Multi-omics biomarkers in endometrial receptivity: from mechanisms to clinical translation

Endometrial receptivity (ER) serves as a critical determinant for successful embryo implantation, yet its molecular complexity and limited clinical assessment methods pose significant challenges. Despite advancements in assisted reproductive technology (ART), recurrent implantation failure (RIF) linked to ER abnormalities persists, creating a need for precise, non-invasive diagnostics. This review outlines ER research, from the biology of the window of implantation (WOI) to the roles of immune components and the microbiome in shaping the receptive microenvironment. Multi-omics integration reveals regulatory networks across transcriptomic, epigenomic, proteomic, and metabolomic levels, with uterine fluid biomarkers emerging as promising non-invasive candidates. The analysis further covers how chronic endometritis (CE), adenomyosis, and polycystic ovary syndrome (PCOS) impair ER: through mechanisms including inflammatory imbalance, microbial dysbiosis, abnormal extracellular matrix remodeling, and hormonal dysregulation. Commercial ER tests face limitations, including insufficient evidence and inconsistent results, which undermine their clinical reliability. A significant translational gap remains between biomarker discovery and clinical application. Current challenges involve technical standardization and data integration, and poor model generalizability. Future progress requires combining multi-omics with artificial intelligence (AI) to establish standardized clinical pathways, advancing ER assessment into precision medicine, and improving global infertility management.