A systematic review on concurrent aneuploidy screening and preimplantation genetic testing for hereditary disorders: What is the prevalence of aneuploidy and is there a clinical effect from aneuploidy screening?

Abstract

Introduction:In assisted reproductive technology, aneuploidy is considered a primary cause of failed embryo implantation. This has led to the implementation of preimplantation genetic testing for aneuploidy in some clinics. The prevalence of aneuploidy and the use of aneuploidy screening during preimplantation genetic testing for inherited disorders has not previously been reviewed. Here, we systematically review the literature to investigate the prevalence of aneuploidy in blastocysts derived from patients carrying or affected by an inherited disorder, and whether screening for aneuploidy improves clinical outcomes. Material and methods:PubMed and Embase were searched for articles describing preimplantation genetic testing for monogenic disorders and/or structural rearrangements in combination with preimplantation genetic testing for aneuploidy. Original articles reporting aneuploidy rates at the blastocyst stage and/or clinical outcomes (positive human chorionic gonadotropin, gestational sacs/implantation rate, fetal heartbeat/clinical pregnancy, ongoing pregnancy, miscarriage, or live birth/delivery rate on a per transfer basis) were included. Case studies were excluded. Results:Of the 26 identified studies, none were randomized controlled trials, three were historical cohort studies with a reference group not receiving aneuploidy screening, and the remaining were case series. In weighted analysis, 34.1% of 7749 blastocysts were aneuploid. Screening for aneuploidy reduced the proportion of embryos suitable for transfer, thereby increasing the risk of experiencing a cycle without transferable embryos. In pooled analysis the percentage of embryos suitable for transfer was reduced from 57.5% to 37.2% following screening for aneuploidy. Among historical cohort studies, one reported significantly improved pregnancy and birth rates but did | 697 TOFT eT al. K E Y W O R D Saneuploidy screening, clinical outcomes, comprehensive chromosome screening, preimplantation genetic diagnosis-preimplantation screening, preimplantation genetic testing, systematic review Key messageOne-third of embryos derived from patients carrying or affected by an inherited disorder are aneuploid. Hence, prioritizing embryos by ploidy status should in theory improve clinical success rates per transfer. The design and quality of the current available data do not allow a conclusion to be drawn with respect to a clinical effect.

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“…It is apparent that, so far, the Nordic countries hesitate to implement PGT‐A clinically. The systematic review by Toft et al 4 regarding aneuploidy screening in PGT‐M/SR could not demonstrate an improved outcome, but the experience is sparse.…”

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“…However, the effect on miscarriage rates is contentious; some recent studies, including multi-centre randomized controlled trials, show a reduced risk of miscarriage ( Verpoest et al, 2018 , Scriven, 2020 ), while others found that it did not affect miscarriage rates ( Munné et al, 2019 , Murphy et al, 2019 , Sato et al, 2019 ), or that miscarriages were rare even following the implantation of embryos classified as ‘abnormal’ ( Patrizio et al, 2019 ). The reduction of implantation cycles is likewise contested; a recent systematic review of 26 studies on PGT-A confirms that the add-on should, in theory, be able to enhance clinical outcomes on a per-transfer basis, but finds that the ‘current available literature is sparse or of insufficient quality’ and concludes that the routine use of PGT-A ‘with the aim of improving clinical outcomes is not supported by substantial evidence’ ( Toft et al, 2020 ). ASRM notes that PGT-A may moreover decrease the birth rate per cycle as a result of the embryo’s culturing conditions and cell biopsy, which could adversely affect the embryo, or due to the risk of unnecessarily discarding embryos that are classified as ‘abnormal’ ( Penzias et al, 2018 ).…”

Causes and Genomic Approaches to Female Reproductive Failure. Doctoral Thesis

“…The failure of embryo to implant can be a consequence of female, male, or embryo factors, or the specific type of IVF protocol (Bashiri et al, 2018). The primary cause of failed embryo implantation in ART is considered aneuploidy (Toft et al, 2020).…”

“…A small number of the cases processed makes it difficult to predict the trend of high pregnancy rates in the long run, but we associate those with the exclusion of embryonic factors of reproductive failure in all transferred embryos (aneuploid embryo rate 37.5%). However, it is highlighted that randomized controlled trials are needed to conclude the clinical effect of PGT-A for PGT-M (Toft et al, 2020).…”