Association of HOMA-IR with Ovarian Sensitivity Index in Women Undergoing IVF/ICSI: A Retrospective Cohort Study

Background: Insulin resistance (IR) may adversely impact the in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) outcomes. However, the association of IR with ovarian sensitivity during controlled ovarian hyperstimulation (COH) remains controversial. Purpose: We aimed to explore the association between homeostasis model assessment of insulin resistance (HOMA-IR) and ovarian Patients and Methods: In this retrospective cohort study, 7836 patients aged between 20 and 39 years with good ovarian reserve were included consecutively between June 2018 and May 2022. HOMA-IR was calculated to evaluate the degree of IR and OSI was used to measure ovarian sensitivity. Owing to skewed distribution, HOMA-IR and OSI were log e transformed to Ln HOMA-IR and Ln OSI. Smoothing splines were generated by generalized additive models to explore the correlation between Ln HOMA-IR and Ln OSI. Then, the relationship between Ln HOMA-IR and Ln OSI was tested with multivariable linear regression model after adjustments for the potential confounders. Results: We observed negative association between Ln HOMA-IR and Ln OSI after adjustment for potential confounders by using smoothing spline fitting curves in generalized additive model. In the multivariable linear regression model, after full adjustments, each one unit increase in Ln HOMA-IR was related to reduced Ln OSI values (beta = -0.12, 95% CI, -0.15, -0.09). As sensitivity analysis, those who had HOMA-IR of quartile 3 (HOMA-IR 2.33-3.43) and quartile 4 (HOMA-IR >= 3.43) had decreases in Ln OSI values (beta = -0.07, 95% CI -0.11, -0.03 and beta = -0.18, 95% CI -0.22, -0.13, respectively) when compared with patients in the quartile 1 (HOMA-IR <1.63). Furthermore, stratified and interaction analysis showed a strong inverse association of Ln HOMA-IR with Ln OSI in subgroups of PCOS patients and overweight/obese populations (P-value for interaction <0.0001). Conclusion: HOMA-IR value was negatively associated with the ovarian sensitivity assessed by OSI. Among the PCOS and overweight/obese populations, this inverse relationship may be strong. These findings will increase the understanding of the contribution of IR to the development of decreased ovarian sensitivity within the assisted reproductive technology (ART) setting. It may have implications for optimizing gonadotropin dose manipulation in patients with IR undergoing IVF/ICSI.