Miscarriage

A miscarriage is the loss of a baby before 24 weeks of gestation. It is a sad fact that one in four women will experience a miscarriage. Tommy’s is dedicated to changing this.

A miscarriage is the loss of a baby before 24 weeks of gestation. It is a sad fact that one in four women will experience a miscarriage and Tommy’s is dedicated to improving this.

Our Manchester centre is studying the role of the placenta in early pregnancy. We have found that a major cause of pregnancy problems such as miscarriage is when the blood vessels in the uterus fail to widen properly, restricting blood flow to the baby. We’ve identified that the placenta controls this process and we’re working to find treatments to improve blood vessel widening in pregnancies where it’s impaired. Another area of focus for our research is the process of nutrient and oxygen transfer from the mother to the baby via the placenta, as problems with this can lead to fetal growth restriction. Our London centre is participating in the large PROMISE clinical trial, which is testing whether treatment with progesterone can prevent pregnancy loss in women with recurrent miscarriage. The London centre is also involved in two trials investigating the effectiveness of a stitch in the cervix (‘cervical cerclage’) in women at risk of miscarriage.

Although there is still a long way to go, our research is already starting to make a real difference. At our centre in London, Tommy’s Professor Andy Shennan sees about 50 women every week who have had multiple pregnancy losses. However, using the research we’re conducting into the function of the placenta and uterus, 90% of those women go on to have a healthy baby.

Individual research projects into miscarriage

Progesterone for the treatment of recurrent miscarriage (the PROMISE trial)

Investigators: Dr Yacoub Khaliff, Annette Briley, Judith Hamilton, Paul Seed, R Rai (Imperial College London)

Funding: Tommy's funds Annette Briley

Summary: Miscarriage is the most common complication of pregnancy, affecting 1 in 6 clinically recognised pregnancies. The incidence of recurrent miscarriage is 1%, and is significantly higher than that expected by chance alone (0.4%). In contrast to women with sporadic miscarriage, those with recurrent miscarriage tend to lose genetically normal pregnancies. Even after comprehensive investigations, a cause for recurrent miscarriage is identified in less than 50% of couples. The PROMISE trial is a multicentre randomised controlled trial that will test whether treatment with progesterone can prevent pregnancy loss in women with recurrent miscarriage.

Progress report: All regulatory approvals for this trial are in place and eligible women are being recruited in 19 centres. To date 754 women have been recruited and 612 randomised (the target is 790 women).

Investigating the effectiveness of a cervical or abdominal stitch (the MAVRIC trial)

Investigators: Professor Andrew Shennan, Annette Briley, Jenny Carter, Paul Seed

Funding: Study taking place in a Tommy's funded centre

Timescale: 2007 onwards

Summary: A 'weak' cervix can gradually open as pregnancy progresses and the fetus is no longer held within the uterus, resulting in miscarriage or early delivery. One of the interventions for a weak cervix is the insertion of a 'stitch', known as a cervical cerclage, which can be inserted either via the abdomen or through the vagina. The vaginal route is preferred as it is less invasive and results in fewer complications. However, some women still miscarry or have early deliveries regardless of the presence of the vaginal stitch. We do not understand why this method works for some women and not for others. In women who have had a failed vaginal stitch, a reasonable option is to insert a stitch via the abdominal route for future pregnancies, or a vaginal stitch that is placed higher. This randomised clinical trial, known as the MAVRIC trial, will compare the outcome of women who have cervical stitches put in via the abdominal route versus the vaginal route.

Progress report: The aim is to recruit 129 women from four tertiary maternity units; so far, 106 women have been recruited and randomised to one of the treatment options.

Rescue cerclage vs bed rest in women with bulging membranes (the RESCUE trial)

Investigators: Professor Andrew Shennan, Dr Natasha Hezelgrave, Dr Rachel Tribe

Funding: Study taking place in a Tommy’s funded centre

Summary: During pregnancy, the cervix provides mechanical support to keep the fetus in the womb. When labour starts, the cervix gets shorter and opens to allow the baby to pass through, but in some women this starts too early in pregnancy and the membranes around the baby bulge through the cervix into the vagina. We do not know how to manage these women who are at risk of threatened miscarriage or preterm delivery. Some doctors advocate putting a stitch in the cervix while others only suggest bed rest as they worry that putting a stitch in could make things worse, or increase infection and cause developmental problems in infants. This study examines the best way of treating women who present at 16–26 weeks of pregnancy with 'bulging membranes'. We will randomly allocate women with bulging membranes to receive a stitch or to bed rest (either as an inpatient or outpatient). We will assess whether putting a stitch in makes a difference to survival of the baby, the length of pregnancy or short- or long-term complications for the mother and baby. We will also investigate whether the presence of certain infection markers in the cervix affects outcome.

Developing a treatment to enhance placental cell survival

Investigators: Dr Ian Crocker, Dr Melissa Westwood, Professor John Aplin, Professor Colin Sibley

Funding: Study taking place in a Tommy's-funded centre

Timescale: 2006-2013

Summary: Abnormal placental function and excessive placental cell death may lead to pre-eclampsia, fetal growth restriction and miscarriage. Treatments that improve the efficiency or survival of placental cells may prolong pregnancy and improve the outcomes for both mother and baby. This project investigates a substance called insulin-like growth factor (IGF-2) that has been shown to enhance growth and survival of placental cells.

Progress report: We are currently developing a treatment that will increase the amount of IGF-2 available to the placenta, thus improving its function by promoting cell survival and cell growth.