Causal relationship between serum uric acid levels and male infertility: a bidirectional two-sample Mendelian randomization study

Background: Uric acid is the final metabolic product of purines in the human body and has been implicated in the pathogenesis of various diseases. Nevertheless, the relationship between serum uric acid levels and male infertility remains inconclusive. This Mendelian randomization (MR) study aims to elucidate the potential impact of serum uric acid levels on the risk of male infertility. Methods: We conducted the bidirectional MR analysis utilizing summary data from genome-wide association studies (GWAS) on serum uric acid levels and male infertility. The inverse variance weighted (IVW) method was employed to evaluate the primary outcomes, and multivariate MR analyses were conducted to combine estimates of the causal effects of multiple risk factors. Additionally, sensitivity analyses were performed to confirm the robustness of the results. Results: In the univariable MR analysis, serum uric acid levels did not exhibit a significant association with the risk of male infertility [IVW odds ratio (OR) 0.92, 95% confidence interval (CI): 0.614-1.390, P=0.70]. Similar conclusions were drawn from the reverse MR analysis (IVW OR 1.000, 95% CI: 0.997-1.003, P=0.96). In the multivariable MR (MVMR) analysis, after adjusting for confounding factors such as body mass index (BMI), type 2 diabetes, alcohol consumption, and smoking, serum uric acid levels remained unassociated with male infertility (IVW OR 0.839, 95% CI: 0.613-1.148, P=0.27). Consistent results were observed in the reverse analysis (IVW OR 1.003, 95% CI: 0.994-1.012, P=0.49). Conclusions: Our study provides genetic evidence indicating no significant causal relationship between serum uric acid levels and male infertility in the general population, suggesting that serum uric acid is not a potential risk factor for male infertility.