Background : This  study aims to determine the effectiveness and safety of adding estrogen and progesterone for luteal phase support to improve the live birth rate in women with unexplained infertility undergoing ICSI cycles using the long ovarian hyperstimulation protocol over the study period.   
Methodology: This randomized, controlled, double-blinded study was conducted at the ART unit of Ain Shams University Maternity Hospital (ASUMH) from July 2020 till June 2021.It included 182 women, all of whom are suffering from unexplained infertility and underwent ICSI using the long protocol. Patients were randomly assigned into two groups: Group A (control): which consisted of patients who received vaginal progesterone supplementation (400mg twice a day), and Group   B (study-estradiol group):2 mg of estradiol valerate were initiated orally along with progesterone, starting on the day of oocyte retrieval and continued until the end of first trimester. Antenatal follow-up: Patients with clinical conception did their antenatal care in the Ain Shams University Maternity Hospital outpatient clinic with follow-up of their outcome using a phone number.  
Results: Regarding main outcome measures, statistical analysis of current results showed that the biochemical, clinical pregnancy, and live birth rates were all comparable in both groups. In group A, 34 (37.4%) had positive biochemical and clinical pregnancy compared with 40 (44.0%) patients in group B (p-value = 0.365). Twenty-six (28.6%) patients in Group A had live birth compared with 29 (31.9%) patients in Group B (p-value = 0.628). There was no statistically significant difference between both groups as regards the rate of twin pregnancy or CS delivery (p-value >0.999 and 0.628, respectively).  
Conclusion: In women with unexplained infertility undergoing long protocol in assisted reproduction cycles, there were no significant differences between the relative effectiveness and safety of administering progesterone versus progesterone combined with estrogen for luteal phase support regarding biochemical, clinical pregnancy and live birth rates.