Preimplantation genetic diagnosis in New Zealand A tool

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 Method of Voluntary Peer regulation Review Process Legislation Comprehensive Legislation and legislation banning delegation to procedures statutory body Jurisdiction UK Victoria Australia Canada New Zealand USA New South Wales And Queensland Australia; India France Slovenia Netherlands Italy Germany Austria Switzerland Ireland 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, s 81(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