No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs.
Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen.
Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42-0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39-0.85; p=0.005; n=55).
VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.
The world journal of men's health. 2023 Jan 01 [Epub ahead of print]
Chi Yuan, Liyuan Xiang, Zhongyu Jian, Banghua Liao
Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China., Department of Clinical Research Management, West China Hospital, Chengdu, Sichuan, China., Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China. .