Circulating markers for endometrial receptivity: current status and future prospects
摘要
Embryo implantation represents a critical bottleneck in human reproduction, and impaired endometrial receptivity is a major contributor to recurrent implantation failure (RIF) and infertility. Current clinical tools for receptivity assessment, such as histological dating and transcriptome-based assays (e.g., ERA), are invasive, cycle-disruptive, and limited in predictive power. Consequently, there is a growing demand for minimally invasive, dynamic biomarkers that can reliably capture the molecular and cellular events underpinning the window of implantation. Circulating markers including proteins, cytokines, growth factors, adhesion molecules, cell-free nucleic acids, and extracellular vesicles have emerged as promising candidates. These molecules, detectable in blood, uterine fluid, or cervicovaginal secretions, reflect immune modulation, tissue remodeling, and embryo–maternal crosstalk essential for implantation. Recent studies highlight the diagnostic potential of serum VEGF, MMP-7, LIF, glycodelin, as well as cfDNA methylation signatures and cfRNAs such as HOXA10 and LIF. Extracellular vesicles enriched in implantation-related proteins and non-coding RNAs further underscore their functional role in embryo–endometrium dialogue. While most candidates remain in early validation stages, integrative multi-marker and multi-omics approaches, supported by AI-based modeling, hold promise for clinical translation. In this review we summarize the emerging technologies, and discuss challenges and future directions for developing non-invasive, biomarker-guided strategies to improve reproductive outcomes.