胚胎单基因病诊断患者辅助生殖累积妊娠率低的原因初探

A preliminary study of low cumulative pregnancy rates in ART patients with pre-implantation genetic test for monogenetic

目的探讨胚胎植入前单基因病检测(PGT-M)患者辅助生殖累积妊娠率低的可能原因,为临床遗传咨询提供理论依据。方法回顾性分析我中心2016年7月至2017年6月期间的PGT-M患者,共31个促排卵周期,102枚胚胎,行高通量测序染色体筛查及单基因病诊断,为PGF-M组。同时收集同期的行胚胎植入前染色体非整倍性检测(PGT-A)患者,共90个周期,350枚胚胎,行高通量测序染色体筛查,为PGT-A组。将PGT-M组患者有效胚胎占比,从染色体筛查及单基因病诊断两个层面,分别与PGT-A组患者胚胎染色体筛查结果,以及单基因病孟德尔遗传规律预测结果比对分析。结果 PGT-M组与PGT-A组在女方平均年龄、平均Gn使用量、平均Gn使用天数、平均获卵数等临床资料无显著性差异(P>0.05);PGT-M组与PGT-A组染色体正常胚胎占比(45.74%vs.48.29%)差异无统计学意义(P>0.05);单基因病诊断完全正常的胚胎,实际占比显著小于理论占比(29.17%vs.42.19%)(P<0.05)。综合染色体筛查及单基因病诊断结果,PGT-M组患者有效胚胎占27.45%,其中完全正常胚胎占12.75%。结论 PGT-M患者胚胎由于较低的染色体整倍性概率及较高的单基因病致病概率,导致最终有效胚胎数较少,进而使得累积妊娠率偏低。

Objective： To explore the possible causes of low cumulative patients with pre imp theoretical basis for c pregnancy rates of gene defects （PGT assisted reproduction M）,so as to provide Methods： The data of PGT M patients in our center from July 2016 to June 2017 were retrospectively analyzed,which included 31 ovulation induction cycles, 102 embryos through high throughput sequencing chromosome screening and monogenic disease diagnosis as PGT M group. At the same time, the patients with pre implantation chromosome aneuploidy test（PGT A）were collected, which included 90 cycles, 350 embryos through high throughput sequencing chromosome screening as PGT A group. The normal embryo percentage confirmed by embryo chromosome screening and single gene disease diagnosis in PGT M patients was compared with the normal embryo percentage confirmed by embryo chromosome screening in PGT A patients, and also compared with the prediction results according to Mendelian genetic law of monogenic diseases. Results： There were no significant differences in age, doses and days of Gn used, and number of oocytes retrieved between the PGT M group and the PGT A group（P〉0.05）. There was no significant differencein percentage of normal embryonic chromosome（45.74% vs. 48.29%,P〉0.05）. The actual percentage of completely normal embryos confirmed by monogenic diseases diagnosis was significantly less than the theoretical proportion （29.17% vs. 42.19%）（P 〈 0.05）. Combined with the results of chromosome screening and single gene disease diagnosis, the effective embryos accounted for 27.45 --00 ,with 12.75% of fully normal embryos in PGT M patients. Conclusions： Due to the lower chromosome euploidy and the higher incidence of single gene disease, PGT M patients have less effective embryos,which lead to the low cumulative pregnancy rate.