title: Morphokinetic Evaluation of Embryo Development in a Mouse Model: Functional and Molecular Correlates.
abstract: Although time-lapse analysis of early embryo cleavage parameters (morphokinetics) predicts blastocyst development, it has not been definitively linked to establishing pregnancy and live birth. For example, a direct comparison of the developmental potential of embryos with optimal kinetic parameters compared to suboptimal kinetics has not been performed with human embryos. To ascertain whether such a linkage exists, we developed a mouse model of morphokinetic analysis of early embryo cleavage using time-lapse microscopy to predict blastocyst formation and tested whether cleavage parameters predict pregnancy outcome by transferring morphokinetically optimal and suboptimal embryos into a single host. Using classification and regression trees, we established that the timing of the second and third mitotic divisions (division from two to three and three to four cells, respectively) predicts blastocyst development in the mouse. Using this prediction model, we found that the incidence of sustained implantation at mid-gestation was significantly higher for the optimal compared to suboptimal embryos. In addition, the incidence of resorption among implanted embryos was significantly higher in the suboptimal compared to the optimal group. Transcript profiling of optimal and suboptimal embryos revealed minimal differences between the two groups, suggesting that time-lapse imaging of early embryo cleavage events provides additional information regarding developmental competence apart from gene expression.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Rachel
authors.initials: R
authors.lastname: Weinerman
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.affiliation: Division of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Teri S
authors.initials: TS
authors.lastname: Ord
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
authors.affiliation: Division of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
authors.affiliation: Division of Reproductive Endocrinology and Infertility, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Monica
authors.initials: M
authors.lastname: Mainigi
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002970:Cleavage Stage, Ovum; D047108:Embryonic Development; D005260:Female; D051379:Mice; D023421:Models, Animal; D011247:Pregnancy; D059008:Time-Lapse Imaging
keywords: blastocyst; embryo development; morphokinetics; pregnancy; time lapse