Effect of follicular phase administration of mifepristone (RU486) on blastocyst implantation in the rhesus monkey

Abstract

In the present study our aim was to test two hypotheses: 1) inhibition of preovulatory phase progesterone action can inhibit or delay ovulation, and 2) inhibition of preovulatory phase progesterone action can inhibit postovulatory phase endometrial receptivity for blastocyst implantation. Female rhesus monkeys showing normal cycle lengths were randomly assigned to two groups: group 1 (n = 5) and group 2 (n = 7). The pretreatment cycles were monitored for ovulatory pattern and, in treatment cycles, females were allowed to cohabit with males from cycle days 6 to 28; group 1 animals received vehicle alone, and group 2 animals received mifepristone (RU486, subcutaneously), 1 mg/animal 3 consecutive 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). Follicular phase mifepristone resulted in a delay of ovulation (p < 0.01) when compared with pooled data of pretreatment and treatment cycles of group 1 and pretreatment cycles of group 2. Despite delay of ovulation, there 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 appearance of CG was noted in follicular phase mifepristone-treated cycles as compared with control treatment cycles. On the other hand, ovulation 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 mifepristone can inhibit or disrupt follicular maturation, and delay ovulation. However, follicular phase mifepristone failed to inhibit implantation, because gonadal hormones, including progesterone, resume normal functions once ovulation takes place.