Lupus

http://lup.sagepub.com/

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza and MA Khamashta
Lupus 2008 17: 416
DOI: 10.1177/0961203308090027
The online version of this article can be found at:
http://lup.sagepub.com/content/17/5/416

Published by:
http://www.sagepublications.com

Additional services and information for Lupus can be found at:

Email Alerts: http://lup.sagepub.com/cgi/alerts
Subscriptions: http://lup.sagepub.com/subscriptions
Reprints: http://www.sagepub.com/journalsReprints.nav
Permissions: http://www.sagepub.com/journalsPermissions.nav
Citations: http://lup.sagepub.com/content/17/5/416.refs.html

>> Version of Record - May 19, 2008

What is This?

Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012

Lupus (2008) 17, 416420

http://lup.sagepub.com

REVIEW

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza1 and MA Khamashta2
1Service

and Department of Internal Medicine, Hospital De Cruces, University of The Basque Country, Bizkaia, Spain; and 2Lupus Research Unit,
The Rayne Institute, St Thomas Hospital, Kings College, London, UK

Pregnancy and systemic lupus erythematosus (SLE)

are closely related. Most patients with lupus are
young women with the possibility of getting pregnant
during the course of the disease. Mutual interactions
between lupus and pregnancy can occur. Patients with
SLE are at a higher risk for obstetric complications,
such as miscarriage and hypertensive disorders, and
drugs for the treatment of SLE can affect the foetus.
As a result, questions regarding pregnancy are usually formulated by women with lupus. We have chosen 10 frequent questions and tried to offer practical
answers.

tion rate is physiologically elevated during pregnancy.

Complement determinations are less useful during
pregnancy due to a natural increase of C3 and C4
levels.9 Activity scales specific for pregnancy, which
take into account these issues, have been
established.10 One of them, the Lupus Activity Index
in Pregnancy is actually validated, showing high sensitivity, specificity and predictive values for detecting
lupus flares during pregnancy.11 However, such scales
are meant for research purposes and physicians have
to take therapeutic decisions based on clinical
grounds.

How does pregnancy affect SLE?

How does SLE affect pregnancy?

Observational studies point to a higher degree of

lupus activity during pregnancy in unselected
populations.1,2 Flare rates are highest among those
women, who were active at conception.3
Flares are also more common in those women,
who stop taking hydroxychloroquine.4,5 Conversely,
women on prolonged remission are less likely to
experience an increase of lupus activity during
pregnancy.6,7 In fact, due to a better selection of
patients, recent series have found a low frequency of
flares.7 Most authors agree that flares are usually
mild and can occur any time during pregnancy and
the puerperium.8
Measuring lupus activity during pregnancy is not
straightforward. Common laboratory tests that are
useful in non-pregnant patients are less reliable during
pregnancy.9 Mild anaemia and thrombocytopenia are
common during this period, due to the expansion of
circulating volume.
Residual proteinuria in women with past lupus
nephritis can also rise as the glomerular filtration
increases during pregnancy. Erythrocyte sedimenta-

Lupus can adversely influence pregnancy in several

ways. Antiphospholipid antibodies (aPL) are the
main predictors of pregnancy complications in
patients with SLE, including miscarriage, foetal
death, prematurity and preeclampsia. Of note, not
all aPL confer the same risk, lupus anticoagulant
(LA) being the most strongly associated with
miscarriage.12 Disease activity has shown a clear association with foetal loss and prematurity.13,14 Renal
disease, past or present, can also affect the course of
pregnancy. In fact, women with severe renal
impairment (serum creatinine over 2.8 mg/dl) have a
chance lower than 30% of having a successful pregnancy,15 with a high risk of associated complications
such as hypertension or worsening of renal function.

Correspondence to: Munther A Khamashta, Research Unit, The Rayne

Institute, St Thomas Hospital, London SE1 7EH, UK.
Email: munther.khamashta@kcl.ac.uk

What makes lupus pregnancy high risk?

Not all women with SLE have the same risk of complications during pregnancy. Thus, pre-pregnancy
counselling is essential to estimate the chance of both
foetal and maternal problems (Table 1). High-risk
patients are shown in Table 2. A previous complicated
pregnancy is, by itself, an important adverse prognostic variable.16 Likewise, the presence of aPL is closely

2008 SAGE Publications Los Angeles, London, New Delhi and Singapore

Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012

10.1177/0961203308090027

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza and MA Khamashta

417

Table 1 Pre-pregnancy counselling

Assess for risk factors
Stratify high/low risk
Give realistic, evidence-based estimates for likely success
and chance of problems
Discuss prematurity and handicap
Advise against pregnancy if appropriate
Make and agree prospective plan of care

Table 2 High-risk lupus pregnancy

Previous poor obstetric history
Renal involvement
Cardiac involvement
Pulmonary hypertension
Interstitial lung disease
Active disease
High-dose steroid therapy
Antiphospholipid antibodies/syndrome
Extractable nuclear antigens (Ro, La)
Multiple pregnancy

associated with maternal thrombosis and embryofetal

demise.17,18 Maternal anti-Ro and anti-La antibodies
may cause congenital heart block in 2% of babies.19
This is fortunately a rare, but very serious condition,
with a high mortality rate and a high chance of permanent pacemaker for the baby.20 Chronic renal failure is also associated with other obstetric complications, such as hypertensive disorders and
miscarriage, which are more likely to occur if renal
impairment is more severe.15 Restrictive pulmonary
disease may also worsen during pregnancy due to
the thoracic compression by the growing uterus.
In some situations, the physicians should advise
against pregnancy (Table 3). Women with current or
recent lupus activity, particularly if affecting internal
organs, should avoid pregnancy. The same recommendation applies to women with APS and recent
thrombosis, particularly in the arterial bed.21
Women with severe kidney, lung or heart disease
should also be discouraged from getting pregnant
due to the high risk of maternal complications.22 Likewise, pregnancy should be considered absolutely contraindicated in women with symptomatic pulmonary
Table 3 Contraindications to pregnancy in women with SLE
Severe pulmonary hypertension (estimated systolic PAP >50 mm Hg
or symptomatic)
Restrictive lung disease (FVC <1 l)
Heart failure
Chronic renal failure (Cr >2.8 mg/dl)
Previous severe pre-eclampsia or HELLP despite therapy with aspirin
and heparin
Stroke within the previous 6 months
Severe lupus fare within the previous 6 months

PAP, pulmonary arterial pressure; FVC, forced vital capacity.

hypertension, which carries a higher than 30% maternal mortality during late pregnancy and the
puerperium.23,24

How to diagnose and treat lupus nephritis

in pregnancy?
A common challenge in lupus pregnancies is to differentiate preeclampsia from a nephritic SLE flare. In
fact, women with kidney disease are at a higher risk
for developing pregnancy-induced hypertension.25 In
the setting of proteinuria and hypertension occurring
after the second trimester, rising uric acid levels points
to toxaemia, whereas the presence of haematuria and/
or cellular casts are suggestive of active lupus. Moreover, extrarenal activity, rising anti-DNA antibody
levels and falling complement levels (even within normal limits for non-pregnant women, as pregnancy
increases C3 and C4 serum levels), point to lupus
nephritis.25,26 However, the differential diagnosis
may be extremely difficult and sometimes only pregnancy termination or the response to empirical treatment gives the final clue.
Treating a renal flare in a pregnant woman is a
difficult task. Both cyclophosphamide and mycophenolate are formally contraindicated during pregnancy
and should not be used unless the life of the mother is
in real danger.27 In such cases, a therapeutic termination of pregnancy is warranted. First-line therapies
during pregnancy include methyl-prednisolone pulses
and azathioprine.9 Both can control mild forms of
nephritis or help buy some time until the baby can
be safely delivered. In cases of proliferative forms,
full treatment with cyclophosphamide should be instituted as soon as pregnancy is completed.

What is the risk of preeclampsia

and how to prevent it?
The relationship between SLE and preeclampsia has
long been debated. A recent systematic review has
identified a previous history of preeclampsia (odds
ratio 7.19) and the presence of antiphospholipid syndrome (APS, odds ratio 9.72) as the two most powerful predictors of preeclampsia in the general
population.28 SLE in general, and the presence of
hypertension and/or renal disease in particular, are
also agreed by most authors to increase the risk for
preeclampsia.29
The usefulness of antiaggregant drugs to prevent
preeclampsia has been a subject of debate. However,
Lupus

Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza and MA Khamashta

418

a recent meta-analysis of individual patients data has

shown a small albeit consistent and statistically significant reduction in the risk of preeclampsia, preterm
delivery before 34 weeks and serious adverse outcomes among women taking low-dose aspirin or
dipyridamole.30 Figures for risk reduction were not
higher than 10% for all the final outcomes (preeclampsia, preterm <34 weeks, perinatal death, small baby,
any serious adverse outcome), however, in high-risk
populations the number needed to treat was estimated
to be between 40 and 60 patients. Thus, extrapolating
these data to SLE patients, treatment with aspirin during pregnancy would be indicated in women with aPL,
history of preeclampsia, hypertension and/or renal
disease.

How to manage SLE in pregnancy?

The ideal management of lupus patients during pregnancy should actually start before pregnancy occurs.
A preconceptional counselling visit is essential to estimate the risk profile of the patient (Table 1), to discuss
with her the potential complications and to establish
the appropriate management plan (Table 4). At that
time, the complete antibody profile of the patient
should be known, including aPL, both anticardiolipin
antibodies (aCL) and LA repeated ideally on separate
occasions, and anti-Ro/anti-La antibodies.25 Women
should ideally be in clinical remission for months, with
no recent thrombotic events and treated with drugs
that are known to be safe in pregnancy (Table 5). If
this is not the case, switching to allowed medications
(also for hypertension, if needed) and waiting for 2
3 months to ensure clinical remission is appropriate.
Hydroxychloroquine should not be discontinued
during pregnancy given its excellent safety profile
and the risk of flare after withdrawal.4 Ideally, predniTable 4 Management plan
Coordinated care by a medical-obstetric team with experience in
autoimmune diseases and high-risk pregnancies
Fully equipped neonatal unit
Full autoantibody profile available before pregnancy
Visits more frequent as pregnancy progresses
Blood pressure and urine dipstick on every visit
Uterine artery Doppler study at 20 weeks in patients with aPL, renal
disease, hypertension or history of preeclampsia. Repeat at 24 weeks if
abnormal
Umbilical artery Doppler study from 20 weeks, with frequency according
to medical and obstetric course, in women with aPL, renal disease,
active disease or previous complicated pregnancy
Foetal echocardiogram from 20th week in women with anti-Ro and/or
anti-La antibodies

aPL, antiphospholipid antibodies.

Table 5 Drugs in pregnancy and lactation (adapted from27)

NSAIDs
Antimalarials
Corticosteroids
Cyclosporine
Azathioprine
Mycophenolate
Methotrexate
Cyclophosphamide
Anti-TNF
Warfarin
Heparin
AAS (low dose)

Pregnancy

Lactation

Yes (avoid after 32 weeks)

Yes
Yes
Yes
Yes
No
No
No
No
No (with caution after first
trimester)
Yes
Yes

Yes
Yes
Yes
Yes?
Yes?
No
No
No
No
Yes
Yes
Yes

NSAIDs, non-steroidal anti-inflammatory drugs; AAS, aspirin.

sone dose should not exceed 7.5 mg/day to minimize

the chance of maternal adverse effects.
The clinical care of pregnant women with SLE
should be carried out in coordination by an obstetrician with experience in high-risk pregnancies and a
physician with experience in autoimmune diseases. It
is also important that a fully equipped neonatal unit is
available. Blood pressure and urine dipstick for proteinuria should be checked on every visit. Doppler
studies of the uterine and umbilical arteries may help
predict complications such as preeclampsia and foetal
distress and should be performed after 20 weeks,31,32
particularly in women with aPL, adverse obstetric history or renal disease. Likewise, specific ultrasound
studies of the foetal heart should be performed in
women with anti-Ro/anti-La antibodies between
weeks 20 and 30, to detect congenital heart block.
However, although intrauterine treatment with fluorinated steroids is frequently tried in such cases, they are
not effective in reverting established third degree heart
block.20 During the puerperium, lupus activity may
increase and all women should be closely monitored
during this period.2

How to treat pregnant women with lupus

and aPL?
The presence of aPL increases the risk for both maternal (thrombosis, preeclampsia) and foetal complications (early and late miscarriage, prematurity). Thus,
specific measures should be taken in women with aPL,
particularly those with APS (i.e. with previous thrombosis and/or obstetric complications), LA or high level
aCL. Therapy does not differ from that given to
women with primary APS. Low-dose aspirin should
be taken by all women with aPL, if possible before

Lupus
Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza and MA Khamashta

419

conception,33 to decrease the risk of miscarriage34 and

preeclampsia.30
Heparin at full antithrombotic doses is indicated in
women with previous thrombosis, in whom warfarin
is contraindicated during organogenesis.35 In patients
with previous poor obstetric history, there is agreement in treating with low-dose heparin those with foetal (late) deaths. On the other hand, some women suffering only early miscarriages do well with low-dose
aspirin alone.34 Drug therapy should, therefore, be
individualized and the different options discussed
with the patient. Adequate thromboprophylaxis is
essential in all women with aPL during 46 weeks
postpartum.35 Women receiving long-term heparin
should be given calcium and vitamin D to prevent
osteoporosis.

How to manage epidural anaesthesia in women

treated with antithrombotic drugs?
One of the important practical issues regarding the
care of pregnant women with SLE is whether those
taking aspirin and/or heparin can receive epidural
anaesthesia during delivery. Evidence is scarce and
the final decision mainly depends on the opinion of
the anaesthesiologist in charge of the patient.36 However, consensus guidelines on this issue do exist,37
recommending that in women receiving prophylactic
doses of low-molecular weight heparin (enoxaparin
40 mg/day or dalteparin 5000 IU/day) the time after
the last dose of heparin should be of at least 12 h
before performing a safe procedure. This period
increases to 24 h in case of higher doses of heparin,
whether given once or twice daily.

Is in vitro fertilization safe in lupus patients?

In vitro fertilization expose women to a high dose of
oestrogen over a short period of time. The main concerns of IVF in patients with SLE are the potential for
inducing disease flares and thrombosis. Published
data are limited to case reports and short, retrospective, case series.3840 In general, most patients did not
suffer major complications. However, longstanding
remission without any recent major organ involvement is recommended before receiving therapy for
IVF.38 Likewise, women with aPL should be considered at high risk for thrombosis and it seems prudent
to prescribe prophylactic heparin and aspirin during
the period of exposure to oestrogens.

Is breastfeeding safe?
Breastfeeding is considered as the best option for the
newborn baby and should be generally encouraged.
However, women with SLE are frequently receiving
therapy for their disease and there is concern regarding the effects of such medication on the baby. In general, the amount of any drug present in maternal milk
is very low. Some drugs are known to be safe for the
nursing baby, such as prednisone at doses below
20 mg/day, hydroxychloroquine, warfarin and
heparin.27 However, cyclophosphamide, methotrexate and mycophenolate mofetil are secreted in maternal milk in an amount sufficient to harm the baby,
thus they are considered incompatible with
nursing.27 There are some doubts regarding the safety
of azathioprine and cyclosporine. In women taking
these drugs, the decision of breastfeeding should be
discussed individually. Due to the lack of information
regarding their safety, biological drugs (anti-TNF
molecules, which are unlikely to be used in women
with SLE, and rituximab) are contra-indicated during
breastfeeding.27 Finally, it should be stressed that
breastfeeding is a major cause of negative calcium balance in the mother. Thus, nursing women at high risk
for osteoporosis (those with low baseline bone mineral
density, or taking long-term steroids or heparin)
should be treated with calcium 1000 mg and vitamin
D 800 IU daily.41

References
1 Petri, M, Howard, D, Repke, J. Frequency of lupus flare in pregnancy. The Hopkins Lupus Pregnancy Center experience. Arthritis
Rheum 1991; 34: 15381545.
2 Ruiz-Irastorza, G, Lima, F, Alves, J, et al. Increased rate of lupus
flare during pregnancy and the puerperium: a prospective study of
78 pregnancies. Br J Rheumatol 1996; 35: 133138.
3 Urowitz, MB, Gladman, DD, Farewell, VT, Stewart, J, McDonald,
J. Lupus and pregnancy studies. Arthritis Rheum 1993; 36: 13921397.
4 Clowse, ME, Magder, L, Witter, F, Petri, M. Hydroxychloroquine in
lupus pregnancy. Arthritis Rheum 2006; 54: 36403647.
5 Levy, RA, Vilela, VS, Cataldo, MJ, et al. Hydroxychloroquine in
lupus pregnancy: double-blind and placebo-controlled study. Lupus
2001; 10: 401404.
6 Le Thi Huong, D, Wechsler, B, Vauthier-Brouzes, D, et al. Outcome
of planned pregnancies in systemic lupus erythematosus: a prospective
study on 62 pregnancies. Br J Rheumatol 1997; 36: 772777.
7 Cortes-Hernandez, J, Ordi-Ros, J, Paredes, F, Casellas, M, Castillo,
F, Vilardell-Tarres, M. Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103
pregnancies. Rheumatology (Oxford) 2002; 41: 643650.
8 Khamashta, MA, Ruiz-Irastorza, G, Hughes, GRV. Systemic lupus
erythematosus flares during pregnancy. Rheum Dis Clin North Am
1997; 23: 1530.
9 Petri, M. The Hopkins Lupus Pregnancy Center: ten key issues in
management. Rheum Dis Clin N Am 2007; 33: 2735.
Lupus

Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012

Lupus and pregnancy: ten questions and some answers

G Ruiz-Irastorza and MA Khamashta

420
10 Buyon, JP, Kalunian, KC, Ramsey-Goldman, R, et al. Assessing disease activity in SLE patients during pregnancy. Lupus 1999; 8: 677
684.
11 Ruiz-Irastorza, G, Khamashta, MA, Gordon, C, et al. Measuring systemic lupus erythematosus activity during pregnancy: validation of
the lupus activity index in pregnancy scale. Arthritis Rheum 2004; 51:
7882.
12 Opatrny, L, David, M, Kahn, SR, et al. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol 2006; 33: 22142221.
13 Clowse, MEB, Magder, LS, Petri, M. The impact of increased lupus
activity on obstetric outcomes. Arthritis Rheum 2005; 52: 514521.
14 Georgiou, PE, Politi, EN, Katsimbri, P, Sakka, V, Drosos, AA. Outcome of lupus pregnancy: a controlled study. Rheumatology (Oxford)
2000; 39: 10141019.
15 Germain, S, Nelson-Piercy, C. Lupus nephritis and renal disease in
pregnancy. Lupus 2006; 15: 148155.
16 Lima, F, Khamashta, MA, Buchanan, NMM, Kerslake, S, Hunt, BJ,
Hughes, GRV. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 1996; 14: 131136.
17 Ramsey-Goldman, R, Kutzer, JE, Kuller, LH, Guzick, D, Carpenter,
AB, Medsger, TA. Pregnancy outcome and anti-cardiolipin antibody
in women with systemic lupus erythematosus. Am J Epidemiol 1993;
138; 10571069.
18 Branch, DW, Khamashta, MA. Antiphospholipid syndrome: obstetric diagnosis, management and controversies. Obstet Gynecol 2003;
101: 13331344.
19 Brucato, A, Frassi, M, Franceschini, F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies
detected by counterimmunoelectrophoresis: a prospective study of 100
women. Arthritis Rheum 2001; 44: 18321835.
20 Izmirly, PM, Rivera, TL, Buyon, JP. Neonatal lupus syndromes.
Rheum Dis Clin N Am 2007; 33: 267285.
21 Cuadrado, MJ, Mendona, LLF, Khamashta, MA, et al. Maternal
and fetal outcome in antiphospholipid syndrome pregnancies with a
history of previous cerebral ischemia. Arthritis Rheum 1999; 42: S265.
22 Ruiz-Irastorza, G, Khamashta, MA, Hughes, GRV. Heart disease,
pregnancy and systemic autoimmune diseases. In: Oakley, C,
Warnes, CA, (eds), Heart disease in pregnancy, second edition.
Blackwell publishing; 2007. p. 136150. Oxford, UK.
23 Bonnin, M, Mercier, FJ, Sitbon, O, et al. Severe pulmonary hypertension during pregnancy. Mode of delivery and anesthetic management
of 15 consecutive cases. Anesthesiology 2005; 102: 11331137.
24 McMillan, E, Martin, WL, Waugh, J, et al. Management of pregnancy in women with pulmonary hypertension secondary to SLE and
anti-phospholipid syndrome. Lupus 2002; 11: 392398.
25 Mackillop, LH, Germain, SJ, Nelson-Piercy, C. Systemic lupus
erythematosus. Br Med J 2007; 335: 933936.
26 Ruiz-Irastorza, G, Khamashta, MA, Nelson-Piercy, C, Hughes,
GRV. Effects of lupus and antiphospholipid syndrome on pregnancy.
Yearb Obstet Gynaecol 2002; 10: 105119.

27 Ostensen, M, Khamashta, M, Lockshin, M, et al. Anti-inflammatory

and immunosuppressive drugs and reproduction. Arthritis Res Ther
2006; 8: 209227.
28 Milne, F, Redman, C, Walker, J, et al. The pre-eclampsia community
guideline (PRECOG): how to screen for and detect onset of preeclampsia in the community. Br Med J 2005; 330: 576580.
29 Clowse, M. Lupus activity in pregnancy. Rheum Dis Clin N Am 2007;
33: 237252.
30 Askie, LM, Duley, L, Henderson-Smart, DJ, Stewart, LA. on behalf
of the PARIS Collaborative Group. Antiplatelet agents for prevention
of pre-eclampsia: a meta-analysis of individual patient data. Lancet
2007; 369: 17911980.
31 Papageorghiou, AT, Roberts, N. Uterine artery Doppler screening for
adverse pregnancy outcome. Curr Opin Obstet Gynecol 2005; 17: 584
590.
32 Le Thi Huong, D, Wechsler, B, Vauthier-Brouzes, D, et al. The second trimester Doppler ultrasound examination is the best predictor of
late pregnancy outcome in systemic lupus erythematosus and/or the
antiphospholipid syndrome. Rheumatology (Oxford) 2006; 45: 332
338.
33 Carmona, F, Font, J, Cervera, R, Muoz, F, Cararach, V, Balasch, J.
Obstetrical outcome of pregnancy in patients with systemic lupus
erythematosus. A study of 60 cases. Eur J Obstet Gynecol Reprod
Biol 1999; 83: 137142.
34 Ruiz-Irastorza, G, Khamashta, MA, Hughes, GRV. Treatment of
pregnancy loss in Hughes syndrome: a critical update. Autoimmun
Rev 2002; 1: 298304.
35 Ruiz-Irastorza, G, Khamashta, MA. Management of thrombosis in
antiphospholipid syndrome and systemic lupus erythematosus in pregnancy. Ann N Y Acad Sci 2005; 1051: 606612.
36 Wetzl, RG. Anesthesiological aspects of pregnancy in patients with
rheumatic diseases. Lupus 2004; 13: 699702.
37 Horlocker, TT, Wedel, DJ, Benzon, H, et al. Regional anesthesia in
the anticoagulated patient: defining the risks (the Second ASRA Consensus Conference on Neuraxial Anesthesia and anticoagulation). Reg
Anesth Pain Med 2003; 28: 172197.
38 Le Thi Huong, D, Wechsler, B, Vauthier-Brouzes, D, et al. Importance of planning ovulation induction therapy in systemic lupus
erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles. Semin Arthritis Rheum 2002;
32: 174-188.
39 Guballa, N, Sammaritano, L, Schwartzman, S, Buyon, J, Lockshin,
MD. Ovulation induction and in vitro fertilization in systemic lupus
erythematosus and antiphospholipid syndrome. Arthritis Rheum 2000;
43: 550556.
40 Lockshin, MD. Autoimmunity, infertility and assisted reproductive
technologies. Lupus. 2004; 13: 669672.
41 Ruiz-Irastorza, G, Khamashta, MA, Nelson-Piercy, C, Hughes,
GRV. Lupus pregnancy: is heparin a risk factor for osteoporosis?
Lupus 2001; 10: 597600.

Lupus
Downloaded from lup.sagepub.com at BROWN UNIVERSITY on November 24, 2012