Is aneuploidy screening an
efficient tool in embryo selection?
Necati Fındıklı
Istanbul International Hospital IVF Center
Best embryo
Symmetrical PNs with equal size, even PNB distribution
On day 1: (25-27 hourn after insemination) EC+
On day 2: (41-44 hours after insemination) 4 cells
On day 3: (66-71 hours after insemination) 7-8 cells
Fragmentation is less than <%10
No multinucleation
Best embryo
Neuber et al. 2003
Aneuploidy vs. Maternal age
Aneuploidy Screening (PGD-AS)
Preimplantation Genetic Screening (PGS)
Detection of chromosomal constitution in an embryo
made by examining a representative sample taken
at a preimplantation stage of development.
ANEUPLOIDY SCREENING
Numerical Chromosomal Abnormalities
Advanced Maternal Age (AMA)
>37 , >35?
Recurrent Pregnancy Loss (RPL)
>2? , >3? abortus; Gestational age 20 – 22 weeks (500 g)
Recurrent Implantation Failure (RIF)
>2? , >3? Trials, >10 good quality embryos
Male Factor (MF)
severe OAT, Azoospermia
Klinefelter’s syndrome
…
Structural Chromosomal Abnormalities
Translocations
Inversions
…
Misinterpretation by the public
With PGD-AS
Without PGD-AS
Embryo Viability
• Ethiology of Infertility
• Abnormal oocyte maturation
• Paternal factors
• Suboptimal culture conditions
• Chromosomal and/or genetic abnormalities
Chromosome abnormalities
in humans
Causes of Aneuploidy
Errors in
meiosis I & meiosis II
Gametogenesis
Errors in
mitosis (postzygotic)
Early Celavage and differentiation
Causes of Aneuploidy
Swang and Höög. 2006
Errors in Meiosis
Errors in Meiosis
Kuliev. 2002
Errors in Mitosis
Defective Spindle
Chatzimeletiou et al. 2005
Errors in Mitosis
Silber et al. 2003
Aneuploidy vs. Embryo morphology
Fragmentation
Multinucleation
Asymmetric Cleavage
Aneuploidy vs. Fragmentation
•Chromosomal abnormality rate is 70-90% in
embryos with >35% fragmentation.
•Aneuploidy rate does not increase, whereas
mosaicism and other post-zygotic abnormalities
increases with fragmentation.
Munne. 2007
Aneuploidy vs. cytoplasmic problems
•Presence of vacuoles and dark inclusions is not
associated with chromosomal abnormalities.
•Embryos with cytoplasmic concentrations show
86% chromosomal abnormalities.
Munne. 2007
Aneuploidy vs. dominant blastomeres
•Usually polyploid or polyploid mosaics.
•Dominant blastomere is also multinucleated in
many cases.
Munne. 2007
Technical Limitations: Embryo biopsy
•Different techniques for zona opening
•(Mechanical-Chemical-Laser)
•Requires high-skilled laboratory and staff
• 1-cell vs. 2 cells? (Survival vs. Reliability?)
Technical Limitations: Diagnosis
 Which chromosomes?
 Cost?
 Anuclear cells?
 Can a biopsied cell represent the embryo ?
Baart et al. 2006
Baart et al. 2007
Blastocysts vs. Aneuploidy
Sandalinas et al. 2001
Cleavage vs. Blastocyst Culture
Evangelos et al. 2008
Conclusions:
 Successful embryo selection is the best
tool for high implantation rates.
 Even with the best embryo selection
approach, 30-50% of embryos can still
be chromosomally abnormal.
Conclusions:
 Blastocyst selection and transfer may
decrease the overall abnormality rate, but
still numerous abnormal and mosaic
embryos may reach blastocyst stage.
 % mosaic embryos tend to increase with
increasing number of chromosomes
analyzed. Therefore, new embryo scoring
systems that can better define differences
in mosaicism will eventually be needed.
Conclusions:
 PGD is an effective embryo selection
tool in cases with single gene disorders
and structural chromosomal
abnormalities.
On the other hand, the possible benefit
of selecting embryos with PGS still
needs to be confirmed by new studies.