The Impact of Uterine Immunity and Its Alterations on the Embryo Implantation Process

NCT07120958 | Enrolling By Invitation

• 1 other identifier: 32/cf/2025
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of uterine immunity, histological picture, and endometrial microbiome for embryo implantation

Conditions

Infertility Assisted Reproductive Technology

Keywords

interleukin; ngs; art; icsi; implantation; euploid; uterine immunity

Outcome Measures

Primary Outcomes (1)

• Characterise the molecular immunologic mechanism underlying embryo implantation

  The main objective of this research is to characterise the molecular immunologic mechanism underlying embryo implantation. These outcomes will be assessed regarding the percentage of expressivity of some interleukins in pregnant couples and those who are not

  from enrollment to the pregnancy test (12 days after embryo transfer)

Secondary Outcomes (1)

• to study the possible correlations of the expression of the interleukins involved in the implantation process of the embryo

  The endometrial biopsy on which the interleukin dosage will be done, will be taken one month before the embryo transfer

Other Outcomes (1)

• to assess whether progesterone levels can alter the immune response

  the same day of the embryo transfer

Study Arms (2)

endometrial biopsy with pregnancy

endometrial biopsy without pregancy

Eligibility Criteria

• Age: 20 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Women who undertake ART treatment in South Italy

You may qualify if:

• Female patients aged \>18 and \<43 years at the time of embryo transfer.
• Transfer of cryopreserved embryos diagnosed as euploid through preimplantation genetic testing for aneuploidy (PGT-A).
• Embryo transfer performed at the blastocyst stage.

You may not qualify if:

• Patients with an intrauterine device (IUD) in situ within the three months prior to study enrollment.
• Presence of autoimmune diseases and/or ongoing treatment with corticosteroids.
• Structural or pathological abnormalities of the uterine cavity, including but not limited to polyps, intramural myomas measuring 2-4 cm, submucosal fibroids, uterine septum, or hydrosalpinx, identified during study participation. Patients with a history of these conditions may be included if the pathology has been resolved prior to the initiation of any study-related procedures or sample collection.
• Presence of severe or uncontrolled fungal or viral infections which, in the opinion of the principal investigator, may compromise the patient's ability to participate or affect the integrity of study outcomes.
• Any medical condition or illness that is unstable, poses a potential risk to patient safety, or may interfere with adherence to the study protocol.
• Patients lacking a confirmed preimplantation genetic diagnosis of euploidy.
• Patients with a clinical diagnosis of endometriosis or adenomyosis.

Sponsors & Collaborators

• Momo Fertilife: lead
• University of Bari: collaborator
• University of Florence: collaborator
• Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo: collaborator

Study Sites (1)

MOMO' Fertilife

Bisceglie, BT, 76011, Italy

Location

Related Publications (12)

• Nagaeva O, Jonsson L, Mincheva-Nilsson L. Dominant IL-10 and TGF-beta mRNA expression in gammadeltaT cells of human early pregnancy decidua suggests immunoregulatory potential. Am J Reprod Immunol. 2002 Jul;48(1):9-17. doi: 10.1034/j.1600-0897.2002.01131.x.

  PMID: 12322898 BACKGROUND

• Vitoratos N, Papadias C, Economou E, Makrakis E, Panoulis C, Creatsas G. Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome. Mediators Inflamm. 2006;2006(4):30485. doi: 10.1155/MI/2006/30485.

  PMID: 17047289 BACKGROUND

• Lombardelli L, Logiodice F, Kullolli O, Haller H, Agostinis C, Bulla R, Rukavina D, Piccinni MP. At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success. Int J Mol Sci. 2022 Apr 28;23(9):4926. doi: 10.3390/ijms23094926.

  PMID: 35563316 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

• Szekeres-Bartho J. The Role of Progesterone in Feto-Maternal Immunological Cross Talk. Med Princ Pract. 2018;27(4):301-307. doi: 10.1159/000491576. Epub 2018 Jun 27.

  PMID: 29949797 BACKGROUND

• Piccinni MP, Raghupathy R, Saito S, Szekeres-Bartho J. Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front Immunol. 2021 Jul 28;12:717808. doi: 10.3389/fimmu.2021.717808. eCollection 2021.

  PMID: 34394125 BACKGROUND

• Mahajan D, Kumar T, Rath PK, Sahoo AK, Mishra BP, Kumar S, Nayak NR, Jena MK. Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy. Arch Immunol Ther Exp (Warsz). 2024 May 23;72(1). doi: 10.2478/aite-2024-0010. eCollection 2024 Jan 1.

  PMID: 38782369 BACKGROUND

• Zhou J, Yan P, Ma W, Li J. Cytokine modulation and immunoregulation of uterine NK cells in pregnancy disorders. Cytokine Growth Factor Rev. 2025 Feb;81:40-53. doi: 10.1016/j.cytogfr.2024.11.007. Epub 2024 Nov 23.

  PMID: 39603954 BACKGROUND

• Parasar P, Guru N, Nayak NR. Contribution of macrophages to fetomaternal immunological tolerance. Hum Immunol. 2021 May;82(5):325-331. doi: 10.1016/j.humimm.2021.02.013. Epub 2021 Mar 11.

  PMID: 33715911 BACKGROUND

• Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J. T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front Immunol. 2020 Aug 18;11:2025. doi: 10.3389/fimmu.2020.02025. eCollection 2020.

  PMID: 32973809 BACKGROUND

• Szekeres-Bartho J. Immunological relationship between the mother and the fetus. Int Rev Immunol. 2002 Nov-Dec;21(6):471-95. doi: 10.1080/08830180215017.

  PMID: 12650238 BACKGROUND

• Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020 Oct 7;11:575197. doi: 10.3389/fimmu.2020.575197. eCollection 2020.

  PMID: 33133091 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Endometrial biopsy stored at -80 C°

Study Officials

• Domenico Baldini, Degree in Medicine and Surgery

  Momo Fertilife

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: IVF Lab Manager

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 13, 2025
• Study Start: May 1, 2025
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)