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中华妇幼临床医学杂志(电子版) ›› 2022, Vol. 18 ›› Issue (06) : 652 -659. doi: 10.3877/cma.j.issn.1673-5250.2022.06.006

论著

染色体相互易位携带者胚胎植入前染色体结构重排遗传学检测结果的影响因素分析
王珺, 张振强, 王茜怡, 苟兴庆, 何玉萍†()   
  1. 空军军医大学唐都医院妇产科生殖医学中心，西安　710038
  • 收稿日期:2022-08-12 修回日期:2022-11-10 出版日期:2022-12-01
  • 通信作者: 何玉萍

Analysis of influencing factors on results of embryo preimplantation genetic testing for chromosome structural rearrangement in chromosomal reciprocal translocation carriers

Jun Wang, Zhenqiang Zhang, Xiyi Wang, Xingqing Gou, Yuping He†()   

  1. Center for Reproductive Medicine, Department of Gynecology & Obsterics, Tangdu Hospital of Air Force Medical University, Xi′an 710038, Shaanxi Province, China
  • Received:2022-08-12 Revised:2022-11-10 Published:2022-12-01
  • Corresponding author: Yuping He
  • Supported by:
    General Project of Key Research and Development Program of Shaanxi Provincial Department of Science and Technology(2021SF-012)
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引用本文：

王珺, 张振强, 王茜怡, 苟兴庆, 何玉萍. 染色体相互易位携带者胚胎植入前染色体结构重排遗传学检测结果的影响因素分析[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(06): 652-659.

Jun Wang, Zhenqiang Zhang, Xiyi Wang, Xingqing Gou, Yuping He. Analysis of influencing factors on results of embryo preimplantation genetic testing for chromosome structural rearrangement in chromosomal reciprocal translocation carriers[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(06): 652-659.

目的

探讨夫妇(亲代)之一的染色体相互易位携带类型，对其囊胚染色体异常的影响。

方法

选择2018年6月至2021年6月于空军军医大学唐都医院采取辅助生殖技术(ART)助孕，并进行胚胎植入前染色体结构重排遗传学检测(PGT-SR)的231对夫妇其中之一为染色体相互易位携带者的1 091枚囊胚为研究对象。回顾性分析亲代的临床病例资料及其囊胚PGT-SR结果。采用成组t检验及χ2检验，对PGT-SR结果为染色体异常与正常囊胚的亲代(染色体相互易位携带者)临床资料进行比较(单因素分析)；采用多因素非条件logistic回归分析，对染色体相互易位携带者的囊胚PGT-SR结果影响因素进行分析。本研究经空军军医大学唐都医院伦理委员会批准(审批文号：K202108-09)，所有受试者签署胚胎PGT-SR知情同意书。

结果

①染色体相互易位携带者的囊胚PGT-SR结果影响因素的单因素分析显示：染色体异常囊胚的亲代为最长和最短易位片段的比值(TSR)≥2及染色体相互易位片段含末端断点的染色体相互易位携带者的比例(76.8%、38.0%)，均高于染色体正常囊胚(68.7%、29.1%)，并且差异均有统计学意义(χ2＝7.67、7.91，P＝0.006、0.005)。②多因素非条件logistic回归分析结果：染色体相互易位携带者为女性(OR＝1.39，95%CI：1.05~1.85，P＝0.021)，TSR≥2(OR＝1.48，95%CI：1.13~1.94，P＝0.005)，染色体相互易位片段含末端断点(OR＝1.50，95%CI：1.13~2.00，P＝0.005)，均是染色体相互易位携带者的囊胚PGT-SR结果为染色体异常的独立危险因素。③TSR≥2与TSR<2，以及染色体相互易位片段含末端断点与不含末端断点的染色体相互易位携带者的囊胚PGT-SR结果(染色体拷贝数正常、易位染色体异常、其他染色体异常)构成比比较，差异均有统计学意义(P<0.05)。

结论

对于夫妇中染色体相互易位携带者为女性，TSR≥2及染色体相互易位片段含末端断点的染色体相互易位携带者，其囊胚染色体异常风险较高，在采取ART助孕过程中建议进行胚胎PGT-SR，并做好充分的遗传咨询。

关键词: 易位，遗传, 性别特性, 囊胚, 减数分裂, 染色体断裂点, 易位片段最长与最短的比值, 易位断点距着丝粒距离最长与最短的比值, 植入前染色体结构重排遗传学检测
Objective

To investigate the effects of one of the couples′ (parents) chromosomal reciprocal translocation carrier types on blastocyst chromosomal abnormalities.

Methods

From June 2018 to June 2021, a total of 1 091 blastocysts of 231 couples (one of the couple was carrier of chromosomal reciprocal translocation) who were assisted pregnancy by assisted reproductive technology (ART) in Tangdu Hospital of Air Force Medical University, and took embryo preimplantation genetic testing-chromosomal structural rearrangements (PGT-SR) were selected as research subjects. The clinical case data of the parents and their blastocyst PGT-SR results were retrospectively analyzed. Independent-samples t test and chi-square test were used to compare the clinical data of the parents (chromosomal reciprocal translocation carriers) between whose blastocysts with PGT-SR results of chromosomal abnormalities and normal (univariate analysis). The influencing factors on PGT-SR results of blastocysts of chromosomal translocation carriers were analyzed by multivariate unconditional logistic regression analysis. This study was approved by Ethics Committee of Tangdu Hospital of Air Force Medical University (Approval No. K202108-09). The guardians of the subjects signed the informed consents for embryo PGT-SR.

Results

① Univariate analysis of influencing factors on PGT-SR results of blastocysts of chromosomal translocation carriers showed that: the chromosomal translocation carriers′ proportion of parents with chromosome abnormal blastocysts whose ratio of the longest to the shortest translocated segments (TSR) ≥2 and chromosomal translocation fragment contained terminal breakpoint (76.8%, 38.0%) were higher than those with chromosome normal blastocysts (68.7%, 29.1%), and the differences were statistically significant (χ2=7.67, 7.91; P=0.006, 0.005). ② Multivariate unconditional logistic regression analysis showed that: female carriers of chromosomal translocation (OR=1.39, 95%CI: 1.05-1.85, P=0.021), TSR ≥2 (OR=1.48, 95%CI: 1.13-1.94, P=0.005), and chromosomal translocation fragments containing terminal breakpoints (OR=1.50, 95%CI: 1.13-2.00, P=0.005) all were independent risk factors for PGT-SR results of chromosomal abnormalities in blastocyst of chromosomal translocation carriers. ③There were significant differences in constituent ratio of blastocyst PGT-SR results (normal chromosome copy number, abnormal translocation chromosome, other chromosomal abnormalities) between TSR≥2 and TSR<2, between chromosomal translocation segments containing terminal breakpoints and translocation segments without terminal breakpoints (P<0.05).

Conclusions

For chromosomal translocation carriers of female, TSR≥2 and chromosomal translocation fragments containing terminal breakpoints, the risk of their blastocysts with chromosome abnormalities is higher. Embryo PGT-SR is recommended during ART to assist pregnancy, and adequate genetic counseling is required.

Key words: Translocation, genetic, Gender identity, Blastula, Meiosis, Chromosome breakpoints, The ratio of the longest to shortest translocation segment (TSR), The ratio of the longest and the shortest centric segments (CSR), Preimplantation genetic testing-chromosomal structural rearrangements
表1 囊胚PGT-SR结果为染色体异常与正常囊胚的亲代(染色体相互易位携带者)临床资料比较
囊胚PGT-SR结果 囊胚数(枚) 女性年龄(岁，±s) 男性年龄(岁，±s) 女性BMI(kg/m2，±s) 不孕年限(年，±s) 血清基础FSH水平(mIU/mL，±s) 血清基础LH水平(mIU/mL，±s) 血清基础雌二醇水平(pg/mL，±s) 血清AMH水平(ng/mL，±s)
染色体异常 771 30.0±3.0 31.7±3.4 21.9±3.2 2.3±2.1 6.1±1.3 6.0±2.8 46.5±32.2 4.3±2.5
染色体正常 320 30.1±2.8 31.9±3.3 22.3±3.0 2.4±2.4 6.1±1.3 6.0±2.6 45.0±22.4 4.3±2.2
统计量 t＝1.80 t＝0.98 t＝1.68 t＝1.03 t＝－0.25 t＝－0.23 t＝－0.18 t＝－0.12
P值 0.058 0.330 0.094 0.304 0.801 0.817 0.829 0.906
囊胚PGT-SR结果 囊胚数(枚) 不孕类型[枚数(%)] 不孕原因[枚数(%)] 卵巢刺激方案[枚数(%)] Gn使用量(IU，±s) Gn使用时间(d，±s)
原发性 继发性 单纯染色体因素 合并其他因素 GnRH长方案 GnRH拮抗剂方案
染色体异常 771 209(27.1) 562(72.9) 552(71.6) 219(28.4) 622(80.7) 149(19.3) 1 958±979 11.3±1.7
染色体正常 320 79(24.7) 241(75.3) 225(70.3) 95(29.7) 257(80.3) 63(19.7) 2 009±988 11.4±1.7
统计量 χ2＝0.68 χ2＝0.18 χ2＝0.02 t＝0.77 t＝1.10
P值 0.409 0.670 0.891 0.442 0.271
囊胚PGT-SR结果 囊胚数(枚) 获卵数(枚，±s) 成熟卵子数(枚，±s) 正常受精数(枚，±s) 囊胚形成数(枚，±s) 易位携带者性别[枚数(%)] 易位是否涉及近端着丝粒染色体[枚数(%)]
男性 女性 否 是
染色体异常 771 17.7±6.0 14.6±5.2 12.5±4.7 8.9±3.7 361(46.8) 410(53.2) 575(74.6) 196(25.4)
染色体正常 320 18.3±6.7 15.3±5.9 12.8±5.1 9.0±3.6 169(52.8) 151(47.2) 236(73.8) 84(26.2)
统计量 t＝1.92 t＝1.85 t＝1.11 t＝0.41 χ2＝3.25 χ2＝0.08
P值 0.054 0.065 0.266 0.682 0.071 0.775
囊胚PGT-SR结果 囊胚数(枚) TSR[枚数(%)] CSR[枚数(%)] 易位片段是否含末端断点[枚数(%)]
<2 ≥2 <2 ≥2 否 是
染色体异常 771 179(23.2) 592(76.8) 253(32.8) 518(67.2) 478(62.0) 293(38.0)
染色体正常 320 100(31.3) 220(68.7) 110(34.4) 210(65.6) 227(70.9) 93(29.1)
统计量 χ2＝7.67 χ2＝0.25 χ2＝7.91
P值 0.006 0.618 0.005
表2 对染色体相互易位携带者的囊胚滋养外胚层细胞PGT-SR结果影响因素的多因素非条件logistic回归分析结果
影响因素(染色体相互易位类型) B SE Wald值 P值 OR值 OR值95%CI
女性携带者(以男性为对照) 0.294 0.143 4.227 0.021 1.39 1.05~1.85
易位涉及近端着丝粒染色体(以未涉及近端着丝粒染色体为对照) 0.030 0.157 0.037 0.968 0.99 0.73~1.35
TSR≥2(以TSR<2为对照) 0.382 0.152 6.316 0.005 1.48 1.13~1.94
CSR≥2(以CSR<2为对照) 0.126 0.147 0.735 0.765 1.05 0.77~1.42
易位片段含末端断点(以易位片段不含末端断点为对照) 0.381 0.149 6.538 0.005 1.50 1.13~2.00
表3 3种类型染色体相互易位携带者的囊胚滋养外胚层细胞PGT-SR结果构成比比较[枚数(%)]
染色体相互易位携带者类型 囊胚数(枚) 染色体拷贝数正常 易位染色体异常 其他染色体异常a χ2值 P值
易位携带者性别 3.63 0.163
男 530 169(31.9) 178(33.6) 183(34.5)
女 561 151(26.9) 193(34.4) 217(38.7)
易位片段大小比值 7.79 0.020
TSR<2 279 100(35.8) 84(30.1) 95(34.1)
TSR≥2 812 220(27.1) 287(35.3) 305(37.6)
易位片段是否含末端断点 11.18 0.004
否 705 227(32.2) 218(30.9) 260(36.9)
是 386 93(24.1) 153(39.6) 140(36.3)
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[1] 费冬梅, 欧阳鲁平, 黄红倩, 孙惟佳, 刘天盛, 苏景玉, 谢意. 中孕期胎儿染色体平衡易位检测结果的细胞遗传学分析[J]. 中华妇幼临床医学杂志(电子版), 2018, 14(02): 207-212.
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