Pituitary response to early follicular-phase minidose gonadotropin releasing hormone agonist (GnRHa) therapy: evidence for a second flare.

Purpose: Our purpose was to determine the pituitary response to minidose follicular-phase GnRHa and see if a second flare can be achieved.

Method: A prospective, consecutive series of 12 couples with tubal-factor infertility underwent 14 cycles of minidose GnRHa. Women were given a 25- or 50-migrograms dose of leuprolide acetate (LA) on cycle days 2 and 5. On cycle days 3 and 4 no LA was given but 2 ampoules of pure follicle stimulating hormone (FSH) was administered. Beginning day 6, a combination of LA and FSH was administered.

Results: Following a dose of only 25 micrograms of LA on cycle day 2, mean FSH, LH, and E2 levels were significantly elevated over the baseline levels. Following no LA on cycle day 3 or 4, a repeat dose of 25 micrograms LA caused a second flare of LH and E2 on cycle day 6. Of the 14 cycles, 6 were canceled because of poor stimulation. Two of the eight patients who underwent retrieval delivered a live birth.

Conclusions: This is the first study to examine both the pituitary response and the recovery time from minidose follicular-phase GnRHa. An extremely small dose of LA is needed to cause a pituitary flare of gonadotropins. Following a flare from 25 micrograms of LA on cycle day 2, the pituitary is able to recover and respond with a repeat flare on cycle day 5.