Advanced maternal age was associated with an annual decline in reproductive success despite use of donor oocytes: a...

To study if there is an increasing risk of poor reproductive outcomes associated with age in in vitro fertilization (IVF) patients using donor oocytes, and when it becomes clinically relevant.

Multicenter, retrospective cohort study.

IVF patients ≥35 years at 19 private fertility clinics in Spain.

A single day 5 embryo from a donor oocyte (<35 years) was transferred to the IVF patient undergoing hormone replacement therapy, between February 2000 and September 2022.

Live birth, implantation failure, and pregnancy loss rates were analyzed using a continuous scale of women's ages to determine the gradual effect of age that is clinically relevant. The relative risks (RRs) of pregnancy loss and implantation failure after 40 years of age were calculated, adjusting for body mass index, IVF cycle parameters, and the embryo's developmental stage and euploidy.

Analysis of 33,141 good-quality, single embryo transfers identified the maternal age at which reproductive rates worsened as 39, 40 and 43 years for implantation failure, live birth, and pregnancy loss rates, respectively. Before live birth rates drastically decreased, there was no significant increment in the RR for negative outcomes. Nevertheless, after the age of 40, the RR of implantation failure increased by 4.2% per year (RR = 1.042, 95% Confidence interval [CI]: 1.028-1.056) whereas that of pregnancy loss increased by 3.2% per year (RR = 1.032, 95% CI: 1.013-1.051).

Challenging traditional paradigms that embryo factors drive the detrimental effect of age on reproductive outcomes, this study reveals that uterine age may also play a significant role in age-related detrimental effects. Given that embryo factors were controlled for, these findings suggest that the worsening of reproductive outcomes is associated with the effects of age in the uterus. In addition, this study design identified the specific age at which the live birth rate decreases, and the implantation failure rate and pregnancy loss rate increase. Our results encourage further study of how uterine age annually impacts pregnancy rates and support the uterus becoming a potential target for antiaging therapies aiming to improve outcomes of assisted reproductive technologies.