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Reproductive Biology and Endocrinology
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Open Access 01-12-2024 | Review

Age-related uterine changes and its association with poor reproductive outcomes: a systematic review and meta-analysis

Authors: Diana Marti-Garcia, Asunta Martinez-Martinez, Francisco Jose Sanz, Almudena Devesa-Peiro, Patricia Sebastian-Leon, Nataly del Aguila, Antonio Pellicer, Patricia Diaz-Gimeno

Published in: Reproductive Biology and Endocrinology | Issue 1/2024

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Abstract

Background

The decline in women's fertility becomes clinically relevant between 35–40 years old, when there is insufficient ovarian activity, and it becomes more difficult to achieve pregnancy naturally and through artificial reproductive technologies. A competent endometrium is required for establishing and maintaining a pregnancy to term, however, experts in the field underestimate the contribution of endometrial age and its impact on reproductive outcomes remains unclear.

Study design

A systematic search of full-text articles available in PubMed was conducted to retrieve relevant studies published until March 2023. Search terms included: endometrium, uterus, age, aging, pregnancy, and oocyte donation. Terms related to reproductive pathologies were excluded. Eligibility criteria included original, rigorous, and accessible peer-reviewed work, published in English on the effect of age on the uterus and endometrium.

Results

From 11,354 records identified, 142 studies were included for systematic review, and 59 were eligible for meta-analysis of endometrial thickness (n = 7), pregnancy rate (n = 22), implantation rate (n = 10), live birth rate (n = 10) and pregnancy loss rate (n = 11). Studies for the meta-analysis of reproductive outcomes only included transfers of embryos from ovum donation (ovum donors < 36 years old). Age shrinks the uterus; depletes endometrial blood supply through narrow uterine veins and a progressive loss of uterine spiral arteries; disrupts endometrial architecture and cellular composition; alters hormone production, shortening menstrual cycle length and impeding endometrial progression to the secretory stage; and dysregulates key endometrial functions such as adhesion, proliferation, apoptosis, and receptivity, among others. Women over 35–40 years old had significantly thinner endometrium (MD 0.52 mm). Advanced maternal age is associated with lower odds of achieving implantation (27%) and clinical pregnancy (20%), or higher odds of experiencing pregnancy loss (44%).

Conclusion

Due to the effect of age on endometrium reported in this review, managing patients with advanced maternal age may require considering the endometrial factor as a potential tissue to treat with anti-aging strategies. This review provides researchers and clinicians with an updated and in-depth summary of this topic, encouraging the development of new tailored anti-aging and preventive strategies for precision medicine in endometrial factor in infertility.

Trial registration

PROSPERO 2023 (CRD42023416947).
Appendix
Available only for authorised users
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Metadata
Title
Age-related uterine changes and its association with poor reproductive outcomes: a systematic review and meta-analysis
Authors
Diana Marti-Garcia
Asunta Martinez-Martinez
Francisco Jose Sanz
Almudena Devesa-Peiro
Patricia Sebastian-Leon
Nataly del Aguila
Antonio Pellicer
Patricia Diaz-Gimeno
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2024
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-024-01323-6

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