Long-acting depot formulation of luprolide acetate as a method of hypothalamic down regulation for controlled ovarian hyperstimulation and oocyte production in Macaca fascicularis

Reproductive function in some nonhuman primate species parallels that of the human. As a result, studies addressing aspects of reproductive function primarily involve the use of non-human primate models. The objective of the present study was to assess the efficiency of two hypothalamic down-regulation techniques combined with a single controlled ovarian hyper-stimulation protocol for mature oocyte production in the cynomolgus macaque (Macaca fascicularis). Hypothalamic GnRH down regulation was first induced using the clinical long protocol of the short-acting GnRH-agonist luprolide acetate combined with controlled ovarian hyperstimulation and oocyte retrieval. Resulting oocyte yield and maturity with this regimen was insufficient for further evaluation of oocyte competency. Hypothalamic down regulation was induced in the second experiment using the long-acting depot formulation of luprolide acetate in conjunction with controlled ovarian hyperstimulation. This regimen allowed for the consistently efficient production of oocytes (15.5 oocytes per oocyte retrieval) and an oocyte maturity rate of 56%. Oocyte competence, as determined by the ability to undergo fertilization or parthenogenic activation and to reach specific cleavage stages at appropriate time intervals, was evaluated. Intracytoplasmic sperm injection resulted in a 59% fertilization rate and a 91% cleavage rate. Parthenogenic activation resulted in a 70% activation rate and an 86% cleavage rate. These data suggest that use of the long-acting form of luprolide acetate in conjunction with controlled ovarian hyperstimulation results in the production of competent, mature oocytes and allows the efficient use of nonhuman primate resources in studies of reproductive function in cynomolgus macaques.