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      Good practice recommendations for the use of time-lapse technology

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          Abstract

          STUDY QUESTION

          What recommendations can be provided on the approach to and use of time-lapse technology (TLT) in an IVF laboratory?

          SUMMARY ANSWER

          The present ESHRE document provides 11 recommendations on how to introduce TLT in the IVF laboratory.

          WHAT IS KNOWN ALREADY

          Studies have been published on the use of TLT in clinical embryology. However, a systematic assessment of how to approach and introduce this technology is currently missing.

          STUDY DESIGN, SIZE, DURATION

          A working group of members of the Steering Committee of the ESHRE Special Interest Group in Embryology and selected ESHRE members was formed in order to write recommendations on the practical aspects of TLT for the IVF laboratory.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          The working group included 11 members of different nationalities with internationally recognized experience in clinical embryology and basic science embryology, in addition to TLT. This document is developed according to the manual for development of ESHRE recommendations for good practice. Where possible, the statements are supported by studies retrieved from a PUBMED literature search on ‘time-lapse’ and ART.

          MAIN RESULTS AND THE ROLE OF CHANCE

          A clear clinical benefit of the use of TLT, i.e. an increase in IVF success rates, remains to be proven. Meanwhile, TLT systems are being introduced in IVF laboratories. The working group listed 11 recommendations on what to do before introducing TLT in the lab. These statements include an assessment of the pros and cons of acquiring a TLT system, selection of relevant morphokinetic parameters, selection of an appropriate TLT system with technical and customer support, development of an internal checklist and education of staff. All these aspects are explained further here, based on the current literature and expert opinion.

          LIMITATIONS, REASONS FOR CAUTION

          Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. The paper provides technical advice, but leaves any decision on whether or not to use TLT to the individual centres.

          WIDER IMPLICATIONS OF THE FINDINGS

          This document is expected to have a significant impact on future developments of clinical embryology, considering the increasing role and impact of TLT.

          STUDY FUNDING/COMPETING INTEREST(S)

          The meetings of the working group were funded by ESHRE. S.A. declares participation in the Nordic Embryology Academic Team with meetings sponsored by Gedeon Richter. T.E. declares to have organized workshops for Esco and receiving consulting fees from Ferring and Gynemed and speakers’ fees from Esco and honorarium from Merck and MSD. T.F. received consulting fees from Vitrolife and Laboratoires Genévrier, speakers’ fees from Merck Serono, Gedeon Richter, MSD and Ferring and research grants from Gedeon Richter and MSD. M.M. received sponsorship from Merck. M.M.E. received speakers’ fees from Merck, Ferring and MSD. R.S. received a research grant from ESHRE. G.C. received speakers’ fees from IBSA and Excemed. The other authors declare that they have no conflict of interest.

          TRIAL REGISTRATION NUMBER

          N/A.

          DISCLAIMER

          This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation .

          ESHRE’s GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type .

          Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring of any of the included technologies by ESHRE .

          ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.

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          Most cited references197

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          The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

          Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Background presentations about current practice were given. The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.
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            Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage.

            We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.
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              Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes.

              Aneuploidy in human eggs is the leading cause of pregnancy loss and several genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg's progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. We analyzed meiosis in more than 100 live human oocytes and identified an error-prone chromosome-mediated spindle assembly mechanism as a major contributor to chromosome segregation defects. Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours. This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.
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                Author and article information

                Journal
                Hum Reprod Open
                Hum Reprod Open
                hropen
                Human Reproduction Open
                Oxford University Press
                2399-3529
                2020
                19 March 2020
                19 March 2020
                : 2020
                : 2
                : hoaa008
                Affiliations
                [1 ] Livio, Stockholm , Sweden
                [2 ] Department of Gynecology, Obstetrics, and Gynecological Endocrinology , Kepler Universitätsklinikum, Linz, Austria
                [3 ] Médecine de la Reproduction, CHU de Nantes , Nantes, France
                [4 ] Center for Reproductive Medicine , UZ Brussel, Brussels, Belgium
                [5 ] Department of Reproductive Medicine and Gynecologic Endocrinology , Univerzitetni klinicni center Maribor, Maribor, Slovenia
                [6 ] European Society of Human Reproduction and Embryology , Grimbergen, Belgium
                [7 ] CEMEARE, Lisbon , Portugal
                [8 ] IVF Laboratory, Instituto Valenciano de Infertilidad , Valencia, Spain
                [9 ] Médecine et Biologie de la Reproduction , Hopital Saint Joseph, Marseille, France
                [10 ] Assisted Reproduction Unit , Eugonia, Athens, Greece
                [11 ] Centre for Atherothrombosis and Metabolic Disease , Hull York Medical School, University of Hull, Hull, UK
                [12 ] 9.baby Family and Fertility Center , Bologna, Italy
                Author notes
                Correspondence address. 9.baby Family and Fertility Center, via Dante 15, 40125 Bologna, Italy. E-mail: giovanni.coticchio@ 123456gmail.com https://orcid.org/0000-0003-1635-9205
                Author information
                https://orcid.org/0000-0003-1635-9205
                Article
                hoaa008
                10.1093/hropen/hoaa008
                7081060
                32206731
                18b1cf4d-84f3-43a1-992a-cdc3b8f56ebc
                © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 5 December 2019
                : 5 December 2019
                : 29 January 2020
                : 29 January 2020
                Page count
                Pages: 26
                Funding
                Funded by: European Society of Human Reproduction and Embryology;
                Categories
                ESHRE Pages

                time-lapse technology,eshre,guideline,embryology,embryo selection,morphokinetics,art

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