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• W2582185329 abstract "To determine whether the phosphodiesterase (PDE) 3 inhibitor ORG 9935 prevents the resumption of meiosis in primate oocytes during natural menstrual cycles. Nonhuman primate, in vivo controlled experiment. Adult female rhesus macaques exhibiting regular menstrual cycles (n=8) underwent daily venipuncture during the follicular phase until serum estradiol levels reached ≥80 but <120 pg/ml. At this point, animals were started on a 2-day treatment regimen of human recombinant gonadotropins to control the timing of ovulation; On day 1 of treatment, a GnRH antagonist (Antide; Ares Serono Group, Ltd; 0.5 mg/kg) and r-hFSH and r-hLH (30 IU each; Repronex, Ferring Pharmaceuticals) were administered at 12:00, and gonadotropins alone at 20:00. On day 2, GnRH antagonist and an ovulatory stimulus (1000 IU r-hCG, Ovidrel, Ares Serono Group, Ltd) were administered at 0600 with laparoscopy performed 27 hours later. Follicles were aspirated using a continuous irrigation technique to recover the oocyte from the single dominant follicle. Monkeys received no further treatment (controls), or the PDE 3 inhibitor ORG 9935 (NV Organon) beginning in the early follicular phase (cycle day 1-2) starting at an initial dose of 50 mg/kg. The dose of ORG 9935 was increased by 50 mg/kg/d each day until a dose of 200 mg/kg/day was given by cycle day 4 - 5, prior to administration of gonadotropins. This dose was continued until laparoscopy. The primary outcome was the meiotic stage of the oocyte (germinal vesicle (GV)-intact, or germinal vesicle breakdown (GVBD)) recovered from the single dominant follicle. Oocytes were incubated at 37 C under oil in TALP with bovine serum albumin and pyruvate for 48 hrs. GVBD oocytes were inseminated in vitro with activated sperm 8 hrs after recovery. Oocytes that progressed to GVBD during culture were inseminated at 24 - 32 hrs. A single unruptured dominant follicle was noted at laparoscopy in 10/11 (91%) experiments. Animals received ORG 9935 during 6 of the 10 successful experiments; 5 of the recovered oocytes were GV-intact, and 1 was GVBD (metaphase (M) I). In contrast, in the 4 control cycles, all 3 recovered oocytes were GVBD (2 at MI, 1 at MII, p < .05, Fisher’s Exact Test). An oocyte was not recovered during one control experiment. Although 3/5 GV oocytes recovered from ORG 9935 treated females progressed to MI during culture, none progressed to MII. None of the oocytes exposed to ORG 9935 in vivo underwent normal fertilization compared with 2/3 (67%) of the oocytes recovered from control animals. These results demonstrate that the PDE3 inhibitor ORG 9935 blocks resumption of meiosis in the dominant follicle of natural menstrual cycles in primates, and suggest that PDE 3 inhibitors have potential clinical use as contraceptives in women." @default.
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• W2582185329 date "2006-09-01" @default.
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• W2582185329 doi "https://doi.org/10.1016/j.fertnstert.2006.07.115" @default.
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