2. Prenatal testing Flashcards
What is the WHO definition of infertility as a disease?
A disease of the reproductive system by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse
Issues with human rights and surrogacy?
It is inconsistent with human dignity that a woman should use her uterus for financial profit
What are the two types of test during pregnancy?
Screening tests
Diagnostic tests
Features of screening tests offered during pregnancy?
Offered to all pregnant women to access likelihood of poor health of mother and baby
Simple tests e.g. Blood test, ultrasound scan or questionnaire
They do not provide a definite diagnosis
What are the Warnock and Brazier report?
Access surrogacy
Warnock in 1984 said “It is inconsistent with human dignity that a woman should use her uterus for financial profit”
Brazier in 1997
What are parental orders
Particular for surrogacy, for the new adoptive parents to become legal mother and father
Features of diagnostic tests used during pregnancy?
Follow-up tests that we carry out to find out whether you baby has a particular condition.
Offered to at risk women, as a consequence of screening.
E.g. Chronionic villus sampling, amniocentesis (risk of miscarriage), detailed ultrasound
Why we carry out screening and testing?
- To reassure parents (but not straightforward if abnormality found)
- To inform and prepare parents for the birth of an affected infant
- To allow in utero treatment, or delivery at a specialist centre for immediate postnatal treatment
- To allow termination of an affected fetus
- To provide information so that parents may choose between 2, 3 or 4 ** key issue here = choice **
Testing in natural conception available?
- Non-invasive screening e.g. ultrasound, serum tests, NIPT (non-invasive prenatal testing)
- Invasive prenatal diagnostic (PND) testi e.g. CVS, aminocentesis
IVF testing available?
Preimplantation genetic diagnosis (PGD)
Ultrasound: What is it? When is it? Why is it? Ethical issues?
What is it: Uses sound waves, painless, no risk
When is it: Dating scan at 12 weeks, anomaly scan at 20 weeks
Why is it:Dating scan for working out when due, looking for miscarriage. Anomaly to look at physical abnormalities e.g. spina bifida
Ethical issues: Everyone is offered anomaly scan, not everyone chooses to take it. Is that fair on the unborn baby if best care isn’t given?
Down's syndrome screen: What is it? When is it? Why is it? Ethical issues?
What is it:
Combination of ultrasound (looks for thickening at back of neck via NT) and serum test (looks for PAPP-A and free beta-hCG markers
When is it: 10-13 weeks
Why is it: It measures the chance of DS but is not a diagnostic test. Can also detect Edwards Syndrome
Ethical issues: Risk, if high then option to take diagnostic tests (amnio or CVS)
What are the markers in the serum test for DS?
PAPP-A: Pregnancy associated plasma protein-A
Free beta-hCG: Free beta-human chorionic gonadotrophin)
How good is the ‘combined’
screening test for DS?
Falso positive: Test abnormal but foetus not affected False negative (related to detection rate): Test normal, but foetus is affected Combined test= FN 16%, FP 2.2%
It is the recommended screening test
How is the quadruple test used during DS screening?
Used if women presents later (14 weeks 2 days onwards)
Blood test: Alpha-fetaprotein (AFP), total human chorionic gonadotrophin (hCG), unconjugated oestriol, inhinit A
FN: 20%, FP:3.5%
Amniocentesis: What is it? When is it? Why is it? Ethical issues?
What is it?
Needle inserted through the abdomen and into amniotic fluid
When is it?
15 weeks +
Why is it?
- Previous history with fetal problems
- Family history
- Over 35 years (i.e. at increased risk of DS)
- Antenatal screening result suggests a problem
Ethical issues?
- 0.5-1% risk of miscarriage
- Infection
- Injury
- FP rate 0.1-0.6%
- FN rate 0.6%
Chorionic villus sampling: What is it? When is it? Why is it? Ethical issues?
What is it: Fine need inserted through abdomen and into uterus; or through cervix and small piece of developing placenta removed
When is it? 11 weeks
Why is it? Tests for inhertied disorders (CF, sickle cell anaemia, muscular dystrophy) and chromosomal disorders, sex, earlier testing
Ethical issues?
- 1-2% risk of miscarriage
- Infection
- Heavy bleeding
- False positive 1-2%, false-neg rate of 2%
Examples of disease for which DNA tests are available?
CF Phenylketonuria Tay-Sachs DMD Huntington's disease Inherited breast and ovarian cancers
What is NIPT
Non-invasive prenatal genetic testing
Cell-free foetal DNA (DNA from placenta, v similar from foetus)
Earlier use: 9-10 weeks
Uses:
-To assess risk of chromosomal abnormalities with more accuracy
-Definitive diagnosis of some conditions (e.g. Cystic fibrosis, achondroplasia)
-Can determine gender
Preimplantation genetic diagnosis:
Offered to?
Process?
Uses?
Offered to couples who are at risk of passing on a genetic disorder
Process: Removing 1 cell from the early embryo
Uses:
- A disorder that may affect capacity for live birth
- Risk of child being born with or developing a serious disability (genetic, chromosomal, mitochondrial)
- If gender related disorder, can use to select gender
- 100+ conditions listed on HFEA site
Code of practice guidance to definition “serious” illness?
- Take into consider the views of those seeking
- Likely degree of suffering
- Availability of effective treatment
- Speed of degeneration
- Extent of intellectual impairment
- Social support available
- Family circumstances
What is Huntington’s disease?
Inhertied, late onset, degenerative
Manifests 30-50 yrs
50/50 chance of inheriting
Issues with testing for huntington’s disease?
- Prenatal genetic testing for HD
– If seek testing, do so on understanding that they will terminate if test positive
– Why? Testing is only available to adults, and not all at risk choose to take it; prenatal testing means that the parents know something about the child’s future that the child has not elected to know - PGD for HD
– Thus select an embryo that does not carry the inherited HD gene
What is PGD?
Preimplantation genetic diagnosis
What is the case for preference FOR disabled embryo’s?
The case of Tomato Lichy and Paula Garfield
Note: They did not want to positively select but it opened the debate
What is saviour siblings?
Creating an embryo (using PGD) that will be a tissue match (“tissue typing” by HLA) for an existing child who has a condition that requires e.g. bone marrow transplant
Legal approval of saviour siblings?
2001: This was approved for removal of cord blood cells (source of stem cells) and the embryo had to be at risk of inheriting the same disorder
2004: Both these conditions were removed, hence bone marrow trans plant now possible (although solid organ donation is prohibited)
Case studies for saviour siblings?
Hashmi family (2002)
- Beta-thalassmeamia, inherited
- UK HFEA granted permission
Whittaker family (2002)
- Diamond Blackfan anaemia, not inhertied
- UK refused, US granted
Fletcher family (2004)
- Diamond Blackfan anaemia, not inherited
- UK HFEA granted approval
Ethical considerations of saviour siblings?
Is the saviour sibling being “used” to help the other child vs just for being them?
-However, people have children for all kinds of reasons…
What is the psychological effect on the saviour sibling (and existing child) and their resultant relationship?
-However, the psychological impact on family of bereavement?
What is CRISPR?
Gene editting technology
Ethical considerations of CRISPR?
Practical and philosophical:
In utero or gene therapy
Extent of disability
