Follicular fluid SCUBE1 as a novel angiogenesis-associated biomarker in women undergoing ART: a pilot study reflecting the follicular vascular microenvironment.

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.