The current clinical applications of preimplantation genetic testing (PGT): acknowledging the limitations of biology and technology

ABSTRACT

Introduction

Preimplantation Genetic Testing (PGT) is a cutting-edge test used to detect genetic abnormalities in embryos fertilized through Medically Assisted Reproduction (MAR). PGT aims to ensure that embryos selected for transfer are free of specific genetic conditions or chromosome abnormalities, thereby reducing chances for unsuccessful MAR cycles, complicated pregnancies, and genetic diseases in future children.

Areas covered

In PGT, genetics, embryology and technology progress and evolve together. Biological and technological limitations are described and addressed to highlight complexity and knowledge constraints and draw attention to concerns regarding safety of procedures, clinical validity, and utility, extent of applications and overall ethical implications for future families and society.

Expert opinion

Understanding the genetic basis of diseases along with advanced technologies applied in embryology and genetics contribute to faster, cost-effective, and more efficient PGT. Next Generation Sequencing-based techniques, enhanced by improved bioinformatics, are expected to upgrade diagnostic accuracy. Complicating findings such as mosaicism, mt-DNA variants, variants of unknown significance, or variants related to late-onset or polygenic diseases will however need further appraisal. Emphasis on monitoring such emerging data is crucial for evidence-based counseling while standardized protocols and guidelines are essential to ensure clinical value and respect of Ethical, Legal and Societal Issues.

KEYWORDS:

• Medically assisted reproduction
• MAR
• preimplantation genetic testing
• PGT
• whole genome amplification
• WGA
• embryo biopsy
• genetic variants
• chromosomal abnormalities
• mosaicism

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Article highlights

• PGT aims to select disease-free embryos, increase chance of pregnancy, and decrease postnatal health risks.

• Technological evolution has led to the ability to perform high quality testing for multiple indications from a single embryo biopsy.

• Current and future technological advancements will promote thorough understanding of embryo biology.

• Validation and success of some PGT applications may be challenging due to biological limitations, such as mosaicism, genetic variants, and epigenetic factors.

• The current expansion of PGT applications foresees PGT for polygenic disease risk and non-invasive PGT, however more scientific evidence is needed for their reliable use in clinical practice.

• Scientific consensus, opinions and guidelines are needed to ensure balancing technological innovation and ethical considerations, towards optimal use of PGT.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded