Preimplantation Genetic Testing for Genetic Kidney Disease: Addressing Moral Uncertainties and Access Inequity : Clinical Journal of the American Society of Nephrology

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Preimplantation Genetic Testing for Genetic Kidney Disease

Addressing Moral Uncertainties and Access Inequity

Burke, Wylie; West, Kathleen M.

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CJASN 15(9):p 1231-1233, September 2020. | DOI: 10.2215/CJN.11790720
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Preimplantation genetic testing involves the genetic analysis of embryos after in vitro fertilization (IVF) to determine whether they have a genetic condition. Only embryos free of the condition are then selected for implantation. The procedure represents one of the first clinical innovations to result from genomic research (1). In this issue of CJASN, investigators from The Netherlands report on a 25-year history in that country of the use of preimplantation genetic testing to prevent the birth of children with kidney diseases (2).

A number of findings stand out in the report (2). First, of couples who elected to use preimplantation genetic testing, two thirds experienced a live birth, a success rate that compared favorably with IVF outcomes in general. Second, among 43 couples with at least one preimplantation genetic testing cycle, 537 embryos were available for biopsy, and 35% were free of the kidney disease assessed and suitable for transfer. Third, the number of genetic diagnoses deemed suitable for preimplantation genetic testing referral increased over the time period of the study. The latter trend reflects technical progress: that is, the increasing ability to perform specific genetic diagnoses on the basis of the discovery of gene variants associated with monogenic kidney disease. It also reflects an increase over time in the set of conditions for which preimplantation genetic testing was considered acceptable (3). The procedure was done in this series for conditions that differed in severity and included both adult- and childhood-onset conditions; however, all involved serious disease.

Underlying these findings are moral concerns with the use of genomics in reproductive medicine. Prior to the availability of preimplantation genetic testing, parents at risk for passing a genetic condition to a child could undergo prenatal testing, with the option of pregnancy termination if the fetus was determined to have the condition, usually in the second trimester. Preimplantation genetic testing allows parents to avoid this difficult choice; instead, it can ensure that an embryo is free of the genetic condition before implantation. There are trade-offs, however. IVF and preimplantation genetic testing are expensive procedures that involve risk. In addition, the use of preimplantation genetic testing, like prenatal testing, reduces the number of people who are born with a particular genetic condition, a goal that has been criticized by the disability rights community as eugenic and having the potential to divert awareness, treatment development, and other resources from those who have the condition (4). With preimplantation genetic testing, high proportions of embryos are deemed unusable because they are genetically affected—more if the condition is inherited in an autosomal dominant or X-linked recessive condition (50% risk for each embryo) than if the condition is inherited as an autosomal recessive (25% risk). Preimplantation genetic testing thus adds to the problem of excess embryos resulting from IVF and to morally contested decisions about appropriate disposition of these embryos, which can be donated, destroyed, or frozen indefinitely (1,5).

Preimplantation genetic testing also involves the moral challenge of determining the conditions for which the procedure is considered appropriate. Enabling parents to avoid the birth of a child with a severe genetic disease was a major driver for development of the technology (1), but it has been used for other more controversial purposes, such as sex selection, avoiding genetic conditions that confer challenges but still enable a high quality of life, and production of a “savior sibling” able to serve as a donor to a child requiring a procedure, such as bone marrow transplant (1). There has been debate about the degree of severity of the diseases for which preimplantation genetic testing should be used, and, when the procedure is done to prevent the birth of a child with an autosomal recessive disease, whether embryos who are carriers of the disease should be excluded.

In this context, it is reasonable that a nationally supported universal health care system would choose to review conditions before determining whether the use of preimplantation genetic testing will be covered by the national payer. In The Netherlands, this oversight occurs through the Preimplantation Genetic Diagnosis National Indications Committee (3). Other European countries provide similar oversight. In France and the United Kingdom, designated oversight agencies focus on severity of the condition, the lived experience of those afflicted, and the likelihood of inheritance as factors in selecting conditions for preimplantation genetic testing coverage (5). In other words, regulation of preimplantation genetic testing in these European countries is consistent with a general understanding that this approach is appropriate, and merits health payer coverage, when parents seek it to prevent the birth of children with serious genetic diseases. People may differ on what they consider a serious disease, pointing to the need for ethically sound deliberation practices when guidelines or coverage decisions are made (6).

What implications do these findings have for the United States? IVF and preimplantation genetic testing are not covered under most private insurance policies and are not available under federal health programs, except for Veterans Affairs coverage of service-related infertility (5). The few professional practice guidelines generally defer decisions about the offer of preimplantation genetic testing to individual physicians (5), allowing for controversial uses, such as sex selection. Arguably, this approach supports the goal of parental autonomy in reproductive decision making—but it does so only for parents of means.

As Snoek et al. (2) demonstrate, the option of preimplantation genetic testing may be highly valued by a small number of couples facing the risk of a child with a serious inherited kidney disease, an application of this technology least likely to be controversial. The authors also show that preimplantation genetic testing can reduce the incidence of serious conditions for which costly and burdensome treatments (such as dialysis or transplant) become necessary, which may reduce cost to the overall health system. Yet, in the absence of insurance coverage, these costly genetic services are primarily available to those who can pay out of pocket. Limits to the coverage of assisted reproductive technology disproportionately burden racially marginalized groups (7), who are less likely to have insurance coverage for these services or the personal means to pay for the cost, more likely to distrust medical providers (8), and more likely to experience adverse birth outcomes and discrimination in reproductive health care (9). As with many new medical technologies, preimplantation genetic testing adoption is socioeconomically and racially divided, thus tending to increase health disparities while improving health prospects for more privileged groups (8).

Yet, health payer coverage of preimplantation genetic testing might be viable in the United States if it were provided for a limited number of rigorously selected conditions for which the use of the procedure had broad support. It is likely that views in the United States will be similar to those in Europe, with severity of disease the most important consideration (10). An approach to coverage that was based on careful selection of appropriate conditions could alleviate disparities in economic access while preventing coverage of procedures that are morally questionable.

In the absence of a governmental forum for deliberation about preimplantation genetic testing, professional organizations have an opportunity to provide leadership in this domain (5). Within each specialty, professional organizations have the expertise needed to assess the clinical implications of conditions for which preimplantation genetic testing might be considered. One of the merits of the report by Snoek et al. (2) is that it offers guidance on this point for kidney disease on the basis of a substantial 25 years of experience. Joint efforts across other specialties would offer the convening power to bring together appropriate stakeholders, including clinicians, individuals and families affected by the diseases under consideration, and members of the general public. These deliberations would need to consider a wide range of stakeholder views and offer ethically reasoned rationales that are respectful of opposing views and remain open to revision as new evidence emerges (6).

Two key goals could be met through this process: (1) addressing moral questions about the acceptable use of preimplantation genetic testing and (2) ensuring access on the basis of need rather than ability to pay. Payers, including government programs, may be more likely to include coverage of preimplantation genetic testing if professional organizations offer stringent guidelines for its use that have the dual goals of preventing the birth of children with serious disease and supporting equitable access. Although the costs of preimplantation genetic testing are often prohibitive for individual families, the overall number of covered procedures is likely to remain small if they are limited to serious (and generally very rare) genetic diseases, particularly as only a subset of parents is likely to choose this option. Any recommendations about the use of preimplantation genetic testing are likely to be controversial. However, failing to address the issue will lead to continuing injustice in access to this procedure.

Disclosures

W. Burke reports receiving grants from the National Institutes of Health during the conduct of the study, unrelated to the study. K.M. West reports receiving grants from the National Human Genome Research Institute during the conduct of the study, unrelated to the study.

Funding

None.

Published online ahead of print. Publication date available at www.cjasn.org.

See related article, “Preimplantation Genetic Testing for Monogenic Kidney Disease,” on pages .

Acknowledgments

The content of this article reflects the personal experience and views of the author and should not be considered medical advice or recommendations. The content does not reflect the views or opinions of the American Society of Nephrology (ASN) or CJASN. Responsibility for the information and views expressed herein lies entirely with the author(s).

References

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Keywords:

preimplantation genetic testing; genetic kidney disease

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