BWH Clinical Ethics Case Review, a monthly newsletter, is published by the BWH Office of Clinical Ethics. Each issue highlights a BWH case that posed an ethical problem for a patient, family members and/or caregivers, leading to an ethics consultation and BWH Ethics Committee discussion. Please note that because cases are based on actual ethics consultations, some details may have been altered in order to protect patient privacy and confidentiality.

Is It Ethically Defensible to Transfer an Embryo That Is Known to Carry a Disease-Causing Mutation?

ethics

This issue of the BWH Clinical Ethics Case Review highlights a case in which a couple undergoing in vitro fertilization (IVF) asked if the IVF team would be willing to transfer embryos that had tested positive for a genetic mutation associated with an adult-onset disease.

The Case

The patients were a husband and wife in their 40s pursuing IVF as treatment for infertility. Genetic screening had revealed that one of them was a carrier of a genetic mutation associated with an adult-onset disease and that their IVF embryos had a 50 percent chance of inheriting this disorder. For various reasons, this was the last time they could attempt IVF.

The couple was considering preimplantation genetic diagnosis (PGD), a method of testing early embryos for genetic abnormalities, in hopes of being able to select a healthy embryo for transfer. Their primary goal, however, was to deliver and parent a genetically related child. The couple had made it clear that they wanted to move forward with IVF, even if PGD revealed that all of their embryos were affected by the mutation. Prior to undergoing PGD, they sought assurance that the IVF team was willing to transfer an affected embryo; otherwise, they would forego PGD and have embryos transferred anyway. The BWH Assisted Reproductive Technology (ART) group asked the BWH Ethics Committee to help think through the ethical issues presented by this situation.

Discussion

PGD is a means of screening early embryos to identify genetic abnormalities associated with serious diseases. It is routinely offered to patients going through IVF. Typically, abnormal embryos are discarded while one or more healthy embryos are subsequently transferred to the woman’s uterus for gestation (Berger et al. 2014). Originally, PGD was used to test for various childhood-onset diseases, such as cystic fibrosis and muscular dystrophy. As technology evolves and the range of identifiable genetic defects expands, PGD is increasingly being used to screen for adult-onset disorders, as well (Berger et al. 2014). Many of these disorders are of variable penetrance and expressivity, meaning it is difficult to predict if and when the carrier of the gene will develop clinical symptoms and how severe they will be.

IVF patients occasionally request transfer of embryos known to carry a diseasecausing genetic mutation, as seen in this case. Often, these patients have undergone their last cycle of IVF and have no other healthy embryos. If the risk to their future offspring is an early-onset disease, they may willingly accept the prospect of parenting a child with health problems. If the risk is a late-onset illness, they may hope for decades of healthy life and the development of treatments before symptoms emerge.

When faced with the request to transfer affected embryos, clinicians confront the ethical challenge of balancing their responsibilities against the rights of the prospective parents. Ethical principles of autonomy, nonmaleficence and justice provide the framework for weighing the competing interests at stake.

The ethical principle of autonomy arguably gives prospective parents the right to select an IVF embryo of their own choice. Our society places high value on freedom of reproductive choice and respect for parental authority. If prenatal testing reveals a fetal abnormality in the early stages of pregnancy, women have the right to decide whether to continue or terminate the pregnancy. Arguably, that same right remains relevant in the context of IVF, and women/couples should be allowed to pursue pregnancy with an abnormal embryo. Respect for parental authority supports this view. Parents have the right to make choices about the welfare of their children, including those yet to be born. “The moral basis for respecting the judgment of parents is the presumption that parents have the best interests of their children at heart, that they of all people can be trusted to do what is best for their children” (Draper et al. 1999).

While parents have significant leeway to make choices for their children, their autonomy is not absolute and should be balanced against the clinician’s countervailing responsibility to avoid actions that they assess to be more harmful than beneficial to patients. This derives from the ethical principle of nonmaleficence, as expressed by the Hippocratic dictum “do no harm.” If the future child faces a very poor quality of life and/or severely shortened life expectancy, clinicians may have a duty to override parental choice and refuse to enable the birth. Concern may extend beyond the potential child to the care team and other patients. Asking clinicians to participate in a process that is expected to bring about a high degree of suffering can cause moral distress, which is not only harmful to the provider but also can have a detrimental effect on the quality of patient care.

The ethical principle of distributive justice—the just allocation of scarce resources—may also come into play if the child will require a lifetime of expensive advanced medical care. Other societal interests that conflict with the transfer of affected embryos are the goals of decreasing the overall burden of disease and reducing the transmission of genetic disorders (Ethics Committee of the American Society of Reproductive Medicine [ASRM Committee] 2013). These goals are controversial, however, as some consider the practice of eliminating affected embryos to devalue the lives of those living with disease (ASRM Committee 2013).

The BWH Ethics Committee recognized that these cases involve many variables and uncertainties, all of which need to be considered in weighing the ethical defensibility of transferring an affected IVF embryo. Such factors include:

  • severity of symptoms
  • age of onset
  • degree of penetrance and expressivity
  • availability of unaffected embryos
  • development of safe and effective treatments

In this case, the BWH Ethics Committee agreed that it would be ethically permissible to transfer an affected embryo if all embryos tested positive for the mutation. The Ethics Committee took into account the fact that the disease in question has a late onset and does not pose a risk of extreme harm; carriers of the mutation do not always develop symptoms; and this was the couple’s last chance to realize their hope of having a genetically related child. Repeat genetic counseling regarding the disorder is advisable in these situations, and an ethics consultation is available to help address areas of uncertainty and conflict. Subsequent to the Ethics Committee meeting, a subcommittee consisting of members of the ART group and Ethics Committee developed a set of guidelines titled “BWH IVF PGD/PGS Guidelines for Transfer” to help inform decisions in future cases.

Supporting Literature

ASRM Ethics Committee. “Use of Preimplantation Genetic Diagnosis for Serious Adult Onset Conditions: A Committee Opinion.” Fertil Steril
2013;100:54–57.

Berger, V, Baker V. “Preimplantation Diagnosis for Single Gene Disorders.” Semin Reprod Med 2014;32:107-113.

Draper, H, Chadwick, L. “Beware! Preimplantation Genetic Diagnosis May Solve Some Old Problems but It Also Raises New Ones.” J Med Ethics
1999;25:114-120.

We welcome your feedback about BWH Clinical Ethics Case Review! Please email your questions and/or comments to BWHEthicsService@partners.org. To learn more about ethics consults, visit the Office of Clinical Ethics website. This newsletter is primarily intended for internal distribution to BWH clinicians. If you’d like to use this content for another purpose, please contact the BWH Office of Clinical Ethics.