Background/objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis.

Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a "leave-one-out" sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study.

Results: The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06-1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran's Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A "leave-one-out" sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings.

Conclusions: In the European population, the urate level is significantly and causally associated with an increased risk of female infertility.