The step-up protocol increases clinical pregnancy rates compared with the step-down in patients with unexplained...

Unexplained infertility is a relevant indication for controlled ovarian stimulation associated to intrauterine insemination. The "step-up" and "step-down" gonadotropin-based protocols were designed to reduce multiple pregnancy and ovarian hyperstimulation syndrome in polycystic ovary syndrome patients, but there is no related evidence in normoovulatory women undergoing intrauterine insemination. Our aim was to compare the efficacy and safety of both protocols with intrauterine insemination in unexplained infertility patients.

Randomized clinical trial including 145 women with unexplained infertility randomly following the step-up (n=73) or step-down (n=72) protocol. In the step-up group, patients started on day 3 of a spontaneous cycle administrating recombinant FSH 75IU sc/day, increasing it to 150IU if no response after 7 days. In the step-down, patients started administrating 150IU sc/day, constantly decreasing it to 75IU after 5 days. Recombinant hCG was administered when a follicle reached ≥18mm diameter.

Clinical pregnancy rate was higher in the step-up group than in the step-down (20.5% vs . 8.3%; p =0.037). Significant differences between step-up and step-down protocols were found regarding days of rFSH administration (8.83±4.01% vs . 7.42±2.18%; p =0.001) and cancellation rate due to hyper response (8.21% vs . 25%; p =0.05). No differences were detected in miscarriage rates, multiple pregnancy rates/cycle and hyper stimulation syndrome incidence.

The step-up protocol is longer-lasting but more effective obtaining pregnancies than the step-down in patients with unexplained infertility undergoing intrauterine insemination. This effect could be explained by lower cancellation rates due to ovarian hyper response than the step-down protocol, with no differences in ovarian hyper stimulation syndrome incidence.