Noninvasive Chromosome Screening for Evaluating the Clinical Outcomes of Patients With Recurrent Pregnancy Loss or Repeated Implantation Failure

Background: This retrospective cohort study determines whether noninvasive chromosome screening (NICS) for aneuploidy can improve the clinical outcomes of patients with recurrent pregnancy loss (RPL) or repeated implantation failure (RIF) in assisted reproductive technology.Methods: A total of 273 women with a history of RPL or RIF between 2018 and 2021 were included in this study. We collected data of all oocyte retrieval cycles and single blastocyst resuscitation transfer cycles.Results: For the RPL patients, NICS reduced the miscarriages rate per frozen embryo transfer (FET), improved the ongoing pregnancies rate and live birth rate: 17.9% vs 42.6%, adjusted OR 0.39, 95% CI 0.16–0.95; 40.7% vs 25.0%, adjusted OR 2.00, 95% CI 1.04–3.82; 38.9% vs 20.6%, adjusted OR 2.53, 95% CI 1.28–5.02, respectively. For the RIF patients, the pregnancy rates per FET in the NICS group were significantly higher than in the non-NICS group (46.9% vs. 28.7%, adjusted OR 2.82, 95% CI 1.20–6.66).Conclusions: This study demonstrated that selection of euploid embryos through NICS can reduce the miscarriage rate of patients with RPL and improve the clinical pregnancy rate of patients with RIF. Our data suggested that NICS could be used as a diagnostic test in clinical practice.

Platelet-Rich Plasma Improves Pregnancy Rate and Repairs Endometrial Injury in Patients with Repeated Implantation Failure

Objective: The effects investigated in this study for the therapy with autologous platelet-rich plasma (PRP) on the thin endometrium in a rat model and patients with repeated implantation failure (RIF). Methods: PRP were immediately injected into uterine cavity after the establishing a model of thin endometrial injury by injection with 95% ethanol into uterus of SD rat. We have used H&E staining to explore the endometrial morphological alteration. The immunohistochemistry, Western blots, and quantitative RT-PCR were used to determine the endometrial receptivity. RL95-2 cells were incubated with RPR at the different concentrations to detect the effect of PRP on the endometrial epithelial cell proliferation. Patients (n = 51) were divided into the control and PRP treatment groups. Patients in the PRP treatment group received PRP by intrauterine perfusion. Results: Endometrial morphology was significantly improved after PRP intrauterine infusion thrice-administered SD rats. PRP increased the thickness of thin endometrium in rats and up-regulate the expression of receptivity markers, including vimentin, vascular endothelial growth factor (VEGF) and integrin β3. In the control (n = 25) and PRP treatment (n = 26) groups, no significant differences were observed in rates of clinical pregnancy (50.0% vs. 44.0%, p = 0.67), implantation (40.5% vs. 26.0%, p = 0.15) and miscarriage (30.8% vs. 18.2%, p = 0.48). Conclusions: The transplantation of PRP repairs the endometrial injury by suppressing receptivity, enhancing endometrial cell proliferation and vascular remodeling. PRP improves the pregnancy rate in RIF patients.

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

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