A study has detailed a new method of inducing egg growth in women suffering from infertility. Created by researchers from the Stanford University School of Medicine, this technique has already resulted in one woman giving birth, while another is pregnant.
The findings are published in the Proceedings of the National Academy of Sciences.
Doctors from the St. Marianna University School of Medicine in Kawasaki, Japan, tested the method in women suffering from primary ovarian insufficiency, also known as premature ovarian failure. This condition involves a loss of normal function in the ovaries before the age of 40.
Aaron Hsueh, professor of obstetrics and gynecology at Stanford and senior author of the study, says:
"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."
IVA action stimulates follicles to produce eggs
The researchers call the new fertility treatment "in vitro activation," or IVA. This work builds on previous research, which showed that a signaling pathway made up of several proteins, including PTEN, controls the growth of follicles in the ovary.
Other research showed that blocking PTEN activity in mouse and human ovaries triggered dormant follicles to produce mature eggs.
For the new study, the researchers found that splitting the ovary into pieces disrupts a growth-arrest pathway called Hippo. The Hippo pathway appears to ensure limitation of the number of follicles that grow at one time, in order to preserve egg supply.
When they then treated the ovary with a substance to modulate the PTEN pathway, they found that these two treatments together activated a significant amount of follicles.
Prof. Hsueh explains:
"Human females have about 800,000 very small, primordial follicles at birth. Most of them remain dormant, and only about 1,000 start to grow each month. One of these reaches maturity each month to produce an egg each menstrual cycle."
"It's not known exactly how the follicles are selected for development, or why these follicles stop developing in women with primary ovarian insufficiency. But our treatment was able to awaken some of the remaining primordial follicles and cause them to release eggs."
Researchers from Stanford explain their new IVA method in the video below:
Technique performed in women
The researchers conducted a minimally invasive procedure involving removal of both ovaries from 27 women with primary ovarian insufficiency, who had an average age of 37 and had stopped menstruating an average of 6.8 years before the procedure.
Of the 27 women, 13 were found to have ovaries that contained residual follicles.
These ovaries were then "mechanically fragmented" and treated with drugs in order to block the PTEN pathway. Small pieces of the women's ovaries were then transplanted near their fallopian tubes.
The researchers then monitored the women through weekly or biweekly ultrasounds and hormone-level tests, in order to detect their follicle growth. Follicle growth was found in eight of the women, who were then treated with hormones to stimulate ovulation.
Of these, five of the women developed mature eggs that were then collected for IVA. The eggs were fertilized with sperm from the women's partners. The four-cell embryos were frozen before being transferred into the women's uteruses.
Of the five women, one woman received one embryo but did not become pregnant. Two of the women are preparing for embryo transfer or undergoing extra rounds of egg collection.
However, one woman received one embryo and is pregnant, while another received two embryos and has given birth to a healthy baby boy.
Dr. Kazuhiro Kawamura, associate professor of obstetrics and gynecology at the St. Marianna University School of Medicine and a lead author of the study, speaks of his delight at the success of the treatment:
"Although I believed, based on our previous research, that this IVA approach would work, I monitored the pregnancy closely and, when the baby was in a breech presentation, I performed the caesarean section myself."
"I could not sleep the night before the operation, but when I saw the healthy baby, my anxiety turned to delight. The couple and I hugged each other in tears. I hope that IVA will be able to help patients with primary ovarian insufficiency throughout the world."
Potential to treat other fertility problems
The researchers are looking to test this procedure in women who have other fertility problems, such as those with early menopause caused by cancer, chemotherapy or radiation, and women who are infertile between the ages of 40 and 45.
Prof. Hsueh says he also plans to look at ways to treat the PTEN and Hippo pathways with drugs, which may eliminate the need for ovary removal.
However, they note that it is likely to be many years before the IVA procedure will become a routine procedure like IVF (in vitro fertilization).
Medical News Today recently reported on a study that suggested a person's fertility is dependent upon their personality.