Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases: ACR Guidelines

ATLANTA - The American College of Rheumatology (ACR) has published the 2020 Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. This is the first, evidence-based, clinical practise guideline related to the management of reproductive health issues for all patients with rheumatic diseases. With 131 recommendations, the guideline offers general precepts that provide a foundation for its recommendations and good practice statements. A draft of the guideline was presented during the 2018 ACR/ARP Annual Meeting in Chicago.

The treatment of rheumatic and musculoskeletal diseases presents some unique considerations for female patients considering becoming pregnant.

Women with rheumatic and musculoskeletal diseases have a higher risk of having pregnancy complications, such as gestational diabetes, preeclampsia, infection, preterm premature rupture of membranes, small for gestational age infants and preterm deliveries.

"This guideline is paramount because it is the first official guidance addressing the intersection of rheumatology and obstetrics and gynaecology (OB-GYN)," said Lisa Sammaritano, MD, lead author of the guideline. "Rheumatic diseases affect many younger individuals; however, little education has been provided to rheumatology professionals on current OB-GYN practices. The guideline [and more detailed online appendices] presents vital background knowledge and recommendations for addressing reproductive health issues in the full spectrum of rheumatology patients, with additional focus on specific diagnoses that require more detailed recommendations such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

The guideline provides 12 ungraded good practice statements and 131 graded recommendations that are intended to guide care for rheumatology patients except where indicated as being for patients with specific conditions or antibodies present. Good practice statements are those in which indirect evidence is compelling enough that a formal vote was considered unnecessary; these are ungraded and are presented as suggestions rather than formal recommendations. The recommendations were separated into six categories: contraception, assisted reproductive technology (fertility therapies), fertility preservation with gonadotoxic therapy, menopausal hormone replacement therapy, pregnancy assessment and management, and medication use.

While some of the recommendations are strong, many of the recommendations presented are conditional due to a lack of data. Pregnant women are not generally enrolled in clinical studies; and few maternal health studies focus on rheumatology patients. A few notable recommendations from each category include:

Contraception

• Strong recommendation for women with rheumatic disease who do not have lupus or APS to use effective contraceptives with a conditional recommendation to preferentially use highly effective IUDs or a subdermal progestin implant.
• Strong recommendation against using combined estrogen-progestin contraceptives in women who test positive for anti-phospholipid autoantibodies (aPL) or APS.

Assisted Reproductive Technology (Fertility Therapies)

• Strong recommendation for fertility therapy in women with uncomplicated rheumatic disease who are receiving pregnancy-compatible medications, whose disease is stable, and who test negative for aPL. Specific recommendations also address patients testing positive for aPL and suggest an anti-blood clotting procedure.
• Conditional recommendation against increasing prednisone dosage during fertility therapy procedures in lupus patients.

Fertility Preservation

• Conditional recommendation against testosterone co-therapy in men with rheumatic disease receiving cyclophosphamide (CYC) and a good practice suggestion to cryopreserve sperm before CYC treatment in men who desire it.
• Conditional recommendation for monthly gonadotropin-releasing hormone agonist co-therapy for premenopausal women with rheumatic disease who are receiving monthly CYC injections/infusions to prevent premature ovarian insufficiency.

Pregnancy Assessment and Management

• Strong good practice suggestion to counsel women with rheumatic disease, who are considering pregnancy, on the improved maternal and fetal outcomes associated with entering pregnancy during low disease activity.
• Conditional recommendation to treat lupus patients with low-dose aspirin daily (81 to 100 mg) starting in the first trimester. For women testing positive for aPL who do not meet the criteria for obstetric or thrombotic APS, it is conditionally recommended to preventatively treat with a daily aspirin (81 to 100 mg) starting early in pregnancy and continuing through delivery.

Menopause and Hormone Replacement Therapy

• A good practice suggestion to use hormone replacement therapy in postmenopausal women with rheumatic disease who do not have lupus or have a positive aPL test; and who have severe vasomotor symptoms, have no contraindications, and desire treatment.
• A conditional recommendation for hormone replacement therapy in women with lupus and without aPL.
• Conditionally recommend against treating with hormone replacement therapy for women with asymptomatic aPL, and strongly recommend against hormone replacement therapy for women with any form of APS.

Medication Use (Paternal and Maternal)

• Strongly recommend against use of CYC and thalidomide in men prior to attempting conception.
• Strong recommendation against the use of NSAIDs in the third trimester.

Individuals involved in the development of the new guideline included rheumatologists, obstetrician/gynecologists, reproductive medicine specialists, epidemiologists, and patients with rheumatic diseases. ACR guidelines are currently developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations that are largely based on the quality of the available evidence.

"This guideline should open avenues of communication between the rheumatologist and the patient, as well as between the rheumatologist and the OB-GYN," said Dr Sammaritano. "A better understanding of the risks and benefits of reproductive health options will enhance patient care by providing safe and effective contraception, improving pregnancy outcomes by conceiving during inactive disease periods, and allowing for continued control of rheumatic diseases during and after pregnancy with the use of well-suited medications."

Since that time, the guideline team has condensed the original three-part draft into a single, concise manuscript, with detailed background and discussion now available online. The guideline development team also incorporated colour-coded flow charts to highlight common decision-making points to make it user-Friendly.

The paper containing the full list of recommendations and supporting evidence is available at https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Reproductive-Health-in-Rheumatic-Diseases.