Elevated follicular fluid 17-hydroxyprogesterone and cortisone are associated with higher live birth rates in PCOS patients undergoing IVF/ICSI: a prospective cohort study

Abstract

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and complex metabolic disturbances that often compromise in vitro fertilization (IVF) outcomes. These systemic imbalances directly alter the follicular fluid (FF) steroid microenvironment, which is crucial for oocyte competence. However, the exact prognostic value of specific intrafollicular steroids remains controversial, largely due to the cross-reactivity of traditional immunoassays. This study aimed to precisely quantify the FF steroid profile using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and evaluate its prognostic capacity for live birth in women with PCOS. This prospective cohort study included 204 infertile women with PCOS who underwent IVF/intracytoplasmic sperm injection (ICSI), evaluating live birth outcomes following their first embryo transfer. Ten steroid hormones were quantified from the FF of a single leading follicle (≥ 18 mm) using LC-MS/MS. Restricted cubic spline (RCS) models and receiver operating characteristic (ROC) curves were employed to characterize dose-response relationships and delineate optimal clinical thresholds. Multivariable logistic regression was utilized to demonstrate the independent associations between these local biomarkers and live birth, adjusting for critical confounders. Patients achieving live birth ( n  = 110) exhibited significantly higher FF levels of 17-hydroxyprogesterone (17-OHP) and cortisone. After adjustment, high levels of 17-OHP (≥ 604 ng/mL; aOR = 2.18, 95% CI: 1.17–4.05) and cortisone (≥ 16.5 ng/mL; aOR = 2.50, 95% CI: 1.33–4.69) were independently associated with improved live birth rates. When evaluated simultaneously in a combined model, cortisone remained a robust independent predictor (aOR = 2.11, 95% CI: 1.10–4.09). Neither biomarker correlated with serum anti-Müllerian hormone (AMH) ( P  > 0.05). Within the PCOS population, relatively elevated intrafollicular 17-OHP and cortisone reflect a favorable local endocrine environment associated with higher live birth rates. Despite providing modest prognostic utility, these local steroid biosignatures act independently of serum AMH and highlight the relevance of the intrafollicular microenvironment in IVF success.