Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate

STUDY QUESTION: How does the duration of estrogen (E2) treatment prior to frozen-blastocyst transfers affect the live birth rate (LBR)? SUMMARY ANSWER: Prolonged E2 exposure as part of artificial endometrial preparation (AEP) significantly decreases the LBR after autologous frozen-thawed blastocyst transfer. WHAT IS KNOWN ALREADY: One effective method for endometrial preparation prior to frozen embryo transfer is AEP, a sequential regimen with E2 and progesterone, which aims to mimic the endocrine exposure of the endometrium in a normal cycle. Nevertheless, the optimal duration of E2 administration prior to transfer remains unknown. STUDY DESIGN, SIZE, DURATION: An observational cohort study was conducted in a tertiary care university hospital between 01/07/ 2012 and 31/12/2015. The main inclusion criteria was having a single frozen-thawed blastocyst transfer with an AEP using exogenous E2. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1377 frozen-thawed blastocyst transfers were assigned to four groups according to the duration of the E2 administration prior to the embryo transfers. These comprised a '<= 21 days' group (n = 330), a '22-28 days' group (n = 665), a '29-35 days' group (n = 289) and a '36-48 days' group (n = 93). The '<= 21 days' group' was taken as the reference group. The main measured outcome was the LBR following frozen-thawed blastocyst transfers. Statistical analysis was conducted using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: LBR significantly decreased when the E2 exposure prior to the frozen-thawed blastocyst transfer exceeded 28 days: OR = 0.66; 95% CI [0.46-0.95]; P = 0.026 and OR = 0.49 [0.27-0.89]; P = 0.018, respectively, for the '29 to 35 days' group and for the '36 to 48 days' group compared to the reference group. Early pregnancy loss rates significantly increased when the E2 exposure lasted more than 35 days prior to the frozen-thawed blastocyst transfer (OR = 2.37 [1.12-5.05]; P = 0.025 vs. the reference group). After multivariate logistic regression, E2 exposure lasting more than 28 days prior to the frozen-thawed blastocyst transfer was associated with a decrease in the LBR, for the '29-35 days' group (OR = 0.65; [0.45-0.95]; P = 0.044) as for the '36-48 days' group (OR = 0.49; [0.26-0.92]; P = 0.035), vs. the reference group. LIMITATIONS, REASONS FOR CAUTION: One limitation is linked to the observational design of this study. WIDER IMPLICATIONS OF THE FINDINGS: In order to give patients the best chance to obtain a live birth after frozen-thawed blastocyst transfer, the length of E2 exposure prior to the frozen-blastocyst transfer should not exceed 28 days. This study provides new insight in regard to endometrial preparation using AEP prior to frozen-blastocyst transfer.