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The current clinical and laboratory protocols of the in vitro fertilization program at the University of Texas at Houston are described and detailed. Most patients treated have tubal disease, with a limited number of couples having male factors. Clomiphene citrate (50 mg/day, cycle days 5-9) with or without added menopausal gonadotropins is the principle agent for enhanced follicular recruitment. Follicular development is monitored primarily with daily ultrasonography, and human chorionic gonadotropin (hCG) is given when the largest follicle reaches or exceeds 20-mm mean diameter. The culture media used are modifications of Ham's F-10. Mature oocytes are preincubated for 5 hr before insemination with 50,000 motile sperm per oocyte. Using these protocols, the clinical pregnancy rate is 11.6% per laparoscopy (11/95) and 16.2% per embryo transfer (11/68).

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.

Recognizing the association between plasma progesterone (P) and an imminent LH surge, we investigated the frequency of P elevation in our stimulation protocol (clomiphene citrate-human menopausal gonadotropins). P was measured retrospectively on the day before, the day of, and the day after human chorionic gonadotropin hCG administration. The means +/- 2 standard deviations for P were as follows: day before hCG, 0.58 +/- 0.86; day of hCG, 0.64 +/- 0.56; and day after hCG, 1.47 +/- 1.22. Seven patients (8%) had P levels greater than 2 SD above the mean. Significant P elevations prior to hCG are infrequent with this protocol, and in the few patients with raised P a trend toward lowered fertilization was noted. The low incidence of P elevation may be secondary to the administration of hCG in a timely manner on the sixth day of estradiol (E2) rise.

To investigate whether the provision of increased gonadotropins would enhance follicular recruitment and selection, women not responding (N = 18) to our standard clomiphene citrate (CC)-human menopausal gonadotropin (hMG) regimen were treated with increased hMG (treatment cycle II). Estradiol levels were higher in treatment cycle II and these differences were significant on days 8 and 9 (P less than or equal to 0.05 and P less than or equal to 0.03, respectively). On day 9, better follicular development was seen in cycle II (P less than or equal to 0.05). While none of the patients responded in cycle I, 10 of 18 responded in cycle II. Of the 10 responders, 2 conceived following in vitro fertilization and embryo placement. Increasing the dose of hMG improved the development of a cohort of follicles so that aspiration and possible pregnancy were achieved in women who were previously unresponsive to therapy.