The IMERR study aims to improve understanding of certain causes of infertility related to recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL), conditions that affect many women undergoing assisted reproductive technology (ART). Despite medical advances, some patients repeatedly fail to achieve pregnancy, or experience repeated miscarriages. These situations may be linked to subtle immune or microbial disturbances in the uterus. This study seeks to identify immune and microbiological profiles in the endometrium during the implantation window-a crucial period when the embryo attaches to the uterine wall. We will compare women who have experienced RIF and/or RPL with women who have had no such history. Blood and uterine samples will be analyzed to investigate whether certain immune or microbial features are associated with these reproductive failures. The ultimate goal is to uncover predictive factors that may explain why some women experience implantation failure or pregnancy loss, and to lay the foundation for future personalized treatments to improve reproductive outcomes.
Female aged ≥18 and <36 years
Undergoing assisted reproductive technology (ART) in a fertility center
Covered by the French national health insurance system
Study group: history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL)
Pregnant at inclusion
Refusal to provide written informed consent
Antibiotic use within one month prior to endometrial biopsy Positive serology for hepatitis B, hepatitis C or HIV
Uterine anatomical abnormalities (e.g., polyps, cavity-distorting fibroids, untreated hydrosalpinx)
Parallel
Endometrial Biopsy
Diagnostic testEndometrial biopsy with Cornier Pipelle (part of the treatment in the RIF/RPL group and some patients of the control group / added for the research for the other patients of the control group)
Vaginal Swab
Diagnostic testVaginal sample collection using a cotton swab. Part of the treatment
Blood sample
Diagnostic testPeripheral blood draw. Part of the treatment + 10 mL additional for research
Pelvic ultrasound (±pelvic MRI)
Diagnostic testPelvic ultrasound (±pelvic MRI). Part of the treatment
Profiling of endometrial immune cell populations
Profiling of endometrial immune cell populations (proportion of subpopulation) during the implantation window using single-cell transcriptomics and/or flow cytometry. Endometrial biopsies will be collected during the implantation window. Immune cell populations will be characterized using either single-cell RNA sequencing (scRNA-seq) and /or multiparametric flow cytometry, depending on technical feasibility and sample quality. For scRNA-seq, transcriptomic analysis will be performed (e.g., using the 10x Genomics platform), and immune cell types will be identified via clustering and annotation algorithms. For flow cytometry, immune subsets will be identified and quantified based on surface marker expression. Comparisons of immune profiles will be made between women with and without a history of RIF and/or RPL.
Microbiological profiling of endometrial tissue
Microbiological profiling of endometrial tissue during the implantation window using next-generation sequencing (NGS) Endometrial microbiota will be characterized by next-generation sequencing (NGS) of DNA extracted from endometrial biopsy samples collected during the implantation window. Diversity metrics (alpha and beta diversity) and relative abundances of microbial taxa will be compared between women with and without a history of RIF and/or RPL.
Characterization of peripheral blood immune cell populations
Characterization of peripheral blood immune cell populations during the implantation window using single-cell transcriptomics and/or flow cytometry Peripheral blood samples will be collected at inclusion. Immune profiling will be performed to characterize circulating immune cell subpopulations. Depending on feasibility and sample quality, either single-cell RNA sequencing (scRNA-seq) and / or multiparametric flow cytometry may be used. Immune profiles will be compared between women with and without a history of RIF and/or RPL.
Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics
This outcome consists of exploratory analyses assessing the associations between previously measured immune and microbiological profiles (from endometrial tissue) and (i) clinical outcomes (e.g., pregnancy, miscarriage, live birth), (ii) radiological findings (e.g., adenomyosis, uterine contractility), and (iii) histological/bacteriological findings (e.g., chronic endometritis with CD138+ cells or vaginal cultures). No new biological measurements will be performed. Each association will be reported as a separate statistical outcome (e.g., odds ratios, p-values)
Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics
This outcome consists of exploratory analyses assessing the associations between previously measured immune and microbiological profiles (from endometrial tissue) and (i) clinical outcomes (e.g., pregnancy, miscarriage, live birth), (ii) radiological findings (e.g., adenomyosis, uterine contractility), and (iii) histological/bacteriological findings (e.g., chronic endometritis with CD138+ cells or vaginal cultures). No new biological measurements will be performed. Each association will be reported as a separate statistical outcome (e.g., odds ratios, p-values)
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Institut National de la Santé Et de la Recherche Médicale, France
Collaborator
ADREGOF
Collaborator
URC-CIC Paris Descartes Necker Cochin
Collaborator
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