POI is characterized by high circulating levels of follicular stimulating FSH along with amenorrhea before 40 years of age. They are infertile due to a lack of follicle growth and ovulation; oocyte donation is the only effective treatment option. Residual ovarian follicles in these patients are not responsive to traditional gonadotropin treatments. Recently, we developed a method for activation of dormant follicles by using in vitro culture of ovarian fragments treated with Akt stimulators (IVA).


Under laparoscopic surgery, ovaries were removed and cut into strips. Ovarian strips from POI patients were vitrified. After thawing, strips were fragmented into 1–2 mm cubes before treatment with Akt stimulators. Two days later, cubes were autografted under laparoscopic surgery beneath serosa of Fallopian tubes. Follicle growth was monitored via transvaginal ultrasound and serum estrogen levels. After detection of antral follicles, patients were treated with FSH followed by hCG when preovulatory follicles were found. Mature oocytes were then retrieved and fertilized with the husband's sperm in vitro before cyropreservation of four-cell stage embryos. Patients then received hormonal treatments to prepare the endometrium for implantation followed by transferring of thawed embryos.
We enrolled 83 patients into the IVA clinical study. Their duration of amenorrhea is 5.7 ± 3.5 years without spontaneous pregnancy. We performed IVA in 46 patients and 28 of 46 patients achieved successful follicle growth by responding to the combining protocol of IVA followed by auto-transplantation of ovarian fragments beneath the serosa of Fallopian tubes. We performed embryo transfer in 6 patients, and achieved successful pregnancy in three patients, and two healthy baby were delivered.
Although oocyte donation is the only effective infertility treatment of POI patients so far, our IVA approach could enable POI patients to become pregnant using their own eggs.

St. Marianna University School of Medicine
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