Fertility and Pregnancy in Systemic

Lupus Erythematosus

Dr. Mais Ajeel Jabbar

Produced by BMJ Publishing Group Ltd (& EULAR). 2016
Indian Journal of Rheumatology 2016
 Introduction
Systemic Lupus Erythematosus (SLE) is a chronic
multisystem autoimmune disease with a heterogeneous
pattern of clinical and serological manifestations. The
predilection for women, particularly of childbearing age,
combined with improved survival has led to increasing
numbers of women with lupus considering pregnancy.
Management of pregnancy in SLE however, requires
careful planning and close medical and obstetric
.monitoring to ensure optimal outcomes
:fertility rates in SLE
There is no evidence that the disease pe rse decreases
. Fertility
However ,Factors which may contribute to reduced fertility
:in lupus patients include
Age: Delays to allow for disease remission and drug washout
Menstrual disturbances :Associated with disease activity
Drugs: Direct effect on ovarian function (CYC) .the risk is
increased by patient age, cumulative CYC dose and with oral
compared with intermittent intravenous CYC. Other drugs
include: (COX)‑2 inhibitors that have been associated with
luteinized unruptured follicle syndrome
and high‑dose corticosteroids have been associated ,
with menstrual disturbances and reduced libido
 Renal failure : through hypothalamic‑pituitary
dysfunction, which manifests s a menstrual irregularity
and anovulatory cycles.
Antiphospholipid syndrome :Unproven link with
infertility
Psychosocial : fatigue and depression and subsequent
.loss of libido/sexual function in women
Fertility preservation

 Cryopreservation of ovarian tissue or embryos are

poorly investigated options and require specialised
.centres, which may not be easily accessible
 The most extensively studied method for POF
prevention in patients with SLE involves gonadotropin-
releasing hormone analogues (GnRH-a), with a good
safety and efficacy profile. It should be considered for all
menstruating women with SLE who are going to
.receive alkylating agents
Management of SLE during Pregnancy

• Clinical review
• Aim for disease remission for at
least 6 months
• Drugs - Ensure adequate washout
of teratogenic drugs
• • Antibodies - Check aPLs and anti-
Preconception Ro antibodies
• • Avoid pregnancy in patients with
severe pulmonary hypertension,
renal failure, previous history of
stroke in last 6 months
:Adverse fetal outcomes in obstetric SLE
include fetal loss (spontaneous abortion and intrauterine
fetal death), IUGR, premature birth, premature rupture of
.membranes, neonatal lupus, and perinatal mortality

: Maternal complications
include SLE activity, PE, and arterial hypertension,
especially in patients with renal involvement
Table Checklist of parameters to be considered for preconception
counselling and risk stratification in women with systemic lupus
erythematosus (SLE) and/or antiphospholipid syndrome (APS)

Prognostic implications Disease-related risk factors

Increased risk for (i) maternal SLE flares (in the last 6–12
disease during pregnancy and months or at conception)
puerperium (ii) hypertensive
complications (iii) fetal morbidity
and mortality (pregnancy loss, for
IUGR , for preterm delivery)
Strong predictor of poor Lupus nephritis (history or
maternal (for renal flare active at conception)
during/after pregnancy) and
fetal outcome(s) ( fetal loss
and preterm delivery)

Increased risk for maternal Serological (serum C3/C4,

SLE flares during anti-dsDNA titres) activity
pregnancy and pregnancy
loss
APS: increased risk for Previous adverse
pregnancy complications pregnancy outcome(s)

APS: increased risk for History of vascular

pregnancy morbidity thrombosis

APS: increased risk for SLE diagnosis

pregnancy morbidity
SLE: strong predictor of adverse maternal aPL profile
and fetal outcomes, especially for patients
with persistent moderate-to-high aPL titres,
LA and multiple aPL positivity (high-risk aPL
profile)APS: high-risk aPL profile correlates
with increased risk of maternal vascular
thrombotic events during pregnancy
(pre-)eclampsia , IUGR , preterm birth
Linked to development of Anti-Ro/SSA, anti-La/SSB
neonatal lupus, including a antibodies
low risk (0.7–2%) for CHB
(especially if moderate-to-
high anti-Ro titres); weak
association with other
pregnancy complications

End-stage organ damage

and associated
comorbidities
 General risk factors

Maternal age

Increased risk for pregnancy Arterial hypertension

loss , preterm birth and IUGR

Diabetes mellitus

Overweight/obesity
Thyroid disease

Nicotine and alcohol

use
 :Contraindications to pregnancy in SLE patients
severe pulmonary hypertension (estimated systolic -1
)PSAP > 50mmHg or symptomatic
advanced heart failure- 2
severe restrictive lung disease- 3
moderate/severe chronic renal failure (creatinine > -4
2,8mg/dL)
current use of cyclophosphamide,methotrexate - 5
.mycophenolate mofetil, leflunomide, statins and ACEI
active renal (24 hr urinary protein > 0.5 g) -6
CNS disease in the past 6 months or recent major - 7
.thrombosis (<2 years)
 • Dictated by disease activity and obstetric
complications
• Check BP, urine dip, full blood count,
renal/liver function, SLE biomarkers each
visit
• Drugs – using safe drugs in pregnancy.
Hydroxychloroquine recommended
throughout. All SLE patients on low dose
Pregnancy Aspirin. Patients with thrombotic APS switch
to Heparin at confirmed pregnancy. Check
BP Medication.
• Antibodies - If anti-Ro positive fetal cardiac
ultrasound scan at 16-20 gestation with
• repeat at 28 weeks if the initial 20-weeks
Predictive biomarkers for maternal disease activity in SLE:
Physicians should be aware of pregnancy physiological
:changes that can resemble SLE flare. These include
ESR rises by pregnancy itself, so it should not be used in -1
.pregnant women with SLE
Serum complement levels tend to increase during pregnancy - 2
. and its fall should be assessed relative to a baseline
thrombocytopenia may occur in about 10% of pregnant -3
women and it becomes difficult to distinguish from lupus
.activity
The urinary excretion of proteins, which normally rises during -4
pregnancy, can reach about 300mg/24 hours without having
physiological elevation of the GFR and - 5
consequent serum creatinine reduction, so values of
0.9mg/dL may suggest an underlying renal disease
.requiring further investigation
Lupus nephritis Preeclampsia Clinical and laboratory features

Any time during pregnancy After 20 weeks of gestation Hypertension

Low-normal Low-normal Platelets

Normal-low Rising titres Complements

Normal to raised Absent or unchanged Anti-dsDNA

Normal to raised Normal to raised Creatinine

Normal Elevated Serum uric acid

195mg/dL> 195mg/dL< hour urine calcium-24

Active Inactive Urinary sediment

Evidence of active nonrenal SLE Occasionally CNS or HELLP Other organs involved

yes No Response to steroids

Drugs for prevention and management of SLE flares
:during Pregnancy
HCQ had beneficial effects in controlling disease .1
.activity and preventing flare-ups during pregnancy
oral glucocorticoids, azathioprine, ciclosporin A and
tacrolimus can be used to prevent or manage SLE flares
.during pregnancy
Moderate-to-severe flares can be managed with . 2
additional strategies, including i.v glucocorticoids pulse
.therapy, i.v immunoglobulin and plasmapheresis
Mycophenolic acid, cyclophosphamide, leflunomide . 3
.and methotrexate should avoided
Adjunct treatment during pregnancy
HCQ is recommended preconceptionally and . 1
.throughout pregnancy for patients with SLE
Women with SLE at risk of pre-eclampsia (especially . 2
those with lupus nephritis or positive aPL) should receive
LDA .In women with SLE-associated APS or primary
APS, combination treatment with LDA and heparin is
recommended to decrease the risk of adverse pregnancy
.Outcomes
Supplementation with calcium, vitamin D and folic acid . 3
should be offered as in the general population.Measuring
blood vitamin D levels should be considered after
 • closely monitor for flare of lupus up to
4 months post-partum
• Drugs ensure compatibility with breast
feeding
Post partum • Antibodies - For thrombotic APS
patients - switch Heparin to Warfarin
Contraceptive measures
The three main types of contraceptives are barrier methods,
.(IUD), and hormonal methods
 Barrier methods are an effective, cheap method of preventing
pregnancy, and sexually transmitted disease. the unintended
pregnancy rate remains at around 17%.
 IUD are available in nonmedicated or medicated
(progesterone) forms.With typical use, the rate of unplanned
pregnancy is around 2%. Complications include irregular
bleeding after placement, the risk of expulsion and the risk of
infection after insertion that may lead to PID.
Progestin-only preparations are not associated with increased
:Recommendation
IUD can be offered to all the patients with SLE and/or . 1
.APS free of any gynaecological contraindication
In patients with stable/inactive SLE and negative aPL, . 2
combined hormonal contraceptives can be considered
.In women with positive aPL with or without definite APS,
hormonal contraception (with progesterone only) must be
carefully weighed against the risk of thrombosis
:Assisted reproduction techniques

Assisted reproduction techniques, such as ovulation . 1

induction treatments and in vitro fertilisation protocols,
can be safely used in patients with SLE with
.stable/inactive disease
Patients with positive aPL/APS should receive . 2
anticoagulation (at the dosage as would be
recommended during pregnancy) and/or low-dose
.Aspirin
Menopause and hormone replacement therapy
HRT should be reserved for the management of severe
and disabling vasomotor menopausal symptoms,
preferably in SLE women with stable/ inactive disease
.and negative aPL
In patients with positive aPL, the use of HRT should be
carefully weighed against thrombotic and cardiovascular
risks and recommend it for the shortest possible
.duration