EFFECT OF MIFEPRISTONE ON FOLLICULOGENESIS IN WOMEN TREATED WITH RECOMBINANT FSH

OBJECTIVE To study the mechanism through which mifepristone interrupts folliculogenesis. DESIGN Normally ovulating women undergoing donor in trauterine insemination (IUI) treatment were investigated during two m enstrual cycles treated with gonadotrophins. In the first cycle (FSH c ycle), 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. Duri ng the second cycle (FSH + mifepristone cycle), the women received rFS H 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 cycl es. PATIENTS Eleven normally ovulating women were studied, The women w ere used as their own controls during the cycle treated with rFSH only . RESULTS Two women became pregnant during the FSH cycle and, therefor e, data for comparison between the two cycles were available in nine w omen, 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 an d ovulation was postponed by 2 days on average. Serum FSH values incre ased significantly in both cycles only during the daily administration of rFSH, i.e. towards the end of the experimental period when a norma l growth of the follicle was re-established. On the day of hCG injecti on, an endogenous LH surge had already started in six of the nine cycl es treated with FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory oestradiol (E-2) levels. Endometrial thickne ss during the follicular phase and serum E-2 and progesterone concentr ations during the luteal phase, although in the normal limits, were si gnificantly lower in the FSH + mifepristone than in the FSH cycles. CO NCLUSIONS These results suggest that mifepristone arrests follicular d evelopment at a stage beyond the recruitment-selection point by delayi ng the growth of the dominant follicle. This is probably achieved thro ugh an effect of mifepristone on the ovary where it reduces the sensit ivity of the selected follicle to FSH. Mifepristone may have a potenti al application for the inhibition of the LH surge in superovulation in duction programmes.