In Vitro Follicle Activation (IVA)

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

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).

Study Overview

• Status: Terminated
• Conditions: Infertility; Primary Ovarian Insufficiency
• Intervention / Treatment: Procedure: In Vitro Follicle Activation (IVA); Drug: Follicle Activation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Fertility Laboratories of Colorado
    • Lone Tree, Colorado, United States, 80124
      • National Foundation for Fertility Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: In Vitro Follicle Activation (IVA); 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); 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.; Drug: Follicle Activation; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Foundation for Fertility Research
• Collaborators: Fertility Laboratories Of Colorado
• Investigators: Principal Investigator: Rebecca L Krisher, Ph.D., NFFR; Principal Investigator: William B Schoolcraft, M.D., Fertility Laboratories of Colorado

Publications and helpful links

General Publications

• Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, Ho CH, Kawamura N, Tamura M, Hashimoto S, Sugishita Y, Morimoto Y, Hosoi Y, Yoshioka N, Ishizuka B, Hsueh AJ. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17474-9. doi: 10.1073/pnas.1312830110. Epub 2013 Sep 30.
• Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, Morimoto Y, Kawamura K. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015 Mar;30(3):608-15. doi: 10.1093/humrep/deu353. Epub 2015 Jan 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: July 7, 2015
• First Submitted That Met QC Criteria: July 9, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Ovarian Follicle; Reproductive Techniques, Assisted
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Infertility; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: NFFR-IVA-2015