Laura Rienzi1, Danilo Cimadomo2, Arantxa Delgado3, Maria Giulia Minasi4, Gemma Fabozzi2, Raquel Del Gallego3, Marta Stoppa2, Jose Bellver3, Adriano Giancani5, Marga Esbert6, Antonio Capalbo7, Jose Remohì3, Ermanno Greco4, Filippo Maria Ubaldi2, Marcos Meseguer3. 1. Clinica Valle Giulia, G.EN.E.R.A. Centers for Reproductive Medicine, Rome, Italy. Electronic address: rienzi@generaroma.it. 2. Clinica Valle Giulia, G.EN.E.R.A. Centers for Reproductive Medicine, Rome, Italy. 3. IVI-RMA, Valencia, Spain. 4. Center for Reproductive Medicine, European Hospital, Rome, Italy. 5. Clinica Valle Giulia, G.EN.E.R.A. Centers for Reproductive Medicine, Rome, Italy; DAHFMO, Unit of Histology and Medical Embryology, "Sapienza" University of Rome, Italy. 6. IVI-RMA, Barcelona, Spain. 7. DAHFMO, Unit of Histology and Medical Embryology, "Sapienza" University of Rome, Italy; Igenomix, Marostica, Italy.
Abstract
OBJECTIVE: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET). DESIGN: Observational cohort study conducted in two phases: training and validation. SETTING: Private in vitro fertilization centers. PATIENT(S): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively. INTERVENTION(S): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set. MAIN OUTCOME MEASURE(S): Live births per SET. RESULT(S): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51). CONCLUSION(S): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.
OBJECTIVE: To investigate whether the morphodynamic characterization of a euploid blastocyst's development allows a higher prediction of a live birth after single-embryo-transfer (SET). DESIGN: Observational cohort study conducted in two phases: training and validation. SETTING: Private in vitro fertilization centers. PATIENT(S): Euploid blastocysts: 511 and 319 first vitrified-warmed SETs from 868 and 546 patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) in the training and validation phase, respectively. INTERVENTION(S): Data collected from time of polar body extrusion to time of starting blastulation, and trophectoderm and inner-cell-mass static morphology in all embryos cultured in a specific time-lapse incubator with a continuous medium. Logistic regressions conducted to outline the variables showing a statistically significant association with live birth. In the validation phase, these variables were tested in an independent data set. MAIN OUTCOME MEASURE(S): Live births per SET. RESULT(S): The average live birth rate (LBR) in the training set was 40% (N = 207/511). Only time of morulation (tM) and trophectoderm quality were outlined as putative predictors of live birth at two IVF centers. In the validation set, the euploid blastocysts characterized by tM <80 hours and high-quality trophectoderm resulted in a LBR of 55.2% (n = 37/67), while those with tM ≥ 80 hours and a low-quality trophectoderm resulted in a LBR of 25.5% (N = 13/51). CONCLUSION(S): Time of morulation and trophectoderm quality are better predictors of a euploid blastocyst's reproductive competence. Our evidence was reproducible across different centers under specific culture conditions. These data support the crucial role of morulation for embryo development, a stage that involves massive morphologic, cellular, and molecular changes and deserves more investigation.