Multi-omics signatures of endometrial receptivity in recurrent implantation failure: a systematic review

Recurrent implantation failure (RIF) affects an estimated 10–15% of women undergoing in vitro fertilisation and may involve impaired endometrial receptivity. This qualitative systematic review synthesised post-2017 multi-omics evidence to identify recurring molecular themes associated with RIF. PubMed, Google Scholar, Scopus, and Web of Science were searched for studies published from January 2017 to March 2026. Of 628 records in the reported screening workflow, 92 publications were retained. Primary/original-data studies informed the formal molecular synthesis, whereas reviews, protocols, and contextual publications were used separately for interpretation and reference screening. Because designs and outcomes were heterogeneous, no meta-analysis was performed. Direct RIF evidence supported three recurring pathway-level themes. First, HOXA10- centred regulation was implicated through epitranscriptomic and non-coding RNA mechanisms, while direct methylation evidence involved NLRP2 and SERPINA5 . Second, immune, metabolic, and microbiome-associated abnormalities suggested an immune–metabolic theme without establishing a single causal inflammatory pathway. Third, mitochondrial and energetic abnormalities were reported across several omics layers. Interpretation was limited by heterogeneous RIF definitions, small cohorts, indirect evidence, and non-standardised analytical pipelines. Current evidence supports pathway-level convergence rather than a single proven molecular mechanism. Prospective multicentre studies using harmonised phenotyping, standardised sample handling, integrated multi-omics analysis, and independent validation are required before candidate biomarkers or treatment strategies can be adopted clinically.