Among women who use donor oocytes to try to become pregnant, the odds of achieving a live birth decrease significantly after age 49, according to research presented at the European Society of Human Reproduction and Embryology (ESHRE) 2026 Annual Meeting in London, England.

Studies showed donor oocytes can help overcome age-related changes that limit fertility, such as a decline in the quantity and quality of eggs. “But our question was does it really eliminate the effect of age?” said Beatrice Crestani, MD, with the Assisted Reproduction Unit of the University Hospital of Verona in Verona, Italy. “Is the ovary really the whole story?”

To examine whether other factors such as uterine changes may play a role, Crestani and colleagues from the IVIRMA Global Research Alliance at IVI Roma analyzed data from 1774 women who underwent 2760 single blastocyst transfers between March 2021 and December 2024.

The researchers grouped single blastocyst transfers by patient age — 35-40 years (n = 496), 41-45 years (n = 1365), 46-49 years (n = 716), and 49 years or older (n = 183, with the oldest being 53-years-old) — and compared pregnancy outcomes and endometrial characteristics.

The clinical pregnancy rate progressively decreased with age, Crestani reported. For women aged 35-40 years, the pregnancy rate was 54% vs 42.6% for those aged 49 years or older. The younger group also had a higher rate of live births (46.2% vs 31.7%) and a lower rate of miscarriages (24.2% vs 37.6%).

Among patients who had all available embryos transferred, the cumulative live birth rate was 80% for the youngest group vs 62.5% for the oldest group.

In analyses that adjusted for factors including BMI, oocyte age, number of inseminated oocytes, day of transfer, endometrial thickness, and age of male partners, women aged 49 years or older had significantly lower odds of live birth (odds ratio [OR], 0.62; P = .02) and about double the risk for miscarriage (OR, 2.07; P = .01).

The proportion of women with a trilaminar endometrial pattern, which may be characteristic of uteruses that are more receptive to embryo implantation, decreased with age, from 94.7% among women aged 35-40 years to 81% among women aged 49 years or older.

The Father’s Age?

Although women in the oldest group also tended to have older male partners, a subgroup analysis found that paternal age was unlikely to explain the decline in reproductive success in the oldest group, Crestani said.

“Donor eggs clearly overcome the problem of egg quality, and outcomes remain very good for many women even into their late forties,” Crestani said in a news release. “However, beyond the age of 49, we observed lower live birth rates and higher miscarriage rates despite the use of donor eggs, suggesting that age-related changes in the uterine environment may also influence reproductive success.”

The data “should not discourage women from pursuing donor-oocyte treatment,” Crestani said.

Success Still Possible

Borut Kovačič, PhD, chair-elect of ESHRE, said the research points to an age threshold at which patients may start to lose some uterine function.

“While this threshold is unlikely to be absolute, it provides important information for patients and offers a valuable foundation for future research aimed at identifying novel biomarkers of uterine aging,” he said in the release.

Ying Cheong, MB ChB, BAO, MD, professor of reproductive medicine at the University of Southampton in Southampton, England, said the different outcomes for women after age 49 “is a genuinely useful clinical signal.”

However, the study does not prove uterine aging is the underlying cause, said Cheong, commenting on the study via the Science Media Centre.

Cheong agreed the results “shouldn’t discourage anyone.” But they do “challenge the assumption that donor eggs fully reset the reproductive clock.”

The retrospective analysis was based on data from a single center and used strict inclusion and exclusion criteria. Some women in the study may have had unreported uterine pathologies, which are more common at older ages. The researchers lacked details about some vascular and metabolic factors that can affect implantation.

Crestani, Kovacic, and Cheong disclosed no relevant conflicts of interest.