Abstract
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 registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx
Highlights
Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF)
In vitro fertilization (IVF) in vitro fertilization, rsERT RNA sequencing (RNA-Seq)-based endometrial receptivity test, BMI body mass index, AMH anti-Mullerian hormone, Follicle-stimulating hormone (FSH) follicle-stimulating hormone, AFC antral follicle count the second phase, 56 of the 142 enrolled patients with RIF were assigned to the experimental group and 86 to the control group by self-selection
48 of 56 patients with RIF received rsERT-guided personalized embryo transfer (pET); for 5 patients had poor-quality or collapsed freeze–thaw embryos, and 3 patients were lost to follow-up
Summary
Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). Inadequate endometrial receptivity (ER), defined as the ability of the endometrium to accept and accommodate a nascent embryo, is responsible for approximately two-thirds of implantation failures [2]. This period of receptivity is known as the “window of implantation” (WOI) [3], which usually occurs on days 19–24 of the menstrual cycle [4], on day 7 after the LH surge (LH + 7) in the natural cycle or on day 5 after progesterone administration (P + 5) in the artificial cycle [2, 5]. An objective and accurate determination of the optimal WOI is crucial for improving the outcomes of pregnancy facilitated by assisted reproductive technology (ART)
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