Insights into Modifiable Risk Factors of Infertility: A Mendelian Randomization Study

Objective: Observational studies have linked lifestyle, diet, obesity, and biochemical measures with infertility. Whether this association is causal is unclear. We sought to identify the causal relationship between modifiable risk factors with infertility. Methods: Using single-nucleotide polymorphisms (SNPs) as a genetic instrument variable, we carried out a two-sample Mendelian randomization (MR) analysis to estimate the causal effects for 22 modifiable risk factors on female infertility (6481 cases; 75,450 participants) and male infertility (680 cases; 73,479 participants). Results: The results of the study showed that BMI (OR: 1.24, 95% CI (1.09, 1.40)), body fat percentage (OR: 1.73, 95% CI (1.13, 2.64)), and alcohol consumption (OR: 6.57,95% CI (1.2, 36.14)) are associated with a higher risk of male infertility, and total fatty acids (OR: 1.16, 95% CI (1.03, 1.30), omega-6 fatty acids (OR: 1.14, 95% CI (1.00, 1.27)), and monounsaturated fatty acids (OR: 1.14, 95% CI (1.03, 1.28) are associated with a higher risk of infertility in women. We observed that higher education (OR: 0.77, 95% CI (0.64, 0.92)) was a protective factor for female infertility. Conclusions: BMI, body fat percentage, and alcohol consumption are risk factors for male infertility; total fatty acids, omega-6 fatty acids, and monounsaturated fatty acids are risk factors for female infertility, and education is a protective factor for female infertility.