Prediction of embryo euploidy and pregnancy outcome by blastocyst morphology and development speed for women receiving single embryo transfer

Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5–2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade. Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.

优质囊胚（blastocyst）的筛选是决定辅助生殖技术（assisted reproductive technology, ART）成功率的最核心因素。本研究旨在评估囊胚形态学质量与发育速度在预测整倍性（euploidy）及临床妊娠结局中的价值。本研究回顾性分析了2018年1月至2019年12月期间的155个植入前遗传学检测（preimplantation genetic testing, PGT）周期（共纳入959个囊胚）及154个整倍体囊胚移植周期。通过单因素及多因素回归分析，评估了囊胚形态学质量、发育速度（D）与染色体核型、临床妊娠率、早期流产率（early miscarriage）及持续妊娠率（ongoing pregnancy）之间的关联。发育至第5天（D5）的囊胚整倍体率显著高于第6天（D6）囊胚（61.4% vs. 38.1%，P < 0.001）；高级别形态学囊胚的整倍体率亦显著高于非高级别形态学囊胚（54.8% vs. 39.2%，P=0.02）。多因素分析显示，发育速度（比值比[odds ratio, OR]=2.7，95%置信区间[confidence interval, CI] 1.8–4.1，P < 0.001）与高级别形态学（OR=2.1，95%CI 1.5–2.9，P=0.01）均为整倍体的独立预测因素。D5囊胚的持续妊娠率显著高于D6囊胚（62.3% vs. 43.8%，P=0.04）。移植高级别形态学整倍体囊胚的持续妊娠率显著高于移植非高级别形态学整倍体囊胚（60.7% vs. 43.2%，P=0.049）。此外，发育速度较慢的D6囊胚是整倍体囊胚移植后早期流产的独立危险因素。校正混杂因素（confounding factors）后的多因素回归分析显示，母亲年龄（maternal age）、囊胚发育速度及囊胚形态学分级均为整倍体的独立预测因素，但并非临床妊娠的独立预测因素。基于本研究提出的胚胎移植优选顺序为：D5高级别囊胚 > D6高级别囊胚 > D5非高级别囊胚 > D6非高级别囊胚。辅助生殖领域的临床医师正积极探索提升胚胎筛选准确性以实现成功妊娠的方法。本研究针对无不孕病史、体外受精（in vitro fertilisation, IVF）失败史或复发性流产（recurrent miscarriage）史且接受整倍体胚胎移植的夫妇，评估了胚胎形态学分级与发育速度和染色体核型及临床结局的关联。年龄小于35岁的女性所获囊胚、高级别形态学囊胚及发育速度更快的囊胚更易为整倍体（即染色体异常概率更低）。反之，移植发育较慢的整倍体囊胚的患者早期流产风险更高。为最大化整倍体胚胎的植入概率并降低妊娠丢失风险，胚胎移植的选择顺序应优先依据胚胎发育速度，其次为形态学分级。