Improving medical abortion : Using mifepristone in combination with a prostaglandin analogue

Abstract: Background: Induced abortion is still a major health problem in the world and the most frequently performed intervention in Obstetrics and Gynaecology with an estimated total of 46 millions worldwide each year. Medical abortion with mifepristone and prostaglandin was first introduced in 1988, and is now approved in 29 countries. It has recently been included in the List of Essential Medicines by WHO. However, the regimen has undergone only minor changes since the introduction. The overall aim of the thesis was to evaluate possible improvements in medical abortion using mifepristone in combination with the prostaglandin E1 analogue misoprostol. Different aspects of the treatment were studied including criteria for evaluation of complete abortion, acceptability, pain management and a new form of slow release misoprostol. Study I + II: Healthy women with an unwanted pregnancy who had chosen medical abortion were recruited. The use of ultrasound and hCG for the interpretation of the follow-up examination (n=217) was evaluated in the first study and acceptance of home use of misoprostol (n=100) in the second. hCG proved to be a more reliable indicator for assessment of outcome when compared to ultrasound, especially in very early pregnancy. Women gave a high priority to the free choice of the place of intake of misoprostol. Almost all women who had chosen home use of misoprostol were satisfied or very satisfied with their choice. Study III: Women undergoing medical abortion in second trimester (n=74) were randomized to receive a prophylactic pain treatment together with misoprostol either including a NonSteroidal Anti-Inflammatory Drug (NSAID) or without NSAID. There was no significant difference between the two groups in the induction-to-abortion interval or the total doses of misoprostol needed. The frequency of surgical intervention was similar. Women in the group treated with NSAID required significantly less opiates. Study IV + V: A new slow-release form of misoprostol was compared with conventional oral misoprostol in women undergoing surgical abortion. Pharmacokinetics (n=31) and uterine contractions (n=30) were analysed. The SR misoprostol demonstrated lower peak plasma levels but longer lasting elevation in plasma levels than conventional oral misoprostol. SR misoprostol acts less on pain inducing uterine tonus than orally administered conventional misoprostol but leads to more regular uterine contractions. Conclusion: The current protocols for medical abortion have the potential for further improvement. The need for surgical intervention could be reduced with criteria for the interpretation of hCG and ultrasound findings at the follow up. Administration of misoprostol at home, gives women more autonomy in the course of medical abortion. NSAIDs do not prolong the time to expulsion in medical abortion and should be integral part of pain treatment, even given as prophylactic. The new oral slow release form of misoprostol may have potential to improve medical abortion as indicated by the effects on uterine contractility and pharmacokinetics.