Table 1

Recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS)

Statement/recommendationMean (SD)Median (IQR)
1. Preconception counselling and risk stratification
  • 1.1 In women with SLE, major risk factors for adverse maternal and fetal outcomes include active/flaring SLE (1/A), especially active nephritis (1/A), history of lupus nephritis (2/B) and presence of aPL/APS* (1/A).

  • 1.1.1 Blood pressure monitoring (2/B), use of safe medications to control disease activity (emphasis on HCQ (2/B)) and limiting glucocorticoids exposure (2/B) are essential measures.

  • 1.2 In women with APS (primary or SLE-APS), risk factors include high-risk aPL profile (lupus anticoagulant, multiple aPL, moderate to high titre aPL) (1/A), coexisting SLE (2/B), history of vascular/thrombotic APS (2/B) and of previous adverse pregnancy complications (2/B).

  • 1.2.1 Blood pressure monitoring (3/C) and use of antiplatelet and/or anticoagulant therapy (rated at statement 9) are of fundamental importance.

10 (0.2)10 (0)
2. Contraceptive measures
  • 2.1 Women with SLE should be counselled about the use of effective contraceptive measures (oral contraceptives, subcutaneous implants, IUD), based on their disease activity and thrombotic risk (particularly aPL status). IUD can be offered to all the patients with SLE and/or APS free of any gynaecological contraindication (1/A).

  • 2.2 In patients with stable/inactive SLE and negative aPL, combined hormonal contraceptives can be considered (1/A). In women with positive aPL with or without definite APS, hormonal contraception (with progesterone only) must be carefully weighed against the risk of thrombosis (2/B).

9.9 (0.4)10 (0)
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 (1/A). Treatment with alkylating agents should be balanced against the risk of ovarian dysfunction.

9.8 (0.4)10 (0)
4. Preservation of fertility
  •  Fertility preservation methods, especially GnRH analogues, should be considered for all menstruating women with SLE who are going to receive alkylating agents (2/B).

9.5 (0.7)10 (1)
5. Assisted reproduction techniques
  • 5.1 Assisted reproduction techniques, such as ovulation induction treatments and in vitro fertilisation protocols, can be safely used in patients with SLE with stable/inactive disease (3/C).

  • 5.2 Patients with positive aPL/APS should receive anticoagulation (at the dosage as would be recommended during pregnancy) and/or low-dose aspirin (3/D).

9.6 (0.6)10 (1)
6. Predictive biomarkers for maternal disease activity in SLE pregnancy
  •  In pregnant women with SLE, assessment of disease activity (1/A)—including renal function parameters (2/B) and serological markers (serum C3/C4, anti-dsDNA titres) (2/B)—is recommended to monitor for obstetrical adverse outcomes and disease flares.

9.9 (0.3)10 (0)
7. Pregnancy monitoring
  • 7.1 Women with SLE and/or APS should undergo supplementary fetal surveillance with Doppler ultrasonography and biometric parameters, particularly in the third trimester to screen for placental insufficiency and small for gestational age fetuses (3/D).

  • 7.2 Fetal echocardiography is recommended in cases of suspected fetal dysrhythmia or myocarditis, especially in patients with positive anti-Ro/SSA and/or anti-La/SSB antibodies (2/C)†.

9.7 (0.5)10 (1)
8. Drugs for the prevention and management of SLE flares during pregnancy
  • 8.1 HCQ (1/B), oral glucocorticoids, azathioprine, ciclosporin A and tacrolimus (all 3/C) can be used to prevent or manage SLE flares during pregnancy.

  • 8.2 Moderate-to-severe flares can be managed with additional strategies, including glucocorticoids intravenous pulse therapy, intravenous immunoglobulin and plasmapheresis (all 3/C).

  • 8.3 Mycophenolic acid, cyclophosphamide, leflunomide and methotrexate should be avoided.

9.7 (0.7)10 (0)
9. Adjunct treatment during pregnancy
  • 9.1 HCQ is recommended preconceptionally and throughout pregnancy for patients with SLE (2/B).

  • 9.2 Women with SLE at risk of pre-eclampsia (especially those with lupus nephritis or positive aPL) should receive LDA (2/C). 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 (1/A).

  • 9.3 Supplementation with calcium, vitamin D and folic acid should be offered as in the general population (–/D). Measuring blood vitamin D levels should be considered after pregnancy is confirmed (–/D).

9.8 (0.4)10 (0)
10. Menopause and HRT
  •  HRT can be used for the management of severe vasomotor menopausal manifestations in SLE women with stable/inactive disease and negative aPL (1/A). The use of HRT in patients with positive aPL should be carefully weighed against the risk of thrombosis and cardiovascular disease (–/D).

9.6 (0.6)10 (1)
11. Screening for malignancies
  •  Women with SLE and/or APS should undergo screening for malignancies similar to the general population (–/D). Women with SLE, especially those exposed to immunosuppressive drugs, are at higher risk of cervical premalignant lesions and should be monitored with vigilance (2/B).

9.8 (0.4)10 (0)
12. HPV vaccination
  •  HPV immunisation can be considered in women with SLE and/or APS and stable/inactive disease (3/D).

9.2 (1.6)10 (1)
  • For each statement or item, the LoE (range 1–3) and the GoR (range A–D) is given in parentheses (refer to online supplementary table S1). In the right-hand columns, the LoA among experts is reported as mean (SD) and median (IQR) values. A score of 10 represents the highest level of agreement.

  • *aPL and APS are defined according to the updated international consensus criteria.6 For aPL assays, please see the footnotes of table 2.

  • †The substatement on fetal echo in women with SLE/APS and positive anti-Ro/La is rated with LoE=2 (ie, sufficient evidence for the association between anti-Ro/La and congenital heart block) but GoR=C due to lack of strong evidence for the clinical implications of this association, namely for the efficacy of interventions.

  • anti-dsDNA, anti-double-stranded DNA antibodies; aPL, antiphospholipid antibodies; GnRH, gonadotropin-releasing hormone; GoR, grade of recommendation; HCQ, hydroxychloroquine; HPV, human papillomavirus; HRT, hormone replacement therapy; IUD, intrauterine devices; LDA, low-dose aspirin; LoA, level of agreement; LoE, level of evidence.