Miscarriage

Description

Following a miscarriage, surgical intervention is needed in some cases to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. The AIMS (Antibiotics in Miscarriage Surgery) trial was a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low- and middle- income countries (LMICs).​

Methods​

Women were randomly assigned to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics.​

The trial included 3412 participants in Malawi, Pakistan, Tanzania, and Uganda. Women were assigned to receive either antibiotic prophylaxis (1705 [50%] of 3412) or placebo (1707 [50%] of 3412). 158 (5%) of 3412 women developed pelvic infection within 2 weeks of surgery, of whom 68 (43%) were in the antibiotic prophylaxis group and 90 (57%) in the placebo group.​

Findings

A cost-effectiveness analysis found that there is 97-98% probability that antibiotic prophylaxis is a cost-effective intervention at expected thresholds of willingness-to-pay per additional pelvic infection avoided. In terms of post-surgery antibiotics, the antibiotic prophylaxis group was US$0·27 (95% CI -0·49 to -0·05) less expensive per woman than the placebo group.​

Conclusions

Therefore, the AIMS trial demonstrated that antibiotic prophylaxis is more effective and less expensive than no antibiotic prophylaxis for surgical management of miscarriage in a LMIC setting.​

Description​

A randomised placebo-controlled trial of mifepristone and misoprostol versus misoprostol alone in the medical management of missed miscarriage​

Aims​

"To investigate the clinical and cost-effectiveness of MifeMiso combination (mifepristone and misoprostol) versus misoprostol alone in the management of missed miscarriage. Primary clinical objective: To test the hypothesis that treatment with mifepristone plus misoprostol is superior to misoprostol alone for the resolution of miscarriage within 7 days in women diagnosed with missed miscarriage by pelvic ultrasound scan in the first 13+6 weeks of pregnancy. Key secondary objective: To test the hypothesis that the addition of mifepristone reduces the need for surgical intervention to resolve the miscarriage."

Description​

The pivotal physiological role of progesterone in the maintenance of a pregnancy is well known. However, whether progesterone deficiency could be a reason for miscarriage in some women, and whether treatment with progesterone hormone could reduce the risk of miscarriage was not known and has been a subject of debate for over 70 years. The Tommy’s Centre conducted two large clinical trials, one called the PROMISE Trial (NEJM, 2015) and the other called the PRISM Trial (NEJM 2019) – the largest randomised trial ever conducted in early pregnancy - to settle this question once and for all.​

The PRISM trial looked at progesterone in spontaneous miscarriage and involved 4153 women across the UK.​

Aims​

To test the hypothesis that in women presenting with vaginal bleeding in the first trimester, progesterone (400 mg vaginal capsules, twice daily), started as soon as possible after a scan has demonstrated a visible intrauterine gestation sac, and continued to 16 completed weeks of gestation, compared with placebo, increases maternities with live births beyond 34 completed weeks by at least 5%.

Miscarriage, defined as the loss of pregnancy before the fetus reaches viability, is the most common complication of pregnancy. As many as 15-25% of pregnancies end in miscarriage, and 25-50% of women experience at least one sporadic miscarriage in their reproductive life. Most miscarriages are sporadic and occur before 12 weeks of gestation. Miscarriages cause both physiological and psychological morbidity. 

Sometimes the uterus empties itself completely without any clinical intervention, but often some or all of the tissue of the ended pregnancy remains in situ, creating vulnerability to complications and necessitating clinical management. Clinical management may take the form of traditional curettage, vacuum aspiration, or medication. Surgery is particularly likely to necessitate inpatient admission, with associated costs to healthcare services. 

View the journal article

Miscarriage is common, affecting one in ten women in their lifetime, with an estimated 23 million miscarriages globally. Despite this, the impact and consequences of miscarriage are underestimated, resulting in an attitude of acceptance of miscarriage and system of care which is currently fragmented and can be of poor quality. This series of 3 papers published in The Lancet reviews this evidence on miscarriage and challenges many misconceptions.

Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage).

Professor Ioannis Gallos, DMS, MD, MRCOG

Professor of Obstetrics and Gynaecology
Co-Director of WHO Collaborating Centre for Global Women's Health
i.d.gallos@bham.ac.uk
@IoannisGallos

Administrative staff 

Rajinder Kaur

Centre Manager for the Tommy's National Centre for Miscarriage Research
Department of Metabolism and Systems Science

Marcelina Podesek

Administrator for the Tommy's National Centre for Miscarriage Research
Department of Metabolism and Systems Science

Chloe Trainor

PA to Professor Coomarasamy

Academic staff

Dr Justin Chu

Sub-Specialist Trainee in Reproductive Medicine, Honorary Academic Clinical Lecturer
Department of Metabolism and Systems Science

Justin is a senior registrar at the Birmingham Women's Hospital. He is one of the senior doctors working at the Tommy's Recurrent Miscarriage clinic. Justin has research and clinical interests in both miscarriage and infertility treatments such as IVF and pregnancy implantation.

Dr Rima Dhillon-Smith

Clinical Lead for the Tommy's National Centre for Miscarriage Research in Birmingham
Department of Metabolism and Systems Science
Clinical Lecturer

Dr Rima Dhillon-Smith is a clinical lecturer based at the Birmingham Women’s Hospital. She combines her academic work with clinical duties as a registrar in Obstetrics and Gynaecology.  Rima’s main research interests lie in reproductive endocrinology, subfertility, paediatric gynaecology and early pregnancy. She is the clinical lead of the Birmingham Tommy’s National Centre for Miscarriage team.

Dr Jennifer Tamblyn

Department of Metabolism and Systems Science
Honorary Clinical lecturer

Dr Jennifer Tamblyn is a clinical lecturer based at the Birmingham Women’s Hospital. She combines her academic work with clinical duties as a registrar in Obstetrics and Gynaecology. Jennifer's main research interests lie in reproductive immunology, disorders of implantation and early pregnancy. 

Clinical staff

Oonagh Pickering

Lead Research Nurse for the Tommy's National Centre for Miscarriage Research
Department of Metabolism and Systems Science

Oonagh leads the nursing team at the Birmingham Women’s Hospital. As well as providing clinical care to patients through the recurrent miscarriage service, Oonagh also leads the recruitment and follow-up of participants in our portfolio of studies.

Rachael Boothe

Research Assistant for the Tommy's National Centre for Miscarriage Research
Department of Metabolism and Systems Science

Post-Doctoral Research Fellow

Dr Amie Wilson, PhD, BSc (Hons), RM

Research Fellow Global Maternal Health
Department of Applied Health Sciences
WHO Collaborating Centre for Global Women's Health
a.wilson.5@bham.ac.uk 
@amiewil

PhD students

Preth De Silva

Clinical Research Fellow

I am currently undertaking a PhD investigating the optimal way of delivering hysteroscopy (the insertion of a telescope into the womb for diagnosis and treatment of certain womb-lining related conditions) in the outpatient setting. Part of my research involves setting up a randomised controlled trial exploring the role of hysteroscopy in treating "retained products of conception", or RPOC for short, where pregnancy tissue remains inside the womb following a miscarriage. We hope to explore the impact of this novel treatment on bleeding pattern, pain, infection rates and fertility.

Pedro Melo, MD, MSc, MRCOG

PhD student

Pedro specialises in Obstetrics & Gynaecology and is currently undertaking a PhD in Reproductive Medicine under the supervision of Professor Coomarasamy. Pedro’s research focuses on the role of progesterone in optimising treatment success and preventing miscarriage in women undergoing assisted conception. Pedro is the national coordinator of the ProFET study – “Serum progesterone in women undergoing frozen embryo transfer: a prospective, multicentre cohort study.”

Dr Yealin Chung BSc MBBS MRCOG

PhD student

Yealin is a specialist trainee in Obstetrics & Gynaecology with research interest in reproductive medicine and early pregnancy. She is currently undertaking a PhD focusing on optimisation of the luteal phase to improve reproductive outcomes in women with history of infertility, subfertility and/or recurrent miscarriage.