Intrauterine administration of drugs for termination of pregnancy in the second trimester

Medical methods have been used for many years to terminate mid-trimester pregnancy, ranging from irritant chemicals and traditional plants to ecbolic agents and solutions instilled locally into the uterus. These methods had serious limitations, with relatively high rates of maternal mortality and morbidity. Surgical evacuation requires special skills not available to all practitioners and many doctors consider second trimester dilatation and evacuation as a surgical taboo. In recent years several approaches evolved and reached the clinics, presenting safer and more effective options. Intra-amniotic instillation of hypertonic solutions, particularly saline or urea, proved in many hands to be a good method for pregnancies beyond 15 weeks of gestation. Due to a long latency period after instillation, these agents are often supplemented by an intravenous oxytocin infusion. Extraovular hypertonic saline or ethacridine (Rivanol) have their advocates, particularly in the grey-zone of pregnancy range from 13-15 weeks. In the last two decades, intrauterine prostaglandins were added to the methods in current use. Extra-amniotic prostaglandins (E2, F2 alpha or 15-methyl F2 alpha) were originally given in repeated doses or as a continuous local drip, but later a single instillation was used, usually mixing the drug with a viscous solution or gel. Intra-amniotic prostaglandins, in much higher doses, particularly the 15-methyl analogue, proved highly effective and relatively safe, especially when combined with laminaria tent insertion in the cervix. Various combinations of methods have provided a wide spectrum of data which is difficult to evaluate at present. Studies comparing different methods were mainly attempted in the mid-seventies. The outcome raised many pertinent questions and left many major issues unresolved. Most of the comparisons were not randomized or well-controlled and only referred to the natural prostaglandin compounds. The analogues, however, seem to offer several advantages and the role of additional methods such as laminaria or antiprogestins remains to be further evaluated.