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.

“I couldn’t sleep the night before the operation, but when I saw the healthy baby my anxiety turned to delight,” says Kawamura. “The couple and I hugged each other in tears.”

Kawamura had just delivered the first baby conceived through an experimental infertility treatment developed in the Stanford laboratory of Aaron Hsueh, PhD, professor of obstetrics and gynecology. The birth was announced in September in a report in the Proceedings of the National Academy of Sciences. Kawamura led the clinical aspects of the study, with all patients receiving their treatment in Japan.

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 and then re-implanted near one of 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.

Twenty-seven women with a condition called primary ovarian insufficiency took part in the study. Normally they would have required an egg donor to become pregnant.

The researchers were able to collect mature eggs for in vitro fertilization from five women. One has had a healthy boy and another a miscarriage. Although the approach 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 treatment as well as infertile women between the ages of 40 and 45.

“Women with primary ovarian insufficiency enter menopause quite early in life, before they turn 40,” says Hsueh. “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.”

Women are born with hundreds of thousands of primordial follicles, each containing one immature egg. Usually, only one follicle develops to maturity and releases an egg each month. About 1 percent of women of reproductive age in this country experience primary ovarian insufficiency, meaning that their ovaries don’t produce normal amounts of estrogen or release eggs regularly.

The successful birth stemmed from two treatments known to induce follicle growth. The researchers found that cutting the ovary into pieces disrupts a growth-arrest pathway called Hippo, which modulates the growth of many organs in the body. In the ovary, the Hippo pathway appears to help ensure that only a few follicles at a time are growing to better conserve a woman’s supply of eggs. Ovaries activated by cutting, or fragmenting, were then treated with a substance to modulate a second follicle-development pathway previously identified in Hsueh’s lab.

“When I first saw the data, my eyes lit up,” says Valerie Baker, MD, chief of Stanford’s division of reproductive endocrinology and infertility and the medical director of the Stanford Fertility and Reproductive Medicine Center. “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.”

 

E-mail Krista Conger