Genetic Liability to Antidepressant Treatment and Risk of Female Infertility: A Two-Sample Bidirectional Mendelian Randomization Study

This study applied a two‑sample bidirectional Mendelian randomization (MR) design using genetic summary statistics from the FinnGen R9 database to examine the causal link between genetic predisposition to antidepressant treatment and female infertility, including relevant subtypes. Seventy-seven independent Single Nucleotide Polymorphisms(SNPs)were selected as instrumental variables for antidepressant treatment liability. The inverse-variance weighted (IVW) analysis suggested that genetically proxied antidepressant treatment was associated with a modestly increased risk of overall female infertility (OR = 1.119, 95% CI: 1.024–1.222, p = 0.013). No significant association was observed for anovulatory infertility. Reverse MR analysis did not support a causal effect of infertility on antidepressant treatment liability. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy. These findings suggest that genetic predisposition to antidepressant treatment is associated with female infertility risk. However, the genetic instrument captures a composite liability reflecting underlying psychiatric vulnerability and treatment decisions rather than a pure pharmacological drug effect. Therefore, the results should not be interpreted as direct evidence of antidepressant-induced infertility. Our findings underscore the clinical importance of considering mental health in the context of reproductive counseling, while cautioning that the genetic instrument does not isolate a pure drug effect.