Abstract:

Objective　Utilizing CNV-seq analysis on chorionic villus tissue obtained from spontaneous abortion, to make a clinical diagnosis for the cause of miscarriage and to provide genetic guidance for subsequent pregnancies. Methods　CNV-seq technology was used to detect the chorionic villi of early spontaneous abortion, and the chromosomal abnormalities were counted. The age, gestational age, previous abortion times, and effect of pregnancy mode on the chromosomal results of 181 female patients who were diagnosed as spontaneous abortion by color ultrasonography in Binzhou Medical University Hospital from January 2019 to June 2023 were retrospectively analyzed. There were 108 cases of natural pregnancy abortion and 73 cases of abortion after assisted reproductive technology (ART). Among them, 42 pregnancies were assisted by in vitro fertilization and embryo transfer (IVF), 24 by intracytoplasmic sperm injection (ICSI), and 7 by artificial insemination (IUI). The age was (32.83±5.34) years old, the gestational age was (57.39±10.05) d, and the number of spontaneous abortion was 0-5 times. One-way analysis of variance and χ² test were applied. Results　Out of the 181 cases of spontaneous abortion, all the chorionic villi were successfully examined. Among them, 74 cases exhibited normal findings, while 107 cases showed abnormalities, resulting in an abnormal rate of 59.12%. There were 98 cases with abnormal chromosome numbers, including 67 cases with trisomy, 13 cases with X monomer, 17 cases with chimera (7 cases with trisomy 16 chimera), and 1 case with triploid. There were 9 cases of gene copy number variations, and the fragment variation ranged from 2.12 to 95.92 (37.32±24.57) Mb. According to different methods of conception, they were divided into a natural pregnancy group and an ART assisted pregnancy group. Out of the 73 cases in the ATR assisted pregnancy group, there were 40 abnormal cases, with an abnormal rate of 54.8%. Out of the 108 cases in the natural pregnancy group, there were 67 abnormal cases, with an abnormal rate of 62.0%. There was no statistically significant difference in the results of chorionic chromosome abnormality between the two groups (χ²=0.954, P=0.331). Conclusions　Chromosomal abnormalities are the primary factors contributing to early embryonic miscarriage, with numerical abnormalities being the major concern. It's worth noting that ART does not elevate the risk of spontaneous abortion. The application of the CNV-seq method to detect chromosomal variations in chorionic villi is of significant importance in unraveling the underlying causes of early spontaneous abortion.

Key words:

Assisted reproduction technology, CNV-seq, Spontaneous abortion, Chorionic tissue, Genetics

摘要：

目的　通过低深度全基因组测序CNV检测技术（CNV-seq）分析自然流产绒毛组织的染色体情况，为流产原因做出临床诊断，为下次妊娠提供遗传学指导。方法　采用CNV-seq检测早期自然流产胚胎绒毛组织，统计染色体异常情况。回顾性分析2019年1月至2023年6月于滨州医学院附属医院就诊经彩超提示诊断为自然流产的181例女性患者的年龄、孕龄、既往流产次数及受孕方式对胚胎染色体结果的影响。自然妊娠流产108例（108/181），经辅助生殖技术（ART）助孕后流产73例（73/181），其中体外受精-胚胎移植（IVF）助孕42例、卵胞浆内单精子注射（ICSI）助孕24例、人工授精（IUI）助孕7例。181例自然流产患者年龄（32.83±5.34）岁，孕龄（57.39±10.05）d，自然流产次数0～5次。统计学方法采用单因素方差分析、χ²检验。结果　181例自然流产绒毛组织均检测成功，74例结果未见异常，107例结果异常，异常率为59.12%。其中染色体数目异常98例，包括三体67例、X单体13例、嵌合体17例（16三体嵌合型7例）、三倍体1例；基因拷贝数变异9例，片段变异范围为2.12～95.92（37.32±24.57）Mb。根据受孕方式不同，分为自然妊娠组与ART助孕组，ATR助孕组共73例，异常40例，异常率54.8%；自然妊娠组共108例，异常67例，异常率62.0%；两组比较差异无统计学意义（χ²=0.954，P=0.331）。结论　染色体异常是胚胎早期流产的主要因素，主要为染色体数目异常；ART助孕不会增加自然流产的风险；CNV-seq方法检测绒毛染色体对明确早期自然流产原因有重大意义。

关键词:

辅助生殖技术, CNV-seq, 自然流产, 绒毛组织, 遗传学