Reprogenetics, Livingston, New Jersey.
Reprogenetics UK, Oxford, United Kingdom; Institute of Reproductive Sciences, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom.
Fertil Steril. 2017 May;107(5):1085-1091. doi: 10.1016/j.fertnstert.2017.03.024. Epub 2017 Apr 6.
A significant proportion of human preimplantation embryos produced during the course of in vitro fertilization (IVF) treatments contain two or more cytogenetically distinct cell lines. This phenomenon, known as chromosomal mosaicism, can involve the presence of cells with different types of aneuploidy in the absence of any normal cells or a mixture of euploid and abnormal cells. Although a high prevalence of mosaicism at the cleavage and blastocyst stages has been appreciated for two decades, the precise frequency of the phenomenon and its consequences for embryo viability have been difficult to quantify. Recent advances in genetic technologies, such as high-resolution next-generation sequencing, have allowed mosaicism to be detected with much greater sensitivity than earlier methods. The application of these techniques to trophectoderm biopsies, taken from embryos before transfer to the uterus, has provided insight into the clinical impact of mosaicism. Data from recent studies show that blastocysts associated with mosaic trophectoderm biopsy specimens implant less often than embryos with a chromosomally normal biopsy. In addition, the mosaic embryos that succeed in establishing a pregnancy are at a significantly higher risk of miscarriage. Because mosaic embryos are less likely to produce a viable pregnancy than their euploid counterparts, we suggest that they are given a lower priority for transfer to the uterus. However, because these embryos can sometimes produce successful pregnancies, it is important that they can be considered for transfer in the absence of fully euploid embryos and after appropriate patient counseling. Unlike aneuploidy of meiotic origin, mosaicism, which is caused by mitotic errors occurring after fertilization, does not increase with advancing maternal age. There may, however, be clinical, treatment, or patient-related factors that contribute to the risk of mosaicism occurring. This review discusses the validation of methods that permit the detection of chromosomal mosaicism in IVF embryos and findings of clinical relevance.
在体外受精（IVF）治疗过程中产生的大量人类胚胎中，有相当一部分存在两个或更多细胞遗传学上不同的细胞系。这种现象称为染色体镶嵌，可能涉及存在具有不同类型非整倍体的细胞，而不存在任何正常细胞或整倍体和异常细胞的混合物。尽管二十年来人们已经认识到卵裂和囊胚阶段存在很高的镶嵌现象，但很难准确量化这种现象的频率及其对胚胎活力的影响。遗传技术的最新进展，如高分辨率下一代测序，使得镶嵌现象的检测灵敏度比早期方法大大提高。这些技术在滋养外胚层活检中的应用，从转移到子宫前的胚胎中获取，深入了解了镶嵌现象的临床影响。最近研究的数据表明，与染色体正常活检的胚胎相比，与镶嵌滋养外胚层活检标本相关的囊胚植入的可能性较小。此外，成功建立妊娠的镶嵌胚胎流产的风险明显更高。由于镶嵌胚胎比其整倍体对应物产生可存活妊娠的可能性更小，因此我们建议将其优先转移到子宫的优先级降低。但是，由于这些胚胎有时可以产生成功的妊娠，因此在没有完全整倍体胚胎且经过适当的患者咨询的情况下，考虑转移这些胚胎非常重要。与减数分裂起源的非整倍体不同，由受精后发生的有丝分裂错误引起的镶嵌现象不会随着母体年龄的增加而增加。然而，可能存在与临床、治疗或患者相关的因素会增加发生镶嵌现象的风险。这篇综述讨论了允许检测 IVF 胚胎中染色体镶嵌的方法的验证以及与临床相关的发现。
