Kazuhiro Kawamura, MD, PhD, an associate professor of obstetrics and gynecology at the St. Marianna University School of Medicine in Japan, doesn’t usually cry after performing a caesarean section. The operation itself is routine. But this birth was special.
Kawamura had just delivered the first baby conceived through the use of a new treatment for infertility developed in the Stanford laboratory of Aaron Hsueh, PhD, professor of obstetrics and gynecology. Kawamura headed the clinical aspects of the research, and all the patients received treatment in Japan. Hsueh is senior author of the work, which was published online today in the Proceedings of the National Academy of Sciences (subscription required).
"I couldn’t sleep the night before the operation, but when I saw the healthy baby my anxiety turned to delight," Kawamura told me. "The couple and I hugged each other in tears."
The technique, which the researchers refer to as “in vitro activation,” or IVA, requires an ovary (or a portion of an ovary) to be removed from the woman, treated outside the body and then re-implanted near her fallopian tubes. The woman is then treated with hormones to stimulate the growth of specialized structures in the ovaries called follicles in which eggs develop.
As I describe in our release:
Twenty-seven women in Japan took part in the experimental study. The researchers were able to collect mature eggs for in vitro fertilization from five of them. Although it has not yet been tested in women with other causes of infertility, the researchers plan to investigate whether the technique can also help women with early menopause caused by cancer chemotherapy or radiation, and infertile women between the ages of 40 and 45.
The women in the study were suffering from a condition called primary ovarian insufficiency, which affects about 1 percent of women of reproductive age in this country. The ovaries of these women don’t produce normal amounts of estrogen or release eggs regularly. As Hsueh explained:
Women with primary ovarian insufficiency enter menopause quite early in life, before they turn 40. Previous research has suggested that these women still have very tiny, primordial primary and secondary follicles, and that even though they are no longer having menstrual cycles they may still be treatable. Our results obtained with our clinical collaborators in Japan make us hopeful that this is a group of patients who can be helped.
Hsueh's laboratory has been studying follicle maturation for years. In 2010, he was awarded $1.4 million from the California Institute for Regenerative Medicine to study the maturation of human eggs for stem cell derivation. This birth represents a combination of two treatments known to induce follicle growth: cutting the isolated ovary into small pieces (which disrupts a growth arrest pathway called Hippo) and treating those bits with a substance to modulate a second follicle-development pathway (described by Gina Kolata in the New York Times) previously identified in Hsueh’s lab. The researchers found that the two treatments together had an additive effect, activating many more follicles than either treatment alone.
Valerie Baker, MD, chief of Stanford’s Division of Reproductive Endocrinology and Infertility and medical director of the Stanford Fertility and Reproductive Medicine Center, wasn't directly involved in the study, but is working with Hsueh to test the treatment on more women. As she described:
These women and their partners come to me in tears. To suddenly learn at a young age that your childbearing potential is gone is very difficult. This technique could potentially help women who have lost their egg supply for any reason.
Photo by Jon Ovington