SHORT-TERM ENDOCRINE RESPONSE TO GONADOTROPIN-RELEASING-HORMONE AGONIST INITIATED IN THE EARLY FOLLICULAR, MIDLUTEAL, OR LATE LUTEAL-PHASE IN NORMALLY CYCLING WOMEN

Objective: To determine short-term pituitary and ovarian hormonal resp onses to GnRH agonist (GnRH-a) administered during various phases of t he menstrual cycle, in the absence of controlled ovarian hyperstimulat ion (COH), to determine its independent effect on hormonal parameters previously demonstrated to influence assisted reproductive technology cycle outcome. Design: Prospective, randomized, controlled crossover s tudy of five regularly cycling women. The GnRH-a, leuprolide acetate ( LA), was administered 1 mg SC daily for 5 days beginning on cycle day 3 (early follicular); 8 days post LH surge (midluteal); or 13 days pos t-LH surge (late-luteal). Setting: Clinical research unit at a tertiar y care medical center. Main Outcome Measures: Serum gonadotropins (LH and FSH) and gonadal steroids (E(2), estrone [E(1)], P, A, and T) meas ured daily during GnRH-a administration begun in the early follicular, midluteal, or late luteal phase of the menstrual cycle. Gonadotropin pulse amplitude and frequency were determined after frequent serum sam pling on the 2nd day of GnRH-a administration in each treatment cycle. Results: Serum LH elevations, 4- to 10-fold greater than observed for FSH, did not differ by cycle day of GnRH-a initiation. Initial increa ses in FSH did not differ by cycle day, however, early follicular init iation resulted in a more pronounced suppression of FSH. Mean LH pulse amplitude and frequency increased to a similar extent in all three gr oups, however, FSH pulse amplitude and frequency varied significantly by cycle day of GnRH-a initiation. Gonadotropin-releasing hormone agon ist initiated in the early follicular phase resulted in significant in creases in E(2), E(1), and P levels compared with both midluteal or la te luteal. Increases in serum androgens were significantly greater aft er early follicular and late luteal initiation as compared with midlut eal GnRH-a initiation. Conclusions: Relative FSH suppression and marke d androgen elevations in both late luteal and early follicular groups, which may have potential detrimental effects on oocytes of the develo ping cohort, suggest little advantage of late luteal or early follicul ar over midluteal initiation of GnRH-a for COH.