Diabetes drug could treat recurrent miscarriage

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A drug designed to treat diabetes could treat recurrent miscarriage, the results of a pilot clinical trial suggest.

The drug increases the amount of stem cells in the lining of the uterus, improving conditions to support pregnancy.

Recurrent miscarriage refers to the loss of two or more consecutive pregnancies. The likelihood of a successful pregnancy goes down with additional miscarriage.

Previous research from Warwick Medical School reported that a lack of stem cells in the uterine lining causes thousands of women to suffer from recurrent miscarriages. The team also demonstrated that stem cells protect specialized cells, called decidual cells, from excessive stress and inflammation. Decidual cells surround the implanting embryo and excessive stress can cause breakdown of the uterine lining in pregnancy.

A new class of diabetes drugs called gliptins targets an enzyme involved in the recruitment of circulating stem cells to the uterus. For the new study in the journal EBioMedicine, researchers investigated whether inhibiting this enzyme, called DPP4, using a particular drug, sitagliptin, would improve conditions in the uterus for pregnancy.

Stem cells before and after

In a pilot clinical trial, 38 women aged 18 to 42 who had experienced a large number of recurrent miscarriages (average 5) were given either an oral course of sitagliptin or a placebo for three menstrual cycles. Biopsies of the womb were taken at the start of the course of treatment and afterwards to determine the number of stem cells present before and after the course.

They found an average increase in stem cell count of 68% in those women who took the full course of sitagliptin. This compares to no significant increase in those in the control group receiving an identical placebo pill. They also saw a 50% decrease in the number of “stressed” cells present in the lining of the womb. There were minimal side effects for the participants.

The researchers now hope to take the treatment to clinical trial and, if successful, it would be the first targeted specifically at the lining of the womb to prevent miscarriage.

“There are currently very few effective treatments for miscarriage and this is the first that aims at normalizing the womb before pregnancy,” says professor Jan Brosens of Warwick Medical School and consultant in Reproductive Health at University Hospitals Coventry and Warwickshire NHS Trust.

“Although miscarriages can be caused by genetic errors in the embryo, an abnormal womb lining causes the loss of chromosomal normal pregnancies. We hope that this new treatment will prevent such losses and reduce both the physical and psychological burden of recurrent miscarriage.”

Very early results

“We have improved the environment that an embryo develops in and in doing so we hope to improve the chances of a successful pregnancy,” says professor Siobhan Quenby from Warwick Clinical Trials Unit and an honorary consultant at University Hospital Coventry and Warwickshire NHS Trust.

“Although this research was specifically designed to test whether we could increase the presence of stem cells in the womb, follow-up of participants found that there were no further losses of normal pregnancies in those who took sitagliptin. These are very early results and the treatment now needs to be further tested in a large-scale clinical trial.”

Stem cells play a key role in creating the decidual cells in the womb lining which support the placenta throughout pregnancy. Insufficient stem cells in the womb lining leads to an excess of stressed and inflammatory decidual cells, which in turn may cause placental bleeding and miscarriage. Sitagliptin was effective not only in increasing stem cells in the womb lining but also decreasing the abundance of stressed decidual cells.

Tommy’s National Miscarriage Research Centre supported the work.

Source: University of Warwick