Women Who Give Birth After Infertility Have Elevated Risk of Systemic Rheumatic Disease

Natalie V. Scime, PhD

Credit: Eurekalert

New research has found that infertility in the absence of fertility treatment may be an important risk marker for developing systemic autoimmune rheumatic disease (SARD) in women who give birth.¹

“While previous research has shown that women with infertility often have unusual immune system activity, there was little research on how infertility might be linked to autoimmune diseases,” Natalie V. Scime, PhD, who was a Banting Postdoctoral Fellow at Institute for Clinical Evaluative Sciences (ICES) and the Department of Health and Society at the University of Toronto Scarborough at the time of the research, said in a statement.² “Our team wanted to see if infertility was associated with future systemic autoimmune rheumatic diseases among women who achieve a livebirth or stillbirth, while also accounting for adverse pregnancy outcomes that may occur around the time of the birth.”

Scime and colleagues conducted a population-based cohort study including linked administrative data for all of Ontario, Canada, between 2012 and 2021 and 568,053 singleton births among 465,078 women aged 18 to 50 years without known pre-existing SARD. Women were stratified by either no infertility with unassisted conception (88.0%), infertility without fertility treatment (9.2%), infertility with non-invasive fertility treatment (ovulation induction or intrauterine insemination; 1.4%), or infertility with invasive fertility treatment (IVF or ICSI; 1.4%). Participants had a median duration of 6.5 years (IQR, 4-9) of follow-up.¹

The investigators found that the incidence rate of SARD was 9.3 per 10 000 person-years in women without infertility, 12.5 per 10 000 person-years in those with infertility and no fertility treatment, 10.9 per 10 000 person-years following non-invasive fertility treatment, and 10.9 per 10 000 person-years after invasive fertility treatment.¹

After adjusting for sociodemographic characteristics, comorbidities, smoking, and adverse pregnancy outcomes, women with infertility without treatment had a controlled direct effect hazard rate (HR) of 1.25 (95% CI, 1.21.40) of developing SARD compared to women without infertility. Women that received non-invasive (total effect HR, 1.06 [95% CI, 0.79-1.42]) or invasive (total effect HR, 0.97 [95% CI, -.69-1.36]) fertility treatments did not have a differing risk of developing SARD compared with women without infertility.¹

“These findings are important because they suggest infertility may be an important risk marker for SARD in women who give birth. SARD can be tricky to diagnose, often taking years of untreated symptoms and multiple health care visits before a proper diagnosis is made. Early detection is crucial for preventing organ damage, improving treatment outcomes, and helping patients maintain the best quality of life possible. Our work showed that infertility care presents an opportunity for doctors to carefully screen women for rheumatic symptoms, such as unexplained fatigue, joint pain, or skin rashes, and overlapping gynecologic symptoms, such as sexual dysfunction, and start a diagnostic work-up or rheumatology referral where necessary,” Scime added.²

Scime and colleagues noted that the lack of differing SARD risk between women without infertility and women who received treatment for their infertility may be due to the ‘healthy patient’ effect wherein these women may have different socioeconomic backgrounds and may be healthier than those without access to fertility treatments.¹

“Our study highlights several ideas for future research, such as exploring whether specific causes of infertility are more strongly associated with SARD risk, and investigating the potential biological pathways through which disease processes in SARD might impact female fertility,” Hilary Brown, PhD, Associate Professor, ICES, who supervised the research, added to the statement.²

REFERENCES
1. Scime NV, Velez MP, Choi MY, Ray JG, Boblitz A, Brown HK. Association between infertility and incident onset of systemic autoimmune rheumatic disease after childbirth: a population-based cohort study. Hum Reprod. Published online December 5, 2024:deae253, doi: 10.1093/humrep/deae253

2. Infertility linked to onset of systemic autoimmune rheumatic disease after childbirth. News release. European Society of Human Reproduction and Embryology. Published online December 5, 2024 https://www.eurekalert.org/news-releases/1066851