染色体结构异常PGT周期中囊胚评估参数与其整倍体率的相关性

Correlation between blastocyst evaluation parameters and euploidy rate in PGT cycles of chromosomal structural abnormality

目的研究染色体结构异常患者胚胎植入前遗传学检测(PGT)周期中囊胚评估参数与其整倍体率的相关性。方法回顾性分析2019年1月至2020年6月在河北医科大学第二医院生殖医学科因夫妇双方或一方染色体结构异常行PGT的83例患者(97个周期)的相关资料,将所有患者按照一般情况、周期基本情况以及活检囊胚情况进行逐层分组,比较各亚组囊胚的PGT检测结果,分别采用周期特征性分析、广义评估方程GEE模型和分类决策树模型分析囊胚的整倍体率与周期特征、囊胚活检时的发育天数、囊胚扩张程度、内细胞团(ICM)级别、滋养层细胞(TE)级别的相关性。结果共活检371枚囊胚,其中整倍体囊胚154枚(41.51%),非整倍体囊胚217枚(58.49%)。(1)周期基本特征统计分析显示:女方18.5≤BMI<24 kg/m^(2)组其囊胚整倍体率(48.37%)显著高于BMI<18.5 kg/m^(2)(23.81%)组和BMI≥24 kg/m^(2)(36.14%)组(P<0.05);平衡易位患者囊胚整倍体率(31.88%)显著低于罗氏易位(52.85%)和倒位(56.10%)患者(P<0.05);Gn使用总量<2250 U组囊胚整倍体率(50.00%)显著高于2250~3000 U组(38.06%)和>3000 U组(34.15%)(P<0.05);活检第5天(D5)囊胚的整倍体率(53.53%)显著高于D6(31.96%)和D7(14.29%)(P<0.05);ICM、TE评级为A级的囊胚整倍体率(67.74%、70.00%)显著高于B级(39.02%、46.98%)和C级(39.62%、36.32%)(P<0.05)。(2)广义评估方程GEE模型分析显示:囊胚发育天数[OR=4.400,95%CI(1.553,12.465)]、囊胚扩张程度[OR=0.344,95%CI(0.128,0.928)]是整倍体率的独立影响因素;而女方年龄、男方年龄、女方体重指数、获卵数、MⅡ卵数、基础激素水平、促排卵情况、囊胚ICM/TE等级等与其整倍体率无关(P>0.05)。(3)分类决策树模型显示共生成3组节点:第1组节点为染色体结构异常类型,倒位及罗氏易位患者的整倍体率显著高于平衡易位患者(χ^(2)=19.164,P<0.001);第2组节点为活检囊胚发育天数,D5的囊胚整倍体率显著高于D6和D7囊胚(χ^(2)=10.824,P=0.003);第3组节点为染色体结构异常来源于男方/女方,倒位及罗氏易位男方核型异常患者囊胚整倍体率显著高于女方核型异常患者(χ^(2)=5.552,P=0.018),但平衡易位女方核型异常患者囊胚整倍体率显著高于男方核型异常患者(χ^(2)=5.320,P=0.021),交叉验证正确百分比64.2%。结论囊胚的整倍体率与囊胚的发育速度即活检时囊胚发育天数和扩张程度显著相关,而与ICM/TE评级无显著相关性。染色体结构异常的类型和患者性别与囊胚的整倍体率亦存在一定的相关性。

Objective:To study the correlation between blastocyst evaluation parameters and euploidy rate in patients with chromosomal abnormalities undergoing preimplantation genetic test(PGT).Methods:The data of 83 patients(97 cycles)who underwent PGT due to abnormal chromosome structure in either or both spouses in the Reproductive Medicine Center of the Second Hospital of Hebei Medical University from Jan.2019 to Jun.2020 were retrospectively analyzed.All patients were grouped according to their general condition,basic condition of cycles and blastocysts biopsy status,and then compare the PGT results of blastocysts in each subgroup.The correlation between the blastocyst euploidy rate and the cycle characteristics,the development days at blastocyst biopsy,the blastocyst expansion extent,the grade of inner cell mass(ICM)and the grade of trophoblast cells(TE)were analyzed by using the periodic characteristic analysis,the generalized evaluation equation GEE model and the classification decision tree model.Results:A total of 371 blastocysts were biopsied,including 154(41.51%)euploidy blastocysts and 217(58.49%)aneuploidy blastocysts.(1)The statistical analysis of the basic characteristics of the cycles showed that the women with 18.5≤BMI<24 kg/m^(2) had the highest blastocyst euploidy rate(48.37%),which was significantly higher than those of women with BMI<18.5 kg/m^(2)(23.81%)and BMI≥24 kg/m^(2)(36.14%)(P<0.05).The blastocyst euploidy rate in the patients with balanced translocation(31.88%)was significantly lower than those in the patients with Roche translocation(52.85%)and inversion patients(56.10%)(P<0.05).The blastocyst euploidy rate in patients with total amount of gonadotropin(Gn)used<2250 U(50.00%)was significantly higher than those in patients with of total amount of Gn between 2250 to 3000 U(38.06%)and>3000 U(34.15%)(P<0.05).The euploidy rate on the Day 5 of embryo development at the time of blastocyst biopsy(53.53%)was significantly higher than those of Day 6(31.96%)and Day 7(14.29%)(P<0.05).The euploidy rates in blastocyst with grade A of ICM and TE(67.74%,70.00%)were significantly higher than those in blastocyst with grade B of ICM and TE(39.02%,46.98%)or grade C of ICM and TE(39.62%,36.32%)(P<0.05).(2)The results of generalized evaluation equation GEE model analysis showed that the days of blastocyst development[OR=4.400,95%CI(1.553,12.465)]and the degree of blastocyst expansion[OR=0.344,95%CI(0.128,0.928)]were independent influencing factors of blastocyst euploidy rate,while the female’s age,male’s age,female’s BMI,number of oocytes retrieved,MⅡoocytes number,the basal hormone level,ovulation induction,and the grade of ICM&TE were not significantly correlated with blastocyst euploidy rate(P>0.05).(3)The results of classification decision tree model showed that three sets of nodes were generated.The first set node was chromosome structure abnormity,i.e.the euploidy rate of patients with inversion and Roche translocation was significantly higher than that of patients with balanced translocation(χ^(2)=19.164,P<0.001).The second node was blastocyst development days,i.e.the euploidy rate of Day 5 blastocysts was significantly higher than those of Day 6 and Day 7 blastocysts(χ^(2)=10.824,P=0.003).The third node was abnormal chromosome structure originated from the man or woman,i.e.the blastocyst euploidy rate of inversion and Roche translocation originated from man was significantly higher than that from woman(χ^(2)=5.552,P=0.018),while the blastocyst euploidy rate of balanced translocation originated from woman was significantly higher than that from man(χ^(2)=5.320,P=0.021).The correct percentage of cross validation was 64.2%.Conclusions:The euploidy rate of blastocysts is significantly corrected with the development speed of blastocysts,that is,the days of blastocyst development and the degree of expansion at blastocyst biopsy,but not significantly corrected with ICM and TE.The type of chromosome structural abnormalities and gender of patient are also correlated with the euploidy rate of blastocysts.