Abstract
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 100 mg 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.
Original language | English (US) |
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Pages (from-to) | 418-422 |
Number of pages | 5 |
Journal | Contraception |
Volume | 91 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2015 |
Keywords
- Germinal vesicle
- Meiosis
- Nonhormonal contraception
- Nonhuman primate
- cAMP
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology