Formerly at the Department of Reproductive Health and Research, WHO, Geneva, Switzerland.
Time to misoprostol after mifepristone: still a bone of contention!
Article first published online: 11 MAR 2011
© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG
BJOG: An International Journal of Obstetrics & Gynaecology
Volume 118, Issue 5, pages 629–630, April 2011
How to Cite
von Hertzen, H. and Piaggio, G. (2011), Time to misoprostol after mifepristone: still a bone of contention!. BJOG: An International Journal of Obstetrics & Gynaecology, 118: 629–630. doi: 10.1111/j.1471-0528.2010.02875.x
- Issue published online: 11 MAR 2011
- Article first published online: 11 MAR 2011
- Accepted 3 December 2010.
We are pleased to note that the results of our research influence clinical practice, as testified by our Indian colleagues above, especially as the main aim of our work is to improve abortion care for women worldwide.
In their letter, Dr Rajaram et al.1 refer to our recent studies on the interval between mifepristone and misoprostol in the early medical abortion regimen,2 and the comparison of two doses of misoprostol administered vaginally or sublingually 24 hours after mifepristone.3 Misoprostol is usually administered 36–48 hours after mifepristone based on findings showing that the uterine muscle is most sensitive to prostaglandin analogues 36–48 hours after mifepristone administration.4 Data from France have also shown the highest efficacy with this interval. We demonstrated, however, that, when 800 μg of misoprostol are used, the interval can be shortened from 48 to 24 hours.2
The effect on uterine contractility is a balance between the degree of sensitivity and the dose of misoprostol. When the interval is shorter, it is likely that higher doses will be needed and a route of administration should be chosen that leads to effective contractions, especially as the gestational age increases. In another study,3 in which we compared single doses of 800 and 400 μg of misoprostol, administered sublingually or vaginally, 24 hours after mifepristone, the higher 800 μg dose may have prevailed over the length of the interval. The efficacy of the 400-μg dose was significantly lower, but perhaps might have been better if the 48-hour interval had been used.
In these two studies, the length of gestation was up to 63 days after the last menstrual period (LMP). The 48-hour interval may, however, be necessary when the duration of gestation is longer, as demonstrated in a second-trimester abortion study:5 the time until abortion occurred was significantly longer (P < 0.0001) in the 24-hour interval (between mifepristone and the start of repeat administration of vaginal misoprostol) compared with the 48-hour interval group. Consequently, the total dose of misoprostol given to women was higher in the 24-hour interval group.
Mifepristone pretreatment also leads to softening and dilation of the uterine cervix, and the 48-hour interval is necessary to achieve maximal softening and dilation, which is important, especially in the second trimester. Our study suggests that, in earlier gestations, the dilation achieved in 24 hours seems to be sufficient.
The Department of Reproductive Health and Research at the World Health Organization (WHO), Geneva, convened a technical consultation in August 2010 to update the document entitled ‘Safe Abortion: Technical and Policy Guidance for Health Systems’. The results of the studies referred to above have been taken into account in this updated document when revising the guidance for clinical care for women undergoing abortion.
- 1Time to misoprostol after mifepristone: still a bone of contention!. BJOG 2011;118:629., , .