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

Официальное название

Study of Immune and Microbiological Modifications of the Endometrium in Cases of Recurrent Implantation Failure and/or Recurrent Pregnancy Loss

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Endometrial 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)
• Диагностический тест Vaginal Swab
  Vaginal sample collection using a cotton swab. Part of the treatment
• Диагностический тест Blood sample
  Peripheral blood draw. Part of the treatment + 10 mL additional for research
• Диагностический тест Pelvic ultrasound (±pelvic MRI)
  Pelvic ultrasound (±pelvic MRI). Part of the treatment

Первичные конечные точки

• Profiling of endometrial immune cell populations [Срок оценки: Baseline]

Вторичные конечные точки (4)

• Microbiological profiling of endometrial tissue [Срок оценки: Baseline]
• Characterization of peripheral blood immune cell populations [Срок оценки: Baseline]
• Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics [Срок оценки: Baseline]
• Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics [Срок оценки: Through 24 months of follow-up]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Франция · 1 центр

• Service de Gynécologie Obstétrique II et Médecine de la Reproduction - Cochin Hospital — Paris

Публикации

• Benner M, Ferwerda G, Joosten I, van der Molen RG. How uterine microbiota might be responsible for a receptive, fertile endometrium. Hum Reprod Update. 2018 Jul 1;24(4):393-415. doi: 10.1093/humupd/dmy012. PMID 29668899
• Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L, Petraglia F, Batteux F, Chapron C. Immunological changes associated with adenomyosis: a systematic review. Hum Reprod Update. 2021 Jan 4;27(1):108-129. doi: 10.1093/humupd/dmaa038. PMID 33099635
• Campo S, Campo V, Benagiano G. Infertility and adenomyosis. Obstet Gynecol Int. 2012;2012:786132. doi: 10.1155/2012/786132. Epub 2011 Dec 26. PMID 22242025
• Chen P, Chen P, Guo Y, Fang C, Li T. Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure. Front Immunol. 2021 Oct 4;12:748447. doi: 10.3389/fimmu.2021.748447. eCollection 2021. PMID 34671363
• Duffy JMN, Adamson GD, Benson E, Bhattacharya S, Bhattacharya S, Bofill M, Brian K, Collura B, Curtis C, Evers JLH, Farquharson RG, Fincham A, Franik S, Giudice LC, Glanville E, Hickey M, Horne AW, Hull ML, Johnson NP, Jordan V, Khalaf Y, Knijnenburg JML, Legro RS, Lensen S, MacKenzie J, Mavrelos D, Mol BW, Morbeck DE, Nagels H, Ng EHY, Niederberger C, Otter AS, Puscasiu L, Rautakallio-Hokkanen S, PMID 33272617
• ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Mcheik S, Peramo B, Quenby S, Nielsen HS, van der Hoorn ML, Vermeulen N, Goddijn M. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023 Mar 2;2023(1):hoad002. doi: 10.1093/hropen/hoad002. eCollection 2023. PMID 36873081
• ESHRE Working Group on Recurrent Implantation Failure; Cimadomo D, de Los Santos MJ, Griesinger G, Lainas G, Le Clef N, McLernon DJ, Montjean D, Toth B, Vermeulen N, Macklon N. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open. 2023 Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023. eCollection 2023. PMID 37332387
• Giuliani E, Parkin KL, Lessey BA, Young SL, Fazleabas AT. Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis. Am J Reprod Immunol. 2014 Sep;72(3):262-9. doi: 10.1111/aji.12259. Epub 2014 May 8. PMID 24807109

Идентификаторы

NCT: NCT07265505 · APHP241344 · 2024-A02100-47

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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