Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Publication Date: February 23, 2020
Last Updated: November 8, 2022

Treatment

Recommendations 

Contraception

All RMD
In fertile women with RMD who have neither SLE nor positive aPL, we strongly recommend use of effective contraceptives (i.e., hormonal contraceptives or IUDs) over less effective options or no contraception. (Strong)
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Among effective methods, we conditionally recommend the highly effective IUDs or subdermal progestin implant (long-acting reversible contraceptives) because they have the lowest failure rates. (Conditional)
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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)
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SLE patients
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)
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and we conditionally recommend the highly effective IUDs or subdermal progestin implant because they have the lowest failure rates. (Conditional)
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We conditionally recommend against use of the transdermal estrogen-progestin patch in patients with SLE. (Conditional)
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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)
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Antiphospholipid antibody–positive patients
We strongly recommend against combined estrogen-progestin contraceptives in women with positive aPL because estrogen increases risk of thromboembolism. (Strong)
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We strongly recommend IUDs (levonorgestrel or copper) or the progestin-only pill in women with positive aPL. (Strong)
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Other special RMD situations
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)
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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)
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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)
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Assisted reproductive technology

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)
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SLE patients
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)
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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)
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Antiphospholipid antibody–positive patients
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)
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We conditionally recommend prophylactic anticoagulation therapy with heparin or low molecular weight heparin in asymptomatic aPL-positive patients during ART procedures. (Conditional)
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We strongly recommend prophylactic anticoagulation with heparin or LMWH in women with OB APS, (Strong)
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and we strongly recommend therapeutic anticoagulation in women with thrombotic APS, during ART procedures. (Strong)
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Embryo and oocyte cryopreservation
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)
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Fertility preservation with cyclophosphamide
Fertility preservation in women with RMD treated with CYC
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)
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Fertility preservation in men with RMD treated with CYC
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)
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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)
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Menopause and hormone replacement therapy

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)
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SLE patients
In SLE patients without positive aPL who desire HRT due to severe vasomotor symptoms and have no contraindications, we conditionally recommend HRT treatment. (Conditional)
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aPL-positive patients
In women with asymptomatic aPL, we conditionally recommend against treating with HRT. (Conditional)
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We strongly recommend against use of HRT in women with obstetric and/or thrombotic APS. (Strong)
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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)
(against)
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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)
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Pregnancy: general assessment, counseling, and management

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)
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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)
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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)
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We strongly recommend testing for anti-Ro/SSA and anti-La/SSB once before or early in pregnancy in women with SLE or SLE-like disorders, Sjögren’s syndrome, systemic sclerosis, and rheumatoid arthritis. (Strong)
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Given the relative persistence and unchanged titers of these antibodies, we strongly recommend against repeating the test during pregnancy. (Strong)
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Patients with scleroderma renal crisis
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)
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SLE patients
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)
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We recommend that all women with SLE take hydroxychloroquine (HCQ) during pregnancy if possible. If a patient is already taking HCQ, we strongly recommend continuing it during pregnancy. (Strong)
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If she is not taking HCQ, we conditionally recommend starting it if there is no contraindication. (Conditional)
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We conditionally recommend treating SLE patients with low-dose aspirin (81 or 100 mg daily), beginning in the first trimester. (Conditional)
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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)
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Antiphospholipid antibody–positive patients
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)
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We strongly recommend combined low-dose aspirin and prophylactic-dose heparin (usually LMWH) for patients meeting criteria for OB APS. (Strong)
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In women with OB APS, we further strongly recommend treating with prophylactic-dose anticoagulation for 6–12 weeks post partum. (Strong)
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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)
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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)
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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)
(against)
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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)
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We conditionally recommend the addition of HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy for patients with primary APS. (Conditional)
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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)
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Anti-Ro/SSA and/or anti-La/ SSB antibodies in pregnancy
In pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies but no history of an infant with CHB or NLE, we conditionally recommend serial fetal echocardiography (less frequent than weekly; interval not determined) starting between 16 and 18 weeks and continuing through week 26. (Conditional)
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For women with a prior infant with CHB or other NLE we conditionally recommend fetal echocardiography weekly, starting at week 16–18 and continuing through week 26. (Conditional)
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We conditionally recommend treating all women who are positive for anti-Ro/SSA and/or anti-La/SSB antibodies with HCQ during pregnancy. (Conditional)
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For pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies and fetal first- or second-degree heart block shown on echocardiography, we conditionally recommend treatment with oral dexamethasone 4 mg daily. (Conditional)
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If CHB ( without other cardiac inflammation) is present, we conditionally recommend against treating with dexamethasone. (Conditional)
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Medication use

Paternal medication use
We strongly recommend against use of CYC and thalidomide in men prior to attempting conception. (Strong)
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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)
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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)
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We conditionally recommend continuation of anakinra and rituximab based on limited data. (Conditional)
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Maternal medication use
As standard good practice, we suggest discussing medications well before the patient attempts to conceive. We also suggest discussing pregnancy plans prior to initiating treatment with medications that may affect gonadal function, such as CYC. (GPS)
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MTX, MMF, CYC, and thalidomide are known teratogens. We strongly recommend discontinuation of these within 3 months prior to conception. (Strong)
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For women treated with leflunomide, we strongly recommend cholestyramine washout if there are detectable serum levels of metabolite prior to or as soon as pregnancy is confirmed. (Strong)
Once metabolite is not detectable in the serum, the risks of pregnancy loss and birth defects are not elevated.
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We conditionally recommend treatment with CYC for life-threatening conditions in the second or third trimester. (Conditional)
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When potentially teratogenic medications are discontinued prior to pregnancy, we strongly recommend a period of observation without medication or transition to pregnancy- compatible medications to ensure disease stability (as discussed above). (Strong)
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In women with inadvertent exposure to teratogenic medications we strongly suggest immediate referral to a maternal-fetal medicine specialist, pregnancy medication specialist, or genetics counselor as standard good practice. (GPS)
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We strongly recommend HCQ, azathioprine/6-mercaptopurine, colchicine, and sulfasalazine, medications commonly used for RMD, as compatible for use throughout pregnancy. (Strong)
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We conditionally recommend calcineurin inhibitors (tacrolimus and cyclosporine) and NSAIDs as compatible for use during pregnancy. (Conditional)
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We conditionally recommend discontinuation of NSAIDs pre-conception if the patient is having difficulty conceiving (and if disease control would not be compromised), due to the possibility of NSAID-induced unruptured follicle syndrome, a cause of subfertility. (Conditional)
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We strongly recommend against use of NSAIDs in the third trimester because of the risk of premature closure of the ductus arteriosus. (Strong)
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We conditionally recommend nonselective NSAIDs over cyclooxygenase 2–specific inhibitors in the first 2 trimesters, due to lack of data on cyclooxygenase 2–specific inhibitors. (Conditional)
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We conditionally recommend continuing low-dose glucocorticoid treatment (≤10 mg daily of prednisone or nonfluorinated equivalent) during pregnancy if clinically indicated. (Conditional)
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We strongly recommend tapering higher doses of nonfluorinated glucocorticoids to <20 mg daily of prednisone, adding a pregnancy-compatible glucocorticoid-sparing agent if necessary. (Strong)
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Although there are only minimal data regarding prolonged treatment with low-dose glucocorticoids during pregnancy, we conditionally recommend against routine administration of stress-dose glucocorticoids at the time of vaginal delivery, but conditionally do recommend such treatment for surgical (cesarean) delivery. (Conditional)
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We conditionally recommend continuing tumor necrosis factor inhibitor therapy with infliximab, etanercept, adalimumab, or golimumab prior to and during pregnancy. The tumor necrosis factor inhibitor certolizumab does not contain an Fc chain and thus has minimal placental transfer. (Conditional)
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We strongly recommend continuation of certolizumab therapy prior to and during pregnancy. (Strong)
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We conditionally recommend continuing treatment with anakinra, belimumab, abatacept, tocilizumab, secukinumab, and ustekinumab while a woman is trying to conceive, but discontinuing once she is found to be pregnant. (Conditional)
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We conditionally recommend continuing treatment with rituximab while a woman is trying to conceive, and we conditionally recommend continuing rituximab during pregnancy if severe life- or organ-threatening maternal disease so warrants. (Conditional)
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Medication use during breastfeeding
We suggest as standard good practice that women with RMD be encouraged to breastfeed if they so desire and are able to do so. (GPS)
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In addition, we suggest that disease control be maintained with lactation-compatible medications and that individualized risks and benefits be reviewed with each patient. (Conditional)
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We strongly recommend treatment with HCQ, colchicine, sulfasalazine, rituximab, and all TNF inhibitors as compatible with breastfeeding. (Strong)
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We also recommend prednisone <20 mg daily (or equivalent nonfluorinated glucocorticoid) as compatible with breastfeeding, ()
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but strongly recommend that with doses of prednisone ≥20 mg a day (or equivalent), women delay breastfeeding or discard breast milk accumulated in the 4 hours following glucocorticoid administration. (Strong)
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We conditionally recommend treatment with azathioprine/6-mercaptopurine, calcineurin inhibitors, NSAIDs and the non–TNF inhibitor biologic agents (anakinra, rituximab, belimumab, abatacept, tocilizumab, secukinumab, and ustekinumab) as compatible with breastfeeding. (Conditional)
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We strongly recommend against use of CYC, leflunomide, MMF, and thalidomide while breastfeeding. (Strong)
(against)
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We conditionally recommend against use of MTX while breastfeeding. (Conditional)
(against)
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Table 1. Reproductive health care in patients with RMD: concise recommendation summarya 

Contraception

All RMD
Contraception/pregnancy discussion early and regularly: Choose contraception based on safety, efficacy, and patient preference. (GPS)
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Use barrier methods if unable to use other methods. (GPS)
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Use emergency contraception if necessary. [6] (Strong)
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Women receiving immunosuppressive medications: Use intrauterine device (IUD) if desired. [7] (Strong)
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Women at risk for osteoporosis: Avoid depot medroxyprogesterone acetate (DMPA). [10] (Conditional)
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Women receiving mycophenolate mofetil (MMF): Use IUD or 2 other methods together. [11] (Conditional)
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RMD without systemic lupus erythematosus (SLE) or antiphospholipid antibody (aPL): Use highly effective or effective methods.b [1] (Strong)
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Highly effective methods preferred to effective methods. [1A] (Conditional)
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SLE
SLE with negative aPL and low/stable disease activity: Use highly effective or effective methods.b [2] (Strong)
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Highly effective methods preferred to effective methods. [2A] (Conditional)
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Avoid transdermal estrogen-progestin patch. [2B] (Conditional)
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SLE with negative aPL and moderate-to-high disease activity: Use progestin-only contraceptives or IUD. [2] (Strong)
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Positive aPL 
Do not use combined estrogen-progestin contraceptives. [3] Use IUD or progestin-only pill. [4] (Strong)
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Assisted reproductive technology 

All RMD

Stable disease with assisted reproductive technology:

In vitro fertilization if pregnancy-compatible medications. [24] (Strong)
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Oocyte cryopreservation: Continue medications except cyclophosphamide (CYC). [28] (Strong)
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Active disease: Defer assisted reproductive technology until disease is stable/quiescent. [27] (Strong)
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SLE
Active SLE: Defer assisted reproductive technology until disease is stable/quiescent. [27] (Strong)
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For patients undergoing assisted reproductive technology, do not treat with prophylactic prednisone. [29] (Conditional)
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Positive aPL
For assisted reproductive technology in patients with asymptomatic aPL and no prior thromboses or history of obstetric antiphospholipid syndrome (OB APS), we conditionally recommend prophylactic heparin or low molecular weight heparin (LMWH). [25A] (Conditional)
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For assisted reproductive technology patients with no prior thromboses but a history of OB APS , we strongly recommend prophylactic heparin or LMWH. [25A2] (Strong)
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For assisted reproductive technology patients with prior thromboses, we strongly recommend therapeutic heparin or LMWH. [26A] (Strong)
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Fertility preservation
Women: Use gonadotropin-releasing hormone agonist therapy during IVCYC treatment. [31] (Conditional)
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Men: Sperm cryopreservation pre–CYC treatment. (GPS)
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Men: Do not use gonadotropin-releasing hormone agonist therapy during IVCYC treatment. [35] (Conditional)
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Menopause/hormone replacement therapy

All RMD
RMD without SLE or aPL: Treat with hormone replacement therapy if indicated.c (GPS)
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SLE
SLE and negative aPL: Treat with hormone replacement therapy if indicated.c [79] (Conditional)
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Positive aPL
If no prior thrombosis or OB APS: Do not treat with hormone replacement therapy. [80] (Conditional)
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If current titers negative, treat with hormone replacement therapy if indicated.c [83] (Conditional)
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If prior thrombosis or OB APS and not receiving anticoagulation treatment: Do not treat with hormone replacement therapy. [81] (Strong)
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If current titers negative, do not treat with hormone replacement therapy. [83A] (Conditional)
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If prior thrombosis or OB APS and receiving anticoagulation treatment: Do not treat with hormone replacement therapy. [82] (Conditional)
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Pregnancy

All RMD
Counseling: Outcomes improved with pregnancy planning, stable disease, compatible medications, and co-management by rheumatology and obstetrics-gynecology/maternal-fetal medicine. (GPS)
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Pre-pregnancy: Change to pregnancy-compatible medication and observe for stability. [42] (Strong)
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If active disease during pregnancy: Initiate pregnancy-compatible medication. [54] (Strong)
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If SLE or SLE-like disease, Sjögren’s syndrome (SS), systemic sclerosis (SSc), or rheumatoid arthritis (RA): Test once (early) for anti-Ro/SSA and anti-La/SSB. [60, 62] (Strong)
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If SSc and renal crisis during pregnancy: Treat with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for life-threatening disease. [55] (Strong)
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SLE
SLE or SLE-like disease: Test once (early) for aPL (anticardiolipin antibody [aCL], anti–β2-glycoprotein [anti-β2GPI], lupus anticoagulant [LAC]). [59, 61] (Strong)
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Continue hydroxychloroquine (HCQ) during pregnancy. [57] (Strong)
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If not taking HCQ, start HCQ during pregnancy if no contraindications. [58] (Conditional)
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Monitor laboratory values at least once per trimester. (GPS)
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Treat with low-dose aspirin starting in first trimester. [56] (Conditional)
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Positive aPL 
Positive aPL only: If no prior thrombosis or OB APS, treat with low-dose aspirin starting in first trimester. [45] (Conditional)
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Positive aPL only: Do not treat with combination prophylactic heparin or LMWH/low-dose aspirin. [46] (Conditional)
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Positive aPL only: Do not treat with HCQ. [44A] (Conditional)
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OB APS: If no thrombosis but meet OB APS criteria, treat with combination prophylactic heparin or LMWH/low-dose aspirin. [48] (Strong)
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OB-APS: Do not treat with combination therapeutic heparin or LMWH/low-dose aspirin. [49] (Conditional)
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OB-APS: Do not treat with addition of IV immunoglobulin (IVIG). [50] (Conditional)
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OB-APS: Do not treat with addition of prednisone. [51] (Strong)
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OB-APS: Treat with addition of HCQ for combination heparin/low-dose aspirin failure. [44B] (Conditional)
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OB-APS: Treat with prophylactic anticoagulation during post partum period. [84] (Strong)
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Thrombotic-APS: If prior thrombosis (meeting or not meeting OB APS criteria), treat with therapeutic heparin or LMWH/low-dose aspirin. [52] (Strong)
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Thrombotic-APS: Treat with addition of HCQ for therapeutic heparin or LMWH/low-dose aspirin therapy failure. [44B] (Conditional)
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Positive anti-Ro/SSA with or without anti-La/SSB
Treat with HCQ during pregnancy. [69, 70] (Conditional)
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If no prior history of neonatal lupus: Serial (interval uncertain) fetal echocardiography in weeks 16–26. [67] (Conditional)
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If prior history of neonatal lupus: Weekly fetal echocardiography in weeks 16–26. [68] (Conditional)
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Abnormal fetal echocardiography: If first-or second-degree heart block, treat with dexamethasone 4 mg daily. [71, 72] (Conditional)
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If isolated third-degree heart block (and no other cardiac inflammation), do not treat with dexamethasone. [73] (Conditional)
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Medication 

Paternal medication 
If planning to father a child: Discuss medication use including CYC. (GPS)
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Discontinue CYC and thalidomide. [133, 139] ()
Strong/Conditiional
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Continue HCQ, AZA, infliximab, etanercept, adalimumab, golimumab, certolizumab, colchicine. [90, 115, 143, 146, 149, 152, 155, 97] (Strong)
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Continue leflunomide, MMF, nonsteroidal anti-inflammatory drugs (NSAIDs), sulfasalazine, cyclosporine, tacrolimus, anakinra, rituximab. [108, 119, 85, 94, 126, 130, 159, 163] (Conditional)
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Maternal medication 
If planning pregnancy: Discuss medication use including CYC. (GPS)
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If pregnant and exposed to teratogenic medications: Discontinue immediately, pursue counseling. (GPS)
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Discontinue NSAIDs if difficulty conceiving. [86] (Conditional)
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Avoid NSAIDs in third trimester. [87] (Strong)
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Use nonselective rather than cyclooxygenase 2 (COX-2)–specific NSAIDs. [88] (Conditional)
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Discontinue methotrexate (MTX), MMF, thalidomide, CYC prior to conception. [102, 120, 140, 134] (Strong)
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Use CYC for life-threatening disease only in second and third trimester. [136] (Conditional)
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Discontinue leflunomide 24 months prior to conception or check serum metabolite levels and treat with cholestyramine washout. [109, 110] (Strong)
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Continue HCQ, sulfasalazine, azathioprine (AZA), colchicine. [91, 95, 116, 98] (Strong)
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Continue cyclosporine and tacrolimus. [127, 131] (Conditional)
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Continue certolizumab. [156] (Strong)
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Continue infliximab, etanercept, adalimumab, golimumab. [144, 147, 150, 153] (Conditional)
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Stop when pregnancy confirmed: rituximab, belimumab, anakinra, abatacept, tocilizumab, secukinumab, ustekinumab. [164, 169, 160, 173, 177, 181, 185] (Conditional)
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Use rituximab for organ-or life-threatening disease during pregnancy. [165] (Conditional)
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No recommendations for tofacitinib, baricitinib, apremilast due to lack of data. [189, 193, 197] ()
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Continue regular low-dose prednisone. [201] (Conditional)
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Taper high-dose prednisone with addition of pregnancy-compatible drug if needed. [202] (Strong)
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Stress-dose steroid at delivery. Do not treat for vaginal delivery. Do treat for cesarean delivery. [206, 207] (Conditional)
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Breastfeeding 
Encourage breastfeeding and maintain disease control with compatible medications if possible. (GPS)
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Compatible medications:
HCQ, infliximab, etanercept, adalimumab, golimumab, certolizumab, rituximab. [92, 143, 146, 149, 152, 155] (Strong)
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NSAIDs, sulfasalazine, colchicine, AZA, cyclosporine, tacrolimus, anakinra, belimumab, abatacept, tocilizumab, secukinumab, ustekinumab. [89, 96, 99, 117, 128, 132, 161, 170, 174, 178, 182, 186] (Conditional)
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Prednisone or nonfluorinated steroid equivalent <20 mg daily. [204] (Strong)
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For prednisone ≥20 mg daily, discard breast milk obtained within 4 hours following medication. [205] (Strong)
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Do not treat with leflunomide, MMF, CYC, thalidomide. [113, 124, 137, 142] (Strong)
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Do not treat with MTX. [106] (Conditional)
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a Recommendation numbers, shown in brackets, allow for cross-referencing with supplementary appendices. For more detailed/complete recommendations, see text or Supplementary Appendix 7 (on the ACR website at https://www.rheumatology.org/Practice-Quality/Clinical-Support/ Clinical-Practice-Guidelines/Reproductive-Health-in-Rheumatic-Diseases).

b Highly effective contraceptives are long-acting reversible contraceptives including progestin or copper intrauterine device (IUD) and progestin implant. Effective contraceptives are estrogen-progestin contraceptives (oral, patch, or vaginal ring) and progestin-only (oral, depot medroxyprogesterone acetate [DMPA]).

c General indication for hormone replacement therapy: Current recommendations suggest limiting hormone replacement therapy use in healthy postmenopausal women and using the lowest dose that alleviates symptoms for the minimum time necessary. Benefit-risk balance is most favorable for severe vasomotor symptoms in women <60 years old or within 10 years of menopause onset.

Table 3. Recommendations regarding medication use for men with rheumatic and musculoskeletal disease who are planning to father a child 

  • Azathioprine/6-mercaptopurine
  • Colchicine
  • Hydroxychloroquine
  • Tumor necrosis factor inhibitors (all)
(Strong)
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  • Anakinra
  • Cyclooxygenase 2 inhibitors
  • Cyclosporine
  • Leflunomide
  • Methotrexate
  • Mycophenolate mofetil
  • Mycophenolic acid
  • Nonsteroidal anti-inflammatory drugs
  • Rituximab
  • Sulfasalazine (semen analysis if delayed conception)
  • Tacrolimus
(Conditional)
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Cyclophosphamide (discontinue 12 weeks prior to attempted conception) (Strong)
Discontinue
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Thalidomide (discontinue 4 weeks prior to attempted conception) (Conditional)
Discontinue
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  • Abatacept
  • Apremilast
  • Baricitinib
  • Belimumab
  • Secukinumab
  • Tocilizumab
  • Tofacitinib
  • Ustekinumab
()
Unable to make a recommendation due to limited data.
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Recommendation Grading

Overview

Title

Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Authoring Organization

Publication Month/Year

February 23, 2020

Last Updated Month/Year

February 19, 2024

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To develop an evidence‐based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).

Inclusion Criteria

Female, Adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse midwife, nurse practitioner, physician, physician assistant

Scope

Management, Prevention

Diseases/Conditions (MeSH)

D060728 - Reproductive Health, D009140 - Musculoskeletal Diseases, D012216 - Rheumatic Diseases

Keywords

rheumatic diseases, Reproductive Health, Musculoskeletal Diseases, assisted reproductive technologies

Source Citation

Sammaritano, L.R., Bermas, B.L., Chakravarty, E.E., Chambers, C., Clowse, M.E.B., Lockshin, M.D., Marder, W., Guyatt, G., Branch, D.W., Buyon, J., Christopher‐Stine, L., Crow‐Hercher, R., Cush, J., Druzin, M., Kavanaugh, A., Laskin, C.A., Plante, L., Salmon, J., Simard, J., Somers, E.C., Steen, V., Tedeschi, S.K., Vinet, E., White, C.W., Yazdany, J., Barbhaiya, M., Bettendorf, B., Eudy, A., Jayatilleke, A., Shah, A.A., Sullivan, N., Tarter, L.L., Birru Talabi, M., Turgunbaev, M., Turner, A. and D'Anci, K.E. (2020), 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol, 72: 529-556. doi:10.1002/art.41191

Supplemental Methodology Resources

Data Supplement