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Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) predominately affect women, most of whom are in their childbearing years. In new guidelines published in July 2016 in the Annals the Rheumatic Diseases, multidisciplinary experts from an array of international universities provided evidence-based recommendations on managing reproductive issues and family planning in women who have SLE, APS, or both.
Noting that improvements in treatment and disease recognition warranted an updated examination of the evidence, the authors reached consensus on the following 12 issues:
1. Preconception counseling and risk stratification. Examples of major risk factors for adverse outcomes in SLE patients include active flaring and history of lupus nephritis, while some of the risk factors for APS patients include high-risk antiphospholipid antibodies (aPL) profile and coexisting SLE. Blood pressure should be monitored in both groups.
2. Contraceptive measures. All patients without gynecological contraindications may consider using an IUD. Those with stable/inactive SLE and negative aPL status could potentially use combined hormonal contraceptives. For patients with positive aPL, the risk of thrombosis due to hormonal contraception should be carefully considered.
3. Risk factors for reduced fertility. “Women with SLE who wish to plan a pregnancy should be counselled about fertility issues, especially the adverse outcomes associated with increasing age and the use of alkylating agents,” the authors wrote. The risk of ovarian dysfunction should also be considered if the use of such agents are considered.
4. Preservation of fertility. If menstruating women with SLE are going to take alkylating agents, they should be counseled about options for fertility preservation methods, particularly gonadotropin-releasing hormone (GnRH) analogues.
5. Assisted reproduction techniques. Techniques such as ovulation induction treatments and in vitro fertilisation protocols are considered safe for SLE patients with stable/inactive disease. “Patients with positive aPL/APS should receive anticoagulation (at the dosage as would be recommended during pregnancy) and/or low-dose aspirin,” according to the authors.
6. Predictive biomarkers for maternal disease activity in SLE pregnancy. Assessment of disease activity in these patients is recommended for monitoring disease flares and potential adverse pregnancy outcomes.
7. Pregnancy monitoring. Doppler ultrasonography and biometric parameters should be used to screen for small fetal size and placental insufficiency. If fetal dysrhythmia or myocarditis are suspected, fetal echocardiography is indicated.
8. Drugs for preventing and managing SLE flares during pregnancy. Drugs such as HCQ, oral glucocorticoids, azathioprine, cyclosporin A, and tacrolimus may be used for these purposes. Strategies such as glucocorticoids intravenous pulse therapy, intravenous immunoglobulin, and plasmapheresis may be used for moderate-to-severe flares. Drugs that should not be used include mycophenolic acid, cyclophosphamide, leflunomide, and methotrexate.
9. Adjunct treatment during pregnancy. For patients with SLE, the authors recommend the use of HCQ before and during pregnancy, and those with preeclampsia risk should use low-dose aspirin (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,” they said.
10. Menopause and HRT. While HRT may be used to address severe vasomotor menopausal manifestations in SLE patients with stable/inactive disease and negative aPL, the risk of thrombosis and cardiovascular disease should be carefully considered for patients with positive aPL.
11. Screening for malignancies. SLE and APS patients should be screened for malignancies. Women with SLE have an elevated risk of cervical premalignant lesions.
12. HPV vaccination. This can be considered for patients with SLE and/or APS and stable/inactive disease.
“Rheumatologists need to know that they have to approach the topic of family planning with their patients without losing too much time, since one of the worst enemies of pregnancy is age,” Angela Tincani, MD, an associate professor of rheumatology at the University of Brescia and one of the authors of the guidelines, told Rheumatology Advisor. “Doctors should explore treatment options with patients and, when possible, adapt the therapy to the patient’s wishes.”
Summary and Clinical Applicability
Most women with SLE and/or APS can have successful pregnancies, and risks can be reasonably managed with the use of careful planning.
The authors declare no competing interests.
Reference
Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2016; doi:10.1136/ annrheumdis-2016-209770.
