Follicle Activation by Inhibition of the Hippo Pathway

Study Overview
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Brief Summary
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The aim of this project is to activate recruitment and growth of resting primordial follicles in the ovaries of women with diminished ovarian reserve, in attempt to increase the chance to become pregnant, either naturally or after assisted reproduction.

Detailed Description
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For this study investigators will carefully select 20 women with low AMH and imminent POI. They will be randomized to have cortical ovarian biopsies taken from either the left or right ovary. The biopsies will be fragmented in 1x1 mm2 pieces and immediately auto-transplanted in a peritoneal pocket under the right ovary. The contralateral untouched ovary will act as the control, making each woman their own control. Follow up: each week in 2,5 months the women will be assessed by transvaginal ultrasound and hormonal status. After 2,5-6 months the women will receive a FSH stimulation cycle (rFSH 300 IU or Corifollitropin) followed by standard IVF/ICSI, Hypothesis: the ovaries contain a pool of resting primordial follicles. By fragmentation of cortical ovarian tissue, manipulation of the local environment in the tissue will inhibit the Hippo Pathway and hereby active recruitment and growth of primordial follicles.

Official Title
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Auto-transplantation of Fragmented Ovarian Cortical Tissue in Infertile Patients With Premature Ovarian Oocyte Depletion - a Study to Promote Follicular Activation and Subsequent Fertility

Conditions
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Infertility

Intervention / Treatment
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* Procedure: Biopsy of ovarian cortical tissue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infertility with indication for IVF/ICSI Imminent POI, still cycling Age 25 - 39 years Two ovaries Serum AMH measurements < 5 pmol/l (two independent measurements) Antral follicle count (AFC) (sum of both ovaries < 5) Exclusion Criteria: Ovarian pathology (endometriosis, cysts) Known chromosomal abnormality Known autoimmune disease (except TPO-antibodies) Patients who have contraindication for laparoscopy

Ages Eligible for Study
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Minimum Age: 25 Years
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biopsy at Right side<br>Biopsy of ovarian cortical tissue (50% right side) | Procedure: Biopsy of ovarian cortical tissue<br>* Biopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket.<br>|
| Experimental: Biopsy at Left side<br>Biopsy of ovarian cortical tissue (50% left side) | Procedure: Biopsy of ovarian cortical tissue<br>* Biopsies will be taken from either right or left side. The cortical tissue will be isolated and fragmented in 1x1 mm2 pieces, followed by auto-transplantation to a peritoneal pocket.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of follicles > 12 mm | Number of follicles > 12 mm in response to controlled ovarian stimulation with corifollitropin from the biopsied ovary versus the contralateral untreated ovary | Up to 6 month after the auto-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side of ovulation | Frequency of ovulations occurring at the biopsy side versus the contralateral side in the subsequent 4- 6 months | Up to 6 months after auto-transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVA, Hippo Pathway, Follicle activation, Low Responder, POI, Poor Ovarian Reserve, Poor Ovarian Response, Salvador/Warts/Hippo pathway