To evaluate whether the incidence of luteinizing hormone (LH) rise is reduced by using a flexible compared with a fixed day-6 protocol of GnRH antagonist administration.Randomized controlled trial.Tertiary university hospital.Patients undergoing in vitro fertilization (n = 146).Ovarian stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist cetrorelix (0.25 mg/d) was started either on day 6 of stimulation (fixed group) or when LH was >10 IU/L, and/or a follicle with mean diameter >12 mm was present, and/or serum E 2 was >150 pg/mL. Patient monitoring was initiated on day 3 of stimulation.Incidence of LH rise.No statistically significant difference was observed between the flexible and fixed groups regarding the incidence of LH rise, which was lower in the flexible group (11.0% vs. 15.1%, difference −4.1%, 95% confidence interval −15.4% to +7.1%). No LH surges were observed in any of the patients studied.Flexible antagonist administration from day 3 onward does not appear to reduce the incidence of LH rises compared with fixed antagonist administration on day 6 of stimulation.