New Breakthrough Tackles the Infertility Issue

By Alisha Jain | UTS Staff Writer | SQ Online (2013-14)

Many women have had their dreams crushed when told they could never have children. Today, infertile women are incapable of becoming pregnant, but a new innovation may give them a fighting chance at pregnancy. A novel technique, developed at Stanford and tested in Japan, has been found that causes egg growth in previously infertile women.

The study targeted primary ovarian insufficiency, a condition that includes the ovaries’ failure to produce enough estrogen or release eggs regularly before the woman turns 40. These individuals have symptoms similar to early menopause, but may not exhibit other effects of menopause such as decreased levels of thyroid hormone, cold sweats, or hot flashes. The major difference, however, is that individuals with primary ovarian insufficiency still have small, primordial, primary and secondary follicles and even though they no longer have their menstrual cycle, they can still become pregnant through this treatment. Stanford’s study yielded women with primary ovarian insufficiency who successfully redeveloped egg production in their ovaries.

The clinical study in Japan tested 27 women. Researchers collected their eggs through in-vitro fertilization for five women out of this test group. In this technique, called in-vitro activation (termed IVA), the woman’s ovary is removed from her body, treated, and then implanted back near her fallopian tubes. The woman is then treated with follicle-stimulating hormone to increase chances of pregnancy.

A signaling pathway called PTEN controls follicle growth in all women, and blocking the PTEN pathway stirs dormant follicles into growing. A researcher could then tap into this new store of follicles that would otherwise have no function. Mature human eggs were developed from follicles after their PTEN activity was blocked. These mature human eggs means pregnancy is now possible.

The other mechanism to produce heightened follicle growth was through an ovary-stimulation process that included drilling small holes in the ovary to stimulate follicles that were arrested because of what is termed the Hippo pathway. Through a combination of inhibiting both the PTEN and Hippo pathways, even more follicles were stimulated and chances for ovulation were increased. Utilizing frozen portions of human ovaries, the researchers blocked the two pathways and then transplanted small pieces of the ovaries back into 8 test subject women. Out of those 8, five women developed mature eggs that were then fertilized with sperm and two women successfully became pregnant. The researchers were able to talk to the women, who were completely elated. Seeing the joy in the patients’ faces grounded the work for these researchers.

IVA treatment could be the saving grace for many families who have been told they could never have biological children. A combination of both PTEN and Hippo inhibition methods also guarantees a higher probability that this new treatment could yield more pregnancies. After a successful birth, one researcher, Kazuhiro Kawamura said, “the couple and I hugged each other in tears.” Kawamura hopes that IVA can help patients with primary ovarian insufficiency globally.