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

NCT07265505 | Not Yet Recruiting

• 2 other identifiers: APHP2413442024-A02100-47
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Uterine Immune Profile; Endometrial Receptivity; Infertility; Recurrent Miscarriage; IVF Failure; Implantation Window; Reproductive Immunology; Endometrial Microbiome; Chronic Endometritis; Adenomyosis; Endometriosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline

Secondary Outcomes (4)

• 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

  Baseline

• Exploratory analysis of associations between immune and microbiological profiles and clinical, radiological, and histological characteristics

  Through 24 months of follow-up

Study Arms (2)

RIF/RPL group

OTHER

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

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

Control group

OTHER

Women undergoing ART without a history of RIF or RPL.

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

Interventions

Endometrial Biopsy DIAGNOSTIC_TEST

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)

Control group; RIF/RPL group

Vaginal Swab DIAGNOSTIC_TEST

Vaginal sample collection using a cotton swab. Part of the treatment

Control group; RIF/RPL group

Blood sample DIAGNOSTIC_TEST

Peripheral blood draw. Part of the treatment + 10 mL additional for research

Control group; RIF/RPL group

Pelvic ultrasound (±pelvic MRI) DIAGNOSTIC_TEST

Pelvic ultrasound (±pelvic MRI). Part of the treatment

Control group; RIF/RPL group

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• ADREGOF: collaborator

Study Sites (1)

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

Paris, IDF, 75014, France

Location

Related Publications (19)

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  PMID: 33099635 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Sadler L, Sarris I, Showell M, Stewart J, Strandell A, Strawbridge C, Vail A, van Wely M, Vercoe M, Vuong NL, Wang AY, Wang R, Wilkinson J, Wong K, Wong TY, Farquhar CM; Priority Setting Partnership for Infertility. Top 10 priorities for future infertility research: an international consensus development study. Fertil Steril. 2021 Jan;115(1):180-190. doi: 10.1016/j.fertnstert.2020.11.014. Epub 2020 Nov 30.

  PMID: 33272617 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Kunz G, Leyendecker G. Uterine peristaltic activity during the menstrual cycle: characterization, regulation, function and dysfunction. Reprod Biomed Online. 2002;4 Suppl 3:5-9. doi: 10.1016/s1472-6483(12)60108-4.

  PMID: 12470555 BACKGROUND

• Ledee N, Petitbarat M, Prat-Ellenberg L, Dray G, Cassuto GN, Chevrier L, Kazhalawi A, Vezmar K, Chaouat G. The uterine immune profile: A method for individualizing the management of women who have failed to implant an embryo after IVF/ICSI. J Reprod Immunol. 2020 Nov;142:103207. doi: 10.1016/j.jri.2020.103207. Epub 2020 Sep 14.

  PMID: 32971456 BACKGROUND

• Marron K, Harrity C. Endometrial lymphocyte concentrations in adverse reproductive outcome populations. J Assist Reprod Genet. 2019 May;36(5):837-846. doi: 10.1007/s10815-019-01427-8. Epub 2019 Mar 7.

  PMID: 30847699 BACKGROUND

• McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014 Apr;101(4):1026-30. doi: 10.1016/j.fertnstert.2013.12.031. Epub 2014 Jan 23.

  PMID: 24462055 BACKGROUND

• Ota H, Tanaka T. Stromal vascularization in the endometrium during adenomyosis. Microsc Res Tech. 2003 Mar 1;60(4):445-9. doi: 10.1002/jemt.10282.

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• Pirtea P, Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM. Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril. 2021 Mar;115(3):546-560. doi: 10.1016/j.fertnstert.2020.12.010. Epub 2021 Feb 11.

  PMID: 33581856 BACKGROUND

• Rimmer MP, Fishwick K, Henderson I, Chinn D, Al Wattar BH, Quenby S. Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review. J Obstet Gynaecol Res. 2021 Feb;47(2):689-697. doi: 10.1111/jog.14585. Epub 2020 Dec 3.

  PMID: 33274569 BACKGROUND

• Romero R, Espinoza J, Mazor M. Can endometrial infection/inflammation explain implantation failure, spontaneous abortion, and preterm birth after in vitro fertilization? Fertil Steril. 2004 Oct;82(4):799-804. doi: 10.1016/j.fertnstert.2004.05.076.

  PMID: 15482749 BACKGROUND

• Vernon M, Stern JE, Ball GD, Wininger D, Mayer J, Racowsky C. Utility of the national embryo morphology data collection by the Society for Assisted Reproductive Technologies (SART): correlation between day-3 morphology grade and live-birth outcome. Fertil Steril. 2011 Jun 30;95(8):2761-3. doi: 10.1016/j.fertnstert.2011.02.008. Epub 2011 Mar 15.

  PMID: 21406305 BACKGROUND

• Von Woon E, Greer O, Shah N, Nikolaou D, Johnson M, Male V. Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2022 Jun 30;28(4):548-582. doi: 10.1093/humupd/dmac006.

  PMID: 35265977 BACKGROUND

• Zhao Y, Chen X, Zhang T, Chan LKY, Liu Y, Chung JP, Kwong J, Li TC. The use of multiplex staining to measure the density and clustering of four endometrial immune cells around the implantation period in women with recurrent miscarriage: comparison with fertile controls. J Mol Histol. 2020 Oct;51(5):593-603. doi: 10.1007/s10735-020-09908-2. Epub 2020 Aug 28.

  PMID: 32857228 BACKGROUND

MeSH Terms

Conditions

Infertility, Female; Uterine Diseases; Endometritis; Endometriosis; Adenomyosis; Infertility; Abortion, Habitual

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pelvic Inflammatory Disease; Adnexal Diseases; Abortion, Spontaneous; Pregnancy Complications

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mathilde Bourdon, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mathilde Bourdon, MD, PhD

CONTACT

00331 58 41 35 51; mathilde.bourdon@aphp.fr

Marie Benhammani-Godard

CONTACT

marie.godard@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: December 4, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

FR (1)