The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of infertility among US adults: A cross-sectional NHANES study

Background: Infertility affects millions worldwide, with a significant proportion of cases remaining unexplained. Recent evidence suggests a potential link between lipid metabolism and reproductive health, prompting investigations into novel biomarkers like the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) for assessing infertility risk.

Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) to conduct a cross-sectional analysis of 5,524 women aged 20-45 in the United States. NHHR was calculated from lipid profiles, and infertility was determined via the Reproductive Health Questionnaire. Multivariate logistic regression and restricted cubic spline (RCS) analyses were performed to examine the relationship between NHHR and infertility, adjusting for confounding factors such as age, BMI (body mass index), and lifestyle habits.

Results: The study found a nonlinear association between NHHR and infertility risk, with the risk peaking in the second and third quartiles of NHHR levels. Notably, women in the higher NHHR quartiles exhibited a 2.15 to 2.36 odds ratio for infertility compared to those in the lowest quartile, suggesting a significant increase in risk. Subgroup analyses revealed that this association was particularly strong in younger women and those with a higher BMI. Moreover, the RCS analysis confirmed the nonlinear pattern of the relationship, highlighting a more pronounced risk at moderate NHHR levels, which plateaued or varied at higher levels. The interaction analyses further suggested that the relationship between NHHR and infertility risk could be influenced by age and BMI, pointing to differential effects in various subpopulations.

Conclusions: Elevated NHHR levels are associated with increased infertility risk, especially in specific subgroups, suggesting a complex link between lipid metabolism and reproductive health. Further research is needed to validate these findings and explore the potential of NHHR as a biomarker for infertility risk.