Serum iron status and the risk of female infertility in European populations: A two-sample Mendelian randomization study

The relationship between iron status and female infertility has been observed in several studies, yet its causal nature remains ambiguous. We employed univariate Mendelian randomization (MR) analyses to explore the potential causal connection between these 2 factors. For our analysis, genetic instrumental variables pertaining to iron status were selected using data from the Iron Status Genetics Consortium, encompassing 48,972 individuals of European descent from 19 cohorts (11 discovery and 8 replication). For female infertility data, we referred to FinnGen Consortium Release 9, which includes 11,442 cases and 107,564 controls. Our MR approach utilized both a conservative strategy (involving single nucleotide polymorphisms pertinent to general iron status) and a liberal strategy (encompassing single nucleotide polymorphisms linked to any iron status indicator). The conservative approach relied on inverse variance-weighted methods, whereas the liberal strategy integrated inverse variance weighted with MR-Egger regression, the weighted median approach, and simple mode techniques. The conservative strategy did not reveal a significant link between iron status and female infertility risk. Conversely, the liberal strategy indicated a positive correlation specifically between serum iron levels and female infertility risk (odds ratio from MR: 1.225; 95% confidence interval: 1.064-1.410; P = .030), while no significant associations were found for other iron indicators (P > 0.05). Our MR investigation suggests a potential positive association between serum iron levels and the risk of female infertility, while other iron markers do not appear to significantly influence this risk. These findings highlight the need for further research into the possible connection between serum iron status and female infertility risk.