PGD

Question 1

what was the first monogenic disorder to which PGD was successfully applied?

Answer 1

CF

Question 2

PGD PCR iparticularly prone to contamination from extra-embryonic material leading to

Answer 2

allele dropout

Question 3

What is Preimplantation genetic (PG) testing?

Answer 3

the practice of obtaining a cellular biopsy sample from a developing human oocyte (prior to fertilisation) or embryo (prior to implantation), obtained via a cycle of in vitro fertilisation (IVF); evaluating the sample’s genetic composition; and using this information to determine which embryos will be optimal for subsequent uterine transfer.

Question 4

PGDiagnosis=

Answer 4

testing cells from embryos created outside the body by IVF for a genetic disorder to prevent birth of affected children from parents (usually fertile) who are affected by, or who are carriers of a known genetic abnormality.

Question 5

PGScreening=

Answer 5

=identify optimal embryos for uterine transfer in an IVF cycle. Parents assumed normal, screen primarily used to look for abnormalities, typically aneuploidy and with aim of improving implantation efficiency and live birth rates. No evidence it works therefore not adopted by NHS.

Question 6

The aims of the NHS England Clinical Commissioning Policy for PGD are to:

Answer 6

• Reduce variation in access to PGD
• Ensure PGD is commissioned for conditions with acceptable evidence of clinical benefit and cost effectiveness
• Reduce unacceptable variation in clinical practise in conditions referred for PGD and
• Promote the cost effective use of healthcare resources.

Question 7

How many cycles of PGD for couples in accordance with criteria outlined in Clinical Commissioning Policy will NHS fund?

Answer 7

3

Question 8

Clinical Commissioning Policy for PGD

Answer 8

• at risk of having a child with a serious genetic condition.
• referred to the PGD provider by an NHS Clinical Genetics Service.
• risk of conceiving a pregnancy affected by a serious genetic condition should be 10% or more.
• received genetic counselling from a clinical geneticist or a registered genetic counsellor.
• female < 40 years of age at the time of treatment (In France it is 43y).
• female BMI of more than 19 and less than 30.
• Both non smokers
• no living unaffected child from the current relationship.
• HFEA must have licensed the indication for PGD.
• The test must be included in the list of UKGTN approved tests, or suitable for inclusion.
• The couple should not be seeking PGD primarily because they are infertile.

Question 9

Clinical Commissioning Policy for PGD Exclusions

Answer 9

• Non medical gender selection
• to address infertility or to prevent miscarriages unknown aetiology.
• Pre-implantation Genetic Screening (PGS); no evidence that improves the rate of pregnancy or live IVF births.

Question 10

PGD for mitochondrial disease less prone to ADO due to

Answer 10

high copy number of mtDNA.

Question 11

PGD for mitochondrial DNA diseases is a process of risk reduction

Answer 11

selected with levels of mutant mtDNA that are likely to be low enough to avoid disease manifestation.

Question 12

Restoration of the epigenome requires two waves of epigenetic reprogramming:

Answer 12

(a) during ontogeny of primordial germ cells; and (b) during preimplantation embryonic development.

Question 13

Main ethical concerns:

Answer 13

1. IS PGD MORALLY ACCEPTABLE?
2. Is it acceptable to include HLA typing?
   3: interesting ethical issues e.g. selection FOR dear child, individuals with acondroplasia avoiding homozygous preg but not minding heterozygous; PGD for sickle-cell in Africa due to < malaria risk and PGS sex selection.