Our research

A number of important adaptations of the maternal immune system occur during pregnancy and recurrent miscarriage has been associated with disruptions to these mechanisms.

In particular, recurrent miscarriage has been associated in human studies with an increased Th1/Th2 ratio, reduced T regulatory cells, increased Th17 cells, and increased peripheral natural killer cells. These findings, coupled with extensive evidence of their importance in animal models of pregnancy loss, have led to suggestions that in some women immunological factors may be the cause of miscarriage.

To date the studies have been exploratory, limited by small sample sizes, single centre recruitment, and heterogeneity of the assays utilised. Such deficiencies in the existing evidence mean that national guidelines do not currently support detailed immunological testing. However, patient and clinician demand has led to a rapid expansion in testing outside NHS settings, without a robust evidence base to aid interpretations of the findings.

Therefore we are conducting research to elucidate the role of immune testing in patients with recurrent miscarriages, and identify potential targets for immune therapy. Our investigations will enable us to ensure that couples seeking help with recurrent miscarriage are given correct advice regarding the significance or not of immunological tests and the implications of the results for their future prognosis.

Project team 

• Project lead: Professor Alex Richter
• Professor Mark Drayson
• Dr Hoda Harb
• Professor Arri Coomarasamy

A missed miscarriage, also known as a missed abortion or a silent miscarriage, occurs when the baby dies, but the body does not recognise this and so the pregnancy sac (where the baby grows) stays inside the body. Women who have had a missed miscarriage often opt for medical management up to 13+6 weeks of pregnancy.

NICE currently recommends that a drug called misoprostol (a vaginal pessary (medication inserted into the vagina) or tablet that makes the womb contract) should be used in the medical treatment of miscarriage. However, there is evidence to suggest that combining this drug with mifepristone (an oral tablet that reduces pregnancy hormones) may be more effective in treating miscarriage. The aim of the MifeMiso trial is to find out whether treating women with mifepristone followed by misoprostol, is more effective than misoprostol alone at resolving missed miscarriage.

Project team

• Project lead: Dr Justin Chu
• Dr Adam Devall
• Professor Tracy Roberts
• Dr Laura Jones
• Professor Arri Coomarasamy

Contact details: mifemiso@trials.bham.ac.uk

Sometimes it is necessary for doctors to suggest surgical treatment for miscarriage. Unfortunately, this can be associated with various problems such as causing a hole in the womb, infection, scarring and bleeding. This can cause problems with periods and decrease the chances of getting pregnant in the future. One of the ways that may improve gynaecological services is to increase the number of procedures performed under direct vision using hysteroscopy (a camera test which looks inside the womb), with the aim of improving treatment success rates and reducing complications.

The aim of the SEE U trial is to assess whether viewing the inside of the womb, with an ultrasound scan, during the surgical management of miscarriage can help with the success of the procedure. The trial is also looking to see if performing the procedure in this way can reduce complications such as infection, bleeding and scarring. To answer this question a multi-centre randomised controlled study with an associated health economic evaluation is required. To ensure the feasibility of a large expensive trial it is essential to perform a pilot study. This pilot study will assess various aspects of the trial design and management and provide preliminary data that can be used to plan a substantive trial.

Project team

• Project lead: Dr Paul Smith
• Dr Adam Devall
• Professor Arri Coomarasamy

Contact details: seeu@trials.bham.ac.uk

Until now, miscarriage has generally been considered an exclusively female problem, with investigations and management targeting only women.

Yet the role of sperm DNA damage in miscarriage is not surprising. This is because while most cell types are able to repair damaged DNA, sperm lose this ability during development and have to rely on repair mechanisms in the egg. As the level of damage in the sperm DNA increases it also becomes increasingly likely that any repairs by the egg may create genetic mutations that could increase the risk of miscarriage.

Most existing tests for sperm DNA damage are insufficiently sensitive to be clinically useful; we are developing a more accurate combined assay system and therapies to achieve repair. One potential cause of sperm DNA damage is exposure to Reactive Oxygen Species (ROS) during production and transit. We are investigating the possibilities for changes in antioxidant balance to reduce the risk of miscarriage.

We are about to commence the pAToMiUM pilot trial to test the effects of a combined vitamin and mineral supplement in 30 men with poor sperm DNA quality in a recurrent miscarriage population. We have worked with one of Europe’s leading producers of nutritional supplements to design the supplement formulation according to the latest evidence.

Project team

• Project lead: Professor Jackson Kirkman-Brown
• Dr Sarah Conner
• Dr Justin Chu
• Dr Adam Devall
• Professor Arri Coomarasamy

Contact details: patomium@trials.bham.ac.uk

We aim to better understand the psychosocial effects of miscarriages, and to harness this understanding to enable early pregnancy doctors, midwives and nurses to improve miscarriage care and support.

In November 2017 the European Society of Human Reproduction and Embryology particularly observed that there is a need for studies of the emotional impact of recurrent pregnancy loss on men. Therefore we would like to talk to men who have recently lived through two or more pregnancies that both ended spontaneously before 16 completed weeks of gestation. We hope to learn from their stories and understand whether and how men who experience multiple miscarriages could be better supported. The results of our research will inform the ongoing efforts of clinical teams and charities to help any individuals and families who find themselves affected by multiple miscarriages.

If you are a man aged 18 years or over who has lived through two or more clinically confirmed pregnancies that both ended in miscarriage before 16 completed weeks of gestation, with the most recent loss no more than 12 months ago, then you could be eligible to contribute to our study. 

We are looking for individuals without any infertility diagnosis, able to hold a conversation in English and willing to participate in audio-recorded telephone interview.

If you believe you could be eligible then we would like to hear from you. Thank you.

The PROMISE trial published in NEJM in 2015 represented a paradigm shift in miscarriage trials in the UK.

Before this trial, miscarriage research was generally conducted by a few specialists in single centre studies. The trials were small and took many years to complete, and often there were questions about the generalisability of the findings. As the first ever miscarriage prevention trial to recruit more than 800 participants, PROMISE created a network of hospitals around the country that is committed and able to carry out miscarriage research.

The network is currently demonstrating its value and tenacity in other trials of thousands of couples experiencing pregnancy loss. It is supported by a broad group of stakeholders, including members of the Association of Early Pregnancy Units, the Early Pregnancy Clinical Studies Group, BCTU (the largest women’s health clinical trials unit nationwide) and various other key academic and clinical institutions across the UK.

We are working together to become a national platform to better identify miscarriage prevention and management strategies, and facilitate the development of our next generation of clinical trial researchers.

Project team

• Project lead: Dr Rima Dhillon-Smith
• Dr Justin Chu
• Dr Adam Devall
• Professor Arri Coomarasamy

We still don’t know enough about why some women experience multiple miscarriages. In addition, different hospitals have different standards of care for women who have had a miscarriage. For example, many couples will only be investigated after they have had three miscarriages. This system causes unimaginable, and unnecessary, pain for the women affected. Tommy’s Net is a database that will help us to collect and store information from hospitals and clinics, as well as access current medical records. This will allow the team to develop new methods to tell which women are at most risk of having a miscarriage.

We are also able to use this cohort of patients to test new treatments using a cohort multiple Randomised Controlled Trial (cmRCT) design. This is a relatively new trial design that simplifies the recruitment and conduct of trials compared with current RCTs. In this trial design, participants are asked to agree to participate in the control arm of any future trials that will be conducted by the research team.

Once a substantial cohort of participants has been established that have given their consent to participate in the cmRCT, one is able to conduct a trial by identifying and selecting a random sample of participants who will receive the intervention, and another group that will continue to receive standard care. Those patients that are allocated to the intervention will be invited to give their written, informed consent to participate in the intervention arm. However, those allocated to standard care (control arm), can continue to be followed up in the usual way with no additional contact required.

Relevant outcomes and other measures are taken on all patients in both arms as part of the regular follow-up process. A large benefit of this trial design is that the same cohort can be used for multiple interventions, so are large number of clinical trials can be conducted within the same core cohort of patients. 

Project team

• Project lead: Dr Rima Dhillon-Smith
• Dr Adam Devall
• Professor Arri Coomarasamy

Contact details: bwh-tr.tommysclinic@nhs.net