New England Fertility Institute
Lifeline Cryogenics
Gad Lavy, M.D., F.A.C.O.G.
Life begins here…
Overview
of
Preimplantation
Genetic
Diagnosis
Gad Lavy, MD
Preimplantation Genetic Diagnosis
(PGD)
• PGD is a state-of-the-art
procedure used in
conjunction with In Vitro
Fertilization (IVF)
in which the embryo is
tested for certain
conditions prior to being
placed in the womb of the
woman.
• PGD was first reported in
1990.
• PGD combines the recent
advances in molecular
genetics and in assisted
reproductive technology
Indications for PGD
•Chromosomal Disorders
Chromosomal
rearrangements
Inversions
Translocations
Chromosome
Deletions
Gender determination for severe
X-linked diseases
Severe monogenic diseases
(cystic fibrosis, ß thalassaemia,
sickle cell anemia, fragile X
syndrome, myopathies)
Recurrent pregnancy loss
Advanced Maternal Age
Couples with >3 IVF failures
Epididymal or Testicular sperm
aspiration with >1 IVF failures.
HOW IS PREIMPLANTATION
GENETIC DIAGNOSIS PERFORMED?
Technically
demanding
Very Complex
Requires special
skills
How is PGD performed?
Ovarian Stimulation Blastomere Biopsy on Day 3
IVF
Transfer of
Unaffected Embryo Genetic Analysis
Outcome
Chromosomally Normal Baby
Blastomere Biopsy
Video
The PGD process provides two
categories of analysis
• Polymerase
Chain Reaction
(PCR)
• Fluorescence In
Situ Hybridization
(FISH).
Benefits of PGD
• Increased Implantation
Rate
• Reduction in Pregnancy
Losses
• Reduction in the Chance
of Having a Child with
Aneuploidy
• .Reduces the possibility
of having to choose to
terminate the pregnancy
following a diagnosis of
a probable genetic
disorder.
Risks
• Embryo damage
Oocyte and Embryo Biopsy are
invasive procedures
• Misdiagnosis The accuracy of the
PGD for translocation is 90%.
False negative result
False positive result
The chance for NO result
The chance for mosaicism
The use of special precautions to avoid
exogenous DNA contamination has
dramatically reduced the main causes
of misdiagnosis
• 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.
Alternatives to PGD
• Conceive naturally and
have prenatal diagnosis
during pregnancy
• Consider assisted
reproduction techniques
in which one or both
partners would not be
the biological parent of
the child.
• Adoption
Future of PGD
• Efforts continue to be
focused on improving
methods to obtain an
accurate diagnosis.
• PGD holds great
promise for the future
as techniques and
genetic tests are
perfected.
• PGD may become
routine in the next few
years.
Conclusions
After 10 years of PGD in
Reproductive Medicine and the
performance of 2500 cycles
the main conclusions are :
• PGD is a reliable procedure in
preventing the birth of affected
children
• PGD of aneuploidy is effective
and results in a high take home
baby rate when implemented in
certain categories of patients.
• Despite the efficiency of the
PGD technique, conventional
prenatal diagnosis is still
required by most PGD
laboratories
The development of PGD is one of
the most exciting and important
milestones in the history of
Assisted Reproductive Technology
Bibliography
H. Handyside et al., "Pregnancy from biopsied human
preimplantation embryos sexed by Y-specific DNA amplification,"
Nature, 244:768-70, 1990.
M. Bielanska et al., "Fluorescence in situ hybridization of sex
chromosomes in spermatozoa and spare implantation embryos of
a Klinefelter 46,XY/47,XXY male," Human Reproduction, 15:440-4,
February 2000.
M.C. Magli et al., "Chromosome mosaicism in day 3 aneuploid
embryos that develop to morphologically normal blastocysts in
vitro," Human Reproduction, 15:1781-86, August 2000.
ASRM Ethics Committee Supports Sex Selection to Prevent
Genetic Diseases, [Link]/Media/Press/[Link]