Abstract
BACKGROUND: Inflammation and metabolic dysregulation can disturb the maternal microenvironment, increasing female infertility risk. High-density lipoprotein cholesterol (HDL-C)-related inflammatory markers have proven useful for diagnosing and predicting inflammatory disorders, and this study investigates their link to infertility in US reproductive-aged women. METHODS: Data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES) were utilized to evaluate the correlation between female infertility and HDL-C-related inflammatory markers. Adjusted multivariable logistic regression models were used to account for confounders, and subgroup analyses and interaction tests were conducted to investigate effect changes. The potential intricate relationship was described using restricted cubic spline (RCS). RESULTS: This study included 3,027 women aged 18-45, with 309 reporting infertility. The mean HDL-C-related inflammatory markers of the women in the infertility group were significantly higher than those of the women in the fertility group (P < 0.001). Female infertility was positively associated with Lymphocyte-high-density lipoprotein ratio(LHR), Monocyte-high-density lipoprotein ratio(MHR), and Neutrophil-high-density lipoprotein ratio(NHR) in models 1 and 2. Univariate analysis showed a positive association between Uric Acid-high-density lipoprotein ratio(UHR), MHR and female infertility in other quarter groups(Q2, Q3, Q4) compared to the lowest quarter group (Q1) across all models. Meanwhile, women in the highest LHR quarter group(Q4) exhibited a significantly higher risk of infertility than the lowest (Q1) in all models. And the third quartile (Q3) and the highest quarter(Q4) of Platelet-high-density lipoprotein ratio(PHR) were significantly positively correlated with female infertility in models 2 and 3 (P < 0.05). The RCS plot displayed a linear relationship between HDL-C-related inflammatory markers and infertility risk (P < 0.05). Subgroup analyses and interaction tests revealed a notable PHR and MHR-infertility association in those aged ≤ 35, and a significant NHR-infertility link in non-smokers (P < 0.05). CONCLUSIONS: Our investigation revealed a substantial association between elevated HDL-C-related inflammatory markers and a heightened risk of female infertility. Future cohort studies with larger populations are necessary to confirm this relationship, considering the limitations of the cross-sectional design and dependence on self-reported data.