囊胚二次活检对胚胎植入前遗传学检测患者临床结局的影响

Effect of the second biopsy on the clinical outcomes of patients with preimplantation genetic testing

目的探究囊胚二次活检对胚胎植入前遗传学检测(preimplantation genetic testing,PGT)患者临床妊娠和新生儿结局的影响。方法回顾性队列研究分析了河南省人民医院生殖医学中心于2019年1月至2022年12月期间行一次活检PGT和二次活检PGT后助孕患者(分别为453例、60例)的临床妊娠和新生儿结局。采用2∶1倾向性评分匹配(propensity score matching,PSM)方法对两组的女方年龄、体质量指数(body mass index,BMI)、不孕年限进行匹配,比较两组PGT患者实验室指标及移植助孕结局和新生儿结局相关指标。同时依据PGT类型对二次活检PGT组进行亚组分析,分为胚胎植入前非整倍体遗传学检测(preimplantation genetic testing for aneuploidy,PGT-A)亚组、胚胎植入前染色体结构异常遗传学检测(preimplantation genetic testing for structural rearrangements,PGT-SR)亚组、胚胎植入前单基因遗传学检测(preimplantation genetic testing for monogenic,PGT-M)亚组,两两比较其二检率、扩增成功率、可移植率等指标。结果PSM后,两组PGT患者间女方年龄、女方BMI、不孕类型、促排卵方案、PGT类型及实验室相关指标的差异均无统计学意义(均P>0.05);同时,二次活检胚胎的种植率、临床妊娠率、活产率均略降低,流产率略增高,但差异均无统计学意义(均P>0.05);然而,二次活检PGT组患者的第3天可利用胚胎率[87.50%(434/496)]明显高于一次活检PGT组[82.19%(812/980),P=0.020],而囊胚形成数[4.00(2.25,6.75)]明显少于一次活检PGT组[5.50(3.00,8.00),P=0.028];同时,二次活检胚胎的染色体整倍体率[35.9%(28/78)]低于一次活检胚胎[49.3%(226/458),P=0.028],且异常率[9.0%(7/78)]高于一次活检胚胎[0.9%(4/458),P<0.001],差异均有统计学意义。二次活检PGT组非整倍体率和多条染色体嵌合体率高于一次活检PGT组,但差异均无统计学意义(均P>0.05)。新生儿出生体质量、胎龄、性别比例、低出生体质量儿、巨大儿、小于胎龄儿、大于胎龄儿、出生缺陷发生率两组间差异均无统计学意义(均P>0.05)。二次活检PGT组亚组之间两两比较,其二检率、扩增成功率、可移植率的差异均无统计学意义(均P>0.05)。结论对于第一次活检失败的患者,经过二次活检行PGT后的临床妊娠率、活产率和新生儿出生体质量、出生缺陷发生率等与一次活检PGT患者相当。

Objective To investigate the effect of rebiopsy blastocyst on clinical pregnancy and neonatal outcomes in patients with preimplantation genetic testing(PGT)before embryo implantation.Methods A retrospective cohort study analyzed the clinical pregnancy and neonatal outcomes of one biopsy and rebiopsy patients(453 and 60 patients,respectively)with PGT in the Reproductive Medicine Center of Henan Provincial People's Hospital from January 2019 to December 2022.The 2∶1 propensity score matching(PSM)method was used to match the age,body mass index(BMI)and infertility duration of women in the two groups,and the laboratory indexes and related indexes of transplant fertility and neonatal outcomes of PGT patients were compared between the two groups.The rebiopsy patients with PGT were divided into PGT for aneuploidy(PGT-A)subgroup,PGT for structural rearrangements(PGT-SR)subgroup and PGT for monogenic(PGT-M)subgroup according to PGT types,and the rebiopsy rate,the success rate of amplification and the rate of transferrable embryo were compared between each two subgroups.Results After PSM,there were no significant differences in women's age,female body mass index,infertility type,ovulation induction program,PGT type and laboratory-related indexes between the two groups(all P>0.05).At the same time,the implantation rate,the clinical pregnancy rate and the live birth rate of rebiopsy embryos decreased,and the miscarriage rate increased,but the differences were not statistically significant(all P>0.05).The rate of day 3 available embryo in the rebiopsy PGT group[87.50%(434/496)]was significantly increased,and the number of blastocyst[4.00(2.25,6.75)]was significantly decreased compared with one biopsy PGT group[82.19%(812/980),P=0.020;5.50(3.00,8.00),P=0.028].Then the chromosomal euploidy rate of the rebiopsy embryo[35.9%(28/78)]decreased and the abnormality rate[9.0%(7/78)]increased in the rebiopsy PGT group compared with one biopsy PGT group[49.3%(226/458),P=0.028;0.9%(4/458),P<0.001],and the differences were statistically significant.The aneuploidy rate and multi-chromosome mosaic rate in the rebiopsy PGT group were higher than those in the one biopsy PGT group,but the difference was not statistically significant(all P>0.05).There were no significant differences in birth weight,gestational age,sex ratio,low birth weight infants,macrosomia,small-for-gestational-age infants,large-for-gestational-age infants,and incidence of birth defects between the two groups(all P>0.05).There was no significant difference in the rebiopsy rate,the success rate of amplification and the rate of transferrable embryo between the subgroups of the PGT group(all P>0.05).Conclusion For patients who fail the first biopsy,the clinical pregnancy rate,the live birth rate,the neonatal birth weight,and the birth defect incidence rate after the second biopsy of PGT are comparable to those of the patients with the first biopsy of PGT.