Mifepristone and misoprostol compared with misoprostol alone for induction of labour of mid-trimester fetal demise

Following fetal death in the second trimester of pregnancy, labour is usually induced to deliver the fetus. This induction process is usually conducted with the synthetic prostaglandin E1 analogue misoprostol. This prostaglandin, although not licensed for use in pregnancy, is now in common prescribed for labour induction in the second trimester with a large accumulated experience both within Australia and internationally. Since 1996, misoprostol has been used at King Edward Memorial Hospital (KEMH) as the principal agent for second trimester pregnancy induction with a non-viable fetus. The sequential combination of the antiprogesterone agent mifepristone and the prostaglanding misoprostol is an established and effective method for second trimester pregnancy termination. Prior studies have demonstrated a significant reduction in the duration of abortion with misoprostol when mifepristone priming is used. Three senior clinicians at KEMH, including the co-investigator Professor Jan Dickinson, have Authorised Prescriber status for use of mifepristone for pregnancy termination and following fetal death. Since January 2008 the combination of mifepristone and misoprostol has been used at KEMH in approximately 500 cases of first and second trimester pregnancy termination of pregnancy, predominantly for circumstances of severe fetal abnormality. Interestingly, there is very limited published data on the use of mifepristone in combination with misoprostol for induction of mid trimester fetal demise, Currently at KEMH misoprostol alone is the most frequent method used for delivery in the presence of a deceased fetus. This is most likely due to the restricted access to mifepristone and the absence of high quality comparative data of its efficacy. In this study we plan to compare the administration of mifepristone prior to misoprostol for induction after fetal death at 14-28 weeks gestation with the use of misoprostol alone (the current KEMH standard protocol). The primary aim of this research protocol will be to compare the induction commencement to delivery interval between these two regimes. Secondary aims of this study will be to assess the incidence of maternal side-effects for each of the two regimens, post partum blood loss, placental retention rates and the need for subsequent curettage for retained placental tissue. We will also review the women’s satisfaction with the two treatment regimens. The amount of progesterone and estrogen circulating in the blood of the women prior to induction will also be assayed, given that mifepristone works by blocking the effect of progesterone. It may be that the efficacy of mifepristone is related to the concentration of progesterone in the setting of fetal loss.