In vivo models demonstrated a similar reduction in oocyte maturation, with the most dramatic reduction in monkeys treated with an extended dose regimen of ORG 9935 (200mg/kg/d) prior to ovulation (8). Additionally, pregnancy rates in macaques treated with ORG 9935 was studied and compared to controls. Overall, there was not a statistically significant decrease in pregnancy rates in those macaques treated with PDE3 inhibitor; however, there did appear to be evidence of a dose response as no animal became pregnant who had serum ORG 9935 levels above 300nM/L (9). Despite a clear dose response, authors of this study acknowledge that PDE3-Is have systemic effects that are also dose-limiting. At higher doses, adverse effects such as tachycardia and hypotension were observed.