Lack of stem cells in womb linked to recurrent miscarriage

Recurrent miscarriage could be caused by a lack of resident stem cells in the lining of the womb, according to a study.

Researchers at the University of Warwick in the UK examined samples of womb lining from 183 women and found that women with recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, were lacking an epigenetic signature typical of stem cells. This suggests that women suffering from RPL have fewer stem cells in their womb lining compared with women in the control group.

'After an embryo has implanted, the lining of the uterus develops into a specialised structure called the decidua, and this process can be replicated when cells from the uterus are cultured in the lab,' said Jan Brosens, professor of obstetrics and gynecology at the University of Warwick, who led the study.

'Cultured cells from women who had had three or more consecutive miscarriages showed that ageing cells in the lining of the womb don't have the ability to prepare adequately for pregnancy,' he said.

Miscarriage affects between 15–25 percent of all pregnancies within the first trimester, and around one percent of women will have RPL. Although many risk factors of RPL are known, up until now the cause has not been well understood.

The lining of the womb relies on resident stem cell populations to renew themselves following each menstruation cycle, miscarriage and birth. The researchers believe that a lack of stem cells could speed up the ageing of the womb, triggering an inflammatory response that predisposes women to an increased risk of pregnancy failure. While an inflammatory response can facilitate embryo implantation, it can produce negative effects later in the embryo's development.

'We have discovered that the lining of the womb in the recurrent miscarriage patients we studied is already defective before pregnancy,' said Professor Brosens. The findings could be used to develop a treatment for RPL, and pilot interventions to improve stem cell populations in the womb are anticipated to start as early as spring 2016.

'I can envisage that we will be able to correct these defects before the patient tries to achieve another pregnancy. In fact, this may be the only way to really prevent miscarriages in these cases,' said Professor Brosens.

Siobhan Quenby, professor of obstetrics at the University of Warwick and co-author of the study, said: 'Our focus will be two-fold. First, we wish to improve the screening of women at risk of recurrent miscarriage by developing new endometrial tests.

'Second, there are a number of drugs and other interventions, such as endometrial "scratch" – a procedure used to help embryos implant more successfully – that have the potential to increase the stem cell populations in the womb lining.'

The findings were published in the journal Stem Cells.