Kearns

Anish A. Shah, MD, MHS, FACOGBoard Certified Reproductive Endocrinologist

Preimplantation Genetic Testing Gateway to the Future of Fertility

Dennis W. Matt, PhD, HCLDHigh Complexity Clinical Laboratory Director

1DisclosuresNothing to discloseNo conflicts of interest2What can you genetically screen?Egg? not reliable because sperm is not present.

Sperm same problem as egg, need the DNA of mom and dad to combine to see if came together normally

Embryo Excellent target to screen

Basic Genetics Men 46 XYWomen 46 XXObjective:Half DNA of Mom needs to be packaged into the Egg Half DNA of Dad needs to be packaged into the SpermNormal Karyotype

The Dance

Normal Chromosomal DivisionPolar Body(Discarded)Haploid OocyteHaploid SpermDiploid EmbryoAneuploidy: Meiotic NondisjunctionMonoploidOocyteDiploidOocyteHaploid SpermTrisomicEmbryoHaploid SpermMonosomicEmbryoAneuploidy: Downs Syndrome

Risk for Downs Syndrome increases with Maternal Age

Age Matters, Why? Aneuploidy

Eggs age, Aneuploidy increases

How do we get the Egg?

How do we get the Egg?

Give FSH and LHHow do we get the Egg?

Give FSH and LHHow do we get the Egg?

Give FSH and LH

PGD vs PGSPreimplantaton Genetic DiagnosisSpecific genetic mutations documented in the parent(s) Cystic FibrosisBreast Cancer gene (BRCA 1 and 2)Etc. Preimplantaton Genetic ScreeningScreen embryos to see which one is genetically NORMAL, or rather which one will not be a miscarriage or unhealthy pregnancy17Stages of Embryo Development

Blastocysthttp://www.reproduction-online.org/content/139/1/35/F2.large.jpghttp://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/9980.jpg

19Blastocyst Stage Embryo Biopsyhttp://www.youtube.com/watch?v=53fzEMYdOUc

20The Evolution Of Pre-implantation Embryo Genetic EvaluationBiopsy Technique

Trophoblast from Day 5, 6, or 7 Embryo

Single Blastomere from Day 3 Embryo

Fluorescence in situ hybridization (FISH)

Single Gene Disorder

Comprehensive Genomic Hybridization (cGH)Day 3 vs Blastocyst Biopsy

Fertility and Sterility2013 100, 624-630DOI: (10.1016/j.fertnstert.2013.04.039) Copyright 2013 American Society for Reproductive Medicine Terms and Conditions

22Implantation rates following a randomized paired analysis of the effects of cleavage- and blastocyst-stage biopsies on embryo reproductive potential. Sustained implantation and delivery of the biopsied embryo were significantly reduced compared with its control sibling when biopsy was performed on day 3 at the cleavage stage (McNemar chi-square: P