Mendelian randomization analysis reveals causal associations between autoimmune diseases and female infertility risk

Infertility is viewed as a significant social challenge globally. Numerous observational studies have documented the link between autoimmune diseases (ADs) and female infertility, yet the underlying cause remained unclear. The primary objective of this study was to ascertain the causal connection between ADs and female infertility.

We evaluated summary statistics from genome-wide association studies (GWAS) for prevalent autoimmune diseases (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis and female infertility. Initial two-sample Mendelian randomization (MR) analyses was conducted to pinpoint causal autoimmune diseases associated with female infertility in the discovery and replication analysis.

Our two-sample Mendelian randomization analysis, using data from the UK Biobank and FinnGen (or IIBDGC), provided evidence for a causal association between genetically predicted rheumatoid arthritis (RA), type 1 diabetes (T1DM), celiac disease (CeD), and ulcerative colitis (UC) and an increased risk of female infertility. These associations were observed across different sub-phenotypes of infertility.

This Mendelian randomization study, based on large-scale GWAS datasets, provides genetic evidence supporting a causal association between several autoimmune diseases and increased female infertility risk. These findings highlight the potential role of immune-mediated mechanisms in reproductive dysfunction and may inform future research into early interventions and fertility-preserving strategies in affected individuals.