50例胚胎植入前遗传学诊断的临床资料分析

Clinical analysis of 50 cases of pre-implantation genetic diagnosis

目的总结胚胎植入前遗传学诊断(PGD)治疗的特点及规律,为临床应用提供参考。方法收集2017年1月至2019年1月在解放军总医院第六医学中心妇产科生殖中心就诊并完成IVF/ICSI助孕周期及PGD的50对夫妇为研究对象,其中40例为夫妻之一携带染色体结构异常者,10例为单基因病家族史、夫妻一方或双方为致病基因携带者。对患者的临床资料进行回顾性分析;采用囊胚活检术获得胚胎细胞,单细胞全基因组扩增后,采用二代测序技术(NGS)检测胚胎染色体拷贝数。选择染色体平衡、无单基因病发病风险的胚胎,行单囊胚移植。妊娠后在孕中期(18~22 W)进行羊水穿刺,产前诊断,对胎儿进行核型分析及基因检测。结果50例行PGD的患者进行了62个促排卵周期,获得218个囊胚,全部采用囊胚活检技术,活检成功率100%。40例染色体病患者共6个病种,获得可移植的囊胚39枚,60%的患者获得可移植囊胚;移植20人,临床妊娠12人,妊娠率60.0%(12/20),流产2人,获得10例健康婴儿。10例单基因疾病患者共7个病种,共获得24个可移植囊胚,100%的患者获得了可移植囊胚;移植9人,临床妊娠5人,妊娠率55.6%(5/9),1例孕24 W自然流产,1例目前孕30 W,共获得3名健康婴儿。孕中期产前诊断,胎儿染色体核型均正常,单基因病家系胎儿基因型与PGD结果相符。结论NGS技术可以有效筛查出携带染色体病和单基因病的囊胚,避免移植此类囊胚,阻断遗传病的传递。PGD技术是解决遗传病高危患者生育问题的有效措施。

Objective:To summarize the characteristics and principles of pre-implantation genetic diagnosis(PGD)treatment,and provide reference for clinical application.Methods:The clinical data of 50 couples undergone PGD who had been treated and completed IVF/ICSI cycle in the Reproductive Center of Department of Obstetrics and Gynecology of our hospital from January 2017 to January 2019 were collected.Among them,40 cases were one of the couples who carried abnormal chromosome structure,10 cases were family history of monogenic disease and one or both were pathogenic gene carrier.The clinical data were analyzed retrospectively.The embryonic cells were obtained by using blastocyst biopsy.The copy number of embryo chromosome was detected by next generation sequencing(NGS)after the single-cell whole genome was expanded.The embryos with balanced chromosomes and no risk of monogenic disease were selected for single blastocyst transfer.After pregnancy,amniocentesis prenatal diagnosis,karyotype analysis and genetic testing for the fetus were performed during the second trimester(18-22 weeks).Results:Fifty patients with PGD underwent 62 cycles of ovulation induction,and 218 blastocysts were obtained.All the blastocysts were biopsied with 100%success rate.Forty patients suffered 6 kinds of chromosomal diseases,39 transplantable blastocysts were obtained,and 60%of patients had transplantable blastocysts.Twenty patients were transplanted,12 patients got clinically pregnant,the pregnancy rate was 60.0%(12/20),2 patients were miscarried,and 10 healthy babies were obtained.Ten patients suffered 7 kinds of monogenic diseases received 24 transplantable blastocysts,and 100%of patients obtained transplantable blastocysts.Nine patients were transplanted,5 patients got clinically pregnant,and the pregnancy rate was 55.6%(5/9).One patient was spontaneously aborted at 24 weeks,and one patient was currently pregnant at 30 weeks.Three healthy babies were obtained.Prenatal diagnosis was performed in the second trimester,fetal karyotypes were normal,and fetal genotypes of monogenic disease families were consistent with PGD.Conclusions:NGS can effectively screen blastocysts carrying chromosomal diseases and monogenic disease,to block the transmission of genetic diseases.PGD is an effective measure to treat the fertility problems of high-risk patients with genetic diseases.