Department of Embryology, Fertility Associates, 7 Ellerslie Racecourse Drive, Remuera, Auckland, New Zealand.
Department of Embryology, Sunfert International Fertility Centre, 7 Jalan Kerinchi, Bangsar South, Kuala Lumpur, Malaysia.
Hum Reprod. 2020 May 1;35(5):1045-1053. doi: 10.1093/humrep/deaa060.
What is the inter-observer agreement among embryologists for decision to freeze blastocysts of borderline morphology and can it be improved with a modified grading system?
The inter-observer agreement among embryologists deciding whether to freeze blastocysts of marginal morphology was low and was not improved by a modified grading system.
While previous research on inter-observer variability on the decision of which embryo to transfer from a cohort of blastocysts is good, the impact of grading variability regarding decision to freeze borderline blastocysts has not been investigated. Agreement for inner cell mass (ICM) and trophectoderm (TE) grade is only fair, factors which contribute to the grade that influences decision to freeze.
STUDY DESIGN, SIZE, DURATION: This was a prospective study involving 18 embryologists working at four different IVF clinics within a single organisation between January 2019 and July 2019.
PARTICIPANTS/MATERIALS, SETTING, METHODS: All embryologists currently practicing blastocyst grading at a multi-site organisation were invited to participate. The survey was comprised of blastocyst images in three planes and asked (i) the likelihood of freezing and (ii) whether the blastocyst would be frozen based on visual assessment. Blastocysts varied by quality and were categorised as either top (n = 20), borderline (n = 60) or non-viable/degenerate quality (n = 20). A total of 1800 freeze decisions were assessed. To assess the impact of grading criteria on inter-observer agreement for decision to freeze, the survey was taken once when the embryologists used the Gardner criteria and again 6 months after transitioning to a modified Gardner criterion with four grades for ICM and TE. The fourth grade was introduced with the aim to promote higher levels of agreement for the clinical usability decision when the blastocyst was of marginal quality.
The inter-observer agreement for decision to freeze was near perfect (kappa 1.0) for top and non-viable/degenerate quality blastocysts, and this was not affected by the blastocysts grading criteria used (top quality; P = 0.330 and non-viable/degenerate quality; P = 0.18). In contrast, the cohort of borderline blastocysts received a mixed freeze rate (average 52.7%) during the first survey, indicative of blastocysts that showed uncertain viability and promoting significant disagreement for decision to freeze among the embryologists (kappa 0.304). After transitioning to a modified Gardner criteria with an additional grading tier, the average freeze rate increased (64.8%; P < 0.0001); however, the inter-observer agreement for decision to freeze was unchanged (kappa 0.301). Therefore, significant disagreement for decision to freeze among embryologists is an ongoing issue not resolved by the two grading criteria assessed here.
LIMITATIONS, REASONS FOR CAUTION: Blastocyst assessment was performed from time-lapse images in three planes, rather than with a microscope in the laboratory. The inter-observer agreement for decision to freeze may be lower for embryologists working in different clinics with different grading protocols.
The decision to freeze a blastocyst with borderline morphology is a common clinical issue that has the potential to arise for any patient during blastocyst culture. Disagreement for decision to freeze these blastocysts, and therefore clinical usability in frozen embryo transfer cycles, affects consistency in patient care due to a potential impact on cumulative live birth rates, as well as financial, emotional and time costs associated with the frozen embryo transfer cycles. We demonstrate significant disagreement for decision to freeze borderline blastocysts among embryologists using the same grading scheme within a large multisite organisation, a phenomenon which was not improved with a modified grading system. Decision-making around borderline embryos is an area requiring further research, especially as studies continue to demonstrate the reduced but modest live birth rates for low quality blastocysts (Grade C). These results provide support for emerging technology for embryo assessment, such as artificial intelligence.
STUDY FUNDING/COMPETING INTEREST(S): None declared.
Not applicable.
胚胎学家在决定冷冻边缘形态的囊胚时的观察者间一致性如何，使用改良的评分系统是否可以提高？
胚胎学家在决定冷冻边缘形态的囊胚时的观察者间一致性较低，使用改良的评分系统并不能提高。
尽管之前关于在一批囊胚中选择要转移的胚胎的决策方面的观察者间可变性的研究很好，但是关于决定冷冻边缘囊胚的分级变异性的影响尚未得到调查。内细胞团（ICM）和滋养外胚层（TE）分级的一致性仅为中等，这是影响决定冷冻的因素之一。
研究设计、规模、持续时间：这是一项前瞻性研究，涉及 2019 年 1 月至 2019 年 7 月期间在一个单一组织内的四个不同 IVF 诊所工作的 18 名胚胎学家。
参与者/材料、设置、方法：邀请所有目前在多站点组织中进行囊胚分级的胚胎学家参加。该调查由三个平面的囊胚图像组成，并询问（i）冷冻的可能性和（ii）根据视觉评估是否会冷冻囊胚。囊胚的质量各不相同，分为顶级（n=20）、边缘（n=60）或非存活/退化质量（n=20）。共评估了 1800 个冷冻决策。为了评估分级标准对冷冻决策观察者间一致性的影响，当胚胎学家使用 Gardner 标准时进行了一次调查，6 个月后，当胚胎学家使用 Gardner 标准的改良版（ICM 和 TE 分为四级）时，再次进行了调查。引入第四个等级的目的是为了在囊胚质量边缘时提高临床可用性决策的一致性。
对于顶级和非存活/退化质量的囊胚，冷冻决策的观察者间一致性接近完美（kappa 1.0），并且这不受使用的囊胚分级标准的影响（顶级质量；P=0.330，非存活/退化质量；P=0.18）。相比之下，在第一次调查中，边缘质量的囊胚的冷冻率为混合（平均 52.7%），表明囊胚的存活能力不确定，导致胚胎学家对冷冻决策的分歧显著（kappa 0.304）。在过渡到改良的 Gardner 标准并增加一个分级层次后，冷冻率平均增加（64.8%；P<0.0001）；然而，冷冻决策的观察者间一致性保持不变（kappa 0.301）。因此，胚胎学家在冷冻决策方面的显著分歧是一个持续存在的问题，这里评估的两种分级标准都无法解决。
局限性、谨慎的原因：囊胚评估是从时间推移图像的三个平面进行的，而不是在实验室的显微镜下进行的。在不同的诊所使用不同的分级方案工作的胚胎学家，对冷冻决策的观察者间一致性可能较低。
冷冻具有边缘形态的囊胚的决定是一个常见的临床问题，任何患者在囊胚培养期间都有可能遇到。这些囊胚的冷冻决策的分歧，以及因此在冷冻胚胎移植周期中的临床可用性，由于对累积活产率的潜在影响，以及与冷冻胚胎移植周期相关的经济、情感和时间成本，会影响患者护理的一致性。我们在一个大型多站点组织内使用相同的分级方案证明了胚胎学家在冷冻边缘囊胚方面的显著分歧，使用改良的分级系统并不能改善这种情况。关于边缘胚胎的决策是一个需要进一步研究的领域，特别是因为研究继续表明低质量囊胚（等级 C）的活产率降低但适度。这些结果为胚胎评估的新兴技术提供了支持，例如人工智能。
研究资助/利益冲突：无。
不适用。
