The endocannabinoid, anandamide as a biomarker of outcome in pregnancies complicated by threatened miscariage

Bleeding in early pregnancy is the most common emergency in obstetrics and gynaecology world wide. Although a significant number of the women would have already lost their pregnancies at the time of presentation, about 15-20% of all pregnant women present with this complication and will have live babies at the time of presetation (threatened miscarriage). Unfortunately 5-10% of these will subsequently miscarry spontaneously. There is currently neither a means of identifying the (90-95%) of cases that will proceed to having a live birth nor interventions to offer those destined to miscarry that will reduce this risk. As a result between 140,000 -160,000 women in the UK every year attend either their General Practitioners or Accident and Emergency Departments or Gynaecological Units repeatedly with this complication for reassurance. For the first time we have identified a molecule, called anandamide produced in the body, the measurement of whose levels in women presenting with a threatened miscarriage has been shown by our group in a small pilot study to predict approximately 94% of those who subsequently had live births and 100% of those who subsequently miscarried spontaneously. The research proposed here is seeking to confirm these pivotal pilot observations in a large population. If confirmed, this will eventually lead to the development of a bedside test which will be used to significantly reduce anxiety and repeated attendance as emergencies by these women and more importantly, will pave the way for us to investigate ways of altering the levels of this molecule to reduce the chances of miscarriage in those destined to lose their pregnancies because of high levels of this molecule. In addition, this test will radically change care pathways in various Recurrent Miscarriage Clinics nationally and internationally.

Human reproduction is notoriously inefficient with only 50-60% of all conceptions progressing beyond 20 weeks. Of the pregnancies that are lost, 75% represent failure of implantation with most of this occurring before clinical confirmation of pregnancy. Approximately 15-20% of ultrasound scan confirmed pregnancies present with threatened miscarriage and 5-10% of these subsequently end in a spontaneous miscarriage. In the UK in 2003, this equated to 139,120 out of 695,600 pregnancies. Threatened miscarriage is the commonest reason for General Practitioner emergency gynaecological referred in the UK. Although a very common emergency, there is currently no reliable test to predict which of the pregnancies will subsequently spontaneously miscarry. Consequently, the women end up having repeated visits to GPs and emergency units for ultrasound scans. For those destined to miscarry, the course of this process cannot unfortunately be modified. The endocannabinoid system has been shown to be the key cytokine-hormone network involved in the regulation of gametogenesis, oviductal transport, embryo development, implantation and maintenance of early pregnancy. This research proposes to measure in a larger population anandamide levels (which we have previously shown to have a 100% negative predictive value for subsequent spontaneous miscarriage) and fatty acid amide hydrolase activity in women presenting with a threatened miscarriage as biomarkers for pregnancy outcome. If confirmed, the results will eventually lead to the development of a reliable biomarker test for miscarriages and consequently open up the potential to modulate this system in those destined to fail.