Late abortion has been defined as pregnancy termination at a gestationed age of more than 14 weeks till the periodof viability is achieved. In India, it is legal to terminate pregnancy up to 20 weeks. In some countries, the upper limit is up to 24 weeks. Before the availability of prostaglandin (PG) analogues, dilatation and evacuation, oxytocin infusion and amnioinfusion of hypertonic saline or urea were the common methods used for termination of pregnancy in the second trimester. The introduction of PG analogues and mifepristone has changed the management of second trimester abortions in the last 2 decades; PG analogues are associated with less side-effects when compared with oxytocin infusion and hypertonic saline or urea. The application of PG analogues for medical abortion is simple and does not require trained expertise.

PGs and their analogues stimulate uterine contractions, cause cervical ripening and dilatation and are effective for termination of pregnancy in the first and second trimester as PG receptors are present throughout in all stages of pregnancy. Naturallyoccurring PGs are rapidly inactivated to PG metabolites with reduced biological activity and are associated with high incidence of gastrointestinal side-effects. Extra or intra-amniotic instillation into the uterus is inconvenient and associated with infection.

On the contrary, PG analogues are relatively resistant to metabolism and, hence, have prolonged action. PGE analogues have more selective action on the myometrium and cause fewer gastro-intestinal sideeffects than natural PG which are rapidly inactivated and are effective only on intra or extra-amnioticinstillation. PG analogues are more resistant to metabolism and have more selective and prolonged action. Three PG analogues commonly used are sulprostone, gemeprost and misoprostol. Sulprostone has been banned due to occurrence of myocardial infarction. Gemeprost is used as a vaginal pessary with a complete abortion rate of 88-96.5%. Cost and need for refrigeration are the main drawbacks with the use of this drug. Misoprostol 400µg every 3 hours for 5 doses (91% success rate) has been shown to be more effective than gemeprost 1 mg every 3 hours for 5 doses (71% success rate) (Wong et al, 1998). Vaginal misoprostol is the PG of choice, given its efficacy, low cost and stability at room temperature. Plasma concentration of misoprostol acid following different routes of administration is shown in Fig.2.3.1

Progesterone maintains the uterus in a quiescent state. The progesterone antagonists bind to the progesterone receptors and prevent endogenous progesterone from exerting its effect. The use of antiprogestin increases the sensitivity of the uterus to PGs.

The use of oral mifepristone 36-48 hours before PGs can increase the abortion rate, shorten the induction to abortion interval and reduce the dose ofPGs required. The recommended dose of mifepristone is 600 mg, but many randomized trials have shown that 200mg is as effective. The complete abortion rate was increased from 72% to 95% in 24 hours when mifepristone pre-treatment was used before gemeprost (1mg every 6 hours). The induction to abortion interval was shortened from 15.7 to 6.6 hours (Thong et al, 1992). The dosage of gemeprost can be further reduced to 0.5mg every 6 hours without jeopardizing its efficacy (Thong et al, 1996).

The abortion rate was 90% in 24 hours when mifepristone pre-treatment was used before vaginal misoprostol (400µg every 3 hours). The median induction to abortion interval was shortened from 15 hours to 8.7 hours (Ho et al, 1996). The dosage of vaginal misoprostol can be further decreased to 200µg (Ngai et al, 2000). The efficacy can be maintained even with oral misoprostol but the dosage should not fall below 400µg (Ho et al, 1997).

A regimen using a combination of vaginal (600- 800µg as first dose) and oral misoprostol (400 µg every 3 hours for 4 doses) gave the highest complete abortionrate (97%) and the shortest induction to abortion interval (6.5 hours) (El-Rafaey et al, 1995 and Ashok et al, 1999).

Laminaria tents (Dilapan and Lamicel) are intracervical tents that can be used for cervical priming before prostaglandin administration. The use of laminaria tents 12 hours before sulprostone injection can reduce the induction to abortion interval (Ho et al, 1995). Laminaria tent is less effective then mifepristone as pre-treatment.

The recommended regimens for mid-trimester abortion are:

1. With mifepristone 36-48 hours before PG:
Gemeprost 0.5-1mg every 6 hours for 4 doses or vaginal misoprostol 600-800µg then oral misoprostol 400µg every 3 hours for 4 doses.

2. Without mifepristone before PG:
Gemeprost 1mg every 3 hours for 5 doses or vaginal misoprostol 400µg every 3 hours for 5 doses and repeat doses if abortion does not occur in 24 hours.