H Nadir Ciray1, Alison Campbell2, Inge Errebo Agerholm3, Jesús Aguilar4, Sandrine Chamayou5, Marga Esbert6, Shabana Sayed7. 1. Division of Reproduction and Early Development, Leeds Institute of Cardiovascular and Metabolic Medicine, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK h.n.ciray@leeds.ac.uk. 2. CARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham NG8 6PZ, UK. 3. The Fertility Clinic, Hospitalsenheden Horsens, Sundvej 30, Horsens 8700, Denmark. 4. IVI VIGO, Plaza Francisco Fernández de Riego 7, 36203 Vigo, Pontevedra, Spain. 5. Unità di Medicina della Riproduzione-Fondazione HERA, Via Barriera del Bosco n.51-53, 95030 Sant'Agata Li Battiati, Italy. 6. IVI BARCELONA, Ronda Gral. Mitre, 17, 08017 Barcelona, Spain. 7. Klinikk Hausken, Karmsundgata 59, 5531 Haugesund, Norway.
Abstract
STUDY QUESTION: Can the approach to, and terminology for, time-lapse monitoring of preimplantation embryo development be uniformly defined in order to improve the utilization and impact of this novel technology? SUMMARY ANSWER: The adoption of the proposed guidelines for defining annotation practice and universal nomenclature would help unify time-lapse monitoring practice, allow validation of published embryo selection algorithms and facilitate progress in this field. WHAT IS KNOWN ALREADY: An increasing quantity of publications and communications relating to time-lapse imaging of in vitro embryo development have demonstrated the added clinical value of morphokinetic data for embryo selection. Several articles have identified similar embryo selection or de-selection variables but have termed them differently. An evidence-based consensus document exists for static embryo grading and selection but, to date, no such reference document is available for time-lapse methodology or dynamic embryo grading and selection. STUDY DESIGN, SIZE AND DURATION: A series of meetings were held between September 2011 and May 2014 involving time-lapse users from seven different European centres. The group reached consensus on commonly identified and novel time-lapse variables. PARTICIPANTS/MATERIALS, SETTING, METHODS: Definitions, calculated variables and additional annotations for the dynamic monitoring of human preimplantation development were all documented. MAIN RESULTS AND THE ROLE OF CHANCE: Guidelines are proposed for a standard methodology and terminology for the of use time-lapse monitoring of preimplantation embryo development. LIMITATIONS, REASONS FOR CAUTION: The time-lapse variables considered by this group may not be exhaustive. This is a relatively new clinical technology and it is likely that new variables will be introduced in time, requiring revised guidelines. A different group of users from those participating in this process may have yielded subtly different terms or definitions for some of the morphokinetic variables discussed. Due to the technical processes involved in time-lapse monitoring, and acquisition of images at varied intervals through limited focal planes, this technology does not currently allow continuous monitoring such that the entire process of preimplantation embryo development may be visualized. WIDER IMPLICATIONS: This is the first time that a group of experienced time-lapse users has systematically evaluated current evidence and theoretical aspects of morphokinetic monitoring to propose guidelines for a standard methodology and terminology of its use and study, and its clinical application in IVF. The adoption of a more uniform approach to the terminology and definitions of morphokinetic variables within this developing field of clinical embryology would allow practitioners to benefit from improved interpretation of data and the sharing of best practice and experience, which could impact positively and more swiftly on patient treatment outcome. STUDY FUNDING/COMPETING INTERESTS: There was no specific funding for the preparation of these proposed guidelines. Meetings were held opportunistically during scientific conferences and using online communication tools. H.N.C. is a scientific consultant for ESCO, supplier of Miri TL. I.E.A. is a minor shareholder in Unisense Fertilitech, supplier of the EmbryoScope. Full disclosures of all participants are presented herein. The remaining authors have no conflict of interest.
STUDY QUESTION: Can the approach to, and terminology for, time-lapse monitoring of preimplantation embryo development be uniformly defined in order to improve the utilization and impact of this novel technology? SUMMARY ANSWER: The adoption of the proposed guidelines for defining annotation practice and universal nomenclature would help unify time-lapse monitoring practice, allow validation of published embryo selection algorithms and facilitate progress in this field. WHAT IS KNOWN ALREADY: An increasing quantity of publications and communications relating to time-lapse imaging of in vitro embryo development have demonstrated the added clinical value of morphokinetic data for embryo selection. Several articles have identified similar embryo selection or de-selection variables but have termed them differently. An evidence-based consensus document exists for static embryo grading and selection but, to date, no such reference document is available for time-lapse methodology or dynamic embryo grading and selection. STUDY DESIGN, SIZE AND DURATION: A series of meetings were held between September 2011 and May 2014 involving time-lapse users from seven different European centres. The group reached consensus on commonly identified and novel time-lapse variables. PARTICIPANTS/MATERIALS, SETTING, METHODS: Definitions, calculated variables and additional annotations for the dynamic monitoring of human preimplantation development were all documented. MAIN RESULTS AND THE ROLE OF CHANCE: Guidelines are proposed for a standard methodology and terminology for the of use time-lapse monitoring of preimplantation embryo development. LIMITATIONS, REASONS FOR CAUTION: The time-lapse variables considered by this group may not be exhaustive. This is a relatively new clinical technology and it is likely that new variables will be introduced in time, requiring revised guidelines. A different group of users from those participating in this process may have yielded subtly different terms or definitions for some of the morphokinetic variables discussed. Due to the technical processes involved in time-lapse monitoring, and acquisition of images at varied intervals through limited focal planes, this technology does not currently allow continuous monitoring such that the entire process of preimplantation embryo development may be visualized. WIDER IMPLICATIONS: This is the first time that a group of experienced time-lapse users has systematically evaluated current evidence and theoretical aspects of morphokinetic monitoring to propose guidelines for a standard methodology and terminology of its use and study, and its clinical application in IVF. The adoption of a more uniform approach to the terminology and definitions of morphokinetic variables within this developing field of clinical embryology would allow practitioners to benefit from improved interpretation of data and the sharing of best practice and experience, which could impact positively and more swiftly on patient treatment outcome. STUDY FUNDING/COMPETING INTERESTS: There was no specific funding for the preparation of these proposed guidelines. Meetings were held opportunistically during scientific conferences and using online communication tools. H.N.C. is a scientific consultant for ESCO, supplier of Miri TL. I.E.A. is a minor shareholder in Unisense Fertilitech, supplier of the EmbryoScope. Full disclosures of all participants are presented herein. The remaining authors have no conflict of interest.