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

He A, Aihua He, Yang T, Tianli Yang, Sijia Lu, Lu S, Zou Y, Yangyun Zou, Cheng Wan, Wan C, Yulin Chen, Chen Y, Jing Zhao, Zhao J, Nenghui Liu, Liu N, Donge Liu, Liu D, Yumei Li, Li Y, Wang Y, Yonggang Wang, Xu B, Bin Xu, Hao J, Jie Hao, Jing Fu, Fu J, Qiong Zhang, Zhang Q, Baisheng Wang, Wang B, Yanping Li
Journal of assisted reproduction and genetics · 2025 · vol. 42(6) , pp. 2067–2082 · doi:10.1007/s10815-025-03468-8 · PMID:40304883 · PMC12229385
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A modified single-time point RNA-sequencing-based endometrial receptivity test accurately predicted the hourly window of implantation and significantly improved pregnancy outcomes for patients with recurrent implantation failure compared to conventional embryo transfer.

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This study developed a modified single-time point RNA-sequencing-based endometrial receptivity test to predict the hourly precision window of implantation for patients with recurrent implantation failure. The researchers validated the model in two phases, demonstrating an average accuracy of 94.51% and high sensitivity and specificity compared to conventional embryo transfer methods. Clinical outcomes including positive beta-hCG, implantation rates, and live birth rates were significantly improved in the experimental group after adjusting for confounders via propensity score matching. Relevance to endometriosis: listed as one indication for GnRH antagonists, though the paper's main focus is uterine fibroids.

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Abstract

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.
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Abstract

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.

Keywords

Endometrial receptivity; Personalized embryo transfer; RNA-sequencing; Recurrent implantation failure; Window of implantation. © 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. Conflict of interest statement Declarations. Ethics approval and consent to participate: The study was approved by the Reproductive Medicine Ethics Committee of Xiangya Hospital, Central South University (CSU) (No. 2017002) and registered in the Chinese Clinical Trial Registry (No. ChiCTR-DDD-17013375). Written informed consent was obtained from all participants, and we conducted it according to the tenets of the Declaration of Helsinki. Conflict of interest: The authors declare no competing interests. Figures

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Embryo Implantation Embryo Implantation Endometrium Endometrium Endometrium Infertility, Female Infertility, Female RNA-Seq RNA-Seq Adult Embryo Transfer Embryo Transfer Female Fertilization in Vitro Fertilization in Vitro Humans Live Birth Pregnancy Pregnancy Rate

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