论文部分内容阅读
目的 :探讨辅助生殖技术是否会增加胚胎染色体异常的风险。方法 :根据不同受孕方式,将2 318例早孕期流产的患者分成体外受精(in vitro fertilization,IVF)组(n=310)、卵细胞质内单精子显微注射(intracytoplasmic sperminjection,ICSI)组(n=86)、自然妊娠(natural conception,NC)组(n=1 922)3组,分析比较3组的异常核型发生率,分析患者年龄与非整倍体发生率间的关系,以及单核苷酸多态性微阵列芯片(single nucleotide polymorphism-based arrays,SNP-array)、下一代测序(next generation sequencing,NGS)、传统细胞培养结合G显带这3种不同检测方法的异常核型检出率。结果:2 318例流产绒毛中,1 420例存在染色体异常,异常率为61.26%,其中异常核型以非整倍体占绝对多数,共发现1 040例,发生率为44.86%(1 040/2 318),占异常核型的73.24%(1 040/1 420),涉及除1号染色体以外所有染色体,且以16-三体发生频率最高,其次为22-三体和45,X单体。IVF组、ICSI组及NC组间的流产物染色体总体异常率差异无统计学意义(57.74%、55.81%、62.02%,P=0.207)。但ICSI组的三倍体发生率明显低于NC组及IVF组(0、7.23%、7.42%,P=0.035)。当根据流产患者年龄分组时,高龄组(≥35岁)的非整倍体发生率明显高于低龄组(<35岁)(60.25%比40.07%,P<0.01)。SNP-array技术、NGS及核型分析对异常核型的总体检出存在差异(62.94%比53.13%、59.92%,P=0.035),SNP-array技术对非平衡性结构异常、三倍体、微重复和微缺失的检出率最高,还能检出单亲二倍体(uniparental disomy,UPD)和杂合性缺失(loss of heterozygosity,LOH),而核型分析对四倍体的检出率最高。结论:胚胎染色体异常是自然流产的最重要原因;IVF不增加胚胎染色体异常的发生率,但ICSI有增加胚胎性染色体非整倍体风险的趋势。随着母亲年龄的增长,胚胎非整倍体的发生率显著升高。以SNP-array和NGS为代表的分子检测技术有望成为流产物染色体检测的一线方法。
Objective: To investigate if assisted reproductive technology may increase the risk of embryo chromosomal abnormalities. Methods: According to different methods of pregnancy, 2 318 cases of abortion in early pregnancy were divided into in vitro fertilization (IVF) group (n = 310), intracytoplasmic sperjection (ICSI) group = 86), three groups of nocturnal pregnancy (NC) (n = 1 922). The incidence of abnormal karyotype in three groups was analyzed. The relationship between age and aneuploidy was analyzed. (SNP-array), next generation sequencing (NGS), traditional cell culture combined with G-banding, three different detection methods of abnormal karyotype Rate out. Results: Of the 2 318 abortions, 1 420 had chromosomal abnormalities with an abnormality rate of 61.26%. Among them, the abnormal karyotypes accounted for the absolute majority with aneuploidy. A total of 1040 cases were found, accounting for 44.86% (1 040 / 2 318), accounting for 73.24% (1 040/1 420) of all the abnormal karyotypes, involving all chromosomes except chromosome 1, with the highest frequency of 16-trisomy followed by 22-trisomy and 45 X-monomer . There was no significant difference in the total chromosomal abnormalities between the IVF group, the ICSI group and the NC group (57.74%, 55.81%, 62.02%, P = 0.207). However, the incidence of triploidy in ICSI group was significantly lower than that in NC group and IVF group (0, 7.23%, 7.42%, P = 0.035). When grouped according to the age of abortion, the incidence of aneuploidy in the advanced age group (≥35 years) was significantly higher than that in the younger age group (<35 years old) (60.25% vs. 40.07%, P <0.01). SNP-array technique, NGS and karyotype analysis showed that there were differences in the overall detection of abnormal karyotypes (62.94% vs 53.13%, 59.92%, P = 0.035). The SNP- The detection rate of microdissection and microdeletion were the highest, but uniparental disomy (UPD) and loss of heterozygosity (LOH) were also detected. The detection rate of tetraploid by karyotype analysis highest. CONCLUSIONS: Abnormal fetal chromosomal abnormalities are the most important cause of spontaneous abortion. IVF does not increase the incidence of embryonic chromosomal abnormalities, but ICSI tends to increase the risk of aneuploid embryos. As maternal age increases, the incidence of embryonic aneuploidy increases significantly. Molecular detection techniques, such as SNP-array and NGS, are expected to be the first-line method for the detection of chromosomes in stream products.