Pre-implantation genetic testing for aneuploidy

M R C O G PA R T 2 · S O S P O C K E T C A R D · K N O W L E D G E A R E A 5 – A N T E N ATA L C A R E

Pre-Implantation Genetic Testing for Aneuploidy: the Past, Present and Future L’Heveder A, Jones BP. Pre-implantation genetic testing for aneuploidy: the past, present and future. TOG 2020;22:293–304. doi:10.1111/tog.12692

9% 30–90% 2.7% vs 39% LIVE BIRTH RATE, WOMEN 40–42Y (VS 29% ANEUPLOID BLASTOCYSTS: EARLY 30S → ≥44Y MISCARRIAGE: PGT-A VS CONTROL (RUBIO <35Y) 2017, AMA)

DO N' T-M IS S FA C TS

  1. PGT-A history: FISH/cleavage-stage biopsy (1990s–2010) was found harmful (9-RCT meta-analysis) → superseded by CCS (aCGH/qPCR/SNP/NGS) on TE biopsy, which shows benefit

  2. NGS is now the preferred CCS platform: highest mosaicism detection (to 20% level), diagnostically superior to aCGH, but usually needs frozen cycles (slowest technique)

  3. Rubio 2017 (AMA RCT): miscarriage 2.7% vs 39.0% with PGT-A (aCGH, cleavage-stage)

  4. STAR trial: no overall ITTA benefit in good-prognosis women, but significant benefit in AMA 35–40y subgroup (50.8% vs 37.2%)

  5. SET + euploid embryo virtually eliminates multiple pregnancy (0% vs 53.4% with DET) without reducing pregnancy rate

  6. Without ITTA, RCT results can overstate benefit – women with no embryo for biopsy/transfer are excluded from analysis

  7. Mosaic embryos are a ‘third category’: can produce healthy live births (41% continuing pregnancy in one study) but implantation lower/miscarriage higher than euploid

  8. Non-invasive PGT-A in development: blastocentesis, spent culture medium cfDNA, time-lapse imaging – none yet validated for routine use

TECHNIQUE EVOLUTION AT A GLANCE

FISH + cleavage-stage: harmful/no benefit CCS (aCGH/qPCR/SNP/NGS) + TE biopsy: improved outcomes

ABBREVIATION KEY

PGT-A — pre-implantation genetic testing for aneuploidy PB — polar body

PGT-M — PGT for monogenic disease SET — single embryo transfer

PGT-SR — PGT for structural chromosomal rearrangements DET — dual embryo transfer

ART — assisted reproductive technology AMA — advanced maternal age

IVF — in vitro fertilisation RM — recurrent miscarriage

FISH — fluorescence in situ hybridisation RPL — recurrent pregnancy loss

CCS — comprehensive chromosome screening RIF — repetitive/recurrent implantation failure

aCGH — array comparative genomic hybridisation RCT — randomised controlled trial

qPCR — real-time quantitative polymerase chain reaction ITTA — intention-to-treat analysis

SNP — single nucleotide polymorphism FET — frozen embryo transfer

NGS — next-generation sequencing RR — relative risk

WGA — whole genome amplification CI — confidence interval TE — trophectoderm OR — odds ratio

Source: The Obstetrician & Gynaecologist (TOG), RCOG journal — doi:10.1111/tog.12692

Clinically reviewed by NHS obstetricians and gynaecologists

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