Progestogens in preterm labour

Pre-term birth (PTB) is a major health challenge to-day. Perinatal mortality is increased more than three times and PTB is the leading cause of short and long-term neonatal/infant morbidity. Many are the risk factors, previous PTB, cervical effacement or dilatation on clinical vaginal examination or shortening of the length of the cervical canal on ultrasound are major predisposing factors. A growing body of evidence suggests that progesterone plays a role in preventing PTB. Progesterone decreases prostaglandin synthesis, reduces cervical stromal degradation, alters the barrier to inflammation and ascending infection in the cervix, reduces gap junction formation, decreases the conduction and frequency of myometrial contractions, increases the stimulation threshold of the myometrium and decreases spontaneous myometrial activity. Progesterone, and other progestogens, have been tested in clinical trials for the prevention of PTB. The three main groups of patients evaluated included: patients with a previous preterm birth, patients with a short cervix at mid gestation and patients with twin pregnancy. Micronized progesterone given by the vaginal route has been found to reduce the incidence of PTB in the first two indications by approximately 50 %, while 17 OH progesterone caproate is effective only on patients with previous PTB. In twin pregnancy neither compound seems to significantly prolong pregnancy although a beneficial effect has been demonstrated on neonatal composite morbidity using vaginal micronized progesterone. Universal cervical length screening and vaginal progesterone treatment (90 mg vaginal gel or 200 mg micronized soft gel suppositories) is also a cost-effective model for the prevention of PTB. The administration of high-dosage micronized progesterone has been advocated as a possible tocolytic agent. However, the slow action requires additional tocolytic agents such as β-agonists, prostaglandin synthesis inhibitors or calcium channel blockers in the case of acute tocolysis. Finally micronised progesterone can be used for the maintenance of uterine quiescence in patients previously treated for an episode of threatened preterm labour.