Low TGF-β and Embryo Implantation in the Context of Assisted Reproductive Technology: Confirmation of a Biomarker Predictive of Success and Characterization of the Immune Microenvironment. (ImmuNoFertilit)

Low TGF-β and Embryo Implantation in the Context of Assisted Reproductive Technology: Confirmation of a Biomarker Predictive of Success and Characterization of the Immune Microenvironment - ImmuNoFertilité 2

Infertility affects about one in seven couples in France. Beyond the medical and personal challenges, it has major societal implications. In vitro fertilization (IVF) offers hope to these couples, but success rates remain modest (about 30% per embryo transfer). The failure of embryo implantation is multifactorial. Among the factors involved, immune status at the time of embryo transfer plays a central role. Embryo transfer induces an acute pro-inflammatory immune response, and inadequate regulation of this response could compromise implantation.

The investigators have previously identified a promising immune biomarker: TGF-β (Transforming Growth Factor Beta). In a prospective cohort of 255 patients undergoing frozen embryo transfer, the investigators demonstrated that low circulating levels of TGF-β following nonspecific stimulation of immune cells on the day of embryo transfer were associated with a significant increase in the likelihood of implantation and live birth.

These results now require independent validation in a new cohort to establish their robustness and explore potential clinical applications. The investigators hypothesize that measuring TGF-β concentration following stimulation can predict the success of embryo implantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Pregnancy Related; Infertility, Female

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

Contacts and Locations

• Study Contact: Name: Pierre-Alexis GAUCI, MD-PHD; Phone Number: +33 4 92 03 61 90; Email: gauci.pa@chu-nice.fr

Study Locations

• France
  • Alpes-Mritimes
    • Nice, Alpes-Mritimes, France, 06200
      • CHU Nice - Hôpital de l'Archet 2
      • Contact: Pierre-Alexis GAUCI, MD-PHD; Phone Number: +33 4 92 03 61 90; Email: gauci.pa@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Infertile woman

Description

Inclusion Criteria:

1. Adult women,
2. Undergoing IVF treatment at the Nice University Hospital for frozen embryo transfer following a semi-natural or stimulated cycle,
3. Enrolled in the social security system,
4. No objection to participating in the study.

Exclusion Criteria:

1. Any contraindication to frozen embryo transfer
2. Patients receiving donated gametes during this embryo transfer attempt
3. Current infectious disease
4. Patients protected by law who are under guardianship or conservatorship, or who are ineligible to participate in a clinical trial pursuant to Article L. 1121-16 of the French Public Health Code;
5. Patients subject to a judicial protective measure.

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low circulating levels of TGF-β	To conduct an exploratory validation, in an independent cohort, of the association between low circulating levels of TGF-β-following nonspecific cellular stimulation at the time of frozen embryo transfer (after a semi-natural or stimulated cycle)-and an increased likelihood of embryo implantation. Embryo implantation will be confirmed by the visualization of an intrauterine gestational sac on an ultrasound performed during the first trimester following embryo transfer.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between TGF-β and the number of live births.	Confirm the correlation between low levels of stimulated TGF-β and the number of live births by noting the final outcome of the pregnancy: live birth or stillbirth.	24 months
Circulating lymphocyte populations	Study circulating lymphocyte populations and their functional profile (intracellular cytokines) by flow cytometry, measuring cytokine levels (IL-1R, IL-2R, IL-6, IL-8, IL-10, IL-18, IFN-γ, TNF-α, IL-17A, IL-4, TGF-β, IL-12p70, IL-5 (in pg/ml)) found in cell supernatants following nonspecific stimulation (anti-CD3 agonist + TLR7/8 ligand), lymphocyte phenotyping (Th1, Th2, Treg, NK), and intracellular cytokine measurement by flow cytometry.	24 months
Impact of exposure to air pollution	Assess the impact of exposure to air pollution on immune status and the success of embryo transfer by measuring average exposure to PM10, PM2.5, NO2, and O3 (in µg/m³) during the 6 months preceding embryo transfer.	24 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: September 30, 2026
• First Submitted That Met QC Criteria: September 30, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 16, 2026
• Last Update Submitted That Met QC Criteria: October 13, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: infertility; pregnancy; TGF-β
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: 26-PP-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No