Protein levels of p-mTOR and p-RPS6 in cumulus cells serve as non-invasive biomarkers for embryo quality and pregnancy outcome in IVF.

To investigate whether the levels of mTOR signaling and ribosome biogenesis proteins in cumulus cells (CCs) can serve as non-invasive biomarkers for predicting embryo quality and pregnancy outcomes in women undergoing IVF. In this prospective study, discarded CCs were collected from 83 IVF patients. The protein levels of mTOR, phosphorylated mTOR (p-mTOR), ribosomal protein S6 (RPS6), and phosphorylated S6 (p-RPS6) were quantified by Western blot and normalized to β-actin. These molecular data were correlated with clinical parameters, including ovarian reserve, embryonic development, and pregnancy outcomes. Statistical analyses were performed to determine optimal predictive thresholds and to evaluate single and combined protein models. Reduced levels of p-mTOR, p-RPS6, and RPS6 in CCs were robustly associated with superior IVF outcomes. Specific cutoff values were identified (e.g., p-mTOR < 0.45, p-RPS6 < 0.80) for predicting enhanced blastocyst formation and higher clinical pregnancy rates. Combining these biomarkers into multi-protein models significantly improved predictive accuracy for both embryonic development and pregnancy success compared to any single protein alone. The assessment of p-mTOR, p-RPS6, and RPS6 in cumulus cells provides a powerful, non-invasive strategy for prognostic assessment in IVF. A molecular profile characterized by lower levels of these proteins is indicative of high oocyte developmental competence and a greater likelihood of successful pregnancy, offering a valuable tool for clinical decision-making prior to embryo transfer.