Objective. To assess the psychological impact (Hospital Anxiety and Depression Scale) of an investigational ovarian stimulation protocol in women with premature ovarian failure (POF). Design. Prospective longitudinal study. Population. Ten women with POF. Methods. Women with idiopathic POF were placed on three consecutive treatment cycles consisting of gonadotropin ovarian stimulation after estrogen priming, gonadotropin-releasing hormone agonist pituitary desensitization, and corticosteroid immune suppression. Results. Median anxiety and depression scores increased significantly from baseline following three consecutive treatment cycles from 4.0 (range 2.0–8.0) to 11.0 (range 10.0–14.0) (p-value 0.041) and from 1.5 (range 0–6.0) to 9.0 (range 7.0–10.0) (p-value 0.039), respectively. There were nine “probable” anxiety (90%) and three “probable” depression (30%) cases on the final treatment cycle compared with none (0%) on baseline (p-value 0.004 and 0.250, respectively). Conclusions. The use of investigational ovarian stimulation protocols in women with idiopathic POF was associated with excessive psychological strain. Women with POF should be cautioned against the potentially harmful aspect of similar treatments of unproven benefit.