Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hariomed Innovation Research Center, Guangzhou, Guangdong, China.
Hum Reprod. 2024 Sep 1;39(9):1942-1951. doi: 10.1093/humrep/deae158.
Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst?
The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth.
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.
STUDY DESIGN, SIZE, DURATION: 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.
PARTICIPANTS/MATERIALS, SETTING, 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.
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.
LIMITATIONS, REASONS FOR CAUTION: 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.
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.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest.
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内细胞团（ICM）的密度是否可以成为人类囊胚质量的新指标？
本研究中开发的密集度指数（DI）可以量化 ICM 密度，并为倍性、妊娠和活产提供积极的指导。
在评估 ICM 质量时，生殖保健诊所仍然使用没有进一步评估的大小指标。这种当前方法的主要缺点是，对囊胚 ICM 的评估相对粗糙，无法满足临床胚胎学家的需求，尤其是当多个囊胚具有相同的 ICM 评分时，这使得它们难以进一步评估。
研究设计、大小、持续时间：本观察性研究包括 2018 年 1 月至 2021 年 11 月期间 1991 个冷冻胚胎移植（FET）周期和 2019 年 1 月至 2023 年 2 月期间 430 个植入前遗传学检测周期中 2272 个囊胚和 1105 个囊胚的数据。
参与者/材料、设置、方法：进行了 FET、ICSI、囊胚培养、滋养外胚层活检、延时（TL）监测和下一代测序。在初步选择样本量后，通过 TL 系统捕获的 11 个焦点平面图像被归一化，并且空间频率被用于构建 ICM 的 DI。
本研究成功构建了一个定量指标 DI，该指标可以反映融合和纹理特征的 ICM 密度程度。DI 值越高，囊胚 ICM 的密度越好，囊胚为整倍体（P < 0.001）的可能性以及妊娠（P < 0.001）和活产（P = 0.005）的可能性越高。在 ICM 分级为 B 的囊胚和 4BB 分级的囊胚中，DI 也与倍性、妊娠和活产呈正相关（P < 0.05）。ROC 分析表明，与单独使用 Gardner 评分系统相比，结合 DI 可以更有效地预测妊娠和活产。
局限性、谨慎的原因：准确计算 DI 值对图像质量要求很高，需要手动选择最清晰的焦点平面和曝光控制。ICM 不完全在视野内的图像不能使用。ICM 密度与染色体镶嵌之间的关联未被评估。ICM 密度与不同的辅助生殖技术之间的关联以及胚胎实验室中不同的培养条件之间的关联也未被评估。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。
ICM 密度评估是囊胚评估的一个新方向。本研究探索了评估囊胚 ICM 密度的新方法，并开发了用于评估囊胚 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，仅需要 TL 设备和图像处理，为临床结果提供了积极的指导。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囊胚评分系统的良好补充。
研究资金/利益冲突：这项工作得到了国家重点研发计划（2021YFC2700603）的支持。作者报告没有财务或商业利益冲突。
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