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Activation of dormant follicles

a new treatment for premature ovarian failure?

Kawamura, Kazuhiro; Kawamura, Nanami; Hsueh, Aaron J.W.

Current Opinion in Obstetrics and Gynecology: June 2016 - Volume 28 - Issue 3 - p 217–222
doi: 10.1097/GCO.0000000000000268
FERTILITY, IVF AND REPRODUCTIVE GENETICS: Edited by Emre Seli and Juan Antonio García Velasco

Purpose of review Premature ovarian failure (POF) is diagnosed by amenorrhea before 40 years of age. Owing to exhaustion of follicles in POF ovaries, egg donation is the only option. Although menstrual cycles cease in POF patients, some of them still contain residual dormant follicles in ovaries. Recently, we developed a new infertility treatment and named it as in-vitro activation (IVA), which enables POF patients to conceive using their own eggs by activation of residual dormant follicles. Here, we summarize data showing the potential of IVA as a new infertility treatment for POF patients.

Recent findings Transgenic mouse studies revealed that the stimulation of phosphatidylinositol-3-kinase-AKT-forkhead box O3 pathway activated dormant primordial follicles. In murine and human ovaries, the phosphatase and tensin homolog inhibitors and phosphatidylinositol-3-kinase activators were demonstrated to activate dormant primordial follicles in in-vitro cultures. Subsequent studies showed that ovarian fragmentation suppressed Hippo signaling pathway, leading to ovarian follicle growth. Combining these two methods in an IVA approach followed by ovarian tissue autotransplantation, successful follicle growth, and pregnancies were reported in POF patients. Currently, two healthy babies were delivered, together with two additional pregnancies.

Summary IVA treatment is a potential infertility therapy for POF patients who have residual follicles.

aDepartment of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

bDepartment of Obstetrics/Gynecology, Stanford University School of Medicine, Stanford, California, USA

Correspondence to Kazuhiro Kawamura, Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamaeku, Kawasakishi, Kanagawa, 216-8511, Japan. Tel: +81 44 977 8111; e-mail:

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