To compare implantation and pregnancy rates (IR and PR) in IVF cycles supported during the luteal phase by two protocols. Prospective, randomized study. Protocol 1: Daily progesterone (P4) injections 100 mg IM beginning the day of oocyte retrieval (day 0) and estradiol Valerate (EV) 2 mg IM injections every-other-day beginning day 10. Protocol 2: Daily P4 50 mg IM beginning day 2, estradiol transdermal patch 0.2 mg (two patches) twice/week beginning day 9. Both protocols were continued until day 15/16 when serum E2, P4, and Beta hCG levels were determined. The patients were randomly assigned to each protocol according to a computer generated randomization table. Detection of beta hCG elevations were considered as positive pregnancy tests, clinical PR was determined when intrauterine gestational sac was present, ongoing PR was defined as the presence of fetal cardiac activity, and IR was calculated based on the number of implantations with cardiac activity per number of embryos transferred. The data were analyzed using Chi-square or student t-test where appropriate. A p value of less or equal to 0.05 was considered significant. There were 57 patients (63 cycles) enrolled to Protocol 1 and 48 patients (51 cycles) to Protocol 2. There were no differences between Protocol 1 and 2 regarding patient’s age (35.0 vs 33.9), E2 at hCG administration (1986 vs 2028 pg/mL), endometrial thickness at hCG (11.4 vs 11.7 mm), number of eggs retrieved (13.3 vs 14.5), number of eggs fertilized (8.4 vs 9.7), or mean number of embryos transferred (2.4 vs 2.5). There were also no differences in clinical PR (50.8 vs 52.9%), ongoing PR (47.6 vs 39.3%), or IR (30.5 vs 27.8%). However, in a subgroup of patients undergoing repeated IVF, there were significant differences. With Protocol 1 and 2, respectively, clinical PR was 64.0 vs 50.0% (P>0.05), ongoing PR 60.0 vs 27.8% (P=0.04), and IR 40.0 vs 14.6% (P=0.003). In this subgroup, early implantation/pregnancy loss (positive pregnancy tests - ongoing pregnancies) was 1 of 16 (6.3%) with Protocol 1 and 5 of 10 (50%) with Protocol 2. As anticipated, Day 15/16 P4 levels were significantly higher with Protocol 1 than Protocol 2 in both pregnant (259 vs 198ng/ml, P=0.04) and non pregnant patients (54 vs 30 ng/ml, P=0.002), while E2 levels were significantly higher on day 15/16 only in non pregnant women (408 vs 161 pg/ml, P=0.0002). It is likely that a better luteal phase support with Protocol 1 contributed to higher pregnancy and implantation rates and fewer early pregnancy losses in the repeated IVF group. High level progesterone and estradiol support during the luteal phase of the IVF cycle may improve implantation and pregnancy rates and decrease early pregnancy losses in women with previous IVF failures.