Anatomiaestiramientos 130305111855 Phpapp02 140129215950 Phpapp02
Daganasrm2009abstracto268 12564089438001-phpapp02
Transcript of Daganasrm2009abstracto268 12564089438001-phpapp02
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Comprehensive chromosomal screening at the blastocyst stage
Dagan Wells, PhD, FRCPath
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Less than half the chromosomes tested
Spreading requires skill and can be inconsistent
Limitations of conventional embryo screening techniques
Cells are in interphase
Mosaicism
Limited range of fluorochromes
Poses a significant problem for diagnosis. However, most mosaic cleavage stage embryos are aneuploid in every cell.
- use FISH
Cleavage stage biopsy may represent a cost to the embryo
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Kallioniemi et al 1992; Wells et al 1999, 2002; Voullaire et al 1999; Wilton et al 2001; Gutierrez et al 2004, 2005; Fragouli et al 2006, 2007
• Technique related to FISH
• Allows the copy number of every chromosome to be determined
Normal Trisomy Monosomy
Normal DNATest DNA
Comparative genomic hybridization- CGH
Gai
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Los
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Chromosome 15
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Embryo screening using CGH
• All chromosomes tested
Benefits
• DNA-based
• No spreading of cells on slides
But what about mosaicism and the impact of biopsy?
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Comprehensive chromosome screening of blastocysts
Trophectoderm biopsy-
3-10 cells (mean 5) biopsied and tested
Courtesy of M. Katz-Jaffe and J. Stevens, CCRM
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Diagnosis more robust and accurate
• Biopsy of several cells is possible
Less risk of misdiagnosis due to mosaicism
Analysis of blastocyst stage
• Can overcoming the principal challenges to accurate screening allow PGS to fulfill the potential predicted by theory?
Reduced impact of embryo biopsy
• Blastocyst cryopreservation (vitrification) necessary
Comprehensive chromosome screening of blastocysts
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•Near 100% survival after biopsy, freeze and thaw
• 170 patients, mean age 38 years, 1-6 previous failed IVF cycles (mean 2)
• Pregnancy rate per cycle with transfer 87%
• Birth rate per cycle with transfer 79%
• Implantation rate per embryo 67%
Blastocyst CGH- clinical results
72%
60%
28% *
Control group matched for: maternal age, day-3 FSH, day of transfer, # oocytes retrieved, # of failed cycles
*p<0.0003 - Extremely promising for single embryo transfer
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• Embryo loss rates are low
• 91% of embryos that produced a fetal sac resulted in an ongoing third trimester pregnancy or live birth
• 97% of embryos that produced a fetal heart beat resulted in an ongoing third trimester pregnancy or live birth
• Expected pregnancy loss rate for IVF patients in this age range is ~25%
Blastocyst CGH- rates of pregnancy loss
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Blastocyst CGH- Pregnancy rates
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30-34 35-38 39-42 43-500
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Positive pregnancy per transfer
Positive pregnancy per cycle with biopsy
Pregnancy rate per transfer shows only a small decline with advancing age
Pregnancy rate per cycle shows a significant decline
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Blastocyst CGH- aneuploidy and implantation rates
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30-34 35-38 39-42 43-500
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Implantation rate
Aneuploidy rate
Cycles with all embryos aneuploid
Why does age still lead to reduced pregnancy rates despite aneuploidy screening?
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• Pregnancy rates were above those typically achieved for all age groups.
• However, pregnancy rates were lower for older patients due to the increased frequency of cycles with no euploid embryos.
• Spontaneous abortion rates were reduced for all patients, including those with a history of multiple miscarriage
• Chromosomally normal embryos from older patients have a similar chance of producing a child as those derived from young patients.
• Aneuploidy is likely to be the principal factor causing reduced IVF success with advancing maternal age
Conclusions
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• Can the results obtained in the current study be replicated in a randomized controlled trial?
• An RCT is currently underway
• What patient groups will benefit the most from this type of screening?
• Young patients may benefit, particularly in countries where single embryo transfer is mandatory
Questions
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United Kingdom (Oxford)Elpida Fragouli
Samer Alfarawati
United States (Livingston, NJ)Pere Colls
Tomas EscuderoN-neka Esprit-Ngachou
Jill FischerCristina Gutierrez-Mateo
Santiago MunneRenata PratesJorge Sanchez
Sophia TormasiJohn Zheng
Colorado Center for Reproductive Medicine
Mandy Katz-JaffeJohn Stevens
Bill Schoolcraft