本篇case report質疑PGS單一切片細胞之準確性
植入8個染色體異常之囊胚, 居然高達5個胎兒日後證實染色體正常
PGS假陽性(染色體異常)比率可能比想像中高
單一位置切片細胞無法代表全體囊胚細胞之染色體狀況
囊胚染色體異常與正常細胞共存之比例可能比想像中高
染色體異常與正常細胞共存下細胞有競合之關係,
物競天擇下, 染色體異常細胞可能會自行淘汰
Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos.
Gleicher N1,2,3,
Vidali A4,5,
Braverman J6,
Kushnir VA4,7,
Barad DH4,8,9,
Hudson C4,
Wu YG4,
Wang Q4,
Zhang L4,
Albertini DF4,10;
International PGS Consortium Study Group.
Abstract
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.
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