Abstract
According to the perspective of psychosomatic medicine, infertility is the consequence of the interaction of individual psychological and physiological factors. Specifically, depression and ovarian cysts are strongly associated with infertility in women. However, the causality and mechanisms are still unclear. This study was conducted to investigate the causal relationships between depression, ovarian cysts and infertility based on large-scale genome-wide association studies pooled statistical Mendelian randomization (MR) analysis. In the primary inverse-variance weighted analysis, there was a genetically predicted causal effect of depression on both female infertility and ovarian cysts, as well as a direct causal association observed between ovarian cysts and female infertility. Multivariable MR (MVMR) analysis revealed that ovarian cysts mediate the causal relationship between depression and infertility. The findings demonstrate from a genetic perspective that depression confers susceptibility to infertility via increasing the risk of ovarian cysts in females. It provides robust evidence for the potential biological link between psychological factors and reproductive health.