Enzyme 'switch' clue to infertility and miscarriage

The findings could help some couples trying to have a baby

Scientists have identified a "fertility switch" protein which appears to increase infertility if levels are too high and fuel miscarriage if too low.

An Imperial College London team took samples from the womb lining of more than 100 women.

Writing in Nature Medicine they said women with unexplained infertility had high levels of the enzyme SGK1, while those who miscarried had low levels.

One fertility expert said the research offered new avenues for research.

About one in six women have difficulty getting pregnant, and one in 100 women trying to conceive experience recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

The Imperial team also carried out mouse studies which found levels of SGK1 in the womb lining decline during the window of time during which they can fall pregnant.

When extra copies of the SGK1 gene were implanted into the womb lining, these mice were unable to get pregnant.

The researchers say this suggests a fall in SGK1 levels is essential for making the uterus receptive to embryos.

However, if low levels of SGK1 persist into pregnancy, this appears to cause different problems.

When the researchers blocked the SGK1 gene, mice had no problem getting pregnant but they had smaller litters and showed signs of bleeding, suggesting a lack of SGK1 made miscarriage more likely.

'Focus for research'

Prof Jan Brosens, who led the research at Imperial's Institute of Reproductive and Developmental Biology, said: "Our experiments on mice suggest that a temporary loss of SGK1 during the fertile window is essential for pregnancy, but human tissue samples show that they remain high in some women who have trouble getting pregnant.

"I can envisage that in the future, we might treat the womb lining by flushing it with drugs that block SGK1 before women undergo IVF."

After an embryo is implanted, the lining of the uterus develops into a specialised structure called the decidua.

The team say lab tests show low levels of the enzyme may impair the ability of cells in the decidua to protect themselves against oxidative stress, a condition in which there is an excess of reactive chemicals inside cells.

Dr Madhuri Salker, who also worked on the study, said: "We found that low levels of SGK1 make the womb lining vulnerable to cellular stress, which might explain why low SGK1 was more common in women who have had recurrent miscarriage.

"In the future, we might take biopsies of the womb lining to identify abnormalities that might give them a higher risk of pregnancy complications, so that we can start treating them before they get pregnant."

Prof Richard Fleming, of the Glasgow Centre for Reproductive Medicine, said the research was "encouraging".

"To have something as clear as this, with a specific enzyme, is great. It is giving us something to focus on."

But, Prof Fleming, who is also a member of the British Fertility Society, warned it would be some time before the discovery translated into day-to-day practice.

"It's all very well to measure something that is missing - whether or not you can correct it is the next step.

"But at least we know somewhere that's directly involved, and can explore that.