‘Ask often and without judgment’: Planning key to pregnancy success with rheumatic disease
A 32-year-old woman visiting your rheumatology clinic says she and her partner have decided the time is right for them to start a family.
Her systemic lupus erythematosus is under control. Her menstrual cycles are regular, but she previously had a miscarriage. She demonstrates positive antiphospholipid antibodies. She’s taking hydroxychloroquine and mycophenolate mofetil.
What is your advice?
Bringing a child into the world is a significant event. However, both rheumatic diseases and the medications used to treat them can pose risks to mother and baby alike.
“Pregnancy may carry greater risk to the mother, and may have more adverse fetal or neonatal outcomes, for women with rheumatology disorders,” Lisa R. Sammaritano, MD, director of the Rheumatology Reproductive Health Program of the Barbara Volcker Center, at the Hospital for Special Surgery, told Healio. “Risks depend on many factors, including the diagnosis, level of disease activity, presence of disease damage, medications and particular autoantibodies.”
Some drugs commonly used in rheumatology — such as cyclophosphamide, methotrexate and, in the above example, mycophenolate mofetil — are teratogenic, meaning they can lead to abnormal development of embryos and fetuses. This can result in birth defects, miscarriage and other adverse pregnancy events.
However, not all rheumatologists are equally comfortable asking patients about issues like sexual activity, use of contraception and plans to become pregnant. Some may not know what to do with their patients’ answers and avoid these topics entirely.
“The challenge is how to bridge this knowledge gap and topic unease with clinicians who are already pressed for time and have a long list of new things to learn,” Cuoghi Edens, MD, a rheumatologist at UChicago Medicine, said. “We don’t want to call out rheumatologists for not ‘doing enough.’”
What to know
Pregnancy is particularly important for rheumatologists because most diseases they treat are chronic, long-term conditions, many of which predominantly impact women or manifest worse outcomes in women, according to Sammaritano.
“As a result, rheumatologists follow many women throughout their reproductive lifespans,” she said.
Sammaritano is the lead author on the first-ever guidelines for managing reproductive health in rheumatic disease, published by the American College of Rheumatology in 2020. The guidelines contain 12 good practice statements and 131 recommendations on “areas of obstetrics and gynecology that rheumatologists might not otherwise see,” Sammaritano said.
“OB-GYNs, as well as rheumatologists, made up the guideline team,” she told Healio. “All worked hard to synthesize the current state of knowledge and practice to provide clear guidance.”
The key reproductive health messages for rheumatologists and their patients are the importance of planning and contraception, according to Sammaritano.
“Unplanned pregnancies may lead to disease flare during pregnancy or adverse pregnancy outcomes due to teratogenic medicine exposure,” she said. “Pregnancy outcomes are usually best when disease activity is quiet or at a low level for about 6 months prior to conception, and when the patient is on pregnancy-safe medications.”
The most effective first-line contraceptives are long-acting reversible options, such as intrauterine devices and arm implants, she added.
“They are safe for almost all rheumatic disease patients since they do not contain estrogen, which is contraindicated in patients with positive aPL antibodies due to risk of blood clotting,” Sammaritano said.
Breastfeeding also poses a risk that babies could be exposed to medications that are not safe for them to ingest. Hydroxychloroquine, colchicine, sulfasalazine, azathioprine, tacrolimus, TNF inhibitors and non-TNF biologic rheumatology medications are compatible with breastfeeding, according to the guidelines. Meanwhile, methotrexate, leflunomide, mycophenolate mofetil and mycophenolic acid, cyclophosphamide and thalidomide are not.
Still, the guidelines largely strike a positive tone, saying it is “standard good practice” to encourage breastfeeding among women with rheumatic diseases who wish to do so.
For men with rheumatic diseases, the main concerns are teratogenic drugs negatively impacting their fertility or potentially being present in their seminal fluid, though risks from the latter are “likely minimal,” according to the ACR guidelines.
The only medication “strongly” recommended to be stopped when planning to father a child is cyclophosphamide, which could entail “lasting effects” on sperm count and morphology, according to Sammaritano. Men should be counseled and offered the opportunity to have their sperm frozen before initiating cyclophosphamide, and it should be stopped 3 months before attempting to conceive, she added.
Sulfasalazine is “conditionally recommended” to be continued, though it could lower sperm counts and make conception more difficult.
Reproductive health care is not only for adults — it is important for children and young people, too. Gaps in this care were recently revealed in a study conducted at the Indiana University School of Medicine/Riley Hospital for Children and associated outreach clinics.
According to the survey results, only 62% of young patients with rheumatic diseases who are on teratogenic medications knew about their potential reproductive health harms. Among these patients, only 23% reported ever being counseled on pregnancy prevention, and 8% said they were counseled on emergency contraception.
“Most pregnancies in this age group are unplanned, meaning there isn’t time to have discussions about coming off a teratogenic medication first or to ensure that their disease is stable before becoming pregnant, which increases risks to both the fetus and to the pregnant person,” lead author Brittany M. Huynh, MD, MPH, told Healio. “Young people need to be armed with the information so they can apply it to their lives and changing circumstances.”
What to do
Becoming well-versed in reproductive health implications is yet one more task on the plate of a medical specialty already straining to address multi-systemic diseases and comorbidities amid a shrinking workforce.
“It’s hard to add additional competencies to a workforce that is increasingly reporting burnout,” said Mehret Birru Talabi, MD, PhD, director of the Women’s and Reproductive Health Rheumatology Clinic at the University of Pittsburgh Medical Center. “Rheumatologists rarely receive the training needed to contribute to the care of pregnant individuals or to provide contraception care — gaps in training that may precede rheumatology fellowships and sometimes reflect differences in medical school and residency training. We need to enhance women’s health training at all levels of the training pathway.”
The multidisciplinary approach taken in forming the ACR’s reproductive health guideline should likewise be applied to clinical care, according to Sammaritano.
“The best reproductive health care is collaborative care from both OB-GYN and rheumatology,” she said. “Patients require both kinds of expertise to navigate these areas of health that often impact each other.”
However, it may fall to a rheumatologist to initiate that collaboration — if it is possible at all. Research has revealed “reproductive health care deserts” in the United States where that kind of care could be out of reach, according to Birru Talabi.
“We just cannot assume that patients with systemic autoimmune and rheumatic diseases will have access to someone who will provide them with family planning care,” she said.
A rheumatologist should bring up reproductive health at a patient’s first visit and then “periodically,” especially when their medications or social situations change, Sammaritano said. She suggested using one key question: “Would you like to become pregnant in the next year?”
“If the answer is no, contraception should be reviewed with the patient, and highly effective, safe contraception suggested,” Sammaritano said. “If the answer is yes, pregnancy planning needs to be reviewed, including the importance of planning ahead of time, as well as the many factors that can influence the outcome. Not all pregnancy risk factors can be modified, but many can before pregnancy is attempted.”
Edens encouraged rheumatologists to “ask often and without judgment.”
“‘Have you thought about becoming pregnant in the last year?’ goes so much further than, ‘You don’t want to get pregnant, right?’ or ‘I hope you are taking your birth control pills,’” she said. “The authoritarian ‘you can’t get pregnant’ days are behind us. We have a savvy, engaged patient population who have easy access to many differing opinions if they don’t like ours, so we have to meet them halfway.”
Likewise, a patient’s safety may be their doctor’s top concern, but it may not always be the patient’s. Some may “want to pursue a high-risk pregnancy that has strong potential to end poorly,” according to Birru Talabi.
“My approach is not to try to convince people to avoid pregnancy, but to talk with them about the various risks, as well as the potential benefits, of a family planning decision,” she said. “Certainly, if the lines of communication are open and people do not feel that they have to hide their pregnancy intentions from me, I hope that I might better support them in pursuing even a high-risk pregnancy with as much support from me and other colleagues as possible.”
Aside from ACR’s guidelines, the organization also has online “tool kits” with PowerPoint presentations, handouts and guides on managing reproductive health in SLE and psoriatic arthritis. Duke University researchers have also developed HOP-STEP, a website with information about managing pregnancy in lupus, as well as ReproRheum, which is tailored to rheumatic diseases more generally.
‘A recipe for disaster’
Since the U.S. Supreme Court’s decision in 2022 to overturn Roe v. Wade — in Dobbs v. Jackson Women's Health Organization — abortion has been banned or restricted in 19 states.
With the legality of abortion no longer guaranteed, an important part of reproductive health for patients with rheumatic diseases is now cast in uncertainty.
“Pregnancy termination has been used in patients with rheumatic diseases not just for undesired pregnancies but, also, in some cases, in the setting of uncontrolled maternal disease activity or in pregnancies that occur while a person is using a teratogenic medication,” Birru Talabi said.
Pregnancy prevention becomes more crucial in states where abortion access is limited or off the table, Sammaritano added.
“Any restrictions in abortion — especially the most stringent ones — make patient education regarding use of highly effective contraception and emergency contraception, such as over-the-counter oral levonorgestrel even more important,” she said.
Since the Dobbs decision, there have been increases in birth control prescriptions and long-acting or permanent contraceptives, according to Edens. Rheumatologists felt the ripple effects, as well, with an early glimpse of their reaction reflected in a survey conducted by Edens, Birru Talabi and other researchers in November 2022, several months after the decision.
Half of all rheumatologists who responded to the survey had had at least one patient become pregnant while on a teratogen prior to Dobbs, and over a third had recommended terminating a pregnancy.
Among rheumatologists in states with abortion restrictions, 83.1% felt comfortable referring patients for abortion before the Dobbs decision. But afterward, only 34.8% were comfortable doing so without fear of reprisal.
Challenges with patients filling prescriptions for methotrexate, a teratogen, were reported by 23.2% of rheumatologists in abortion-restrictive states. Still, 89.9% of those rheumatologists responded that they had no plans to change the way they prescribe teratogens to reproductive-aged women.
According to Edens, the restrictions serve to highlight “the access that rheumatology patients need to this vital aspect of health care.”
“I’m apprehensive about what the future holds for the health care and wellbeing of women in the United States, but particularly those with rheumatic diseases,” said said, noting low rates of contraception counseling, pap smears, mammograms and other “well-woman care,” as well as other vulnerabilities.
“These issues are challenging enough on their own, but add in lack of access to reliable, effective contraceptives or emergency contraception, diminished social services and insurance coverage restrictions, and it’s a recipe for disaster,” Edens added.
Unanswered questions
Going forward, more can be learned about reproductive health in rheumatic disease by studying the patients who are impacted, rather than drawing conclusions from other populations.
Even ACR’s 2020 guidelines on reproductive health drew much of its backing evidence from research that was not specific to people with rheumatic diseases, according to Sammaritano.
“We had to extrapolate from data in the general population,” she said. “We need more data on safety and efficacy of contraception in our patient populations, better ways to predict and prevent adverse pregnancy outcomes and more information on fertility and fertility therapies in our patients.”
Birru Talabi agreed that more targeted research on pregnancy is needed.
“We have had explosive growth in therapies in rheumatology, but rarely study these medications in a robust way in pregnant populations,” she said. “This means that we do not have a strong evidence basis for the use of many newer therapies in pregnancy — and when pregnant women experience disease activity, we have relatively few effective treatments in our armamentarium as compared to what we might offer someone who isn’t pregnant. This also affects men who use anti-rheumatic drugs and wish to have a family.”
References:
Sammaritano LR, et al. Arthritis Rheumatol. 2020;doi:10.1002/art.41191.
Bermas BL, et al. Arthritis Rheumatol. 2023;doi:10.1002/art.42699.
Huynh B, et al. Pediatr Rheumatol. 2025;doi:10.1186/s12969-025-01056-9.
For more information:
Lisa Sammaritano, MD, can be reached at SammaritanoL@hss.edu.
Cuoghi Edens, MD, can be reached at cedens@bsd.uchicago.edu.
Mehret Birru Talabi, MD, PhD, can be reached at birrums@upmc.edu.
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