摘要
目的通过胚胎时差成像技术(TLT)结合人工智能(AI)探索体外胚胎发育曲线(EDM)中的卵裂球计数曲线"跳变值"与胚胎形态学特征的相关性,并探讨其在体外受精(IVF)胚胎评估中应用的可行性。方法本研究为自主研发的AI胚胎评估软件的诊断性试验,即临床数据AI再评估,为回顾性研究。收集2020年12月至2021年12月于重庆医科大学附属妇女儿童医院生殖医学中心行IVF的1226例患者共6545个胚胎,其中2869个胚胎进行囊胚培养。所有胚胎通过TLT培养并进行观察,由TLT记录软件Embryo Viewer依据胚胎发育动力学绘制EDM。本课题组自主研发的AI胚胎评估软件对胚胎发育过程中的卵裂球数目进行实时识别、记录,并与EDM进行比较,分析由卵裂球计数变化而形成的跳变值与胚胎结局的相关性。采用Spearman相关性及logistic回归分析跳变值与胚胎形态学评估、胚胎着床及活产的相关性,使用受试者工作特征(ROC)曲线评估各指标对胚胎着床、活产的预测价值。结果Spearman相关性分析显示,受精卵受精后72 h卵裂球计数曲线提取的总跳变值与卵裂模式、囊胚形成、培养至第3天胚胎(D3胚胎)的形态学评级、D3胚胎的细胞均一度、D3胚胎的细胞碎片率均呈显著负相关(β值分别为-0.268、-0.116、-0.213、-0.159、-0.222;P均<0.001),与D3胚胎的细胞数呈显著正相关(β=0.034;P<0.001)。多因素logistic回归分析显示,胚胎总跳变值排序与囊胚形成(OR=0.97,95%CI为0.93~0.99;P=0.034)、胚胎着床(OR=0.96,95%CI为0.93~0.98;P=0.044)呈显著负相关;ROC曲线分析显示,胚胎总跳变值排序预测胚胎着床能力与传统胚胎形态学评估方法相近[其曲线下面积(AUC)分别为0.679、0.620]。多因素logistic回归分析显示,活产与患者年龄(OR=0.91,95%CI为0.88~0.93;P<0.001)、D3胚胎形态学评级(OR=0.77,95%CI为0.59~0.99;P=0.045)及胚胎总跳变值排序(OR=0.98,95%CI为0.96~0.99;P=0.038)呈显著负相关,而与获卵数(OR=1.08,95%CI为1.05~1.11;P<0.001)及移植日子宫内膜厚度(OR=1.09,95%CI为1.06~1.12;P<0.001)呈显著正相关;ROC曲线分析显示,纳入建模的以上多个因素预测活产的AUC值为0.666。结论跳变值及其排序是对体外胚胎卵裂期发育的系统量化,其与胚胎发育质量及临床结局相关,可能是胚胎体外评估及选择的有益补充。
Objective To explore the correlation between blastomere count variations“skip value”which extracted from by time-lapse technology(TLT)combined with artificial intelligence(AI)and morphological features of in vitro fertilization(IVF)embryo,and to test its feasibility in clinical applications.Methods This study was a diagnostic experiment(AI reassessment of embryo transferred patients),a total of 6545 embryos from 1226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed,of which 2869 embryos were attempted to cultured to blastocyst stage by TLT.The embryo dynamic map(EDM)was drawn by Embryo Viewer,a TLT recording software,based on embryo developmental kinetics.The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development,and compared with the EDM,the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed.The correlation among skip value,morphological score of embryo,implantation rate and live birth rate were performed by Spearman and step-up logistic regression.The receiver operating characteristic(ROC)curve was selected for reporting there relationship of skip value and morphology.Finally,predicting power of skip value for implantation and live birth rate were performed by ROC analysis.Results The total skip values extracted from the blastomere count of embryos(72 hours post-fertilization)were negatively correlated with abnormal cleavage,blastocyst formation rate,day 3(D3)-cell score,uneven size and fragmentation(the β values were-0.268,-0.116,-0.213,-0.159 and-0.222,respectively;all P<0.001);positively correlated with D3-cell number(β=0.034;P<0.001);negatively correlated with blastocyst formation rate and implantation rate(OR=0.97,95%CI:0.93-0.99,P=0.034;OR=0.96,95%CI:0.93-0.98,P=0.044).The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria[area under curve(AUC):0.679 vs 0.620].Live birth rate were negatively correlated with female age(OR=0.91,95%CI:0.88-0.93;P<0.001),D3 general score(OR=0.77,95%CI:0.59-0.99;P=0.045)and order selection of skip values(OR=0.98,95%CI:0.96-0.99;P=0.038),while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred(OR=1.08,95%CI:1.05-1.11,P<0.001;OR=1.09,95%CI:1.06-0.12,P<0.001,respectively)from multivariate regression analysis,and the power of predicting live birth was 0.666 for AUC.Conclusions The skip value and its order form is a systematic quantification of embryo development,correlated with embryo developmental quality and clinical outcome.It could be an addition parameter for embryo culture and selection.
作者
杨静薇
韩伟
刘卫卫
刘军霞
黄国宁
张孝东
Yang Jingwei;Han Wei;Liu Weiwei;Liu Junxia;Huang Guoning;Zhang Xiaodong(Center for Reproductive Medicine,Women and Children's Hospital of Chongqing Medical University,Chongqing 400013,China)
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2024年第7期548-558,共11页
Chinese Journal of Obstetrics and Gynecology
基金
国家自然科学基金(82371728)
重庆市技术创新与应用发展专项(CSTB2022TIAD-KPX0146)。
关键词
分裂球
胚胎培养技术
人工智能
胚胎移植
胚胎发育
体外受精
延时成像
回顾性研究
Blastomere
Embryo culture techniques
Artificial intelligence
Embryo transfer
Embryonic development
Fertilization in vitro
Time-lapse imaging
Retrospective studies
