Effect of the mode of clomiphene citrate administration on ovarian response in an in vitro fertilization program

To increase oocyte recovery for in vitro fertilization, superovulation treatment combining clomiphene citrate (CC) and human menopausal gonadotropin (hMG) is often used. However, CC may also have undesirable effects, e.g., on the endometrium, and therefore, high CC doses should be avoided. We studied the effects of three different modes of CC administration on ovarian estradiol (E2) responses and additive follicular diameters developed during 42 stimulated cycles. The treatments were (1) 150 mg CC on cycle days 5 to 9, (2) 50 mg CC on cycle days 3 to 7, or (3) 50 mg CC on cycle days 5 to 9. On the seventh cycle day, 300 IU hMG was given to all patients and this was continued for 3 to 4 days in decreasing doses depending on the ovarian responses, followed by daily E2 analyses and ultrasound measurements. The peripheral E2 concentrations during the different modes of CC administration were identical on cycle days 7 to 12. In addition, the additive follicular diameters on the day of hCG administration and the total hMG doses used did not differ significantly between the three CC-administration groups. Thus, a dose of 50 mg CC daily seems to be large enough to lead to maximal ovarian response in combination with hMG, and a treatment period of cycle days 3 to 7 appears to be suitable. In this way the interval between the cessation of CC and embryo transfer is maximal, and possible deleterious effects on the endometrium are minimized.