Low-dose gonadotropin step-up protocol is highly successful for the PCOS patient

Objective: Women with polycystic ovarian syndrome (PCOS) are notoriously difficult to stimulate with gonadotropins. The PCO-like ovary has numerous preantral follicles and subtle overdoses of gonadotropins may result in an overabundance of mature follicles, thus making them particularly susceptible to higher-order multiples and ovarian hyperstimulation. A common method used for ovulation induction in the PCOS population is the “step-up” protocol. We reviewed our experience with gonadotropin stimulation and intrauterine insemination (IUI) in patients with PCOS to evaluate if the number of large follicles (> 14 mm) produced is predictive of success. Design: Retrospective study. Materials and Methods: A retrospective chart review was performed on 122 cycles of gonadotropin stimulation with IUI performed on women with PCOS from March 2001 to February 2002. For ovulation induction, we traditionally stimulated patients utilizing a “step-up” protocol, starting with a low dose of gonadotropins, typically 1 ampule for 3–6 days, and increasing the dose by 1/2 ampule increments as needed until the estradiol (E2) level begins to rise, and finally decreasing the dose near the end of stimulation as the follicles reach the appropriate size for triggering ovulation. Patient characteristics including age, height, weight, pregnancy history, total dose of gonadotropins, number of follicles > 14 mm at the time of hCG, and pregnancy outcome were analyzed. We designated > 14 mm as an appropriate size for follicular maturity based on our prior experience with in-vitro fertilization. Patients were split into two groups: patients with > 3 follicles > 14 mm on the day of HCG administration (Group A) and patients with < 3 follicles > 14 mm on day of HCG (Group B). Patient demographics and cycle characteristics were evaluated using t-test and pregnancy outcome was analyzed using chi-square test. Results: No statistical difference was noted between groups with regards to age, height, weight, amount of medication used, or length of stimulation. Peak E2 was 900 + 323 pg/ml for group A and 550 + 310 pg/ml for group B, p < 0.0001. Overall pregnancy rate for group A was 54.3% (25/46 patients) and 30.1% for group B (22/73 patients), p < 0.01. Clinical pregnancy rate for group A was 45.7% (21/46 patients) and 21.9% for group B (16/73 patients), p < 0.01. On initial ultrasound, two patients had twins and one had triplets, for an overall multiple pregnancy rate of 2.45% (3/122 patients). All three patients with multiples were in group A. Table 1 summarizes the patient demographics and cycle characteristics among groups A and B. Where applicable, data are expressed as the mean + the standard deviation. Tabled 1 Conclusion: A finding of > 3 follicles measuring > 14 mm on the day of HCG administration shows a statistically significant improvement in clinical and overall pregnancy results. However, with this benefit comes the increased risk of multiple pregnancy, albeit a very small increased risk.