(London, United Kingdom) A major new study suggests that age-related changes in the uterus may contribute to poorer pregnancy outcomes, with women aged 49 and over experiencing lower live birth rates and higher miscarriage risk despite donor-oocyte treatment.[1]
Presented today at the 42nd Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), the findings challenge the assumption that donor eggs can fully 'reset' the reproductive clock by eliminating the effects of reproductive ageing.
In recent decades, maternal age at childbirth has increased steadily due to social, economic and technological changes.[2] While age-related fertility decline has traditionally been attributed largely to declining egg quality,[3] growing evidence suggests that uterine and endometrial ageing may also exert independent effects.[4]
However, until now, clinical evidence quantifying the contribution of uterine ageing to reproductive outcomes has remained limited.
To investigate this, researchers from the IVIRMA Global Research Alliance at IVI Roma, Italy, analysed 2,760 single blastocyst transfers performed in 1,774 women undergoing donor-oocyte treatment between March 2021 and December 2024, allowing them to examine uterine factors while largely controlling for the effects of egg ageing.
Pregnancy outcomes were compared across four recipient age groups (35–40, 41–45, 46–49 and ≥49 years), with live birth rates, miscarriage rates and endometrial characteristics assessed while adjusting for embryo-, maternal- and paternal-related factors.
The analysis identified 49 years as a clinically meaningful threshold, after which reproductive outcomes declined despite the use of donor eggs. Clinical pregnancy rates fell from 54.0% in women aged 35–40 to 42.6% in those aged ≥49, while live birth rates declined from 46.2% to 31.7%. Miscarriage rates increased from 24.2% to 37.6%.
Compared with women aged 35–40, women aged 49 and over had significantly lower odds of achieving a live birth and more than double the odds of miscarriage. Cumulative live birth rates also declined substantially with age, from 80.0% among women aged 35–40 to 62.5% among women aged ≥49 who transferred all available embryos.
The study also found age-related changes in the lining of the uterus, known as the endometrium. While the thickness of the uterine lining remained similar across age groups, the proportion of women with a trilaminar endometrial pattern – a feature generally associated with a uterus that is receptive to embryo implantation – declined significantly with age, from 94.7% among women aged 35–40 to 81.0% among women aged ≥49.
Lead author Dr Beatrice Crestani said: “For many years, reproductive ageing has been seen primarily as an ovarian issue, meaning that if you replace older eggs with donor oocytes, you essentially ‘reset’ the reproductive clock. Our findings suggest the picture is more complex.”
“Donor eggs clearly overcome the problem of egg quality, and outcomes remain very good for many women even into their late forties. 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,” Dr Crestani explained.
Discussing the implications of the findings, Dr Crestani added: “These findings should not discourage women from pursuing donor-oocyte treatment, because success rates remain meaningful even at advanced ages. However, patients should be counselled that donor eggs cannot completely eliminate the effects of reproductive ageing, particularly beyond 49 years.”
Looking ahead, the researchers hope to better understand the biological mechanisms underlying uterine ageing, including the potential roles of vascular, immune, hormonal and molecular changes. Future studies should focus on identifying biomarkers of ‘uterine biological age’ and exploring ways to predict, prevent or potentially improve age-related declines in uterine function.
Commenting on the study, Professor Borut Kovacic, Chair-elect of ESHRE, said: “In recent years, increasing research efforts have focused on understanding the processes that enable cross-talk between the embryo and the endometrium, marking the onset of implantation. This study identifies an age threshold associated with the beginning of loss of 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 ageing.”
The study abstract will be published today in Human Reproduction , one of the world’s leading reproductive medicine journals.
ENDS
Notes to editors:
A reference to the ESHRE Annual Meeting must be included in all coverage and/or articles associated with this study.
For more information or to arrange an expert interview, please contact the ESHRE Press Office at: press@eshre.eu
About the author:
Dr Beatrice Crestani is a consultant in Obstetrics and Gynaecology with a special interest in Reproductive Medicine and Reproductive Endocrinology. She currently works at the Assisted Reproduction Unit of the University Hospital of Verona, Italy, where she is involved in the clinical management of infertility and reproductive disorders. She completed a Clinical Research Fellowship at IVI Roma, where she developed a strong academic and clinical interest in oocyte donation, a field that remains one of her main areas of expertise and research. She currently collaborates with the IVIRMA Group on several research projects in reproductive medicine. Dr Crestani is currently completing a Postgraduate Master’s Degree in Reproductive Biology at the University of Pavia, further strengthening her expertise in the field of human reproduction.
About the European Society of Human Reproduction and Embryology:
The main aim of ESHRE is to promote interest in infertility care and to aim for a holistic understanding of reproductive biology and medicine.
ESHRE collaborates world-wide and advocates universal improvements in scientific research, encourages and evaluates new developments in the field, and fosters harmonisation in clinical practice. It also provides guidance to enhance effectiveness, safety and quality assurance in clinical and laboratory procedures, psychosocial care, and promotes ethical practice. ESHRE also fosters prevention of infertility and related educational programmes and promotes reproductive rights regardless of the individual’s background. ESHRE’s activities include teaching, training, professional accreditations, mentoring and career planning for junior professionals, as well as developing and maintaining data registries. It also facilitates and disseminates research in human reproduction and embryology to the general public, scientists, clinicians, allied personnel and patient associations.
Website: https://www.eshre.eu/
About Human Reproduction:
Human Reproduction is a monthly journal of ESHRE and is one of the top three journals in the world in the field of reproductive biology, obstetrics and gynaecology. It is published by Oxford Journals, a division of Oxford University Press.
References:
[1] Crestani, B., et al. (2026). Advanced maternal age independently affects live birth and increases miscarriage risk in donor oocyte cycles. Human Reproduction.
[2] Ye, X., Baker, P.N., & Tong, C. (2024). The updated understanding of advanced maternal age. Fundamental Research , 4(6), 1719–1728.
[3] Cimadomo, D., Fabozzi, G., Vaiarelli, A., et al. (2018). Impact of Maternal Age on Oocyte and Embryo Competence. Frontiers in Endocrinology (Lausanne) . 29:9:327. doi: 10.3389/fendo.2018.00327.
[4] Tinelli, A., Andjić, M., Morciano, A., et al. (2023). Uterine aging and reproduction: Dealing with a puzzle biologic topic. International Journal of Molecular Sciences , 25(1), 322. https://doi.org/10.3390/ijms25010322