Melatonin to improve induction of labour: a double blind, randomised, placebo controlled trial.

Induction of labour is a common obstetric intervention that 1 in 4 women will experience. The ultimate goal of induction of labour is to achieve a vaginal birth, however in almost 40% of first time mothers it fails. The outcome of a failed induction, a caesarean delivery is associated with vast range of adverse effects, both short and long term for the mother and her baby. In this application we propose that a simple and inexpensive intervention will increase the success of induction of labour. Lessons from successful spontaneous births tell us that labour occurs more frequently, and is shorter with less intervention when it occurs at night. The driver of this is thought to be the endogenous hormone, melatonin. Melatonin is synthesised by the placenta. Healthy pregnant women have higher concentrations of melatonin compared to non-pregnant women. Melatonin levels also increase with gestation, peaking during labour and then falling rapidly after delivery. The biological reason for an altered melatonin cycle in pregnancy is unclear. However, the myometrium of the pregnant uterus expresses melatonin receptors and these receptors have been shown to be up-regulated in labouring compared to non-labouring women. Intriguingly, both melatonin and oxytocin activate the same signalling pathway that results in uterine contractions. Specifically, melatonin treatment of myometrium increases it’s sensitivity, enhances oxytocin-induced contractions and improves myometrium cell communication and synchronization. Taken together this suggests an important role of melatonin in the onset and progress of labour. We therefore hypothesise that supplementing women undergoing induction of labour with melatonin will improve the success rate of induction of labour. We will undertake a double-blinded randomised controlled trial of melatonin supplementation to improve the success of induction of labour in healthy first time mothers.