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Use of GnRH antagonists (GnRH-ant) in Egg Donation Cycles is Associated with Reduced Serum Estradiol (E2) and LH Levels Compared to Agonist Cycles with and Without LH Supplementation, but has no effect on Implantation or Pregnancy Rates.

Research presented at the American Society for Reproductive Medicine (ASRM), New Orleans, 2006.

C. Adams, J. Juanengo, L. Anderson and S. Wood

Objective: There are several practical advantages to the use of GnRH-ant in egg donation cycles, but persistent concerns about the potential detrimental effect of antagonists on clinical outcome has kept this type of protocol from gaining widespread acceptance. The aim of this study was to compare cycle stimulation characteristics from GnRH-ant cycles with those utilizing a GnRH agonist (GnRH-a) with or without LH supplementation to investigate the potential relationship of these parameters to clinical outcome.
Design: A retrospective study of data from 80 completed oocyte donor cycles performed between August 2004 and December 2005 in a private IVF clinic.
Materials and Methods: Oocyte donors (mean age: 24±2.9, range 19-31y) underwent ovarian stimulation with one of three protocols: (1) a flexible-start GnRH-ant (cetrorelix, Cetrotide) protocol with FSH and LH containing gonadotropins after oral contraceptive pre-treatment (n=24), (2) the standard GnRH-a (leuprolide acetate, Lupron) long protocol with FSH only (n=19), and (3) GnRH-a long protocol with FSH and LH (n=37). Donors received recombinant FSH (Gonal-F), 150-225 IU/day starting day 3 of the cycle, with or without hMG (Repronex or Menopur), 75-150 IU/day starting day 3 of stimulation. Cycles were monitored by ultrasound and hormonal levels with gonadotropin doses adjusted accordingly. GnRH-ant was commenced when the lead follicle was 12-14 mm. HCG was administered when at least two follicles had a mean diameter of 18 mm. Clinical and laboratory parameters were recorded. Data were analyzed using ANOVAs and chi-squares as appropriate.
Results: Mean days of stimulation, total units of FSH, number of large follicles, number of oocytes retrieved, fertilization rates and cleavage rates were comparable among the three stimulation regimens. Mean day of hCG serum LH levels were significantly higher in GnRH-a cycles without LH supplementation (GnRH-a no LH) as compared to GnRH-a cycles + LH and GnRH-ant cycles + LH (4.6 vs. 2.8 and 0.6 mIU/ml respectively). Mean day of hCG E2 levels were significantly higher in GnRH-a + LH cycles as compared to GnRH-ant cycles and approached significance when compared to GnRH-a no LH cycles (3199 vs. 2459 vs. 2726 pg/ml, respectively). There was a non-significant trend towards higher progesterone levels on the day of hCG in the GnRH-a + LH group (2.6 ng/ml) as compared to the other two groups (both 1.7 ng/ml). Although the mean percent of highest quality cleavage stage embryos was higher in GnRH-a no LH compared to GnRH-a +LH and GnRH-ant cycles (63% vs. 48% vs. 44% respectively), there was no significant difference in pregnancy and implantation rates between the three protocols, with overall pregnancy and implantation rates (76% and 58%).
Conclusions: Oocyte donors treated with a GnRH-ant protocol have decreased serum LH levels on the day of hCG as compared to agonist containing protocols, even with LH supplementation. Estradiol levels were also significantly lower in the GnRH-ant group as compared to the GnRH-a + LH group. However, since implantation and pregnancy rates were not decreased, the hormonal differences seen in the GnRH-ant do not appear to be clinically significant.