Study of Immune and Microbiological Modifications of the Endometrium in Cases of Recurrent Implantation Failure and/or Recurrent Pregnancy Loss
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Profiling of endometrial immune cell populations
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
RIF/RPL group
Women undergoing ART with a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).
干预措施: Endometrial Biopsy (Diagnostic Test)
RIF/RPL group
Women undergoing ART with a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).
干预措施: Vaginal Swab (Diagnostic Test)
RIF/RPL group
Women undergoing ART with a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).
干预措施: Blood sample (Diagnostic Test)
RIF/RPL group
Women undergoing ART with a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).
干预措施: Pelvic ultrasound (±pelvic MRI) (Diagnostic Test)
Control group
Women undergoing ART without a history of RIF or RPL.
干预措施: Endometrial Biopsy (Diagnostic Test)
Control group
Women undergoing ART without a history of RIF or RPL.
干预措施: Vaginal Swab (Diagnostic Test)
Control group
Women undergoing ART without a history of RIF or RPL.
干预措施: Blood sample (Diagnostic Test)
Control group
Women undergoing ART without a history of RIF or RPL.
干预措施: Pelvic ultrasound (±pelvic MRI) (Diagnostic Test)
结局指标
主要结局
Profiling of endometrial immune cell populations
时间窗: 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.
次要结局
- Microbiological profiling of endometrial tissue(Baseline)
- Characterization of peripheral blood immune cell populations(Baseline)
- Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics(Through 24 months of follow-up)
- Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics(Baseline)