The association between daily sitting time and infertility ：a population-based cross-sectional observational study and Mendelian randomization analysis

Objective The relationship between sedentary behavior and infertility remains ambiguous and contentious. This study seeks to elucidate this association by analyzing data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), coupled with Mendelian randomization (MR) analyses. Methods Our analysis comprised 3,128 female participants, aged 20 to 49 years, enrolled in the National Health and Nutrition Examination Survey (NHANES) during the 2013-2018 cycles.A logistic regression model was employed to examine the association between daily sitting time and infertility, with subgroup analyses conducted to validate the robustness of the findings. To further investigate potential causal relationships, a two-sample Mendelian Randomization (MR) analysis was conducted leveraging summary-level data from a Genome-Wide Association Study (GWAS). This analysis specifically examined the association between self-reported sedentary behaviors (e.g., commuting and workplace sitting) and infertility.Causal relationships were assessed using multiple MR methods, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger, and Weighted Mode. The MR-Egger intercept was utilized to evaluate pleiotropy in genetic variants, while Cochran’s Q test and leave-one-out analysis were conducted to assess the sensitivity of the results. Results After adjusting for potential confounders, multivariable logistic regression analysis demonstrated that, although the prevalence of infertility tended to increase with longer daily sitting time, this association did not reach statistical significance (OR = 1.03, 95% CI: 0.99–1.06, P = 0.104). Subgroup analyses revealed a significant independent association between daily sitting time and infertility in older women (aged ≥ 38 years) and individuals with hypertension, with ORs and 95% CIs of 1.05 (1.00–1.09) and 1.09 (1.01–1.17), respectively. The IVW-MR analysis showed no significant causal relationship between sedentary commuting (OR: 1.19, 95% CI: 0.88–1.62, P = 0.257) or sedentary behavior at work (OR: 0.99, 95% CI: 0.83–1.19, P = 0.930) and infertility. Sensitivity analyses further supported the robustness and reliability of these findings (P > 0.05). Conclusion Our study found no evidence of a significant association or genetic causality between sedentary behavior and infertility. However, a notable association was identified between sedentary behavior and infertility in older women and individuals with hypertension. These findings suggest that sedentary behavior may represent a potential risk to fertility in these high-risk groups, underscoring the importance of increased awareness and proactive management of sedentary lifestyles, particularly among older and hypertensive individuals.