Anti-nidatory effect of a single, early post-ovulatory administration of mifepristone (RU 486) in the rhesus monkey

The hypothesis that post-coital administration of mifepristone(RU 486) as a single dose in the early luteal phase can be aneffective anti-nidatory strategy was tested using the rhesusmonkey as the experimental model. Incidence of pregnancy, vaginalbleeding patterns, profiles of menstrual cyclicity and of serumlevels of progesterone and oestrogen were examined followingadministration of RU 486 as a single dose of 10 mg/kg and 2mg/kg body weight on the second day after ovulation. In controlmonkeys (group 1; n = 5) receiving the vehicle alone (benzylbenzoate: olive oil, 1: 4, v/v) there was a 60% pregnancy rate.Following s.c. administration of RU 486 at both doses, no pregnancywas recorded in a total of 33 treatment cycles in 12 monkeys.Five monkeys received RU 486 at 10 mg/kg s.c. (group 2) in threeconsecutive cycles. All animals had complete inhibition of implantation;in addition, the treatment cycle length was prolonged (P <0.001) due to an extension of the luteal phase. The subsequentfollicular phase was unaffected. Mild, premature vaginal bleedingduring the luteal phase was recorded in five treatment cycles,3–5 days after drug application. Though the serum profilesof progesterone and oestrogen in these monkeys showed markedindividual variations, there was a characteristic progesteronerebound about 18–20 days after drug administration. Monkeysin group 3 were given RU 486 at 2 mg/kg, s.c. either for threeconsecutive cycles (group 3a; n = 4) or for two consecutivecycles (group 3b; n = 3). Premature luteal phase vaginal bleedingoccurred only in four treatment cycles, within 2–6 dayspost-treatment. An increase in both the duration (P < 0.001)and degree (P < 0.001) of menstrual flow as compared withthe pre-treatment cycles was recorded in six treatment cyclesof three monkeys in group 3. These animals did not have prematureluteal phase vaginal bleeding. Collectively, 100% protectionagainst pregnancy with no change in the cycle length was obtainedin all seven monkeys in 18 treatment cycles. Analysis of pooleddata revealed that the subsequent follicular phase, as wellas the ovarian steroid hormone profiles of treatment cycleswere unaffected. Thus, a single application of RU 486 in theearly secretory phase appears to be a potential anti-implantationstrategy for intercepting pregnancy in the primate.