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Is aneuploidy screening an efficient tool in embryo selection ?

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+

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Is aneuploidy screening an efficient tool in embryo selection ?

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  1. Is aneuploidyscreening an efficienttool in embryoselection? Necati Fındıklı IstanbulInternationalHospital IVF Center

  2. Bestembryo • SymmetricalPNswithequal size, even PNB distribution • On day 1: (25-27 hournafterinsemination) EC+ • On day 2: (41-44 hoursafterinsemination) 4 cells • On day 3: (66-71 hoursafterinsemination) 7-8 cells • Fragmentation is lessthan <%10 • No multinucleation

  3. Bestembryo Neuber et al. 2003

  4. Aneuploidy vs. Maternalage

  5. AneuploidyScreening (PGD-AS)PreimplantationGeneticScreening (PGS) Detection of chromosomalconstitutionin an embryo made by examining arepresentative sample taken at a preimplantation stage of development.

  6. NumericalChromosomalAbnormalities AdvancedMaternalAge (AMA) >37 , >35? RecurrentPregnancyLoss (RPL) >2? , >3? abortus; Gestationalage 20 – 22 weeks (500 g) RecurrentImplantationFailure (RIF) >2? , >3? Trials, >10 goodqualityembryos MaleFactor (MF) severe OAT, Azoospermia Klinefelter’ssyndrome … StructuralChromosomalAbnormalities Translocations Inversions … AneuploidyScreening

  7. Without PGD-AS Misinterpretationbythepublic With PGD-AS

  8. EmbryoViability • Ethiology of Infertility • Abnormaloocytematuration • Paternalfactors • Suboptimalcultureconditions • Chromosomaland/orgeneticabnormalities

  9. Chromosome abnormalities in humans • Mature oocytes~25% • Spermatozoa ~10% • Embryos~ 40-70% • Spontaneous miscarriage ~ 50% • Live births ~0.5-1%

  10. Causes of Aneuploidy Errors in mitosis (postzygotic) Errors in meiosis I & meiosisII Gametogenesis EarlyCelavageanddifferentiation

  11. Causes of Aneuploidy SwangandHöög.2006

  12. Errors in Meiosis

  13. Errors in Meiosis Kuliev. 2002

  14. Errors in Mitosis

  15. Defective Spindle Chatzimeletiou et al. 2005

  16. Errors in Mitosis Silber et al. 2003

  17. Aneuploidy vs. Embryomorphology Fragmentation Multinucleation AsymmetricCleavage

  18. Aneuploidy vs. Fragmentation • Chromosomalabnormality rate is 70-90% in embryoswith >35% fragmentation. • Aneuploidy rate does not increase, whereasmosaicismandother post-zygoticabnormalitiesincreaseswithfragmentation. Munne. 2007

  19. Aneuploidy vs. cytoplasmicproblems • Presence of vacuolesanddarkinclusions is not associatedwithchromosomalabnormalities. • Embryoswithcytoplasmicconcentrationsshow 86% chromosomalabnormalities. Munne. 2007

  20. Aneuploidy vs. dominant blastomeres • Usuallypolyploidorpolyploidmosaics. • Dominant blastomere is alsomultinucleated in manycases. Munne. 2007

  21. TechnicalLimitations: Embryobiopsy • Differenttechniquesfor zona opening • (Mechanical-Chemical-Laser) • Requireshigh-skilledlaboratoryandstaff • 1-cell vs. 2 cells? (Survival vs. Reliability?)

  22. TechnicalLimitations: Diagnosis • Whichchromosomes? • Cost? • Anuclearcells? • Can a biopsiedcellrepresenttheembryo ?

  23. Baart et al. 2006

  24. Baart et al. 2007

  25. Sandalinaset al. 2001 Blastocysts vs. Aneuploidy

  26. Evangelos et al. 2008 Cleavage vs. BlastocystCulture

  27. Conclusions: • Successfulembryoselection is thebesttoolforhighimplantationrates. • Evenwiththebestembryoselectionapproach, 30-50% of embryos can still be chromosomallyabnormal.

  28. Conclusions: • Blastocystselectionand transfer maydecreasetheoverallabnormality rate, but stillnumerousabnormalandmosaicembryosmayreachblastocyststage. • % mosaicembryostendtoincreasewithincreasingnumber of chromosomesanalyzed. Therefore, newembryoscoringsystemsthat can better define differences in mosaicismwilleventually be needed.

  29. Conclusions: • PGD is an effectiveembryoselectiontool in caseswithsingle gene disordersandstructuralchromosomalabnormalities. On theotherhand, thepossiblebenefit of selectingembryoswith PGS stillneedsto be confirmedbynewstudies.

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