GENERA, Center for Reproductive Medicine, Clinica Valle Giulia, Via G. De Notaris 2b, 00197 Rome, Italy.
Hum Reprod. 2014 Jun;29(6):1173-81. doi: 10.1093/humrep/deu033. Epub 2014 Feb 26.
Does conventional blastocyst morphological evaluation correlate with euploidy (as assessed by comprehensive chromosome screening (CCS) of trophectoderm (TE) biopsies) and implantation potential?
A moderate relation between blastocyst morphology and CCS data was observed but the ability to implant seems to be mainly determined by the chromosomal complement of preimplantation embryos rather than developmental and morphological parameters conventionally used for blastocyst evaluation.
Combined with improving methods for cryopreservation and blastocyst culture, TE biopsy and CCS is considered to be a promising approach to select euploid embryos for transfer. Understanding the role of morphology in blastocyst stage preimplantation genetic screening (PGS) cycles may help in further optimizing the cycle management and clinical outcomes.
STUDY DESIGN, SIZE, DURATION: This is a multicenter retrospective observational study performed between January 2009 and August 2013. The study includes the data analysis of 956 blastocysts with conclusive CCS results obtained from 213 patients following 223 PGS cycles. Single frozen embryo transfer (FET) cycles of 215 euploid blastocysts were performed where it was possible to track the implantation outcome of each embryo transferred.
PARTICIPANTS/MATERIALS, SETTING, METHODS: PGS was offered to infertile patients of advanced maternal age (>35 years) and/or with a history of unsuccessful IVF treatments (more than two failed IVF cycles) and/or previous spontaneous abortion (more than two spontaneous miscarriages). Prior to TE biopsy for CCS, blastocyst morphology was assessed and categorized in four groups (excellent, good, average and poor quality). The developmental rate of each embryo reaching the expanded blastocyst stage was defined according to the day of biopsy post-fertilization. Day 5 and Day 6 biopsied blastocysts were defined as faster and slower growing embryos, respectively. A novel blastocyst biopsy method, not requiring the opening of the zona pellucida at the cleavage stage of embryo development, was used. Linear regression models were used to test the relationship between blastocyst morphology and developmental rate CCS data and FET cycle outcomes of euploid blastocysts.
Among the embryological variables assessed (morphology and developmental rate), only blastocyst morphology was predictive of the CCS data. The euploidy rate was 56.4, 39.1, 42.8 and 25.5% in the excellent, good, average and poor blastocyst morphology groups, respectively. A diagnosis of complex aneuploidy was also associated with blastocyst morphology (P < 0.01) with 6.8, 15.2, 17.4 and 27.5% of excellent, good, average and poor quality embryos, respectively, showing multiple chromosome errors. Faster and slower growing embryos showed a similar aneuploidy rate. Regression logistic analysis showed that none of the parameters used for conventional blastocyst evaluation (morphology and developmental rate) was predictive of the implantation potential of euploid embryos. The implantation potential of euploid embryos was the same, despite different morphologies and developmental rates.
LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective nature. A higher sample size or a prospective randomized design could be used in future studies to corroborate the current findings.
This study provides knowledge for a better laboratory and clinical management of blastocyst stage PGS cycles suggesting that the commonly used parameters of blastocyst evaluation are not good enough indicators to improve the selection among euploid embryos. Accordingly, all poor morphology and slower growing expanded blastocysts should be biopsied and similarly considered for FET cycles. This knowledge will be of critical importance to achieve similar cumulative live birth rates in PGS programs compared with conventional IVF, avoiding the potential for exclusion of low quality but viable embryos from the biopsy and transfer procedures. Future research to identify non-invasive biomarkers of reproductive potential may further enhance selection among euploid blastocysts.
STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained for the study. All authors have no conflicts to declare.
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传统的囊胚形态评估是否与整倍体（通过对滋养外胚层活检的全面染色体筛查 (CCS) 评估）和着床潜能相关？
囊胚形态与 CCS 数据之间存在中度相关性，但胚胎着床能力似乎主要由着床前胚胎的染色体组成决定，而不是传统用于囊胚评估的发育和形态参数。
结合冷冻保存和囊胚培养方法的改进，TE 活检和 CCS 被认为是选择用于转移的整倍体胚胎的有前途的方法。了解形态学在囊胚阶段植入前遗传筛查 (PGS) 周期中的作用可能有助于进一步优化周期管理和临床结局。
研究设计、规模、持续时间：这是一项多中心回顾性观察性研究，于 2009 年 1 月至 2013 年 8 月进行。该研究分析了 213 名患者的 223 个 PGS 周期中获得的 956 个具有明确 CCS 结果的囊胚的数据。对 215 个整倍体囊胚进行了单次冷冻胚胎移植 (FET) 周期，在这些周期中可以追踪每个移植胚胎的着床结局。
参与者/材料、设置、方法：PGS 提供给高龄（>35 岁）和/或不孕治疗失败（两次以上 IVF 周期失败）和/或自然流产史（两次以上自然流产）的不孕患者。在进行 CCS 的滋养外胚层活检之前，评估囊胚形态并将其分为四个组（优秀、良好、一般和差质量）。根据受精后活检日将每个胚胎的发育速度定义为扩展囊胚阶段的发育速度。第 5 天和第 6 天活检的囊胚分别定义为快速和慢速生长的胚胎。使用一种新的囊胚活检方法，在胚胎发育的卵裂阶段不需要打开透明带。使用线性回归模型测试囊胚形态与发育率 CCS 数据以及整倍体囊胚 FET 周期结局之间的关系。
在所评估的胚胎学变量（形态和发育速度）中，只有囊胚形态可以预测 CCS 数据。优秀、良好、一般和差质量囊胚形态组的整倍体率分别为 56.4%、39.1%、42.8%和 25.5%。复杂非整倍体的诊断也与囊胚形态相关（P < 0.01），优秀、良好、一般和差质量的胚胎中分别有 6.8%、15.2%、17.4%和 27.5%出现多个染色体错误。快速和慢速生长的胚胎具有相似的非整倍体率。回归逻辑分析显示，用于常规囊胚评估的参数（形态和发育速度）均不能预测整倍体胚胎的着床潜能。尽管形态和发育速度不同，但整倍体胚胎的着床潜能相同。
局限性、谨慎的原因：该研究受到其回顾性性质的限制。未来的研究可以使用更大的样本量或前瞻性随机设计来证实当前的发现。
本研究为更好地管理囊胚阶段 PGS 周期的实验室和临床提供了知识，表明囊胚评估中常用的参数不足以提高整倍体胚胎的选择。因此，所有形态差和发育缓慢的扩张囊胚都应该进行活检，并同样考虑用于 FET 周期。这一知识对于在 PGS 计划中实现与传统 IVF 相比类似的累积活产率至关重要，避免了从活检和转移过程中排除低质量但有活力的胚胎的潜在可能性。未来研究确定生殖潜力的非侵入性生物标志物可能会进一步提高整倍体囊胚的选择。
研究资金/利益冲突：本研究未获得任何资金。所有作者均无利益冲突。
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