Establishment and application of an RNA-seq-based predictive model for the hourly precision window of implantation (WOI) in patients with recurrent implantation failure.

PURPOSE: This study aims to establish a single-time point RNA-sequencing-based endometrial receptivity test (rsERT) to provide hourly precision of endometrial WOI for patients with recurrent implantation failure (RIF). METHODS: A two-phase study was conducted. In the first phase, a total of 70 patients with successful intrauterine pregnancy after personalized embryo transfer (pET) guided by three-time points rsERT were recruited for modified rsERT. Another 21 patients who underwent the prototype of single-time point rsERT were further included for optimization. In the second phase, another cohort of 574 patients with RIF that was recruited and assigned to the experimental group underwent pET guided by the modified rsERT (n = 261) or the control group underwent conventional ET (n = 313). The positive β-human chorionic gonadotropin (β-hCG), intrauterine pregnancy rate (IPR), implantation rate (IR), ongoing pregnancy rate, and live birth rate of the two groups were analyzed. RESULT: The modified rsERT provided an hour-based predictive result of endometrial WOI with an average accuracy of 94.51% and sensitivity and specificity of 92.73% and 96.29%, respectively. The positive β-hCG, IPR, IR, ongoing pregnancy rate, and live birth rate of the experimental group were significantly different from those in the control group. After propensity score matching (PSM) control for the confounders, positive β-hCG, IR, and early spontaneous abortion rate showed significant differences. CONCLUSION: The modified rsERT provided hourly precision WOI prediction using a single-time point endometrial biopsy and pregnancy outcomes were significantly improved, providing an enhanced endometrial receptivity test as an alternative requiring only a single-time point sampling for patients with RIF.