Highlights
•Receptive and non-receptive endometria display different protein abundance patterns.
•AHNAK, DSP, and KRT1 are more abundant proteins in receptive endometrium.
•MSN and FBLN1 are more abundant proteins in non-receptive endometrium.
•MSN has the highest accuracy to discriminate receptive endometrium in main cohort.
•FBLN1 has the highest accuracy to discern non-receptive group in independent cohort.
Abstract
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 in vitro fertilization -frozen embryo transfer (IVF-FET) patients two days before embryo transfer. 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 analyzed using tandem mass tag labeling 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. Meanwhile, biological processes such as receptor internalization, negative regulation of cell junctions, the immune response and inflammation, and actin cytoskeleton organization were enriched in the non-receptive group. The key proteins, including desmoplakin, keratin type II cytoskeletal 1, and the neuroblast differentiation-associated proteins AHNAK (more abundant proteins in the receptive group) and moesin and fibulin-1 (less abundant proteins in the receptive group) 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 ET cycle, potentially improving personalized embryo transfer timing in clinical settings.
https://www.rbmojournal.com/article/S1472-6483(25)00290-1/abstract