Assisted Conception: Research, Ethics and Law

Research, Ethics and Law

Jennifer Gunning

• Publisher: Taylor & Francis
• Year: 2017
• eBook ISBN: 9781351723305
• Edition: 1
• Topic: Social Sciences
• Subtopic: Sociology
• Index: Social Sciences

This title was first published in 2003. Assisted conception is an area where it often seems that all the ethical and legal issues have been covered and then technology advances and the discussions start all over again. The book is an anthology of papers presented during a project looking at thearaputic research in assisted conception (TRAC). It is divided into three areas addressing research, ethics and law. Each chapter begins with an overview of the issues, with the aim being to present new perspectives rather than covering old ground. The European Convention on Human rights and Biomedicine came into force on December 1, 1999. The Convention allows thearaputic research and research on spare embryos but forbid fundamental research, which may be essential to the safe development of new techniques. This also means that people may become part of an experimental process without their consent. The project brings together clinicians, embryologists, lawyers and ethicists to ascertain whether there might be a risk of infertility patients being exposed to insufficiently tested procedures and to see if there is a need for fundamental research in this area. It also looks at the legislative safeguards that exist and whether a European standard for treatment should be set.

Part I

RESEARCH

2 Overview: Human Embryo Research

BRUNO BRAMBATI AND ANDRE VAN STEIRTEGHEM

Regulation of embryo research and its transfer into clinical practice

In Europe different attitudes prevail regarding the regulation of human embryo research and the transfer of these research results into clinical practice. The attitudes in the United Kingdom, Belgium and Germany will be reviewed.

United Kingdom

In the UK research on human gametes and embryos used in studies on the process of fertilisation is regulated by the Human Fertilisation and Embryology (HFE) Act of 1990. The Act functions through a system of licensing for storage, for treatment or for research. There are relatively few prohibitions and the approach to legislation is fundamentally flexible. There are two underlying assumptions: (1) licensing is entrusted by Parliament (the lawmakers) to a non-elected body of people (The Human Fertilisation and Embryology Authority – HFEA) acting on Parliament’s behalf. HFEA members have to accept the law administered by HFEA. (2) a legally pragmatic or ethically consequentialist view on complex issues with advantages and disadvantages discounts the possibility that specific prohibitions are often not in society’s long term interest. HFEA’s approach to legislation is very flexible and may interpret the law in relation to the current situation and may take into account continuous scientific advances. A new therapeutic technique, which involves the creation of embryos, cannot be used unless an application for a licence has been approved. This allows the HFEA to control the introduction and dissemination of new techniques fairly robustly. The application for a licence for a new technique must meet a general set of requirements; it is unlikely that centres would be granted licences for new techniques until they have demonstrated competence at standard techniques. The requirements include evidence from work on animals, from research on human gametes and embryos (without replacement into patients)

• that the local operatives at the therapeutic centre have the skills required to carry out the technique efficiently

• that the patient population for the initial treatments must be specified

• that the patient information must be submitted together with details of how it will be used and

• that the consent form must be submitted.

If a technique is used without either enquiry or license application and the HFEA considers the technique to be new, the center is considered in breach of its license or, less likely, to have performed a licensable technique illegally. Thus, the HFEA can control the introduction and dissemination of new techniques fairly robustly.

Quality control is also applied on the well established techniques: clinical standards are monitored by a centralised data bank receiving data in real time from each clinical centre; a periodical audit is regularly organised.

Germany

The Embryo Protection Law (December 1990) includes a number of restrictions for clinical practice; this includes prohibition of egg donation, surrogacy and the fertilisation of an oocyte for any other purpose than the establishment of pregnancy. From the moment of the fusion of the two pronuclei the fertilised oocyte is considered as a human individual. The question whether research could be carried out before syngamy (the fusion of the two pronuclei), is irrelevant since experimentation is only possible on such fertilised oocytes if the procedure is undertaken for the well-being of the embryo itself, which would have to be replaced. The limited research possible in Germany involves certain aspects of in-vitro maturation of immature oocytes.

Belgium

A law on the protection of the human embryo in-vitro is still pending. Notwithstanding the current absence of legal framework, ethical recommendations for research on human embryos were already formulated in the mid-eighties: the Ethical Committee of the Belgian Fund for Medical Research adopted the recommendations of the British Warnock Committee. Research projects on human gametes and embryos need prior approval of the local ethical committee. Several new procedures related to Assisted Reproductive Technology (ART) such as Intra-Cytoplasmic Sperm Injection (ICSI) and preimplantation genetic diagnosis (PGD) were correctly introduced into the clinic by self-regulation and continuous audit of the clinical and research activities. Clinical subzonal insemination (SUZI) was preceded by experimental assessment in the mouse. For ICSI, animal models were inappropriate and pre-clinical observations on ICSI embryos were carried out. The first clinical success with ICSI occurred in Belgium. Initially ICSI was carried out under strict conditions including prenatal diagnosis and a prospective follow-up of all the pregnancies and the children born. This ongoing study has allowed providing correct information of the outcomes of ICSI to prospective parents.

PGD, another novel procedure of the nineties, was developed into clinical practice after extensive pre-clinical evaluation and assessment of the different steps in the PGD procedure: embryo biopsy, single-cell genetic diagnosis using fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR). Like ICSI, clinical PGD should also be monitored very closely including the follow-up of the children born.

A proposal of law on the protection of human embryos in vitro was introduced in Parliament after approval by the Council of Ministers. It describes the framework in which research on supernumerary or in vitro created embryos can be carried out; research topics, which are possible or not possible, are also enumerated in the proposal of law. The flow chart for allowing research on human embryos includes approval by the Local Ethical Committee and evaluation by a Federal Commission.

Future directions in human embryo research

Three future areas involving research on human embryos will be discussed: pre-implantation genetic diagnosis, the case of the embryo in relation to the ethics of cloning and other future possible directions of human embryo research.

Preimplantation genetic diagnosis (PGD).

Since its introduction 10 years ago the number of centres offering PGD has grown steadily but slowly. So far there has been a lack of systematic longitudinal registration of the PGD activity world-wide. The absence of such data collection precludes an evaluation of the current status of PGD, which should still be considered as an experimental procedure. PGD aims towards the transfer of unaffected embryos. It would avoid the selective termination of pregnancies after prenatal diagnosis (by chorionic villus sampling or amniocentesis) in couples at high risk of transferring genetic diseases to their offspring. PGD, involving ART, is not without potential problems, such as risks related to IVF-ICSI and the embryo biopsy procedure, which is needed to obtain the diagnostic specimen. The success of PGD including its efficiency and accuracy is largely unknown. A systematic study of PGD has been initiated by the PGD consortium of the European Society of Human Reproduction and Embryology (ESHRE). The aims of the ESHRE consortium are described in chapter 3. A first report of the ESHRE PGD Consortium was published in December 1999 in the Journal of Human Reproduction.¹

There are many possible future developments related to PGD including aneuploidy screening in human pre-implantation embryos, removal of blastomeres or trophoblast biopsy, uterine flushing of embryos, karyotyping of single cells, multiplex PCR to look simultaneously at different diseases, sex determination in embryos for non-medical indications, whole genome amplification, carrier selection in X-linked diseases, Y-chromosome deletions, mitochondrial DNA and gene therapy.

The case of the embryo in relation to the ethics of cloning

A wide variety of activities have been included under the general heading of ‘cloning’. Those that involve the creation and use of embryos can be divided into two distinct types based on the ultimate objective. Where the objective is deliberately to create genetically identical individuals, this is often referred to as ‘reproductive cloning’. This technique may, theoretically, be used either to create an individual with the same genetic make-up as an existing individual – by cell nuclear replacement techniques – or to deliberately produce monozygotic twins – either by cell nuclear replacement or embryo splitting – with the primary intention of increasing the number of embryos available for transfer in an IVF cycle. Although the ethical arguments differ, both of these techniques have been prohibited in a broad statement in the Additional Protocol to the Human Rights and Biomedicine Convention.

The second category of activities does not involve the creation of genetically identical individuals, but aims to produce an unlimited source of tissue for transplantation. It is proposed that undifferentiated embryonic stem cells, from early embryos, could be stimulated to differentiate into whatever type of tissue was needed – neural tissue for the treatment of degenerative diseases such as Parkinson’s disease, bone marrow for leukaemia sufferers, islet cells for diabetes, muscle tissue for the repair of a damaged heart or skin for treating burns victims. A further development would be to produce tissue which was immunologically compatible to the recipient. This could be achieved by transferring the nucleus from one of the patient’s own somatic cells into an enucleated donor egg which would then be stimulated to begin cell-division but only to the stage needed to separate and culture the embryonic stem cells. This would succeed, not only in overcoming the shortage of tissue for transplantation but also, because the cells would be generated using the patient’s own DNA, the tissue would be fully compatible so there would be no need for the use of immunosuppressive drugs. This use of cloning techniques has potentially huge implications for a vast number of people.

Other future directions in human embryo research

Without considering their deeper ethical or legal implications possible new developments in human embryo research may include:

- Non-invasive methods for more efficient selection of spermatozoa, eggs or embryos which have the greatest potential for development. Criteria assessed have included tests for selection of immotile sperm, blood flow in the growing follicle, free radical production in fertilisation medium, location and size of pronuclei, blastomere morphology and division rate, metabolic activity, blastocyst formation in-vitro as well as the use of vital dyes.

- Improvement of embryo quality by improving the quality of culture media.

- Research to actively improve the quality of the embryo. This more controversial approach includes cytoplasmic or gene therapy.

- Research into the production of more embryos which may be achieved by in-vitro maturation of oocytes, the use of cadavers and fetuses as a source of oocytes, the use of embryonic stem cells as a source of gametes, maturation of human gametes in living incubators, the induction of cells to undergo meiosis in vitro, oocyte cryopreservation and embryo splitting.

- New technical routes to parenthood to satisfy new patterns of parenting.

- Improvement of implantation by procedures on the zona pellucida or the embryo itself.

- Advances in contraceptive technology would benefit all human beings. Many of the problems in the world stem from inexorably rising birth rates and in the difficulty of providing acceptable methods for safe, efficient, and reversible contraception.

These issues are considered in more detail in chapter 4.

Note

1 ESHRE PGD Consortium Steering Committee (1999) ‘ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: preliminary assessment of data from January 1997 to September 1998’, Human Reproduction, vol. 14, pp. 3138–3148.

3 Preimplantation Genetic Diagnosis

JENNIFER GUNNING

Introduction

The vast majority of pregnancies, whether conceived as a result of assisted conception or through normal sexual intercourse, proceeds without difficulty and results in the birth of a normal child. To help ensure the best outcome for their pregnancy, women may be offered a number of tests to check that their fetus is normal and healthy.

These prenatal tests generally fall into two categories; screening tests and diagnostic tests. Screening tests are carried out on the whole population or on a particular population which has a higher risk of transmitting a genetic disorder. Diagnostic tests are used to confirm pregnancy or to determine whether the fetus has a genetic disorder. Most testing will help women to decide whether to terminate a pregnancy if they are carrying an affected fetus or, if they wish to continue the pregnancy, attempt treatment if appropriate and enable doctors to decide how to treat the child when it is born.

Screening tests

Prenatal screening tests give information about the level of risk of the condition being screened for. Diagnostic tests may then be used to confirm or refute a positive result. The most commonly used screening tests are biochemical tests on maternal blood to determine t...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• List of Tables
• List of Contributors
• Preface
• Acknowledgements
• List of Abbreviations
• INTRODUCTION
• 1 Introduction
• PART I: RESEARCH
• 2 Overview: Human Embryo Research
• 3 Preimplantation Genetic Diagnosis
• 4 Future Directions in Research on Human Embryos
• PART II: ETHICS
• 5 Overview: Ethical Issues
• 6 Between Pragmatism and Principles?
• 7 Information Disclosure and Consent
• 8 The Influence of Pluralism in the Perception of the Status of the Embryo
• 9 Human Cloning: The Case of the (Preimplantation) Embryo, an Ethical Exploration
• PART III: LAW
• 10 Overview: Legislative Approaches
• 11 Legal Approaches: France
• 12 The Regulation of Human Embryo Research in the UK: What Implications for Therapeutic Research?
• 13 The Role of Ethics Committees in Framing Legislation on Assisted Reproduction and Embryo Research?
• 14 The Hungarian Legislative Approach to Assisted Procreation: An Attempt at Transparency
• 15 Health Council Report on Embryo Research: Perspectives on New Legislation in the Netherlands
• 16 Legal Approaches in Germany
• 17 Regulating Reproductive Technologies: Ten Years Down the Tube?
• 18 Regulation of Assisted Conception Services: The Need for Technical Standardization