to assemble the team and commence
laparotomy. This availability and time required for obstet-
ric, anesthetic, and pediatric services to attend such an
emergency should be fully discussed with the woman.
Women who live in areas where local hospitals cannot pro-
vide a timely Caesarean section should be offered the
opportunity for transfer to a facility where this service is
available, in order to permit a TOL after Caesarean.13 The
members of the team who could be called urgently in the
case of an intrapartum complication (anesthetic, pediatric,
and obstetric services) should be notified that the woman is
in hospital and in labour, and their availability should be
confirmed.
Guidelines for Vaginal Birth After Previous Caesarean Birth
Labour and delivery in women who have had a previous
Caesarean section should be conducted in a hospital setting
with facilities for a laparotomy.
Recommendation
3. For a safe labour after Caesarean section, the woman
should deliver in a hospital where a timely Caesarean sec-
tion is available. The woman and her health care provider
must be aware of the hospital resources and the availability
of obstetric, anesthetic, pediatric, and operating-room staff
(II-2A).
4. Each hospital should have a written policy in place
regarding the notification and (or) consultation for the phy-
sicians responsible for a possible timely Caesarean (III-B).
5. In the case of a TOL after Caesarean, an approximate
time frame of 30 minutes should be considered adequate in
the set-up of an urgent laparotomy (III-C).
Maternal Monitoring
Women planning a TOL after Caesarean should have
appropriate monitoring in labour. The presence of a
devoted birth attendant is ideal. Progress of labour should
be assessed frequently, as there is some evidence that pro-
longed or desultory labour is associated with an increased
risk of failure and uterine rupture.19,36,37 Epidural analgesia
is not contraindicated.7,19,34,38
Fetal Monitoring
Continuous electronic fetal monitoring in labour is recom-
mended for all women attempting TOL after Caesar-
ean.19,34,39 The most reliable first sign of uterine rupture is a
nonreassuring fetal heart tracing.34 This may be sudden in
onset and may not be related to contractions.40
Recommendation
6. Continuous electronic fetal monitoring of women
attempting TOL after Caesarean is recommended (II-2A).
POSTPARTUM EVALUATION
Routine digital exploration of the Caesarean scar
postpartum is not necessary, except when signs or symp-
toms suggest uterine rupture.41
UTERINE RUPTURE
Uterine rupture, the most serious complication of a TOL
after Caesarean, is defined as complete separation of the
myometrium with or without extrusion of the fetal parts
into the maternal peritoneal cavity and requires emergency
Caesarean section or postpartum laparotomy.19,42 It is an
uncommon complication of VBAC but is associated with
significant maternal and perinatal morbidity and mortal-
ity.1,7 The most common sign or symptom of uterine rup-
ture is nonreassuring fetal heart rate monitoring.18,20,43
Other clinical signs include the cessation of contractions,
FEBRUARY JOGC FÉVRIER 2005 l 167
SOGC CLINICAL PRACTICE GUIDELINES
loss of the presenting part on vaginal examination, abdomi-
nal pain, vaginal bleeding, hematuria, or maternal cardio-
vascular instability.16,44
The type and location of the previous uterine incision helps
to determine the risk of uterine rupture. The incidence of
uterine rupture is 0.2% to 1.5% in women who attempt
labour after a transverse lower uterine segment inci-
sion14,16,18,27,45 and 1% to 1.6% in women who have had a
vertical incision in the lower uterine segment.46–49 The risk
is 4% to 9% with a classical or “T” incision; thus TOL after
Caesarean is contraindicated in these situations.16,19,30
Shimonovitz et al. found the risk of uterine rupture after 0,
1, 2, and 3 VBAC deliveries to be 1.6%, 0.3%, 0.2%, and
0.35%, respectively, indicating that the risk of uterine rup-
ture decreases after the first successful VBAC.50
Since uterine rupture is a rare event, a realistic appraisal of
potential maternal and perinatal risks is difficult to accom-
plish outside of large series, literature reviews, or meta-
analyses. The most important published reports in this area
are discussed below, as well as those applicable to the Cana-
dian population.
In 1991 Rosen et al. performed a meta-analysis of 10 studies
that examined a total of 4617 women who had a TOL after
Caesarean compared with 3831 women who had ERCS
births.28 The rate of uterine rupture was similar in the 2
groups: TOL 0.18% and ERCS 0.19% (P = 0.5). There was
no difference in the rate of maternal death (0.028% vs.
0.024%) or perinatal death (0.3% vs. 0.4%) in the TOL
group, compared with the ERCS group.28
In 2000 Mozurkewich and Hutton published a meta-
analysis of 15 studies that examined a total of 28 813
women undergoing a TOL compared with ERCS between
1989 and 1999.32 There was an increased rate of uterine rup-
ture (0.39% vs. 0.16%; OR, 2.1; 95% CI, 1.45–3.05) and
perinatal mortality (0.58% vs. 0.28%; OR, 1.71; 95% CI,
1.28–2.28) in the TOL group. The rates of maternal mortal-
ity and low 5-minute Apgar scores were not different.32
In 2002 Keiser et al. reviewed the incidence and conse-
quences of uterine rupture in Nova Scotia from 1988 to
1997.51 Among 4516 women undergoing a TOL, 18
(0.39%) uterine ruptures were documented over 10 years.
All women underwent laparotomy, and there were no
maternal deaths. Of those who had a uterine rupture, 3
women underwent hysterectomy, 10 required transfusion,
and 5 suffered a cystotomy. After excluding lethal anoma-
lies, there was 1 perinatal death (0.02%) and 6 neonates with
severe asphyxia (0.13%).51
In 2002 Bujold et al. examined the risk factors for serious
neonatal morbidity associated with 23 cases of uterine rup-
ture among 2233 women attempting a TOL (rate 1.03%).52
Nine neonates (0.4%) had a pH < 7.0 (severe metabolic aci-
dosis), 3 (0.13%) were diagnosed with hypoxic ischemic
168 l FEBRUARY JOGC FÉVRIER 2005
encephalopathy, and 1 (0.04%) died.52 The presence of pla-
cental or fetal part extrusion at laparotomy was associated
with severe metabolic acidosis (P < 0.001).52 Other vari-
ables (e.g., induction, birth weight, or use of epidural) did
not demonstrate an association with uterine rupture. Even
in situations where very rapid decision to delivery times
were recorded, some cases of perinatal acidosis could not
be avoided.52
Smith et al. published a large series of 15 515 women under-
going a TOL after Caesarean compared with 9014 women
who underwent ERCS between 1992 and 1997.53 The rate
of perinatal death in the TOL group was 0.129%, 11.6 times
higher than that of the ERCS group (OR, 11.6; 95% CI,
1.6–86.7).53 Smith compared this to the risk of perinatal
death in other common obstetrical situations: TOL com-
pared with multiparous women in labour (OR, 2.2; 95% CI,
1.3–3.5) and TOL compared with nulliparous women in
labour (OR, 1.3; 95% CI, 0.8–21).53
In 2003 Chauhan et al. published a review of data on the
maternal and perinatal complications of uterine rupture in
those attempting a TOL after Caesarean.54 Examining 142
075 trials of labour revealed an overall rate of uterine rup-
ture of 0.62%.54 The rate of maternal death was 0.002%;
hysterectomy, 0.09%; transfusion, 0.18%; and genitouri-
nary tract injury, 0.08%.54 In this study, the rate of neonatal
acidosis was 0.15%, and the rate of perinatal death was
0.04%.54 Oxytocin was involved in 43% of the uterine rup-
tures in this series.54
The data indicate that the relative risk of uterine rupture,
maternal morbidity, and perinatal mortality or severe mor-
bidity is increased in women undergoing a TOL after Cae-
sarean, compared with ERCS, but that the absolute risk
remains very low.
The treatment of suspected uterine rupture is timely
laparotomy after maternal stabilization and anaesthesia.
Urgent intervention is mandatory to obtain the best possi-
ble outcome for both mother and fetus. Once the fetus is
delivered, maternal hemorrhage must be arrested, and if the
uterus cannot be salvaged, hysterectomy may be required.
Although the risk of uterine rupture has been found to be
increased in situations of prolonged labour with augmenta-
tion,55 when Phelan et al. retrospectively examined the pat-
terns of uterine activity before uterine rupture, no associa-
tion with frequency or intensity of contractions could be
discerned.40
In 1996 Rozenberg et al. examined ultrasonographic mea-
surement of the lower uterine segment’s myometrial thick-
ness at 36 to 38 weeks’ gestation as a predictor of uterine
rupture and found that if the lower segment thickness was
less than 3.5 mm, the risk of uterine rupture or dehiscence
was 11.8%; if the measurement was greater than 3.5 mm,
the risk of uterine rupture was minimal.56 However, the

incidence of uterine rupture in this population was 2.3%,
significantly greater than the usually quoted 1%. Therefore,
the positive predictive value of this test in clinical practice
will be much lower.56 In a follow-up open study, Rozenberg
et al. found that the use of the lower-uterine-segment mea-
surement helped clinicians select women for a TOL after
Caesarean.57 The rate of successful VBAC for those with 1
previous Caesarean section did not change but was
increased in those with 2 previous Caesarean deliveries.57
These findings will need to be confirmed in further ran-
domized studies before ultrasonography can be used to
make a decision about the safety of TOL after Caesarean.
Recommendation
7. Suspected uterine rupture requires urgent attention and
expedited laparotomy to attempt to decrease maternal and
perinatal morbidity and mortality (II-2A).
OXYTOCICS AND TOL AFTER
CAESAREAN SECTION
Augmentation
In 1987 Flamm et al. performed a multicentre examination
of 485 women who received oxytocin to augment their
spontaneous labour in a planned TOL after Caesarean.58
No increase in the risk of uterine rupture, maternal morbid-
ity, or perinatal morbidity or mortality was detected.58
Zelop et al. supported the same conclusion about the risk of
uterine rupture with augmentation in a 1999 study (OR, 2.3;
95% CI, 0.8–7.0).59 Goetzl et al. examined the relation
between the dose of oxytocin used and the risk of uterine
rupture in women undergoing a TOL after Caesarean.60 No
significant association was detected between exposure to
oxytocin and the risk of uterine rupture.60 Careful surveil-
lance for progress of labour is required, especially when the
diagnosis of dystocia is being considered.19,34 There are
insufficient studies examining the use of other agents to
augment labour, such as prostaglandins, and their safety in a
TOL after Caesarean.
Induction
In 2000 Ravasia et al. reviewed the risk of uterine rupture in
women undergoing an induction TOL after Caesarean.61 In
575 women with a previous Caesarean section, labour was
induced with prostaglandin E2 gel (n = 172), intracervical
foley catheter (n = 129), or amniotomy and (or) oxytocin
(n = 274).61 Outcomes were compared with women under-
going a TOL with spontaneous labour. The risk of uterine
rupture was not increased in women who underwent either
amniotomy/oxytocin or foley catheter induction but was
significantly increased in those who underwent a prosta-
glandin E2 induction (P = 0.004).61
Also in 2000, Sanchez-Ramos et al. performed a meta-
analysis looking at the efficacy and safety of prostaglandin
Guidelines for Vaginal Birth After Previous Caesarean Birth
E2 for cervical ripening in women with a previous Caesar-
ean section and found it to be effective and not associated
with an increased risk of uterine rupture (OR, 1.46; 95% CI,
0.96–2.22), compared with spontaneous labour.62
In 2003 Delaney and Young reported the examination of
3746 women with a prior Caesarean delivery who under-
went either induced or spontaneous labour.63 They found
that induced labour was associated with a greater risk of
early postpartum hemorrhage (7.3% vs. 5.0%: OR, 1.66;
95% CI, 1.18–2.32), Caesarean delivery (37.5% vs. 24.2%:
OR, 1.84; 95% CI, 1.51–2.25), and admission to a neonatal
intensive care unit (13.3% vs. 9.4%: OR, 1.69; 95% CI,
1.25–2.29).63 There was a trend toward a higher rate of uter-
ine rupture, but this was not statistically significant (0.7%
vs. 0.3%, P = 0.128).63
In another retrospective study of 560 women, the rate of
uterine rupture in women whose labour was induced with
oxytocin was 2%, with prostaglandin was 2.9%, and with
both was 4.5%.59
Up to 2001, there were conflicting data on the risk of labour
induction with prostaglandin E2. Several other smaller stud-
ies reported that it appeared to be safe, effective, and not
associated with an increased risk of uterine rupture.45,64–66
In the largest study published to date, conducted by
Lydon-Rochelle et al., the incidence of uterine rupture was
reviewed retrospectively in 20 095 women with a previous
Caesarean section and was reported as follows: ERCS (no
labour) 0.16%; spontaneous labour 0.52% (RR, 3.3; 95%
CI, 1.8–6.0); labour induced without prostaglandin 0.77%
(RR, 4.9; 95% CI, 2.4–9.7); and labour induced with prosta-
glandin 2.45% (RR, 15.6; 95% CI, 8.1–30.0).67
As for all inductions, the indication for induction in women
undergoing a planned TOL after Caesarean should be com-
pelling and documented. The possibility that the use of
oxytocin and (or) prostaglandin for labour induction in
women considering TOL after Caesarean may be associated
with an increased risk of uterine rupture and its sequelae
must be discussed with the parturient. The absolute risks of
uterine rupture are low, but the relative risks (especially with
the use of prostaglandin E2, compared with spontaneous
labour) are greater.
Misoprostol
Misoprostol has been proposed as an effective and eco-
nomical agent for cervical ripening and induction.68 In 1998
Sciscione et al. reported a case of uterine rupture in a woman
with 2 previous Caesarean deliveries after misoprostol was
administered as a cervical ripening agent.69 Several small
series reported a risk from 0% to 11.7% of uterine rupture
with misoprostol in women undergoing a TOL after Cae-
sarean 43,70–73 Blanchette et al. compared prostaglandin E2 to
misoprostol in women undergoing induction TOL after
FEBRUARY JOGC FÉVRIER 2005 l 169
SOGC CLINICAL PRACTICE GUIDELINES
Caesarean and found them to be equally effective, but
misoprostol was associated with a higher incidence of uter-
ine rupture (18.8% compared to no ruptures in the prosta-
glandin E2 group).74 The numbers in all these studies are
small, and it is difficult to draw meaningful conclusions.
Until further randomized studies are completed,
misoprostol should be discouraged as a method of induc-
tion or cervical ripening in women with previous Caesarean
delivery.74,75
CERVICAL PREPARATION
In situations where delivery is indicated and the cervix is
unfavourable, TOL after Caesarean can be considered.
Various methods of cervical ripening have been examined.
In a cohort study published in 2002, Ben-Aroya et al. com-
pared women undergoing a trial of labour after Caesarean
section in 3 situations: spontaneous labour (n = 1432),
prostaglandin cervical ripening (n = 55), and cervical ripen-
ing by foley catheter (n = 161).76 There was a significantly
higher rate of dystocia (30.4% vs. 11.6%, P < 0.01) and
repeat Caesarean section in the second stage (49.1% vs.
35.2%, P < 0.01) in the foley catheter group, compared with
the control group.76 There was no difference in the rate of
uterine rupture, fetal distress, or Apgar scores.76 In a Cana-
dian study published in 2004, Bujold et al. compared the rate
of uterine rupture in 1807 women who presented in sponta-
neous labour, 417 induced with amniotomy with or without
oxytocin, and 255 induced with transcervical foley cathe-
ter.77 The rate of successful vaginal birth was 78% in the
spontaneous group, 77.9% in the amniotomy group, and
55.7% in the transcervical foley group (P < 0.001).77
However, the rates of uterine rupture did not differ signifi-
cantly: 1.1%, 1.2%, and 1.6%, respectively (P = 0.81).77
These data support the use of the foley catheter for cervical
ripening of an unfavourable cervix in women undergoing a
TOL after Caesarean.
Recommendations
8. Oxytocin augmentation is not contraindicated in women
undergoing a TOL after Caesarean (II-2A).
9. Medical induction of labour with oxytocin may be associ-
ated with an increased risk of uterine rupture and should be
used carefully after appropriate counselling (II-2B).
10. Medical induction of labour with prostaglandin E2
(dinoprostone) is associated with an increased risk of uter-
ine rupture and should not be used except in rare circum-
stances after appropriate counselling (II-2B).
11. Prostaglandin E1 (misoprostol) is associated with a high
risk of uterine rupture and should not be used as part of a
TOL after Caesarean (II-2A).
12. A foley catheter may be used safely to ripen the cervix in
a woman planning a TOL after Caesarean (II-2A).
170 l FEBRUARY JOGC FÉVRIER 2005
SPECIAL CIRCUMSTANCES
More Than 1 Previous Low Transverse Caesarean
Section
Several authors have assessed the rate of successful VBAC
and the risk of uterine rupture in women with more than 1
previous low transverse Caesarean section.8,78–84 All indi-
cated success rates between 62% and 89% and uterine rup-
ture rates between 0% and 3.7%. In the largest study, Miller
et al. demonstrated a VBAC success rate of 75.3% in 1827
women with 2 or more previous low transverse Caesarean
deliveries, with a uterine rupture rate of 1.7% versus 0.6%
in the ERCS group (OR, 3.06; 95% CI, 1.95–4.79).8 Unfor-
tunately, the use of prostaglandins or oxytocin for induction
or augmentation was not considered. Caughey et al.
reported a uterine rupture rate of 3.7% versus 0.8% (RR,
4.8; 95% CI, 1.8–13.2) in a retrospective review of 134
women undergoing labour after 2 previous Caesarean deliv-
eries after correction for prostaglandin, oxytocin, and
epidural use.84
Recommendation
13. The available data suggest that a trial of labour in
women with more than 1 previous Caesarean is likely to be
successful but is associated with a higher risk of uterine rup-
ture (II-2B).
Multiple Pregnancy
Seven studies have examined a total of 233 women attempt-
ing VBAC in multiple pregnancy.85–91 All support a trial of
VBAC in multiple pregnancy as being safe and effective,
with success rates of 69% to 84% and without increased
maternal or fetal morbidity or mortality.85–91 In one study,
uterine dehiscence was noted in 1 woman on manual explo-
ration after successful vaginal delivery of both twins, and no
treatment was required.86 Each of these studies examined a
small number of women, however, and greater numbers
would be required to detect rare outcomes such as uterine
rupture and maternal and perinatal mortality.
Recommendation
14. Multiple gestation is not a contraindication to a TOL
after Caesarean (II-2B).
Breech Presentation
A large multicentre trial by Hannah et al. demonstrated that
a planned Caesarean birth is associated with better perinatal
and neonatal outcomes in breech presentation at term.92
This recommendation has been adopted by the SOGC and
would therefore preclude a planned TOL after Caesarean in
women presenting with a singleton fetus in breech presen-
tation at term.92,93 Vaginal delivery of premature fetuses and
the second twin were not addressed in the study; therefore,
no recommendations can be made in this regard. It would
seem appropriate to consider these cases individually.

External cephalic version is not contraindicated in women
with a previous Caesarean birth.94,95
Diabetes Mellitus
In a retrospective cohort study, Coleman et al. examined the
issue of TOL after Caesarean in women with gestational
diabetes mellitus (GDM).96 Coleman examined 156 women
with GDM and planned TOL after Caesarean and com-
pared them with women with no GDM and attempting
TOL after Caesarean. They reported that the success rate
for VBAC of 64.1% in women with GDM was lower than
the 77.2% of women without GDM (P < 0.001).96 Maternal
and fetal morbidities were comparable.96 A retrospective
study of TOL after Caesarean in women with pregestational
or gestational diabetes found similar results.97 Based on
these studies, diabetes mellitus should not be considered a
contraindication to TOL after Caesarean.
Recommendation
15. Diabetes mellitus is not a contraindication to TOL after
Caesarean (II-2B).
Macrosomia
In a study examining the outcome of 365 women who
underwent a TOL after Caesarean and who were giving
birth to neonates weighing more than 4000 g, Zelop et al.
demonstrated a success rate of 60%, with no increase in
maternal or fetal morbidity and no increase in the risk of
uterine rupture.98 These data support previously reported
findings by Flamm (success rate 58%)99 and Phelan (success
rate 67%).100 In 2003 Elkousy et al. reported an examination
of 9960 women with a previous Caesarean section planning
a trial of labour. The study was further stratified by neonatal
birth weights and birth history (primarily, whether they had
a previous vaginal delivery and whether it occurred before
or after their Caesarean).101 Their results indicate that the
likelihood of successful VBAC decreases with increasing
birth weight and is lowest in women who have never had a
successful vaginal birth.101 According to these results, sus-
pected macrosomia is not a contraindication to TOL after
Caesarean, though it may be associated with a lower chance
of success.
Recommendation
16. Suspected fetal macrosomia is not a contraindication to
a TOL after Caesarean (II-2B).
Interdelivery Interval
Four studies have examined the relation between the
interdelivery interval and the rate of successful VBAC and
uterine rupture.102–105 Esposito et al. examined 23 cases of
uterine rupture and compared them with 127 control sub-
jects.102 There was an increased risk of uterine rupture with
a short interpregnancy interval (< 6 months between preg-
nancies; < 15 months between deliveries), compared with
Guidelines for Vaginal Birth After Previous Caesarean Birth
control subjects (17.4% vs. 4.7%, P = 0.05).102 Shipp et al.
reviewed 311 women who underwent a TOL after Caesar-
ean less than 18 months after their Caesarean section and
compared them with 2098 women who underwent a TOL
after Caesarean after more than 18 months.103 The shorter
interval was associated with a threefold increase in the risk
of uterine rupture (2.25% vs. 1.05%: OR, 3.0; 95% CI,
1.2–7.2).103 Huang et al. reviewed 1185 women undergoing a
TOL after Caesarean and noted no difference in the success
of vaginal delivery in women with a shorter interval of less
than 19 months (79% vs. 85.5%, P = 0.12); however, they
did note a significant difference in successful VBAC in
women who underwent medical induction, compared with
spontaneous labour (14.3% vs. 86.1%, P < 0.01).104 Their
study noted no difference in the rate of uterine rupture.104
In 2002 Bujold et al. reported an observational study of 1527
women undergoing a planned TOL after Caesarean at dif-
ferent intervals from the index Caesarean delivery.105 The
rates of uterine rupture were as follows: < 12 months, 4.8%;
13 to 24 months, 2.7%; 25 to 36 months, 0.9%; and > 36
months, 0.9%.105 After adjusting for such confounders as
number of layers in the uterine closure, induction, oxytocin,
and epidural use, the odds ratio for uterine rupture in a
woman less than 24 months from her last delivery was 2.65
(95% CI, 1.08–6.46).105
Recommendation
17. Women delivering within 18 to 24 months of a Caesar-
ean section should be counselled about an increased risk of
uterine rupture in labour (II-2B).
Postdatism
Three studies have examined postdatism and TOL after
Caesarean.106–108 In 2 of these studies, the rate of successful
VBAC and uterine rupture in women who delivered at less
than 40 weeks’ gestation was compared with those who
delivered at more than 40 weeks.106,107 Success rates for
VBAC after 40 weeks were reported from 65.6%107 to
73.1%106 and were comparable to success rates for women
who delivered before 40 weeks’ gestation.106,107 Zelop et al.
also compared the risk of uterine rupture in women who
delivered before and after 40 weeks’ gestation in spontane-
ous labour and induced labour.108 They reported that the
risk of uterine rupture in a TOL after Caesarean after 40
weeks’ gestation was not significantly increased when com-
pared with women who delivered before 40 weeks, whether
in spontaneous labour (1.0 % vs. 0.5%, P = 0.2, adjusted
OR, 2.1; 95% CI, 0.7–5.7) or after induction (2.6% vs.
2.1%, P = 0.7, adjusted OR, 1.1; 95% CI, 0.4–3.4).108
Recommendation
18. Postdatism is not a contraindication to a TOL after Cae-
sarean (II-2B).
FEBRUARY JOGC FÉVRIER 2005 l 171
SOGC CLINICAL PRACTICE GUIDELINES
One- Versus 2-Layer Closure of Low Transverse
Caesarean Section
In 1992 Hauth et al. published data comparing operative
time, endometritis, transfusion, and placement of extra
hemostatic sutures in women undergoing uterine closure in
1 layer compared with 2 layers.109 The only significant dif-
ference was in operative time: 44 minutes with 1-layer clo-
sure, compared to 48 minutes with 2-layer closure (P <
0.05).109 Ohel et al. published similar findings in 1996.110
The trend shifted in many centres toward single-layer
closure.
In 1997 Chapman et al. published a review of 145 women
who underwent a TOL after Caesarean after being random-
ized to either 1-layer or 2-layer closure in the previous Cae-
sarean section.111 They reported no significant difference in
the outcome of the next pregnancy.111 In a 2002 review of
2142 women who underwent a TOL after Caesarean,
Bujold et al. noted that a 1-layer interlocking closure was
associated with an increased risk of uterine rupture when
compared with a 2-layer closure (3.1% vs. 0.5%, P < 0.001;
OR, 3.95; 95% CI, 1.35–11.49).112 Further study in this area
is recommended.
Unknown Scar
All records available or obtainable describing the woman’s
previous Caesarean section should be reviewed. If unavail-
able, information about the circumstances of the Caesarean
section will help determine the likelihood of a vertical uter-
ine incision.113,114 Most unknown scars will be lower trans-
verse incisions (92%) and therefore at low risk for uterine
rupture.115 If the history suggests a reasonable likelihood of
a classical incision, it would be prudent to recommend a
repeat Caesarean section, but in settings where the history
indicates a high likelihood of lower transverse uterine inci-
sion and the woman wishes to proceed after counselling,
TOL after Caesarean is acceptable.115
Recommendation
19. Every effort should be made to obtain the previous
Caesarean operative report to determine the type of uterine
incision used. In situations where the scar is unknown,
information concerning the circumstances of the previous
delivery is helpful in determining the likelihood of a low
transverse incision. If the likelihood of a lower transverse
incision is high, TOL after Caesarean can be offered
(II-2B).
Other Factors
Factors such as maternal obesity,116 presence of postpartum
fever after Caesarean section,117 type of suture material,
müllerian duct anomalies,118 and maternal age119 and their
relation to the risk of uterine rupture have been examined in
small studies, but definitive conclusions cannot yet be
drawn.
172 l FEBRUARY JOGC FÉVRIER 2005
CONCLUSION
Trial of labour after Caesarean section should be considered
in women who have no contraindications after appropriate
discussion. The efficacy and safety of a TOL after Caesar-
ean in appropriately selected women about to give birth in a
hospital where timely Caesarean section facilities are avail-
able is well supported. Support of the woman in labour,
including close observation of herself and her fetus for
signs of complications, is recommended.
Augmentation of labour with oxytocin is safe. Induction of
labour may be provided when the indication for induction is
compelling and the risks have been fully discussed. The use
of prostaglandin E2 (dinoprostone) and prostaglandin E1
(misoprostol) in women planning a TOL is not recom-
mended. The use of a foley catheter for cervical ripening in
situations where the cervix is unfavourable is associated
with a lower chance of success but no increased risk of uter-
ine rupture.
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