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University of Southern California

1. Sech, Laura Ann. Cilostazol and its effects on human oocyte maturation in vivo: a pilot study.

Degree: MS, Clinical, Biomedical and Translational Investigations, 2014, University of Southern California

Background: Combined hormonal contraceptive pills (COCs) are the most frequently used method of contraception by women in the United States. However, COCs are frequently discontinued secondary to hormonal side effects. Moreover, COCs are contraindicated in women with certain medical problems. Development of a non-hormonal birth control pill could overcome these problems. In recent studies, phosphodiesterase 3 inhibitors (PDE3s) have been shown to inhibit oocyte maturation and impair fertility in macaques, mice, and pigs. Cilostazol, a class IIIa PDE, is currently FDA approved for the treatment of intermittent claudication. Additionally, this drug has demonstrated fertility impairment, despite the occurrence of ovulation, with complete reversibility in both mice and pigs. To date, no in vivo studies of Cilostazol in humans have been undertaken to determine its effects on oocyte maturation. ❧ Methods: This research design is a pilot study that enrolled 4 healthy women who have previously been oocyte donors. All participants were given the study drug, Cilostazol, at the current FDA approved dose of 100mg PO BID. The study drug was administered twice daily during the 10-14 days of ovarian stimulation with hMG until ovulation was induced with hCG. Participants underwent oocyte and follicular fluid retrieval following cycle stimulation. The stage of oocyte maturation (Germinal vesicle (GV), Metaphase I (MI), Metaphase II (MII)) was evaluated at the time of ovum retrieval and at 24 hours. The oocyte maturational stages obtained from subjects during Cilostazol treatment were compared to those documented from these same subjects during oocyte donation from a previous stimulation cycle while not taking study drug. Additionally, plasma as well as follicular fluid cilostazol levels were collected for analysis. ❧ Results: There was not a significant difference in percent of oocyte maturation retrieved at baseline vs during treatment with Cilostozol (t₃ = 0.36, p = 0.74). Plasma and follicular fluid levels of Cilostazol were obtained and a small correlation between Cilostazol levels in both the follicular fluid and plasma and oocyte maturation was demonstrated. There was a significant difference in diastolic blood pressure (DBP) (p = 0.008) and heart rate (HR) (p = 0.027) from baseline to measurements made during the study. These findings are likely not clinically relevant. ❧ Conclusions: Our findings indicate that the FDA approved dose of Cilostazol, given at 100mg PO BID, does not impair oocyte maturation in the human. Future studies using a higher dose of Cilostazol are indicated but this may prove difficult given potential for toxicity at higher doses. Advisors/Committee Members: Azen, Stanley P. (Committee Chair), Mishell, Daniel (Committee Member), Natavio, Melissa (Committee Member).

Subjects/Keywords: non-hormonal contraception; oocyte maturation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Sech, L. A. (2014). Cilostazol and its effects on human oocyte maturation in vivo: a pilot study. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/516457/rec/1364

Chicago Manual of Style (16th Edition):

Sech, Laura Ann. “Cilostazol and its effects on human oocyte maturation in vivo: a pilot study.” 2014. Masters Thesis, University of Southern California. Accessed December 03, 2020. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/516457/rec/1364.

MLA Handbook (7th Edition):

Sech, Laura Ann. “Cilostazol and its effects on human oocyte maturation in vivo: a pilot study.” 2014. Web. 03 Dec 2020.

Vancouver:

Sech LA. Cilostazol and its effects on human oocyte maturation in vivo: a pilot study. [Internet] [Masters thesis]. University of Southern California; 2014. [cited 2020 Dec 03]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/516457/rec/1364.

Council of Science Editors:

Sech LA. Cilostazol and its effects on human oocyte maturation in vivo: a pilot study. [Masters Thesis]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/516457/rec/1364

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