Focus on Sexual and Reproductive Health of Patients in Rheumatology

Decisions about parenthood among patients with rheumatic disease may be challenging due to reasons related to disease activity and the potential risks associated with pharmacologic treatments.¹

Previous research findings have shown that 31% to 62% of women with inflammatory arthritis discontinue treatment with disease-modifying antirheumatic drugs (DMARDs) during pregnancy or while breastfeeding. Although this may be an effective approach for some patients due to the potential association between DMARDs and fetotoxicity, discontinuation of medications for other patients, especially those with poorly controlled arthritis, may lead to adverse outcomes.²

These factors bring up a host of challenges for this patient population.

Patients with rheumatoid arthritis (RA) have also reported a lack of sufficient information to guide them on pregnancy planning, lactation, and early parenting.¹ Results of a qualitative survey to determine the preferences of women with rheumatic disease showed that patients wanted rheumatologists to play a more active role in the management of their sexual and reproductive health.³

Therefore, co-management with specialists, including obstetricians and gynecologists, and effective counseling strategies have been proposed to improve the reproductive health of women with rheumatic disease.⁴ In 2020, the American College of Rheumatology (ACR) also released guidelines for the management of reproductive health to enable a shared decision-making process between patient and provider on concerns related to reproductive health.⁵

In addition to the challenges that women with rheumatic disease and their providers have to address, experts fear that the Supreme Court’s potential overturn of Roe v Wade could negatively impact all aspects of reproductive health, not limited to abortions, but including fertility treatments as well.⁶

The overturning of Roe v Wade could pose a significant barrier for women in rheumatology. Research has shown an increased prevalence and impact of arthritis among certain racial and ethnic groups, including Black and Hispanic/Latinx. In the US, Black women have unintended pregnancies and maternal mortality at a higher rate than White women, making termination of pregnancies potentially unsafe. Experts urge that these disparities be addressed.⁷

In light of Arthritis Awareness and Women’s Health Month, Mehret Birru Talabi, MD, PhD, speaks to us about the importance of discussing reproductive health with patients with rheumatic disease. Dr Talabi is an assistant professor of medicine and associate program director of the Rheumatology Fellowship in the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh School of Medicine (UPMC), as well as assistant dean and co-director of Pittsburgh-Carnegie Mellon University Medical Science Training Program.

The immunopathologic mechanism of pregnancy in rheumatic disease has intrigued researchers for many decades. Based on available literature, can you describe the immune and inflammatory responses seen during pregnancy among patients with rheumatic disease?

Dr Talabi: In pregnancy, the immune system must adjust to accommodate a fetus that has a different genetic signature than the mother; otherwise, the maternal immune system could attack and destroy the fetus. This adaptation is critical in supporting the expansion of the human race.

The issue is that patients with rheumatic/autoimmune diseases have dysfunctional immune systems at baseline. During pregnancy, the immune system may naturally shift towards a dysfunctional pathway involved in some rheumatic diseases, leading to a potentiation of symptoms. We think this might be one of the reasons why some patients with systemic lupus erythematosus (SLE) may experience disease flares during pregnancy. In contrast, the immune system may shift away from dysfunctional pathways complicit in other rheumatic diseases, leading to an improvement of symptoms during pregnancy. We think this may explain why some patients with RA experience better disease control during pregnancy.

According to clinical observations, a large percentage of women with RA have reported improvements in their condition during pregnancy, reducing the need for extensive therapy.⁸ However, for those patients whose disease does not improve or enter remission, antirheumatic medications are required. Can you summarize the available therapeutic options for these patients?

Dr Talabi: We need to discuss medication management during pregnancy and lactation with patients with RA who are pregnant or contemplating pregnancy. Undertreated RA during pregnancy has been associated not only with physical [impact on] the pregnant person but also adverse neonatal outcomes, including preterm birth.⁹ I think it can be helpful for some patients to understand that “healthy babies” require “healthy moms.” And to be healthy, some pregnant people will need to use safe medications and therapies.

It may reassure patients to learn that many effective therapeutic options are safe to use during pregnancy and breastfeeding. For example, hydroxychloroquine, sulfasalazine, and tumor necrosis factor (TNF)-alpha inhibitors are safe to use during pregnancy and lactation. Therapy with TNF inhibitors can be continued through delivery if a patient has active disease. In fact, gastroenterology colleagues in my health care system routinely continue TNF therapy during delivery and lactation for pregnant patients with inflammatory bowel disease.

As rheumatologists, we can consider tapering TNF inhibitors during the third trimester, as the medication will pass to the fetus and could suppress the neonatal immune system; however, safety data suggest that discontinuation of TNF inhibitors is not required at any stage during pregnancy.⁵

I would favor limiting prednisone as much as possible as higher doses have been found to be detrimental to maternal and fetal health. NSAIDs can be used in the first trimester of pregnancy but should be avoided in the second and third trimesters of pregnancy. The US Food and Drug Administration (FDA)’s guidance [for women in] the second trimester is relatively new and based on some evidence that NSAID use can cause oligohydraminos at that stage of pregnancy.¹⁰ Acetaminophen remains safe to use in pregnancy at this point, although there are growing concerns about the safety profile of higher and regular doses of acetaminophen through pregnancy.

Speaking of shared decision-making, how can rheumatologists take a more active role in patients’ reproductive and sexual health? Can you also speak to the importance of patient education in this regard?

Dr Talabi: Rheumatologists acknowledge that sexual and reproductive health is important to address in the rheumatology context, but also describe some challenges to doing so in practice, including competing priorities, lack of access to updated information, inadequate care coordination with obstetrician-gynecologists, etc.

Some practical approaches to advancing sexual and reproductive health care in rheumatology might be through training opportunities for clinicians about pregnancy management, contraception, and safe medication use during pregnancy and lactation. Clinicians might also consider integrating prompts and reminders to address reproduction in their workflow through the electronic health record, for example, or intake forms that the patient completes in the waiting room prior to their visit. The ACR has developed a number of educational resources that are freely available to rheumatology clinicians.

An additional challenge is that we might consider pregnancy as a decision that must be made with consideration of a patient’s health status. Some patients do not consider pregnancy as a medical decision. And, as we all know, some patients will choose to become pregnant at times at which their diseases are active or they are at particularly high risk for adverse outcomes.

That is a reason why our research team advocates for a patient-centered family planning approach, which is framed by established concepts of reproductive autonomy and justice. Patient-centeredness requires open communication between the patient and rheumatologist about the patients’ reproductive goals and preferences. Ideally, the rheumatologist’s role is to explain the risks and benefits of various approaches in meaningful ways that people can understand. The patient is then able to make a well-informed decision that best aligns with what is important to them. Sometimes patients’ decisions will not be medically advisable. However, people do have a basic human right to reproduce or not to reproduce. People who don’t feel that their clinicians will support their decisions may understandably be reluctant to share their real preferences and intentions around reproduction.

While the emphasis of our interview has been about patients with childbearing potential, I’d also mention that patients who are men also have sexual and reproductive health needs. We also need more information about how to meaningfully integrate men’s reproductive health care within rheumatology clinical care.

The ACR recommends that women with rheumatic disease of reproductive age use effective contraception.⁵ However, use of contraception has been reported to be more complicated for patients with lupus or those with antiphospholipid (aPL) antibodies. So, how can rheumatologists counsel this subset of patients, especially those who are considering pregnancy?

Dr Talabi: Not all women with rheumatic diseases of reproductive age should [be advised to use effective contraception because some patients want to become pregnant.

Rheumatologists who have questions about the safety of contraception use in the context of rheumatic disease can review the ACR reproductive health guidelines, which includes evidence-based recommendations for the reproductive health care of patients with rheumatic diseases.⁵

People with aPL antibodies should ideally avoid estrogen-containing contraceptives because of the increased thrombotic risks associated with these methods. Some of the safest options for these patients include a copper intrauterine device (IUD), which is nonhormonal. The progestin-containing IUD, as well as the progestin-only pill, is another safe alternative. The [birth control] shot, which contains progestin and no estrogen may be associated with an increased risk for thrombosis,¹¹ so it is not an ideal method for patients with aPL antibodies at this time; although I’ll note that its safety has not been evaluated among patients with rheumatic diseases. We do not have much safety information about the subdermal implant, which is a highly effective progestin-based method of contraception.

Patients with well-controlled lupus who don’t have aPL antibodies can use hormones as well, including the estrogen-containing oral contraception pill and the estrogen-containing vaginal ring. The estrogen patch is not recommended right now as it appears to deliver a higher concentration of estrogen than the other forms of estrogen-containing contraception on the market, and has not yet been studied in patients with lupus.

Patients with lupus and moderate or high disease activity have great options for effective and safe contraception. From a safety perspective, we would show preference to methods that do not contain estrogen.

However, it’s worth noting that some patients do not only choose contraceptive options based on safety and efficacy and may have other preferences and priorities that affect their selection of a contraceptive method.

Please describe the multidisciplinary approach that is needed before, during, and after pregnancy. Research has shown that postpartum care is also important as disease flare may occur and disease activity may worsen during this period.¹²

Obstetrician-gynecologists are critical resources for us to help patients to prepare for pregnancy or safely experience pregnancy. While many of us would defer to the obstetrician-gynecologist when managing pregnancy, patients want us to be involved in their care and to advise on issues related to their diseases and medications.

In light of the possibility of the Roe v Wade case being overturned, would you be able to comment on how this could potentially affect patients in rheumatology?

Some of our patients seek elective pregnancy terminations because they became pregnant at a time when using an antirheumatic drug with teratogenic potential. If this option no longer exists for some patients, some of these pregnancies may culminate in neonatal deformities and/or neurodevelopmental disorders. It is painful to think about the distress that this may cause a patient and family. Rheumatologists need to carefully consider how we prescribe teratogens to patients with childbearing capacity. Some patients will not want to use effective contraception to prevent pregnancy for any number of reasons, including intolerance to the contraception, concern about an indwelling method, and desire for pregnancy, and we must consider whether or not it is worthwhile to prescribe potential teratogens to these patients.

In addition, rheumatologists routinely prescribe methotrexate, which is a highly effective medication for many patients with rheumatic diseases, but is also an abortifacient. As patients and providers seek options for pregnancy termination, we might see changes in the prescribing patterns and demand for methotrexate.

The demand to terminate pregnancy will not be ameliorated [if] Roe v Wade is overturned, rather we might see more desperate acts as people attempt to gain control over their reproductive lives.

References

1. Krause ML, Makol A. Management of rheumatoid arthritis during pregnancy: challenges and solutions. Open Access Rheumatol. 2016;8:23-36. doi:10.2147/OARRR.S85340

2. Talabi MB, Eudy AM, Jayasundara M, et al. Tough choices: exploring medication decision-making during pregnancy and lactation among women with inflammatory arthritis. ACR Open Rheumatol. Published online June 11, 2021. doi:10.1002/acr2.11240

3. Wolgemuth T, Stransky OM, Chodoff A, et al. Exploring the preferences of women regarding sexual and reproductive health care in the context of rheumatology: a qualitative study. Arthritis Care Res. 2021;73(8):1194-1200. doi:10.1002/acr.24249

4. Østensen M. Sexual and reproductive health in rheumatic disease. Nat Rev Rheumatol. 2017;13:485-493. doi:10.1038/nrrheum.2017.102

5. Sammaritano L, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529-556. doi:10.1002/art.41191

6. Kirkland T. Experts fear potential Roe v. Wade overturn will negatively impact IVF treatments. WPXI-TV. Published online May 5, 2022. Accessed online May 9, 2022. https://www.wpxi.com/news/local/experts-fear-potential-roe-v-wade-overturn-will-negatively-impact-ivf-treatments/HSPNCKWF5BGAFBWF3LPBXCZCPA/

7. The Lancet. Why Roe v. Wade must be defended. 2022;399(10338): P1845. doi:10.1016/S0140-6736(22)00870-4

8. Gerosa M, Schioppo T, Meroni PL. Challenges and treatment options for rheumatoid arthritis during pregnancy. Expert Opin Pharmacother. 2016;17(11):1539-1547. doi:10.1080/14656566.2016.1197204

9. Soh MC, Nelson-Piercy C. High-risk pregnancy and the rheumatologist. Rheumatology (Oxford). 2015;54(4):572-584. doi:10.1093/rheumatology/keu394

10.  US Food and Drug Administration. FDA recommends avoiding use of NSAIDs in pregnancy at 20 weeks or later because they can result in low amniotic fluid. Updated October 16, 2020. Accessed May 11, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic

11.  La Moigne E, Tromeur C, Delluc A, et al. Risk of recurrent venous thromboembolism on progestin-only contraception: a cohort study. Haematologica. 2016;101(1):e12-e14. doi:10.3324/haematol.2015.134882

12.  Davis-Porada J, Kim MY, Guerra MM, et al. Low frequency of flares during pregnancy and post-partum in stable lupus patients. Arth Res Ther. Published online March 2020. doi:10.1186/s13075-020-2139-9