Comparative proteomic analysis of receptive and non-receptive endometria-derived uterine fluid suggests a panel for endometrial receptivity assessment

Research question: Can proteomic analysis of uterine fluid identify a panel of proteins that could potentially improve targeted embryo transfer strategies in IVF? Design: Uterine fluid samples were collected from 18 patients who had undergone in vitro fertilization (IVF) with frozen embryo transfer 2 days before embryo transfer (11 patients in the main cohort and 7 patients in the independent cohort). Seven weeks later, patients were categorized into receptive and non-receptive groups based on ultrasonography results confirming clinical pregnancy. The proteins in these samples were analysed using tandem mass tag labelling and mass spectrometry. Differentially abundant proteins between the two groups were identified, and the candidate protein panel was selected based on the variable of importance in projection score and protein database analysis. The accuracy of the candidate panel was assessed using logistic regression, and findings were confirmed through western blot analysis. Results: Bioinformatics analysis revealed that proteins related to protein synthesis, cell adhesion, keratinization, peroxisome proliferator-activated receptors, arachidonic acid metabolism and vascular endothelial growth factor were enriched in the receptive group. Biological processes, such as receptor internalization, negative regulation of cell junctions, the innate immune response, inflammatory response, and actin cytoskeleton organization were enriched in the non-receptive group. The key proteins, including desmoplakin, keratin type II cytoskeletal 1, the neuroblast differentiation-associated proteins AHNAK, moesin, and fibulin-1 were confirmed as potential biomarkers for assessing endometrial receptivity via western blot analysis. Conclusion: The candidate panel may provide an approach for evaluating endometrial receptivity in the embryo transfer cycle, potentially improving personalized embryo transfer timing in clinical settings.