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The Addition of Endometrial Injury to Freeze-All Strategy in Women with Repeated Implantation Failures.

ABSTRACT: (1) Background: Recurrent implantation failure (RIF) after IVF remains a challenging topic for fertility specialists and a frustrating reality for patients with infertility. Various approaches have been investigated and applied towards the improvement of clinical outcomes. Through a nonrandomized clinical trial, we evaluated the effect of the combination of hysteroscopic endometrial injury and the freeze-all technique on pregnancy parameters in a cohort of RIF patients; (2) Methods: The study group comprised of 30 patients with RIF that underwent a hysteroscopic endometrial injury prior to a frozen embryo transfer cycle; another 30 patients with RIF, comprising the control group, underwent a standard frozen cycle with no adjuvant treatment before. Live birth comprised the primary outcome. Logistic and Poisson regression analyses were implemented to reveal potential independent predictors for all outcomes. (3) Results: Live birth rates were similar between groups (8/30 vs. 3/30, p = 0.0876). Biochemical and clinical pregnancy and miscarriages were also independent of the procedure (p = 0.7812, p = 0.3436 and p = 0.1213, respectively). The only confounding factor that contributed to biochemical pregnancy was the number of retrieved oocytes (0.1618 ± 0.0819, p = 0.0481); (4) Conclusions: The addition of endometrial injury to the freeze-all strategy in infertile women with RIF does not significantly improve pregnancy rates, including live birth. A properly conducted RCT with adequate sample size could give a robust answer.

SUBMITTER: Rigos I

PROVIDER: S-EPMC8156614 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:IntroductionWomen with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation of genetically aberrant or poor-quality embryos) versus RIF representing an overly selective endometrium (no implantation even with good quality embryos). In both cases, often no explanation for reproductive failure can be found and although promising add-on treatments have been introduced, therapeutic options are frequently limited to supportive care. Both RM and RIF are multifactorial and research indicates that the interplay between steroidogenesis, uterine natural killer (uNK) cells and the microbiome determine the capacity of the endometrium to be a biosensor for invading embryos. Our objective is to elucidate whether there is a difference in endometrial receptivity parameters (ie, steroid metabolism, uNK cells and the microbiome) between women aged 18-38 years with reproductive failure (RIF and RM), and fertile controls.Methods and analysisSingle-centre, observational cohort study. Endometrial biopsies, vaginal swabs and peripheral blood will be collected during the window of implantation and menstrual blood in the subsequent menstruation. The study parameters are the steroid profile (steroid levels and mRNA levels, protein expression and activity of steroid enzymes) in endometrial tissue and peripheral blood, as well as the activating or inhibitory phenotype of uNK cells based on receptor expression in menstrual blood and endometrial tissue and determination of the vaginal and endometrial microbiome using the inter spacer bacterial profiling technique.Ethics and disseminationThe protocol is approved by the local medical ethical review committee at the Maastricht University Medical Centre. Findings from this study will be shared with the academic and medical community and the patient organisations to optimise and individualise medical care of patients with implantation failure and miscarriages.Trial registration numberNTR7571, registered 28 February 2019.

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The Addition of Endometrial Injury to Freeze-All Strategy in Women with Repeated Implantation Failures.

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