Multi-omics review maps molecular pathways tied to recurrent implantation failure

Recurrent implantation failure, a frustrating outcome for an estimated 10–15% of women undergoing in vitro fertilisation, may in part reflect impaired endometrial receptivity. A new qualitative systematic review published in BMC Medical Genomics on 5 October 2026 synthesised multi-omics evidence published after 2017 to identify recurring molecular themes associated with the condition, and its authors conclude that the field shows pathway-level convergence rather than a single proven molecular mechanism.

The review, led by Asmita Govekar and Shalaka Ramgir-Naidu, searched PubMed, Google Scholar, Scopus and Web of Science for studies published from January 2017 to March 2026. Of 628 records in the reported screening workflow, 92 publications were retained. Primary and original-data studies informed the formal molecular synthesis, while reviews, protocols and contextual publications were used separately for interpretation and reference screening. Because the designs and outcomes of the included studies were heterogeneous, the authors performed no meta-analysis.

Direct evidence from recurrent implantation failure studies supported three recurring pathway-level themes. The first centred on HOXA10 regulation, implicated through epitranscriptomic and non-coding RNA mechanisms, while direct methylation evidence involved the genes NLRP2 and SERPINA5.

The second theme linked immune, metabolic and microbiome-associated abnormalities. The authors describe this as an immune–metabolic theme, but they are careful to note that the evidence does not establish a single causal inflammatory pathway. The third theme involved mitochondrial and energetic abnormalities, which were reported across several omics layers, suggesting that cellular energy metabolism may be a recurring feature of the receptive endometrium in affected patients.

The review’s interpretation is bounded by important limitations. The authors cite heterogeneous definitions of recurrent implantation failure, small cohorts, indirect evidence and non-standardised analytical pipelines as factors that constrain the conclusions.

According to the summary of the review, 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. In other words, the molecular signals identified so far are promising leads for future research, but they are not yet ready for use in fertility clinics.

The article is published open access and is currently available as an early-release version, which the publisher notes is subject to further edits and will be replaced by the final Version of Record.

For patients and clinicians, the review offers a structured map of where molecular research on endometrial receptivity is converging, while tempering expectations about immediate clinical translation. The identified themes — HOXA10-centred regulation, immune–metabolic abnormalities and mitochondrial dysfunction — provide a framework for designing the larger, standardised studies that the authors say are needed before any molecular test or intervention can be justified in practice.

Subject of Research: Multi-omics signatures of endometrial receptivity in recurrent implantation failure

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

Article References: Govekar, A., & Ramgir-Naidu, S. (2026). Multi-omics signatures of endometrial receptivity in recurrent implantation failure: a systematic review. BMC Medical Genomics. https://doi.org/10.1186/s12920-026-02467-7

Image Credits: AI Generated

DOI: 10.1186/s12920-026-02467-7

Keywords: recurrent implantation failure, endometrial receptivity, multi-omics, systematic review, HOXA10, NLRP2, SERPINA5, mitochondrial dysfunction, in vitro fertilisation, BMC Medical Genomics, biomarkers, epitranscriptomics