UTERINE ACTIVITY AND DECIDUAL PROSTAGLANDIN PRODUCTION IN WOMEN IN EARLY-PREGNANCY IN RESPONSE TO MIFEPRISTONE WITH OR WITHOUT INDOMETHACIN INVIVO

Mifepristone stimulates uterine activity in pregnant women in the first trimester. In-vitro studies have shown that the addition of mifepristone to culture medium increases the ability of decidual cells to generate prostaglandins. In this study, pregnant women of < 56 days gestation were treated with mifepristone (600 mg) 24, 36 or 48 h prior to surgical termination of pregnancy. Another cohort of women were similarly treated with mifepristone, but also received indomethacin (100 mg b.d.). Control groups, given indomethacin alone (100 mg b.d. for 48 h) or no treatment, were also included. Uterine activity was measured immediately prior to surgical termination of pregnancy and the ability of decidua obtained at operation to generate prostaglandins in culture was measured. Uterine activity was increased in all groups pretreated with mifepristone, an increase which was not prevented by co-administration of indomethacin. In the groups pretreated with mifepristone 36 h previously, the production of prostaglandin F2-alpha (PGF2-alpha) by decidua in vitro was increased. In the group in whom indomethacin was given in addition to mifepristone 36 h prior to the study, there was a marked reduction in the ability of decidua to generate PGF2-alpha. In spite of this suppression, the increase in uterine activity was similar to the group which had not received indomethacin. These results suggest that factors other than an increase in decidual prostaglandin production are responsible for the increase in uterine activity seen following mifepristone administration in vivo.