Objectives: We sought to assess whether the use of norethindrone and gonadotropin-releasing hormone agonist therapy in the early follicular phase reduces the occurrence of functional ovarian cysts and shortens the duration of pituitary desensitization. We also assessed whether the use of norethindrone impairs implantation rates after in vitro fertilization treatment. Study Design: We performed a prospective, randomized, single-blind study involving 117 patients who were randomized to receive norethindrone 24 hours before gonadotropin-releasing hormone agonist therapy (n = 63, treatment group) or gonadotropin-releasing hormone agonist alone (n = 54, control group) for pituitary desensitization. Results: The incidence of functional ovarian cyst formation after 1 week of gonadotropin-releasing hormone agonist therapy was significantly lower in the treatment group compared with the control group. Furthermore, the duration of pituitary suppression was significantly shorter in the treatment group than in the control group. There were no significant differences between the 2 groups in the follicular response and embryo quality. Adjusted for age, the implantation rate (22% vs 9%, P = .02) and clinical pregnancy rate (34% vs 18%, P = .04) were significantly higher in the treatment group than in the control group. Conclusion: A combination of norethindrone and gonadotropin-releasing hormone agonist therapy is therefore more effective in achieving prompt pituitary suppression and should be considered for routine use during in vitro fertilization cycles. (Am J Obstet Gynecol 1999;181:576-82.)