The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure.
The role of transcriptomic biomarkers of endometrial receptivity in personalized embryo transfer for patients with repeated implantation failure.
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子宫内膜容受性转录组生物标志物在反复植入失败患者个性化胚胎移植中的作用
DOI：
10.1186/s12967-021-02837-y
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发表时间：
2021-04-28
影响因子：
7.4
通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
He A;Zou Y;Wan C;Zhao J;Zhang Q;Yao Z;Tian F;Wu H;Huang X;Fu J;Hu C;Sun Y;Xiao L;Yang T;Hou Z;Dong X;Lu S;Li Y
着床窗口（WOI）移位是胚胎着床失败，尤其是反复着床失败（RIF）的子宫内膜成因之一。子宫内膜容受性（ER）的准确预测工具是精确指导胚胎植入成功的迫切需要。我们旨在使用转录组生物标志物建立基于rna - seq的子宫内膜容受性测试（rsERT）工具，并评估由该工具指导的RIF患者个性化胚胎移植（pET）的益处。方法本研究分为两阶段，包括回顾性数据的工具建立和前瞻性非随机对照试验的获益评估。在第一阶段，通过对50例WOI时间正常的IVF患者子宫内膜组织的RNA进行测序和分析，建立rsERT。在第二阶段，招募142例RIF患者，根据患者自我选择分组（实验组，n = 56；对照组，n = 86）。实验组采用rsERT引导下的pET，对照组采用常规ET。结果rsERT包含175个生物标记基因，经10倍交叉验证，平均准确率为98.4%。第3天胚胎移植时，实验组的宫内妊娠率（IPR）为50.0%，显著高于对照组（23.7%）（RR, 2.107; 95% CI 1.159 ~ 3.830；P= 0.017）。虽然差异无统计学意义，但实验组的IPR（63.6%）仍比对照组（40.7%）高20个百分点（RR, 1.562; 95% CI 0.898 ~ 2.718；P= 0.111）。结论rsERT能准确预测WOI期，显著改善RIF患者妊娠结局，显示了rsERT引导pET的临床潜力。中国临床试验注册中心：ChiCTR-DDD-17013375。2017年11月14日注册，http://www.chictr.org.cn/index.aspx
BackgroundWindow 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.MethodsThis 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.ResultsThe 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.ConclusionsThe 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 registrationChinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx