EULAR Recommendations on Reproductive Issues in Lupus and Anti-Phospholipid Syndrome Save

There is a significant unmet need with regard to counseling and managing SLE and APS patients who become pregnant or who may be planning for pregnancy. 

A multinational group of experts comprised a EULAR committee charged with making recommendations for women's health issues in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).

With the goal of developing an evidence-based approach, a systematic review of the evidence and a modified Delphi method was used to develop consensus and specific recommendations for women's health issues and family planning.

These recommendations have been published in the Annals of Rheumatic Disease. These are their key recommendations:

1. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes.
2. Preconception Counseling. SLE patients (with or without APS) have a 1-30% risk of prematurity, pre-eclampsia and eclampsia and the HELLP syndrome (hemolysis, Elevated Liver enzyme, Low Platelets). Hence family planning should be discussed as early as possible after diagnosis. Preconception counselling should also assess for risk factors for adverse maternal and fetal outcomes in pregnant women with SLE and/or APS.
3. Risk Stratification. Should include disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants).
4. Contraception. SLE/APS patients should be counselled about contraception, to prevent pregnancies during high disease activity or with the intake of teratogenic drugs. Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Safe alternatives include and IUD, combined estrogen plus progestin or progestin-only pill in inactive or stable active SLE and negative aPL. In women with positive aPL antibody or definite APS, contraception with combined hormones (oral pill, vaginal ring, transdermal patch) should be discouraged.
5. Subfertility. There is no clear concrete concrete evidence that the the disease decreases fertility. However, active disease, lupus nephritis, and immunosuppressive drugs may negatively impact fertility. Cyclophosphamide (CYC) may cause menstrual irregularities and premature ovarian failure (age- and dosage dependent).
6. Fertility Preservation. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents.
7. Assisted Reproduction. The efficacy and safety of ovulation induction therapy and in vitro fertilisation comes from observational studies, and appear to have pregnancy success rates comparable to the general population (up to 30%). These techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin.
8. Biomarkers for Maternal Disease during Pregnancy. Renal activity should be followed by quantifying urine protein excretion, urine sediment changes (hematuria, casts) and serum creatinine level/glomerular filtration rate. Usual lupus serological markers are useful in monitoring SLE activity and in the differentiation between disease exacerbation (declining serum C3/C4 levels (even within the normal range) and/or increasing anti-double stranded DNA titres) and pre-eclampsia. Serological activity during pregnancy may be associated with increased risk for fetal loss, intrauterine growth restriction and preterm birth
9. Pregnancy Monitoring. Fetal monitoring includes Doppler ultrasonography and fetal biometry, is indicated with fetal dysrhythmia and also in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. The cost-effectiveness of intensive surveillance with fetal echocardiography in patients with positive anti-Ro/SSA and anti-La/SSB antibodies and no previous child with congenital heart block remains to be established.
10. Prevention of Lupus Flares during Pregnancy. Good evidence favors the use of hydroxychloroquine (HCQ) during pregnancy to control disease activity and prevent flares. Uncontrolled studies suggest the potential valud of steriods, azathioprine, cyclosporin A and tacrolimus during pregnancy. CyC should be avoided in the first trimester. The protective role of low dose aspirin (LDA) against preterm and severe pre-eclampsia has been established in non-autoimmune patients and should be applied to lupus patients.
11. Menopause and HRT. Hormone replacement therapy (HRT) (estrogen plus progestin) in SLE has been shown to benefit vasomotor and other hypoestrogenism symptoms, without an increased risk of lupus exacerbations and no increased risk of thrombosis and cardiovascular events.
12. Cancer Screening. Should be the same as the general population. Lupus patients exposed to immunosuppressive drugs should be screened for cervical premalignant lesions.
13. HPV.  Human papillomavirus immunisation can be used in women with stable/inactive disease.

The full report can be read by clicking below.