Kazuhiro Kawamura, M.D., Ph.D. - Department of Obstetrics and Gynecology, St. Marianna University School of Medicine

Dr. Kawamura is a physician scientist. He had clinical training from Akita University in Japan and spent two years at Stanford University as a postdoctoral fellow working on ovarian physiology. He is now the Director of Reproduction and Fertility Center at St. Mariana University.

Dr Kawamura has done more than  85 publications, including 54 international papers, and has been the recipient of more than  31 very prestigous Scientific Awards, including the Japan society for Reproductive Medicine, Research Award (2004), the Japan Society for Fertilization and Implantation, Research Award (2005), the Japan society for Obstetrics and Gynecology, Research Award (2008),  the International Ovarian Conference 2009, Poster Award (2009) and the Japan society for Obstetrics and Gynecology, Excellent Paper Award (2012).

Project: Infertility treatment of patients with diminished ovarian reserve using in vitro activation of follicles

The main feature of reproductive aging in women is the depletion of ovarian follicular pool. In addition, 1% of women suffer from infertility due to primary ovarian insufficiency (POI) with early exhaustion of ovarian follicles. These women are infertile due to impaired follicle growth.

We found that fragmentation of ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. We further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then treated infertile POI patients by fragmenting their ovaries followed by Akt stimulator treatment in vitro and auto-transplantation. This in vitro activation procedure was named as IVA. We successfully retrieved mature oocytes in POI patients. Following IVF-ET, patients became pregnant and a healthy baby was delivered. Our IVA approach could enable POI patients to become pregnant using their own eggs. We are now expanding this treatment to the patients with diminishing ovarian reserve.

Our objective is to improve the clinical outcome of the IVA approach. Because our histological analyses indicated that IVA is only effective for patients with residual follicles, we propose to identify suitable serum markers to predict the presence of residual follicles. Because graft survival is low after auto-transplantation, we will investigate methods to improve graft survival by testing angiogenic factors important for neovascularization. In addition to grafting ovarian fragments beneath the serosa of Fallopian tubes, we will check if other transplantation sites are suitable for graft neovascularization, as well as convenient for trans-vaginal ultrasound monitoring of follicle growth and oocyte retrieval. To further evaluate the safety of IVA approach, we will perform genetic analyses using samples from placentas and fetal leucocytes from umbilical cord blood during delivery in pregnant patients after IVA.

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