A total of 156 patients were randomly treated with exogenous natural progesterone (intramuscularly, 50 mg/day) and vaginal gel (90 mg/day) P or nothing (Controls) from the day before embryo transfer (ET) for two weeks. In case of positive beta-HCG, the treatment was continued for 12 weeks. Plasma P and 17 beta-Estradiol concentrations were estimated and compared with the control not supplemented group. Both treatments were able to increase significantly the luteal plasmatic values of P versus controls. The ongoing pregnancy and the living birth rates per transfer were significantly higher in the patients supplemented with intramuscular P than in those treated with vaginal gel P. The intramuscular natural P appears the most suitable route of administration for luteal phase support in IVF-ET procedures.