For women with primary ovarian insufficiency (POI), getting pregnant
can feel like nothing more than a dream. Characterized by entering
menopause early before the age of 40, this kind of infertility has no
current treatment options, and women cannot have a baby that shares
their genetic information.But now, there may be an answer for these women who want to have a child of their own. Researchers from Stanford University School of Medicine have developed a brand new technique called in vitro activation, which involves inducing the ovaries to produce eggs.
The scientists tested their treatment on 27 women in Japan with POI and were able to collect viable eggs from five of them. After going through the treatment, one woman gave birth to a healthy baby boy, and another is currently pregnant.
“Right now the main options people have for this diagnosis is to either do egg donation and fertilize with the intended father’s sperm, or they may adopt the child,” Dr. Valerie Baker, associate professor of obstetrics and gynecology at Stanford, told FoxNews.com. “Various fertility medications really don’t work well for this condition at all, which is why this is such a ray of hope.”
Awakening sleeping follicles
The key to developing their technique came when researchers discovered a signaling pathway responsible for controlling the growth of follicles in ovaries.
“The human ovary is a very interesting organ in that you have 800,000 follicles at birth,” senior author Dr. Aaron Hsueh, professor of obstetrics and gynecology at Stanford, told FoxNews.com. “…The follicles sit there, and they don’t grow, but then about 1,000 of this 800,000 begin to grow every month.”
Of those 1,000 follicles, only one matures into an egg that is released during ovulation each month. During the course of her lifetime, a woman will ovulate only around 400 mature eggs.
It had previously not been known why one particular follicle became an egg and the others did not, but in 2010, Hsueh discovered that several proteins, including one called PTEN, regulate this growth process. He showed that PTEN acts as a brake in the ovaries, keeping the small follicles from maturing fully.
“This is a system that’s found in a lot of organs in the body, and originally found in the fly,” Hsueh said. “It is a very used signaling pathway that makes sure your heart or liver do not overgrow when they reach the right size.”
Hsueh found that by blocking this PTEN “brake” system, he could stimulate dormant follicles in the ovaries to grow and produce mature eggs. He explained that although women with POI no longer have menstrual cycles, some of them still have unused small follicles in their ovaries.
In vitro activation
Utilizing this science, Hsueh and his colleague Yuan Cheng, a postdoctoral scholar in Hsueh’s lab, came up with a complex method called in vitro activation, which ultimately led to the successful birth in their study cohort.
First they removed the ovaries from their 27 participants, which were
then cut into pieces – a process known as fragmenting. Previous
research has shown that mechanically disrupting the ovary through
cutting or drilling small holes in it can help stimulate follicular
development.Once the ovaries were cut into small pieces, the scientists treated them with drugs to block the PTEN pathway, in order to further stimulate the smaller follicles to grow. The ovary pieces were then transplanted through small incisions near the fallopian tubes of the women from which they were removed.
Of the 27 participants, five women went on to develop mature eggs – much more quickly than originally expected.
“This is where the interesting thing comes in,” Hsueh said. “This small sleeping follicle usually takes six months to grow” – based on pervious tests using mouse models. “However, in his original study (Cheng) found that within three weeks, several of his patients had mature follicles and mature eggs.”
The mature eggs were then collected and fertilized with the intended husband’s sperm through in vitro fertilization. The resulting embryos were then frozen and transferred back into the uterus.
Of these five women, one received her embryo but failed to become pregnant, one received the embryo and is currently pregnant, and one became pregnant, ultimately giving birth to a seemingly healthy baby boy. The other two women are still preparing for their embryo transfer and undergoing further rounds of egg collection.
Providing hope
Hsueh and his team hope that in vitro activation will aid an entire group of women who previously thought they could never have a child of their own. They noted that their technique can also be used to help women who have beaten cancer.
“A lot of people survive cancer, but because their chemotherapy damages the ovaries, they have fewer follicles,” Hsueh said. “They’ll reach early menopause, but some of them still have smaller follicles and those baby follicles will be helped to wake up by this procedure.”
However, as shown in their study, only a fraction of women who reach early menopause will go on to successfully grow mature eggs.
“If they don’t have follicles left, there’s nothing you can do,” Hsueh said. “So 25 to 30 percent of this type of patient can eventually have a baby.”
But according to Baker, who is working with Hsueh to continue investigating the treatment in Japan and at Stanford, these small odds are enough for these women.
“It’s so devastating for the women who have this,” Baker said. “For most people, the most important element in life is to have a family or have a child. It can be devastating to a woman and her partner, not having a child genetically related… So I’m incredibly excited. It’s the first thing I’ve seen that looks like it could be hopeful.”
The research was published in the Proceedings of the National Academy of Sciences.
