Time-Lapse Imaging

延时成像
  • 文章类型: Systematic Review
    子宫内膜异位症已被证明与卵母细胞的发育和成熟有关。以及胚胎发育的异常,包括受精后的逮捕,体外受精(IVF)。延时监测(TLM)可以在IVF过程中对胚胎形态动力学进行连续和非侵入性监测,并且可能有助于评估子宫内膜异位症女性的胚胎。在这次审查中,对5项符合条件的研究进行了评估,以确定子宫内膜异位症患者在TLM下评估的胚胎形态动力学是否不同,并随后预测胚泡质量。植入和成功怀孕。研究表明,与对照组相比,子宫内膜异位症患者胚胎的形态动力学参数总体较差,与子宫内膜异位症的严重程度无关。具有最佳早期形态动力学参数的胚胎(t2,s2,t5,tSB,tEB)和晚期发育事件(压实,malulation,和囊胚形成)的着床率高于次优范围的着床率。然而,由于很少有研究主要是回顾性数据,这些发现的有效性及其在临床实践中的普遍性需要进一步评估.需要更大样本量的前瞻性研究来确定使用TLM进行子宫内膜异位症的胚胎选择是否可以改善妊娠和活产结局。
    Endometriosis has been shown to be associated with unfavorable development and maturation of oocytes, as well as aberrancies in embryonal development, including arrest after fertilization, following in vitro fertilization (IVF). Time-lapse monitoring (TLM) enables continuous and non-invasive monitoring of embryo morphokinetics during the IVF process and might be useful in the assessment of embryos from women with endometriosis. In this review, five eligible studies were evaluated to determine if embryo morphokinetics assessed under TLM differ in patients with endometriosis and subsequently predict blastocyst quality, implantation and success of pregnancy. The studies showed overall inferior morphokinetic parameters of embryos from endometriosis patients when compared to controls, independent of the severity of endometriosis. Embryos with optimal early morphokinetic parameters (t2, s2, t5, tSB, tEB) and late developmental events (compaction, morulation, and blastulation) had better implantation rates than those who had suboptimal ranges. However, due to few studies available with mostly retrospective data, the validity of these findings and their generalizability for clinical practice needs to be further assessed. Prospective studies with larger sample sizes are needed to determine whether using TLM for embryo selection in endometriosis improves pregnancy and live birth outcomes.
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  • 文章类型: Meta-Analysis
    目的:探讨延时监测(TLM)系统与常规形态学选择(CMS)相比,胚胎选择对体外受精/卵胞浆内单精子注射(IVF/ICSI)结局的影响。
    方法:我们搜索了PubMed,Ovid-Embase,和Cochrane库用于以下研究:在比较1中,在基于形态学的TLM培养箱中使用TLM图像进行胚胎选择,而在基于形态学的常规培养箱中使用CMS进行胚胎选择;在比较2中,使用基于形态动力学的TLM进行胚胎选择,而使用基于形态学的CMS进行胚胎选择。主要结果是活产率(LBR),持续妊娠率(OPR),临床妊娠率(CPR),和植入率(IR),次要结局是流产率(MR)。
    结果:共纳入14项随机对照试验。两者都基于形态学,TLM孵化器增加了IR(风险比[RR]:1.10;95%置信区间[CI]:1.01,1.18;I2=0%,中等质量的证据)与传统孵化器相比。低到中等质量的证据表明,TLM孵化器并没有改善LBR,OPR,CPR,和MR与传统孵化器相比。此外,低到中等质量的证据表明,使用基于形态动力学的TLM进行胚胎选择并不能改善LBR,OPR,CPR,IR,或MR与基于形态学的CMS相比。
    结论:低到中等质量的证据表明,TLM孵化器和使用基于形态动力学的TLM的胚胎选择均未改善临床结局(LBR,OPR,CPR,和MR)与基于形态学的CMS进行比较。TLM仍然是IVF/ICSI实践的研究程序。
    OBJECTIVE: To explore the effect of embryo selection using the time-lapse monitoring (TLM) system compared with conventional morphological selection (CMS) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes.
    METHODS: We searched PubMed, Ovid-Embase, and The Cochrane Library for the following studies: At Comparison 1, embryo selection using TLM images in a TLM incubator based on morphology versus embryo selection using CMS in a conventional incubator based on morphology; at Comparison 2, embryo selection using TLM based on morphokinetics versus embryo selection using CMS based on morphology. The primary outcomes were the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), and implantation rate (IR), and the secondary outcome was the miscarriage rate (MR).
    RESULTS: A total of 14 randomized control trials (RCTs) were included. Both based on morphology, TLM incubators increased the IR (risk ratio [RR]: 1.10; 95% confidence interval [CI]: 1.01, 1.18; I2  = 0%, moderate-quality evidence) compared to conventional incubators. Low- to moderate-quality evidence suggests that TLM incubators did not improve LBR, OPR, CPR, and MR compared to conventional incubators. In addition, low- to moderate-quality evidence indicates that embryo selection using TLM based on morphokinetics did not improve LBR, OPR, CPR, IR, or MR compared to CMS based on morphology.
    CONCLUSIONS: Low- to moderate-quality evidence suggests that neither TLM incubators nor embryo selection using TLM based on morphokinetics improved clinical outcomes (LBR, OPR, CPR, and MR) compared with CMS based on morphology. TLM is still an investigational procedure for IVF/ICSI practice.
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  • 文章类型: Review
    高质量人类胚胎的培养和选择对于体外受精-胚胎移植的成功至关重要。延时成像技术(TLI)为胚胎提供了稳定的培养环境,可以连续观察和记录早期胚胎的发育过程,以便医生可以更准确地记录胚胎发育时间参数。在这项研究中,本文综述了TLI中主要胚胎动力学参数的观察和研究现状,并讨论了它们对胚胎发育潜力的意义和发展。分析和总结,TLI的应用和研究现状,我们搜索了PubMed,WebofScience,和中国国家知识基础设施,使用TLI,胚胎动力学参数,胚胎发育潜力作为关键词,在最初的89篇精选文献中引用了50篇,并进行了总结。通过比较分析和研究,我们发现TLI提供的胚胎动力学参数在临床经验和观察研究中得到了深入研究,大量实验数据验证了其在胚胎发育潜力评估中的有效性和优势。TLI为胚胎动力学参数提供技术支持,这也可能成为优越胚胎和妊娠预测的定量指标。现有研究表明,TLI培养提供的某些动力学参数可以预测胚胎植入,但是还没有一个参数被证实是绝对相关的生物学指标。在这篇综述中,我们认为需要进一步的研究来验证这些初步的,有时是矛盾的结果,并探讨各种胚胎动力学参数依托TLI技术对胚胎发育潜能的预测意义。
    Cultivation and selection of high-quality human embryos are critical for the success of in vitro fertilization-embryo transfer. Time-lapse imaging technology (TLI) provides a stable culture environment for embryos, which can continuously observe and record the development process of early embryos, so that doctors can record embryo development time parameters more accurately. In this study, we review the current observation and research on the main embryo dynamics parameters in TLI and discusses their significance and development for embryo development potential. To analysis and summary, the application and research situation of TLI, we searched PubMed, Web of Science, and China National Knowledge Infrastructure, using TLI, embryo dynamics parameters, embryo development potential as Keywords, cited 50 out of the initial 89 selected literatures and summarized. With comparative analysis and research, we found that the embryo dynamic parameters provided by TLI has been intensively studied in clinical empirical and observational research, extensive experimental data verified its effectiveness and advantages in embryo development potential assessment. TLI provides technical support of embryo dynamic parameters, which may become the quantitative indicators for superior embryos and pregnancy prediction as well. Existing studies have shown that certain kinetic parameters provided by TLI culture can predict embryo implantation, but no parameter has been confirmed as the absolute correlation biological indicators yet. In this review we believe that further research is needed to verify these preliminary and sometimes contradictory results, and explore the predictive significance of various embryo kinetic parameters relying on TLI technology for embryo development potential.
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  • 文章类型: Journal Article
    人工智能(AI)和深度学习算法在医疗保健中的集成一直是过去十年的发展重点。特别是在辅助生殖技术和体外受精(IVF)领域。胚胎形态学是IVF临床决策的基石,IVF领域高度依赖于视觉评估,视觉评估可能容易出错和主观性,并且依赖于观察胚胎学家的培训水平和专业知识.在IVF实验室中实施AI算法可以实现可靠,目标,并及时评估临床参数和显微镜图像。这篇综述讨论了人工智能算法在IVF胚胎学实验室中不断扩大的应用,旨在讨论试管婴儿过程多个方面的许多进展。我们将讨论AI将如何改进各种过程和程序,例如评估卵母细胞质量,精子选择,施肥评估,胚胎评估,倍性预测,胚胎移植选择,细胞追踪,胚胎见证,显微操作,和质量管理。总的来说,人工智能提供了巨大的潜力和希望,不仅可以改善临床结果,还可以改善实验室效率。这是一个重点,因为全国IVF临床量持续增加。
    The integration of artificial intelligence (AI) and deep learning algorithms into medical care has been the focus of development over the last decade, particularly in the field of assisted reproductive technologies and in vitro fertilization (IVF). With embryo morphology the cornerstone of clinical decision making for IVF, the field of IVF is highly reliant on visual assessments that can be prone to error and subjectivity and be dependent on the level of training and expertise of the observing embryologist. Implementing AI algorithms into the IVF laboratory allows for reliable, objective, and timely assessments of both clinical parameters and microscopy images. This review discusses the ever-expanding applications of AI algorithms within the IVF embryology laboratory, aiming to discuss the many advances in multiple aspects of the IVF process. We will discuss how AI will improve various processes and procedures such as assessing oocyte quality, sperm selection, fertilization assessment, embryo assessment, ploidy prediction, embryo transfer selection, cell tracking, embryo witnessing, micromanipulation, and quality management. Overall, AI provides great potential and promise to improve not only clinical outcomes but also laboratory efficiency, a key focus because IVF clinical volume continues to increase nationwide.
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  • 文章类型: Journal Article
    目的:研究使用延时(TL)监视器评估胚胎的卷积神经网络(CNN)模型的准确性。
    方法:于2016年1月至2022年12月在PubMed和WebofScience数据库中进行了系统搜索。通过使用关键字和MeSH术语来执行搜索策略。
    方法:如果报道了使用TL评估胚胎的CNN模型的准确性,则包括研究。审查是在PROSPERO注册的,前瞻性国际系统评价登记册(识别号CRD42021275916)。
    方法:两位评审作者使用Covidence系统评审软件独立筛选结果(VeritasHealthInnovation,墨尔本,澳大利亚)。当研究符合纳入标准或存在任何不确定性时,对全文进行了审查。未达成共识由第三位审阅者解决。使用QUADAS-2工具和修改后的JoannaBriggs研究所(JBI)清单评估偏倚和适用性的风险。
    结果:在对文献进行系统搜索之后,22项研究被确定为符合纳入条件.所有研究均为回顾性研究。总共分析了222,998个胚胎的522,516个图像。评估了三个主要结局:成功的体外受精(IVF),囊胚分期分类,和胚泡质量,大多数研究报告准确率>80%,和一些优秀的胚胎学家。十项研究的偏倚风险很高,主要是由于患者的偏见。
    结论:AI在TL监测仪中的应用具有更高的效率,准确,和客观的胚胎评价。检查胚泡阶段分类的模型显示出最佳预测。预测活产的模型有较低的偏倚风险,使用了最大的数据库,并进行了外部验证,提高了它们与临床应用的相关性。我们的系统评价受到研究之间高度异质性的限制。研究人员应共享数据库并进行标准化报告。
    背景:这项研究没有从公众的资助机构获得任何特定的资助,商业,或非营利部门。
    This study aimed to investigate the accuracy of convolutional neural network models in the assessment of embryos using time-lapse monitoring.
    A systematic search was conducted in PubMed and Web of Science databases from January 2016 to December 2022. The search strategy was carried out by using key words and MeSH (Medical Subject Headings) terms.
    Studies were included if they reported the accuracy of convolutional neural network models for embryo evaluation using time-lapse monitoring. The review was registered with PROSPERO (International Prospective Register of Systematic Reviews; identification number CRD42021275916).
    Two reviewer authors independently screened results using the Covidence systematic review software. The full-text articles were reviewed when studies met the inclusion criteria or in any uncertainty. Nonconsensus was resolved by a third reviewer. Risk of bias and applicability were evaluated using the QUADAS-2 tool and the modified Joanna Briggs Institute or JBI checklist.
    Following a systematic search of the literature, 22 studies were identified as eligible for inclusion. All studies were retrospective. A total of 522,516 images of 222,998 embryos were analyzed. Three main outcomes were evaluated: successful in vitro fertilization, blastocyst stage classification, and blastocyst quality. Most studies reported >80% accuracy, and embryologists were outperformed in some. Ten studies had a high risk of bias, mostly because of patient bias.
    The application of artificial intelligence in time-lapse monitoring has the potential to provide more efficient, accurate, and objective embryo evaluation. Models that examined blastocyst stage classification showed the best predictions. Models that predicted live birth had a low risk of bias, used the largest databases, and had external validation, which heightens their relevance to clinical application. Our systematic review is limited by the high heterogeneity among the included studies. Researchers should share databases and standardize reporting.
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  • 文章类型: Journal Article
    During human in vitro culture, a morphological microscope analysis is normally performed to select the best embryo to transfer, with the hope of obtaining a successful pregnancy. The morphological evaluation may combine number and size of blastomeres, fragmentation, multinucleation, blastocyst expansion, inner-cell mass and trophectoderm appearance. However, standard microscopy evaluation involves the removal of the embryos from the incubator, exposing them to changes in pH, temperature, and oxygen level. Additionally, morphological assessments might include high inter-observer variability. Recently, continuous embryo culture using time-lapse monitoring (TLM) has allowed embryologists to analyse the dynamic and morphokinetic events of embryo development and, based on that, the embryologist is able to scrutinize the complete sequence of embryonic evolution, from fertilization to the blastocyst formation. Therefore, TLM allows an uninterrupted culture condition, reducing the need to remove embryos from the incubator. The monitoring system is normally composed of a standard incubator with an integrated microscope coupled to a digital camera, which is able to collect images at regular times, and subsequently processed into video. These data can be annotated and analyzed using an integrated software, therefore this allows embryologists to facilitate the process of embryo selection for transfer. The main aim of this paper is to discuss the potential benefits and uses of the TLM in the embryology laboratory.
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  • 文章类型: Journal Article
    目的:使用定性和定量延时参数研究胚胎选择/去选择有效性的实验室间可重复性。
    方法:对MEDLINE进行了系统搜索,EMBASE,和Cochrane图书馆(截至2020年2月),没有日期限制,语言,文档类型,和出版状态。测量结果包括植入,囊胚形成,优质的胚泡形成,和整倍体胚泡。
    结果:我们检测到6项回顾性队列研究,外部验证了第一个强调定量参数的临床延时模型(Meseguer),其中3个(包括1个涉及2个独立中心)纳入合并分析.接收器操作特性分析显示,当包括或不包括姐妹临床验证时,模型的预测能力降低。15项评估定性参数的队列研究被纳入荟萃分析,平均纽卡斯尔-渥太华量表为5.3。总的来说,荟萃分析显示,≥1卵裂异常的存在与胚胎着床率之间存在显着不利关联(11项研究,n=7266;RR=0.39[0.28,0.55]95%CI;I2=57%)。进一步分析显示直接裂解的不利影响(7项研究,n=7065;RR=0.28[0.15,0.54]95%CI;I2=46%),反向裂解(2项研究,n=3622;RR=0.16[0.03,0.75]95%CI;I2=0%),混沌分裂(2项研究,n=3643;RR=0.11[0.02,0.69]95%CI;I2=24%),和多核化(5项研究,n=2576;RR=0.59[0.50,0.69]95%CI;I2=0%),但不是4细胞阶段的<6个细胞间接触点(1项研究,n=185;RR=0.17[0.02,1.15]95%CI)。
    结论:定性延时参数与实验室中的胚胎发育潜力可靠相关,而强调定量参数的延时胚胎选择模型的可重复性在外部应用时可能会受到影响。
    OBJECTIVE: To investigate the between-laboratory reproducibility of embryo selection/deselection effectiveness using qualitative and quantitative time-lapse parameters.
    METHODS: A systematic search was performed on MEDLINE, EMBASE, and the Cochrane Library (up to February 2020) without restriction on date, language, document type, and publication status. Measuring outcomes included implantation, blastulation, good-quality blastocyst formation, and euploid blastocyst.
    RESULTS: We detected 6 retrospective cohort studies externally validating the first clinical time-lapse model (Meseguer) emphasizing quantitative parameters, of which 3 (including one involving 2 independent centers) were included for the pooled analysis. Receiver operating characteristics analysis showed reduced predictive power of the model when either including or not including sister clinic validation. Fifteen cohort studies evaluating qualitative parameters were included for meta-analysis, and the mean Newcastle-Ottawa Scale was 5.3. Overall, meta-analysis showed significantly adverse association between the presence of ≥ 1 cleavage abnormalities and embryo implantation rates (11 studies, n = 7266; RR = 0.39[0.28, 0.55]95% CI; I2 = 57%). Further analysis showed adverse impacts of direct cleavage (7 studies, n = 7065; RR = 0.28 [0.15, 0.54] 95% CI; I2 = 46%), reverse cleavage (2 studies, n = 3622; RR = 0.16 [0.03, 0.75] 95% CI; I2 = 0%), chaotic cleavage (2 studies, n = 3643; RR = 0.11 [0.02, 0.69] 95% CI; I2 = 24%), and multinucleation (5 studies, n = 2576; RR = 0.59 [0.50, 0.69] 95% CI; I2 = 0%), but not the < 6 intercellular contact points at the 4-cell stage (1 study, n = 185; RR = 0.17 [0.02, 1.15] 95% CI).
    CONCLUSIONS: Qualitative time-lapse parameters are reliably associated with embryo developmental potential among laboratories, whereas the reproducibility of time-lapse embryo selection model that emphasizes quantitative parameters may be compromised when externally applied.
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  • 文章类型: Journal Article
    在辅助生殖技术(ART)中选择胚胎移植的最佳工具存在争议。延时监测(TLM)是一种非侵入性工具,建议每5-20分钟捕获每个胚胎。鉴于现有研究的不一致,我们对RCT进行了荟萃分析,以总结与ART中胚胎发育常规评估相比,形态动力学预测能力的现有证据.
    主数据库MEDLINE,EMBASE,科克伦,NHS,WHO,对于截至2018年11月发布的RCT,我们咨询了其他非索引引文,没有语言限制.
    我们的综述包括6项RCT(n=2057例患者)。数据显示活产TLM改善(约9%)(OR1.43;95%CI1.10-1.85;P=0.007),低质量的证据。没有证据表明两组之间在持续怀孕方面存在显着差异,临床妊娠和植入率。数据进一步表明,形态动力学与早期妊娠损失率降低有关。由于统计和临床异质性以及由此得出任何有意义的结论的困难,必须谨慎解释这些估计。
    Debate exists for the optimal tool to select embryos for transfer in assisted reproductive technology (ART). Time-lapse monitoring (TLM) is a noninvasive tool suggested where each embryo can be captured every 5-20 min. Given the inconsistency in the existing studies, we conducted this meta-analysis of RCTs to summarize the evidence available concerning the predictive ability of morphokinetics compared with the routine assessment of embryo development in ART.
    The primary databases MEDLINE, EMBASE, Cochrane, NHS, WHO, and Other Non-Indexed Citations were consulted for RCTs that have been published until November 2018, with no language restriction.
    Our review includes 6 RCTs (n = 2057 patients). The data showed an improvement (~ 9%) in live birth TLM (OR 1.43; 95% CI 1.10-1.85; P = 0.007), with low-quality evidence. There was no evidence of a significant difference between both groups concerning ongoing pregnancy, clinical pregnancy and implantation rates. The data further showed that morphokinetics is associated with decreased early pregnancy loss rate. These estimates must be interpreted with caution owing to the statistical and clinical heterogeneities and the consequent difficulty in drawing any meaningful conclusion.
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  • 文章类型: Journal Article
    胚胎形态评估在预测植入方面表现相对较差。胚胎非整倍体筛查(PGS)最近有所改善,但其临床价值仍有争议,并且开发一种廉价的非侵入性方法来评估胚胎倍性状态是一个非常理想的目标。延时装置的日益普及,导致一些团队测试形态动力学参数作为胚胎倍性预测因子的有效性,结果相互矛盾。这项研究的目的是对形态动力学参数对胚胎倍性状态的预测价值的文献进行全面回顾。在PubMed上进行了系统的搜索,使用以下关键字:延时,形态动力学,非整倍体,IVF,植入前遗传筛查,PGS,染色体状态。共有13项研究纳入分析。他们在设计上是异质的,病人,胚胎活检日,统计方法和结果衡量标准。没有单一或组合的形态动力学参数被一致地鉴定为胚胎倍性状态的预测。总之,现有研究的异质性太大,无法得出延时分析对胚胎非整倍体筛查的预测价值的确切结论.因此,形态动力学参数不应用作PGS的替代指标,以确定体外胚胎倍性。
    Embryo morphology assessment performs relatively poorly in predicting implantation. Embryo aneuploidy screening (PGS) has recently improved, but its clinical value is still debated, and the development of a cheap non-invasive method for the assessment of embryo ploidy status is a highly desirable goal. The growing implementation of time-lapse devices led some teams to test the effectiveness of morphokinetic parameters as predictors of embryo ploidy, with conflicting results. The aim of this study was to conduct a comprehensive review of the literature on the predictive value of morphokinetic parameters for embryo ploidy status. A systematic search on PubMed was conducted using the following key words: time-lapse, morphokinetic, aneuploidy, IVF, preimplantation genetic screening, PGS, chromosomal status. A total of 13 studies were included in the analysis. They were heterogeneous in design, patients, day of embryo biopsy, statistical approach and outcome measures. No single or combined morphokinetic parameter was consistently identified as predictive of embryo ploidy status. In conclusion, the available studies are too heterogeneous for firm conclusions to be drawn on the predictive value of time-lapse analysis for embryo aneuploidy screening. Hence, morphokinetic parameters should not be used yet as a surrogate for PGS to determine embryo ploidy in vitro.
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  • 文章类型: Journal Article
    通过提高妊娠率和同时降低多胎妊娠的风险来优化体外受精程序的效率是当前辅助生殖技术计划的主要目标。随着单胚胎移植的发展,对于移植前胚胎选择的更具成本效益的非侵入性方法的需求至关重要.这些目标需要在使用高科技设备的更多获取配子/胚胎测试和选择程序中取得进步。因此,本综述的目的是评估现有文献中的无创成像系统的疗效,重点介绍在接受辅助生殖技术治疗的不孕患者中的潜在临床应用。在这方面,三种先进的能动精子细胞器形态学检查成像系统,充分介绍了偏振显微镜和延时监测,以最佳选择配子和植入前胚胎。
    Optimizing the efficiency of the in vitro fertilization procedure by improving pregnancy rates and reducing the risks of multiple pregnancies simultaneously are the primary goals of the current assisted reproductive technology program. With the move to single embryo transfers, the need for more cost-effective and noninvasive methods for embryo selection prior to transfer is paramount. These aims require advancement in a more acquire gametes/embryo testing and selection procedures using high-tech devices. Therefore, the aim of the present review is to evaluate the efficacy of noninvasive imaging systems in the current literatures, focusing on the potential clinical application in infertile patients undergoing assisted reproductive technology treatments. In this regards, three advanced imaging systems of motile sperm organelle morphology examination, polarization microscopy and time-lapse monitoring for the best selection of the gametes and preimplantation embryos are introduced in full.
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