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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Single Embryo Transfer, Fertilization in Vitro

Intervention / Treatment
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* Procedure: Blank culture transfer
* Procedure: Sham transfer


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 39 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: With blank culture<br> | Procedure: Blank culture transfer<br>* 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<br>|
| Sham Comparator: Without blank culture<br> | Procedure: Sham transfer<br>* An intermediate transfer step is added two or three days before the planned transfer of the frozen embryo but with an empty catheter.<br>|

What is the study measuring?
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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) |