Benefit of Early Intrauterine Transfer of "Blank" Culture Medium Prior to Transfer of a Thawed Embryo From 1st in Vitro Fertilization (TRABLAN)

Benefit of Early Intrauterine Transfer of "Blank" Culture Medium Prior to Transfer of a Thawed Embryo From 1st in Vitro Fertilization - Randomized, Single-blind, Multicenter Controlled Trial.

Despite technical advances in Medically Assisted Reproduction (AMP), the success of fertility treatments is sometimes limited by embryo implantation failure. The coordinated development of the embryo and the uterine endometrium requires close communication between the maternal tissue and the embryo. In in vitro fertilization (IVF), embryo transfer generally takes place between the 2nd (D2) and the 6th (D6) day following oocyte fertilization. Recent studies have shown the advantages of sequential transfer (transfer of an embryo on D2/D3 followed by the transfer of another embryo on D5/D6), with higher implantation and clinical pregnancy rate, fewer miscarriages, more live births, and yet no increase in multiple pregnancies. However, the American Society for Reproductive Medicine recommendations continue to prioritize the transfer of a single embryo for all patients aged under 38. To improve pregnancy rates for patients having a single embryo transferred, the study investigators wish to carry out on "blank" transfer, based on the principle of sequential transfer. The study investigators hypothesize that a culture medium, placed in the uterus before the time of embryo transfer, will modify immune tolerance. The study will test whether transferring the same culture medium in an equivalent quantity as during the real transfer into the uterus 2/3 days before the embryo transfer will improve tolerance to this foreign medium and, therefore, embryo implantation. The aim of this study is thus to evaluate the impact of a "blank" transfer with culture medium alone, on the results of frozen embryo transfers (FET) from IVF.

Study Overview

• Status: Recruiting
• Conditions: Fertilization in Vitro; Single Embryo Transfer
• Intervention / Treatment: Procedure: Blank culture transfer; Procedure: Sham transfer

• Study Type: Interventional
• Enrollment (Estimated): 1154
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie Rougier; Phone Number: 04.66.68.32.24; Email: nathalie.rougier@chu-nimes.fr

Study Locations

• France
  • Clamart, France
    • Not yet recruiting
    • Hôpital Antoine Béclère
    • Contact: Michaël Grynberg; Email: michael.grynberg@aphp.fr
    • Principal Investigator: Michaël Grynberg
  • Contamine-sur-Arve, France
    • Not yet recruiting
    • Centre Hospitalier Alpes Léman
    • Contact: Béatrice Dorphin; Email: beatrice.dorphin@biogroup.fr
    • Principal Investigator: Béatrice Dorphin
  • Montpellier, France
    • Not yet recruiting
    • CHU Arnaud de Villeneuve
    • Principal Investigator: Noémie Ranisavljevic
    • Contact: Noémie Ranisavljevic; Email: n-ranisavljevic@chu-montpellier.fr
    • Sub-Investigator: Tal Anahory
  • Nîmes, France, 30029
    • Recruiting
    • CHU de Nîmes
    • Contact: Anissa Megzari; Phone Number: 04.66.68.42.36; Email: drc@chu-nimes.fr
    • Principal Investigator: Nathalie Rougier
    • Sub-Investigator: Stéphanie Huberlant
    • Sub-Investigator: Julien Sigala
  • Perpignan, France
    • Not yet recruiting
    • Clinique Saint-Pierre
    • Contact: Emmanuelle Petit; Email: emmapetit@gmail.com
    • Principal Investigator: Emmanuelle Petit
• Réunion
  • Saint-Pierre, Réunion
    • Not yet recruiting
    • CHU de la Réunion
    • Contact: Helene Flye Sainte Marie; Email: helene.flye@chu-reunion.fr
    • Principal Investigator: Helene Flye Sainte Marie

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Having had a first "fresh" or frozen embryo transfer, whatever the embryo's stage of development, transfer followed by pregnancy failure ;
• Having at least two embryos eligible for transfer or freezing during a 1st IVF attempt (one fresh + one frozen or two frozen);
• Frozen embryos must be at least D3 stage;
• The patient must have given their free and informed consent and signed the consent form
• The patient must be a member or beneficiary of a health insurance plan

Exclusion Criteria:

• The subject is participating in an interventional study, or is in a period of exclusion determined by a previous study
• The patient is under safeguard of justice or state guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: With blank culture	Procedure: Blank culture transfer; A maximum of 0.1 ml of gassed embryo culture medium preheated to 37°C is injected into the uterine cavity transcervically using an embryo transfer catheter placed just beyond the internal os, two to 3 days before transfer of the thawed embryo
Sham Comparator: Without blank culture	Procedure: Sham transfer; An intermediate transfer step is added two or three days before the planned transfer of the frozen embryo but with an empty catheter.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically progressive pregnancy rate between groups	Measured on first-trimester ultrasound	12 weeks of amenorrhea

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of pregnancy between groups	Defined by a positive beta HCG test ≥ 100 IU/ml	Day 14
Occurrence of a biochemical pregnancy between groups	Defined by a positive beta HCG test ≥ 10 IU/ml and < 100 IU/ml	Day 14
Occurrence of a clinical pregnancy between groups	Defined by a positive beta HCG test ≥ 100 IU/ml and presence of at least one gestational sac on dating ultrasound	6 weeks of amenorrhea
Occurrence of an early miscarriage between groups	Defined by the presence of a pregnancy defined by a positive beta HCG test ≥ 100 IU at D14 and the absence of an evolving clinical pregnancy at first-trimester ultrasound	12 weeks of amenorrhea
Occurrence of live birth	Yes/no	Upon giving birth (maximum month 9)
Differential cost-result ratio	Ratio of the cost differential and the number of additional live births (additional progressive clinical pregnancies) between the two strategies, to evaluate the cost per additional live birth.	End of study (Year 3)
Total estimated expenditure for the two care strategies compared (budget impact analysis) over a one-year time horizon.	Calculated at national level (implementation of the system and consumption of care)	End of study (Year 3)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Nathalie Rougier, CHU de Nîmes

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 11, 2023
• First Submitted That Met QC Criteria: December 11, 2023
• First Posted (Actual): December 20, 2023

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PHRC-I/2022/NR-01

Drug and device information, study documents

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