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通过开发实验室适应的延时模型来提高胚胎选择。

Improving embryo selection by the development of a laboratory-adapted time-lapse model.

机构信息

Division of Reproductive Endocrinology and In Vitro Fertilization (IVF), Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Haifa, Israel.

Division of Reproductive Endocrinology and In Vitro Fertilization (IVF), Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Haifa, Israel.

出版信息

F S Sci. 2021 May;2(2):176-197. doi: 10.1016/j.xfss.2021.02.001. Epub 2021 Feb 16.

DOI:10.1016/j.xfss.2021.02.001
PMID:35559752
Abstract

OBJECTIVE

To study whether a powerful, in-house, embryo-selection model can be developed for a specific in vitro fertilization (IVF) laboratory where embryos were already selected for transfer using general models.

DESIGN

In total, 12,944 fertilized oocytes were incubated in an EmbryoScope (Vitrolife, Göteborg, Sweden) at our laboratory. Embryos were selected for transfer or freezing using general models. There were 1,879 embryos with known implantation data (KID), of which 425 had positive KIDs. For the outcome, we set 3 endpoints for KID's definition: gestational sac, clinical pregnancy, and live birth. Results of a comparison between KID-positive and -negative embryos for cell division timings were analyzed separately for intracytoplasmic sperm injection (ICSI) and IVF embryos in patients aged 18-41 years.

SETTING

IVF center.

PATIENTS

The study included 1,075 women undergoing IVF or ICSI treatment between June 2013 and February 2019.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The KID-positive and -negative embryos were analyzed for statistical differences in cell division timing and cell cycle intervals. We used the EmbryoScope Stats software (Unisense FertiliTech, Aarhus, Denmark) for model development. The statistically different timing parameters were tested for their contribution to scoring in the model. The algorithms were tested for area under the receiver operating characteristic curve (AUC) in the KID embryos for developing day-2, -3, and -5 embryo-selection models. The validation of these algorithms was performed using calibration/validation procedures.

RESULTS

Because significant differences in morphokinetics were found between the KID-positive and KID-negative embryos in our laboratory, it was possible to use our specific KID data to develop an in-house model. The algorithms were developed for embryo selection on days 2, 3, and 5 in the ICSI embryos. In most cases, AUC was >0.65, which indicated that these models were valid in our laboratory. In addition, these AUC values were obtained from all gestational sac, clinical pregnancy, and live birth KID embryo databases tested. An increase in the predictability of the models was observed from days 2-3 to day 5 models. The AUC test results ranged between 0.657 and 0.673 for day 2 and day 3, respectively, and 0.803 for the day 5 model.

CONCLUSION

A model based on laboratory-specific morphokinetics was found to be complementary to general models and an important additive tool for improving single embryo selection. Developing an in-house laboratory-specific model requires many stages of sorting and characterization. Many insights were drawn about the model developing process. These may facilitate and improve the process in other laboratories.

摘要

目的

研究在已经使用通用模型选择胚胎转移的特定体外受精(IVF)实验室中,是否可以开发出强大的内部胚胎选择模型。

设计

在我们的实验室中,总共孵育了 12944 个受精卵在胚胎培养箱(Vitrolife,哥德堡,瑞典)中。胚胎使用通用模型选择进行转移或冷冻。有 1879 个具有已知植入数据(KID)的胚胎,其中 425 个具有阳性 KID。对于结果,我们为 KID 的定义设定了 3 个终点:孕囊、临床妊娠和活产。分别分析了年龄在 18-41 岁的患者的胞浆内精子注射(ICSI)和 IVF 胚胎的 KID 阳性和阴性胚胎之间的细胞分裂时间比较。

地点

IVF 中心。

患者

这项研究包括了 1075 名在 2013 年 6 月至 2019 年 2 月期间接受 IVF 或 ICSI 治疗的女性。

干预措施

无。

主要观察指标

分析 KID 阳性和阴性胚胎的细胞分裂时间和细胞周期间隔的统计差异。我们使用胚胎培养箱统计软件(Unisense FertiliTech,奥胡斯,丹麦)开发模型。对具有统计学差异的时间参数进行了测试,以确定其在模型评分中的贡献。对第 2、3 和 5 天的胚胎选择模型的 KID 胚胎进行了接收者操作特征曲线(AUC)的算法测试。使用校准/验证程序对这些算法进行了验证。

结果

由于我们实验室中 KID 阳性和 KID 阴性胚胎的形态动力学存在显著差异,因此可以使用我们特定的 KID 数据来开发内部模型。该算法是在 ICSI 胚胎的第 2、3 和 5 天开发的。在大多数情况下,AUC >0.65,这表明该模型在我们实验室中是有效的。此外,这些 AUC 值是从所有测试的孕囊、临床妊娠和活产 KID 胚胎数据库中获得的。从第 2 天到第 3 天的模型预测能力增加,从第 2 天到第 3 天的 AUC 测试结果分别为 0.657 和 0.673,第 5 天的模型为 0.803。

结论

基于实验室特定形态动力学的模型被发现与通用模型互补,是提高单个胚胎选择的重要附加工具。开发内部实验室特定模型需要经过多个阶段的分类和特征描述。我们对模型开发过程有了很多深入的了解。这些可能会促进和改善其他实验室的进程。

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