New England Fertility Institute Lifeline Cryogenics Gad Lavy, M.D., F.A.C.O.G. Life begins here…

Overview of Preimplantation Genetic Diagnosis Gad Lavy, MD

Preimplantation Genetic Diagnosis (PGD) PGD is a state-of-the-art procedure used in conjunction with In Vitro Fertilization (IVF) in which the embryo is tested for certain conditions prior to being placed in the womb of the woman. n Vitro Fertilization (IVF)n Vitro Fertilization (IVF) PGD was first reported in PGD combines the recent advances in molecular genetics and in assisted reproductive technology

Indications for PGD Indications for PGD Chromosomal Disorders Chromosomal rearrangements Chromosomal rearrangements Inversions Inversions Translocations Translocations Chromosome Deletions Chromosome Deletions Gender determination for severe X-linked diseases Severe monogenic diseases (cystic fibrosis, ß thalassaemia, sickle cell anemia, fragile X syndrome, myopathies) Recurrent pregnancy loss Advanced Maternal Age Couples with >3 IVF failures Epididymal or Testicular sperm aspiration with >1 IVF failures.

HOW IS PREIMPLANTATION GENETIC DIAGNOSIS PERFORMED ?  Technically demanding  Very Complex  Requires special skills

How is PGD performed? Ovarian Stimulation IVF Blastomere Biopsy on Day 3 Genetic Analysis Transfer of Unaffected Embryo Outcome Chromosomally Normal Baby

Blastomere Biopsy Video

The PGD process provides two categories of analysis Polymerase Chain Reaction (PCR) Fluorescence In Situ Hybridization (FISH).

Benefits of PGD Increased Implantation Rate Reduction in Pregnancy Losses Reduction in the Chance of Having a Child with Aneuploidy.Reduces the possibility of having to choose to terminate the pregnancy following a diagnosis of a probable genetic disorder.

Risks Embryo damage Oocyte and Embryo Biopsy are invasive procedures Misdiagnosis The accuracy of the PGD for translocation is 90%. False negative result False positive result False positive result The chance for NO result The chance for mosaicism The use of special precautions to avoid exogenous DNA contamination has dramatically reduced the main causes of misdiagnosis IVF Risks Not Achieving Pregnancy There may not be any normal embryos available for transfer. The embryos may not implant and develop even if they do not have the defect. The workup for PGD is expensive and labor intensive PGD can only detect a specific genetic disease in an embryo. It cannot detect many genetic disorders at a time and cannot guarantee that the fetus will not have an unrelated birth defect.

Alternatives to PGD Conceive naturally and have prenatal diagnosis during pregnancy Consider assisted reproduction techniques in which one or both partners would not be the biological parent of the child. in which one or both partners would not be the biological parent of the child.Adoption

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

Conclusions After 10 years of PGD in Reproductive Medicine and the performance of 2500 cycles the main conclusions are : PGD is a reliable procedure in preventing the birth of affected children PGD of aneuploidy is effective and results in a high take home baby rate when implemented in certain categories of patients. Despite the efficiency of the PGD technique, conventional prenatal diagnosis is still required by most PGD laboratories

The development of PGD is one of the most exciting and important milestones in the history of Assisted Reproductive Technology

H. Handyside et al., "Pregnancy from biopsied human preimplantation embryos sexed by Y-specific DNA amplification," Nature, 244:768-70, Nature M. Bielanska et al., "Fluorescence in situ hybridization of sex chromosomes in spermatozoa and spare implantation embryos of a Klinefelter 46,XY/47,XXY male," Human Reproduction, 15:440-4, February M.C. Magli et al., "Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro," Human Reproduction, 15: , August ASRM Ethics Committee Supports Sex Selection to Prevent Genetic Diseases, ASRM Ethics Committee Supports Sex Selection to Prevent Genetic Diseases, Bibliography