Aneuploidy 16 in human embryos increases significantly with maternal age
Aneuploidy 16 in human embryos increases significantly with maternal age
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DOI：
10.1016/s0015-0282(16)58448-9
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发表时间：
1996-08-01
影响因子：
6.7
通讯作者：
Munne, S
中科院分区：
文献类型：
--
作者：
Benadiva, CA;Kligman, I;Munne, S
目的：为了在与临床NF相容的时间范围内，通过在植入前人类胚胎中使用多探针荧光原位杂交对X、Y、18、13和21号染色体进行分析的细胞核再循环来确定16号染色体的非整倍性，并评估与母体年龄相关的胚胎中16号染色体非整倍性的发生率，设计：前瞻性实验研究。在三级中心的体外受精程序。患者：104同意接受IVF的患者。主要结果测量：16号染色体倍体分析，共195个胚胎。在89个胚胎中，对X、Y、18和16号染色体（系列1）使用标准的多探针荧光原位杂交。剩余的106个胚胎（系列2）用新的16号染色体程序进行再分析，该程序包括在完成X、Y、18、13和21号染色体的标准分析后，用地高辛标记的cr卫星探针进行再杂交。根据女性的年龄将胚胎分为三组之一;第1组：小于或等于34岁（n = 34），第2组：35至39岁（n = 47）;第3组：大于或等于40岁（n = 23）。成功的分析，包括活检，固定和荧光原位杂交在大约10小时内实现了86%的卵裂球。发现16号染色体非整倍体率与母亲年龄增加之间存在显著关系：第1组：0%，第2组：6.3%，第3组：11.7%。在携带16号染色体异常的II型胚胎中，72.7%的胚胎为16号染色体单体，其余3个胚胎为2个三体和1个四体。临床应用该方案对5例非整倍体再植入患者进行了评估。16号染色体的非整倍体被发现在5个胚胎从这些patients.Conclusions：这项研究表明，植入前的主要人类非整倍体的遗传学诊断是可以实现的时间框架内兼容IVF。此外，这项研究证实，对于胚胎，现有的自然流产数据表明，16号染色体非整倍体随着母亲年龄的增加而增加。在自然流产中很少发现的胚胎单体性的高患病率表明，单体性16可能是与植入失败相关的因素，以及指出涉及16号染色体非整倍体产生的不同机制。
Objectives: To determine aneuploidy for chromosome 16 by recycling nuclei of cells already analyzed for chromosomes X, Y, 18, 13, and 21 using multiple-probe fluorescence in situ hybridization in preimplantation human embryos in a time frame compatible with clinical NF and to assess the incidence of chromosome 16 aneuploidy in embryos related to maternal age,Design: Prospective experimental study.Setting: In vitro fertilization program in a tertiary center.Patients: One hundred four consenting patients undergoing IVF.Main Outcome Measures: Chromosome 16 ploidy was analyzed in a total of 195 embryos. In 89 embryos, a standard multiple-probe fluorescence in situ hybridization was used for chromosomes X, Y, 18, and 16 (series 1). The remaining 106 embryos (series 2) were reanalyzed with a new procedure for chromosome 16, which involves rehybridization with a digoxigenin-labeled cr satellite probe after the standard analysis for chromosomes X, Y, 18, 13, and 21 was completed. The embryos were assigned to one of three groups according to the women's age; group 1: less than or equal to 34 years (n = 34), group 2: 35 to 39 years (n = 47); group 3: greater than or equal to 40 years (n = 23).Results: Successful analysis, including biopsy, fixation, and fluorescence in situ hybridization was achieved in 86% of the blastomeres within approximately 10 hours. a significant relationship was found between the rate of aneuploidy for chromosome 16 and increasing maternal age: group 1: 0%, group 2: 6.3%, and group 3: 11.7%. Monosomy for chromosome 16 was found in 72.7% of the II embryos carrying chromosome 16 anomalies, with the remaining three embryos having two trisomies and one tetrasomy. This new protocol was applied clinically to five patients undergoing reimplantation aneuploidy assessment. Aneuploidy for chromosome 16 was found in five embryos from three of those patients.Conclusions: This study demonstrates that preimplantation genetic diagnosis of the major human aneuploidies is achievable within a time frame compatible with IVF. In addition, this study confirms, for embryos, the existing data from spontaneous abortions suggesting that chromosome 16 aneuploidy increases with maternal age. The high prevalence of embryonic monosomy, which is rarely found in spontaneous abortions, suggests that monosomy 16 could be a factor-associated with failure of implantation, as well as pointing to a different mechanism involved in the generation of chromosome 16 aneuploidy.