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

Abstract

Abstract: Background: Accurate 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. Methods: A 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. Results: The 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 β-hCG positive rate, intrauterine pregnancy rate (IPR) and implantation rate (IR) of the experimental group were significantly improved (β-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 (β-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). Conclusions: The 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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ChiCTR-DDD-17013375

Funding Statement

This study was supported by the Hunan Provincial Natural Science Foundation General Program (2023JJ30823) and Postdoctoral Fellowship Program of CPSF (GZC20233157).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Reproductive Medicine Ethics Committee of Xiangya Hospital, Central South University (CSU) (No. 2017002) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

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