ArticleFrontiers in cell and developmental biology2026
Advanced maternal age as a risk factor for endometrial receptivity in repeated implantation failure: intersectional transcriptomic analysis and gene validation.
Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Repeated implantation failure (RIF) remains a significant challenge in assisted reproductive technology. Endometrial receptivity (ER) plays a critical role in embryo implantation. However, the impact of advanced maternal age (AMA) on ER in this population remains unclear. The study aimed to evaluate whether maternal age is associated with displacement of the window of implantation (WOI) and explore potential endometrial transcriptomic characteristics. Methods: This retrospective observational study included 254 women with RIF who underwent evaluation of ER between January 2020 and March 2024. ER status and WOI timing were determined using a transcriptome-based receptivity assessment. Clinical characteristics were compared between women with normal receptivity and those with a 2-day pre-receptive endometrium. Endometrial biopsies were analyzed by RNA sequencing to identify differential gene expression associated with age and receptivity status. An independent small validation cohort was used for qRT-PCR validation. Results: Women in the impaired receptivity group (2-day pre-receptive) were significantly older than those in the normal receptivity group (34.3 ± 3.1 vs. 33.0 ± 4.1, Conclusion: AMA was independently associated with an increased likelihood of WOI displacement in women with RIF, suggesting that aberrant endometrial timing may be associated with implantation failure in this population. These findings provide a rationale for further investigation of personalized embryo transfer strategies in older patients, while the identified candidate genes should be regarded as preliminary molecular associations requiring further functional validation.
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