Recurrent Implantation Failure, Recurrent Pregnancy Loss, Infertility, Female, Endometrial Diseases, Endometritis, Endometriosis, Adenomyosis
Conditions
Keywords
Uterine Immune Profile, Endometrial Receptivity, Infertility, Recurrent Miscarriage, IVF Failure, Implantation Window, Reproductive Immunology, Endometrial Microbiome, Chronic Endometritis, Adenomyosis, Endometriosis
Brief summary
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.
Detailed description
The IMERR study is a prospective, monocentric, controlled interventional study aiming to identify immune and microbiological signatures in the eutopic endometrium of women undergoing ART (IVF/ICSI), with and without a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL). RIF is defined as the absence of clinical pregnancy after at least three embryo transfers of good-quality blastocysts, and RPL as two or more consecutive pregnancy losses before 24 weeks of gestation. Participants will be divided into two groups: a study group (with RIF and/or RPL) and a control group (without RIF or RPL). Endometrial biopsies will be collected during the implantation window, alongside peripheral blood and vaginal samples. These samples will undergo immunological and microbiological analyses, including histology, immunophenotyping, and microbiota profiling. The study aims to (i) Characterize immune cell populations in the endometrium and blood, (ii) Investigate the endometrial microbiome and its potential dysbiosis, (iii) Explore associations between these biological profiles and clinical features such as endometriosis, adenomyosis, chronic endometritis, or uterine contractility disorders. The study includes 100 participants and spans a total duration of 60 months (36 months for inclusion and 24 months of follow-up). A subgroup analysis will assess the association between immuno-microbiological profiles and clinical outcomes after embryo transfer within the 24-month post-inclusion period. By identifying predictive markers of RIF and RPL, this study may help establish new diagnostic tools and personalized treatment strategies in reproductive medicine.
Interventions
DIAGNOSTIC_TESTEndometrial Biopsy
Endometrial 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)
DIAGNOSTIC_TESTVaginal Swab
Vaginal sample collection using a cotton swab. Part of the treatment
DIAGNOSTIC_TESTBlood sample
Peripheral blood draw. Part of the treatment + 10 mL additional for research
DIAGNOSTIC_TESTPelvic ultrasound (±pelvic MRI)
Pelvic ultrasound (±pelvic MRI). Part of the treatment
Sponsors
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
ADREGOF
URC-CIC Paris Descartes Necker Cochin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Female aged ≥18 and \<36 years * Undergoing assisted reproductive technology (ART) in a fertility center * Covered by the French national health insurance system * Belonging to one of two groups: * Study group: history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL) * Control group: no history of RIF or RPL
Exclusion criteria
* 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) * Known chromosomal abnormality in either partner * Known autoimmune disease, thrombophilia, or antiphospholipid antibody syndrome * Persons under legal protection (e.g., guardianship, curatorship)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Profiling of endometrial immune cell populations | Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microbiological profiling of endometrial tissue | Baseline | 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 | Baseline | 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 | Baseline | 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) |
Countries
France
Contacts
CONTACTMathilde Bourdon, MD, PhD
CONTACTMarie Benhammani-Godard
PRINCIPAL_INVESTIGATORMathilde Bourdon, MD, PhD
Service de Gynécologie Obstétrique II et Médecine de la Reproduction - Cochin Hospital
Outcome results
None listed