In Vitro Follicle Activation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of an experimental treatment, known as in vitro activation (IVA) of dormant ovarian follicles, for infertility in women diagnosed with primary ovarian insufficiency (POI).

Detailed Description
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The purpose of this study is to evaluate the effectiveness of an experimental treatment, known as in vitro activation (IVA) of dormant ovarian follicles, for infertility in women diagnosed with primary ovarian insufficiency (POI; also known as premature ovarian failure). Patients diagnosed with POI are infertile due to a lack of follicle growth and ovulation; oocyte donation is the only treatment option currently available to enable these women to have a child. IVA treatment may result in the rescue of the remaining primordial follicles within the ovary, thus making oocytes available for IVF, embryo production, transfer and pregnancy. In this experimental treatment, ovarian tissue is removed from the patient and cultured in vitro for 48 hours with specific compounds to activate dormant primordial follicles. Following activation ovarian tissue is auto-grafted to the serosa of the fallopian tube, and the patient is monitored for signs of follicle growth. Growing follicles are stimulated with exogenous hormones, followed by oocyte retrieval and IVF.

Official Title
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In Vitro Activation of Primordial Follicles as a Method to Treat Infertility Caused by Primary Ovarian Insufficiency

Conditions
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Primary Ovarian Insufficiency, Infertility

Intervention / Treatment
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* Procedure: In Vitro Follicle Activation (IVA)
* Drug: Follicle Activation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with primary ovarian insufficiency (POI), seeking pregnancy and eligible for IVF at Colorado Center for Reproductive Medicine (Lone Tree, CO). Patients can be of any race, culture, sexual orientation or ethnicity. Exclusion Criteria: Minors are excluded from participation in this study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: In Vitro Follicle Activation (IVA)<br>Ovarian tissue will be removed and cultured in vitro with compounds to activate dormant follicles. Following activation, ovarian tissue will be auto-grafted and the patient monitored for follicular growth. | Procedure: In Vitro Follicle Activation (IVA)<br>* Laparoscopic removal of ovarian tissue, followed by in vitro activation of dormant ovarian follicles and autografting back to the patient for follicle growth and egg retrieval.<br>Drug: Follicle Activation<br>* Ovarian cortical pieces will be treated in vitro with a PTEN activator (bpV(hopic)) and a PI3K inhibitor (740YP) in vitro to activate primordial ovarian follicles, prior to autografting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antral follicle development measured by ultrasound examination | Ultrasound analysis of the number of follicles developing in the grafted ovarian tissue following activation in vitro | 1 year after auto-grafting | 
| Recovery of oocytes by trans-vaginal ultrasound guided oocyte aspiration | The number of oocytes recovered from follicles developing in the grafted ovarian tissue following in vitro activation | 1 year after auto-grafting | 
| Pregnancy | The incidence of implantation and pregnancy following transfer of embryos produced from oocytes recovered from follicles developing in the activated ovarian tissue. | 1.5 years after auto-grafting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Offspring weight | The birth weight of children born | 1 year after egg retrieval | 
| Offspring gender | The gender of children born | 1 year after egg retrieval | 
| Development of good quality blastocysts using the Gardner morphological blastocyst grading system | The proportion of good quality blastocyst stage embryos developed during in vitro fertilization (IVF) cycle(s), of the total number of fertilized eggs | 1 week after egg retrieval | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reproductive Techniques, Assisted, Ovarian Follicle