COMPARISON OF NATURAL WITH CLOMIPHENE CITRATE-STIMULATED CYCLES IN IN-VITRO FERTILIZATION - A PROSPECTIVE, RANDOMIZED TRIAL

Objective: To compare the outcome of natural with clomiphene citrate ( CC)-stimulated cycles in IVF. Design: Prospective, randomized study. S etting: Tertiary referral center for assisted conception. Subjects: Th irty patients randomized to receive either no treatment (n = 14) or CC , 100 mg, from days 2 to 6 (n = 16). Interventions: Daily ultrasound ( US) scan and measurements of serum LH and E(2). Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was admin istered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later . Main Outcome Measures: The number of patients reaching oocyte recove ry; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorde d. Results: Ten cycles in the natural cycle group were abandoned befor e oocyte recovery compared with none in the CC group. There were signi ficantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/ - 0.2) and higher peak levels of E(2) (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients tr eated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compare d with only 4 in the natural cycle group (1 oocyte each). The oocyte r ecovery rate was 95%. Two patients conceived in the CC group (PR per E T, 18%) compared with none in the natural cycle group. Patients with p olycystic ovaries developed more large follicles than those with norma l ovaries. No patient developed ovarian hyperstimulation syndrome. Con clusions: Patients undergoing natural cycle IVF are more likely to hav e abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene cit rate should be considered for use in the context of a conventionally o rganised IVF-ET program if a mild degree of ovarian stimulation is des ired.