Oocyte-intrinsic aging drives whole-chromosome aneuploidy independent of ovarian reserve beyond maternal age as risk factor.

This retrospective cross-sectional study investigated whether maternal age functions as an independent risk factor for chromosomal aneuploidy in day-5 blastocysts through oocyte-intrinsic aging mechanisms rather than quantitative ovarian reserve reduction. A total of 490 infertile couples (2472 day-5 blastocysts) underwent preimplantation genetic testing for aneuploidy (PGT-A) at An Sinh Hospital (Vietnam, 2023). Patients were stratified into three maternal age groups: < 35 years (n = 244, 1261 embryos), 35-40 years (n = 217, 1085 embryos), and ≥ 40 years (n = 29, 126 embryos). Trophectoderm biopsies were analyzed using next-generation sequencing with BlueFuse Multi software. Multivariate logistic regression evaluated maternal age, oocyte quantity, and blastocyst development as independent predictors of aneuploidy. Results demonstrated significant age-related decline in euploid rates from 36.24% in women < 35 years to 20.63% in women ≥ 40 years (p < 0.0001), with corresponding increase in aneuploidy from 20.86% to 41.27% (p < 0.0001). Maternal age remained independently predictive after adjusting for oocyte quantity (OR 1.052/year; 95% CI 1.031-1.073; p < 0.001), demonstrating that age operates through oocyte-intrinsic aging mechanisms rather than reserve-related effects. Day-5 blastocyst count emerged as a prognostic biomarker (OR 0.965; p = 0.002) compared to initial oocyte quantity. Mosaic embryo rates remained age-independent (approximately 40-43%; p = 0.383), indicating post-zygotic rather than meiotic origins. These findings imply that this indication‑enriched PGT‑A cohort (advanced maternal age, prior IVF failure, male-factor infertility, and a history of genetic disease) has higher aneuploidy rates than non-selected IVF patients and support age-group patient counseling, use of day-5 blastocyst development as a practical biomarker of oocyte and embryonic potential, and systematic consideration of PGT‑A in women ≥ 35 years, particularly in those ≥ 40 years.