胚胎染色体异常与女性年龄和FMR1基因相关性分析

Correlation analysis of fetal chromosome abnormalities with female age and FMR1 gene

目的探讨稽留流产中胚胎染色体异常的影响因素。方法回顾性分析2017—2020年在首都医科大学附属北京妇产医院计划生育科就诊的稽留流产要求刮宫手术的743名女性患者的临床资料。记录患者的一般情况及胚胎染色体和夫妻双方染色体结果,以及FMR1基因的CGG拷贝数(结果以CGG1和CGG2形式表达)。根据胚胎染色体检查结果将患者分为胚胎染色体异常组(n=409)和胚胎染色体正常组(n=334),比较两组患者的基本情况、实验室检查以及妊娠结局。结果743名患者中,胚胎染色体异常检出率为54.50%(409/743),胚胎染色体异常以染色体三体为主,占82.15%(336/409)。与胚胎染色体正常组比较,胚胎染色体异常组患者的年龄显著升高[(32.66±4.60)vs.(31.17±3.74),P<0.05],孕、产次显著增多[分别为(2.01±1.29)vs.(1.83±1.05);(0.33±1.21)vs.(0.17±0.48)](P<0.05),FMR1基因CGG2序列重复数更小[(28.98±2.16)vs.(29.44±2.14),P<0.05],但FMR1基因CGG2序列均为正常型。以不同年龄分组比较发现,32岁为易发胚胎染色体异常的临界年龄(P<0.05)。Logistics多因素回归分析表明,随着年龄的增长,胚胎染色体异常发生率增加(β=0.04,P<0.05);随着正常型的FMR1基因CGG2拷贝数增加,胚胎染色体异常发生率轻微降低(β=-0.08,P<0.05)。结论年龄为胚胎染色体异常的危险因素,32岁及以后胚胎染色体异常风险增加。正常型的FMR1基因CGG拷贝数不是胚胎染色体异常的危险因素。

Objective:To investigate the influencing factors of embryo chromosome abnormality in missed abortion.Methods:The clinical data of 743 women with missed abortion requiring curettage in the Beijing Obstetrics and Gynecology Hospital,Capital Medical University from 2017 to 2020 were retrospectively analyzed.The general information of the patients,the result of embryo chromosome and couple chromosome and copy number of CGG of FMR1 gene(the results were expressed as CGG1 and CGG2)were recorded.According to the results of embryo chromosome,the patients were divided into abnormal embryo chromosome group(n=409)and normal embryo chromosome group(n=334).The basic information,laboratory examination and pregnancy outcome of the two groups were compared.Results:Among 743 patients,409(54.50%)were abnormal chromosome.Trisomy(82.15%,336/409)was the main embryo chromosomal abnormality.Compared with the normal embryo chromosome patients,the age of the patients with abnormal embryo chromosome was older[(32.66±4.60)vs.(31.17±3.74),P<0.05],the gravidity and parity were increased[(2.01±1.29)vs.(1.83±1.05),(0.33±1.21)vs.(0.17±0.48),respectively](P<0.05),the repeat number of CGG2 sequence of FMR1 gene was smaller[(28.98±2.16)vs.(29.44±2.14),P<0.05],but CGG2 sequence of FMR1 gene was normal.Analysis of different age groups showed that 32 years old was the critical age for embryo chromosome abnormality(P<0.05).Logistic regression analysis showed that the incidence of embryo chromosome abnormality increased with the increase of age(β=0.04,P<0.05),and the incidence of embryo chromosome abnormality decreased with the increase of the CGG2 copy number of FMR1 gene(β=-0.08,P<0.05).Conclusions:Age is the risk factor of embryo chromosome abnormality,and the risk of embryo chromosome abnormality increases at 32 years old and older.Normal copy number of CGG2 of FMR1 gene is not a risk factor of embryo chromosome abnormality.