Alan R. Thornhill Ph.D.
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Alan R. Thornhill Ph.D.






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  • Many IVF centers across the nation are now offering preimplantation testing. We believe that Mayo can offer a superior PGD treatment for a number of reasons: The MCART program has IVF success rates which are consistently in the top 5% in the US. Successful PGD requires a multidisciplinary approach, Mayo Clinic Rochester has all the necessary disciplines (REI, Lab Genetics, Medical Genetics, Psychology on campus. The dialogue and integration between departments required to provide the patient with high quality treatment is already in place and will only be strengthened as preimplantation testing comes on-line. By making a commitment to the follow-up of pregnancies and children resulting from PGD from the beginning of the program, Mayo will hold a unique position in preimplantation testing and will take a leading role in defining the responsible way to implement novel treatments in this area. The comprehensive ethical review undertaken prior to clinical implementation of PGD further emphasizes Mayo’s responsible position in this area of genetic testing. Finally, a flexible and periodic review process for the development of new preimplantation tests (to coincide with rapid accumulation of genomic information) will allow Mayo to stay at the cutting edge of genetic testing
  • Mayo - initially using cleavage stage. Micromanipulators set up in picture for acid drilling and blastoemre aspiration Other methods: Mechanical (make a slice with sharp needle and squeeze cells out) Laser (quick, easy and reproducible) but not yet FDA approved for clinical use) Becoming widespread in Europe

Alan R. Thornhill Ph.D. Alan R. Thornhill Ph.D. Presentation Transcript

  • Alan R. Thornhill Ph.D. Scientific Director, The London Bridge Fertility, Gynaecology and Genetics Centre Assistant Director, Bridge genoma Organisation of a PGD centre Basic genetics for ART practitioners March 23, 2007
  • Organisation of a PGD centre
    • What makes an excellent PGD centre?
    • Building the PGD puzzle
    • Patient vs centre experience of PGD
    • Satellite/transport PGD - Pros and Cons
    • More to come from PGD?
  • What makes an excellent PGD centre?
    • Excellent Genetic Evaluation and Counselling
    • Excellent IVF Platform
    • Excellent Diagnostics Laboratory
    • Excellent Patient experience
    • Integration of Services
    • Rigorous Quality Control/Quality Assurance
    • Commitment to Follow-up/Comprehensive Ethical Review
  • Building the PGD puzzle
    • Ensure appropriate testing (counselling/testing)
    • In Vitro Fertilization
    • Embryo biopsy
    • Diagnostic test on biopsied blastomere
    • Reporting and explaining results
    • Transfer of selected embryos to the uterus
    • Follow-up of pregnancy and resulting child
  • Genetics Diagnostics Fertility Embryology
  • Genetics
    • Family and medical history
    • Assess severity of condition
    • Estimate genetic risk
    • Provide realistic expectations
    • Explain process, disorder and tests
    • Ensure appropriate tests offered
    • Discuss options (risk/benefit)
    • Obtain consent
  • Options for potential ‘PGD’ patients
    • Contraception
    • Childlessness
    • Prenatal testing ( ± pregnancy termination)
    • Donation (egg, sperm, embryo)
    • Adoption
    • Reproductive roulette (emotional, physicial & financial cost of affected child?)
  • Genetics Ensure appropriate testing Ensure PGD valid option Provide realistic expectations
  • Fertility
    • Reproductive and medical history
    • Provide realistic expectations
    • Explain IVF process and tests
    • Discuss options (risk/benefit)
    • Obtain consent
    • Prescribe IVF medication
    • Perform IVF procedures (EC and ET)
  • Set realistic expectations Facilitate high quality eggs Obtain appropriate consents Ensure appropriate stimulation Fertility
  • Embryology
    • Prepare and introduce gametes in vitro
    • Culture embryos
    • Biopsy embryos
    • Prepare diagnostic sample (single cells)
    • Culture biopsied embryos
    • Select embryo(s) for transfer (based on genetic result and morphology)
  • Embryo Biopsy Polar Body Cleavage stage Blastocyst Day 1 Day 3 Day 5/6
  • Biopsied blastomere Polymerase Chain reaction (PCR) Fluorescent In Situ Hybridization (FISH)
  • A 38 year old woman… Select the best two embryos for transfer 1 2 3 4 5 6 7 8 9 10 Monosomy 21 Trisomy 21 Monosomy 22 Trisomy 22 and 16 Monosomy 16 Chaotic Chaotic   
  • Provide accurate & comprehensive documentation Embryology Obtain high quality embryos Obtain high quality embryos Prepare high quality samples Meet diagnostic centre’s acceptance criteria
  • Diagnostics
    • Develop and validate single cell test
    • Receive and accession sample
    • Run test
    • Report results
    • Provide interpretation
  • Diagnostics Provide high quality test Provide appropriate test Meet rapid turn-around time Provide user- friendly report
  • Patient experience of PGD
    • Confusing
    • Complex
    • Control (lack of)
    • Communication (absolutely necessary)
    Centre’s experience of PGD
  • Satellite/transport PGD - Pros and Cons
    • Pros
      • Improved patient access and convenience
      • Lower costs
      • Experienced reference diagnostics lab
      • Centres of excellence model
    • Cons
      • Quality of sample preparation
      • Transportation risks and timings
      • Inadequate counselling/pre-cycle screening
      • Negligible follow-up /responsibilities
  • More to come from PGD?
    • More quality control/quality assurance
    • More tests (whole genome amplification)
    • More screening (aneuploidy, gene expression, protein)
    • More funding for PGD
    • More satellite and transport PGD
    • More access for patients
    • More efficient but more complex
  • Relevant bibliography
    • Kuliev A, Verlinsky, Y. (2004) Thirteen years' experience of preimplantation diagnosis: report of the Fifth International Symposium on Preimplantation Genetics. Reprod Biomed Online. 8(2):229-35.
    • Robertson JA. (2003) Extending preimplantation genetic diagnosis: the ethical debate Ethical issues in new uses of preimplantation genetic diagnosis. Hum Reprod. 18(3):465-71
    • ESHRE PGD Consortium Steering Committee (2002) ESHRE Preimplantation Genetic Diagnosis Consortium: data collection III (May 2001). Hum Reprod. 17(1):233-46
    • Geraedts et al. (2001) Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres. Prenat Diagn. 21(12):1086-92.
    • Soini et al. (2006) The interface between assisted reproductive technologies and genetics: technical, social, ethical and legal issues. Eur J Hum Genet. 14(5):588-645.
    • Thornhill et al (2005) ESHRE PGD Consortium 'Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)'. Hum Reprod. 20(1):35-48.