Endometrial factors in the implantation failure spectrum: protocol of a MUltidisciplinary observational cohort study in women with Repeated Implantation failure and recurrent Miscarriage (MURIM Study)

Abstract

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.

The clinical efficacy evaluation of endometrial receptivity analysis (ERA) and Study on the influence factors of displaced window of implantation (WOI): A 6-year retrospective study on a large sample

“…This is a new discovery, indicating that the displacement of the implantation window may be related to early abortion. However, for RIF patients, pET did not have such an effect, we believe the possible reasons are that patients with RIF have numerous other factors that can lead to miscarriage, including factors such as aneuploidy [28][29][30][31]. But we need to pay attention to another point of endometrial scraping, which is an intentional damage to the endometrium that is carried out with the aim of improving outcomes from fertility treatment or the chance of natural conception [32,33].…”

Local production of 17β-oestradiol in the endometrium during the implantation window: a pilot study

“…Besides, non-invasive methods for endometrial assessment in the cycle of the transfer such as a liquid biopsy (i.e. sampling endometrial fluid) could eliminate intercyclic variation in the future ( Schobers et al 2021 , Stevens Brentjens et al 2022 ).…”