A multidimensional follicular profile integrating oxidative stress, apoptosis and PI3K/AKT/mTOR signaling in relation to oocyte developmental competence in in vitro fertilization cycles

PURPOSE: Accurate assessment of oocyte developmental competence remains challenging in IVF, as morphology alone offers limited insight into intrinsic oocyte quality. Emerging evidence indicates that oocyte competence reflects coordinated regulation of the follicular microenvironment rather than a single biomarker. This study aimed to evaluate a multidimensional follicular marker panel integrating oxidative stress parameters, hormonal environment, granulosa cell apoptosis, chromatin integrity and PTEN/PI3K/AKT/mTOR signaling in relation to IVF outcomes. METHODS: Thirty women undergoing ICSI were included, yielding a total of 211 oocytes. Individual follicles were analyzed according to oocyte maturity, embryo quality and pregnancy outcome. Follicular fluid oxidative stress parameters (TAC, TOC, OSI and MDA) and hormonal mediators (FSH, AMH, melatonin, TGF-β and β-hCG) were assessed. Granulosa cells were evaluated for DNA fragmentation, chromatin integrity and expression of PTEN/PI3K/AKT/mTOR pathway proteins. RESULTS: Favorable IVF outcomes were associated with higher total antioxidant capacity and lower oxidative stress index and malondialdehyde levels, alongside reduced granulosa cell DNA fragmentation and improved chromatin integrity (p < 0.05). These outcomes were characterized by increased PI3K and AKT expression with concomitant mTOR suppression, while PTEN, PDK1, TSC1 and TSC2 levels remained unchanged. Follicular FSH and AMH were primarily linked to oocyte maturity, whereas melatonin, TGF-β and β-hCG were elevated in follicles yielding good-quality embryos and positive pregnancy outcomes (p < 0.05). CONCLUSIONS: Oocyte developmental competence in IVF reflects a coordinated follicular microenvironment integrating oxidative balance, granulosa cell integrity, hormonal regulation, and PI3K/AKT/mTOR signaling, supporting a multidimensional, panel-based framework for integrated follicular assessment.