A Trial Evaluating Autologous Endometrial Co-Culture Versus Conventional Medium in the Treatment of Infertility

Study Overview
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Brief Summary
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One of the main factors in the success of in-vitro fertilization is the quality of the environment of the embryo. In contrast to maternal age, the environment in which the embryo develops is a modifiable factor. Many techniques, such as assisted hatching and perfecting culture media have been attempted in order to reproduce as much as possible the natural, physiological environment of the mother for the embryo in in-vitro fertilization. However, the different new culture media used are devoid of growth factors normally secreted by uterine cells that enhance the interaction between the embryo and its environment. Because the endometrial lining of the uterus secretes many different cytokines necessary for growth of the embryo, a new procedure has been developed to mimic the natural environment of the growing embryo using autologous (patient's own) endometrial cells in co-culture with the embryo. Endocell, a product developed by Genévrier Laboratories, received commercial authorization in France in 2011. It is the only system of autologous embryo-endometrium co-culture available on the actual market. The process consists of developing the embryo on a monolayer of the patient's own endometrial cells in order to favor its growth until the blastocyst stage (day 5) and to improve its implantation.

Official Title
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A Randomized Trial Evaluating Autologous Endometrial Co-Culture Versus Conventional Medium in the Treatment of Infertility

Conditions
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Infertility

Intervention / Treatment
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* Procedure: Endometrial biopsy
* Other: Autologous Endometrial Co-Culture
* Other: Conventional media culture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing In Vitro Fertilization (IVF) or IVF/Intra Cytoplasmic Sperm Injection (ICSI) at OVO clinic Having a prescription of a long, short or an antagonist IVF protocols using both urinary and synthetic gonadotropins Having a single embryo transfer Regular menstrual cycles Basal follicle stimulating hormone levels less than 10 IU/l within 6 months prior to entering the study anti-mullerian hormone more than 1 ng/ml measured within a year Normal sonohysterogram or hysteroscopy done within the last 2 years Previously undergone a maximum of 3 IVF cycles Documented negative serology tests within 1 year prior recruitment for: Hepatitis B, Syphilis, HIV based on Health Canada recommendations for treatment in an IVF laboratory. Exclusion Criteria: Amenorrhea Anovulatory cycles Polycystic Ovarian syndrome Chronic endometritis Severe endometriosis Hydrosalpinx Uterine synechia or Asherman's syndrome Submucosal uterine fibroids or intra-cavitary polyps greater than 1cm Uterine anomalies Use of anticoagulants Secretory Azoospermia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Endometrial Co-Culture<br>The embryos will be transferred to Endocell co-culture media for Autologous Endometrial Co-Culture between day 2 and day 5. | Procedure: Endometrial biopsy<br>* A luteal phase endometrial biopsy will be performed in the cycle prior to the patient's In Vitro Fertilization stimulation cycle using a standard Pipelle Endometrial Suction curette in all participants between days ovulation+5 and ovulation+7 of the cycle preceding the stimulation cycle<br>Other: Autologous Endometrial Co-Culture<br>* embryos will be transferred to Endocell co-culture media for Autologous Endometrial Co-Culture between day 2 and day 5<br>|
| Active Comparator: Conventional media culture<br>Patients in this arm will have their embryos cultured in conventional media | Procedure: Endometrial biopsy<br>* A luteal phase endometrial biopsy will be performed in the cycle prior to the patient's In Vitro Fertilization stimulation cycle using a standard Pipelle Endometrial Suction curette in all participants between days ovulation+5 and ovulation+7 of the cycle preceding the stimulation cycle<br>Other: Conventional media culture<br>* embryos are cultured in conventional media<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy rates | Confirmed clinical pregnancy with positive fetal heart on the day of viability ultrasound | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Embryo quality | The number of cells and the grade of the embryos will be assess throughout their development. | 5 days | 
| Blastulation rate | Percentage of embryos that develops into blastocyst compared to the total number of embryos in culture | 5 days | 
| Cumulative pregnancy rate with frozen embryos | Pregnancy rate per patient including all transfer with frozen embryos | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In vitro fertilization, Autologous Endometrial Co-Culture