PI3K is a family of enzyme involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3K-Akt signaling pathway negatively is regulated by PTEN. Recently, we developed the method for activation of dormant follicles by using in vitro culture of ovarian fragments treated with PTEN inhibitor and PI3K activator (IVA, in vitro activation). We applied this approach to infertility treatment of patients with primary ovarian insufficiency (POI). POI patients are infertile due to a lack of follicle growth and ovulation; oocyte donation is the only effective treatment option. We performed laparoscopic surgery to remove ovaries. Ovaries were cut into strips and vitrified. After thawing, the strips were fragmented into small cubes and cultured with PTEN inhibitor and PI3K activator. After two days culture to activate dormant residual follicles, the cubes were autografted under laparoscopic surgery beneath serosa of Fallopian tubes. Follicle growth was monitored via transvaginal ultrasound and serum estrogen levels. With estrogen replacement therapy to maintain normal levels of LH together with estrogen, patients were treated with FSH/HMG for up to 4 weeks followed by hCG when preovulatory follicles were found. Mature oocytes were then retrieved and fertilized before cyropreservation of four-cell stage embryos. Patients received hormonal treatments to prepare the endometrium for implantation followed by transferring of thawed embryos. We enrolled 37 patients into the IVA clinical study Histological analyses in ovaries after laparoscopic ovariectomy revealed that 20 of 37 patients contained residual follicles. Among 20 patients, nine patients achieved successful follicle growth. We could obtain mature oocytes from seven patients, and achieved the successful pregnancy following IVF-ET in three patients, and two healthy babies were delivered from two patients. In this presentation, I will introduce our basic and clinical studies of IVA and some recent progress in the IVA approach.
11 Jul 2016 - 11 Jul 2016