EFFECT OF FOLLICULAR PHASE ADMINISTRATION OF MIFEPRISTONE (RU486) ON BLASTOCYST IMPLANTATION IN THE RHESUS-MONKEY

In the present study our aim was to test two hypotheses: 1) inhibition of preovulatory phase progesterone action can inhibit or delay ovulat ion, and 2) inhibition of preovulatory phase progesterone action can i nhibit postovulatory phase endometrial receptivity for blastocyst impl antation. Female rhesus monkeys showing normal cycle lengths were rand omly assigned to two groups: group 1 (n = 5) and group 2 (n = 7). The pretreatment cycles were monitored for ovulatory pattern and, in treat ment cycles, females were allowed to cohabit with males from cycle day s 6 to 28; group 2 animals received vehicle alone, and group 2 animals received mifepristone (RU486, subcutaneously), 1 mg/animal 3 consecut ive cycle days (days 7, 8, and 9 for 26-day pretreatment cycle length; and days 8, 9, and 10 for 28-day pretreatment cycle length). Follicul ar phase mifepristone resulted in a delay of ovulation (p < 0.01) when compared with pooled data of pretreatment and treatment cycles of gro up 2 and pretreatment cycles of group 2. Despite delay of ovulation, t here was only a 20% decrease in the incidence of pregnancy in group 2 as compared with that in group 1. However, a delay (p < 0.05) in the a ppearance of CG was noted in follicular phase mifepristone-treated cyc les as compared with control treatment cycles. On the other hand, ovul ation could not be detected in three monkeys in group 2; and, of these , two cycles were extended but all three cycles were negative for CG. These results support earlier reports that follicular phase mifepristo ne can inhibit or disrupt follicular maturation, and delay ovulation. However, follicular phase mifepristone Jailed to inhibit implantation, because gonadal hormones, including progesterone, resume normal funct ions once ovulation takes place. (C) 1997 Elsevier Science Inc. All ri ghts reserved.