The Association Between Sleep Disorder and Female Infertility: A Mediation Analysis of Inflammatory and Oxidative...

Background: Sleep disorder in women of reproductive age may contribute to infertility development, but there is a lack of substantial evidence linking sleep disorder to inflammation and oxidative stress, and the subsequent risk of infertility. Methods: A total of 2365 women aged 18-45 years from the National Health and Nutrition Examination Survey (NHANES) were included in this analysis. Sleep disorder and infertility were assessed according to NHANES questionnaire data module. Inflammatory and oxidative biomarkers such as high-sensitivity C-reactive protein (hs-CRP), white blood cell (WBC), gamma-glutamyl transpeptidase (GGT), albumin, ferritin, and total bilirubin were derived from the laboratory data module, and systemic immune inflammation index (SII), and system inflammation response index (SIRI) were calculated based on complete blood cell counts. A sophisticated multistage sampling design and weighted multivariable adjusted regression models were employed to conduct comprehensive analysis. Mediation models were applied to explicate the mediating role of biomarkers of inflammation and oxidative stress. Results: Compared to the noninfertility group, the infertile participants had a higher incidence of sleep disorder (34% vs. 25%, p < 0.05). In models with fully adjusted covariates, sleep disorder was positively associated with infertility risk (OR: 1.58; 95%CI: 1.01-2.50, p < 0.05), particularly in subgroups of individuals aged over 30 years old (OR: 1.75; 95%CI: 1.00-3.04, p < 0.05) or with a body mass index (BMI) ≥ 30 kg/m² (OR:2.05; 95%CI: 1.00-4.22, p < 0.05). In terms of mechanisms, there were significant correlations between inflammatory and oxidative markers and both sleep disorder and infertility. Mediation analysis indicated that hs-CRP, SII, SIRI, GGT, and total bilirubin played a significant mediating role in the relationship between sleep disorder and infertility, accounting for 0.4822%, 6.0515%, 1.2485%, 5.1584%, and 0.4738%, respectively. Conclusions: Sleep disorder is a significant risk factor for infertility, particularly in women aged >30 years or with obesity. Furthermore, the presence of inflammation and oxidative stress status in the body, which also significantly mediate the association between sleep disorder and infertility, can be swiftly and repeatedly identified through blood tests. Sleep, as a modifiable behavioral pattern, can be regarded as a new strategy to cope with infertility.