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New trial could benefit half of women with recurrent miscarriage


A major new clinical trial jointly funded by the NIHR and MRC will investigate whether a course of antibiotics prior to conceiving could reduce the likelihood of miscarriage in up to 50% of cases.

Researchers at the University of Warwick Clinical Trials Unit are leading the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, which aims to discover whether using the antibiotic doxycycline in women with the condition endometritis can improve their chances of having a baby and treat recurrent miscarriage by improving the balance of bacteria present in their reproductive system.

The trial has received £1.9 million funding from the Efficacy and Mechanism Evaluation (EME)
Programme – an NIHR and MRC partnership - and will involve over 3,000 women in NHS hospitals in the United Kingdom who have recurrent miscarriage. It is launched today (12 September) at the British Science Festival, this year held in partnership with the University of Warwick.

In some women the lining of the womb (the endometrium) is inflamed, a condition called endometritis, and researchers have found a link between this and miscarriage. Some women will experience symptoms such as bleeding and pain, and it is commonly treated using an antibiotic called doxycycline. However, some women exhibit no obvious symptoms from endometritis and there is currently no standard screening test for the condition for those who have experienced miscarriage.

Not everyone who has recurrent miscarriage has endometritis so, using a test for endometritis optimised by scientists at Warwick Medical School, the researchers will first identify women with the condition. To find out if doxycycline can reduce miscarriage and increase the number births in women who have experienced two or more early miscarriages, the researchers will carry out a double blind randomised controlled trial, by comparing a 14-day course of doxycycline against a placebo. Women will be advised to start trying to conceive once they have finished the course.

Doxycycline is a common antibiotic prescribed for a number of bacterial infections. Treatment for recurrent miscarriage using doxycycline is currently available in some European countries and the USA, but this will be the first time that the womb lining test and treatment will be thoroughly tested in a clinical trial.

Warwick Medical School’s Professor Siobhan Quenby, Principal Investigator on the trial, said: “This is potentially a new treatment for up to half of people with recurrent miscarriage. We know that doxycycline is given to some women experiencing miscarriage in other countries, but there has never been a proper trial conducted. And instead of just having your blood tested to look for causes of miscarriage, as is current practice, you will have the lining of the womb tested too so that we can identify those who will benefit from this treatment.

“Our aim is to try to improve the womb before you get pregnant. Most miscarriages occur within the first trimester (12 weeks) of pregnancy and our aim is to see a reduction in these early miscarriages.”

Researchers suspect that endometritis may be caused by an imbalance of the bacteria (microbiome) that live in the reproductive tract (the vagina, cervix, womb, fallopian tubes and ovaries). A healthy endometrium is important for the embryo to be able to attach to the womb and it is thought that endometritis disrupts this process, and can lead to a miscarriage. Treating endometritis with antibiotics may reduce endometritis by reducing disruptive bacteria and allowing the healthy bacteria to grow.