Transcript Vlachos – IVF-PGD

In Vitro Fertilization and
Preimplantation Genetic
Diagnosis
ADRIANNA VLACHOS, MD
DBA CAMP 2015
In Vitro Fertilization and
Pre-Implantation Genetic Diagnosis

Goal:


Child unaffected by a genetic (hereditary) illness defined by a
known genetic mutation
Secondary goal:

“Creating” a child unaffected by the genetic illness who is a
transplant donor for the affected child
In Vitro Fertilization and
Pre-Implantation Genetic Diagnosis

IVF

Hormonal therapy to the mother to get many eggs for ovulation

Number of eggs depends on age of mother

Side effects of these medications to mother

Eggs harvested (under anesthesia)

Eggs are fertilized with sperm outside of mother (“in the test
tube”)
In Vitro Fertilization and
Pre-Implantation Genetic Diagnosis

PGD

Fertilized egg reaches 8-cell stage

One cell taken for RP/HLA testing

“RP neg, HLA matched” fertilized egg implanted in mother (1/8
chance)

Hormonal therapy to continue pregnancy, usually until 10-12
weeks

CVS (10 wks) or Amnio (18 wks) for confirmation
Pre-natal
vs Pre-implantation diagnosis
Dr. I. Souter, MGH Fertility Center
Pre-natal Diagnosis

Amniocentesis

Chorionic Villus Sampling (CVS)
Pre-implantation Diagnosis

Introduced initially in 1990

Biopsy of a single cell per embryo

followed by its genetic diagnosis
through different techniques

the subsequent replacement to
the patient of those embryos
classified by genetic diagnosis as
unaffected
PGD Indications
Primary Goal
Procedure is offered to couples:
 With known single gene disorders
that can be detected by PGD DBA
 With known chromosomal
abnormalities that can be detected
by PGD
 requesting sex selection for X-linked
disorders – DBA
PGD Indications
Secondary Goal
Requesting PGD for HLA-typing (to allow selection of
embryos that are histocompatible with live siblings)
Single Gene Disorders
PGD Process

Ovulation Induction

Retrieval

Fertilization

Embryo Bx on Day-3

Genetic Analysis

Embryo Transfer
Ovulation induction
Oocyte Retrieval
Fertilization


Conventional Insemination
Intracytoplasmic Sperm
Injection (ICSI)
Embryo Culture
Day 3/Cleavage Stage Embryo
Cleavage Stage Biopsy
Genetic Analysis/PCR

DNA amplification


sequence harboring the
mutation
Mutation Characterization
FISH
 PCR


HLA Matching
Embryo Transfer
Early Pregnancy
Risks

Embryo damage
Oocyte and Embryo Biopsy are invasive procedures

Misdiagnosis
•
•
•
•




False negative result
False positive result
The chance for NO result
The chance for mosaicism
IVF Risks
Not Achieving Pregnancy
There may not be any normal embryos available for transfer.
The embryos may not implant and develop even if they do not have the defect.
The workup for PGD is expensive and labor intensive
PGD can only detect a specific genetic disease in an embryo. It cannot detect many
genetic disorders at a time and cannot guarantee that the fetus will not have an
unrelated birth defect.
Summary
•
•
Before PGD is performed, genetic counseling must be
provided to ensure that patients fully understand the

risk for having an affected child

the impact of the disease

the available options

the multiple technical limitations including the possibility of an
erroneous result
Prenatal diagnostic testing is strongly encouraged to
confirm the results of PGD
Conclusions
•
•
•
It is a personal choice!!!
This requires identification of your family’s DBA gene.
Obstacles
Practical
• Religious
• Ethical
• Financial
•
•
There are other options available
Adoption
• Sperm/egg donation
• Just having a baby
•