Depression is increasingly recognised as a factor affecting infertility but the causal relationship between them remains controversial. The aim of this study was to explore the relationship between depression and infertility using Mendelian randomisation (MR) and a cross-sectional study, and to explore the potential mediating role of obesity.
The cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Multivariate-adjusted logistic regression was used to assess the association between depression and infertility risk, and mediation analysis involved examining the mediating effect of obesity. Next, the authors performed RM 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 data for infertility were obtained from the FinnGen database (6,481 cases and 68,969 controls).
In the cross-sectional study, a total of 2,915 participants aged between 18 and 45 were included, 389 of whom were infertile. 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 (OR = 1.74, 95% CI: 1.02, 2.99) depression.
Mediation analysis showed that obesity accounted for 7.15% and 15.91% of the relationship between depression and infertility for body mass index and waist circumference. Depression significantly increased the risk of infertility in the general obese (OR = 1.81, 95% CI = 1.20-2.73, P<0.01) and abdominal obese (OR = 1.57, 95% CI = 1.08-2.27, P = 0.02) populations. Furthermore, MR analysis also revealed a significant positive causal relationship between genetically predicted depression and infertility (OR = 1.32, 95% CI: 1.03, 1.70).
Conclusion: Depression is associated with an increased risk of infertility, with obesity playing an important mediating role. This study highlights the importance of integrating mental health and weight management into infertility treatment strategies.
