Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

Abstract

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided.

Maternal and Paternal Infertility Disorders and Treatments and Autism Spectrum Disorder: Findings from the Study to Explore Early Development

“…This study was limited in that data regarding specific infertility conditions were not presented. A second case-control study of children residing in several regions in California reported similar proportions of maternal or paternal infertility diagnoses for children with ASD and typically-developing control children (Lyall et al 2013); however, specific infertility conditions could not be fully assessed because of very small numbers of both case and control mothers reporting individual infertility conditions. A third study, using a nested case-control design drawn from the Nurse's Health Study (NHS), which had a larger sample to assess individual conditions, also reported no association between infertility conditions and ASD (Lyall et al 2012).…”

“…One study reported no differences between ASD cases and typically developing controls in either ART use or use of various non-ART infertility treatments (Lyall et al 2013). Two other studies reported positive associations between use of non-ART ovulation induction medications and ASD, findings that were particularly noteworthy in that neither observed associations with ART, a treatment that nearly always includes high doses of ovulation induction medications (Lyall et al 2012; Hvidtjorn et al 2011).…”

“…The few studies that examined a range of both ART and non-ART treatments reported mixed results. One reported no associations between ASD and any of the treatments examined (Lyall et al 2013). In contrast, two studies found no associations with ART, but significant positive associations between ASD and less invasive treatments—non-ART ovulation induction and/or assisted insemination (Hvidtjorn et al 2011; Lyall et al 2012).…”

“…Only a few studies have directly examined the relationship between ASD and infertility disorders (Grether et al 2013; Lyall et al 2012, 2013). While one study initially documented associations between ASD and several infertility indicators, the associations were attenuated and no longer reached statistical significance when limited to singleton births (Grether et al 2013).…”

“…Two other case-control studies observed no association between ASD and infertility. One was limited by small sample sizes which precluded detailed analyses of specific types of infertility (Lyall et al 2013). The other had a larger sample size, but had potential methodological shortcomings, particularly in ascertainment of infertility in mothers; further, the findings from this study might have limited generalizability, given the study population was a very select group of predominantly white nurses and their children (Lyall et al 2012).…”