Patients living with rheumatic diseases often experience substantial challenges due to their illness and its associated comorbidities, as well as the effects of treatment.1 For many women with rheumatic diseases, there are also important considerations pertaining to various aspects of reproductive health.2 For example, certain anti-rheumatic agents, including methotrexate and mycophenolate mofetil, exert teratogenic effects.

Pregnancy and contraception may increase disease activity and progression in systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and other diseases.2 In addition, evidence shows that women with rheumatoid arthritis, SLE, and inflammatory myopathies, who had well-controlled disease at conception, had better outcomes in terms of birthweight and full-term deliveries, while those with poor disease control at conception were at a higher risk for pre-eclampsia, cesarean section, intrauterine growth restriction, and/or fetal loss.2

“Patients and providers may be reassured to learn that many pregnancies for women with rheumatic diseases are normal and uncomplicated,” according to a 2017 review, published in Arthritis Care & Research,led by Mehret Birru Talabi, MD, PhD, assistant professor of medicine in the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh.2 Since family planning methods may help optimize pregnancy outcomes in these patients or help them avoid pregnancies, if desired, the American College of Rheumatology has recommended that patients contemplating pregnancy receive risk counseling from their physicians and aim to have well-controlled disease for at least 3-6 months before conception.3

“While appropriate, these recommendations assume that patients plan their pregnancies in advance, patients and providers effectively communicate about reproductive health issues, and patients prioritize disease control above desire to have children,” wrote the researchers of the study.2 However, they identified significant gaps in family planning counseling for this patient group. In another survey, only about 56% of rheumatologists reported that they provided routine family planning counseling to female patients of reproductive age.4

Contraception

These gaps in counseling may be partially due to some providers’ lack of training or their comfort levels while discussing these issues, such as contraception. A survey published in 2011 indicated that 22% of women of reproductive age, with SLE, had either used contraception inconsistently or not at all, and 59% of them had not received contraceptive counseling from their providers in the past year.5 These figures did not differ for women being treated with potentially teratogenic drugs. In another survey, women with SLE, especially those with the highest levels of disease activity, were the ones least likely to have received contraceptive counseling.6

It is believed that most contraceptive methods appear to be safe for women with rheumatic diseases, but with certain exceptions. “Method selection is best guided by an individual woman’s preferences, with considerations of reversibility, safety, noncontraceptive benefits, side effects, costs, and convenience,” wrote Dr Birru Talabi, et al.2 “Contraceptive efficacy may be particularly important for women whose chronic diseases increase risk of pregnancy complications.”

The authors discuss a range of methods, including those shown to be highly effective (such as progestin-only subdermal implants and intrauterine devices), those which are moderately effective (such as combined hormonal contraceptives), and the least effective ones like male and female condoms and diaphragms. For women with active SLE, SLE with antiphospholipid antibodies, APS, or a history of venous thromboembolism, estrogen-containing contraceptives may increase disease activity and thrombosis risk, and are, thus, generally contraindicated in such patients. Progestin-only contraception presents lower thrombotic risks. It should be noted that pregnancy confers greater thrombotic risks than any other method of contraception.2

Communication and Collaboration

Dr Birru Talabi and his colleagues stated that specialty and subspecialty training programs should begin providing education in family planning. In the meantime, they advised that clinicians “initiate a family‐planning conversation with every reproductive‐age female patient at the time of diagnosis of a rheumatic disease and before initiating or changing potentially teratogenic medications.” To this end, they provided detailed recommendations in their paper that could help clinicians optimize these discussions, including considerations for assessment and referral, potential questions to ask patients, and suggested phrasing in line with a patient-centered approach.2 

In addition, multidisciplinary collaboration between providers is essential to adequately address patients’ reproductive health needs. “Pregnant patients should be comanaged by a rheumatologist, obstetrician‐gynecologist, and maternal‐fetal medicine specialist if appropriate, to ensure that the rheumatic disease remains quiescent, flares are treated expediently, and maternal and fetal health are optimized.”

Rheumatology Advisor interviewed Dr Birru Talabi to further discuss reproductive health and family planning in this patient population. 

Rheumatology Advisor: What are some of the challenges pertaining to reproductive health in women with rheumatic disease?

Dr Birru Talabi: Many women are concerned about the safety of anti-rheumatic drugs with respect to pregnancy. Some women struggle with infertility. Access to contraception appears to be limited among women with rheumatic diseases.

Rheumatology Advisor: What are some key treatment considerations regarding pregnancy planning in these patients?

Dr Birru Talabi: New guidelines from the American College of Rheumatology are forthcoming to give patients and providers additional insight into  the safety of specific anti-rheumatic drugs. Some comprehensive consensus guidelines already exist, such as the EULAR Points and the BSR guidelines.7,8 

However, some women who use medications that are compatible with pregnancy are reluctant to continue even the safe anti-rheumatic drugs throughout their pregnancies due to concerns that the drugs may pose a theoretical risk to the child. This is really not a surprise since we counsel patients to have their labs regularly checked for “medication toxicity” and often describe in detail even the rarest of side effects of relatively well-tolerated medications, such as retinal toxicity associated with hydroxychloroquine. 

This is probably something that we as rheumatologists must consider when counseling our patients. These sessions may inadvertently undermine patients’ adherence to therapy, particularly when it comes to pregnancy. We do know that across the rheumatic diseases, women who have well-controlled disease at the time of conception and during pregnancy appear to have healthier pregnancies and better outcomes. Therefore, we must also be prepared to discuss the safety profiles of various anti-rheumatic drugs with respect to pregnancy, and why medication adherence – if the anti-rheumatic drug is compatible with pregnancy – can be important, not only for the mother’s health, but for the child’s health as well. 

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Rheumatology Advisor: What are important considerations pertaining to infertility and contraception?

Dr Birru Talabi: With regards to infertility, studies have found that assisted reproductive technologies can be very effective in facilitating pregnancy among women with rheumatoid arthritis.2 Clinicians should consider early referrals of patients to a specialist, such as a reproductive endocrinologist, if they suspect infertility. 

Many rheumatologists do not feel comfortable prescribing contraception, according to a recent qualitative study.9 This may explain why contraception prescription rates are so low among women with rheumatic diseases, which we also described in prior work.2 In fact, compared to the general population, women with rheumatic diseases are less frequently prescribed contraception, despite the fact that they are more likely to use fetotoxic medications and have diseases that could be exacerbated by pregnancy. This is an important issue, and the root causes are likely multifactorial.

Many women see their rheumatologists as primary care providers and may not regularly see healthcare professionals who can prescribe contraception. A rheumatologist may help refer patients to gynecologists or primary care providers who can prescribe contraception. In certain cases, rheumatologists may be requested to comment on the safety of a certain contraceptive method for a patient. They typically  refer to the US Medical Eligibility Criteria for Contraceptive Use for contraception safety for women with rheumatoid arthritis, SLE, or APS.10

Some patients may also be hesitant to use contraception because of concerns about the effects of hormones on their diseases. At present, there is not much evidence to suggest that hormonal contraception exacerbates rheumatic disease. There are some theoretical risks related to hormones associated with SLE with antiphospholipid antibody positivity; these risks are reflected in the US Medical Eligibility Criteria.10

However, it is important to note that the copper intrauterine device is hormone-free. Nearly all women with rheumatic diseases may use this form of contraception safely. Even if rheumatologists are  not the prescribers of the contraception, they may decide to share this information with patients to help to reduce the risk of unintended pregnancy among patients who do not wish for pregnancy.

Rheumatology Advisor: What are the remaining research needs pertaining to this topic?

Dr Birru Talabi: Research has focused on immunologic dysregulation and disease activity during pregnancy as a predictor of pregnancy outcomes. While this is important, there may be other risk factors for adverse pregnancy outcomes that are related to non-immunologic factors, such as inability of patients to receive adequate family planning care before pregnancy. In addition, patients continue to have concerns about the effects of hormones on disease activity across the various rheumatic diseases. Additional research should be done to examine if exogenous hormones do indeed contribute to disease flares across these disease states. Research has not  shown this aspect consistently to date, but it is one of the questions that greatly concerns patients in our studies.

References

  1. Nikiphorou E, Nurmohamed MT, Szekanecz Z. Editorial: comorbidity burden in rheumatic diseases. Front Med (Lausanne). 2018;5:197.
  2. Birru Talabi M, Clowse MEB, Blalock SJ, Moreland L, Siripong N, Borrero S. Contraception use among reproductive-age women with rheumatic diseases. Arthritis Care Res (Hoboken). 2018;70:169-174.
  3. American Academy of Rheumatology. Pregnancy and rheumatic disease. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Living-Well-with-Rheumatic-Disease/Pregnancy-Rheumatic-Disease Accessed on June 25, 2019.
  4. Chakravarty E, Clowse ME, Pushparajah DS, Mertens S, Gordon C. Family planning and pregnancy issues for women with systemic inflammatory diseases: patient and physician perspectives. BMJ Open. 2014;4(2):e004081.
  5. Yazdany J, Trupin L, Kaiser R, et al. Contraceptive counseling and use among women with systemic lupus erythematosus: a gap in health care quality? Arthritis Care Res (Hoboken). 2011;63(3):358-365.
  6. Ferguson S, Trupin L, Yazdany J, Yelin E, Barton J, Katz P. Who receives contraception counseling when starting new lupus medications? The potential roles of race, ethnicity, disease activity, and quality of communication. Lupus. 2016;25(1):12-17.
  7. Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810.
  8. Flint J, Panchal S, Hurrell A, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55(9):1693-1697.
  9. Birru Talabi M, Clowse MEB, Blalock SJ, Hamm M, Borrero S. Perspectives of adult rheumatologists regarding family planning counseling and care: a qualitative study [published online March 15, 2019]. Arthritis Care Res (Hoboken). doi:10.1002/acr.23872
  10. Curtis KM, Tepper NK, Jatlaoui TC, et al. US medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(3):1-103.