Preimplantation genetic diagnosis in New Zealand:
A tool for pre-birth screening
A presentation by
The Human Genome Research Project
University of Otago
Introduction
•The Human Genome Research Project: Year One
•PGD as a tool for pre-birth screening
“Screening is a health service in which members of a
defined population, who either do not necessarily
perceive they are at risk of, or are already affected by a
disease or its complications, are asked a question or
offered a test, to identify those individuals who are
more likely to be helped than harmed by further tests or
treatment to reduce the risk of a disease or its
complications.”
National Health Committee 2003
The Science of PGD
• PGD combines recent advances in genetics
and reproductive medicine, “reprogenetics”
• Requires IVF cycle
– ovarian stimulation
– egg harvest
– In vitro fertilisation
• Embryo Biopsy
Embryo biopsy
• Removal of one or two cells
from a day three eight cell
pre-embryo
• Genetic testing:
-fam single gene disorder
-fam chromosomal disorders
-Aneuploidy
Selection of viable embryo and transfer
Science subject to limitations:
-possible lack of suitable transferable embryos
-IVF/PGD pregnancy rate (25-30%)
-misdiagnosis rate (rare), PGD generally reliable
-congenital conditions not screened for (3.8%)
-cost
Marjoribanks et al, “Systematic Review of the Quantifiable Harms and Benefits of Preimplantation
Genetic Diagnosis” 2004
Reproductive Opportunities
• Diagnosis of heritable disorder (gene mutations,
chromosomal disorder) at preimplantation stage
Alternative options:
-take chances with pregnancy
-prenatal diagnosis with option of
termination
-utilise donor gametes and IVF
-remain childless, adopt
• PGD with Aneuploidy Screening
-infertility / recurrent miscarriage
-risks associated with reproductive age
Reproductive Opportunities
Testing for disease susceptibility, (not fully penetrant)
• BRCA-1, BRCA-2
Cancers with defined genetic basis (FAP)
• Selection for Third Party Benefit
HLA tissue typing for donation
• Non-medical selection of traits (currently limited)
Raises controversial ethical questions
Reasons for Caution
“Technology has made all kinds of
things possible that were
impossible, or unimaginable in an
earlier age. Ought all these things
to be carried out in practice? This
is the most general ethical question
to be asked …”
Baroness Mary Warnock
Welfare of the child
“The likely significance of this fact is subtle but
profound. The attitude of parents toward their child
may be quietly shifted from unconditional
acceptance to critical scrutiny: the very first act of
parenting now becomes not the unreserved
welcoming of an arriving child, but the judging of
his or her fitness, while still an embryo, to become
their child, all by the standards of contemporary
genetic screening. Moreover, as the screening
technology itself grows more refined, more able to
pick out serious but not life-threatening genetic
conditions (from dwarfism and deafness to dyslexia
and asthma) and then genetic markers for desirable
traits, the standards for what constitutes an
acceptable birth may grow more exacting.”
President’s Council on Bioethics
The disability critique
Concerns:
• PGD may lead to discrimination against, and the
stigmatization of, persons living with disability
• Eugenics, and parallels to the Holocaust
“It’s a terrifying thought that people out there believe
my life isn’t worth living, isn’t worth replicating – so
they would try to breed that out.”
Paul Gibson, Policy Manager CCS, blind
NZ Herald, 17 September 2005
The disability critique cont…
Responses:
•
•
•
•
Experience of prenatal screening
“Disability” vs “people with disabilities”
Reproductive autonomy
Moral duty to prevent and relieve suffering
The moral status of the embryo
Is it permissible to create and discard embryos for this
purpose?
• NO - the embryo is a person. It has a right to life and
should not be destroyed. PGD should be prohibited
• YES - the embryo is no more a person than a lettuce.
It has no right to life, and PGD should proceed
• MAYBE - the embryo has weak moral status and can
be created and discarded for legitimate reasons where
the benefits of the proposed use outweigh its weak
moral status – PGD should proceed in limited
circumstances
Playing God
• The gene pool is God’s sacred creation
and should be preserved. We cross the
limits of human sovereignty when we
decide to change human nature itself
• Biological processes and products have evolved over
billion-year geological time scales and have thereby
proved their robustness. Natural life-forms come with
the quality assurance of exceptionally prolonged
testing under the most searching conditions. Genetic
“tinkering” will reduce biodiversity
Models of Regulatory Frameworks for PGD
Professional
Guidelines
Facilitative Restrictive Prohibitive
Legislation Legislation Legislation
Method of Voluntary Peer
regulation Review Process
Legislation
Comprehensive
and
legislation
delegation to
statutory body
Legislation
banning
procedures
Jurisdiction
UK
Victoria
Australia
Canada
New Zealand
Italy
Germany
Austria
Switzerland
Ireland
USA
New South Wales
And Queensland
Australia;
India
France
Slovenia
Netherlands
Adapted from poster presentation by Lexi Neame, Infertility Treatment Authority,
Victoria, Australia.
NZ Legal Response
• Human Assisted Reproductive Technology Act 2004
Categories of assisted reproductive procedures
Prohibited activities
Regulated activities
Established procedure
Creates two decision-making bodies
ACART (advisory committee) and
ECART (ethics committee)
Incorporates NECAHR Guidelines on PGD as
Interim ACART Guidelines
Prohibited Activities
• Embryo selection on the basis of sex
(Defence if selection was performed to prevent or treat
a genetic disorder)
Regulated activities
• PGD that’s neither an established procedure nor a
prohibited activity
• Require prior approval of ECART, case by case basis
• ECART approves, declines applications on the basis
of guidelines formulated by ACART
• ACART only publish guidelines after interested
parties and public have opportunity to make
submissions
Regulated Activities
• PGD with HLA tissue typing
– Approval on case by case basis
– Sick child - familial single gene disorder or
familial sex-linked disorder
– No other possibilities for treatment or sources of
tissue and
– Planned treatment to utilise only cord blood
• Embryo sibling, at risk familial single gene / sexlinked disorder for which PGD test is available
Established procedures
Aneuploidy screening (most common application)
Familial single gene disorders (very wide scope)
Familial sex-linked disorders,
Familial chromosomal disorders
•
•
•
•
disorder identified in family / whanau
25% or greater risk of affected pregnancy
no available test for sex-linked mutation
Evidence future individual may be ‘seriously
impaired’ (No definition in Order)
Interim Guidelines
• Provides for PGD in circumstances covered by
established procedures order
• “it is the responsibility of PGD providers, in
collaboration with a clinical geneticist, to determine
whether a disorder is likely to be serious in the
offspring” (Not parents)
Prohibited uses of PGD Interim Guidelines
• Prohibit PGD for social selection
• Altering genetic constitution of embryo
• Selection of an embryo with a genetic impairment
seen in a parent
- decisional asymmetry?
- limits reproductive choice?
eg what if all embryos affected?
Obligations on Providers
• PGD providers must be certified under Health and Disability
Services (Safety) Act 2001, requires accreditation by RTAC of the
Fertility Society Australia, s81(4)
• Comply RTAC Code of Practice (Relevant interim standard for
purposes of HDS(S) Act, pursuant to s 82 HART Act, fertility
services standard 2007 )
• Comply with HART Act, interim guidelines:
Information and Counselling Requirements
• All PGD providers must get initial approval for NECAHR, annual
reporting
• Subject to medico-legal restraints (Code of Rights, Disciplinary
Law, Civil law)
Summary
• PGD currently limited to the prevention or
treatment of a genetic disorder or disease
• No established category of single gene disorders
• Serious impairment determined by clinicians
Further discussion necessary
• Current considerations:
Funding
Triaging of applications
• Future considerations:
Increased opportunities – therapeutic, nontherapeutic: Should the Guidelines be
narrowed or broadened?
Led by: Prof Mark Henaghan, Dean of Law, Otago
Sponsored by: NZ Law Foundation
web: www.otago.ac.nz/law/genome
e-mail: genome.lawpolicy@otago.ac.nz