Inflammatory proteomics of uterine fluid is potentially a non-invasive predictor for endometrial receptivity: a pilot study

Objective: To evaluate if the inflammatory proteomics of uterine fluid could define the endometrial receptivity phase. Methods: Inflammatory proteomics of uterine fluid were measured using the OLINK Target-96 Inflammation panel. Endometrial receptivity testing (ERT) combined with endometrial dating was a gold standard for defining the endometrial receptivity phase. A predictive model based on proteomics of uterine fluid was established to predict the endometrial receptivity phase. Results: The inflammatory factors in uterine fluid were differentially expressed between window of implantation (WOI) and displaced WOI groups, and the displaced WOI group was characterized by the increased expression of a variety of inflammatory factors. The predictive model established based on the top 5 differential proteins could accurately classify the endometrial receptive phase. Transcriptomic data from endometrial tissues showed that the differential gene sets between different receptive phases were mostly enriched in immune-related processes, and the expression of immune-related genes in the WOI group was significantly lower than that in the displaced WOI group. Conclusions: Detection of inflammatory proteins from the uterine fluid using the OLINK inflammation panel could be a novel non-invasive method to define the endometrial receptive phase. The inflammatory immune response during the embryo implantation window was inhibited to adapt to the implantation of the semi-alloimmune embryos.