Effect of mifepristone on folliculogenesis in women treated with recombinant FSH.

Abstract

To study the mechanism through which mifepristone interrupts folliculogenesis. Normally ovulating women undergoing donor intrauterine insemination (IUI) treatment were investigated during two menstrual cycles treated with gonadotrophins. In the first cycle (FSH cycle), the women were given 150 IU recombinant FSH (rFSH) s.c. on days 2, 4, 6, 8 and daily thereafter until the administration of hCG. During the second cycle (FSH + mifepristone cycle), the women received rFSH as above plus mifepristone tablets at a dose of 50 mg/day from cycle day 2 until the hCG injection. IUI was performed only in the FSH cycles. Eleven normally ovulating women were studied. The women were used as their own controls during the cycle treated with rFSH only. Two women became pregnant during the FSH cycle and, therefore, data for comparison between the two cycles were available in nine women. In both cycles, only one follicle reached the preovulatory stage. However, during treatment with FSH + mifepristone the growth of the dominant follicle was temporarily arrested after day 8 of the cycle and ovulation was postponed by 2 days on average. Serum FSH values increased significantly in both cycles only during the daily administration of rFSH, i.e. towards the end of the experimental period when a normal growth of the follicle was re-established. On the day of hCG injection, an endogenous LH surge had already started in six of the nine cycles treated with FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory oestradiol (E2) levels. Endometrial thickness during the follicular phase and serum E2 and progesterone concentrations during the luteal phase, although in the normal limits, were significantly lower in the FSH + mifepristone than in the FSH cycles. These results suggest that mifepristone arrests follicular development at a stage beyond the recruitment-selection point by delaying the growth of the dominant follicle. This is probably achieved through an effect of mifepristone on the ovary where it reduces the sensitivity of the selected follicle to FSH. Mifepristone may have a potential application for the inhibition of the LH surge in superovulation induction programmes.