Royal Society of Medicine Forum: Mixed blessings - ethical issues in assisted conception.
This is a report of a meeting of the Forum on Maternity and the Newborn of the Royal Society of Medicine, held on Thursday 14th November 2002. The meeting was chaired by Mrs. Sally Gordon-Boyd, President of the Open Section.
This report first appeared in the RCM Midwives Journal.
The IVF viewpoint
From Miss Melanie Davies, Consultant Obstetrician & Gynaecologist, University College Hospital, London
Infertility affects about 1 in 6 women in Britain. About 1% of children in developed countries are now conceived through IVF. This year there will be at least 8000 IVF babies born in Britain. In the year 2000 - 2001 21.8% of IVF cycles were successful (all ages; 25.1% for ages under 38 years). About 1600 pairs of twins and 100 sets of triplets were born.
IVF is not the only fertility treatment, but it is now the most common form of assisted conception. It was first used to overcome blocked Fallopian tubes by taking eggs outside the body to fertilize them (in a Petri dish not a test tube); the speaker showed a number of slides illustrating the process. But now any degree of male subfertility can also be treated. 15% of treated couples are in the increasing group affected - largely with tubal damage due to chlamydia - by sexually transmitted disease; other indications are low sperm count, for which intracytoplasmic sperm injection (ICSI) has been devised; endometriosis; unexplained subfertility; and the failure of simpler treatment e.g. clomiphene and artificial insemination by husband or donor.
More women are leaving conception too late, usually in the interests of their careers, leading to later marriage or other delay in starting their families. Perhaps contraception is too reliable, but conception is further delayed as infertility investigations take time.
Concerns about unregulated practice, mainly in the private sector, led to the Warnock Report (1983) and legislation of several areas in gynaecology; the only other branch of medicine similarly controlled is mental health. Why is this? The law defines the boundaries evolved by society as a system of protection for the individual and for society at large. The Human Fertilization and Embryology Act of 1990 covered everything to do with human gametes, defined as mature sperm and eggs, and embryos and the storage of these, and regulates assisted reproduction and embryo research. There is also legislation to cover cloning, surrogate birth, and feticide, the reduction of fetuses in multiple pregnancies.
The Human Fertilization and Embryology Authority (HFEA), set up in 1991 in response to great unease about the unfettered development of fertility treatment and the public fears of embryo research, was the first of its kind in the world. It is tasked with inspecting and licensing clinics - currently there are 120 in the UK - and also with making policy decisions on developments in technology, and on ethical issues such as posthumous reproduction. The HFEA also issues guidelines on codes of practice, and it holds a central register of donors and their children. It records all IVF activity in the UK.
Much care is taken to ensure the welfare of children born of IVF and related technologies; we are under the obligation to behave ethically, to do good, avoid harm, apply the principle of justice and respect autonomy. We need to balance the good we do by assisting the birth of healthy babies to loving families against the risks of harm in making decisions on treatment. The lack of equity in access to treatment interferes with the concept of justice; in the absence of a national policy we experience "postcode prescribing". Now that the National Institute for Clinical Excellence (NICE ) is reviewing fertility treatment guidelines there are some hopes that we may have a national policy and thus equitable access to treatment.
1% of IVF stimulation cycles lead to severe ovarian hyperstimulation syndrome (OHSS) and its widespread effects; there has been at least one death in Britain. There is a theoretical risk of ovarian cancer associated with the use of fertility drugs (Rossing 1994). Largely due to multiple pregnancies and to the woman's age and nulliparity there are higher incidences of pre-eclampsia, premature labour, and caesarian section; even where singletons are developing early pregnancy bleeding occurred in 15.7% following IVF, compared with 2.5% of spontaneous pregnancies. The IVF figure for hypertension was 6.3% (2.1%), gestational diabetes 4.0% (0.8%), and the caesarian section rate almost doubled (Beck 2001).
Triplet and higher order multiples have been the cause of great anxiety in the public and among clinicians; they are even more frequent where clomiphene or injected human chorionic gonadotrophin (HCG) have been used. Multiple pregnancy alone is responsible for increases in prematurity, congenital anomalies, and the selective termination of pregnancy with a 10% risk of miscarriage. How terrible it must be to go through this in a wanted pregnancy. Which baby to select? Prevention of multiple births is possible by refining the techniques with better embryo selection and transfer of fewer embryos. Britain, Australia and New Zealand have attempted to reduce the number of embryos transferred to two.
In patients with very low sperm counts, it is well documented that the sperm have high frequency of chromosomal abnormalities, and a recent report details a doubling of fetal malformations following ICSI.
It should still be considered to be a novel technique with an uncertain risk of fetal abnormality. The HFEA and the Medical Research Council (MRC) are collaborating in a study of the problem led by epidemiologist Professor Catherine Peckham.
Some of the children of donor insemination are anguished by an awareness of the secrecy imposed by their parents, and by the feeling that the anonymity of the donor has deprived them of a part of their identity. In British law, this anonymity is protected, and indeed to disclose the identity of a donor is a criminal offence. Though counsellors advise parents to tell their children, in a European study (Golombok S 2002) 90% of donor sperm families had not told their child by the age of 12. Children may approach the HFEA at age 18 to have confirmation of the mode only of their conception. A double track system, where donors may reveal their identities is under consideration.
Egg donation remains a voluntary procedure; where relatives are the donors this may lead to problems of identity for the children. A woman in an IVF programme may be asked to supply eggs for donation (egg-sharing) as a condition of treatment. Is this coercion or mutual benefit? The losers may be the children, particularly the donor child, who may grow up to know that his genetic mother was desperate for children but still gave him away.
"In the absence of decent state provision.....the stark choice for infertile people will be between spending vast sums in commercial clinics or foregoing the chance of ever having children". This prophetic quotation comes from a report prepared for Frank Dobson when he was shadow Minister of Health. Access to fertility treatment in Britain is not equitable, because provision depends on the local purchasing authority, with the result that private IVF outnumbers NHS about 7 to 1. I think everyone must accept that as resources are not limitless, there must be some form of rationing or control over access to NHS treatment - for example an age limit (successful embryo implantation after age 44 is not to be expected).
Public consultation and information remain very important. Most scientists would wish these techniques to be subject to regulation and to informed public debate as they become available, and indeed wish that the public were better educated in science. Very few scientists want to play at being God.
Beck A, Herrero J, Stalf T, Mehnert C, Gips H, Lang U. High pregnancy risk and poorer perinatal outcome after IVF. (abstract) Hum Reprod 2001:16:140.
Golombok S, Breways A, Giavazzi MT et al. The European study of assisted reproduction families: The transition to adolescence. Hum Reprod 2002 (in press)
Rossing MA, Daling JR, Weiss NS, Moore DE, Self SG. Ovarian tumors in a cohort of infertile women. New England Journal of Medicine. 331(12): 771-6, Sep 1994
Assisted reproduction, multiple births and neonatal intensive care: a difficult ethical issue
From Dr Neena Modi, Senior Lecturer/Consultant in Neonatal Paediatrics, Hammersmith
The impact of the artificial reproductive techniques began to be felt in the late 1980s and 1990s. During this decade the births of triplets and higher order births almost quadrupled. Compare the 1.44% total twin or higher order births in England and Wales with the 56% such births resulting from artificial reproductive techniques in the USA, 26% in Europe. Again, compare the stillbirth and neonatal and postneonatal death rates for singleton and multiple births: in multiple births the stillbirth rates are over three times the singleton rate, over seven times for neonatal deaths, and almost six times for infant deaths. It is the mortality rates in the babies of birthweight under 1000 grams that mostly contribute to these figures; they represent about 5% of multiple births, but less than 1% of singleton births.
The bulk of the work of the neonatologist is represented by those babies born from 24 to 27 weeks gestation. To put this into a personal context - what they mean to any mother undergoing these techniques - the gross figures are not too frightening. But if you are a mother expecting triplets or more, you have a 12% chance of delivering your babies in this gestational range, as compared with the 0.4% likelihood of this occurring with a single baby. These are the hard facts which couples contemplating assisted reproduction must face.
The EPIcure Study, started in 1995, looks at the survival and long term outcomes for all children born in the UK below 26 weeks gestation; at 30 months the group concluded: Severe disability is common among children born as extremely preterm infants (Wood 2000); it is about to report on the 5½ year outcomes for the children in the study. Of live births at 22 weeks, only 12% survive to reach an intensive care unit (ICU); by 25 weeks survival to reach an ICU has improved to 92%. At 22 weeks 88% will die in the ICU; at 25 weeks this figure is 52%.
At age 30 months 23% of children from the 22 to 25-week groups will have survived with a major disability; a similar proportion will survive with no major or moderate disability. There are grounds also for concern about the babies born at 26 to 29 weeks. 10% of children born below 1500 grams and surviving will have cerebral palsy; an additional 25% will have much more subtle problems of cognition or behaviour sufficient to prevent these children from functioning to their full potential (Volpe 2001).
Monochorionic twins share a placenta, and they have their own problems, caused by twin to twin blood transfusion; they are at greatly increased risk of dying in utero and of requiring fetal medicine interventions, aside from their need for care in a neonatal ICU. Assisted reproductive techniques increase the rates of this condition and of monozygosity (identical twins).
A former chairman of the HFEA has said that clinics responsible for the births of triplets due to the implantation of three or more embryos should contribute to the excess costs of their care which are at present falling upon the NHS. The cost of keeping a baby in an ICU, often for many months, is now about £1000 daily. The families themselves incur great financial, social and personal costs. Divorce and family breakdown are more frequent in these families, whose members live on the rollercoaster of day to day conflicting messages about their babies' progress; living with this uncertainty takes its toll. The children who receive this care, and no less other children in their families, who always find themselves taking second place to a disabled sibling, also pay a great cost. Consider the two healthy triplets going short of the attention received by the third, who has cerebral palsy.
Parents need to be fully informed about the route they take through assisted conception, and then to be left to make their own decisions, while we must be aware that they need some help in this, being under such pressure from their need for a baby that they can hardly be expected to view the information dispassionately.
Wood, Nicholas S., Marlow, Neil, Costeloe, Kate, Gibson, Alan T.,Wilkinson, Andrew R. (2000), "Neurologic and Developmental Disabilityafter Extremely Preterm Birth, EPIcure Study Group" The New EnglandJournal of Medicine, vol. 343, no. 6, August 10, 2000.
Volpe J. Neurobiology of periventricular leucomalacia in the premature infant. Pediatric Research 2001; 50:553-62
A fragile hold on life: the ethics of intensive care of children born through assisted conception
From Dr Richard Ashcroft, Leverhulme Senior Lecturer in Medical Ethics, Imperial College, London
Recent papers have suggested that babies born through medically assisted conception are at a significantly increased risk of congenital abnormality or low birth weight, with serious short term consequences for their viability at birth and long term consequences for their health and development. It has been known for some time that multiple pregnancy holds a risk of serious disabilities for the babies. The use of in vitro fertilization (IVF) techniques usually involves the creation of a number of embryos of which two, three or more may be implanted, and it has been suggested that any observed health risks to babies so conceived may be ascribable to the multiple implantation of embryos; however, a recent study (Hansen et al. 2002), and a commentary by Winston and Hardy (2002), suggest that even controlling for such factors as maternal age, multiple pregnancy and birth weight there is a raised relative risk of IVF resulting in fetal abnormality additional to risks due to the same causes which led to parental infertility in the first place (e.g. chromosomal abnormality, acquired mutation, or mitochondrial weakness).
What is the ethical significance of these observations, if true? I propose three positions, the first being The Simple Answer: informed consent. This is now the standard approach to obtaining ethical authorisation for a risky medical procedure.
Although this is the best answer we are likely to arrive at as a matter of public policy, the health professionals involved in the decision are not passive agents. They have a moral responsibility to act ethically, including the responsibility not to offer unsafe or ineffective treatments, and probably the responsibility not to offer treatments which will harm third parties. Perhaps the medical choice precedes the parental choice. For practitioners in the field of assisted conception there are no particular responsibilities to the conceptus, since this is not considered to be a person or to bear interests, at least until much later in the pregnancy. This No Special Concern view, implying no special moral concern requiring the restriction of IVF use, is very close to The Simple Answer.
My third position, The Special Concern view, seems to be highly contentious, implying as it does that doctors could be wrong even to offer the technique, and parents could be wrong to request or choose to use it, if the interests of the individual thus conceived could be harmed. The HFEA has a statutory responsibility to ensure that the interests of the future child are considered, and for them the existence of a relative risk of congenital abnormality or perinatal harm is necessarily of moral concern.
How can we talk of an individual or individuals at all until well into pregnancy? How can one be harmed by being brought into existence? Yet natural worries about knowingly conceiving a child who is more than usually at risk of serious disability seem to be consonant with the Special Concern view. Witness the recent controversy over whether it could be morally acceptable deliberately to conceive a child with the expectation - indeed hope - that it would be congenitally deaf.
Perhaps we can make more sense of the choice by starting, as the HFEA seems to imply we should, from the situation of the child born through assisted conception and born sick or disabled. Suppose that we can ascribe this with near certainty to the method of conception. Has he been wronged? If he has, does this permit us to frame a rule which would bar the use of the technique in general, or bar its use for some parents who can be characterised as being at a qualitatively greater risk than baseline? One answer to this question is to assert that the very idea of harming a baby through the mode of his conception is incoherent, since this amounts to asserting that he has been wronged simply by being born. But the general approach to prenatal care of mother and fetus is orientated to the reduction of risks of harm to the mother or fetus. Hence there has been general trend away from multiple implantations in assisted conception, and from the controversial practice of "fetal reduction" in some high order multiple pregnancies.
There is no policy of compelling certain risk avoidance behaviours (such as the limitation of alcohol use), but while women are not obliged to reduce risks to themselves or their fetuses, they are certainly encouraged to do so. Professionals are expected, by the standards expected of them in tort law and professional regulation, to reduce risks in pregnancy so far as this is possible and concordant with the consent of the mother.
In recognising that the reasons for avoiding compulsion have to do with the acknowledgement of the moral autonomy of women, their physical privacy, and the variety of cultural, religious, moral and social factors which are involved in determining "harm" or "risk, then the risk minimisation approach does not coincide with the Special Concern view. Indeed, it could be worth the mother's while undergoing a high risk pregnancy. The Special Concern view seems to imply that a woman could simply be wrong about this, and that there is an objective way of deciding which risks can and cannot be run.
The welfare consideration has come under a lot of scrutiny lately, in discussions of the permissibility of the use of pre-implantation diagnosis to permit preferential implanting of an embryo of the right HLA type to be a tissue donor for a sick sibling, or for sex selection, and it appears to have motivated the recommendation that no more than 2 embryos be implanted at any time, and the drift toward single embryo implantation. It seems to intend the welfare of any child born as a result of treatment, including the need of the child for a father, and the welfare of any other child who might be affected by the birth (HFE Act 1990). In this broader understanding, it seems perfectly plausible to state that the issue is not the safety of a particular IVF technique, but the case-by-case consideration of the needs of particular couples and their concern for their future children. Our worry might be whether they discount the risks irrationally in the light of the alternative (failure to conceive at all), and whether there is moral culpability in assuming this risk.
This thought is troubling. If we knew for certain that IVF techniques created some disabled babies, then there would perhaps be an issue about whether it was legitimate to offer it under some or any circumstances (witness the licensing of drugs to be used in pregnancy, following thalidomide). But aside from that, we must also address the question of whether taking some risks can entail responsibility for their outcomes, should harm materialise. Could there be recklessness in use of IVF? Part of the answer here might be found in distinguishing between foresight and intention. No would-be parent can surely be thought to intend harm to their child. For instance, the 40 year old mother who refuses amniocentesis, or who proceeds with a pregnancy even where the baby is found to have Down's syndrome surely does not intend any concomitant harm that may ensue to the child. Nonetheless such harm can be foreseen. Is she reckless? Or selfish in wishing to exercise her preference in having a child rather than putting the welfare of the child first? There seems here to be room for private conscience and evaluation, rather than a hard and fast public policy.
IVF is not one technique but many. Some clinics will offer some services but not others, purely on the grounds of a preferential ranking of such techniques by the degree and kind of risk posed. Some techniques may drop out of use because patients and doctors together may concur that they are not worth the risk. Others may prosper.
One big issue remains for public policy - the burden imposed on the NHS. If significant numbers of babies born through IVF require intensive care, and this is foreseeable and preventable, surely there is a public interest in restricting access to the technique, so that access to neonatal intensive care can be concentrated upon babies who require it through unforeseen disasters and emergencies? And further, where need for neonatal intensive care is foreseeable at a certain rate originating from the use of IVF, should not some of the costs of this be shared with the reproductive medicine services (or passed on to parents)? This abuts onto the vexed question of whether IVF should be available at all within the NHS, but extends it still further. A baby conceived through IVF privately, if born with very low birth weight or prematurely, would be admitted (normally) into NHS care. Since the NHS recovers part of the costs of intensive care for road accident victims from motor insurers, should not some sort of recovery of costs apply here too?
The central issue here concerns the requirements of justice, which requires at least the following:
· Fair treatment of individuals consistent with their human rights and dignity
· Fair distribution of resources
Central here is the tension between two low-level moral principles:
· To permit couples (and individuals) to exercise their right to found a family by assuring fair access to reproductive health services and obstetric care
· To require individuals who are knowingly and competently taking a risk to their welfare or the welfare of others to bear responsibility for their actions
Different societies take different approaches to striking this balance, and much depends on the particular economic, social and medical circumstances that obtain. We allow that people have a strong interest in trying to conceive a child, and we allow them knowingly to assume certain risks in doing so, including putative risks to the child. We have permitted people to obtain the assistance they need from the NHS, albeit in a haphazard manner. If IVF were to be barred on the grounds of expected cost per cycle or expected lifetime cost to the NHS of a birth following IVF treatment, then this should be justified explicitly. But barring IVF on safety grounds and barring it on cost grounds are different, and these rationales should be kept clearly separate in discussion.
Finally, suppose the NHS were from now on to refuse to purchase IVF on the basis of a recalculated expected cost of IVF treatment cycles (to include the expected cost of neonatal intensive care). On the basis of the moral argument above, private clinics should be permitted to continue, subject to HFEA regulation. Much depends on the particular economic, social and medical circumstances that obtain. Some of these clinics offer a complete conception to birth service, but most do not. Should patients at these clinics be expected to bear the full private cost of obstetric care and neonatal intensive care? Or should they be required to take out insurance against the risk of a need for neonatal intensive care as part of their purchase of IVF services? Or should the NHS apply the rule of rescue to such cases, and admit babies to NHS neonatal care facilities, irrespective of whether it could have been foreseen that they would require admission? The NHS does not recover costs from mothers of babies born with fetal alcohol syndrome; it operates on the basis of providing services on the basis of need, free at the point of use, and does not inquire too closely, in most situations, into whether the patient was responsible for the illness or injury requiring treatment, even where this could have been foreseen (say in sporting injuries). Whether this ethos is rational and well-founded is a much larger issue.
Hansen M et al. - The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization New England J Med 2002; 346: 725-730
Winston R, Hardy K - Are we ignoring potential dangers of in vitro fertilization and related treatments? Nature Cell Biology & Nature Medicine 2002: Fertility Supplement s14-s18
Jane Denton, a member of the HFEA and director of the Multiple Births Foundation, attended the meeting, and spoke first. She has worked in an infertility clinic. She described the responsibilities of the HFEA in communicating with the professions and others with an interest. They are considering licensing stem cell research and cloning techniques such as cell nuclear replacement, and they strongly favour the follow up of babies born by IVF and in particular by ICSI. Since the high costs of neonatal care can be reduced thereby they are looking at encouraging the transfer of only one embryo in the future, perhaps two and only exceptionally three. Responding to a question about the other babies occupying neonatal intensive care cots Neena Modi (NM) emphasised that they represent a very small number compared with the multiple birth group.
Professor Wendy Savage asked whether more harm than good is done to couples, four out of five currently, whose IVF fails. Would they not have done better to adopt at an earlier stage in their lives? Melanie Davies (MD) said that gynaecological investigations which may take up to five years could have easily be done in six months, so saving much delay. With the results of investigation before them couples can then consider their options, rather than finding themselves aged 39 with IVF the only option. Success rates of 40% are within sight, although sets of twins are likely to number prominently in the results. (NM) Aware of the successes of IVF couples now feel a pressure to undertake it. Counselling has an important part to play in helping them come to their decisions.
Is disclosure about their conceptions what children want or need? What parents say they will tell often does not correspond with what they do tell. Disclosure is easier for mothers and children who have benefited from egg rather than sperm donation, presumably because they feel secure in knowing the identity of the donor.
Family secrets may have profound and lifelong effects; if full disclosure is inappropriate (a sperm donor may have many children so conceived) even a pen portrait would suffice to give a child the needed security. (MD) Keeping a DNA sample for later reference would solve this.
In view of the possible dire outcomes of assisted conception fully informed consent is essential. A reckless practitioner would have to answer for such outcomes. Are there not lessons to be learned from adoption and fostering? Richard Ashcroft (RA) responded that either disclosure or non-disclosure may cause a child unhappiness, and this is unpredictable. (MD) Conditions of work in the NHS are inimical to properly obtaining informed consent; although an IVF clinic provides almost ideal conditions for this, the degree to which couples can be fixated on getting the treatment means that one could obtain consent even for the transfer of 100 embryos. To them the notion of being pregnant at all is so remote that discussion of problems such as multiple pregnancy seems irrelevant to them.
Does the manipulation inherent in the techniques cause mitochondrial damage? (NM) Studies based on hypotheses are currently taking precedence over an important issue such as this, where a hypothesis is being sought. (RA) Procedures which, while seeking to guarantee a better outcome, such as pre-implantation genetic diagnosis, may cause mitochondrial or chromosomal damage, raise serious questions of this kind.
The techniques of IVF effectively double the risk of producing a disabled baby, quite contrary to the normal intention in medical practice to do good. (MD) This is another case where benefit has to be balanced against the risk. (RA) The decision making process deserves maximum support.
The felt need to transmit ones genes to the next generation is denied by donor techniques. A member of such a denied generation, conceived by sperm donation, having no complete genetic history was refused permission to adopt.
The chair ended the meeting by casting a doubt on the currently assumed right to turn to assisted conception rather than adoption as a solution to childlessness.