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Controlled Clinical Trial
. 2021 Apr 28;19(1):176.
doi: 10.1186/s12967-021-02837-y.

The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure

Aihua He  1   2 , Yangyun Zou  3 , Cheng Wan  3 , Jing Zhao  1   2 , Qiong Zhang  1   2 , Zhongyuan Yao  1   2 , Fen Tian  1   2 , Hong Wu  4   5 , Xi Huang  1   2 , Jing Fu  1   2 , Chunxu Hu  3 , Yue Sun  3 , Lan Xiao  1   2 , Tianli Yang  1   2 , Zhaojuan Hou  1   2 , Xin Dong  3 , Sijia Lu  6 , Yanping Li  7   8
Affiliations
Controlled Clinical Trial

The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure

Aihua He et al. J Transl Med. .

Abstract

Background: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.

Methods: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.

Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts.

Conclusions: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.

Keywords: Biomarkers; Endometrial receptivity; Personalized embryo transfer; RNA-Seq; Repeated implantation failure; Window of implantation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of participants in the rsERT-guided pET trial (the second phase of the current study)
Fig. 2
Fig. 2
Hierarchical clustering of the RNA expression data from 50 individuals; three samples per individual were obtained, one at each ER stage
Fig. 3
Fig. 3
Establishment and validation of the RNA-Seq-based endometrial receptivity test (rsERT). a Linear discriminant analysis (LDA) of endometrial receptivity conditions based on selected predictive markers. b ROC curves generated by 100 random splits into a training set and a test set
Fig. 4
Fig. 4
Comparison of pregnancy outcomes in experimental and control group. a–c IPR, LBR and IR for patients transferred day 3 embryos; d–f IPR, LBR and IR for patients transferred blastocysts
See this image and copyright information in PMC

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