Fertility Clinic, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus, Denmark.
Hum Reprod. 2013 Dec;28(12):3215-21. doi: 10.1093/humrep/det366. Epub 2013 Sep 26.
How consistent is the time-lapse annotation of dynamic and static morphologic parameters of embryo development, within and between observers?
The assessment of dynamic parameters is characterized by almost perfect agreement within and between observers.
The commonly employed method used to assess embryos in IVF treatments is based on static evaluation of morphology in a microscope, but this is limited by substantial intra- and inter-observer variation. Time-lapse imaging has been proposed as a method to refine embryo selection by adding new dynamic predictors of viability to the assessment. Yet, there are no data regarding the consistency of estimates of the time-lapse parameters.
STUDY DESIGN, SIZE, DURATION: Infertile patients were recruited at the Fertility Clinic, Arhus University Hospital from February 2011 to June 2012. All embryos were cultured for 6 days in a time-lapse incubator (EmbryoScope(™)). Automated image recording was performed every 20 min.
PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 158 fertilized embryos from 20 different patients were annotated. Three observers made independent annotations on time-lapse recordings. One observer performed the assessment twice. Twenty-five parameters were annotated and the inter- and intra-observer agreement was assessed by calculating intra-class correlation coefficients (ICCs).
Extremely close agreement (ICC 0.99) was found for dynamic parameters including the timing of the following: pronuclei breakdown, completion of blastocyst hatching and the appearance and disappearance of the first nucleus after the first division. Observations of cleavage divisions were strongly correlated (ICC > 0.8), indicating close agreement. Measurements of the static morphologic parameters, i.e. multi-nucleation and evenness of blastomeres at 2-cell stage showed fair-to-moderate agreement (ICC ≤ 0.5).
LIMITATIONS, REASON FOR CAUTION: The study was conducted at a single clinic. Only embryos with a good prognosis were included. The influence of training sessions was not measured.
Consistency is crucial to the validity of embryo scoring and selection. All of the time-lapse parameters suggested by the literature showed in our study high intra- and inter-observer correlation, thus validating the precision of time-lapse annotations. This provides the basis for further investigation of embryo assessment and selection by time-lapse imaging in prospective trials.
STUDY FUNDING/COMPETING INTEREST(S): Research at the Fertility Clinic was funded by an unrestricted grant from Ferring and MSD. The authors have no competing interests to declare.
NCT01139268.
胚胎发育的动态和静态形态参数的时间推移注释在观察者内部和之间的一致性如何？
动态参数的评估在观察者内部和之间具有几乎完美的一致性。
体外受精治疗中常用的评估胚胎的方法是基于显微镜下的形态静态评估，但这受到观察者内和观察者间差异的限制。延时成像已被提议作为一种通过将新的胚胎活力动态预测指标添加到评估中来改进胚胎选择的方法。然而，关于时间推移参数的估计一致性，尚无数据。
研究设计、规模、持续时间：2011 年 2 月至 2012 年 6 月，在奥胡斯大学医院的生育诊所招募了不孕患者。所有胚胎均在延时培养箱（EmbryoScope(™)）中培养 6 天。每隔 20 分钟进行自动图像记录。
参与者/材料、设置、方法：总共对 20 名不同患者的 158 个受精卵进行了注释。三位观察者对延时记录进行了独立注释。一位观察者进行了两次评估。注释了 25 个参数，并通过计算组内相关系数（ICC）评估了观察者内和观察者间的一致性。
发现动态参数（包括以下参数的时间）具有非常密切的一致性：原核分解、囊胚孵化完成以及第一次分裂后第一个核的出现和消失。卵裂分裂的观察结果密切相关（ICC>0.8），表明一致性很高。2 细胞期多核化和卵裂球均匀性等静态形态参数的测量结果具有适度至良好的一致性（ICC≤0.5）。
局限性、谨慎的原因：该研究仅在单个诊所进行。仅纳入了预后良好的胚胎。未测量培训课程的影响。
一致性对于胚胎评分和选择的有效性至关重要。文献中提出的所有时间推移参数在我们的研究中均显示出观察者内和观察者间的高度相关性，从而验证了时间推移注释的精确性。这为通过延时成像在前瞻性试验中进一步研究胚胎评估和选择提供了基础。
研究资金/竞争利益：生育诊所的研究由 Ferring 和 MSD 的一项无限制赠款资助。作者没有利益冲突需要声明。
NCT01139268。
