Association of Sleep, Inflammation and Female Infertility: A Cross-Sectional Survey and Genetic Approach

Abstract

Introduction: Inflammation has been implicated in both reproduction and sleep; however, the relationships remain unclear, and conclusive evidence for genetic associations is lacking.

Methods: This study utilized the 2013-2020 National Health and Nutrition Examination Survey (NHANES) data and conducted a Mendelian randomization (MR) analysis to investigate the associations among inflammation, sleep, and female infertility. A cross-sectional study was performed on 370 infertile women aged 20-44 years. Multiple linear regression was applied to evaluate the associations between sleep and the inflammatory markers. Subgroup and interaction analyses were conducted to assess the robustness of the findings. MR analysis was performed on 91 circulating inflammatory proteins, 11 sleep traits, and infertility to examine potential genetic associations.

Results: A total of 370 infertile participants aged 20-44 years were included. The logarithmic platelet-lymphocyte ratio (PLR) was significantly higher in the sleep disorder group (p < 0.05). After adjusting for potential confounders, sleep disorders remained associated with a reduction in PLR (β = -0.145, 95% CI: -0.267 to -0.023, p < 0.05). MR analysis using the inverse variance weighted (IVW) method indicated that insomnia, subjective long sleep duration, and high sleep efficiency were associated with increased levels of oncostatin-M, artemisinin, and adenosine deaminase, all of which are implicated in infertility. Additionally, the morning type was associated with increased levels of C-X-C motif chemokine 5, which reduced the risk of infertility.

Conclusion: Sleep is associated with various inflammatory factors in the body and may contribute to infertility. Inflammation appears to play a key role in mediating the complex interplay between sleep and reproduction. These findings highlight the potential value of screening and managing specific inflammatory markers in infertile patients with sleep disorders to improve reproductive outcomes. However, further clinical studies and mechanistic experiments are needed to validate the genetic associations identified in this study.

Keywords: Mendelian randomization; NHANES; genetic association; infertility; inflammation.