New England Fertility InstituteNew England Fertility InstituteLifeline CryogenicsLifeline CryogenicsGad Lavy, M.D., F.A.C.O.G.Gad Lavy, M.D., F.A.C.O.G.

Life begins here…Life begins here…

Overview Overview of of

Preimplantation Preimplantation Genetic Genetic

DiagnosisDiagnosisGad Lavy, MDGad Lavy, MD

Preimplantation Genetic DiagnosisPreimplantation Genetic Diagnosis(PGD)(PGD)

PGD is a state-of-the-art PGD is a state-of-the-art procedure used in procedure used in conjunction with conjunction with In Vitro In Vitro Fertilization (IVF)Fertilization (IVF)in which the embryo is in which the embryo is tested for certain tested for certain conditions prior to being conditions prior to being placed in the womb of the placed in the womb of the woman.woman.

PGD was first reported in PGD was first reported in 1990. 1990.

PGD combines the recent PGD combines the recent advances in molecular advances in molecular genetics and in assisted genetics and in assisted reproductive technologyreproductive technology

Indications for PGDIndications for PGDChromosomal DisordersChromosomal Disorders

Chromosomal Chromosomal rearrangementsrearrangements

InversionsInversions Translocations Translocations Chromosome Chromosome

DeletionsDeletionsGender determination for severe Gender determination for severe X-linked diseasesX-linked diseasesSevere monogenic diseases Severe monogenic diseases (cystic fibrosis, ß thalassaemia, (cystic fibrosis, ß thalassaemia, sickle cell anemia, fragile X sickle cell anemia, fragile X syndrome, myopathies)syndrome, myopathies)Recurrent pregnancy lossRecurrent pregnancy lossAdvanced Maternal Age Advanced Maternal Age Couples with >3 IVF failuresCouples with >3 IVF failuresEpididymal or Testicular sperm Epididymal or Testicular sperm aspiration with >1 IVF failures.aspiration with >1 IVF failures.

HOW IS PREIMPLANTATION HOW IS PREIMPLANTATION GENETIC DIAGNOSIS PERFORMEDGENETIC DIAGNOSIS PERFORMED? ?

Technically Technically demandingdemanding

Very ComplexVery ComplexRequires special Requires special

skillsskills

How is PGD performed?How is PGD performed?

Ovarian StimulationOvarian Stimulation

IVFIVFBlastomere Biopsy on Day 3Blastomere Biopsy on Day 3

Genetic AnalysisGenetic AnalysisTransfer of Transfer of

Unaffected EmbryoUnaffected Embryo

OutcomeOutcome

Chromosomally Normal BabyChromosomally Normal Baby

Blastomere BiopsyBlastomere BiopsyVideoVideo

The PGD process provides two The PGD process provides two categories of analysiscategories of analysis

Polymerase Polymerase Chain Reaction Chain Reaction (PCR) (PCR)

Fluorescence In Fluorescence In Situ Hybridization Situ Hybridization (FISH).(FISH).

Benefits of PGDBenefits of PGD

Increased Implantation Increased Implantation RateRate Reduction in Pregnancy Reduction in Pregnancy LossesLosses Reduction in the Chance Reduction in the Chance of Having a Child with of Having a Child with AneuploidyAneuploidy

..Reduces the possibility Reduces the possibility of having to choose to of having to choose to terminate the pregnancy terminate the pregnancy following a diagnosis of following a diagnosis of a probable genetic a probable genetic disorder.disorder.

Risks Risks Embryo damageEmbryo damageOocyte and Embryo Biopsy are Oocyte and Embryo Biopsy are invasive procedures invasive procedures Misdiagnosis Misdiagnosis The accuracy of the The accuracy of the PGD for translocation is 90%.PGD for translocation is 90%.

False negative resultFalse negative result False positive resultFalse positive result

The chance for NO result The chance for NO result The chance for mosaicismThe chance for mosaicism

The use of special precautions to avoid The use of special precautions to avoid exogenous DNA contamination has exogenous DNA contamination has dramatically reduced the main causes dramatically reduced the main causes of misdiagnosisof misdiagnosisIVF RisksIVF RisksNot Achieving PregnancyNot Achieving Pregnancy

TThere may not be any normal here may not be any normal embryos available for transfer.embryos available for transfer.

TThe embryos may not implant he embryos may not implant and develop even if they do not have and develop even if they do not have the defect.the defect.The workup for PGD is expensive The workup for PGD is expensive and labor intensiveand labor intensivePGD can only detect a specific genetic PGD can only detect a specific genetic disease in an embryo. It cannot detect disease in an embryo. It cannot detect many genetic disorders at a time and many genetic disorders at a time and cannot guarantee that the fetus will not cannot guarantee that the fetus will not have an unrelated birth defect. have an unrelated birth defect.

Alternatives to PGDAlternatives to PGD

Conceive naturally and Conceive naturally and have prenatal diagnosis have prenatal diagnosis during pregnancyduring pregnancy

Consider assisted Consider assisted reproduction techniquesreproduction techniques

in which one or both in which one or both partners would not be partners would not be the biological parent of the biological parent of the child.the child.

AdoptionAdoption

Future of PGDFuture of PGDEfforts continue to be Efforts continue to be focused on improving focused on improving methods to obtain an methods to obtain an accurate diagnosis. accurate diagnosis. PGD holds great PGD holds great promise for the future promise for the future as techniques and as techniques and genetic tests are genetic tests are perfected.perfected.PGD may become PGD may become routine in the next few routine in the next few years. years.

ConclusionsConclusionsAfter 10 years of PGD in After 10 years of PGD in

Reproductive Medicine and Reproductive Medicine and the performance of 2500 the performance of 2500 cycles the main conclusions cycles the main conclusions are :are :PGD is a reliable procedure in PGD is a reliable procedure in preventing the birth of affected preventing the birth of affected children children PGD of aneuploidy is effective PGD of aneuploidy is effective and results in a high take and results in a high take home baby rate when home baby rate when implemented in certain implemented in certain categories of patients.categories of patients.Despite the efficiency of the Despite the efficiency of the PGD technique, conventional PGD technique, conventional prenatal diagnosis is still prenatal diagnosis is still required by most PGD required by most PGD laboratorieslaboratories

The development of PGD is one of The development of PGD is one of the most exciting and important the most exciting and important

milestones in the history of milestones in the history of Assisted Reproductive TechnologyAssisted Reproductive Technology

H. Handyside et al., "Pregnancy from biopsied human H. Handyside et al., "Pregnancy from biopsied human preimplantation embryos sexed by Y-specific DNA amplification," preimplantation embryos sexed by Y-specific DNA amplification," NatureNature, 244:768-70, 1990. , 244:768-70, 1990.

M. Bielanska et al., "Fluorescence in situ hybridization of sex M. Bielanska et al., "Fluorescence in situ hybridization of sex chromosomes in spermatozoa and spare implantation embryos of chromosomes in spermatozoa and spare implantation embryos of a Klinefelter 46,XY/47,XXY male," a Klinefelter 46,XY/47,XXY male," Human ReproductionHuman Reproduction, 15:440-4, , 15:440-4, February 2000. February 2000.

M.C. Magli et al., "Chromosome mosaicism in day 3 aneuploid M.C. Magli et al., "Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in embryos that develop to morphologically normal blastocysts in vitro," vitro," Human ReproductionHuman Reproduction, 15:1781-86, August 2000. , 15:1781-86, August 2000.

ASRM Ethics Committee Supports Sex Selection to Prevent ASRM Ethics Committee Supports Sex Selection to Prevent Genetic Diseases, Genetic Diseases, www.asrm.org/Media/Press/ethics1099.htmlwww.asrm.org/Media/Press/ethics1099.html

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