Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials

Objective The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF). Methods Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups. Results Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94–1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06–1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80–1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review. Conclusions Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.

[1]  E. Çalışkan,et al.  Reproducibility of a time-lapse embryo selection model based on morphokinetic data in a sequential culture media setting. , 2014, Journal of the Turkish German Gynecological Association.

[2]  Markus Montag,et al.  New approaches to embryo selection. , 2013, Reproductive biomedicine online.

[3]  J. Lemmen,et al.  Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI-fertilized oocytes. , 2008, Reproductive biomedicine online.

[4]  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.

[5]  R. Milewski,et al.  Do morphokinetic data sets inform pregnancy potential? , 2016, Journal of Assisted Reproduction and Genetics.

[6]  C. Bergh,et al.  No benefit of culturing embryos in a closed system compared with a conventional incubator in terms of number of good quality embryos: results from an RCT. , 2015, Human reproduction.

[7]  Shehua Shen,et al.  Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study. , 2014, Reproductive biomedicine online.

[8]  Samantha Duffy,et al.  Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. , 2013, Reproductive biomedicine online.

[9]  M. Meseguer,et al.  The use of morphokinetics as a predictor of  implantation: a multicentric study to define and validate an algorithm for embryo selection. , 2015, Human reproduction.

[10]  U. Kesmodel,et al.  A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator , 2012, Journal of Assisted Reproduction and Genetics.

[11]  Thomas Fréour,et al.  External validation of a time-lapse prediction model. , 2015, Fertility and sterility.

[12]  Catherine Racowsky,et al.  A critical appraisal of time-lapse imaging for embryo selection: where are we and where do we need to go? , 2015, Journal of Assisted Reproduction and Genetics.

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

[14]  Roy Homburg,et al.  Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms. , 2017, Fertility and sterility.

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

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

[17]  M. Meseguer,et al.  Embryo quality, blastocyst and ongoing pregnancy rates in oocyte donation patients whose embryos were monitored by time-lapse imaging , 2011, Journal of Assisted Reproduction and Genetics.

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

[19]  D. Payne,et al.  Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. , 1997, Human reproduction.

[20]  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.

[21]  Gerald Gartlehner,et al.  [GRADE guidelines: 1. Introduction - GRADE evidence profiles and summary of findings tables]. , 2012, Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen.

[22]  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.

[23]  M. Erlandsen,et al.  Timing of human preimplantation embryonic development is confounded by embryo origin , 2015, Human reproduction.

[24]  Waldemar Kuczyński,et al.  A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development , 2015, Journal of Assisted Reproduction and Genetics.

[25]  G. Adamson,et al.  Improved implantation rates of day 3 embryo transfers with the use of an automated time-lapse-enabled test to aid in embryo selection. , 2016, Fertility and sterility.

[26]  Samantha Duffy,et al.  Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. , 2013, Reproductive biomedicine online.

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

[28]  Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScopeTM) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study , 2016, Reproductive Biology and Endocrinology.

[29]  A. Hellani,et al.  Morphokinetic analysis of cleavage stage embryos and its relationship to aneuploidy in a retrospective time-lapse imaging study , 2014, Journal of Assisted Reproduction and Genetics.

[30]  Peter Roberts,et al.  Time-lapse deselection model for human day 3 in vitro fertilization embryos: the combination of qualitative and quantitative measures of embryo growth. , 2016, Fertility and sterility.

[31]  N. Raine-Fenning,et al.  Time‐lapse embryo imaging for improving reproductive outcomes: systematic review and meta‐analysis , 2014, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[32]  Akira Iwase,et al.  Evaluation of the safety of time-lapse observations for human embryos , 2010, Journal of Assisted Reproduction and Genetics.

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

[34]  Cindy Farquhar,et al.  Time-lapse systems for embryo incubation and assessment in assisted reproduction. , 2018, The Cochrane database of systematic reviews.

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

[36]  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.

[37]  Andreas Makris,et al.  Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study , 2015, Journal of Assisted Reproduction and Genetics.

[38]  D. C. Kieslinger,et al.  Embryo selection using time-lapse analysis (Early Embryo Viability Assessment) in conjunction with standard morphology: a prospective two-center pilot study. , 2016, Human reproduction.

[39]  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.

[40]  M. Vera-Rodríguez,et al.  Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis , 2015, Nature Communications.

[41]  Yuzhu Peng,et al.  Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. , 2010, Reproductive biomedicine online.

[42]  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.

[43]  K. Kirkegaard,et al.  Hatching of in vitro fertilized human embryos is influenced by fertilization method. , 2013, Fertility and sterility.

[44]  D. Barad,et al.  Is it time for a paradigm shift in understanding embryo selection? , 2015, Reproductive Biology and Endocrinology.

[45]  S. Chamayou,et al.  The use of morphokinetic parameters to select all embryos with full capacity to implant , 2013, Journal of Assisted Reproduction and Genetics.

[46]  Caroline Pirkevi,et al.  Comparison of Blastocyst Development and Cycle Outcome in Patients with eSET Using Either Conventional or Time Lapse Incubators. A Prospective Study of Good Prognosis Patients , 2012 .

[47]  Time-lapse embryo selection for single blastocyst transfer – results of a multicenter, prospective, randomized clinical trial , 2013 .

[48]  Nina Desai,et al.  Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. , 2016, Fertility and sterility.

[49]  M. Gissler,et al.  Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE. , 2013, Human reproduction.

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