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Mixed double-embryo transfer: A promising approach for patients with repeated implantation failure.

ABSTRACT: The purpose of this study was to evaluate the efficacy of frozen mixed double-embryo transfer (MDET; the simultaneous transfer of day 3 and day 5 embryos) in comparison with frozen blastocyst double-embryo transfer (BDET; transfer of two day 5 blastocysts) in patients with repeated implantation failure (RIF).A total of 104 women with RIF who underwent frozen MDET (n=48) or BDET (n=56) with excellent-quality embryos were included in this retrospective analysis. All frozen embryo transfers were performed in natural cycles. The main outcome measures were the implantation rate, clinical pregnancy rate, multiple pregnancy rate, and miscarriage rate. These measures were compared between the patients who underwent MDET or BDET using the chi-square test or the Fisher exact test, as appropriate.The implantation and clinical pregnancy rates were significantly higher in patients who underwent MDET than in those who underwent BDET (60.4% vs. 39.3%, p=0.03 and 52.1% vs. 30.4%, p=0.05, respectively). A significantly lower miscarriage rate was observed in the MDET group (6.9% vs. 10.7%, p=0.05). In addition, the multiple pregnancy rate was slightly, but not significantly, higher in the MDET group (27.1% vs. 25.0%).MDET was found to be significantly superior to double blastocyst transfer. It could be regarded as an appropriate approach to improve in vitro fertilization success rates in RIF patients.

SUBMITTER: Stamenov GS

PROVIDER: S-EPMC5545218 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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Project description: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.

Project description:IntroductionSuccessful embryo implantation, is the initiating step of pregnancy, relies on not only the high quality of the embryo but also the synergistic development of a healthy endometrium. Characterization and identification of biomarkers for the receptive endometrium is an effective method for increasing the probability of successful embryo implantation.MethodsEndometrial tissues from 22 women with a history of recurrent implantation failure (RIF) and 19 fertile controls were collected using biopsy catheters on 7-9 days after the peak of luteinizing hormone. Differentially expressed proteins (DEPs) were identified in six patients with RIF and six fertile controls using isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis.ResultsTwo hundred and sixty-three DEPs, including proteins with multiple bioactivities, such as protein translation, mitochondrial function, oxidoreductase activity, fatty acid and amino acid metabolism, were identified from iTRAQ. Four potential biomarkers for receptive endometrium named tubulin polymerization-promoting protein family member 3 TPPP3, S100 Calcium Binding Protein A13 (S100A13), 17b-hydroxysteroid dehydrogenase 2 (HSD17B2), and alpha-2-glycoprotein 1, zinc binding (AZGP1) were further verified using ProteinSimple Wes and immunohistochemical staining in all included samples (n=22 for RIF and n=19 for controls). Of the four proteins, the protein levels of TPPP3 and HSD17B2 were significantly downregulated in the endometrium of patients with RIF.DiscussionPoor endometrial receptivity is considered the main reason for the decrease in pregnancy success rates in patients suffering from RIF. iTRAQ techniques based on isotope markers can identify and quantify low abundance proteomics, and may be suitable for identifying differentially expressed proteins in RIF. This study provides novel evidence that TPPP3 and HSD17B2 may be effective targets for the diagnosis and treatment of non-receptive endometrium and RIF.

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Mixed double-embryo transfer: A promising approach for patients with repeated implantation failure.

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