McPhee SJ, Bottles K, Lo B, et al. To redeem them from death: reactions of family members to autopsy. Am J Med 1986; 80:665.
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2 Preimplantation Genetic Testing
Anver Kuliev and Svetlana Rechitsky
Herbert Wertheim College of Medicine, Florida International University, Miami, FL and Reproductive Genetic Innovations, Northbrook, IL, USA
Preimplantation genetic testing (PGT1) is a practical option for couples at risk of having offspring with serious/fatal chromosomal or monogenic diseases. It has been used for up to 600 monogenic disorders (PGT‐M1). Moreover, it has been used for human leukocyte antigen (HLA) typing (PGT‐HLA1), enabling the births of many children whose matched bone marrows have proved life‐saving for siblings with congenital and acquired disorders requiring stem cell transplantation treatment.
Analysis of single cells or a few cells with a limited amount of available DNA has always presented a technical challenge, especially when PGT is faced with the need for accurate and rapid results from whole‐genome amplification (WGA), followed by polymerase chain reaction (PCR) assays that are robust and sensitive. Next‐generation sequencing (NGS) has allowed for accurate identification and transfer of euploid embryos (PGT for aneuploidies (PGT‐A)1).
PGT‐M was initially applied for the same indications as prenatal diagnosis,2–4 but was then expanded to conditions that had never been considered, such as late‐onset diseases with genetic predisposition and preimplantation HLA typing with or without testing for genetic disorders.5–7
PGT represents a natural evolution of the genetic disease prevention technology, from a period with limited genetic counseling and no prenatal diagnosis or treatment to a time when many options, including PGT, have become available.8 Furthermore, PGT has been applied in order to improve access to the new treatment methods for some severe conditions by stem cell transplantation, for which no traditional treatment approaches are available. The impact of PGT and stem cell treatment on existing policies for the prevention of genetic disease (see Chapter 36) is clear from the increasing use of PGT to avoid unnecessary termination of many wanted pregnancies and for preimplantation HLA typing.
Approaches to preimplantation genetic testing
When prenatal genetic diagnosis was first considered in perspective, in 1984, the World Health Organization (WHO) emphasized the relevance of developing earlier approaches for genetic analysis with the possibility of diagnosis before implantation.9, 10 The following possibilities for PGT were mentioned: genetic analysis of the first or second polar bodies and embryo biopsy at the cleavage or blastocyst stage.10, 11 However, these approaches became possible only after introduction of the PCR assay12 and success in micromanipulation and embryo biopsy.
First attempts at PGT were undertaken in mammalian embryos over 30 years ago,13–18 when it was demonstrated that cells could be removed from mammalian preimplantation embryos and analyzed successfully without destroying the viability of the embryo in in vitro fertilization (IVF). PGT for human genetic disease was first demonstrated by Handyside et al.19 for X‐linked diseases and by Verlinsky et al.20 for autosomal recessive disorders. Tens of thousands of children without detectable birth defects have been born following these procedures,21–25 demonstrating that PGT