Biomarkers identified with time-lapse imaging: discovery, validation, and practical application.

"Time-lapse markers," which are defined by time-lapse imaging and correlated with clinical outcomes, may provide embryologists with new opportunities for improving embryo selection. This article provides an overview of noninvasive biomarkers defined by time-lapse imaging studies. In addition to comprehensively reviewing the discovery of each time-lapse marker, it focuses on the criteria necessary for their successful integration into clinical practice, including [1] statistical and biological significance, [2] validation through prospective clinical studies, and [3] development of reliable technology to measure and quantify the time-lapse marker. Because manual analysis of time-lapse images is labor intensive and limits the practical use of the image data in the clinic, automated image analysis software platforms may contribute substantially to improvements in embryo selection accuracy. Ultimately, time-lapse markers that are based on a foundation of basic research, validated through prospective clinical studies, and enabled by a reliable quantification technology may improve IVF success rates, encourage broader adoption of single-embryo transfer, and reduce the risks associated with multiple gestation pregnancies.

[1]  Farshid Moussavi,et al.  Dynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage , 2012, Nature Communications.

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

[3]  Michael P. Diamond,et al.  The clinical need for a method of identification of embryos destined to become a blastocyst in assisted reproductive technology cycles , 2012, Journal of Assisted Reproduction and Genetics.

[4]  N. Johnson,et al.  Cleavage stage versus blastocyst stage embryo transfer in assisted conception. , 2002, The Cochrane database of systematic reviews.

[5]  Ying-pu Sun,et al.  Effect of culture medium volume and embryo density on early mouse embryonic development: Tracking the development of the individual embryo , 2012, Journal of Assisted Reproduction and Genetics.

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

[7]  G. Vajta,et al.  Pregnancy achieved by transfer of a single blastocyst selected by time-lapse monitoring. , 2010, Reproductive biomedicine online.

[8]  J. Harper,et al.  The clinical benefit and safety of current and future assisted reproductive technology. , 2012, Reproductive biomedicine online.

[9]  K. Barnhart,et al.  Extended Embryo Culture and an Increased Risk of Preterm Delivery , 2012, Obstetrics and gynecology.

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

[11]  Lars D. M. Ottosen,et al.  Light exposure of the ovum and preimplantation embryo during ART procedures , 2007, Journal of Assisted Reproduction and Genetics.

[12]  B. Källén,et al.  Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? , 2010, Fertility and sterility.

[13]  R. Edwards,et al.  Internalization of cellular fragments in a human embryo: time-lapse recordings. , 2002, Reproductive biomedicine online.

[14]  W. Krause,et al.  Quality assessment of computer‐assisted semen analysis (CASA) in the andrology laboratory , 1999, Andrologia.

[15]  M. Zernicka-Goetz,et al.  Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability , 2011, Nature communications.

[16]  Gaudenz Danuser,et al.  Computer Vision in Cell Biology , 2011, Cell.

[17]  W. Holt,et al.  Use of computer-assisted sperm motility assessment and multivariate pattern analysis to characterize ejaculate quality in Mohor gazelles (Gazella dama mhorr): effects of body weight, electroejaculation technique and short-term semen storage. , 2001, Reproduction.

[18]  G. Vajta,et al.  New method for culture of zona‐included or zona‐free embryos: The Well of the Well (WOW) system , 2000, Molecular reproduction and development.

[19]  A L Mikkelsen,et al.  The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture. , 2012, Human reproduction.

[20]  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.

[21]  N. Amso,et al.  Phospholipase C-ζ-induced Ca2+ oscillations cause coincident cytoplasmic movements in human oocytes that failed to fertilize after intracytoplasmic sperm injection , 2012, Fertility and sterility.

[22]  D Hlinka,et al.  Time-lapse cleavage rating predicts human embryo viability. , 2012, Physiological research.

[23]  H. Tournaye,et al.  Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study. , 2005, Human reproduction.

[24]  J. Harper,et al.  When and how should new technology be introduced into the IVF laboratory? , 2012, Human reproduction.

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

[26]  Michel Camus,et al.  In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos. , 2006, The New England journal of medicine.

[27]  Yasuyuki Mio,et al.  Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. , 2008, American journal of obstetrics and gynecology.

[28]  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.

[29]  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.

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

[31]  R. Pedersen,et al.  Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development. , 2001, Development.

[32]  M. Meseguer,et al.  Limited implantation success of direct-cleaved human zygotes: a time-lapse study. , 2012, Fertility and sterility.

[33]  K. Barnhart,et al.  Biomarkers in reproductive medicine: the promise, and can it be fulfilled? , 2013, Fertility and sterility.

[34]  B. Dziura,et al.  Performance of an Imaging System vs. Manual Screening in the Detection of Squamous Intraepithelial Lesions of the Uterine Cervix , 2006, Acta Cytologica.

[35]  Farshid Moussavi,et al.  Development and validation of an automated computer vision algorithm for real-time embryo viability prediction , 2012 .

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

[37]  Yoshiharu Morimoto,et al.  Selection of high-potential embryos by culture in poly(dimethylsiloxane) microwells and time-lapse imaging. , 2012, Fertility and sterility.

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

[39]  Jacob F Mayer,et al.  Interobserver and intraobserver variation in day 3 embryo grading. , 2006, Fertility and sterility.

[40]  Richard L Lozano,et al.  Comparison of computer-assisted and manual screening of cervical cytology. , 2007, Gynecologic oncology.

[41]  E. Coonen,et al.  Elective single embryo transfer (eSET) policy in the first three IVF/ICSI treatment cycles. , 2005, Human reproduction.