Infertility linked to onset of autoimmune disease after childbirth

Women who experience infertility but do not use fertility treatments have a higher risk of developing a group of conditions called systemic autoimmune rheumatic diseases (SARD) in the nine years after a naturally conceived birth compared to women without fertility problems.

The new research, published in Human Reproduction, found that this was true even after accounting for higher rates of pre-eclampsia (high blood pressure during pregnancy), preterm birth (babies born alive earlier than 37 weeks) and stillbirth, all of which are associated with infertility and its treatments.

Researchers from the University of Toronto Scarborough, Canada, said their findings should alert doctors to the possibility that women with infertility may be at risk of future SARD or may have undiagnosed and untreated SARD – rare but debilitating conditions in which the immune system becomes overactive and attacks the body’s own tissues.

The researchers analysed data on 568,053 singleton births between 2012 and 2021 among 465,078 women aged 18 to 50 years without known pre-existing SARD. ICES collected the data from Ontario’s publicly funded health insurance plan.

The studylooked at women with no infertility who conceived naturally (88% of the group) and used them as the reference group against which to measure outcomes for three further groups: women with infertility who did not have fertility treatment (9.2% of the group); women with infertility who had non-invasive fertility treatment such as ovulation induction or intrauterine insemination (1.4%); and women with infertility who had invasive fertility treatment such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), 1.4% of the group.

They adjusted for age at delivery, pre-existing conditions such as diabetes, obesity and endometriosis, maternal smoking, and reproductive history, including pre-eclampsia, previous births and stillbirths.

‘We found that women who experienced infertility but didn’t use fertility treatments were 25% more likely to develop SARD up to nine years following childbirth,’ said  Dr Natalie V. Scime. ‘This increased risk persisted even after we accounted for other immune-related pregnancy complications these women might have faced.’

To put this in perspective, for every 10,000 women followed for a year, there were about nine new cases of SARD in women without infertility and 13 new cases in women with infertility who did not use fertility treatments.

‘Interestingly, women who used fertility treatments, whether non-invasive methods like ovulation-inducing medications or more invasive procedures like in vitro fertilisation, didn’t show this increased risk,’ Dr Scime. ‘They had similar rates of autoimmune diseases as women without infertility issues, about 11 new cases of SARD for every 10,000 women followed for a year.’

The fact that we found no increased risk of SARD in women who used fertility treatments compared to fertile women may be due to the ‘healthy patient’ effect, she added. ‘Women who receive fertility treatments may come from more privileged backgrounds and may be healthier overall than those without access to these treatments, which puts them at generally lower risk of SARD.’

‘These findings are important because they suggest infertility may be an important risk marker for SARD in women who give birth,’ Dr Scime said. ‘Early detection is crucial for preventing organ damage, improving treatment outcomes, and helping patients maintain the best quality of life possible.’

Associate Professor Dr Hilary Brown who supervised the research, said: ‘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.’