目的:内细胞团密度(ICM)能否成为人类胚泡质量的新指标?
结论:本研究建立的致密化指数(DI)可以量化ICM密度,为倍性提供积极指导,怀孕,和活产。
背景:在评估ICM的质量时,生殖保健诊所仍使用尺寸指标,而无需进一步评估。目前这种方法的主要缺点是胚泡ICM的评估相对粗糙,不能满足临床胚胎学家的需求,特别是当多个胚泡具有相同的ICM评分时,这使得它们难以进一步评估。
方法:这项观察性研究包括了2018年1月至2021年11月1991年冻融胚胎移植(FET)周期的2272个囊胚和2019年1月至2023年2月430个植入前遗传检测周期的1105个囊胚的数据。
方法:FET,ICSI,胚泡培养,滋养外胚层活检,延时(TL)监测,并进行了下一代测序。经过初步的样本量选择,对TL系统捕获的11幅焦平面图像进行归一化处理,并使用空间频率构造ICM的DI。
结果:本研究成功构建了定量指标DI,该指标可在融合和纹理特征方面反映ICM密度的程度。DI值越高,胚泡ICM的密度越好,胚泡为整倍体(P<0.001),妊娠(P<0.001)和活产(P=0.005)的机会越高。在具有ICM分级B和囊胚分级4BB的囊胚中,DI也与倍性呈正相关,怀孕,和活产(P<0.05)。ROC分析表明,结合Gardner评分系统和DI可以更有效地预测妊娠和活产,与单独使用Gardner评分系统相比。
结论:DI值的精确计算对图像质量提出了很高的要求,需要手动选择最清晰的焦平面和曝光控制。不能使用ICM不完全在视场内的图像。未评估ICM密度与染色体镶嵌性之间的关联。还没有评估ICM密度与胚胎实验室中不同辅助生殖技术和不同培养条件之间的关联。需要进行前瞻性研究以进一步研究ICM密度对临床结果的影响。
结论:ICM密度评估是胚泡评估的新方向。本研究探索了评估囊胚ICM密度的新方法,并开发了ICM密度的定量指标和相应的定性评估方案。本研究开发的囊胚ICM的DI易于计算,只需要TL设备和图像处理,为临床结局提供积极指导。ICM密度的定性评估方案可以帮助没有TL设备的胚胎学家手动评估ICM密度。ICM密度是一个简单的指标,可以在实践中使用,是目前大多数中心使用的胚泡评分系统的良好补充。
背景:这项工作得到了国家重点研究发展计划(2021YFC2700603)的支持。作者报告没有财务或商业利益冲突。
背景:不适用。
OBJECTIVE: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst?
CONCLUSIONS: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth.
BACKGROUND: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further.
METHODS: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023.
METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM.
RESULTS: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone.
CONCLUSIONS: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes.
CONCLUSIONS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers.
BACKGROUND: This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest.
BACKGROUND: N/A.