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In an attempt to improve the pregnancy rate following in vitro fertilization and embryo transfer by increasing the numbers of embryos available for transfer to each patient, a prospective, randomized comparison of clomiphene citrate alone (50 mg/day, cycle days 5 to 9) with the combination of clomiphene as above plus human menopausal gonadotropin (2 ampules/day, cycle days 6, 8, and 10) was undertaken from January through April 1983, with 17 patients in each group. The combination produced increased follicular development, compared with clomiphene alone, resulting in the retrieval of more fertilizable oocytes. Two clinical pregnancies resulted in each group. These results show that a fixed combination of clomiphene and human menopausal gonadotropin produces a greater degree of enhanced follicular recruitment, resulting in the recovery of an increased number of fertilizable oocytes. The lack of a statistically significant increase in the number of embryos transferred per patient in the combination group as well as the identical number of clinical pregnancies in both groups suggests that this particular combination of clomiphene and human menopausal gonadotropin offers no advantage over the use of clomiphene alone for enhanced follicular recruitment.

Induction of ovulation is difficult to achieve in patients with PCOD when they are resistant to therapy with clomiphene citrate; moreover, treatment with human menopausal gonadotropins subjects the PCOD patient to the risk of multifollicular ovulation and hyperstimulation. This article summarizes the hormonal picture and the initial therapeutic approach to the patient with PCOD. The proper administration, usage, and monitoring of conventional ovulation-inducing agents for these patients are discussed. Some of the newer approved agents that can be used in special patients who have not responded to conventional ovulation induction are also described.

A combination of clomiphene citrate and human menopausal gonadotropin was employed for enhanced follicular recruitment in an in vitro fertilization program. All patients received 50 mg of clomiphene and 1 ampule of human menopausal gonadotropin daily from cycle day 5 through cycle day 9. Follicular monitoring was begun on day 10 using a combination of ultrasound measurement of follicular size and number and determination of peripheral estradiol levels. Based on the size and number of follicles, the peripheral levels of estradiol, and the rate of follicular growth and increase in estradiol, human menopausal gonadotropin was continued at a dosage of 1 to 3 ampules/day through the day of human chorionic gonadotropin administration. Human chorionic gonadotropin was administered on the evening of the day the largest follicle reached or exceeded 20 mm in mean diameter if the estradiol levels had been rapidly rising or reaching a plateau and had exceeded a minimal level of 300 pg/ml. Using this protocol, 30 of 33 patients underwent laparoscopy, 29 patients had successful oocyte recovery, and 23 patients underwent embryo replacement, with the establishment of six clinical pregnancies.

In view of the increasing pregnancy rate associated with increased numbers of embryos transferred to the uterus, it is optimal to transfer more than one embryo to each patient. This requires treatment with ovulation-inducing agents to increase the number of preovulatory follicles developing. However, the degree of ovarian "hyperstimulation" must be limited to prevent subsequent luteal-phase dysfunction. In all probability, the ideal regimen for enhanced follicular recruitment to achieve these goals has not as yet been determined. Up to this time multiple different regimens have been used throughout the world, all of which have achieved an increase in the number of embryos available for uterine replacement. Unfortunately, as the degree of augmented follicular development is increased, there appears to be a progressive shortening of the luteal length. It remains to be determined whether or not this shortening of the luteal length can be overcome by pharmacologic support of the luteal phase. In addition, if all embryos recovered are to be transferred to the uterus in the treatment cycle, there is a substantial risk (ranging from 10% to 35%) that if a woman becomes pregnant, she will have a multiple pregnancy. As ethical constraints challenge the advisability of selecting only some of the available embryos for uterine replacement, the development of cryopreservation for subsequent uterine replacement appears highly desirable.