Miscarriage syndrome: Linking early pregnancy loss to obstetric and age-related disorders
Pietro Bortoletto,
Emma S. Lucas,
Pedro Melo,
Ioannis D. Gallos,
Adam J. Devall,
Tom Bourne,
Siobhan Quenby,
Phillip R. Bennett,
Arri Coomarasamy,
Jan J. Brosens
Affiliations
Pietro Bortoletto
Boston IVF-The Eugin Group, Waltham, Massachusetts, USA; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusett, USA
Emma S. Lucas
Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Pedro Melo
Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Ioannis D. Gallos
Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Adam J. Devall
Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Tom Bourne
Tommy's National Centre for Miscarriage Research, Institute for Reproductive and Developmental Biology, Imperial College London, London, UK
Siobhan Quenby
Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Phillip R. Bennett
Tommy's National Centre for Miscarriage Research, Institute for Reproductive and Developmental Biology, Imperial College London, London, UK
Arri Coomarasamy
Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Corresponding author at: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Jan J. Brosens
Tommy's National Centre for Miscarriage Research, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
Summary: Upon embryo implantation, the uterine mucosa - the endometrium - transforms into a robust decidual matrix that accommodates the fetal placenta throughout pregnancy. This transition is driven by the differentiation of endometrial fibroblasts into specialised decidual cells. A synchronised influx of circulating natural killer (NK) cells and bone marrow-derived mesenchymal stem/progenitor cells (BM-MSC) is pivotal for decidual homeostasis and expansion in early pregnancy. We hypothesise that pathological signals interfering with the recruitment or activity of extrauterine cells at the maternal-fetal interface link miscarriage to subsequent adverse pregnancy outcomes, including further pregnancy losses and preterm labour. NK cells and BM-MSC are key homeostatic regulators in multiple tissues, pointing towards a shared aetiology between recurrent miscarriage and age-related disorders, including cardiometabolic disease. We propose the term ‘miscarriage syndrome’ to capture the health risks associated with miscarriage and discuss how this paradigm can inform clinical practice and accelerate the development of preventative strategies.
