Proteomic Analysis of Receptive and Non-receptive Endometria-derived Uterine Fluid by LC-MS/MS

The current diagnostic tools used to determine the precise timing of embryo transfer for in vitro fertilization (IVF)-frozen embryo transfer (FET) patients are not non-invasive or accurate. As uterine fluid is collected via a minimally invasive procedure and reflects alterations in the molecular composition of the endometrium during the menstrual cycle, it can be considered an accurate diagnostic source for identifying endometrial receptivity-related proteins. Therefore, we aimed to identify a panel of molecular biomarkers for endometrial receptivity by investigating uterine fluid lavage (UFL). The UFLs of 18 IVF-FET patients were collected two days before FET. After seven weeks, the patients were divided into receptive and non-receptive groups on the basis of ultrasonography results for clinical pregnancy. Protein profiling of the collected UFLs was performed via tandem mass tag labeling and mass spectrometry liquid chromatography. Next, differentially abundant proteins between the two groups were identified. Additionally, the largest contributions of the variable to the differences based on the variable of importance in projection (VIP) score value were inspected. The candidate protein panel was selected on the basis of the VIP score and protein database analysis. The accuracy of the candidate panel was assessed via logistic regression as a machine learning approach. Finally, western blot analysis confirmed the results.