INTRODUCTION

Ovulation induction (OI) that is not part of an in vitro fertilization (IVF) cycle is the cause of 40–70 percent of high-order multiple pregnancies (HOMP), pregnancies with three or more conceptus, and 11–21 percent of twins, in countries where modern infertility treatment is practiced (Levene et al., 1992; Corchia et al., 1996; Reynolds et al., 2003; Figure 28.1). The high incidence of HOMP due to OI is primarily due to use of gonadotropins, follicular stimulation hormone (FSH), and human menopausal gonadotropin (HMG), but also occurs with use of clomiphene citrate (CC). In IVF cycles, twin and HOMP pregnancies can be prevented 99 percent of the time by transferring no more than one or two embryos. In OI cycles, twin and HOMP pregnancies can be prevented by canceling cycles when more than one or two preovulatory follicles are present or estrogen levels are too high and by aspirating supernumerary follicles. Recommendations to prevent multiple birth have included withholding human chorionic gonadotropin (hCG) administration when more than six follicles are 12 mm or larger (Valbuena et al., 1996; Dickey et al., 2001); when more than three follicles are 14 mm or larger (Pittrof et al., 1996; Takokoro et al., 1997), or 16 mm or larger (Yovich and Matson, 1988); when more than two (Zikopoulos et al., 1993) or three (Tomlinson et al., 1996; Hughes et al., 1998) follicles are 18 mm or larger; and when E2 exceeded 400 pg/mL (Kemmann et al., 1987), 600 pg/mL (Schenker et al., 1981), 1,000 pg/mL (Valbuena et al., 1996; Hughes et al., 1998), or 2,000 pg/mL (Vollenhoven et al., 1996; Remohi et al., 1989).