Objective: Studies in mice suggest that cilostazol, an FDA-approved phosphodiesterase 3 (PDE3) inhibitor, might have a contraceptive effect within the approved dose range. We sought to evaluate the potential contraceptive effects of cilostazol in a nonhuman primate model.
Study design: Adult female rhesus macaques were stimulated to develop multiple preovulatory follicles by administering human recombinant gonadotropins, and oocytes were collected by follicle aspiration 36 h after an ovulatory stimulus (human chorionic gonadotropin). Monkeys received no further treatment (controls) or the PDE3 inhibitor cilostazol at the maximum approved human dose of 100mg twice daily starting 6 days prior to follicle aspiration. Recovered oocytes were scored for meiotic stage [germinal vesicle (GV) intact, GV breakdown], and metaphase II stage oocytes were fertilized in vitro and observed for normal embryo development.
Results: Similar proportions of GV stage oocytes were recovered from control (27%±4%) and cilostazol (27%±9%)-treated females, and the proportion of embryos that developed into blastocysts was also similar for both groups (7%±5% control vs. 15%±8% cilostazol).
Conclusion: Oral dosing of cilostazol tablets during controlled ovarian stimulation protocols did not prevent oocyte maturation or embryo development in macaques.
Implications: Since administration of the maximum approved human dose of cilostazol (an FDA-approved PDE3 inhibitor) to macaques did not prevent oocyte maturation or fertilization, it is not likely that this dose would be contraceptive in women.
Keywords: Germinal vesicle; Meiosis; Nonhormonal contraception; Nonhuman primate; cAMP.
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