ESHRE 2026 • critical appraisal
A study led by Beatrice Crestani reported lower success rates in the oldest donor-oocyte recipients. It did not prove that the uterus suddenly becomes non-receptive after age 49.
A young oocyte does not make the whole body younger
For years, counselling around egg donation has relied on a simple explanation: if the main age-related problem is oocyte ageing and the resulting increase in aneuploidy, replacing an older oocyte with one from a young donor should largely reset the reproductive clock. This is only partly true. Donor eggs reduce the oocyte-related component of age, but they do not reverse vascular, metabolic, immune or obstetric ageing in the recipient.
What did the Crestani team study?
The IVI Rome team retrospectively analysed 1,774 women who underwent 2,760 single blastocyst transfers using donor oocytes between 2021 and 2024. Recipients were divided into four age groups: 35–40, 41–45, 46–49 and over 49 years.
The live birth rate per transfer fell from 46.2% in the youngest group to 31.7% in recipients over 49. Miscarriage among implanted pregnancies increased from 24.2% to 37.6%. After adjustment for selected factors, the odds ratio for miscarriage in the oldest group was 2.07.
Why “twice the risk” is an oversimplification
An odds ratio is not the same as a relative risk. When an outcome is common, the difference matters. In the raw data, miscarriage rose by 13.4 percentage points. The ratio of the two observed percentages was approximately 1.55, not 2.07. The finding remains clinically important, but it should be communicated accurately.
Did the study prove uterine ageing?
No. It showed an association between recipient age and reproductive outcome in this cohort. It did not measure the biological age of the uterus, molecular receptivity, gene expression, immune profile, perfusion or a causal mechanism for miscarriage.
The investigators observed a higher prevalence of a non-trilaminar endometrial pattern in older recipients. However, another 2026 IVIRMA analysis of more than 14,000 donor-oocyte transfers found that this ultrasound pattern was not independently associated with live birth. The most defensible interpretation is therefore that the data are compatible with a late recipient-age effect, but do not establish its mechanism.
Why the result cannot be applied to every patient
This was a retrospective study from a single large, highly protocol-driven centre. Approximately 93–99% of cycles used hormone replacement therapy. Some women contributed more than one transfer, but the within-patient correlation was not modelled. The oldest group included 183 transfers and 35 miscarriages. Women with BMI above 30, thin endometrium and recognised major uterine pathology were excluded.
What does individual endometrial assessment add?
Chronological age is easy to record, but it is not a test of endometrial function. In our clinical model, assessment does not stop at age and endometrial thickness. We consider donor selection, embryo quality, uterine anatomy, the preparation protocol and, in appropriately selected patients, molecular receptivity and the endometrial immune profile using REIA. These variables were not available in the Crestani database.
An important caution about REIA
REIA should not be presented as a way to erase age. ESHRE guidance does not support routine use of every commercial receptivity test in all patients, although assessment of selected aspects of endometrial function may be considered in specific clinical situations. Our observation that no abrupt decline is seen at a single birthday in a personalised model of care is a clinical hypothesis that requires prospective testing.
What should patients be told?
Donor-oocyte treatment can still offer a meaningful chance of live birth at very advanced reproductive age. At the same time, careful medical and obstetric assessment becomes increasingly important. One retrospective study should not be used to create an automatic age cut-off. The appropriate response is better counselling, more individualised diagnostics and shared decision-making.
Sources
- Crestani et al., Journal of Assisted Reproduction and Genetics, 2026
- Sodani et al., ESHRE 2026
- Molinaro et al., ESHRE 2026
- ESHRE good practice recommendations on recurrent implantation failure
Educational material only. It does not replace individual medical advice.