Preimplantation Genetic Testing

By

Osama Abdalmageed

Assistant Lecturer of Obstetric & Gynecology, Assiut University,

Assiut, Egypt

Research Fellow, American Center for Reproductive Medicine,

Cleveland, Ohio

Points to be covered in this presentation

Introduction: Overview

History

Important terms

Indications: PGD

PGS

Techniques: Embryo biopsy

Genetic analysis

Challenges: Risks

Legal challenges

Future:

Introduction

Overview-1

Def. of PGT:

IntroductionOverview-2

Preimplantation Vs. Prenatal:

IntroductionOverview-3

PGT

Diagnosis

PGD

Screening

PGS

IntroductionHistory-3

1968• Edward and Gardner

• 1st embryo biopsy.

1978• Conventional IVF

• Robert Edward & Patrick Steptoe

1980s• First human PGT for sexing

1990

• Handyside et al

• First child born after PGT (sexing)

2000• PGT is available for most of the known genetic disorders.

IntroductionImportant terms

Chromosomes:

Gene:

Allele:

Homozygous:

Heterozygous:

Introduction

Important terms

Dominant Allele:

Introduction

Important terms

Recessive Allele:

Introduction

Important terms

Sex-Limited trait:

Indications

PGD

X-linked disorder: Sex determination

Chromosomal translocation: FISH

Carrier of Autosomal recessive disease: PCR

Carrier of Autosomal dominant disease: PCR

HLA matches:

Indications

PGD/Controversies

Embryo sexing for non-medical:

Testing of non medical indications (eye colour,

hair colour)

HLA for prospective donors:

Indications

PGS

Advanced mat. age:

RIF:

RPLs:

Previous aneuploidy:

Sever male factor:

Indications

PGS/Controversies

Brizina et al, 2012

Indications

ESHRE, 2012

Techniques

TechniquesEmbryo biopsy

Weakening of the outer layer of the oocyte or the embryo (Usually laser)

Mechanical extraction of the cell (for genetic testing)

Biopsies

Polar body biopsy

Cleavage stage biopsy

Blastocyst stage biopsy

TechniquesPolar body biopsy

TechniquesCleavage stage biopsy

TechniquesBlastocyst stage biopsy

TechniquesGenetic Analysis

PGD

PCR FISH Microarray

PGS

FISHMicroarray (single

nucleotide polymorphism)

Microarray (comparative genomic

hybridization)

TechniquesPCR

TechniquesFISH

TechniquesMicroarrays

TechniquesMicroarrays (single nucleotide polymorphism)

TechniquesMicroarrays (comparative genomic hybridization)

ChallengesRisks

Could > medical conditions.

Physical damage to embryo from biopsy.

Misdiagnosis

Mosaicism. (developing embryos)

Unknown risksBrezina et al; 2012

Risks of Misdiagnosis & Mosaicism

CVS or Amniocentesis to confirm the GD

ASRM, 2008

ChallengesLegal challenges

1- Limit the use of PG testing. (e.g. Germanand Italy)

2- Sexing. (prohibited in Australia, India,China and Tiland).

Reproductive Tourism

PG Testing Future

1- Advances in the genetic testing

detailed evaluation of the humanembryos.

2- PGS evaluation in large studies.