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).

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.

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.

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.

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.

Ultrasound analysis of the number of follicles developing in the grafted ovarian tissue following activation in vitro

The number of oocytes recovered from follicles developing in the grafted ovarian tissue following in vitro activation

The incidence of implantation and pregnancy following transfer of embryos produced from oocytes recovered from follicles developing in the activated ovarian tissue.

The proportion of good quality blastocyst stage embryos developed during in vitro fertilization (IVF) cycle(s), of the total number of fertilized eggs

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.

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.