Background: With the advent of GnRH antagonists, another option has become available to the Reproductive Endocrinologist in the individualization of COH protocols for each patient. The divergent mechanisms used to obtain the ultimate goal of preventing the premature LH surge by GnRH-agonist and GnRH-antagonist has implications on the resulting oocyte. This would have particular importance in patients 35 years and older, a population known to have limited numbers of available mature oocytes and at higher risk for aneuploidy.

Objective: The purpose of this study was to test the hypothesis that the mechanism of pituitary suppression during COH for IVF (i.e. antagonist vs. agonist) influences embryo quality as measured by aneuploidy.

Materials and Methods: This prospective study will randomize 40 patients, ages 35 to 42 years, with day 3 FSH measurements <10 mIU, to either undergo COH for IVF using a GnRHa (Lupron®, Tap Pharmaceuticals) for pituitary downregulation or a GnRH antagonist (Ganirelix Acetate, Organon Pharmaceuticals, USA, Inc.) for pituitary suppression. Following OCP therapy, all patients are to receive rFSH (Follistim®, Organon Pharmaceuticals USA, Inc.). Under the agonist protocol, patients start leuprolide acetate 40 mcg bid on the 3rd pill-free day and 150 IU rFSH bid on the 5th pill-free day. Under the antagonist protocol, patients start on 150 IU rFSH bid on the 3rd pill-free day and 250 mcg of ganirelix acetate daily when the lead follicle has reached 14 mm in size. Subsequently, the rFSH dosage is to be individualized depending on the response. Preimplantation genetic diagnosis (PGD) will be performed to assess chromosomes 13, 18, 21, X, and Y on all embryos amenable to biopsy for aneuploidy screening. Parameters assessed include age, FSH, days of stimulation, and total Follistim® dosage. Outcome measures were number of oocytes retrieved, percent oocytes fertilized, percent abnormal embryos and pregnancy outcome.

Results: These data represent the initial 21 patients who have proceeded through the study. In the ganirelix acetate arm (8 patients), mean number of ocoytes retrieved were 6.2, 3.7 (59.7%) oocytes fertilized, and 3.3 embryos were analyzed by PGD per cycle. Similarly, in the leuprolide acetate arm (13 patients), mean number of oocytes retrieved were 8.2, 4.3 (52.4%) oocytes fertilized, and 4.1 embryos were analyzed by PGD per cycle. Both groups yielded almost identical rates of abnormal embryos, 57.7% and 61.3% for Ganirelix and leuprolide, respectively. On average, per cycle, the number of normal (pgd) embryos that were available for transfer was, 1.8 in Lupron and 1.1 in Ganirelix. Of those patients proceeding through stimulation (intent-to-treat group), 38.0% in the Ganirelix group and 15.4% in the leuprolide group had positive pregnancy tests (+hCG).

Conclusions: Though, this study has yet to reach its completion, the data thus far do not suggest that the mechanism of pituitary suppression, either by an antagonist’s competitive inhibition or an agonist-mediated down regulation, effects genomic quality as measured by aneuploidy. In fact, though sufficient data has not been accumulated to make any conclusions, the trend in pregnancy rates reveals that, at a minimum, antagonist suppression is equivalent to agonist down regulation.

Support: This study has been supported by an unrestricted educational grant from Organon Pharmaceuticals, USA.

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