Abstract
OBJECTIVE: To evaluate follicular fluid (FF) SCUBE1 levels as a novel angiogenesis-associated biomarker and investigate its role in reflecting the follicular vascular microenvironment and predicting ovarian response in women undergoing assisted reproductive technology (ART). METHODS: This prospective pilot study included 63 women undergoing IVF/ICSI. Paired serum and FF samples were analyzed. Patients were stratified into Poor (< 4 oocytes), Normal (4-10), and High (> 10) responders. SCUBE1 levels were measured via ELISA. The study primarily investigated the relationship between intrafollicular SCUBE1 and the magnitude of ovarian response as an indicator of the follicular "angiogenic switch." RESULTS: Serum SCUBE1 levels decreased significantly during ovarian stimulation (p < 0.001). However, FF SCUBE1 levels were approximately twofold higher in High Responders compared to Poor Responders (174.04 ± 112.45 vs. 84.66 ± 73.15 ng/mL, p = 0.043). A significant upward trend was confirmed across responder categories (Jonckheere-Terpstra, p = 0.032). In ROC analysis, FF SCUBE1 demonstrated promising predictive value for high ovarian response (AUC = 0.718, 95% CI: 0.532-0.904, p = 0.048). Notably, a cut-off of 59.13 ng/mL yielded a clinically useful 100% Negative Predictive Value (NPV). SCUBE1 levels did not correlate with oocyte maturation, fertilization, or clinical pregnancy. CONCLUSION: Follicular fluid SCUBE1 is a dynamic marker of the follicular vascular microenvironment rather than a direct indicator of oocyte genetic competence. Elevated levels in high responders reflect the intensified angiogenic support required for multiple follicle development. Low FF SCUBE1 may serve as a clinical "red flag" for compromised follicular vascularization in cases of unexpected poor response.