Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

We strongly recommend discussing use of emergency contraception with all patients, including those with SLE or positive aPL, because risks of emergency contraception are low compared to those of unplanned pregnancy. (Strong)

In SLE patients with stable or low disease activity who are not positive for aPL, we strongly recommend use of effective contraceptives (i.e., hormonal contraceptives or IUDs) over less effective options or no contraception, (Strong)

and we conditionally recommend the highly effective IUDs or subdermal progestin implant because they have the lowest failure rates. (Conditional)

We conditionally recommend against use of the transdermal estrogen-progestin patch in patients with SLE. (Conditional)

We strongly recommend progestin-only or IUD contraceptives over combined estrogen-progestin contraception in SLE patients with moderate or severe disease activity, including nephritis, because estrogen-containing contraceptives have not been studied in SLE patients with moderate or severe disease activity. (Strong)

We strongly recommend against combined estrogen-progestin contraceptives in women with positive aPL because estrogen increases risk of thromboembolism. (Strong)

We strongly recommend IUDs (levonorgestrel or copper) or the progestin-only pill in women with positive aPL. (Strong)

Since IUDs are the most effective contraceptive options, we strongly recommend the IUD (copper or progestin) for women with RMD who are receiving immunosuppressive therapy, despite hypothetical infection risk. (Strong)

In women with RMD who are at increased risk for osteoporosis from glucocorticoid use or underlying disease, we conditionally recommend against using DMPA as a longterm contraceptive because data suggest that bone mineral density declines by up to 7.5% over 2 years of use in a healthy population. (Conditional)

We conditionally recommend that women with RMD taking mycophenolate mofetil/mycophenolic acid (MMF) use an IUD alone or 2 other methods of contraception together, because MMF may reduce serum estrogen and progesterone levels (in turn reducing the efficacy of oral contraceptives). (Conditional)

We strongly recommend proceeding with ART if needed in women with uncomplicated RMD who are receiving pregnancy-compatible medications, whose disease is stable/quiescent, and who are negative for aPL. (Strong)

We strongly recommend deferring ART procedures in patients with any RMD while disease is moderately or severely active. This recommendation is based on extrapolated evidence that RMD disease activity increases pregnancy risks. (Strong)

We conditionally recommend against an empiric dosage increase of prednisone during ART procedures in patients with SLE. Instead, we suggest monitoring the patient carefully and treating for flare if it occurs. (Conditional)

In subfertile patients with RMD who desire pregnancy, have stable/quiescent disease, and have asymptomatic positive aPL, OB APS, or treated thrombotic APS, we conditionally recommend ART with anticoagulation, as described below. (Conditional)

We conditionally recommend prophylactic anticoagulation therapy with heparin or low molecular weight heparin in asymptomatic aPL-positive patients during ART procedures. (Conditional)

We strongly recommend continuation of necessary immunosuppressive and/or biologic therapies (except CYC, which directly impacts maturing follicles) in treated patients whose condition is stable, when the purpose of ovarian stimulation is oocyte retrieval for oocyte or embryo cryopreservation. (Strong)

To prevent inducing primary ovarian insufficiency in premenopausal women with RMD receiving monthly intravenous CYC, we conditionally recommend monthly gonadotropin- releasing hormone agonist co-therapy. (Conditional)

We conditionally recommend against testosterone co-therapy in men with RMD receiving CYC, as it does not preserve fertility in men undergoing chemotherapy for malignancy. (Conditional)

Because sperm cryopreservation prior to treatment preserves a man’s ability to conceive a healthy child, we strongly suggest sperm cryopreservation as good practice for CYC-treated men who desire it. (Strong)

We strongly suggest as good practice the use of HRT in postmenopausal women with RMD without SLE or positive aPL who have severe vasomotor symptoms, have no contraindications, and desire treatment with HRT. (GPS)

In SLE patients without positive aPL who desire HRT due to severe vasomotor symptoms and have no contraindications, we conditionally recommend HRT treatment. (Conditional)

In women with asymptomatic aPL, we conditionally recommend against treating with HRT. (Conditional)

We strongly recommend against use of HRT in women with obstetric and/or thrombotic APS. (Strong)

We conditionally recommend against HRT use in patients with APS who are receiving anticoagulation treatment and in patients with APS who are currently negative for aPL. (Conditional)

We conditionally recommend consideration of HRT, if desired, in women who have a history of positive aPL but are currently testing negative for aPL and have no history of clinical APS. (Conditional)

As standard good practice, we strongly suggest counseling women with RMD who are considering pregnancy regarding the improved maternal and fetal outcomes (based on many studies) associated with entering pregnancy with quiescent/low activity disease. As additional good practice, we suggest maintaining concurrent care with specialists in obstetrics-gynecology, maternal-fetal medicine, neonatology, and other specialists as appropriate. (GPS)

In women with RMD planning pregnancy who are receiving medication that is incompatible with pregnancy, we strongly recommend switching to a pregnancy-compatible medication and observing for sufficient time to assess efficacy and tolerability of the new medication. (Strong)

In women with RMD who are currently pregnant and have active disease that requires medical therapy, we strongly recommend initiating or continuing a pregnancy-compatible steroid-sparing medication, as both active RMD and continuous high-dose glucocorticoid treatment have potential for maternal and fetal harm. (Strong)

We strongly recommend use of angiotensin-converting enzyme inhibitor or angiotensin receptor blockade therapy to treat active scleroderma renal crisis in pregnancy, because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy. (Strong)

In women with SLE who are considering pregnancy or are pregnant, we strongly recommend testing for LAC, aCL, and anti-β2GPI antibodies once before or early in pregnancy, and against repeating these tests during pregnancy. (Strong)

We conditionally recommend treating SLE patients with low-dose aspirin (81 or 100 mg daily), beginning in the first trimester. (Conditional)

Because active disease affects maternal and pregnancy outcome, we strongly suggest, as good practice, monitoring SLE disease activity with clinical history, examination, and laboratory tests at least once per trimester. (GPS)

In pregnant women with positive aPL who do not meet criteria for obstetric or thrombotic APS, we conditionally recommend treating with prophylactic aspirin, 81 or 100 mg daily, during pregnancy as preeclampsia prophylaxis. (Conditional)

We strongly recommend combined low-dose aspirin and prophylactic-dose heparin (usually LMWH) for patients meeting criteria for OB APS. (Strong)

In women with OB APS, we further strongly recommend treating with prophylactic-dose anticoagulation for 6–12 weeks post partum. (Strong)

In pregnant women with thrombotic APS, we strongly recommend treating with low-dose aspirin and therapeutic-dose heparin (usually LMWH) throughout pregnancy and post partum. (Strong)

We conditionally recommend against using the combination of prophylactic-dose heparin and low-dose aspirin therapy for patients with positive aPL who do not meet criteria for OB APS. (Conditional)

We conditionally recommend against treatment with intravenous immunoglobulin or an increased LMWH dose, as these have not been demonstrably helpful in cases of pregnancy loss despite standard therapy with low-dose aspirin and prophylactic heparin or LMWH. (Conditional)

We strongly recommend against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin in patients in whom standard therapy has been unsuccessful, since there are no controlled studies demonstrating a benefit. (Strong)

We conditionally recommend the addition of HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy for patients with primary APS. (Conditional)

In pregnant women with positive aPL who do not meet criteria for APS and do not have another indication for the drug (such as SLE), we conditionally recommend against treating with prophylactic HCQ. (Conditional)

We conditionally recommend treating all women who are positive for anti-Ro/SSA and/or anti-La/SSB antibodies with HCQ during pregnancy. (Conditional)

We strongly recommend against use of CYC and thalidomide in men prior to attempting conception. (Strong)

In men with RMD who are planning to father a pregnancy, we strongly recommend continuation of HCQ, azathioprine, 6-mercaptopurine, colchicine, and tumor necrosis factor inhibitors. (Strong)

In men with RMD who are planning to father a pregnancy, we conditionally recommend, based on a smaller body of evidence, continuing treatment with MTX, MMF, leflunomide, sulfasalazine, calcineurin inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs). (Conditional)

We conditionally recommend continuation of anakinra and rituximab based on limited data. (Conditional)