Abstract: Human pregnancy is unusual as it involves genetically diverse embryos, cyclical breakdown and regeneration of the uterine mucosa (endometrium), and close integration of fetal and maternal cells at the uteroplacental interface. Not surprisingly, pregnancy often falters in early gestation. This presentation describes the discovery of an implantation checkpoint designed to limit prolonged maternal investment in a failing pregnancy or low-fitness conceptus. Mechanistic studies, including culturing of human blastocysts in endometrial organoids/assembloids, demonstrate that implantation checkpoint failure presents the embryo with an endometrium that is easy to invade but also vulnerable to breakdown in early pregnancy. Further, in contrast to the current clinical paradigm, implantation checkpoint failure provides a much more robust explanation for the epidemiological characteristics of recurrent miscarriage. It also points towards a novel strategy for miscarriage prevention, first evaluated in a randomised placebo-controlled feasibility trial at UHCW.

Biography: Jan Brosens graduated from the KU Leuven, Belgium, in 1990 and pursued postgraduate training in Obstetrics and Gynaecology in the United Kingdom. He became a Member of the Royal College of Obstetricians and Gynaecologists in 1995 and a Fellow of the College in 2008. He obtained a Ph.D. from the University of London in 1999. He was awarded a Wellcome Trust Clinical Scientist Fellowship in 1998. He joined Imperial College London, first as Chair of Reproductive Sciences (2004) and then as Chair of Reproductive Medicine (2008). In May 2011, he was appointed as Chair of Obstetrics and Gynaecology at the University of Warwick and Head of the Division of Reproductive Health. Currently, Jan Brosens is a Wellcome Trust Investigator, co-director of the Centre of Early Life at the University of Warwick, and scientific director of Tommy’s National Miscarriage Research Centre, a partnership between Imperial College London, University of Birmingham, University of Warwick and their affiliated national health service trusts.