Fertility Treatment, Female-Factor Infertility, and Autism Spectrum Disorder: Study to Explore Early Development

Prior research on fertility treatments and autism spectrum disorder (ASD) suggests minimal association but confounding by indication limits inference. To make clinically relevant conclusions, studies should include populations who receive treatment specifically for female-factor infertility.

We investigated the association between ovulation-inducing medications and assisted reproductive technology (ART) and ASD. We conducted analyses in a subsample reporting female-factor infertility to reduce confounding by indication.

We used data from the Study to Explore Early Development (SEED), a 2007-2020 U.S. population-based case-control study. Children 2.5-5 years old with and without ASD were classified using in-person assessments. We identified fertility treatment via interview and included ovulation-inducing medications, ART, and a combination of both. The subsample included those who were told it would be difficult to conceive and/or who attempted to conceive for > 12 months. We estimated odds ratios and 95% confidence intervals for the whole sample and the subsample using logistic regression models adjusted for age, education, parity, pre-pregnancy body mass index, pregnancy history, smoking status, pre-existing hypertension, and other hormonal fertility treatments.

There were 5210 participants in the whole sample and 1091 in the subsample. There was no association between ovulation-inducing medications and ASD in the full sample (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 0.77, 1.39) and the subsample (aOR 0.87, 95% CI 0.61, 1.2). There was an increased likelihood of ASD for ART and a combination of treatments in the whole sample (ART: aOR 1.33, 95% CI 0.70, 2.52; combination: aOR 1.39, 95% CI 0.95, 2.03) compared to the subsample (ART: aOR 1.16, 95% CI 0.57, 2.36; combination: aOR 1.08, 95% CI 0.69, 1.68).

In our data, fertility treatment was not associated with ASD. Additional research should restrict analyses to populations with similar indications to untangle whether observed associations are due to treatment or factors related to uptake.