Anish A. Shah, MD, MHS, FACOG B OARD C ERTIFIED R EPRODUCTIVE E NDOCRINOLOGIST Preimplantation Genetic Testing Gateway to the Future of Fertility Dennis W. Matt, PhD, HCLD H IGH C OMPLEXITY C LINICAL L ABORATORY D IRECTOR

DisclosuresDisclosures Nothing to discloseNothing to disclose No conflicts of interestNo conflicts of interest

What can you genetically screen? Egg?  not reliable because sperm is not present.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 normallySperm  same problem as egg, need the DNA of mom and dad to combine to see if came together normally Embryo  Excellent target to screenEmbryo  Excellent target to screen

Basic Genetics Men  46 XYMen  46 XY Women  46 XXWomen  46 XX Objective:Objective: –Half DNA of Mom needs to be packaged into the Egg –Half DNA of Dad needs to be packaged into the Sperm

Normal Karyotype

The Dance

Normal Chromosomal Division Polar Body (Discarded) Haploid Oocyte Haploid Sperm Diploid Embryo

Aneuploidy: Meiotic Nondisjunction Monoploid Oocyte Diploid Oocyte Haploid Sperm Trisomic Embryo Haploid Sperm Monosomic Embryo

Aneuploidy: Down’s Syndrome

Risk for Down’s Syndrome increases with Maternal Age

Age Matters, Why? Aneuploidy

Eggs age, Aneuploidy increases

How do we get the Egg?

Give FSH and LH

How do we get the Egg? Give FSH and LH

How do we get the Egg? Give FSH and LH

PGD vs PGS Preimplantaton Genetic DiagnosisPreimplantaton Genetic Diagnosis –Specific genetic mutations documented in the parent(s) Cystic FibrosisCystic Fibrosis Breast Cancer gene (BRCA 1 and 2)Breast Cancer gene (BRCA 1 and 2) Etc….Etc…. Preimplantaton Genetic ScreeningPreimplantaton Genetic Screening –Screen embryos to see which one is genetically NORMAL, or rather which one will not be a miscarriage or unhealthy pregnancy

Stages of Embryo Development

BlastocystBlastocyst

Blastocyst Stage Embryo Biopsy

The Evolution Of Pre-implantation Embryo Genetic Evaluation Biopsy 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 Sterility , DOI: ( /j.fertnstert ) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions Terms and Conditions

Results of PGS

4,873 Embryos from 571 PGS Cycles Percentage of IVF Cycles Resulting in Live Birth Brezina PR, Tobler K, Benner AT, Du L, Boyd B, Kearns WG. Evaluation of 571 In Vitro Fertilization (IVF) Cycels and 4,873 Embryos Using 23-Chromosome Single Nucleotide Polymorphism (SNP) Microarray Preimplantation Genetic Screening (PGS). Pacific Coast Reproductive Society Annual Meeting, Rancho Mirage, CA, April [Accepted December 22, 2011] [Poster Presentation]

PGS Conclusions Appropriate patient populationAppropriate patient population –RPL –Balanced parental translocation Day 5 preferable to day 3Day 5 preferable to day 3 Must evaluate all 23 pairs of chromosomesMust evaluate all 23 pairs of chromosomes

Future Directions  NOW!!!!!! Next Generation (Gen) SequencingNext Generation (Gen) Sequencing –Fast –Cheaper –More Sensitive MAJORITY Frozen Embryo TransferMAJORITY Frozen Embryo Transfer –Higher live birth rate than fresh transfer (randomized control trials) –Healthier delivery outcomes of babies and mothers

Anish A. Shah, MD, MHS, FACOG B OARD C ERTIFIED R EPRODUCTIVE E NDOCRINOLOGIST Dennis W. Matt, PhD, HCLD H IGH C OMPLEXITY C LINICAL L ABORATORY D IRECTOR THANK YOU