CNV-seq联合STR在胚胎停滞发育患者妊娠产物中的应用

Application of CNV-seq combined with STR in products of conception in patients with embryonic arrest and development

目的探讨染色体拷贝数变异测序(CNV-seq)联合短串联重复序列(STR)在胚胎停滞发育患者流产产物(POC)中的应用。方法选取2020年2月至2024年2月在阜阳市肿瘤医院就诊的367例胚胎停滞发育患者为研究对象,采集POC进行CNV-seq及STR检测。对比不同孕周、年龄段患者的异常染色体的检出情况。结果367例POC中,检出染色体异常197例,检出率为53.68%,其中非整倍体占67.51%(133/197)、嵌合体12.18%(24/197)、三倍体13.20%(26/197)、致病性拷贝数变异(PCNVs)2.54%(5/197)、结构异常4.06%(8/197);染色体非整倍体中以Chr16三体和ChrX单体最常见,Chr22三体、Chr18三体、Chr21三体次之。248例孕早期患者POC中异常染色体检出率为62.50%(155/248),其中以三倍体(14.19%)和染色体非整倍体最常见,染色体非整倍体以Chr16三体(13.55%)、Chr18三体(2.58%)、Chr21三体(5.16%)、Chr22三体(7.74%)、ChrX单体(11.61%)最常见;119例孕中期染色体异常检出率为35.29%(42/119),以染色体非整倍体[Chr16三体(9.52%)、Chr18三体(16.67%)、Chr21三体(7.14%)、Chr22三体(2.38%)、ChrX单体(11.90%)]和三倍体(9.52%)为主;孕中期与孕早期染色体异常总检出率及Chr18三体检出率比较,差异均有统计学意义(χ2=23.94、6.219,P<0.05)。177例<35岁患者染色体异常检出率为48.02%(85/177),136例30~<35岁患者为57.35%(78/136),54例≥35岁患者为62.96%(34/54);<30岁患者与≥35岁患者的染色体异常检出率比较,差异有统计学意义(P<0.05),但<30岁患者和≥35岁患者分别与30~<35岁患者的染色体异常检出率比较,差异均无统计学意义(P>0.05)。结论采用CNV-seq联合STR检测胚胎停滞发育患者的POC,可深入探寻胚胎停滞发育的原因,评估下次妊娠的复发风险,为遗传咨询和生殖规划提供有价值的信息。

Objective To explore the application of chromosomal copy number variation sequence(CNV-seq)combined with short tandem repeat(STR)in products of conception(POC)in patients with embryonic arrest and development.Methods A total of 367 patients with embryonic arrest and development who came to Fuyang Cancer Hospital from February 2020 to February 2024 were selected for the study,and POC were collected for CNV-seq and STR detection.The detection rate of abnormal chromosomes in patients of different gestational weeks and ages were compared.Results Among the 367 POC,197 cases of chromosomal abnormalities were detected,with detection rate of 53.68%,including aneuploidies accounted for 67.51%(133/197),chimeras 12.18%(24/197),triploids 13.20%(26/197),pathogenic chromosomal copy number variation(PCNVs)2.54%(5/197)and chromosomal structural abnormalities 4.06%(8/197),respectively;chromosomal aneuploidy was the most common in Chr16 trisomy and ChrX monosomy,followed by Chr22 trisomy,Chr18 trisomy and Chr21 trisomy.The detection rate of chromosomal abnormality of 248 patients in the first trimester pregnancy was 62.50%(155/248),which mostly common in triploidy(with detection rate of 14.19%)and chromosomal aneuploidy,which was the most common in Chr16 trisomy(13.55%),Chr18 trisomy(2.58%),Chr21 trisomy(5.16%),Chr22 trisomy(7.74%),and ChrX haplogroup(11.61%);the detection rate of chromosomal abnormality of 119 patients in the second trimester pregnancy was 35.29%(42/119),with chromosomal aneuploidy[Chr16 trisomy(9.52%),Chr18 trisomy(16.67%),Chr21 trisomy(7.14%),Chr22 trisomy(2.38%),and ChrX monosomy(11.90%)]and triploidy(with detection rate of 9.52%)were predominant;the total detection rate of chromosomal abnormalities and the detection rate of Chr18 trisomy of patients between the first trimester pregnancy and the second trimester pregnancy had statistically significant differences(χ2=23.94,6.219,P<0.05).The detection rate of chromosomal abnormality of 177 patients<30 years old was 48.02%(85/177),which in 136 patients 30-<35 years old was 57.35%(78/136)and 54 patients≥35 years old was 62.96%(34/54);The difference in chromosomal abnormality detection rate between the patients<30 years old and≥35 years old was statistically significant(P<0.05),but comparison of patients<30 years old and≥35 years old with 30-<35 years old,respectively,had no statistically significant differences(P>0.05).Conclusion Application of CNV-seq combined with STR in POC of patients with embryonic arrest and development can deeply explore the causes of embryo arrest,evaluate the risk of recurrence of the next pregnancy abortion,and provide valuable information for genetic counseling and reproductive planning.