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Cilostazol and its Effects on Human Oocyte Maturation in Vivo: A
Pilot Study
Master of Clinical Science (MsC) Degree Dissertation
December 2014
Dr. Laura Sech
Dr. Daniel Mishell, Jr., Dr. Richard Paulson, Dr. Kristen Bendikson
University of Southern California
December 2014
Object Description
| Title | Cilostazol and its effects on human oocyte maturation in vivo: a pilot study |
| Author | Sech, Laura Ann |
| Author email | sech@usc.edu;laurasech30@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Clinical, Biomedical and Translational Investigations |
| School | Keck School of Medicine |
| Date defended/completed | 2014-11-13 |
| Date submitted | 2014-11-13 |
| Date approved | 2014-11-13 |
| Restricted until | 2014-11-13 |
| Date published | 2014-11-13 |
| Advisor (committee chair) | Azen, Stanley P. |
| Advisor (committee member) |
Mishell, Daniel Natavio, Melissa |
| Abstract | 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. |
| Keyword | non-hormonal contraception; oocyte maturation |
| Language | English |
| Format (imt) | application/pdf |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Sech, Laura Ann |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Filename | etd-SechLauraA-3086.pdf |
| Archival file | Volume1/etd-SechLauraA-3086.pdf |
Description
| Title | Page 1 |
| Repository email | cisadmin@lib.usc.edu |
| Full text | 1 Cilostazol and its Effects on Human Oocyte Maturation in Vivo: A Pilot Study Master of Clinical Science (MsC) Degree Dissertation December 2014 Dr. Laura Sech Dr. Daniel Mishell, Jr., Dr. Richard Paulson, Dr. Kristen Bendikson University of Southern California December 2014 |
