Application of RNA-sequencing based predictive model for endometrial WOI in patients with recurrent implantation failure: a prospective cohort study

BackgroundAccurate prediction for endometrial window of implantation (WOI) would maximize the effectiveness of assisted reproductive technology. Previously, we have established a predictive model for endometrial WOI (rsERT) by three-time points sampling from the same patient at 48-hour intervals during one menstrual cycle. However, it is imperative to build a modified rsERT by single time point sampling in order to prevent multiple sampling and collateral harm. MethodsA two-phase study was conducted. In the first phase, patients with successful clinical pregnancy after personalized embryo transfer (pET) guided by three-time points rsERT were recruited. Endometrial tissues obtained from single time point were used for the modified rsERT establishment. In the second phase, recurrent implantation failure (RIF) patients were recruited and assigned to experimental group underwent pET guided by modified rsERT or control group underwent conventional ET. Pregnant outcomes were recorded and analyzed. ResultsThe modified rsERT was established using 91 eligible participants and could provide hour-based predictive result of endometrial WOI with an average accuracy of 94.51% with sensitivity and specificity being 92.73% and 96.27% using 10-fold CV. 176 RIF patients were recruited in the second phase (experimental group: n=88; control group: n=88). 40 of 88 (45.45%) patients showed WOI displacement, and 5.00% (2/40) of them were with advanced WOI, and the remaining 95.00% (38/40) with delayed WOI. The {beta}-hCG positive rate, intrauterine pregnancy rate (IPR) and implantation rate (IR) of the experimental group were significantly improved ({beta}-hCG positive rate: 67.05% vs. 39.77%, P=0.000; IPR: 61.36% vs. 31.82%, P=0.000; IR: 42.86% vs. 24.66%, P=0.001). While, pregnancy outcomes were not significantly different using different endometrial preparation protocols ({beta}-hCG positive rate: 42.86% vs. 35.90%, P=0.508; IPR: 38.78% vs. 23.08%, P=0.116; IR: 30.12% vs. 17.46%, P=0.085). ConclusionsThe modified rsERT allowed WOI prediction using a single time point endometrial biopsy and pregnancy outcomes were significantly improved. This could provide an enhanced endometrial receptivity test as an alternative, requiring only a single time point sampling for RIF patients. FundingResearch grants from Hunan Provincial Natural Science Foundation General Program (2023JJ30823) and Postdoctoral Fellowship Program of CPSF (GZC20233157).