Primary ovarian insufficiency, also called premature ovarian failure, happens when a woman loses her normal ovarian function before she turns 40. When the ovaries stop working properly, estrogen production goes down significantly and ovulation and menstruation both become problematic.
Premature ovarian failure isn't the same as premature menopause, since women experiencing it do still have the occasional menstrual period in many cases. Though they may sometimes ovulate and even become pregnant, women with this condition often suffer from infertility.
This condition has been frustrating to patients and doctors alike, but a new technique that induces the growth of the primordial eggs these women still have is offering hope. The technique, created by researchers from the Stanford University School of Medicine, has been examined in a study. Though it is still in its early phases, one woman has already given birth after being treated with the technique, and another is pregnant!
Senior study author Aaron Hsueh, who is a professor of obstetrics and gynecology at Stanford, says: "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."
Invitro Activation Explained
The new fertility treatment was called "in vitro activation". "Human females have about 800,000 very small, primordial follicles at birth," Professor Huseh explains. "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."
Huseh goes on to say that it is not clear why certain follicles are selected to mature, or why follicles stop developing in women who have primary ovarian insufficiency.
Previous studies showed that which showed that a signaling pathway made up of several proteins controls the growth of follicles in the ovary, and the key protein is apparently one called PTEN. PTEN is important, because it was already known that blocking the activity of this protein in both mouse and human ovaries can cause dormant follicles to develop.
Huseh's research team figured out that they could disrupt a growth-arrest pathway called "Hippo", by breaking the ovary into pieces. They then treated the ovaries with a substance that regulates the PTEN pathway, resulting in the stimulation of a signifcant number of follicles.
OK — But What Does That Mean In Practice?
Twenty-seven women who suffered from primary ovarian insufficiency participated in the study. They had an average age of 37, and had stopped menstruating an average of 6.8 years before participating in the project.
Both ovaries were surgically removed from these women, after which the team found that 13 of them had residual follicles that could be used for further treatment. Then, the ovaries were split (or "mechanically fragmented") as described above, and treated with drugs that regulate the PTEN pathway. After that, tiny parts of the women's ovaries were transplanted to a site near the fallopian tubes, and carefully monitored with ultrasound scans. The woman also underwent hormone-level tests.
Now for the exciting part: eight of the 13 women showed signs of follicle growth. When they were given ovulation-stimulating hormones, five of the study subjects ended up developing mature eggs. They were then harvested for the IVA — invitro activation — procedure, and fertilized with their partners' sperm.
This procedure is still in its infancy, and not all the women who went through this procedure ended up pregnant. In one of the cases, an embryo was transferred to the uterus but pregnancy did not follow. Two are now going through additional egg-collection cycles.
The other senior author of the study, Dr Kazuhiro Kawamura, is an associate professor of obstetrics and gynecology at the St. Marianna University School of Medicine. He was obviously very satisfied with the success of the brand new treatment, but he was still concerned and followed the new mother throughout her pregnancy.
Dr Kawamura shares: "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 cesarean section myself."
The new treatment is unlikely to find its way to a fertility clinic near you in the foreseeable future, but it clearly has enormous potential. Once it is researched and developed more, IVA may also help women who suffered a premature menopause or are infertile as a result of cancer.