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register hereBackground: Depression is increasingly recognized as a factor affecting infertility and the causal relationship between them remains controversial. The aim of this study was to explore the relationship between depression and infertility using Mendelian randomization (MR) and cross-sectional study, and to explore the potential mediating role of obesity..

背景：抑郁症越来越被认为是影响不孕症的一个因素，两者之间的因果关系仍然存在争议。本研究的目的是使用孟德尔随机化（MR）和横断面研究探讨抑郁症与不孕症之间的关系，并探讨肥胖的潜在中介作用。。

Methods: The cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Multivariable-adjusted logistic regression was used to assess the association between depression and infertility risk, and mediation analysis was to examine the mediating effect of obesity.

方法：横断面研究使用2013-2018年国家健康与营养调查（NHANES）的数据。多变量调整后的逻辑回归用于评估抑郁症与不孕症风险之间的关联，中介分析用于检查肥胖的中介作用。

Then, we performed MR analyses to investigate the causal effect of depression on infertility. Instrumental variables for depression were obtained from a genome-wide association meta-analysis (135,458 cases and 344,901 controls), and summary level data for infertility were obtained from the FinnGen database (6,481 cases and 68,969 controls).

然后，我们进行了MR分析，以调查抑郁症对不孕症的因果关系。抑郁症的工具变量来自全基因组关联荟萃分析（135458例和344901例对照），不孕症的汇总水平数据来自FinnGen数据库（6481例和68969例对照）。

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Results: In the cross-sectional study, a total of 2,915 participants between the ages of 18 and 45 were included, of whom 389 were infertile. We observed that depression was strongly associated with an increased risk of infertility (OR=1.66, 95%CI: 1.19, 2.33), and this relationship remained significant in mild (OR=1.45, 95% CI: 1.09, 1.93), moderate (OR=1.89, 95% CI: 1.26, 2.84), and severe depression (OR=1.74, 95% CI: 1.02, 2.99).

结果：在横断面研究中，共纳入2915名年龄在18至45岁之间的参与者，其中389名不育。我们观察到抑郁症与不孕症风险增加密切相关（OR=1.66，95%CI:1.19，2.33），这种关系在轻度（OR=1.45，95%CI:1.09，1.93），中度（OR=1.89，95%CI:1.26，2.84）和重度抑郁症（OR=1.74，95%CI:1.02，2.99）中仍然显着。

Mediation analysis showed that obesity mediated 7.15% and 15.91% of the relationship between depression and infertility for body mass index and waist circumference. Furthermore, depression significantly increased the risk of infertility in both the general obesity (OR=1.81, 95%CI=1.20-2.73, P<0.01) and abdominal obesity populations (OR=1.57, 95%CI=1.08-2.27, P=0.02) populations.

中介分析显示，肥胖介导了体重指数和腰围与抑郁症和不孕症之间关系的7.15%和15.91%。此外，抑郁症显着增加了一般肥胖人群（OR=1.81，95%CI=1.20-2.73，P＜0.01）和腹部肥胖人群（OR=1.57，95%CI=1.08-2.27，P=0.02）的不孕风险。

In addition, the MR analysis also revealed a significant positive causal relationship between genetically predicted depression and infertility (OR=1.32, 95% CI: 1.03, 1.70)..

此外，MR分析还显示，遗传预测的抑郁症与不孕症之间存在显着的正因果关系（OR=1.32，95%CI:1.03，1.70）。。

Conclusion: Depression is associated with an increased risk of infertility, with obesity playing a significant mediating role. This study underscores the importance of incorporating mental health and weight management in infertility treatment strategies.

结论：抑郁症与不孕症风险增加有关，肥胖起着重要的中介作用。这项研究强调了将心理健康和体重管理纳入不孕症治疗策略的重要性。