Correlation between Castelli risk index-I and female infertility: A cross-sectional study

Abstract

Background: The association between metabolic syndrome and female reproductive health has garnered increasing attention; however, the relationship between the Castelli risk index I (CRI-I, total cholesterol/high-density lipoprotein cholesterol ratio) and infertility remains unclear. This study was designed to explore the potential association between CRI-I and female infertility.

Methods: The study population was derived from data collected in three consecutive two-year cycles (2013-2018) of the National Health and Nutrition Examination Survey (NHANES), ultimately including 2,629 female participants aged 18-45 years. Weighted multivariable logistic regression models were used to assess the association between CRI-I and infertility following adjustment for covariates such as demographic characteristics, medical history, and lifestyle factors, among others. Restricted cubic spline and threshold effect analyses were conducted to examine possible nonlinear associations. Subgroup analyses and ROC curves were used to assess robustness and predictive capacity.

Results: CRI-I scores were significantly elevated in the infertile group in comparison with the non-infertile group (median [interquartile range, IQR]: 3.38 [2.77-4.07] vs. 3.08 [2.53-3.80]; P = 0.001). CRI-I showed a positive monotonic association with infertility risk, with each unit increase corresponding to a 17% higher likelihood (adjusted OR = 1.17, 95% CI: 1.01-1.36; P = 0.042). Nonlinear analysis identified a threshold effect between CRI-I and infertility risk (inflection point = 3.73): the risk increased significantly when CRI-I was < 3.73 (OR = 1.54, 95% CI: 1.20-1.98), whereas the association attenuated above this threshold. Subgroup analysis revealed a significant interaction by hypertension status (interaction P < 0.05). CRI-I demonstrated modest predictive utility for female infertility (AUC = 0.580, 95% CI: 0.548-0.613).

Conclusions: Elevated CRI-I scores were positively associated with female infertility, particularly in specific subgroups (e.g., younger, married, non-hypertensive, or alcohol-consuming individuals). These findings underscore the potential role of dysregulated lipid metabolism in female reproductive dysfunction.

Keywords: Castelli risk index-I (CRI-I); Cross-sectional study; Infertility; NHANES.

Fig. 1

Flow chart for participants selection

Fig. 2

The nonlinear association between CRI-I and infertility risk was characterized using restricted cubic spline(RCS). (A) Weighted RCS of unadjusted. (B) Weighted RCS adjusted for age, race, poverty-Income ratio (PIR), educational levels, marital status, smoking status, hypertension, diabetes, menstrual regularity, drinking status, sleep troubles, physical activity, contraceptive drug use, history of pelvic infection disease, triglycerides, use of hormonal medications, estradiol. CI: Confidence interval. The red curve represents the nonlinear relationship between CRI-I and infertility risk.The green shaded area depicts the 95% CI. The dash line indicated the referent line of OR = 1

Fig. 3

Weighted Subgroup analysis for the association between CRI-I and infertility. Age, race, PIR, educational level, marital status and smoking status, hypertension, diabetes, menstrual regularity, drinking status, sleep troubles, triglyceride, physical activity, contraceptive drug use, history of pelvic infection, use of hormonal medications, estradiol were adjusted. OR: Odds radio. Lower represents the lower bound of the 95% confidence interval (CI). Upper denotes the upper bound of the 95% CI