Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269

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Taiwanese Journal of Obstetrics & Gynecology

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Review Article

Systematic review: What is the best rst-line approach for cesarean

section ectopic pregnancy?
Mine Kanat-Pektas a, *, Serkan Bodur b, Ozgur Dundar c, Vuslat Lale Bakr d
a
Department of Obstetrics and Gynecology, Afyon Kocatepe University Medical Faculty Hospital, Afyonkarahisar, Turkey
b
Department of Obstetrics and Gynecology, Beytepe Military Hospital, Ankara, Turkey
c
Department of Obstetrics and Gynecology, Gulhane Military Academy of Medicine Haydarpasa Military Education Hospital, Istanbul, Turkey
d
Department of Obstetrics and Gynecology, Haseki Education and Research Hospital, Istanbul, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: This systematic review aims to analyze the case reports, case series, or clinical studies describing the
Accepted 30 March 2015 women with cesarean scar ectopic pregnancy (CSEP), and thus, to determine the efcacy and safety of
different primary treatment modalities in the management of CSEP.
Keywords: A thorough search of electronic databases showed that 274 articles on CSEP were published between
cesarean scar ectopic pregnancy January 1978 and April 2014.
ectopic pregnancy
Systemic methotrexate, uterine artery embolization, dilatation and curettage (D&C), hysterotomy, and
treatment
hysteroscopy were the most frequently adopted rst-line approaches. The success rates of systemic
methotrexate, uterine artery embolization, hysteroscopy, D&C, and hysterotomy were 8.7%, 18.3%, 39.1%,
61.6%, and 92.1%, respectively. The hysterectomy rates were 3.6%, 1.1%, 0.0%, 7.3%, and 1.7% in CSEP cases
that were treated by systemic methotrexate, uterine artery embolization, hysteroscopy, D&C, and hys-
terotomy, respectively. The ability to achieve a subsequent term pregnancy is related to successful sys-
temic methotrexate treatment (p 0.001) or hysterotomy (p 0.009). Future term pregnancy was
signicantly more frequent in the hysterotomy group (p 0.001).
Hysteroscopy and laparoscopic hysterotomy are safe and efcient surgical procedures that can be
adopted as primary treatment modalities for CSEP. Uterine artery embolization should be reserved for
cases with signicant bleeding and/or a high suspicion index for arteriovenous malformation. Systemic
methotrexate and D&C are not recommended as rst-line approaches for CSEP, as these procedures are
associated with high complication and hysterectomy rates.
Copyright 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This
is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
4.0/).

Introduction
Cesarean scar ectopic pregnancy (CSEP) refers to implantation of
pregnancy within the myometrial tissue that corresponds to the
site of prior hysterotomy. However, CSEP usually occurs as a late
complication of a previously performed cesarean section [1].
Up to date, caesarean scar pregnancy (CSEP) is considered as the
rarest form of the ectopic pregnancies. Although its exact incidence
is unknown, the incidence of CSEP has been estimated to be 1/3000
for the general obstetric population, 1/1800e1/2500 for all
* Corresponding author. Selcuklu Mah. Adnan Kahveci Cad., Number 16/2, D: 4,
Afyonkarahisar, Turkey.
E-mail address: minekanat@hotmail.com (M. Kanat-Pektas).
cesarean deliveries, and 1/531 for women who had at least one
cesarean delivery [2].
The diagnosis of CSEP is often difcult, and a false-negative
diagnosis may result in major complications such as severe hem-
orrhage, uterine rupture, and emergency hysterectomy. The
following criteria are required for the diagnosis of CSEP: (1) empty
uterus and empty cervical canal; (2) development of gestational sac
or placental tissue in the anterior wall of the cervical isthmus; (3)
discontinuity on the anterior uterine wall as demonstrated on a
sagittal plane of the uterus running through the amniotic sac; (4)
absent or diminished healthy myometrium between the bladder
and gestational sac/placental tissue; and (5) high velocity with low
impedance peritrophoblastic vascular ow clearly surrounding the
sac in Doppler examination [2,3].

http://dx.doi.org/10.1016/j.tjog.2015.03.009
1028-4559/Copyright 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
264 M. Kanat-Pektas et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269
Up to date, there is no standard treatment modality for CSEP.
Therapeutic options can be medical, surgical, or a combination of
both. Since there is a dramatic rise in the prevalence of cesarean
delivery, it is obvious that more women will be diagnosed with
CSEP in the near future. Therefore, a set of criteria should be
developed for the therapeutic options [3].
This systematic review aims to analyze the case reports, case
series, or clinical studies describing the women with CSEP, and thus,
to determine the efcacy and safety of different primary treatment
modalities in the management of CSEP. To the best of our knowl-
edge, the present review is the most extensive and comprehensive
account of rst-line approaches that have been adopted for the
treatment of CSEP cases.
Materials and methods
Literature search
In order to conduct the present meta-analysis, a detailed search
was conducted within the following electronic databases: CENTRAL
(in the Cochrane Library, current issue), PUBMED/MEDLINE (Silver
Platter, from January 1978 to April 2014), and EMBASE (from
January 1978 to April 2014). A search was initiated to acquire all the
related publications using the keyword cesarean section ectopic
pregnancy. After that, all free text MH exact subject headings and
MH exact subject heading terms were explored. Any new terms
found were fed into the search strategy so that new searches could
be run. After the relevant articles were identied and scanned,
reference lists of the relevant papers were scrutinized for further
studies. Besides, relevant articles were re-entered into PubMed (up
to April 2014), and using the related articles feature, a further
search was carried out. There was no language restriction so that
the papers in all languages were sought and translated. Full texts of
the identied articles were selected with nal inclusion or exclu-
sion decisions made after independent and duplicate examination
of the papers. This systematic review included the case reports,
case series, and clinical studies that reported on the diagnosis and
treatment of CSEP. The year 1978 was chosen as a starting point for
literature search because it was the year of the rst published
report on CSEP [4].
Study selection
A thorough search of electronic databases showed that 274 ar-
ticles were published between January 1978 and April 2014. All
included manuscripts were assessed by at least two reviewers
(M.K.P. and O.D.) for study and reporting quality using validated
tools. Disagreements were resolved by consensus or arbitration of a
third reviewer. By the abstract evaluation of those 274 articles, 243
articles were found to be associated with the diagnosis, presenta-
tion, and treatment of CSEP.
Whenever multiple/duplicate publications of the same data set
are noticed, only the most recent and/or complete study was
included. Multiple/duplicate publications (n 6) and articles pre-
senting insufcient data (n 8) were excluded. Similarly, reviews,
letters, comments, and editorials (n 35) were also eliminated.
Consequently, data about 1647 women with CSEP were retrieved
from 126 individual case reports, 45 case series, and 23 clinical
studies, which were included for nal analysis. The procedure for
study selection is summarized in Figure 1.
Data extraction
Data related to maternal age, gravidity, parity, the number of
prior cesarean deliveries, indication for previous cesarean delivery,
interval to prior cesarean delivery, gestational age, crownerump
length measurements, existence of embryonic/fetal cardiac activity,
serum concentration of beta-human chorionic gonadotropin (b-
HCG) at the time of admission, clinical symptoms, treatment mo-
dalities, resolution time, and future fertility were retrieved from the
original manuscript.
Limitation and bias
The major limitation of the study was the dependence on
nonstandardized knowledge gathered from anecdotal case reports
and series. The methods of b-HCG measurement, the methods of
crownerump length measurement, the quality of ultrasonography
equipment, and the experience or skillfulness of the sonographers
were not uniform and lacked standardization. Moreover, the rep-
resentation and reportage of data related to CSEP lacked constancy
and uniformity.
Statistical analysis
Collected data were analyzed by SPSS version 18.0 (SPSS Inc.,
Chicago, IL, USA). Continuous variables were expressed as
mean standard deviation or median, and categorical variables
were denoted as numbers or percentages where appropriate. Chi-
square test, ManneWhitney U test, and multiple logistic regres-
sion analysis were performed. A p values < 0.05 was considered to
be statistically signicant.
Results
Systemic methotrexate, uterine artery embolization, dilatation
and curettage (D&C), and hysteroscopy were the most frequently
adopted rst-line approaches for CSEP (Table 1).
Systemic methotrexate was successful in only 8.7% of the cases.
Secondary treatment was D&C, uterine artery embolization, hys-
teroscopy, and transvaginal sonography-guided intragestational
methotrexate injection in, respectively, 40.5%, 24.8%, 12.3%, and
11.6% of CSEP cases that underwent methotrexate treatment. Hys-
terectomy was indicated in 20 cases, corresponding to a rate of
3.6%. Higher parity, a higher number of prior cesarean deliveries,
lower gestational age, absence of bleeding and embryonic cardiac
activity, and longer duration of resolution were signicantly asso-
ciated with the success of systemic methotrexate (p 0.023,
p 0.018, p 0.001, p 0.002, p 0.029, and p 0.001, respec-
tively; Table 2).
The success rate of uterine artery embolization was only 18.3%.
Secondary treatment was D&C, transvaginal sonography-guided
intragestational methotrexate injection, hysteroscopy, and sys-
temic methotrexate in, respectively, 50.2%, 16.9%, 15.9%, and 14.2%
of CSEP cases that were primarily treated with uterine artery
embolization. Hysterectomy was required in four cases, yielding a
rate of 1.1%. Lower maternal age, lower gravidity, lower parity, a
higher number of prior cesarean deliveries, and longer duration of
resolution were signicantly associated with successful uterine
artery embolization (p 0.007, p 0.001, p 0.001, p 0.001, and
p 0.001, respectively; Table 3).
Hysteroscopic resection of gestational tissue was performed in
60 cases and hysteroscopic hysterotomy was performed in 36 cases.
By contrast, intragestational methotrexate injection was adminis-
tered in 12 cases, intragestational ethanol injection was adminis-
tered in one case, and gestational sac was aspirated following
intragestational methotrexate injection in one case. The success
rate of hysteroscopy was 39.1%, and 60.9% of the cases required
complementary treatment. Secondary treatment was systemic
mifepristone, systemic methotrexate, hysterotomy, and D&C in,
 M. Kanat-Pektas et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269 265

Potentially relevant citations identified from electronic searches to identify primary articles on

cesarean section ectopic pregnancy (n = 274)

Primary articles retrieved for detailed evaluation References excluded after screening

From electronic searches (n = 237) titles and abstracts (n = 31)

From reference lists (n = 6)

Articles excluded

-Multiple/duplicate publication (n = 6)

-Reviews/letters/comments/editorials (n = 35)

-Insufficient data to be included in systematic review (n = 8)

Primary articles included in systematic review (n = 194)

Case reports (n = 126)

Case series (n = 45)

Clinical studies (n = 23)

Figure 1. Literature search and study selection process for cesarean section ectopic pregnancy.

Table 1
Primary treatment modalities of cesarean section ectopic pregnancy.

Primary modality n (%)

Systemic methotrexate 559 (33.9)

Uterine artery embolization 361 (21.9)
Dilatation and curettage 232 (14.1)
Hysterotomy 174 (10.6)
Hysteroscopy 110 (6.7)
Hysteroscopic removal of gestational tissue 60
Hysteroscopic hysterotomy 36
Hysteroscopic intragestational methotrexate injection 12
Hysteroscopic intragestational ethanol injection 1
Hysteroscopic aspiration of gestational sac after intragestational methotrexate injection 1
Transvaginal sonography-guided gestational sac aspiration 61 (3.7)
Transabdominal sonography-guided local intragestational methotrexate injection 59 (3.6)
Transvaginal sonography-guided local intragestational methotrexate injection 50 (3.0)
Hysterectomy 25 (1.5)
Transvaginal sonography-guided local intragestational vasopressin injection 6 (0.4)
Transvaginal sonography-guided local intragestational KCl injection 6 (0.4)
Transabdominal sonography-guided local intragestational KCl injection 3 (0.2)
Bilateral hypogastric artery ligation 1 (0.1)
Total 1647 (100.0)
266 M. Kanat-Pektas et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269

Table 2
Cesarean section ectopic pregnancies primarily treated with systemic methotrexate.

Successful Unsuccessful p
(n 144) (n 415)

Maternal age (y) 33.3 3.5 33.1 4.3 0.670

Gravidity 3.6 1.6 3.4 1.4 0.310
Parity 2.0 1.5 1.5 1.0 0.023*
Prior cesarean delivery 1.5 0.8 1.2 0.5 0.018*
Time from prior cesarean delivery (mo) 5.8 3.4 5.4 4.0 0.556
Indication for cesarean delivery 0.016*
Cephalopelvic disproportion 0 (0.0) 8 (1.9)
Fetal distress 0 (0.0) 4 (1.0)
Bleeding 20 (13.9) 172 (41.4) 0.002*
Gestational age (wk) 7.2 1.1 7.8 1.3 0.001*
Crownerump length (mm) 13.3 1.2 12.3 5.5 0.768
Beta-HCG (IU/mL) 25,522.7 22,080.2 42,142.2 25,129.2 0.588
Fetal cardiac activity 5 (3.5) 64 (15.4) 0.029*
Resolution time (d) 60.1 18.9 39.2 31.7 0.001*
Future term pregnancy 17 (11.8) 6 (1.4) 0.001*

Data are presented as n (%) or mean standard deviation.

*p < 0.05 was accepted to be statistically signicant.
HCG human chorionic gonadotropin.

Table 3
Cesarean section ectopic pregnancies primarily treated with uterine artery embolization.

Successful Unsuccessful p
(n 66) (n 295)

Maternal age (y) 31.6 2.0 33.1 5.1 0.007*

Gravidity 3.0 0.3 3.7 1.4 0.001*
Parity 2.2 0.6 1.3 0.5 0.001*
Prior cesarean delivery 3.9 1.0 1.2 0.5 0.001*
Time from prior cesarean delivery (mo) 5.5 1.2 5.6 3.1 0.808
Bleeding 22 (33.3) 113 (38.3) 0.181
Gestational age (wk) 7.7 1.3 8.0 1.8 0.192
Beta-HCG (IU/mL) 33,409.9 5880.7 40,807.7 40,434.2 0.079
Resolution time (d) 58.5 4.3 35.0 20.5 0.001*
Future fertility
Term pregnancy 1 (1.5) 6 (2.0) 0.361
Miscarriage 0 (0.0) 9 (3.1) 0.001*

Data are presented as n (%) or mean standard deviation.

*p < 0.05 was accepted to be statistically signicant.
HCG human chorionic gonadotropin.

respectively, 53.7%, 26.9%, 16.4%, and 3.0% of CSEP cases that were The success rate of D&C was 61.6% in the CSEP cases. Secondary
primarily treated with hysteroscopy. However, no hysterectomy treatment was uterine artery embolization, systemic methotrexate,
was needed. Lower gravidity, lower parity, a higher number of prior hysterotomy, and intragestational vasopressin injection in,
cesarean deliveries, lower gestational age, and shorter duration of respectively, 60.7%, 10.1%, 6.7%, and 5.6% of CSEP cases that were
resolution were signicantly associated with successful hysteros- primarily treated with D&C. Hysterectomy was indicated in 17
copy (p 0.006, p 0.001, p 0.001, p 0.016, and p 0.001, cases, yielding a rate of 7.3%. Shorter time from prior cesarean de-
respectively; Table 4). livery, presence of embryonic cardiac activity, and absence of
symptoms were signicantly related with successful D&C
(p 0.031, p 0.044, and p 0.001, respectively; Table 5).
Table 4
Cesarean section ectopic pregnancies primarily treated with hysteroscopy. Hysterotomy was performed by laparoscopy (48.3%), laparot-
omy (44.8%), and transvaginal route (6.9%). Hysterotomy was suc-
Successful Unsuccessful p
cessful in 92.1% of the cases. Secondary treatment was D&C,
(n 43) (n 67)
systemic methotrexate, uterine artery embolization, and hysteros-
Maternal age (y) 32.2 3.3 30.4 3.9 0.124 copy in, respectively, 50%, 14.3%, 7.1%, and 7.1% of the cases who
Gravidity 2.4 0.5 3.3 0.8 0.006*
Parity 1.3 0.5 2.1 0.3 0.001*
underwent hysterotomy. Hysterectomy was performed in three
Prior cesarean delivery 1.3 0.4 3.6 1.1 0.001* cases, corresponding to a rate of 1.7%. No factors were signicantly
Bleeding 3 (7.0) 14 (20.9) 0.051 associated with successful hysterotomy (Table 6).
Gestational age (wk) 6.8 1.0 8.2 1.4 0.016* Table 7 compares the most frequently adopted rst-line ap-
Beta-HCG (IU/mL) 34,132.3 14,284.8 30,116.1 11,143.0 0.367
proaches for CSEP. Maternal age, gravidity, parity, and serum b-HCG
Fetal cardiac activity 8 (18.6) 2 (3.0) 0.398
Resolution time (d) 19.7 7.2 35.8 8.6 0.001* levels were signicantly higher in the hysterotomy group. The
Future term pregnancy 1 (2.3) 5 (7.5) 0.381 number of previous cesarean deliveries was signicantly higher
Data are presented as n (%) or mean standard deviation.
and the time from prior cesarean delivery was signicantly longer
*p < 0.05 was accepted to be statistically signicant. in the uterine artery embolization group. Bleeding and embryonic
HCG human chorionic gonadotropin. cardiac activity were signicantly more frequent, and gestational
 M. Kanat-Pektas et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269 267

Table 5
Cesarean section ectopic pregnancies primarily treated with dilatation and curettage.

Successful Unsuccessful p
(n 143) (n 89)

Maternal age (y) 33.9 3.9 33.1 4.5 0.253

Gravidity 4.0 1.2 4.2 1.4 0.467
Parity 1.9 0.9 1.6 0.8 0.067
Prior cesarean delivery 1.6 0.9 1.5 0.7 0.230
Time from prior cesarean delivery (mo) 3.7 2.3 5.8 3.0 0.031*
Indication for cesarean delivery 0.190
Cephalopelvic disproportion 0 (0.0) 2 (2.2)
Fetal distress 0 (0.0) 1 (1.1)
Asymptomatic 73 (51.0) 21 (23.6) 0.001*
Gestational age (wk) 8.4 4.0 8.0 1.5 0.408
Crownerump length (mm) 12.4 0.5 15.0 8.7 0.710
Beta-HCG (IU/mL) 32,105.6 24,443.3 25,684.8 25,169.9 0.270
Embryonic cardiac activity 18 (12.6) 7 (7.9) 0.044*
Resolution time (d) 46.3 26.9 37.2 17.6 0.451
Future fertility
Term pregnancy 5 (3.5) 3 (3.4) 0.256
Miscarriage 10 (7.0) 2 (2.2) 0.001*

Data are presented as n (%) or mean standard deviation.

*p < 0.05 was accepted to be statistically signicant.
HCG human chorionic gonadotropin.

Table 6
Cesarean section ectopic pregnancies primarily treated with hysterotomy.

Successful Unsuccessful p
(n 160) (n 14)

Maternal age (y) 34.4 3.2 34.1 6.2 0.855

Gravidity 3.8 1.6 4.2 1.5 0.437
Parity 2.0 0.9 1.9 0.7 0.577
Prior cesarean delivery 1.7 0.7 1.5 0.7 0.595
Time from prior cesarean delivery (mo) 5.5 2.7 3.5 2.1 0.318
Indication for cesarean delivery 0.609
Cephalopelvic disproportion 2 (1.3) 0 (0.0)
Breech presentation 2 (1.3) 0 (0.0)
Bleeding 44 (27.5) 2 (14.3) 0.443
Gestational age (wk) 7.9 1.8 8.5 2.3 0.294
Crownerump length (mm) 9.7 7.6 10.0 8.6 0.754
Beta-HCG (IU/mL) 60,754.8 60,092.1 47,722.6 39,599.4 0.303
Embryonic cardiac activity 24 (15.0) 9 (64.3) 0.358
Resolution time (d) 20.2 10.2 21.9 12.4 0.637
Future fertility
Term pregnancy 23 (14.4) 0 (0.0) 0.009*
Miscarriage 4 (2.5) 2 (14.3) 0.009*

Data are presented as n (%) or mean standard deviation.

*p < 0.05 was accepted to be statistically signicant.
HCG human chorionic gonadotropin.

Table 7
Comparison of most frequently adopted rst-line approaches for cesarean section ectopic pregnancy.

Hysterotomy (n 160) Systemic methotrexate (n 144) D&C (n 143) UAE (n 66) H/S (n 43) p

Maternal age (y) 34.4 3.2 33.3 3.5 33.9 3.9 31.6 2.0 32.2 3.3 0.001*
Gravidity 3.8 1.6 3.6 1.6 4.0 1.2 3.0 0.3 2.4 0.5 0.001*
Parity 2.0 0.9 2.0 1.5 1.9 0.9 2.2 0.6 1.3 0.5 0.001*
Prior C/S 1.7 0.7 1.5 0.8 1.6 0.9 3.9 1.0 1.3 0.4 0.001*
Time from prior C/S (mo) 5.5 2.7 5.8 3.4 3.7 2.3 5.5 1.2 d 0.001*
Indication for C/S 0.364
CPD 2 (1.3) 0 (0.0) 0 (0.0) d d
Fetal distress 2 (1.3) 0 (0.0) 0 (0.0) d d
Bleeding 44 (27.5) 20 (13.9) 73 (51.0) 22 (33.3) 3 (7.0) 0.001*
Gestational age (wk) 7.9 1.8 7.2 1.1 8.4 4.0 7.7 1.3 6.8 1.0 0.001*
CRL (mm) 9.7 7.6 13.3 1.2 12.4 0.5 d d 0.308
Beta-HCG (IU/mL) 60,754.8 60,092.1 25,522.7 22,080.2 32,105.6 24,443.3 33,409.9 5880.7 34,132.3 14,284.8 0.001*
Fetal cardiac activity 24 (15.0) 5 (3.5) 18 (12.6) d 8 (18.6) 0.001*
Resolution time (d) 20.2 10.2 60.1 18.9 46.3 26.9 58.5 4.3 19.7 7.2 0.001*
Future term pregnancy 23 (14.4) 17 (11.8) 5 (3.5) 1 (1.5) 1 (2.3) 0.001*

Data are presented as n (%) or mean standard deviation.

CPD cephalopelvic disproportion; CRL crownerump length; C/S cesarean section; D&C dilatation and curettage; H/S hysteroscopy; HCG human chorionic
gonadotropin; UAE uterine artery embolization.
*p < 0.05 was accepted to be statistically signicant.
268 M. Kanat-Pektas et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 263e269
age was signicantly higher in the D&C group. Future term preg-
nancy was signicantly more frequent in the hysterotomy group
(p 0.001 for each).
Discussion
In case of CSEP, successful births have been described with
expectant management, but the prognosis for an uneventful term
pregnancy is poor. The hysterectomy rates in these cases are
considerably high because of the increased risk of placenta previa/
accreta, uterine rupture, and related life-threatening massive
hemorrhage [5,6]. Therefore, termination of pregnancy in the rst
trimester is generally recommended. The treatment of CSEP should
aim at the prevention of massive blood loss and conservation of
uterus so that health status, life quality, and future fertility of
affected women should be maintained [6,7].
The incidence of CSEP has been substantially elevated, probably
owing to the increasing rate of caesarean deliveries and awareness
of this pathology. Despite this prominent increase, no universal
treatment guidelines have been established till now, and the
management of CSEP in daily clinical practice is still based on
anecdotal case reports and small series [8,9].
Initially, systemic methotrexate has been adopted as a rst-line
approach for the CSEP treatment [10]. At rst, the success rate of
systemic methotrexate was reported to range between 71% and
80%, with a hysterectomy rate of only 6% [11]. Later, it was
concluded that systemic methotrexate alone had a 62.1% compli-
cation rate [12]. This systematic review also showed that rst-line
systematic methotrexate was successful in only 8.7% of CSEP
cases, and hysterectomy rate was approximately 4%. However, the
ability to achieve a subsequent term pregnancy was found to be
related to successful systemic methotrexate treatment.
These ndings point out the inappropriateness of recommend-
ing systemic methotrexate as a rst-line approach for CSEP. The
reason is that it may take a long time before systemic methotrexate
exerts its effects on embryonic cardiac activity and placental
growth, and there is a possibility that these effects may never occur.
If this is the case, complementary treatment is aimed at a larger
gestational sac with an enriched vascularization. Wasting such
precious time may eventually result in with more severe compli-
cations that may harm the patients.
Uterine artery embolization was originally developed as a con-
servative treatment for postpartum hemorrhage, uterine leiomyo-
mas, and cervical pregnancy. Utilization of uterine artery
embolization in association with systemic or local administration of
methotrexate for the treatment of CSEP was reported in several
case series [13e16]. A recently published expert review stated that
uterine artery embolization alone had a complication rate of 80%,
and thus, uterine artery embolization should be used as a spare
method in uncomplicated cases of CSEP [12]. As for the present
review, complementary treatment was required in 82% of the CSEP
cases that were primarily treated with uterine artery embolization,
and the inability to maintain a subsequent pregnancy was associ-
ated with the failure of unsuccessful uterine artery. These ndings
suggest that the use of uterine artery embolization as a rst-line
approach should be limited to cases with signicant bleeding
and/or a high suspicion index for arteriovenous malformation.
Hysteroscopy allows direct visualization of the gestational sac
and coagulation of the related vascular texture at the implantation
site so that any profuse bleeding may be prevented. Other advan-
tages of this minimally invasive procedure over systemic metho-
trexate and uterine artery embolization are the avoidance of
toxicity, shorter duration of resolution, and rapid return to fertility.
However, the procedure requires general anesthesia, trained health
staff, and operative equipment [17e19].
The rst application of this minimally invasive procedure in the
treatment of CSEP was described by Wang et al [17]. Similar studies
have since reported encouraging data about the hysteroscopic
management of CSEP and claimed that this procedure offers less
blood loss, shorter postoperative hospital stay, and shorter reso-
lution time [18e23]. An expert review also designated hysteros-
copy as an optimal rst-line approach for CSEP with the lowest
complication rate (15.7%) [12]. Accordingly, this review showed
that hysteroscopy was successful in 39% of the reviewed CSEP cases,
and there was no need for hysterectomy.
Arslan et al [24] described the rst case of CSEP that was suc-
cessfully treated with D&C alone. Although the same technique failed
or caused complications in other case series [11,24e31], it was argued
that D&C could be performed under sonographic control if gesta-
tional age was < 7 weeks and myometrial thickness was > 3.5 mm
[23,24,31]. A recent review demonstrated that D&C alone had a
complication rate of 63% in the treatment of CSEP [32]. This sys-
tematic review showed that D&C was successful in 62% of cases, and
the hysterectomy rate was nearly 7%. Therefore, it would be rational
to avoid D&C as a rst-line approach, since it can lead to profuse
bleeding and complementary treatment procedures, requiring gen-
eral anesthesia, blood transfusion, and laparotomy. In addition, D&C
as a rst-line approach is associated with infertility and poor obstetric
outcome irrespective of whether it is successful or not.
Wedge excision of CSEP by hysterotomy is mandatory when
uterine rupture is conrmed or strongly suspected. This conven-
tional surgery allows complete removal of the CSEP and simulta-
neous repair of the myometrial scar, so that any probable
recurrence is hindered and the resolution time is shortened [6e9].
Yet, this approach results in larger surgical wounds, postoperative
adhesions, longer hospital stay, and longer recovery time, with a
possible higher risk of future placenta previa/accreta [33,34].
Laparoscopic wedge resection of CSEP is justied in hemodynam-
ically stable women who have deeply implanted gestational sacs
growing toward the abdominal cavity and bladder. Similar to hys-
teroscopy, this technique also requires general anesthesia, opera-
tive skills, and equipment. The rst case of CSEP managed with
laparoscopy was reported by Lee et al [35]. The following reports
suggest that laparoscopic evacuation of CSEP is a safe and less time-
consuming procedure [19,35e37].
An expert review also designated hysteroscopy as an optimal
rst-line approach for CSEP with a lower complication rate (20%)
[12]. This systematic review demonstrated that hysterotomy suc-
cessfully treated 92% of the reviewed CSEP cases, and hysterectomy
was required in only 2% of the cases. Moreover, the ability to ach-
ieve a subsequent term pregnancy was found to be related to
successful hysterotomy, whereas the inability to maintain a sub-
sequent pregnancy is associated with unsuccessful hysterotomy.
Hysteroscopy and laparoscopic hysterotomy appear as safe and
efcient surgical procedures that can be adopted as primary
treatment modalities for CSEP. Uterine artery embolization should
be reserved for CSEP cases with signicant bleeding and/or a high
suspicion index for arteriovenous malformation. Systemic metho-
trexate and D&C are not recommended as rst-line approaches for
CSEP, as these procedures are associated with high complication
rates and require hysterectomy.
Conicts of interest
The authors have no conicts of interest relevant to this article.
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