Study of Endometrial Immune and Microbiological Modifications in Cases of Recurrent Implantation Failure and/or Recurrent Pregnancy Loss (IMERR)

Assistance Publique - Hôpitaux de Paris

Status: Begins enrollment in 1 month

Conditions: Recurrent Pregnancy Loss; Endometritis; Endometrial Diseases; Adenomyosis; Endometriosis; Recurrent Implantation Failure; Infertility, Female

Treatments: Diagnostic Test: Vaginal Swab; Diagnostic Test: Endometrial Biopsy; Diagnostic Test: Pelvic ultrasound (±pelvic MRI); Diagnostic Test: Blood sample

Study type: Interventional

Funder types: Other

Identifiers

NCT07265505

2024-A02100-47 (Other Identifier)

APHP241344

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

RIF/RPL group

Other group

Description:

Women undergoing ART with a history of recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL).

Treatment:

Diagnostic Test: Blood sample

Diagnostic Test: Pelvic ultrasound (±pelvic MRI)

Diagnostic Test: Endometrial Biopsy

Diagnostic Test: Vaginal Swab

Control group

Other group

Description:

Women undergoing ART without a history of RIF or RPL.

Treatment:

Diagnostic Test: Blood sample

Diagnostic Test: Pelvic ultrasound (±pelvic MRI)

Diagnostic Test: Endometrial Biopsy

Diagnostic Test: Vaginal Swab