Mechanisms of Maternal Immune Tolerance in Early Pregnancy

This study explores the mechanisms of maternal immune tolerance in early pregnancy by characterizing immune cell profiles and functional pathways during the first trimester. The goal is to identify immunological factors that support healthy gestation and prevent complications such as miscarriages.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; In Vitro Fertilization; Immune Tolerance
• Intervention / Treatment: Other: Blood sampling

Detailed Description

Maternal immune tolerance is essential for a successful pregnancy, as the maternal immune system must accept the semi-allogeneic fetus while maintaining defense against pathogens. Failure in this delicate balance can lead to complications such as recurrent miscarriage, preeclampsia, or implantation failure. Although several immune cell types, including T cells and regulatory pathways, are thought to play a role, the precise mechanisms underlying maternal immune adaptation during early pregnancy remain poorly understood.

This observational study investigates immunological changes occurring before and during early pregnancy and miscarriage in women undergoing in vitro fertilization (IVF). Blood samples will be collected at multiple predefined time points: prior to embryo transfer and during the first trimester of pregnancy as well as after miscarriage. These samples will be analyzed for immune cell composition, activation status, and cytokine profiles using advanced immunological assays. The longitudinal design allows for tracking dynamic changes in immune regulation from pre-implantation through early gestation.

The primary objective is to identify cellular and molecular signatures associated with maternal immune tolerance and successful implantation. Insights gained from this study may inform future strategies to predict and prevent pregnancy complications such as early miscarriage related to immune dysregulation.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Ursula Gobrecht-Keller, MD; Phone Number: +41 61 265 93 37; Email: ursula.gobrecht@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Ursula Gobrecht-Keller, MD; Phone Number: +41 61 265 93 37; Email: ursula.gobrecht@usb.ch
    • Principal Investigator: Ursula Gobrecht-Keller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Women undergoing in vitro fertilization (IVF) treatment at the University Hospital Basel who consent to participate in the study.

Description

Inclusion Criteria:

Blood from patients will be included before and during pregnancies (or failed implantation) conceived through IVF/ICSI (Intracytoplasmic Sperm Injection) treatment and in case of miscarriage.

1. where the patient (pregnant person) was ≥ 18 years of age.
2. where the patient (pregnant person) signed a written informed consent.

Exclusion Criteria:

1. Certain maternal infections (HIV, Hepatitis B, Hepatitis C, Syphilis)
2. Patients under immunosuppressive medications (at time of blood sample collection)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women undergoing IVF and early pregnancy; This cohort includes women undergoing in vitro fertilization (IVF)	Other: Blood sampling; Blood samples will be analyzed before and during early pregnancy as well as after early miscarriage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune cell composition in peripheral blood	Characterization of immune cell subsets (e.g., T cells, regulatory T cells, natural killer cells (NK cells)) in blood samples collected at predefined time points (before embryo transfer and during early pregnancy and in case of early miscarriage).	Before conception, week 6-7 of pregnancy, and following implantation failure or spontaneous miscarriage, up to 12 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptional profiles of peripheral blood mononuclear cell (PBMC) subsets associated with pregnancy outcome (scRNA-seq)	Single-cell RNA sequencing analysis to characterize transcriptional phenotypes of PBMCs. This includes identification of differentially expressed genes, gene modules, and transcription factor activity profiles associated with pregnancy and pregnancy failure.	Before conception, week 6-7 of pregnancy, and following implantation failure or spontaneous miscarriage, up to 12 weeks of gestation
T-cell and B-cell receptor repertoire dynamics (TCR/BCR sequencing)	Assessment of clonal expansion and contraction in TCR and BCR (B cell receptor) repertoires using bulk and single-cell sequencing.	Before conception, week 6-7 of pregnancy, and following implantation failure or spontaneous miscarriage, up to 12 weeks of gestation

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Study Director: Ursula Gobrecht-Keller, MD, University Hospital of Basel

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cytokines; T cells; Immune Regulation; Early Pregnancy; Maternal Immune Tolerance
• Additional Relevant MeSH Terms: Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 2025-02262;bb25GobrechtKeller

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