Luteal-phase supplementation has proved necessary in Gn-RH analog and human gonadotropin-stimulated cycles. We studied the effects of vaginally and intramuscularly delivered progesterone on the endometrium. Thirty patients enrolled in an IVF program without embryo transfer due to absence of fertilization were included in the study. Patients were randomly allocated to two treatment groups. Group A (n = 15) was administered 200 mg progesterone b.i.d. by the vaginal route (Esolut, Angelini) starting on the day of oocyte pick up and group B (n = 15) was given 100 mg intramuscular progesterone once daily (Prontogest, Amsa). Six days after HCG administration, biopsies were obtained for endometrial histological maturation and estrogen (ER) and progesterone (PR) receptor analyses. In addition, ultrasound measurements of endometrial thickness were made and uterine and myometrial artery flow was determined. Serum concentrations of estriol and progesterone were measured on the day of HCG, at oocyte pick up and at endometrial biopsy. The two treatment groups were similar in terms of follicular phase parameters during superovulation with Gn-RH analog and gonadotropin. Histologic, receptor and ultrasonographic analyses showed no significant differences between the two treatment groups. Our results indicate that both intramuscular and vaginal progesterone are equally effective on the endometrium.