ANTI-NIDATORY EFFECT OF A SINGLE, EARLY POSTOVULATORY 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 an effective anti-nidatory strategy was tested using the rhesus monkey as the experimental model. Incidence of pregnancy, vaginal bleeding patterns, profiles of menstrual cyclicity and of serum levels of progesterone and oestrogen were examined following administration of RU 486 as a single dose of 10 mg/kg and 2 mg/kg body weight on the second day after ovulation. In control monkeys (group 1; n = 5) receiving the vehicle alone (benzyl benzoate:olive oil, 1:4, v/v) there was a 60% pregnancy rate. Following s.c. administration of RU 486 at both doses, no pregnancy was 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 three consecutive 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 subsequent follicular phase was unaffected. Mild, premature vaginal bleeding during the luteal phase was recorded in five treatment cycles, 3-5 days after drug application. Though the serum profiles of progesterone and oestrogen in these monkeys showed marked individual variations, there was a characteristic progesterone rebound about 18-20 days after drug administration. Monkeys in group 3 were given RU 486 at 2 mg/kg, s.c. either for three consecutive cycles (group 3a; n = 4) or for two consecutive cycles (group 3b; n = 3). Premature luteal phase vaginal bleeding occurred only in four treatment cycles, within 2 - 6 days post-treatment. An increase in both the duration (P < 0.001) and degree (P < 0.001) of menstrual flow as compared with the pre-treatment cycles was recorded in six treatment cycles of three monkeys in group 3. These animals did not have premature luteal phase vaginal bleeding. Collectively, 100% protection against pregnancy with no change in the cycle length was obtained in all seven monkeys in 18 treatment cycles. Analysis of pooled data revealed that the subsequent follicular phase, as well as the ovarian steroid hormone profiles of treatment cycles were unaffected. Thus, a single application of RU 486 in the early secretory phase appears to be a potential anti-implantation strategy for intercepting pregnancy in the primate.