In Vitro Fertilization and Preimplantation Genetic Diagnosis ADRIANNA

In Vitro Fertilization and Preimplantation Genetic Diagnosis ADRIANNA VLACHOS, MD DBA CAMP 2015

In Vitro Fertilization and Pre-Implantation Genetic Diagnosis Goal: Child unaffected by a genetic (hereditary) illness defined by a known genetic mutation Secondary goal: “Creating” a child unaffected by the genetic illness who is a transplant donor for the affected child

In Vitro Fertilization and Pre-Implantation Genetic Diagnosis IVF Hormonal therapy to the mother to get many eggs for ovulation Number Side of eggs depends on age of mother effects of these medications to mother Eggs harvested (under anesthesia) Eggs are fertilized with sperm outside of mother (“in the test tube”)

In Vitro Fertilization and Pre-Implantation Genetic Diagnosis PGD Fertilized egg reaches 8 -cell stage One cell taken for RP/HLA testing “RP neg, HLA matched” fertilized egg implanted in mother (1/8 chance) Hormonal therapy to continue pregnancy, usually until 10 -12 weeks CVS (10 wks) or Amnio (18 wks) for confirmation

Pre-natal vs Pre-implantation diagnosis Dr. I. Souter, MGH Fertility Center

Pre-natal Diagnosis Amniocentesis Chorionic Villus Sampling (CVS)

Pre-implantation Diagnosis Introduced initially in 1990 Biopsy of a single cell per embryo followed by its genetic diagnosis through different techniques the subsequent replacement to the patient of those embryos classified by genetic diagnosis as unaffected

PGD Indications Primary Goal Procedure is offered to couples: With known single gene disorders that can be detected by PGD - DBA With known chromosomal abnormalities that can be detected by PGD requesting sex selection for X-linked disorders – DBA

PGD Indications Secondary Goal Requesting PGD for HLA-typing (to allow selection of embryos that are histocompatible with live siblings)

Single Gene Disorders

PGD Process Ovulation Induction Retrieval Fertilization Embryo Bx on Day-3 Genetic Analysis Embryo Transfer

Ovulation induction

Oocyte Retrieval

Fertilization Conventional Insemination Intracytoplasmic Sperm Injection (ICSI)

Embryo Culture

Day 3/Cleavage Stage Embryo

Cleavage Stage Biopsy

Genetic Analysis/PCR DNA amplification sequence harboring the mutation Mutation Characterization FISH PCR HLA Matching

Embryo Transfer

Early Pregnancy

Risks Embryo damage Oocyte and Embryo Biopsy are invasive procedures Misdiagnosis • • False negative result False positive result The chance for NO result The chance for mosaicism 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.

Summary • Before PGD is performed, genetic counseling must be provided to ensure that patients fully understand the Ø risk for having an affected child Ø the impact of the disease Ø the available options Ø the multiple technical limitations including the possibility of an erroneous result • Prenatal diagnostic testing is strongly encouraged to confirm the results of PGD

Conclusions It is a personal choice!!! • This requires identification of your family’s DBA gene. • Obstacles • Practical • Religious • Ethical • Financial • • There are other options available Adoption • Sperm/egg donation • Just having a baby •