Aihua He1,2, Yangyun Zou3, Cheng Wan3, Jing Zhao1,2, Qiong Zhang1,2, Zhongyuan Yao1,2, Fen Tian1,2, Hong Wu4,5, Xi Huang1,2, Jing Fu1,2, Chunxu Hu3, Yue Sun3, Lan Xiao1,2, Tianli Yang1,2, Zhaojuan Hou1,2, Xin Dong3, Sijia Lu6, Yanping Li7,8. 1. Department of Reproductive Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, Hunan, China. 2. Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, 410000, Hunan, China. 3. Department of Clinical Research, Yikon Genomics Company, Ltd., #301, Building A3, No. 218, Xinghu Street, Suzhou, 215123, Jiangsu, China. 4. Department of ENT, Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China. 5. Key Laboratory of Otolaryngology in Hunan Province, Changsha, 410000, Hunan, China. 6. Department of Clinical Research, Yikon Genomics Company, Ltd., #301, Building A3, No. 218, Xinghu Street, Suzhou, 215123, Jiangsu, China. lusijia@yikongenomics.com. 7. Department of Reproductive Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, Hunan, China. liyanp@csu.edu.cn. 8. Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, 410000, Hunan, China. liyanp@csu.edu.cn.
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.
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 IVFpatients 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.
Authors: Lukasz T Polanski; Miriam N Baumgarten; Siobhan Quenby; Jan Brosens; Bruce K Campbell; Nicholas J Raine-Fenning Journal: Reprod Biomed Online Date: 2014-01-17 Impact factor: 3.828