The ethics of preimplantation genetic diagnosis
Cheryl Pui-Yan Au B Med Sci* |

*Medical student, The University of Sydney


couple in their early forties, Mr and Mrs R, came to the fertility clinic for their first consultation regarding In Vitro Fertilisation (IVF) treatment. Mrs R has a strong family history of colorectal, breast and ovarian cancers on her paternal side, with her father confirmed to have the Breast Cancer Type 1 Susceptibility Protein (BRCA1)  mutation. She herself has not been tested for the BRCA1 mutation, but has had regular mammograms, all of which have been normal thus far. Because she has a 50% chance of inheriting the BRCA1 mutation, the fertility doctor offered the possibility of prenatal genetic diagnosis (PGD) for the embryos harvested from the IVF cycles, which is available at IVF Australia. This would add another $4000 per cycle to the cost of IVF.

BRCA1 and BRCA2 gene mutations confer significant lifetime risks for both breast and ovarian cancer ranging from 36-90% for breast cancer and 18-56% in BRCA1 mutation carriers and 14-27% in BRCA2 mutation carriers for ovarian cancer (1,2). BRCA1/2 mutation carriers thus have medically and ethically complicated decisions to make, not only regarding their cancer risk and treatment, but also their childbearing plans. Preimplantation genetic diagnosis (PGD) involving in vitro fertilisation (IVF) and embryo biopsy opens the door to preventing pregnancies affected with debilitating and/or lethal genetic diseases, such as cystic fibrosis, Huntington’s disease and Duchenne muscular dystrophy (3,4). In such cases, if the embryos carry the genetic mutation(s), they will definitely get the disease. There has been recent debate about extending use of PGD to encompass lower penetrance, adult-onset diseases such as hereditary breast and ovarian cancer, where there is less certainty that the condition will occur in the offspring (3,4). My paper will briefly describe the main ethical issues in the general use of PGD, and then more specific ethical, legal and professional implications related to PGD among the BRCA 1/2 population.

A major ethical objection arises from the need in creating and selecting embryos based on genetic criteria. The deselected embryos are then usually discarded. Those who view the preimplantation embryo or foetus as a person will object to the creation and destruction of embryos, and oppose PGD (3). Others view preimplantation embryos as the first stage of a human being and thus deserve special respect, but lack interests or rights due to their ‘rudimentary’ development (3). With this perspective, PGD may be ethically acceptable in order to prevent serious genetic diseases in offspring. Another set of ethical objections arise from the embryo selection process itself. The deontological perspective is that no matter what the intentions are, it is wrong to choose traits in offspring. The consequentalist objection stems from the view that engineering children according to genetic criteria is a highly instrumental approach to reproduction. There are societal fears that PGD will move us towards a eugenic world in which children are valued more for their genotype than for their inherent worth and dignity (3–5).

In addition to these strong objections to PGD, the new indications of PGD for susceptibility conditions such as hereditary breast and ovarian cancer create additional ethical issues. Here, the question is whether the burdens of carrying susceptibility genes for the child exceed the financial, psychological and ethical burdens of IVF and PGD, to justify these reproductive measures to avoid affected children (4,5).

Critics of PGD for BRCA 1/2 carriers argue that a mutation predisposes to but is not 100% predictive of cancer, and that most cancers have an adult onset and are multifactorial. Known carriers may improve their chances of survival through early detection by regular screening, and lifestyle measures such as healthy eating and the cessation of smoking (4). The parental burdens of IVF and PGD should be weighed against the psychological burdens of their offspring as adults, which includes psychological harms – stress, anxiety, depression, grief and feelings of guilt (2,6). In addition, PGD often has an uncertain outcome and is costly, time and labour-intensive. Even with a successful IVF and PGD procedure, there is no guarantee of pregnancy after transfer, and no guarantee of a term or near-term delivery (3,7).

It has been argued that couples who carry cancer susceptibility genes such as BRCA 1/2 should have the freedom to choose PGD. Using the principles of reproductive freedom and family autonomy, there is a view that parents have a presumptive right to obtain and use genetic information in making reproductive decisions (4). If they don’t opt for PGD, they have to face the prospect of wondering whether their daughters will develop breast cancers in their 20s and 30s and/or seeing their daughters deciding whether to undergo prophylactic bilateral mastectomies to prevent breast cancer. In addition, for those who survive breast and ovarian cancer, treatment entailing surgery, chemotherapy and/or radiotherapy is distressing and psychologically effects individuals and families. Thus, some view the avoidance of offspring with susceptibility genes to be procreative liberty (2). However, such procreative liberty should be considered in light of duties of care and of justice. This duty of care is specifically on clinicians and healthcare workers to inform patients of reproductive options, within the boundaries of their ethical stance. Equity and justice in society also come into consideration as there should be equitable distribution and access to limited resources that reflects need priority (4). In such cases, there may be legitimate restriction of procreative liberty if scarce resources need to be shifted to other ‘needier’ patients.

In Mr and Mrs R’s case, they are primarily seeking IVF to facilitate reproduction.  On the one hand, the most viable embryo for implantation is needed for reproductive success. On the other hand, IVF provides the opportunity to screen for the BRCA1 gene, but those without the mutated gene may have lesser implantation potential (7). Moreover, the long term effects on the embryos selected for IVF (i.e. without mutated genes) are not clear, and due to the multiple genetic and environmental pathways in carcinogenesis, such offspring may develop cancer regardless (5). It is important to remember that PGD does not guarantee a child with a healthy future.

In this case at least, the couple already opted for IVF for infertility due to advanced maternal age. Non-IVF patients, however, would seek PGD only if they did not want an affected pregnancy or did not want to risk abortion later on (3). Harm potential exists for these patients with a shift of cancer burden from offspring to healthy mothers. Ovulation induction is a necessary part of IVF, and this may put women involved at increased risk of developing ovarian cancer, particularly if they are already at higher risk (2).

Generalising PGD for cancer to other late-onset or multifactorial diseases, there needs to be extreme caution in weighing competing professional, ethical and medico-legal values from the doctor, the patient, the family and society. Clinicians who oppose PGD outright may not be comfortable in advising PGD as an option for BRCA mutation carriers who are making reproductive decisions.  However, the couple may be referred to reproductive specialists for consultation if they are interested. In this case, the doctor informed Mrs R that she needs to consider testing for BRCA1 carrier status before proceeding further, however did not refer the couple to genetic counselling specifically. As per the NHMRC guidelines, it is critical that those seeking PGD understand the technology, its technical limitations and the ethical implications, in order for them to make informed decisions (8). Genetic counselling should be undertaken by qualified counsellors who have an understanding of family processes and relevant psychosocial, ethical and religious factors, and who do not exert coercive pressure (5).

Potential parents do have significant obligations regarding the foreseeable future of their offspring, but this does not mean that they have a duty to have a child with the best opportunities in life using reproductive methods that are costly and that have significant ethical implications. The boundaries of preventative medicine probably do not encompass the use of PGD to predict risk of developing a late-onset multifactorial disease. PGD for cancer susceptibility should not be introduced just because the technology is available. Implications must be recognised at all levels such that there are measures to ensure acceptable risk-benefit ratios.


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