Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization

Abstract

To determine if women who previously had demonstrated poor ovarian responsiveness during ovulation induction for IVF would obtain an improved follicular response by the administration of microdoses of GnRH agonist (GnRH-a). Prospective evaluation using the same patients' previous assisted reproductive technology cycles as historic controls. Large military tertiary care center. Thirty four patients who were low responders (peak E2 < 500 pg/mL [conversion factor to SI unit, 3.67]) during ovulation induction with luteal phase GnRH-a suppression followed by exogenous gonadotropins. Follicular phase administration of 20 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and supplemented with exogenous gonadotropins beginning on cycle day 5. Paired analysis of initial E2 response, peak E2 level attained, number of follicles > or = 16 mm, duration of stimulation, ampules of gonadotropins required, late follicular LH levels, number of mature oocytes retrieved, and fertilization rates. Ovarian responsiveness was enhanced during the microdose GnRH-a stimulation cycle when compared with the previous stimulation cycle. Specifically, the patients had a more rapid rise in E2 levels, much higher peak E2 levels, the development of more mature follicles, and the recovery of larger numbers of mature oocytes at the time of retrieval. None of the patients had premature LH surges as evidenced by a significant rise in LH levels or a significant decline in E2 levels. There were no differences in the fertilization rates. Microdose GnRH-a administration beginning in the early follicular phase may result in an augmented ovarian response when compared with traditional GnRH-a-exogenous gonadotropin stimulations. Additionally, it may decrease gonadotropin requirements while effectively preventing premature LH surges.