Menopause reversal restores periods and produces fertile eggs

Never too old?

Women who have already passed through the menopause may be able to have children following a blood treatment usually used to heal wounds

MENOPAUSE need not be the end of fertility. A team claims to have found a way to rejuvenate post-menopausal ovaries, enabling them to release fertile eggs, New Scientist can reveal.

The team says its technique has restarted periods in menopausal women, including one who had not menstruated in five years. If the results hold up to wider scrutiny, the technique may boost declining fertility in older women, allow women with early menopause to get pregnant, and help stave off the detrimental health effects of menopause.

“It offers a window of hope that menopausal women will be able to get pregnant using their own genetic material,” says Konstantinos Sfakianoudis, a gynaecologist at the Greek fertility clinic Genesis Athens.

“It is potentially quite exciting,” says Roger Sturmey at Hull York Medical School in the UK. “But it also opens up ethical questions over what the upper age limit of mothers should be.”

Women are thought to be born with all their eggs. Between puberty and the menopause, this number steadily dwindles, with fertility thought to peak in the early 20s. Around the age of 50, which is when menopause normally occurs, the ovaries stop releasing eggs – but most women are already largely infertile by this point, as ovulation becomes more infrequent in the run-up. The menopause comes all-too-soon for many women, says Sfakianoudis.

The age of motherhood is creeping up, and more women are having children in their 40s than ever before. But as more women delay pregnancy, many find themselves struggling to get pregnant. Women who hope to conceive later in life are increasingly turning to IVF and egg freezing, but neither are a reliable back-up option .

The menopause also comes early – before the age of 40 – for around 1 per cent of women, either because of a medical condition or certain cancer treatments, for example.

“It offers hope that menopausal women will be able to get pregnant using their own genetic material“

To turn back the fertility clock for women who have experienced early menopause, Sfakianoudis and his colleagues have turned to a blood treatment that is used to help wounds heal faster.

Platelet-rich plasma (PRP) is made by centrifuging a sample of a person’s blood to isolate growth factors – molecules that trigger the growth of tissue and blood vessels. It is widely used to speed the repair of damaged bones and muscles, although its effectiveness is unclear.. The treatment may work by stimulating tissue regeneration.

Sfakianoudis’s team has found that PRP also seems to rejuvenate older ovaries, and presented some of their results at the European Society of Human Reproduction and Embryology annual meeting in Helsinki, Finland, this month. When they injected PRP into the ovaries of menopausal women, they say it restarted their menstrual cycles, and enabled them to collect and fertilise the eggs that were released.

“I had a patient whose menopause had established five years ago, at the age of 40,” says Sfakianoudis. Six months after the team injected PRP into her ovaries, she experienced her first period since menopause.

Sfakianoudis’s team has since been able to collect three eggs from this woman. The researchers say they have successfully fertilised two using her husband’s sperm. These embryos are now on ice – the team is waiting until there are at least three before implanting some in her uterus.

The team isn’t sure how this technique works, but it may be that the PRP stimulates stem cells. Some research suggests a small number of stem cells continue making new eggs throughout a woman’s life, but we don’t know much about these yet. It’s possible that growth factors encourage such stem cells to regenerate tissue and produce ovulation hormones. “It’s biologically plausible,” says Sturmey.

 

Fertilised eggs

Sfakianoudis’s team says it has given PRP in this way to around 30 women between the ages of 46 and 49, all of whom want to have children. The researchers say they have managed to isolate and fertilise eggs from most of them.

“It seems to work in about two-thirds of cases,” says Sfakianoudis. “We see changes in biochemical patterns, a restoration of menses, and egg recruitment and fertilisation.” His team has yet to implant any embryos in post-menopausal women, but hopes to do so in the coming months.

PRP has already been helpful for pregnancy in another group of women, says Sfakianoudis. Around 10 per cent of women who seek fertility treatment at his clinic have a uterus that embryos find difficult to attach to – whether due to cysts, scarring from miscarriages or having a thin uterine lining. “They are the most difficult to treat,” says Sfakianoudis.

But after injecting PRP into the uteruses of six women who had had multiple miscarriages and failed IVF attempts, three became pregnant through IVF. “They are now in their second trimester,” says Sfakianoudis.

Fertility aside, the technique could also be desirable for women who aren’t trying to conceive. The hormonal changes that trigger menopause can also make the heart, skin and bones more vulnerable to ageing and disease, while hot flushes can be very unpleasant. Many women are reluctant to take hormone replacement therapy to reduce these because of its link with breast cancer. Rejuvenating the ovaries with PRP could provide an alternative way to boost the supply of youthful hormones, delaying menopause symptoms.

However, Sfakianoudis’s team hasn’t yet published any of its findings. “We need larger studies before we can know for sure how effective the treatment is,” says Sfakianoudis.

“One woman had been in menopause for 5 years. Six months after treatment, she had a period“

Some have raised concerns about the safety and efficacy of the procedure, saying the team should have tested the approach in animals first. “This experiment would not have been allowed to take place in the UK,” says Sturmey. “The researchers need to do some more work to make sure that the resulting eggs are OK,” saysAdam Balen  at the British Fertility Society.

To know if the technique really does improve fertility, the team will also need to carry out randomised trials, in which a control group isn’t given PRP.

Virginia Bolton, an embryologist at Guy’s and St Thomas’ Hospital in London, is also sceptical. “It is dangerous to get excited about something before you have sufficient evidence it works,” she says. New techniques often find their way into the fertility clinic without strong evidence, thanks to huge demand from people who are often willing to spend their life savings to have a child, she says.

If the technique does hold up under further investigation, it could raise ethical questions over the upper age limits of pregnancy – and whether there should be any. “I lay awake last night turning this over in my mind,” says Sturmey. “Where would the line be drawn?”

Health issues like gestational diabetes, pre-eclampsia and miscarriage are all more common in older women. “It would require a big debate,” says Sturmey.

 

SOURCE: NEW SCIENTIST