During in vitro fertilization (IVF) cycles, a large bolus of human chorionic gonadotropin (hCG) is used to induce periovulatory events, but the efficacy of lower doses is undefined. In this study, oocyte nuclear maturation, granulosa cell luteinization and corpus luteum function following 100, 300 and 1000 IU recombinant (r)-hCG were compared to 1000 IU u-hCG. Rhesus monkeys received r-hFSH (Serono) with GnRH antagonist (Antide; Serono) to stimulate multiple follicular growth followed by r-hCG (Serono) or u-hCG (Profasi, Serono) injection (n=4-5 animals/group). Bioactive hCG rose to peak levels within 2 hr post-hCG that were proportional to the dose administered (79 q 10 ng/ml, 100 IU r-hCG; 287 q 69, 300 IU r-hCG; 1360 q 208, 1000 IU r-hCG; 945 q 153, u-hCG). Peak levels were evident in all groups for 8 hr. The interval of surge (r100 ng/ml) levels was dose-dependent (0 hr, 100 IU r-hCG; 24 hr, 300 IU r-hCG; >48 hr, 1000 IU r-hCG and u-hCG). The proportions of oocytes resuming meiosis (metaphase I + II), were similar among groups (88-94%). IVF rates of inseminated oocytes were similar among the 100 (34 q 20%), 300 (25 q 15%) and 1000 IU r-hCG (50 q 17%) and u-hCG (50 q 18%) groups. Fertilization occurred in 5/9 animals after 100 and 300 IU r-hCG compared to 9/10 following 1000 IU r-hCG and u-hCG. In vitro progesterone (P) production and immunocytochemical staining for P receptor in granulosa cells were comparable among groups. While peak levels of serum P in the luteal phase were similar among groups, levels declined 2 days earlier following 100 and 300 IU r-hCG relative to 1000 r-hCG and u-hCG. Thus, 3- to 10-fold lower doses of r-hCG elicit low amplitude surges of short duration that can induce reinitiation of oocyte meiosis and granulosa cell luteinization. However, standard doses of 1000 IU r-hCG or u-hCG produce surges of higher amplitude and longer duration which may be required for optimal oocyte fertilization and normal luteal function.
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