ReceptIVFity & Immunology in ART (R-IMinART)

Increasing the Accuracy to Predict Pregnancy Success After Assisted Reproductive Therapy (ART) by Combining the ReceptIVFIty Test with Immunological Parameters

The goal of this clinical non-invasive observational pilot study is to improve the prediction of pregnancy success after In Vitro Fertilisation (IVF)/IVF -Intracytoplasmic Sperm Injection (ICSI) treatment by examining the vaginal microbiome and the immunological profile of menstrual blood in women (18-42) years old) undergoing their first IVF/IVF/ICSI treatment.

The main questions it aims to answer are:

What is the ReceptIVFity profile (low, medium, or high) of the vaginal microbiome in these women? How do the endometrial-derived lymphocytes respond to different immune stimuli and microbiota? Can the endometrial stromal cells decidualize effectively in the presence or absence of specific microbiota?

Participants will:

Self-perform a vaginal swab to determine the ReceptIVFity profile of their vaginal microbiome.

Self-collect menstrual blood during 24 hours in 2 blocks of 12 hours for immunological analysis.

Study Overview

• Status: Enrolling by invitation
• Conditions: Infertility (IVF Patients); Infertility Assisted Reproductive Technology
• Intervention / Treatment: Device: Vaginal microbiome swab; Device: Menstrual Blood Collection via Menstrual Cup

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Netherlands
  • South-Holland
    • Rotterdam, South-Holland, Netherlands, 3015GD
      • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women aged 18-42 expected to undergo their first IVF/IVF-ICSI cycle within the next two months. The routine IVF/IVF-ICSI procedure will occur irrespective of their participation or the test outcomes.

Description

Inclusion Criteria:

1. Indication for an IVF or IVF/ICSI procedure.
2. 18 years - 42 years.
3. European origin
4. Willing to provide a vaginal swab with the ReceptIVFity-test.
5. Willing to provide informed consent.

Exclusion Criteria:

1. No transferable embryos after IVF or IVF/ICSI.
2. Emergency IVF for cancer or other reasons.
3. Women with endometriosis pre-treated with an Gn-RH analogue.
4. The use of (hormonal) contraceptives or antibiotics 3 months prior to start IVF or IVF/ICSI.
5. Women unable or unwilling to agree with the procedures.
6. Women unable or unwilling to give written informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Cell Phenotype and Function in Menstrual Blood Stratified by Vaginal Microbiome in IVF Patients	Analysis of monocyte, Natural Killer (NK) cell, T lymphocytes, regulatory T lymphocytes, and T helper cell phenotypes in menstrual blood. Immune responses, including cytokine production and immune marker regulation, will be quantified. Unit of Measure: Percentage of cell type, cytokine concentrations in pg/mL.	Baseline and 3 months
Genotyping of Maternal KIR and HLA-C	Determination of maternal Killer cell immunoglobulin-like receptor (KIR) and Major Histocompatibility Complex (HLA-C) genotypes. Unit of Measure: Genotype classification.	Baseline
RNA Analysis of Stromal Fibroblast Cells	Analysis of RNA from stromal fibroblast cells to determine expression of tissue adaptation markers (pre-decidualization). Gene expression levels (e.g., fold change, normalized counts).	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolite Analysis as Immune Signaling Modulators in IVF Patients	Analysis of host- and microbiome-derived metabolites serving as signaling molecules that regulate immune function. Unit of Measure: Metabolite concentrations (µmol/L).	Baseline

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Vaginal microbiome; Assisted reproductive technology (ART); IVF success prediction; Menstrual blood immunology; Infertility biomarkers
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: OZBS72.19236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No