- 1.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
2. Organisation of a PGD centre
- What makes an excellent PGD centre?
- Patient vs centre experience of PGD
- Satellite/transport PGD- Pros and Cons
3. What makes an excellent PGD centre?
- Excellent Genetic Evaluation and Counselling
- Excellent Diagnostics Laboratory
- Excellent Patient experience
- Rigorous Quality Control/Quality Assurance
- Commitment to Follow-up/Comprehensive Ethical Review
4. Building the PGD puzzle
- Ensure appropriate testing (counselling/testing)
- Diagnostic test on biopsied blastomere
- Reporting and explaining results
- Transfer of selected embryos to the uterus
- Follow-up of pregnancy and resulting child
5. Genetics Diagnostics Fertility Embryology 6. Genetics
- Family and medical history
- Assess severity of condition
- Provide realistic expectations
- Explain process, disorder and tests
- Ensure appropriate tests offered
- Discuss options (risk/benefit)
7. Options for potential PGD patients
- Prenatal testing( pregnancy termination)
- Donation (egg, sperm, embryo)
- Reproductive roulette(emotional, physicial & financial cost
of affected child?)
8. Genetics Ensure appropriate testing Ensure PGD valid option
Provide realistic expectations 9. Fertility
- Reproductive and medical history
- Provide realistic expectations
- Explain IVF process and tests
- Discuss options (risk/benefit)
- Perform IVF procedures (EC and ET)
10. Set realistic expectations Facilitate high quality eggs
Obtain appropriate consents Ensure appropriate stimulation
Fertility 11. Embryology
- Prepare and introduce gametes in vitro
- Prepare diagnostic sample (single cells)
- Select embryo(s) for transfer (based on genetic result and
morphology)
12. Embryo Biopsy Polar Body Cleavage stage Blastocyst Day 1 Day
3 Day 5/6 13. Biopsied blastomere Polymerase Chain reaction (PCR)
Fluorescent In Situ Hybridization (FISH) 14. 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 15. Provide accurate & comprehensive
documentation Embryology Obtain high quality embryos Obtain high
quality embryos Prepare high quality samples Meet diagnostic
centres acceptance criteria 16. Diagnostics
- Develop and validate single cell test
- Receive and accession sample
17. Diagnostics Provide high quality test Provide appropriate
test Meet rapid turn-around time Provide user- friendly report 18.
Patient experience of PGD
- Communication (absolutely necessary)
Centres experience of PGD 19. 20. Satellite/transport PGD- Pros
and Cons
-
- Improved patient access and convenience
-
- Experienced reference diagnostics lab
-
- Centres of excellence model
-
- Quality of sample preparation
-
- Transportation risks and timings
-
- Inadequate counselling/pre-cycle screening
-
- Negligible follow-up /responsibilities
21. More to come from PGD?
- More quality control/quality assurance
- More tests (whole genome amplification)
- More screening (aneuploidy, gene expression, protein)
- More satellite and transport PGD
- More efficient but more complex
22. 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.