The Impact of Age Beyond Ploidy: Outcome Data from 8175 Euploid Single Embryo Transfers

Purpose: The rate of embryonic aneuploidy increases with increasing female age and is the primary cause of lower pregnancy and live birth rates (LBR) in older reproductive age women. This retrospective cohort study evaluates single euploid embryo transfers to determine whether an age-related decline in reproductive efficiency persists.

Methods: A total of 8175 non-donor single embryo transfers (SET) after pre-implantation testing for aneuploidy (PGT-A) and cryopreservation were included. These were divided into five groups by patient age: < 35 years old (n = 3789 embryos transferred), 35-37 (n = 2200), 38-40 (n = 1624), 41-42 (n = 319), and > 42 (n = 243). Implantation rate (IR), clinical pregnancy rate (CPR), and LBR were calculated for each group as a percentage of embryos transferred and compared. CPR was also analyzed as a percentage of implanted pregnancies, and LBR as a percentage of clinical pregnancies, to determine when age has the greatest impact. These results were then adjusted for confounding variables via a multivariate logistic regression model.

Results: Implantation rates negatively correlated with age. After adjusting for confounders, women 38 years or older had a significantly lower IR than those under 35 (OR 0.85, 95%CI 0.73-0.99 for 38-40 years old; 0.69, 0.53-0.91 for 41-42, and 0.69, 0.51-0.94 for > 42). These differences are also apparent in CPR and LBR. The rates of progression to clinical pregnancy and live birth did not differ significantly by age group. Other factors observed to affect IR independently were anti-Müllerian hormone (AMH), day of embryo transfer, and embryo morphology.

Conclusion: While selection of euploid embryos may be effective in overcoming a significant proportion of the age-related decline in reproductive efficiency, a decrease in IR, CPR, and LBR persists even when analyzing only euploid embryo transfers. The observed impact of aging is, therefore, independent of ploidy, as well as of other variables that affect reproductive efficiency. These results indicate that factors other than aneuploidy contribute to reproductive senescence.