Abstract
BackgroundTo 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.MethodsThis 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.ResultsOnly 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.ConclusionsThough 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.
Highlights
To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy
Once embryo biopsy moved from cleavage- to blastocyst-stage, and selected chromosome investigation to full chromosomal complement analyses with highly accurate newly developed diagnostic platforms, the widely held assumption was that PGS, would show its clinical effectiveness
PGS laboratories and PGS platforms The Center for Human Reproduction (CHR) received 11 donated embryos for Part 1 of here reported manuscript. These embryos had previously at two national referral laboratories of international repute been reported as aneuploid: Reprogenetics (Livingston, N.J., a division of Cooper Surgical, Trumbull, CT) served one couple utilizing array CGH [14], and the not-for-profit Foundation for Embryonic Competence (FEC), utilizing an in-house developed test, called Select Comprehensive Chromosome Screening (CCS) based on real-time polymerase chain reaction technology, developed by Reproductive Medicine Associates of New Jersey (Basking Ridge, N.J.) [15] served the other couple
Summary
To preclude transfer of aneuploid embryos, current preimplantation genetic screening (PGS) usually involves one trophectoderm biopsy at blastocyst stage, assumed to represent embryo ploidy. Avoiding transfers of aneuploid embryos in association with in vitro fertilization (IVF) has been proposed since the early 1990s [2] under the assumption it would lead to better pregnancy rates and fewer miscarriages [3] This effort was given the acronym preimplantation genetic screening (PGS) but over almost two decades has failed to demonstrate promised improvements of in vitro fertilization (IVF) outcomes. Once embryo biopsy moved from cleavage- to blastocyst-stage (trophectoderm), and selected chromosome investigation to full chromosomal complement analyses with highly accurate newly developed diagnostic platforms, the widely held assumption was that PGS, would show its clinical effectiveness. When this did not happen, the ability of different PGS platforms to accurately determine embryo ploidy was questioned [9]
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