Study offers hope of fertility after early menopause
Scientists say they have found a way to beat the menopause by waking up dormant follicles, offering new hope to women who run out of eggs early in life.
The experimental technique has been tested on a group of infertile women who reached the menopause at around the age of 30.
Of the 13 treated women, one has given birth to a healthy baby boy while another is said to be pregnant.
Until now the only option available to women with this form of infertility has been to accept IVF treatment using donor eggs, which means raising a child with another biological mother.
The researchers now plan to see if the technique can help other categories of women, including those affected by cancer treatment, and who become infertile between the ages of 40 to 45.
Around 1% of women suffer from a condition called primary ovarian insufficiency which brings on the menopause at a very young age.
On average the women taking part in the study were 37 years old and had stopped menstruating 6.8 years earlier.
The “In-Vitro Activation” (IVA) technique involves removing the ovaries, cutting them into small one to two millimetre square cubes, and treating the fragments with special stimulating drugs for two days.
The fragments are then implanted within the Fallopian tubes and hormones administered to trigger egg development.
Lead scientist Dr Kazuhiro Kawamura, from St Marianna University School of Medicine in Kawasaki, Japan, said: “For patients with primary ovarian insufficiency, egg donation is the only option for bearing a baby.
“These patients are eager to find a way to become pregnant with their own eggs. I hope that IVA will be able to help patients with primary ovarian insufficiency throughout the world.”
The research builds on work in the laboratory showing that women who suffer premature menopause still retain tiny, dormant, “primordial” follicles.
Arousing these immature follicles can result in women previously thought to have untreatable infertility producing viable eggs.
The scientists developed a two-step approach to the problem of waking up the sleeping primordial follicles.
First, the ovaries were removed an broken up - a technique that already forms the basis of some infertility treatments.
Fragmenting the ovaries is thought to disrupt a biological signalling pathway that normally stops too many follicles maturing at once, thereby conserving a woman’s egg supply.
Next, the ovary fragments were exposed to chemicals that stimulate another signalling pathway called Akt. This has been shown to stir dominant follicles into growing and producing mature eggs.
A total of 27 Japanese women with primary ovarian insufficiency took part in the study and had both ovaries removed by keyhole surgery. Of these, 13 were found to have ovaries containing dormant follicles.
Follicle growth was observed in eight cases, the scientists reported in the journal Proceedings of the National Academy of Sciences.
Eventually five women developed mature eggs that were collected for in-vitro fertilisation. The eggs were fertilised with sperm from their partners to produce embryos that were frozen and then transferred to the womb.
One woman received an embryo but failed to become pregnant. Another was still pregnant, said the researchers, and a third who received two embryos had given birth to a healthy baby boy. The other two women were either preparing for embryo transfer or undergoing further rounds of egg collection.
Dr Kawamura himself performed a Caesarean section on the woman who gave birth.
“I could not sleep the night before the operation, but when I saw the healthy baby, my anxiety turned to delight,” he said. “The couple and I hugged each other in tears.”
Scientists at Stanford University in California, United States, worked with the Japanese team and led the laboratory development of the technique.
Dr Valerie Baker, director of the university’s Program for Primary Ovarian Insufficiency, said: “Although there are too little data available about this experimental treatment to guarantee any kind of success rate, the approach does look quite promising for women who have run out of eggs.
“When I first saw the data, my eyes lit up. These women and their partners come to me in tears. To suddenly learn at a young age that your child-bearing potential is gone is very difficult.
“This technique could potentially help women who have lost their egg supply for any reason.”
Women are born with around 80,000 primordial follicles in their ovaries, most of which remain dormant.
Only about 1,000 start to grow each month, and of these just one reaches maturity to produce an egg when a woman starts menstruating.
“It’s not known exactly how the follicles are selected for development, or why these follicles stop developing in women with primary ovarian insufficiency,” said co-author Professor Aaron Hsueh, from Stanford University. “But our treatment was able to awaken some of the remaining primordial follicles and cause them to release eggs.”
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