Objective To employ Mendelian randomization (MR) to assess the potential causal relationship between 15 micronutrients in serum and male infertility, so as to provide a scientific basis for the etiological prevention of male infertility. Methods Male infertility was taken as the outcome variable, and 15 serum micronutrients was regarded as the potential influencing factors. A two-sample MR analysis was conducted using genome-wide association study with the European population. Multivariable MR analysis was employed to explore the independent effects of potential micronutrients on male infertility. Results A total of 198 single nucleotide polymorphisms across 15 groups were included as instrumental variables to assess the causal association between micronutrients and male infertility. Univariate analysis showed that increased serum iron levels were positively causally associated with a higher risk of male infertility (odds ratio=2.917, P=0.015). Besides, multivariate MR analysis suggested that this positive causal relationship between iron and male infertility remains significant (odds ratio=3.253, P=0.029). Meanwhile, this study found a negative association between elevated vitamin D levels and the risk of male infertility (odds ratio=0.403, P=0.020).Conclusion Elevated serum iron levels and increased vitamin D levels are associated with significant positive and negative causal effects on male infertility, respectively.
