A major new study suggests that age-related changes in the uterus may contribute to poor pregnancy outcomes, with women over 49 having lower live birth rates and higher risk of miscarriage despite donor egg treatment.
The findings, presented today at the 42nd annual meeting of the European Society for Human Reproduction and Embryology (ESHRE), challenge the assumption that donor eggs can completely ‘reset’ the reproductive clock by eliminating the effects of aging on reproductive function.
In recent decades, social, economic, and technological changes have steadily increased the age at which mothers give birth. Age-related decline in fertility has traditionally been thought to be primarily due to a decline in oocyte quality, but increasing evidence suggests that aging of the uterus and endometrium may also have an independent effect.
However, so far, clinical evidence quantifying the contribution of uterine aging to reproductive outcomes remains limited.
To investigate this, researchers at the IVIRMA Global Research Alliance in IVI Rome, Italy, analyzed 2,760 single blastocyst transfers performed on 1,774 women undergoing donor egg treatment between March 2021 and December 2024. This makes it possible to examine factors in the uterus while greatly controlling the effects of egg aging.
Pregnancy outcomes were compared in four recipient age groups (35-40 years, 41-45 years, 46-49 years, and 49 years and older), and live birth rates, miscarriage rates, and endometrial characteristics were assessed, adjusting for fetal, maternal, and paternal-related factors.
The analysis identified 49 years as a clinically meaningful threshold after which reproductive performance decreased despite the use of donor eggs. The clinical pregnancy rate decreased from 54.0% for women aged 35 to 40 years to 42.6% for women aged 49 years and older, and the live birth rate decreased from 46.2% to 31.7%. The miscarriage rate increased from 24.2% to 37.6%.
Compared to women aged 35 to 40, women aged 49 and older were significantly less likely to give birth and more than twice as likely to miscarry. Cumulative birth rates also declined significantly with age, from 80.0% for women aged 35 to 40 years who had all available embryos transferred to 62.5% for women aged 49 years and older.
The study also found age-related changes in the lining of the uterus, known as the endometrium. Although endometrial thickness was similar across age groups, the proportion of women with a three-layer endometrial pattern (a characteristic commonly associated with a uterus receptive to embryo implantation) decreased significantly with age, from 94.7% in women aged 35 to 40 years to 81.0% in women aged 49 years and older.
For many years, reproductive aging has been viewed primarily as an ovarian problem. This means that when you replace your old eggs with donor eggs, you are essentially “resetting” your reproductive clock. Our findings suggest that the situation is more complex. ”
Dr. Beatrice Crestani, first author
”Donor eggs have clearly overcome egg quality issues, and for many women, good results remain well into their late 40s. However, after age 49, lower live birth rates and higher miscarriage rates have been observed despite the use of donor eggs, suggesting that age-related changes in the uterine environment may also affect reproductive success rates.” explained Dr. Crestani.
Dr. Crestani discussed the implications of this finding and added, “These findings should not deter women from undergoing donor egg therapy, as the success rate remains significant at older ages. However, patients should be advised that donor eggs cannot completely eliminate the effects of aging on reproductive function, especially after age 49.”
Looking forward, the researchers hope to better understand the biological mechanisms underlying uterine aging, including the potential role of vascular, immune, hormonal and molecular changes. Future research should focus on identifying biomarkers of “uterine biological age” and exploring ways to potentially predict, prevent, or ameliorate age-related declines in uterine function.
Professor Bort Kovačić, ESHRE’s incoming chair, commented on the study:In recent years, increasing research activity has focused on understanding the processes that enable crosstalk between the embryo and the endometrium that mark the initiation of implantation. This study identifies an age threshold associated with the onset of loss of uterine function. Although this threshold is unlikely to be absolute, it provides important information for patients and provides a valuable basis for future studies aimed at identifying new biomarkers of uterine aging.. ”
The research summary is today. human reproductionone of the world’s leading reproductive medicine journals.
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European Society of Human Reproduction and Embryology
