The Socioethical Issues of Preimplantation Genetic Diagnosis (PGD)

Preimplantation genetic diagnosis (PGD), the technique by which early embryos are genetically screened has been available since 1990 for the testing of aneuploidy, single gene disorders and X-linked disorders in at risk couples. In the UK, the Human Fertilisation and Embryology Authority (HFEA) regulated the use of reproductive technologies such as PGD. Although the procedure of PGD has been available for over two decades now, embryo selection remains a highly controversial topic which continues to raise many legal and ethical issues. This essay aims to address the socioethical issues surrounding PGD by initially looking at the differences between PGD and prenatal diagnosis (PND), and then discussing the ethical issues surrounding the use of PGD, both for medical and non-medical reasons.

What is Preimplantation Genetic Diagnosis (PGD)?

PGD combines in-vitro fertilisation (IVF) with genetic testing. Two main techniques are currently used; blastomere biopsy and polar body biopsy. In the blastomere biopsy, one or two blastomeres are removed at the 6"10 cell stage using an inferred laser. The cells DNA is then tested for the genetic or chromosomal condition; usually by polymerase chain reaction (PCR), fluorescent in situ hybridisation (FISH) and more recently by comparative genomic hybridisation (CGH) (Metwally and Ledger, 2010). The genetically ‘unaffected’ embryos are then transferred into the mother’s uterus with the aim of establishing a healthy pregnancy. The number of blastomeres used in the biopsy has various advantages and disadvantages. The use of one blastomere has the advantage of being minimally invasive but it has the potential of yielding false negative results due to possible mosaicism. A two blastomere biopsy although potentially more accurate, is more invasive raising concerns regarding future embryonic development (Michiels et al., 2006).

The polar body biopsy involves the removal of polar bodies from oocytes during meiosis. The technique is often used for the detection of the maternal contribution to single gene defects such as X linked, autosomal recessive or dominant disorders. The polar body has been reported to be non essential for embryonic development and can be removed without any adverse effect on fertilisation and embryonic development (Gitlin et al., 2003). Polar body analysis may also overcome the ethical dilemmas associated with the testing of human embryos, since identification of abnormalities would lead only to the exclusion of that oocyte from fertilisation and not the exclusion and destruction of embryos. The main disadvantage of this technique is that it only allows for the examination of the maternal chromosomes and therefore any problem with paternal chromosomes will not be detected.

The ethical difference between Preimplantation Genetic Diagnosis (PGD) and Prenatal Diagnosis (PND)

Prenatal diagnosis (PND) is a procedure which involves testing the fetus in early pregnancy. Testing techniques include ultrasound/material serum screening (between 10 and 20 weeks gestation), amniocentesis (from 16 weeks gestation), chorionic villus sampling (CVS) (10-13 gestation) and fetal blood sampling (FBS) (from 18 weeks gestation). Most of the techniques used are invasive and can increase the risk of physical disruption of extra-embryonic and fetal structures as well as increasing the risk of infection. If the fetus is affected a decision then has to be made whether to continue with the pregnancy or to abort the fetus. Many countries, including the UK accept the termination of a pregnancy as acceptable when the fetus is shown by PND to be affected by a serious medical condition.

The main ethical arguments arise from people differing opinions on when human life begins. Does life begin at the moment of fertilisation, at implementation of the embryo in the uterus (8 days), at the point when a central nervous system (CNS) has developed (14 days), when the pregnancy is established clinically at the end of the first trimester (13 weeks) or when the mother can feel fetal movement (approximately 15-18 weeks)? If we believe that life begins at fertilisation, then PND and subsequent abortion involves the killing of a fetus. The affected embryos in PGD are allowed to die, which again can be viewed as killing therefore, is there really any ethical difference? Both PND and PGD involve the selection of embryos without illness or disability and some disability activists argue that this kind of selection discriminates against those people living with a disability or a genetic condition. By allowing selection in this way are you saying that you believe that a life with disability or a genetic condition is not worth living?

Those who see the early embryo as having no rights or interests until the development of a CNS may see no objection to PGD, as the embryos are allowed to die before this 14 day window. PGD may even present some advantages as it may help to eliminate the anxiety experienced throughout the procedure of PND. In PND, the fetus is aborted when embryonic development is well advanced and many women see abortion as a personal physical violation. The mother and indeed the family as a whole may have indentified and bonded with the fetus, giving it ethical status. However, the same may also be true for PGD, which often involves repeated cycles of ovarian stimulations, IVF and frozen embryo transfers which again can lead to anxiety, depression and maternal-fetal attachment (Karatas et al., 2011).

Medical Reasons for Preimplantation Genetic Diagnosis (PGD)

The primary aim of PGD is to provide couples at risk of having a child with a genetic condition, the chance to have a healthy child without having to face the dilemma of whether or not to abort a pregnancy following the detection of a genetic disorder using PND. The different diagnostic techniques used in PGD can detect a diverse range of genetic conditions. Polymerase chain reaction (PCR) allows for the amplification of a target DNA sequence. Standard PCR methods can detect single gene defects such as cystic fibrosis and Tay Sachs disease, and multiplex PCR can be used can be used to diagnose multiple single gene defects. Chromosome visualisation by fluorescent in-situ hybridisation (FISH) can be used to screen for aneuploidy, to determine sex in X-linked disorders and to detect chromosomal translocations, and the relatively new technique of comparative genomic hybridisation (CGH) can be used to detect copy number variations in chromosomes.

An extension to this would be to use these techniques to screen for susceptibility conditions, such as carriers of the p53 and BRCA1&2 mutations in order to prevent the birth of children who have an increased risk of cancer, and would therefore require close monitoring and other preventative measures. An individual carrier of the p53 or BRCA1&2 mutations is at an increased risk of developing the associated malignancies, there is a chance however that they may not. Screening for these susceptibility genes would result in the destruction of all embryos that tested positive for these genes and would ultimately lead to the destruction of embryos that may not have developed the condition during the lifetime of the individual.

There is also to option to use PGD to screen for highly penetrant late onset conditions such as Alzheimer’s or Huntington’s disease in order to prevent the birth of a child who the third or fourth decade of life may experience the onset of progressive neurological disease which will ultimately result in early death (Asscher and Koops, 2010). If PGD is seen as acceptable to screen for early onset genetics conditions, should it also be acceptable for later onset conditions such as Huntington’s disease? Genetic testing for Huntington’s disease has been available for some time, allowing individuals to who choose to be tested to make more informed choices about their life, including the decision of whether to reproduce or not (Towner and Loewy, 2002). If PGD is used to screen for late onset genetic disorders, will this result in a healthy child being born to an individual who is likely to die or become incompetent whilst the child is still dependant? Although a valuable risk to consider, it has been tolerated in other cases such as intrauterine insemination with sperm of a man who is HIV positive, IVF for women with cystic fibrosis and the storage of gametes prior to cancer therapy (Asscher and Koops, 2010). If a good family network or competent carers are available for the child, then does the likely death or disability of the parent justify stopping the use. Any parent could be killed or disabled in an accident at any time during their life; does this prevent them from having children? Is it not a case of the parent wanting the best possible opportunity at life for that child by preventing the risk of substantial health problems in later life?

Preimplantation Human Leukocyte Antigen (HLA) Typing

PGD can also be used in conjunction with human leukocyte antigen (HLA) typing. Preimplantation HLA typing is used to identify an embryo that is tissue matched for a child who is suffering from a sever disease, requiring haematopoietic stem cell (HSC) transplantation from cord blood or bone marrow. HSC transplantations can provide curative therapy for many malignant and some non-malignant disorders including leukaemia, lymphoma, haemoglobinopathies and immunodeficiencies. In the media, children born following this procedure have been referred to as saviour siblings, a brother or sister capable of donating life saving stem cells.

One point to note is that the use of PGD is not necessary to create a HLA matched child. All humans inherit half of their HLA type from their mother and half from their father; therefore each sibling has a one in four chance of being HLA matched to another sibling through natural reproduction or IVF. However, the sooner a donor match is found the greater the success rate of the HSC transplantation, therefore waiting to conceive a matched child through natural reproduction may not be a feasible option.

The main ethical argument surrounding the deliberate creating of saviour siblings involve the potential harm to the donor child, the family and society as a whole. In the case of HLA typing, PGD is used to select an embryo in order to serve the needs of an ill sibling and not to ensure the birth of a healthy child. According to Kant’s universal prescription, every human has inherent value and must be treated as an end in itself and not merely as a means (Kant, 1997). Therefore, conceiving a child in order to harvest cord blood stem cells or bone marrow is unethical as the child is being treated as a commodity, a source of stem cells. The deontological view is that it is wrong to choose traits of offspring, no matter how well intentioned. They believe that human reproduction is a gift, and that any form of selection turns the child into a manufacture.

In response, Kant's argument doesn’t distinguish between creating a child as a saviour sibling and creating a child for some other instrumental purpose. Why do people have children? There are many different, if sometimes controversial reasons why people choose to have children including to make a relationship complete, to carry on the family name, to provide a playmate for an existing child, to bring a daughter into a family full of boys, to ensure we have someone to look after us in our old age, to move up the waiting list to get a council flat, or simply because we forgot the contraception. Although different from saviour sibling, most of these reasons described can be seen as instrumental, the child is still being used as a means. It would obviously be wrong to create a child using HLA-PGD and then just discard him or her once it had served the purpose, but this is clearly not the intension of the parents. The fact that the parents are prepared to conceive another child in order to protect an existing child suggests that they are highly committed to the well-being of their children, and that they will value the second child for its own sake as well (Sheldon and Wilkinson, 2003).

HLA-PGD initially sets out to use umbilical cord stem cells following birth, the umbilical cord is seen as waste material and the procedure is not harmful to the newborn in anyway. In this case the donor child will not be harmed and a desperately sick child can be saved. However, if the cord blood transfusion fails or if further bone marrow donations are required the donor child may be at lifelong risk of exploitation. Repeated testing and harvesting procedures may be required and the donor child may feel obliged to commit or may even feel pressured by the parents and family (Wolf et al., 2003).

In addition to the physical harm the donor child may experience from future bone marrow donations, there are also concerns over the emotional and psychological harm to both the donor child and the recipient. The donor child may experience feelings of inadequacy if the stem cell transfusion fails, particularly if the sick sibling condition deteriorates. They may also lose the feeling of unconditional love from their parents, by being born even in part to serve a purpose. They may feel guilty for being healthy and not having a genetic disorder. The recipient child may also feel guiltily as they are preventing their sibling from having a ‘normal’ childhood / life. Conversely, research has shown that the levels of pain experience by bone morrow donors are low and that the discomfort and psychological impact can be reduced through good counselling and monitoring (Fortanier et al., 2002).

Non medical reasons for Preimplantation Genetic Diagnosis (PGD)

The use of PGD for non medical reasons is highly controversial. The consequentialist concerns are that by allowing the use of PGD to screen for genetic conditions and for HLA typing you are taking a step onto the slippery slope towards allowing the selection of traits such as intelligence, height, sexual orientation and so on. The fear is that children will be valued more for their genotype than for their inherited characteristics as human beings. The media have jumped on board, sensationalising the concept by using such terms as ‘eugenics’ the ‘perfect child’ or ‘designer babies’. The reality is however, that the genetic basis of many of these traits is very complex and likely to involve many different genes that are not easily screened for. The procedure is too complex and would require large numbers of embryos from which to select, thus considerable extra cost and discomfort. Therefore, it is reasonable to think that screening for such desirable traits will not occur anytime soon. Also allowing the selection of unaffected embryos or HLA matched embryos does not mean we will become permissive about so called ‘designer babies’.

In the search for the best possible child, one ‘realistic’ use of PGD would be to select the sex of a child. This procedure is seen as a relatively weak reason for creating, selecting and discarding embryos and the use of PGD for sex selection is not currently available, except in the case of X-linked genetic disorders. The main argument against PGD for sex selection is that if the procedure was carried out on a large scale, it could lead to discrepancies in the sex ratio of the population. The bias is likely to reflect cultural notions of male privilege and may reinforce sexism towards women (Robertson, 2002). Despite this there are many reasons why parents may wish for a particular gender. For example, a couple with a girl may want their next child to be a boy in order to meet certain cultural norms like having a male heir. Reproductive autonomy is the main argument in favour of sex selection for social purposes. The genetic tests are available; therefore based on the principle of procreative beneficence parents should not only be free to select a child free of disease but also to select the gender of their child. Parents should be able to select a child who they expect to have the best opportunity of the best life (Savulescu, 2001).

Another ‘realistic’ possibility of PGD is for disabled parents to select embryos with certain disabilities such as deafness or short stature, in the expectation that the affected child will integrate into the family. Disabled parents may feel that they would be better parents to a disabled child. There is also the concept of a disabled community, in which people with a particular disability feel connected with other disabled people. In these communities, unaffected individuals cannot fully sympathise with those that are affected and therefore do not ‘fit in’. In this concept, the unaffected child may not be fully welcomed into the family or the larger social community. There are many that see this argument as flawed, particularly for deafness as non deaf children can still be taught and use sign language and those who become deaf in later in life are still able to integrate into the so called community.

Is there a moral and social duty to have a healthy child in situations where there is a choice? If so what counts as healthy? The main argument against the deliberate creation of a disabled child is that of nonmaleficence; the duty of physicians and of the community as a whole not to inflict evil or harm. By intentionally selecting a child with a certain disability such as deafness are you inflicting harm on that child? Using PGD, you are not creating a deaf child, you are just selecting one. Are you then causing harm by denying that child the best opportunity at the best possible life? Not necessarily as that particular embryo would not have had an alternative better life, if not selected for implantation the embryo would have been destroyed (Shakespeare, 1998). Does the health professional have the right to object if they have concerns about the quality of life that is being created, or is it the parent’s right to choose which embryos they implant?

As you can see the use of PGD to screen embryos raises many ethical, legal issues some of which have been discussed in this essay. Whilst the procedure itself appears to poses minimal harm to the fetus and postnatal development, there are many complex issues that arise. Although I can see the many benefits of PGD, I believe that there needs to be tight regulation in order to prevent people using PGD for their own selfish interests. I remain to be convinced that PGD should be used to screen for incompletely penetrant conditions, susceptibility genes and late onset conditions.