复发性流产染色体异常及影响因素分析

Analysis of chromosome abnormalities and influencing factors in recurrent spontaneous abortion

目的探讨复发性流产染色体异常及影响因素。方法选取2015年1月至2017年11月在郑州大学第二附属医院就诊的复发性流产患者73例,其中52例清宫术后新鲜绒毛组织同时行G显带染色体核型分析和高通量测序（NGS）检测;21例因自然流产或药物流产后绒毛组织行NGS检测,其父母均行外周血染色体核型分析。结果 （1）52例清宫术后绒毛染色体核型正常37例,数目异常15例;NGS检测正常14例（26.9%）,数目异常7例,数目异常且存在拷贝数变异（CNV）7例,仅存在CNV〉10 Mb的重复或缺失24例;1例染色体核型分析为45,XO,NGS结果为正常。21例自然流产后绒毛仅行NGS患者中,数目异常5例,CNV〉10 Mb的重复或缺失2例,正常14例。73例患者中,父方染色体均正常,母方染色体异常4例（5.5%）,其中2例染色体平衡易位者胚胎染色体分别为14-三体合并CNV和7-三体,1例染色体平衡易位和1例10号染色体长臂内倒位者胚胎染色体正常。（2）73例患者中,年龄≥35岁者绒毛染色体异常发生率（76.7%,23/30）高于年龄〈35岁者（53.5%,23/43）（P=0.044）。自然流产3次者绒毛染色体异常发生率（73.3%,33/45）高于自然流产≥4次者（46.4%,13/28）（P=0.021）;排除胚胎染色体异常因素后,自然流产≥4次者自身免疫抗体阳性率（60.0%,9/15）高于自然流产3次者（8.3%,1/12）（P=0.006）。结论高通量测序技术可检测染色体微粒缺失,高龄是引起复发性流产胚胎染色体异常的高危因素,自然流产≥4次者自身免疫抗体阳性率增加。

Objective To explore the chromosomal abnormalities and influencing factors in recurrent spontaneous abortions（RSA）. Methods 73 RSA patients were selected at the Second Affiliated Hospital of Zhengzhou University from January 2015 to November 2017. 52 cases of fresh villi were examined by G-banding karyotype analysis and high-throughput sequencing（NGS）; 21 cases of spontaneous abortion or medical abortion were examined by NGS. Peripheral blood karyotype of all parents were tested. Results（1） 52 cases of curettage villis were normal in 37 cases and number abnormal in 15 cases; the NGS results were normal in 14 cases（26.9%）, number abnormal in 7 cases, number abnormal number with CNV in 7 cases and only with 10 Mb CNV of chromosome duplications or deletions in 24 cases; 1 case of G-band karyotype was 45, XO while NGS result was normal. 21 patients who only tested by NGS were number abnormal in 5 cases, 10 Mb CNV duplication or deletion in 2 cases and normal in 14 cases. Peripheral blood results of fathers were normal in all 73 patients, the mothers＇ were abnormal in 4 cases（5.5%）. 14-trisomy with CNV and 7-trimosy of embryo＇s chromosome in 2 chromosome balance translocations of mother. One chromosomal balance translocation and one inverted chromosome 10 in the long arm of mother both had normal embryo chromosome.（2） The incidence of chromosomal abnormalities in chorionic villi of ≥35 years old RSA patients（76.7%, 23/30） was higher than those of 〈35 years old（53.5%, 23/43）（P =0.044） in 73 patients. Abortion of 3 times（73.3%, 33/45） was higher than≥4 times（46.4%, 13/28）（P=0.021）; Excluding embryo chromosome abnormalities, abortion of≥4 times had a higher positive rate of autoimmune antibody（60.0%, 9/15） than those of 3 times（8.3%, 1/12）（P =0.006）. Conclusions The NGS technology can detect chromosome microdeletions, advanced age is the high risk factor of embryo chromosome abnormalities of RSA, autoantibody antibody positive rate is increasing in abortion of ≥4 times.