植入前基因筛查（PGS）的准确性受到人类胚胎嵌合程度的影响。
Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos.
作者信息
Gleicher Norbert, Vidali Andrea, Braverman Jeffrey, Kushnir Vitaly A, Barad David H, Hudson Cynthia, Wu Yang-Guan, Wang Qi, Zhang Lin, Albertini David F
机构信息
The Center for Human Reproduction, 21 East 69th Street, New York, NY, 10021, USA.
The Foundation for Reproductive Medicine, New York, NY, USA.
出版信息
Reprod Biol Endocrinol. 2016 Sep 5;14(1):54. doi: 10.1186/s12958-016-0193-6.
BACKGROUND
To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Whether one such biopsy can correctly assess embryo ploidy has recently, however, been questioned.
METHODS
This descriptive study investigated accuracy of PGS in two ways. Part I: Two infertile couples donated 11 embryos, previously diagnosed as aneuploid and, therefore, destined to be discarded. They were dissected into 37 anonymized specimens, and sent to another national laboratory for repeat analyses to assess (i) inter-laboratory congruity and (ii) intra-embryo congruity of multiple embryo biopsies in a single laboratory. Part II: Reports on human IVF cycle outcomes after transfer of allegedly aneuploid embryos into 8 infertile patients.
RESULTS
Only 2/11 (18.2 %) embryos were identically assessed at two PGS laboratories; 4/11 (36.4 %), on repeat analysis were chromosomally normal, 2 mosaic normal/abnormal, and 5/11 (45.5 %) completely differed in reported aneuploidies. In intra-embryo analyses, 5/10 (50 %) differed between biopsy sites. Eight transfers of previously reported aneuploid embryos resulted in 5 chromosomally normal pregnancies, 4 delivered and 1 ongoing. Three patients did not conceive, though 1 among them experienced a chemical pregnancy.
CONCLUSIONS
Though populations of both study parts are too small to draw statistically adequately powered conclusions on specific degrees of inaccuracy of PGS, here presented results do raise concerns especially about false-positive diagnoses. While inter-laboratory variations may at least partially be explained by different diagnostic platforms utilized, they cannot explain observed intra-embryo variations, suggesting more frequent trophectoderm mosiaicsm than previously reported. Together with recentl published mouse studies of lineages-specific degrees of survival of aneuploid cells in early stage embryos, these results call into question the biological basis of PGS, based on the assumption that a single trophectoderm biopsy can reliably determine embryo ploidy.
背景
为了避免非整倍体胚胎的移植，目前的植入前基因筛查（PGS）通常在囊胚期进行一次滋养外胚层活检，假定其能代表胚胎的倍性。然而，最近有人质疑这样一次活检能否正确评估胚胎倍性。
方法
这项描述性研究通过两种方式调查PGS的准确性。第一部分：两对不孕夫妇捐赠了11个胚胎，这些胚胎先前被诊断为非整倍体，因此注定要被丢弃。将它们解剖成37个匿名样本，并送往另一个国家实验室进行重复分析，以评估（i）实验室间的一致性和（ii）单个实验室中多个胚胎活检的胚胎内一致性。第二部分：关于将据称是非整倍体的胚胎移植到8名不孕患者后的人类体外受精周期结果的报告。
结果
在两个PGS实验室中，只有2/11（18.2%）的胚胎得到了相同的评估；4/11（36.4%）在重复分析时染色体正常，2个为正常/异常嵌合体，5/11（45.5%）报告的非整倍体完全不同。在胚胎内分析中，5/10（50%）的活检部位之间存在差异。先前报告的非整倍体胚胎的8次移植导致了5次染色体正常的妊娠，4例分娩，1例仍在进行中。3名患者未受孕，其中1名经历了生化妊娠。
结论
尽管两个研究部分的样本量都太小，无法就PGS的具体不准确程度得出统计学上有充分说服力的结论，但这里呈现的结果确实引发了人们的担忧，尤其是对假阳性诊断的担忧。虽然实验室间的差异至少部分可以由所使用的不同诊断平台来解释，但它们无法解释观察到的胚胎内差异，这表明滋养外胚层嵌合体比先前报道的更为常见。连同最近发表的关于早期胚胎中非整倍体细胞谱系特异性存活程度的小鼠研究，这些结果对基于单次滋养外胚层活检能够可靠地确定胚胎倍性这一假设的PGS生物学基础提出了质疑。
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