In Vitro Fertilization and Preimplantation Genetic DiagnosisADRIANNA 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 of eggs depends on age of mother

Side 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 GoalRequesting 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

risk for having an affected child the impact of the disease the available options 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