Autograft of Human Ovarian Tissue : Efficiency and Safety

Study Overview
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Brief Summary
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Ovarian tissue cryopreservation is a new technique for female fertility preservation. One way to restore fertility is autotransplantation of ovarian tissue. The principal purpose of this study will be to evaluate the efficiency and safety of this procedure.

Detailed Description
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Ovarian tissue cryopreservation is a new technique for female fertility preservation before gonadotoxic treatments. The first ovarian tissue cryopreservations were performed 10 years ago. There are two main methods to use frozen ovarian cortex: autograft of ovarian fragments and in vitro follicular growth. At the present time, none mature oocytes were obtained after culture. Since 2000, around twenty publications stating autografts of ovarian cortex reported 8 pregnancy and 6 life birth of healthy babies. Since 1998 until 2008, in the unit of reproduction biology of pitie-salpetriere hospital in Paris, France, 330 patients have had an ovarian tissue cryopreservation for fertility preservation before gonadotoxic treatment. Among them, at the present time, 180 have a procreative age and in consequence, could ask for the use of their ovarian cortex. The general aim of this protocol will be to propose to women wishing to have a baby, an ovarian tissue transplantation if the patients have an premature ovarian failure. The principal aim of this study will be to evaluate the efficiency and the safety of ovarian transplantation. Before grafting, the absence of contra- indication will be check. An informed consent will be signed by the patient. Autograft of ovarian cortex will be performed either in orthotopic or in heterotopic localization according to the pathology and a possible contra-indication to orthotopic position. After graft, each month hormonal assessment, ovarian echography and, after 3 months, an MRI, will be performed. Assisted Reproductive Technologies (ART) will be performed in case of heterotopic graft and if necessary in case of orthotopic graft. The efficiency of ovarian tissue autograft will be appreciated by the delay before the recovery of the ovarian function, the oocyte and embryos qualities in case of ART. Finally, the number of pregnancies and live births will be also appreciated as well as a possible recurrence of the pathology.

Official Title
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Autograft of Human Ovarian Tissue: Efficiency and Safety Evaluation

Conditions
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Ovarian Tissue Transplantation

Intervention / Treatment
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* Procedure: orthotopic graft
* Procedure: heterotopic graft


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : adult women (age ≥ 18 years old) who stored ovarian fragments before gonadotoxic treatments Women who desire to conceive Married women or in stable couple Cured women or in remission Women suffering of Premature ovarian failure Consenting women women with health insurance Exclusion criteria : age < 18 years women with normal ovarian function women with a disease at high risk for ovarian metastasis women with contraindication for surgery women with contraindication for pregnancy not cured women or not in remission women without health insurance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1- orthotopic graft<br> | Procedure: orthotopic graft<br>* (1) laparoscopy (2) ovarian fragments can be put back inside the pelvic cavity close to the natural location of the ovaries or<br>* Other names: ovarian tissue autotransplantation;|
| Experimental: 2- heterotopic graft<br> | Procedure: heterotopic graft<br>* put under the skin the ovarian fragments can be put under the skin of the abdomen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological (FSH, LH, E2 and AMH) changes from graft until the revovery of ovarian function | FSH, LH, E2 and AMH follow up every month after graft until the recovery of ovarian function, up to 18 months | every month after graft, up to 18 months | 
| Radiological (ultrasonography and MRI) changes in ovarian imaging from graft until the revovery of ovarian function | Radiological (only ultrasonography the first 3 months and after ultrasonography and MRI) follow up every month after graft until the recovery of ovarian function, up to 18 months | every month after graft, up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft vascularization |  | every month up to 18 months | 
| Relapse of the pathology |  | every month up to 18 months | 
| Delay and quality of the ovarian function recovery between ortho and heterotopic graft |  | after ovarian function recovery, up to 18 months | 
| Number of ovarian fragments necessary for ovarian function recovery |  | up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian tissue transplantation, Cryopreserved ovarian tissue