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      Morphology vs morphokinetics: a retrospective comparison of inter-observer and intra-observer agreement between embryologists on blastocysts with known implantation outcome

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          Abstract

          Objective

          Our primary aim was to compare the morphology and morphokinetics on inter- and intra-observer agreement for blastocyst with known implantation outcome. Our secondary aim was to validate the morphokinetic parameters' ability to predict pregnancy using a previous published selection algorithm, and to compare this to standard morphology assessments.

          Methods

          Two embryologists made independent blinded annotations on two occasions using time-lapse images and morphology evaluations using the Gardner Schoolcraft criteria of 99 blastocysts with known implantation outcome. Inter- and intra-observer agreement was calculated and compared using the two methods. The embryos were grouped based on their morphological score, and on their morphokinetic class using a previous published selection algorithm. The implantation rates for each group was calculated and compared.

          Results

          There was moderate agreement for morphology, with agreement on the same embryo score in 55 of 99 cases. The highest agreement rate was found for expansion grade, followed by trophectoderm and inner cell mass. Correlation with pregnancy was inconclusive. For morphokinetics, almost perfect agreement was found for early and late embryo development events, and strong agreement for day-2 and day-3 events. When applying the selection algorithm, the embryo distributions were uneven, and correlation to pregnancy was inconclusive.

          Conclusions

          Time-lapse annotation is consistent and accurate, but our external validation of a previously published selection algorithm was unsuccessful.

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          Most cited references30

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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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              Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study.

              To quantify the effect on reproductive outcome of culturing and selecting embryos using a novel time-lapse monitoring system (TMS). Retrospective observational cohort study. University-affiliated private center. Donation and autologous intracytoplasmic sperm injection (ICSI) cycles from ten IVF clinics using similar procedures, cultured in TMS (n = 1,390) or in a standard incubator (SI; n = 5,915). None. Clinical pregnancy rate confirmed by ultrasound in week 7. A logistic regression analysis, which included all significant confounding factors, was used to evaluate the effect of culturing and selecting embryos with the use of TMS. Comparing clinical pregnancy rates per oocyte retrieval with TMS and SI treatments gave a crude effect of odds ratio [OR] 1.190 (95% confidence interval [CI] 1.058-1.337). Oocyte source, maternal age, day of transfer, and number of retrieved oocytes were identified as significant confounding factors. After accounting for confounding factors, the effect of TMS culture was OR 1.201 (95% CI 1.059-1.363). Limiting analysis to treatments with embryo transfer and including number of transferred embryos as a confounding factor likewise gave a significant effect of TMS with OR 1.157 (95% CI 1.018-1.315). Analysis of retrospective data indicated that culturing and selecting embryos by TMS significantly improved the relative probability of clinical pregnancy (+20.1% per oocyte retrieval, +15.7% per embryo transfer). The elevated clinical pregnancy rate was attributed to a combination of stable culture conditions and the use of morphokinetic parameters for embryo selection. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                JBRA Assist Reprod
                JBRA Assist Reprod
                jbra
                JBRA Assisted Reproduction
                Brazilian Society of Assisted Reproduction
                1517-5693
                1518-0557
                Jul-Sep 2018
                Jul-Sep 2018
                : 22
                : 3
                : 228-237
                Affiliations
                [1 ]Örebro University Hospital. Department of Laboratory Medicine. Örebro, Sweden
                [2 ]Örebro University Hospital. Fertility Unit, Department of Women Health. Örebro, Sweden
                Author notes
                Corresponding Author: Emma Adolfsson, Örebro University Hospital, Department of Laboratory Medicine, Örebro, Sweden. Email: emma.adolfsson@ 123456regionorebrolan.se
                Article
                10.5935/1518-0557.20180042
                6106622
                29912521
                38e410b1-5873-4492-9e63-abc251d7212b

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 September 2017
                : 15 May 2018
                Categories
                Original Article

                ivf,embryo development,time lapse,morphokinetics,observer agreement

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