4. Chromosomal abnormalities often
neglected at the time of
embryo selection
Conventional methods of embryo selection
• Embryoscopy
• Physical identification
• Morphological characteristics
5. • Aneuploidy: atypical number of chromosomes results from
error in cell division
• Translocations: a piece of chromosome go and attached to a
wrong chromosome.
• Chromosome Deletions : loss of a chromosome segment
resulting in an imbalance in the number of genes present
• Chromosome inversions: when a single chromosome breaks
in two places and the material is reconstituted upside down
……leading to embryo death, miscarriage or live birth of an infant
with substantial medical problems.
6. • A healthy baby has 46 chromosomes in each cell of
the body
• Chromosomal abnormality refers to an atypical
number of chromosomes and is generally caused by
an error in cell division in either the egg or sperm or
in the first few days of embryo development.
7. Normal cell
Meiosis
Embryos with chromosomal abnormalities are less likely
to implant and more likely to end in miscarriage
8. Age in Normal Aneuploidy Other
years embryos (%) embryos (%) abnormalities (%)
25-35 61 8 31
36-37 60 10 30
38-39 47 18 35
40-41 43 26 31
42-44 39 30 31
http://www.fertilityindia.com/indications-for-pgd.php
9. • Decreased embryo transfer
• Implantation failure,
• Recurrent pregnancy loss, or miscarriage
• Birth defects
• Mental or physical problems in offspring
10. Babies born with chromosome abnormalities
have mental retardation and / or birth defects
Ex: Down syndrome
12. • Age more than 35 years (chances of embryo transfer
(<75%)
• Couples with a family history of X-linked disorders
(25% risk of having an affected embryo)
• Carriers of autosomal recessive diseases: means
two copies of an abnormal gene (the risk an embryo
may be affected is 25%.)
• Carriers of autosomal dominant diseases: abnormal
gene in one parent (the risk an embryo may be
affected is 50%.)
13. Typical scenario
Carrier mother + Normal father
25% chances 25% chances 25% chances 25% chances
of Normal boy of disease boy of Normal girl of carrier girl
Disease father + Normal mother
100% chances of 100% chances of
Normal boy carrier girl
Carrier: Some one has one abnormal gene (No symptoms) is called a carrier
14. Women with X-linked recessive disorder are rare, since women has two X-chromosomes.
Two scenarios:
Carrier mother + Disease father
25% chances 25% chances 25% chances 25% chances
of Normal boy of disease boy of carrier girl of disease girl
Disease father + Disease mother
100% chances disease boy or girl
http://www.fertilityindia.com/indications-for-pgd.php
15.
16. Egg Sperm
Embryo 8 cell stage
Remove one cell
On day 3rd
Test DNA or Test results
chromosomes
Healthy gen Unhealthy gen
conditions conditions
Embryo implanted Embryo
on day 4 discarded
17. • Couples with advanced maternal age (>35)
• Unexplained infertility
• Y-chromosome deletion: found in 5-20% men with low sperm
count
• Couples who have experienced repeated miscarriages
• Couples who have experienced repeated IVF failures
• Couples who have previously had a pregnancy with a
chromosomal abnormality
• Couples at risk of having children with a particular X-linked
disorder
• couples where one partner carries a balanced chromosomal
translocations
18. • In only few centers it is available in India
• Most well known center is Jaslok Hospital, Mumbai
• It takes 3 days
• It is limited to chromosomes 13, 18, 21 only
19. • PGD is highly accurate across all chromosomes
• It yields quick results which allows for a fresh embryo
transfer on day 4 when it is tested on day 3
• PGD prevents transmission of genetic disorders onto
future generations.
20.
21. • There are two main types of preimplantation
genetic screening
– Aneuploidy screening by fluorescent in situ
hybridization (FISH) and
– Aneuploidy screening by Molecular Array
Comparative Genomic Hybridization (CGH-24)
22. • It screens the most common chromosomes seen in
miscarriages and live born abnormality disorders like
Down syndrome-chromosomes 13, 16, 18, 21 and 22.
• When one parent is carrier of heritable X-linked disease
such as Muscular dystrophy, Hemophilia A, or
ectodermal Dysplasia.
• FISH examines chromosomes X and Y plus chromosomes
13, 18, and 21
23. • This is single cell technology to test
aneuploidy, translocations, inversion and chromosomal
abnormality
• It is unique and it can make thousands of independent
measurements of each chromosome at molecular level
• No freezing and ICISI is required
• It is automated and high degree of results accuracy
• It gives the results with 20 hours than the standard 36-48
hours
24. • On day 3rd: Biopsy of a blastomere from an embryo
at IVF center
– The fixation of blastomere on slides for FISH analysis or
transfer into PCR tube with lysis buffer for CGH analysis
– Test for FISH or CGH at genetic center : results within 12-20
hours
• Day 4: Embryo transfer on day 4
