1. Preimplantation Genetic Diagnosis (PGD)
Catherine Hartigan
Genetic Counsellor
N W Thames Regional Genetics Service
Prenatal testing has become an almost universal part of pregnancy and employs a variety of techniques to determine the health and condition of an unborn fetus.
I am going to talk about the aims, reasons for and methods of prenatal testing and go through some of the issues around prenatal testing
The aims of prenatal testing are:

2. Aims & Objectives Overview of family planning options Prenatal testing
Pre-implantation genetic diagnosis (PGD)
Psychosocial aspects associated with reproductive decision-making
Question and answer

3. Reproductive options
Where there is a known reproductive risk, the options for having children include:
Conceive naturally, no prenatal testing
Conceive naturally, have prenatal testing
Use of egg and/or sperm donors
Adoption
Pre-implantation genetic diagnosis (PGD)

4. Prenatal Tests
Offered if there is a gene alteration identified in the family
Offered following natural conception, IVF or PGD
Book in with midwife
Ultrasound in pregnancy
Early dating scan
Ultrasound is a non-invasive procedure that does not harm the mother or fetus. High frequency sound waves are utilised to produce visible images from the pattern of echoes made by the different tissues and organs.
Provides important information about baby.

5. Early / Dating Scan Early/dating scan
The developing embryo can be visualised from about 6 weeks gestations. However at this stage, ultrasound is only useful to confirm a pregnancy, that the fetus is living and where the fetus is situated (NB if you suspect an ectopic pregnancy) and twins etc.

6. Prenatal testing Chorionic Villus Sampling (CVS) 11-14 weeks
1-2% risk of miscarriage
Transabdominal or transvaginal
Takes sample of chorionic villi – part of developing placenta – same DNA as fetus
Allows patient to have an earlier result than amnio - important for many patients who would not want to continue with an affected pregnancy

7. Amniocentesis Amniocentesis From 16 weeks
Takes sample of amniotic fluid which contains fetal cells
Risks
Up to 1% risk
of miscarriage
Amniocentesis is an invasive procedure in which a needle is passed through the mother’s abdomen into the amniotic cavity. Amniotic fluid is aspirated and taken to the laboratory for analysis.
Women are advised to rest for about 24 hours after either procedure to help miminise risks

8. What tests are done with the DNA sample?
Test for the genetic disorder in question
Timing for results dependent upon condition
QF-PCR for all:
Looks for t13, 18 & 21 (plus sex chromosomes if sex chromosome disorder suspected)
Result within hours

9. Pre-implantation genetic diagnosis
Uses IVF with an additional step to genetically test the embryo before implantation
PGD is particularly requested by couples who do not want terminate an affected pregnancy

10. The process of PGD
Following hyper-stimulation of the ovaries, many eggs are hopefully removed.
Intracytoplasmic Sperm Injection (ICSI)
single sperm injected into the centre of each egg
Pictures from

11. Embryo Biopsy

12. Pre-implantation Genetic Diagnosis (PGD)
PGD not always an easy option:
Emotional and physical implications
Can be lengthy process
12 – 18 months
Success rates ~30% per cycle; ~40% per embryo transfer
there may not be many eggs to collect
some eggs may not have fertilised
all embryos may have been affected
some embryos may not have survived the biopsy procedure.

13. Where is PGD available? At UCH: http://www.crgh.co.uk/ Costs ~ £13000
At Guy’s Hospital:
Costs ~£12,000

14. Pre-implantation Genetic Diagnosis (PGD)
PGD is now nationally funded
A licence is required from the HFEA for each genetic condition or indication
Requires a referral from clinical genetics
PGD is a relatively new test. It involves IVF, when embryo is at 8-16 cell stage one cell is taken for analysis and only healthy embryos replaced.
Success rate is just below success rate for IVF ( I think it is about 1 in 30)
Expensive
Traumatic
Avaialble for several conditions such as

15. Eligibility criteria for PGD
Female partner is under 39
Female partner has a BMI of 19-30
Both partners are non-smokers
Female partner has hormone levels that suggest she will respond to treatment
An accurate genetic test is available
Couple are living together in a stable relationship
No living unaffected children from the relationship
Known risk of having a child affected by a ‘serious’ genetic condition (at least 10%)
No welfare concerns for the unborn child
A licence is required from the HFEA for each genetic condition or indication
Eligible couples are usually funded for three rounds of PGD.
Eligibility criteria:
No healthy children from relationship
Female partner under 40

16. Decision Making In the context of: Previous experience
Family situation
Religion
Personal beliefs
Psychosocial situation
Balancing miscarriage risk with genetic risk
Coping with decision making
Couples do not always agree

17. Any Questions?