Insulin resistance as a determinant of fertilization efficiency in polycystic ovary syndrome patients undergoing IVF/ICSI: a retrospective cohort study

Zhang et al. Reproductive Biology and Endocrinology https://doi.org/10.1186/s12958-025-01453-5 (2025) 23:120 Reproductive Biology and Endocrinology Open Access RESEARCH Insulin resistance as a determinant of fertilization efficiency in polycystic ovary syndrome patients undergoing IVF/ICSI: a retrospective cohort study Ruiteng Zhang1,2, Xuejin Wang1, Meilan Mo1, Zhiqiang Liu1 and Su Liu1,2* Abstract Background This retrospective cohort study aimed to evaluate the impact of insulin resistance (IR) on clinical outcomes in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Methods A total of 1,768 PCOS patients undergoing IVF/ICSI cycles at Shenzhen Zhongshan Obstetrics & Gynecology Hospital between October 2010 and November 2024 were stratified into two cohorts: non-IR group (HOMA index < 2.69, n = 867) and IR group (HOMA index ≥ 2.69, n = 901). Baseline characteristics and clinical outcomes were compared between the groups. Linear logistic regression and multivariate logistic regression analysis were conducted to assess the independent impact of IR on fertilization efficiency and pregnancy outcomes. Results Patients with IR exhibited significantly higher BMI (25.44 ± 3.55 vs. 21.59 ± 3.20, p < 0.001), longer infertility duration (3.74 ± 2.75 vs. 3.25 ± 2.43, p < 0.001), increased antral follicle counts (26.74 ± 10.74 vs. 25.05 ± 9.79, p < 0.001) and lower basal follicle-stimulating hormone (FSH) level (9.78 ± 3.25 vs. 10.64 ± 3.83, p < 0.001) compared to those without IR. Additionally, the fertilization rate (82.02% vs. 83.86%, p = 0.005) and 2PN rate (81.07% vs. 83.96%, p < 0.001) were significantly lower in PCOS patients with IR. Linear regression indicated that IR had a more pronounced inverse effect on 2PN rate (B: -2.540, p = 0.009) than on fertilization rate (B: -0.664, p = 0.490). Subgroup analysis and interaction analysis demonstrated that IR functioned as an independent risk factor for impaired oocyte fertilization in normalweight PCOS patients (B: -22.694, p = 0.011). No statistically significant associations between IR status and clinical or live birth pregnancy outcomes were observed in the regression models. Conclusions IR adversely affects oocyte fertilization competence and early embryonic development in normalweight PCOS patients undergoing assisted reproductive technology (ART). These effects may be attributable to IR-induced metabolic dysregulation, which compromises folliculogenic and cytoplasmic maturation processes critical to gamete competence. These findings underscore the importance of addressing metabolic dysfunction in IR-affected PCOS populations to optimize ART outcomes. *Correspondence: Su Liu Full list of author information is available at the end of the article © The Author(s) 2025. 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To view a copy of this licence, visit http://creati vecommons.org/licenses/by-nc-nd/4.0/. Zhang et al. Reproductive Biology and Endocrinology (2025) 23:120 Page 2 of 10 Trial registration This is a retrospective study. Keywords Polycystic ovary syndrome, Insulin resistance, HOMA, IVF/ICSI, Fertilization rate Introduction Polycystic ovary syndrome (PCOS) is acknowledged as a prevalent infertility and endocrine disease affecting up to 6–21% of reproductive-age women based on racial diversity and various diagnostic criteria [1]. Abnormalities in gonadotropins secretion, ovarian folliculogenesis, steroidogenesis, and insulin secretion have been observed in individuals with PCOS [2]. Recent studies have indicated that genetic predispositions, epigenetic alterations, environmental factors, oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, and metabolic disorders are involved in the aetiology of PCOS and thus affect normal ovarian function [3–6]. Although PCOS manifests heterogeneously, IR emerges as a central pathophysiological hub, affecting 35–80% of patients and driving both metabolic dysregulation and reproductive dysfunction [7]. From a mechanistic perspective, IR impairs endometrial receptivity in PCOS patients by reducing glucose transporter 4 expression, leading to insufficient glucose supply in endometrial cells and finally causing abortion [8]. IR not only disrupts physiological glucose homeostasis but also serves as a pivotal driver in the pathogenesis and progression of metabolic disorders, including dyslipidemia, nonalcoholic fatty liver disease, atherosclerosis, and type 2 diabetes mellitus (T2DM) [9]. IR also leads to a series of cellular reactions that affect the clinical characteristics of PCOS. For instance, IR can lower the levels of hepatic sex hormone-binding globulin (SHBG), increase the pituitary responsiveness to gonadotropin-releasing hormone (GnRH), stimulate theca cells to produce androgens and elevate both total and free testosterone levels, thereby contributing to hyperandrogenism [9]. This is a key factor in ovulatory dysfunction and infertility [10]. Beyond the systemic metabolic effect of IR, accumulating evidence suggests that IR may directly impair clinical reproductive outcomes among patients with or without PCOS who are undergoing in vitro fertilization (IVF) [11, 12]. It is widely acknowledged that a significant proportion of women with PCOS, ranging from 50 to 70%, are at an elevated risk of miscarriage, with insulin resistance (IR) identified as key contributing factors [13–15]. A metaanalysis study with 6137 PCOS patients revealed that IR was associated with a decreased risk of clinical pregnancy rate (OR: 0.77, 95% CI: 0.59 to 0.99, p = 0.042) and an increased risk of spontaneous abortion (OR: 1.11, 95% CI: 1.02 to 1.22, p = 0.017) in patients undergoing assisted reproductive technology (ART) treatment [16]. Another meta-analysis involving 11,182 patients with PCOS further corroborated the detrimental impact of IR on spontaneous abortion risk (MD: 0.32, 95% CI: 0.15 to 0.49) [17]. Despite these associations, the mechanistic interplay between IR and early reproductive processes— particul (...truncated)