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CGH in the PGD program: a new tool for improved IVF outcomes?
 

CGH in the PGD program: a new tool for improved IVF outcomes?

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Presentation by Maria Traversa

Presentation by Maria Traversa
Senior Scientist, Genea Limited

Presented at the World Congress on Human Reproduction 2011, Melbourne

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    CGH in the PGD program: a new tool for improved IVF outcomes? CGH in the PGD program: a new tool for improved IVF outcomes? Presentation Transcript

    • CGH in the PGD program –a new tool for improved IVF outcomes?a new tool for improved IVF outcomes?Maria TraversaMaria TraversaSenior Scientist, Genea LimitedPresented at the World Congress on Human Reproduction 2011, MelbournePresented at the World Congress on Human Reproduction 2011 Melbourne Dec 2011 1
    • PGD chromosome techniquesAnalysis of an embryo’s chromosomes before it is transferred back into the uterusb k i t th tThree main techniques:> FISH ‐ for small chromosome regions FISH  for small chromosome regions > PCR ‐ for chromosome regions (and genes)> CGH complete set of all 24 chromosomes CGH ‐ l t t f ll 24 h Dec 2011 2 © 2011 Genea Limited | genea.com.au
    • Current biopsy techniques> Polar body biopsy ‐ maternal markers only> Day 3 biopsy Day 3 biopsy ‐ remove 1 or 2 cells> Blastocyst biopsy l b ‐ more labs now implementing Dec 2011 3 © 2011 Genea Limited | genea.com.au
    • Blastocyst biopsy – our approach since 2004 > Why wait till blastocyst stage? – blastulation‐ best developing embryos identified > fe er embr os need to be anal sed fewer embryos need to be analysed – fewer resources needed > more cells can be taken = more DNA – improved analysis with less error rate > reduced impact on embryo? Dec 2011 4 © 2011 Genea Limited | genea.com.au
    • Summary – blastocyst biopsy> Outcomes are better than cleavage stage biopsy – Improved embryo viability? Improved embryo viability?> The number of cycles achieving transfer is lower but outcome per IVF  cycle started is similar l d i i il – Fewer futile transfers> Clinical pregnancy rate per embryo transferred is higher – sET is possible> Reduced costs for PGD – Number of embryos analysed is reduced y y Dec 2011 5 © 2011 Genea Limited | genea.com.au
    • The problems with FISH:> Accuracy/Error rates y/ ‐Cell loss ‐Signal overlap/splitting ‐Variable cell fixation (residual cytoplasm) ‐Hybridization efficiency/times (multiple) ‐Cell overlap (blastocyst biopsy) Cell overlap (blastocyst biopsy)> Limit on fluorophors available‐ 5 ‐up to 12 chromosomes‐ 3 hybridisations! p y> Diploid‐aneuploid mosaicism (blastocyst biopsy) ‐small proportion of aberrant cells in sample Dec 2011 6 © 2011 Genea Limited | genea.com.au
    • PGD trial outcomes: > A randomised clinical trial of blastocyst biopsy to ascertain whether chromosome  screening improves IVF outcomes screening improves IVF outcomes ‐ terminated early when we were not able to show any advantage for PGS Human Reproduction Vol.23, No.7 pp. 1476–1478, 2008Conclusion:  We needed a more accurate and extensive test for chromosomal error Dec 2011 7 © 2011 Genea Limited | genea.com.au
    • Comparative genetic diagnosis – CGH • CGH is a process that allows us to look at all 24  chromosomes in an embryo • Female = 46, XX Female  46, XX • Male = 46, XY • Process takes several days to achieve results therefore all  embryos need to be vitrified b d t b it ifi d • Cryo embryo transfer in subsequent cycle Dec 2011 8 © 2011 Genea Limited | genea.com.au
    • Array CGH> 60 000 points on chromosomes  measured> y y p 8 sub arrays = 8 embryos per slide> embryo karyotype Dec 2011 9 © 2011 Genea Limited | genea.com.au
    • CGH – Analysis Log ratio Log ratio Moving average Dec 2011 10 © 2011 Genea Limited | genea.com.au
    • Aneuploid chromosomes  25.0 20.0 neuploidy rate (%) 15.0 IVF miscarrage samples 10.0 PGD Embryos PGD Embryos An 5 panel = 35% 5.0 9 panel = 72% 12 panel = 78% 0.0 25% of abnormal  10 11 12 13 14 15 16 17 18 19 20 21 22 1 2 3 4 5 6 7 8 9 X/Y embryos still  Chromosome missed Dec 2011 11 © 2011 Genea Limited | genea.com.au
    • CGH patients Patient data Couples with biopsy cycles 105 with transfer (so far) 56 Average maternal Average maternal age 38.1 38 1 No. previous IVF treatments             <38yrs 2.2 >38yrs 2.1 embryos biopsied 404 (av. 5.7 for <38yrs and 3.9 >38yrs) aneuploid embryos detected 181 (49%) y py Cycles with no biopsy 58% successful analyses ~94 % Dec 2011 12 © 2011 Genea Limited | genea.com.au
    • CGH outcomes Pregnancy outcomes embryos transferred 60 implantation rate (# implantations) 52% (31) <38yrs 61% (23/38)  >38yrs 41% (8/22) Clinical pregnancy rate (FH)/oocyte retrieval with transfer Clinical pregnancy rate (FH)/oocyte retrieval with transfer 67% (28/42) 67% (28/42) <38yrs 81% (21/26) >38yrs 44% (7/16) Dec 2011 13 © 2011 Genea Limited | genea.com.au
    • CGH results – Effects of aneuploidy with age Dec 2011 14 © 2011 Genea Limited | genea.com.au
    • CGH results – Comparison to age matched IVF cryo cycles Dec 2011 15 © 2011 Genea Limited | genea.com.au
    • CGH results:  aCGH vs FISH Dec 2011 16 © 2011 Genea Limited | genea.com.au
    • CGH – Conclusion> Whilst this is a retrospective review of outcomes, Whilst this is a retrospective review of outcomes,  when compared to general IVF patients, applying PGS  with aCGH in poor prognosis patients shows an  with aCGH in poor prognosis patients shows an improved implantation rate. ‐ Several randomised trials currently underway> Other factors, such as uterine receptivity, may also be  contributing to the improved outcomes when  ib i h i d h applying aCGH to this cohort of patients Dec 2011 17 © 2011 Genea Limited | genea.com.au
    • Thank youThank youDec 2011 18 © 2011 Genea Limited | genea.com.au