The use of luteal phase support has been demonstrated in patients undergoing IVF/ET in cycles stimulated after pituitary desensitization with gonadotrophin releasing hormone agonists. However, it is still not clear which is the most suitable kind of supplementation. This study was designed to compare the absorption and the efficacy of three different luteal support. We randomly administered progesterone i.m. (50 mg/day), human chorionic gonadotrophin (hCG) (2000 IU every three days), progesterone vaginal cream (100 mg/day) or nothing (controls) to 176 women treated for assisted procreation. We were not able to show any statistical differences for the percentage of pregnancy rate between groups. The serum progesterone (P) and 17-beta-estradiol (E2) and E2/P ratio levels of the luteal phase were compared with the control not supplemented group. All the treatments were able to increase significantly the luteal P values versus controls (p < 0.01). Moreover, vaginal cream and natural P im significantly decreased E2/P ratio (p < 0.05). Serum P levels were more steady with P vaginal cream than im injection. Vaginal cream for better bioavailability and acceptance appear the most suitable and comfortable method for luteal phase support.