External validation of a time-lapse prediction model.

OBJECTIVE To study the performance of a previously published implantation prediction model based on morphokinetics in a different setting, in an unselected population and with various embryo transfer strategies. DESIGN Retrospective monocentric study. SETTING University-based assisted reproduction technology (ART) center. PATIENT(S) 450 unselected couples undergoing intracytoplasmic sperm injection (ICSI) cycle with embryo culture in the EmbryoScope (Unisense Fertilitech), corresponding to 528 embryos with known implantation. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Implantation rates (IR) in embryo categories defined by the model in the overall population and in subgroups according to the day of embryo transfer. RESULT(S) The distribution of IR among detailed morphokinetic categories in the overall population and in subgroups according to the day of embryo transfer was more heterogeneous than expected according to the published model. The distribution corresponded better to the original when a simplified version of the model was used, although it worked better in the cleavage-stage group than in the blastocyst-stage group. CONCLUSION(S) This study was unsuccessful in replicating the sensitivity of the previously published model for predicting implantation rate of embryos ranked according to morphokinetic categories. Further work is required to assess the utility of the model for embryo selection. Each team using time-lapse technology should build a center-specific prediction model based on its own data and transfer policy.

[1]  Patrick Bossuyt,et al.  Selection of embryos for transfer in IVF: ranking embryos based on their implantation potential using morphological scoring. , 2014, Reproductive biomedicine online.

[2]  U. Kesmodel,et al.  Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study. , 2013, Human reproduction.

[3]  T. Baer,et al.  Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage , 2010, Nature Biotechnology.

[4]  M. Meseguer,et al.  The use of morphokinetics as a predictor of embryo implantation. , 2011, Human reproduction.

[5]  V. Goossens,et al.  Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. , 2008, Human reproduction.

[6]  María Cruz,et al.  Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality. , 2012, Reproductive biomedicine online.

[7]  S. Ziebe,et al.  Association between blastocyst morphology and outcome of single-blastocyst transfer. , 2013, Reproductive biomedicine online.

[8]  K. Kirkegaard,et al.  Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. , 2013, Fertility and sterility.

[9]  Y Vergouwe,et al.  Comparison of two models predicting IVF success; the effect of time trends on model performance. , 2014, Human reproduction.

[10]  Limitations of a time-lapse blastocyst prediction model: a large multicentre outcome analysis. , 2014, Reproductive biomedicine online.

[11]  C. Racowsky,et al.  Reply: Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. , 2014, Human reproduction update.

[12]  Hans Jakob Ingerslev,et al.  Time-lapse monitoring as a tool for clinical embryo assessment. , 2012, Human reproduction.

[13]  Elena De Ponti,et al.  Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. , 2012, Reproductive biomedicine online.

[14]  Marcos Meseguer,et al.  Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. , 2012, Fertility and sterility.

[15]  A. Revelli,et al.  Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval. , 2007, Human reproduction.

[16]  M. Bahçeci,et al.  Time-lapse evaluation of human embryo development in single versus sequential culture media—a sibling oocyte study , 2012, Journal of Assisted Reproduction and Genetics.

[17]  Patrick M M Bossuyt,et al.  Prediction models in reproductive medicine: a critical appraisal. , 2009, Human reproduction update.

[18]  C. Racowsky,et al.  National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate. , 2011, Fertility and sterility.

[19]  Marcos Meseguer,et al.  Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. , 2014, Fertility and sterility.

[20]  V. Goossens,et al.  Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†. , 2014, Human reproduction.

[21]  G. Collins,et al.  External validation of multivariable prediction models: a systematic review of methodological conduct and reporting , 2014, BMC Medical Research Methodology.

[22]  L. Ohno-Machado,et al.  Is there an advantage in scoring early embryos on more than one day? , 2009, Human reproduction.

[23]  D. Royère,et al.  Does early morphology provide additional selection power to blastocyst selection for transfer? , 2010, Reproductive biomedicine online.

[24]  B Giraudeau,et al.  Limited value of morphological assessment at days 1 and 2 to predict blastocyst development potential: a prospective study based on 4042 embryos. , 2007, Human reproduction.

[25]  M. Meseguer,et al.  The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[26]  Alice A. Chen,et al.  Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial. , 2013, Fertility and sterility.

[27]  M. Wikland,et al.  Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. , 2011, Human reproduction.

[28]  J D Fisch,et al.  The Graduated Embryo Score (GES) predicts blastocyst formation and pregnancy rate from cleavage-stage embryos. , 2001, Human reproduction.

[29]  D. Royère,et al.  Top quality embryos at day 2: a prerequisite for single blastocyst transfer? An observational cohort study in women under 36 , 2009, Journal of Assisted Reproduction and Genetics.

[30]  Christos Stylianou,et al.  Embryo morphology as a predictor of IVF success: An evaluation of the proposed UK ACE grading scheme for cleavage stage embryos , 2012, Human fertility.

[31]  P. Bossuyt,et al.  Templeton prediction model underestimates IVF success in an external validation. , 2011, Reproductive biomedicine online.

[32]  M. Meseguer,et al.  Type of culture media does not affect embryo kinetics: a time-lapse analysis of sibling oocytes. , 2013, Human reproduction.

[33]  D. De Neubourg,et al.  Calculating the implantation potential of day 3 embryos in women younger than 38 years of age: a new model. , 2001, Human reproduction.

[34]  Catherine Racowsky,et al.  Reply: Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. , 2014, Human reproduction update.