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23 - Clomiphene Citrate for Ovulation Induction

from PART II - INFERTILITY EVALUATION AND TREATMENT

Published online by Cambridge University Press:  04 August 2010

Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
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Summary

INTRODUCTION

Clomiphene revolutionized the management of infertility in 1967 when it was approved for treatment of anovulation due to polycystic ovaries (PCO). The clinical introduction of clomiphene followed six years of research (Greenblatt et al., 1961; Tyler et al., 1962; Vorys et al., 1964; Dickey et al., 1965; Kistner, 1966) cumulating in a report of results in 3,220 patients and 1,032 conceptions (Table 23.1) (Macgregor et al., 1967; Macgregor et al., 1968). Today, clomiphene remains the first-line treatment for WHO Group II anovulation in which ovarian activity can be demonstrated by withdrawal bleeding from progesterone. In addition to treatment of anovulation, clomiphene is now also used alone and in combination with human menopausal gonadotropin (HMG) and follicle-stimulating hormone (FSH) to increase the number of preovulatory follicles in patients with unexplained infertility (Melis et al., 1987; Deaton et al., 1990; Glazener et al., 1990), in patients requiring husband or donor intrauterine insemination (IUI) (Shalev et al., 1989; Dickey et al., 1992), and to increase progesterone in patients with luteal insufficiency (Hammond and Taubert, 1982; Fukuma et al., 1983; Dickey, 1984; Guzick and Zeleznik, 1990). The advantages of clomiphene over gonadotrophin for ovulation induction include low incidence of multiple pregnancies, low cost, ease of treatment, absence of need for daily cycle monitoring, and low incidence of ovarian hyperstimulation syndrome (OHSS) (Rizk, 2006, 2008; Rizk and Dickey 2008).

PHARMACOKINETICS AND PHARMACODYNAMICS

The pharmacokinetics and pharmacodynamics of clomiphene explain its characteristic actions. Clomiphene, chemical name 1-[p(β-diethylaminoethoxy)phenyl]-1,2-diphenylchloroethylene (Holtkamp et al., 1960), is related to other trianyl ethylene compounds chlorotrianisene, triparanol (a cholesterol inhibitor), and tamoxifen, a class of drugs called selective estrogen receptor modulators (Figure 23.1) and is distantly related to the nonsteroidal estrogen diethylstilbestrol.

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Publisher: Cambridge University Press
Print publication year: 2008

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