Pre‐implantation genetic testing for aneuploidy: the past, present and future

Abstract

Embryonic aneuploidy is often found in women undergoing assisted reproduction and is a common cause of poor outcomes, particularly in women of advanced maternal age and those with recurrent miscarriage and repetitive implantation failure. The aim of pre-implantation genetic testing for aneuploidy (PGT-A) is to select the most competent embryo for transfer, thus improving reproductive outcome. Initial PGT-A techniques failed to show an improvement in delivery rates and, in some trials, demonstrated inferior outcomes; however, advances in technology, combined with robust culture media and vitrification techniques, have significantly improved outcomes. Recent debate has argued for the increased clinical application of PGT-A, particularly in women of advanced maternal age; we provide an overview of PGT-A, including its past and associated limitations, the evolution in technology and latest outcomes, and address potential future implications. Learning objectives To understand the rationale behind the use of PGT-A. To review the evidence against and in favour of PGT-A. To understand the new techniques being used and how these have led to emerging evidence in favour of PGT-A. Ethical issues Risk of damage to embryos during biopsying process. PGT-A may result in either no embryos available for transfer or only embryos displaying mosaicism being available to transfer, with little long-term data on the outcomes of transferring mosaic embryos. PGT-A increases the cost of an already expensive treatment.

Preimplantation Genetic Testing for Aneuploidy: Current Perspectives

“…31 A recent Cochrane review which included 11 studies on PGT-A using FISH also concluded that the evidence currently available does not support the routine use of PGT-A and highlighted that this method could be harmful. 17 The reasons for the unexpected results from the FISH PGT-A studies are summarized in a recent clinical review, 2 and are generally agreed to be secondary to the limitations of FISH as a chromosome screening technique and the drawbacks associated with cleavage-stage biopsies. FISH enables screening of only up to 9 to 12 chromosomes as defined by the chosen probes; 16 as such, FISH is unable to reliably detect up to 30% of the aneuploidies and segmental abnormalities present in embryos.…”

“…12 It is possible to biopsy an embryo at three different time points. 2 The choice of timing of the embryo biopsy is also thought to be fundamental in the failure of initial PGT-A studies. 12,15,16 Eight of the nine RCTs included in the metaanalysis of early PGT-A studies used cleavage-stage biopsy, and one used polar body (PB) biopsy.…”

“…12 Various noninvasive methods have been investigated, all of which require further validation before they can be used in the clinical setting. 2,12,34 Blastocentesis: This refers to the aspiration of blastocoelic fluid from the blastocoelic cavity which contains DNA and proteins key to the regulation of embryo development. 12 Although one study demonstrated a 97.1% concordance rate between blastocentesis diagnoses and TE biopsy, DNA was obtained only in 82% of fluid samples and there were issues with false positive and false negative (in up to 7.1% of cases).…”

“…This was achieved via platforms such as array comparative genomic hybridization (aCGH), quantitative real-time polymerase chain reaction (qRT-PCR), and next-generation sequencing (NGS), as well as improvements in culture media and better vitrification techniques. 2 These developments led to renewed interest in PGT-A, 18 and significant improvements in outcomes including improved implantation, pregnancy, and live birth rates, as well as a reduction in miscarriage and multiple pregnancy rates. 9,12,13,19 The beneficial effect of PGT-A has also been replicated in women with less favorable characteristics including AMA, 7,9,11,14,15,18,[20][21][22][23][24][25] RM, 5,26,27 and RIF.…”

Uterine Transplantation: Review of Livebirths and Reproductive Implications

“…78 Moreover, this stage embryo facilitates the capability of undertaking preimplantation genetic testing for aneuploidy (PGT-A), in which embryo biopsy from the trophectoderm during the blastocyst stage is favorable. 79 PGT-A facilitates embryo selection by enabling the opportunity to use chromosomally normal embryos, 80 avoiding those which are aneuploid, which may cause fetal abnormality and are accountable for more than half of miscarriages. 81 PGT-A has been shown to increase implantation and pregnancy rates and reduce the risk of miscarriage following single embryo transfer, 82,83 and results in a higher livebirth rate per embryo transfer.…”