Infertile woman gives birth after boost to ovaries

A baby boy has been born following a new fertility treatment that awakens dormant eggs in women who have stopped menstruating.

The treatment could help women who have left child-bearing too late, or have been left infertile after treatment for cancer. But some have raised concerns that the technique has been rushed to the clinic before being properly tested.

Women are born with millions of immature eggs, or follicles, but only around 400 mature to the point where an egg is released into the fallopian tubes and could be fertilised. But some of these follicles remain, even after a woman has stopped menstruating.

Now researchers have found a way to wake these dormant follicles and produce eggs that are capable of being fertilised. The first test of this technique has resulted in a baby boy, born in December 2012 in Japan.

Chop and change

Immature follicles are usually kept in a dormant state by the PTEN gene, which suppresses a signalling pathway involved in cell growth. Aaron Hsueh at Stanford University Medical School in California and his colleagues had previously showed that immature mouse follicles could be stimulated to mature if pieces of ovary were incubated with a molecule that stimulates the signalling pathway that PTEN inhibits.

Hsueh's team also discovered that the physical act of cutting up the ovaries disrupts a second signalling pathway, called the Hippo pathway, which normally suppresses the growth of many of the body's other organs as well.

When the cut up and incubated tissue was implanted back into the mice, eggs were released and fertilised, resulting in the birth of live pups.

Now the team has used a similar process to give women with premature menopause a shot at being mothers, using their own eggs.

Follicle growth

Twenty-seven women who had been diagnosed with premature menopause volunteered to have their ovaries removed. Of these, only 13 had any residual follicles left. These women had their ovaries diced up and incubated with a PTEN inhibitor, before pieces were transplanted into their fallopian tubes. Ultrasound was used to monitor follicle growth.

In all, eight of the women produced mature follicles, and were given drugs to trigger the release of an egg. Five of them produced mature eggs which were harvested and fertilised by IVF. So far, three have had their embryos implanted, resulting in one birth and one on-going pregnancy. The third failed to implant.

Ultimately, Hsueh says the technique could be used to help women who have stopped menstruating, and may not be responding to conventional treatment. "This data shows that there are small follicles still sitting there after women have stopped menstruating. This is a way that you can get them to work."

However, Evelyn Telfer, a fertility researcher at the University of Edinburgh, UK, says much more work is needed to ensure the technique is safe before it is routinely used in the clinic. "It's an interesting first step, but we need to do many controlled studies ? without implanting the embryos ? to show that at each stage of the procedure these eggs are normal," she says. "People say it's a baby at all costs, but if the baby is compromised in any way then that's a problem."

It's also not clear whether the women would have produced mature follicles, and ultimately eggs, if their ovaries had been diced up and re-implanted without exposing them to a PTEN inhibitor.

Journal reference: PNAS, DOI: 10.1073/pnas.1312830110

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