Beyond aneuploidy: embryo morphology, maternal age, and miscarriage dynamics in PGT-A selected single embryo transfer

The study addresses whether maternal age, embryo morphology, and blastocyst developmental timing interact to influence pregnancy success rates in PGT-A selected single embryo transfer (PGT-A sSET), confirmed as euploid or exhibiting low-level (≤ 40%) mosaicism; and whether the chromosomal health of the embryo mitigates all aspects of age-related fertility decline.

We retrospectively analyzed 822 frozen PGT-A sSET cycles performed at Villa Mafalda private clinic (July 2020-December 2024): 771 autologous and 51 donor-oocyte transfers. Outcomes were ongoing pregnancy/live birth, implantation, and miscarriage rates, evaluated in relation to maternal age, considered both as categorical brackets (≤ 34, 35-38, 39-41, ≥ 42 years) and as a continuous variable.

Women ≥ 42 yr showed lower ongoing-pregnancy and live-birth rates, poorer morphology, delayed blastocyst expansion than younger groups (all p < 0.05); no differences emerged among the younger brackets. In the multivariable logistic-regression model, embryo morphology emerged as the strongest determinant of success: Good-quality embryos showed 2.8-fold increase in ongoing pregnancy/live-birth odds (95% CI 1.61-4.92; p = 0.0003) and Excellent-quality embryos 4.6-fold increase (95% CI 2.63-8.05; p < 0.0001) versus Poor-quality category. Finally, each additional year of maternal age increased miscarriage risk by 11% (RR 1.11, 95% CI 1.03-1.19; p = 0.005).

Our results reinforce that, even among chromosomally normal blastocysts, morphological quality predominates over maternal age and blastocyst developmental timing in predicting pregnancy success. Maternal age exerts its effect largely by compromising embryo competence-beyond simply increasing aneuploidy rates-pointing to additional, age-related alterations in embryonic physiology.