The future of cryopreservation in assisted reproduction alpha handyside_alan_2010

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he future of cryopreservation in assisted reproduction _(by Handyside_Alan_2010)

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The future of cryopreservation in assisted reproduction alpha handyside_alan_2010

  1. 1. ALPHA 2010 8th Biennial Conference Budapest, Hungary 30th April - 2nd May, 2010 The future of cryopreservation in assisted reproduction Alan H Handyside London Bridge Fertility, Gynaecology And Genetics Centre London United Kingdom
  2. 2. SELECTION FREEZING GENETIC SCREENING
  3. 3. Which single embryo to select for transfer?
  4. 4. Which single embryo to select for transfer?
  5. 5. Comparative Genomic Hybridisation (CGH)
  6. 6. CONTROL TEST
  7. 7. CONTROL TEST 1.5 1.0 0.5
  8. 8. CONTROL TEST 1.5 1.0 0.5
  9. 9. CONTROL TEST 1.5 1.0 0.5
  10. 10. First or first and second polar body biopsy on day 0 or day 1 Array comparative genomic hybridisation (CGH) following whole genome amplification
  11. 11. September 2nd 2009 New IVF test – Array  CGH – produces baby  Oliver, offering hope  to infertile 13 previous failed IVF  cycles 8/12 first polar bodies  aneuploid
  12. 12. 6.7 Mb intersitial duplication in 11q24.2g25 aascoiated with  infertility, minor dysmorphic features and normal  psyshomotor development Gohring et al (2008) Eur J Med Genet Epub
  13. 13. Clinical application of comprehensive chromosome screening at the blastocyst stage • Zona drilling and blastocyst biopsy • Vitrification using Crytop • Chromosome copy number assessment by metaphase comparative genomic hybridisation (CGH) following whole genome amplification Schoolcraft et al (2009) Fertility and Sterility in press
  14. 14. • 45 patients (mean maternal age 37.7 yrs) • 287 blastocysts (6.4 per cycle) • 93.7% CGH successful • 138 (51.3%) blastocysts aneuploid • 100% survival following biopsy/vitirifcation/thawing • 82.2% pregnancy rate per cycle (mean 2.0 blastocysts transferred) • 68.9% FHB/ blastocyst transferred • 55% multiple pregnancies
  15. 15. Single nucleotide polymorphism genotyping and karyomapping Handyside et al (2009) J Med Genet
  16. 16. Single nucleotide  polymorphisms (SNPs) • 10 million SNPs across  human genome • Many biallelic (AA, AB, BB) • Major contribution to  genetic diversity, inherited  disease and variants  associated with common  multifactorial conditions
  17. 17. ♂ ♀ A A A B A A A A B B B A A A B A A B B B B A A A
  18. 18. A ♂ ♀ Karyomapping combines genome wide linkage based detection of single gene defects (A) with chromosomal aneuploidy including monosomy/deletions (B) and trisomies involving inheritance of two different meiotic B chromosomes from one parent (D). Chromosome duplication is not detected (C). C D
  19. 19. Family 2 Preimplantation genetic diagnosis for cystic fibrosis Whole genome amplification by isothermal multiple displacement amplification of 2-10 cells in each biopsy/embryo
  20. 20. Improved cryopreservation methods ? Improved implantation rates in unstimulated cycles ? Improved birth weights and health Highly resolution 24 chromosome screening Less invasive polar body or blastocyst biopsy Maximise live birth rates per cycle Avoid multiple pregnancies Reduce pregnancy loss and miscarriage Minimise FETs

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