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dc.contributor.authorPathare, Amruta D.S.
dc.contributor.authorLoid, Marina
dc.contributor.authorSaare, Merli
dc.contributor.authorGidlöf, Sebastian Brusell
dc.contributor.authorEsteki, Masoud Zamani
dc.contributor.authorAcharya, Ganesh Prasad
dc.contributor.authorPeters, Maire
dc.contributor.authorSalumets, Andres
dc.date.accessioned2024-01-15T11:40:08Z
dc.date.available2024-01-15T11:40:08Z
dc.date.issued2023-07-19
dc.description.abstractBACKGROUND Modern lifestyle has led to an increase in the age at conception. Advanced age is one of the critical risk factors for female-related infertility. It is well known that maternal age positively correlates with the deterioration of oocyte quality and chromosomal abnormalities in oocytes and embryos. The effect of age on endometrial function may be an equally important factor influencing implantation rate, pregnancy rate, and overall female fertility. However, there are only a few published studies on this topic, suggesting that this area has been under-explored. Improving our knowledge of endometrial aging from the biological (cellular, molecular, histological) and clinical perspectives would broaden our understanding of the risks of age-related female infertility. OBJECTIVE AND RATIONALE - The objective of this narrative review is to critically evaluate the existing literature on endometrial aging with a focus on synthesizing the evidence for the impact of endometrial aging on conception and pregnancy success. This would provide insights into existing gaps in the clinical application of research findings and promote the development of treatment options in this field.<p> <p>SEARCH METHODS - The review was prepared using PubMed (Medline) until February 2023 with the keywords such as ‘endometrial aging’, ‘receptivity’, ‘decidualization’, ‘hormone’, ‘senescence’, ‘cellular’, ‘molecular’, ‘methylation’, ‘biological age’, ‘epigenetic’, ‘oocyte recipient’, ‘oocyte donation’, ‘embryo transfer’, and ‘pregnancy rate’. Articles in a language other than English were excluded.<p> <p>OUTCOMES - In the aging endometrium, alterations occur at the molecular, cellular, and histological levels suggesting that aging has a negative effect on endometrial biology and may impair endometrial receptivity. Additionally, advanced age influences cellular senescence, which plays an important role during the initial phase of implantation and is a major obstacle in the development of suitable senolytic agents for endometrial aging. Aging is also accountable for chronic conditions associated with inflammaging, which eventually can lead to increased pro-inflammation and tissue fibrosis. Furthermore, advanced age influences epigenetic regulation in the endometrium, thus altering the relation between its epigenetic and chronological age. The studies in oocyte donation cycles to determine the effect of age on endometrial receptivity with respect to the rates of implantation, clinical pregnancy, miscarriage, and live birth have revealed contradictory inferences indicating the need for future research on the mechanisms and corresponding causal effects of women’s age on endometrial receptivity.<p> <p>WIDER IMPLICATIONS - Increasing age can be accountable for female infertility and IVF failures. Based on the complied observations and synthesized conclusions in this review, advanced age has been shown to have a negative impact on endometrial functioning. This information can provide recommendations for future research focusing on molecular mechanisms of age-related cellular senescence, cellular composition, and transcriptomic changes in relation to endometrial aging. Additionally, further prospective research is needed to explore newly emerging therapeutic options, such as the senolytic agents that can target endometrial aging without affecting decidualization. Moreover, clinical trial protocols, focusing on oocyte donation cycles, would be beneficial in understanding the direct clinical implications of endometrial aging on pregnancy outcomes.en_US
dc.identifier.citationPathare, Loid, Saare, Gidlöf, Esteki, Acharya, Peters, Salumets. Endometrial receptivity in women of advanced age: an underrated factor in infertility. Human Reproduction Update. 2023;29(6):773-793en_US
dc.identifier.cristinIDFRIDAID 2207521
dc.identifier.doi10.1093/humupd/dmad019
dc.identifier.issn1355-4786
dc.identifier.issn1460-2369
dc.identifier.urihttps://hdl.handle.net/10037/32491
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.relation.journalHuman Reproduction Update
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/952516/Estonia/Ethically Responsible INnovations in reproductive medicine/ERIN/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleEndometrial receptivity in women of advanced age: an underrated factor in infertilityen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)