Chengdu University of Traditional Chinese Medicine.
Hospital of Chengdu University of Traditional Chinese Medicine, International Ward (Gynecology), Chengdu, China.
Medicine (Baltimore). 2024 Oct 25;103(43):e40220. doi: 10.1097/MD.0000000000040220.
The relationship between iron status and female infertility has been observed in several studies, yet its causal nature remains ambiguous. We employed univariate Mendelian randomization (MR) analyses to explore the potential causal connection between these 2 factors. For our analysis, genetic instrumental variables pertaining to iron status were selected using data from the Iron Status Genetics Consortium, encompassing 48,972 individuals of European descent from 19 cohorts (11 discovery and 8 replication). For female infertility data, we referred to FinnGen Consortium Release 9, which includes 11,442 cases and 107,564 controls. Our MR approach utilized both a conservative strategy (involving single nucleotide polymorphisms pertinent to general iron status) and a liberal strategy (encompassing single nucleotide polymorphisms linked to any iron status indicator). The conservative approach relied on inverse variance-weighted methods, whereas the liberal strategy integrated inverse variance weighted with MR-Egger regression, the weighted median approach, and simple mode techniques. The conservative strategy did not reveal a significant link between iron status and female infertility risk. Conversely, the liberal strategy indicated a positive correlation specifically between serum iron levels and female infertility risk (odds ratio from MR: 1.225; 95% confidence interval: 1.064-1.410; P = .030), while no significant associations were found for other iron indicators (P > 0.05). Our MR investigation suggests a potential positive association between serum iron levels and the risk of female infertility, while other iron markers do not appear to significantly influence this risk. These findings highlight the need for further research into the possible connection between serum iron status and female infertility risk.
几项研究观察到铁状态与女性不孕之间的关系，但因果关系仍不清楚。我们采用单变量孟德尔随机化（MR）分析来探讨这两个因素之间潜在的因果关系。为了进行分析，我们使用铁状态遗传联合体的数据选择了与铁状态相关的遗传工具变量，该数据包含来自 19 个队列的 48972 名欧洲血统个体（11 个发现队列和 8 个复制队列）。对于女性不孕数据，我们参考了 FinnGen 联合体发布的 9 号版本，其中包括 11442 例病例和 107564 例对照。我们的 MR 方法既采用了保守策略（涉及与一般铁状态相关的单核苷酸多态性），也采用了自由策略（包括与任何铁状态指标相关的单核苷酸多态性）。保守策略依赖于逆方差加权方法，而自由策略则综合了逆方差加权与 MR-Egger 回归、加权中位数方法和简单模式技术。保守策略并未显示铁状态与女性不孕风险之间存在显著关联。相反，自由策略表明血清铁水平与女性不孕风险之间存在正相关（MR 比值比：1.225；95%置信区间：1.064-1.410；P=0.030），而其他铁指标则没有显著相关性（P>0.05）。我们的 MR 研究表明，血清铁水平与女性不孕风险之间存在潜在的正相关，而其他铁标志物似乎不会显著影响这种风险。这些发现强调了需要进一步研究血清铁状态与女性不孕风险之间可能存在的联系。
