Genomic Justice as Reproductive Justice: Universal Coverage for Preimplantation Genetic Testing for Hereditary Breast and Ovarian Cancer Syndrome

With increasing limitations on reproductive choice in the past several years, reproductive justice—rooted in the principles of the right to have a child, the right to not have a child, and the right to parent children in safe and healthy environments ¹ —has become a critical consideration for American clinicians and patients. Correspondingly, clinicians have increasingly advocated for reproductive justice, although adopting a narrower vision of reproductive choice focused on increased access to abortion services and contraception options. We implore the medical community to widen this lens by illuminating another population for whom reproductive options must be considered—those with hereditary breast and ovarian cancer (HBOC) syndrome.

With more individuals undergoing genetic testing, there is an increased need for reproductive services tailored to communities at high risk for breast, ovarian, and other cancers. For those with pathogenic/likely pathogenic variants in cancer susceptibility genes that carry a 50% inheritance pattern, such as BRCA, preimplantation genetic testing for monogenic disorders (PGT-M) offers life-altering technology. This service allows for the selection and implantation of embryos that are negative for the pathogenic/likely pathogenic variant, which halts the potential generational legacy of cancer. Unfortunately, the universal lack of insurance coverage for this service renders it cost-prohibitive. This financial barrier creates an underinterrogated disparity that not only directly impacts families unable to afford the service who wish to utilize it but also has the potential to form entire generational shifts in future gene pools based on socioeconomic status. This is a healthcare, reproductive, and genomic injustice, for which the medical community can and should advocate for urgent solutions.

Background

Preimplantation genetic testing was first developed in the 1990s in England to identify a pathogenic/likely pathogenic variant in a single gene (either monogenic, aneuploidy, or chromosomal structural rearrangements). This service was historically limited to highly-penetrant autosomal dominant diseases such as osteogenesis imperfecta and X-linked diseases such as fragile-X syndrome and Hemophilia A/B.^2,3 However, in 2001, Verlinsky et al presented the first documented case of PGT-M for a cancer susceptibility gene for a healthy child born with a family history of Li-Fraumeni syndrome, ⁴ which confers an elevated risk of numerous malignancies such as breast cancer, soft tissue cancers, and sarcomas. By 2003, this service was offered to BRCA1/2 mutation carriers, ⁵ with official approval by the Human Fertilization and Embryology Authority in 2006. ⁶

Since then, debate has ensued over the use of PGT-M in such disorders, even amid its use. One argument is that associated cancer risks with HBOC generally present in adulthood and for which there are available screenings, treatments, and preventive options. Another argument is that such patients may never even express disease despite carrying a pathogenic/likely pathogenic variant in a cancer susceptibility gene such as BRCA. However, in 2024, the American Society for Reproductive Medicine deemed the use of PGT-M for certain adult-onset conditions as ethically feasible. ⁷

PGT-M presents the opportunity to halt the generational legacy of cancer for carriers of BRCA pathogenic/likely pathogenic variants and others with HBOC. Not all patients with HBOC may wish to utilize PGT-M. Some patients with HBOC may not even be aware of their diagnosis at the time of conception, or have the ability or desire to “plan a pregnancy”. ⁸ However, our focus is rather to advocate for the option and financial accessibility of PGT-M for those who do wish to utilize reproductive technologies. In tandem with the concept of reproductive justice, the focus here is not the patient's decision but the choice of whether and how to use these technologies. Unfortunately, due to costs, these services remain out of the realm of possibility for many.

Financial Barriers to Reproductive Technologies

A necessary step in PGT-M is in vitro fertilization (IVF). While barriers to access are numerous, cost remains one of the most substantial. One particular multicenter prospective cohort noted that couples utilizing IVF had the highest costs of all those accessing infertility services at $19,234, ⁹ with another prospective cohort estimating IVF costs to reach $24,373. ¹⁰ IVF is not covered by many insurance policies, with only some states nationwide having a form of infertility insurance law. Only 14 states, plus the District of Columbia, require the inclusion of IVF in infertility services. ¹¹ While state mandates may help enhance utilization of fertility services, ¹² significant variation in coverage and requirements between insurers persists. ¹³ For instance, although Maryland passed the first IVF mandate in 1985, caveats remain, such as required waiting periods or certain stipulations for unmarried couples. ¹⁴ Furthermore, few insurance plans, if any, cover the additional costs of PGT-M for those with HBOC, with out-of-pocket costs reaching upwards of $30,086 for IVF with PGT-M ¹⁵ (representing almost 40% of an average person's annual income in America). ¹⁶

In addition to socioeconomic barriers, disparities related to race and ethnicity have been well established regarding fertility services. IVF is grossly underutilized by racial and ethnic minoritized communities (namely Black and Hispanic people) and those of middle or low socioeconomic status with impaired fertility. ¹⁷ Although Black women in particular have been found to have higher rates of infertility compared with White women, ¹⁸ they are less likely to have a doctor's visit concerning infertility. ¹⁹ Even after treatment, Black women are less likely to achieve a live birth and more likely to have a miscarriage. ²⁰ There is also data demonstrating under-representation of Black communities in fertility care even in areas with state mandates, ²¹ indicating that factors beyond cost could also contribute to disparities.

Cancer Risk with HBOC

The burden of cancer screenings and decision-making regarding risk-reducing surgeries can be astronomical for those with HBOC. Carriers of the BRCA1 pathogenic/likely pathogenic variant, for instance, have a 60–72% lifetime risk of breast cancer for which annual breast MRI starting at 25 and annual mammogram at 30 are recommended, with the options of chemoprevention and risk-reducing mastectomies. ²² Due to the 39–58% lifetime risk of ovarian cancer, bilateral salpingo-oophorectomy between 35 and 40 years old is recommended, given the high mortality rates and lack of effective screening tools for this cancer. In these scenarios, affected patients face early surgical menopause and increased cardiovascular mortality (a common cause of mortality nationwide), as well as facing tough, time-sensitive reproductive decisions. Furthermore, this is not an exhaustive review of all cancer risk that a patient must consider.

Decision-making in this context can be challenging. Some studies demonstrate that those with BRCA1/2 may experience guilt from the possibility of passing on the pathogenic/likely pathogenic variant to offspring, ²³ for which some may decide not to conceive altogether. Financial barriers to PGT-M ultimately strip individuals of their reproductive autonomy, interrupt their ability to mitigate the continuation of cancer in their families, and perpetuate oncologic burdens in already financially disadvantaged populations. The downstream global impact is even more profound. This man-made genetic pressure carries the possibility of creating entire shifts in future genome pools simply based on financial constructs.

Genomic Justice and its Considerations

Genomic justice is central to the discussion of access to reproductive technologies and the financial barriers that can preclude their utilization. While the concept of genomic justice is not novel,^24–26 it is rarely paired with reproductive justice. We posit that genomic justice, specifically within the framework of reproductive justice, demands that all communities have the ability to choose whether and how they will use genomic technologies to align with their reproductive goals and values (Figure 1). In the context of HBOC, enacting genomic justice means that all patients should have access to potentially life-altering medical services such as PGT-M, irrespective of race, ethnicity, and socio-economic status. Choice is stripped from patients when services are cost-prohibitive, and as current practices stand, this inaccessibility creates a passive state of eugenics in which eliminating cancer in one's progeny through PGT-M is determined not by will, but by wealth. This service should be available to all carriers of pathogenic/likely pathogenic variants in HBOC who wish to utilize it.

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Figure 1.

 Defining genomic justice as reproductive justice.

Despite the promise of increased access with universal subsidies for PGT-M, limitations remain. To utilize PGT-M, genetic testing must first be performed to identify the presence of a cancer susceptibility gene. Unfortunately, gross underutilization of genetic testing nationwide prevails, particularly among racially and ethnically minoritized communities. Some reasons include lack of information on the benefits of genetic testing and concerns regarding genetic discrimination.^27–31 Provider bias and lack of physician referral also play a role, ³² with data suggesting that Black and Hispanic patients are less likely to be offered genetic testing.^33,34 These barriers could also have implications for immigrant communities, for whom healthcare access may be limited, and for whom race, ethnicity, and language discordance could pose impediments to overall healthcare access. Genetic counseling communication remains a key component of service uptake, yet little research has been conducted in immigrant communities.

Another barrier could be the actionability of genetic testing results, which is necessary for PGT-M. Even in the context of genetic testing, communities of non-European ancestry are more likely to have variants of unknown or uncertain significance (VUS).^35,36 These equivocal results are non-actionable and are monitored over time for changes in reclassification as data and analysis evolve. While ancestral diversity in genomic data has improved over time, the majority of genome-wide association studies, from which many variant classifications are extrapolated, consist primarily of populations of European ancestry.^37,38 While it is possible that a person with a VUS result may miss a window to benefit from PGT-M if the VUS is later upgraded after fetal conception, the reality is that the majority of VUS are later downgraded to benign/likely benign.^39,40 However, it is unclear whether this can be extrapolated to communities of non-European ancestry in the same way. Few studies have been conducted on this topic, with one retrospective study demonstrating a higher frequency of VUS among Black and Asian communities compared to White populations, but with no statistical significance in VUS reclassification of breast cancer susceptibility genes. ⁴¹ These results suggest that those of non-European ancestry are also likely to have a VUS downgraded over time (as is the case for those of European ancestry). However, one limitation of this study was that VUS data are still extrapolated using genomic data and reclassification strategies for those of European ancestry, which could be confounding. While this should not be a barrier to genetic testing in ancestrally diverse communities, it remains an area that requires further research to better understand genetics across populations.

Finally, it is important to address the ongoing debate about the ethical dilemmas of PGT-M. One critique is that PGT-M facilitates the creation of “designer babies” and introduces too much human intervention in the creation of life, raising the question of who decides what constitutes disease. The moral argument of PGT-M has largely pertained to disability, highlighting that PGT-M could devalue certain lives deemed unhealthy, diseased, or disabled. ⁴² Our proposed framework does not require defining disability or assigning value, nor does it insist on the use of PGT-M for all HBOC patients. Rather, this framework is intended to ensure options for the use of reproductive technologies if and when a patient may wish to access them. Present financial barriers limit whether that choice is available and could passively stratify genetic makeup based on socioeconomic status.

Recommendations and the Way Forward

Solutions to ensure genomic justice must be multifaceted. Cost is one of the most significant barriers to PGT-M. We implore the medical community to advocate for full financial coverage for patients with HBOC who wish to utilize PGT-M. State mandates should be universal and broadened to include both IVF and PGT-M. In addition, those with pathogenic/likely pathogenic variants in cancer susceptibility genes, such as BRCA, who desire to access this service but who may fall outside of the state mandate, should also be offered subsidies. Health insurance companies and policymakers can and must address this disparity through universal access to this service, which may shape future generations.

While cost is an obvious barrier and the focus of this manuscript, genomic justice also includes other up- and downstream challenges to the utilization of PGT-M. Creating more systematic referral systems to reproductive endocrinology could increase access for minoritized groups that are otherwise less likely to receive fertility care. There is a need for more research evaluating the differences in IVF treatment success among some groups compared to others.

Concerning genetic testing, there is a critical need to increase the number of certified genetic counselors to address the national shortage. ⁴³ Greater healthcare provider training in genetic medicine could increase the number of referrals to genetic counselors and allow for improved, early identification of those with HBOC.^44,45 Anti-bias training among healthcare providers regarding genetic testing would bolster genomic justice, along with new approaches to genetic risk stratification that refine genetic eligibility and reduce the need for provider selection.^46,47

Improved education and communication are also critical, particularly for communities with increased patient concern about discrimination or language barriers. ⁴⁸ One particular qualitative pilot study revealed the importance of multiple appointments and effective medical interpretation in a cohort of Latina immigrants to address issues with literacy and language when counseling for genetic breast cancer risk. ⁴⁹ Another pilot study utilized a culturally appropriate decision aid video to increase the uptake of genetic counseling among Black women at elevated risk for HBOC, demonstrating an increased post-intervention intention to pursue genetic counseling. ⁵⁰

Genomic justice and reproductive justice are critical, intertwined imperatives in our current political, scientific, and medical climate. As we write this commentary, both reproductive autonomy and support for cancer research are under serious compromise. Healthcare providers have a scientific and professional responsibility to advocate for policies that offer patients options that could reduce generational cancer susceptibility. Mandates that fully cover IVF and PGT-M costs nationwide would ensure genomic justice for this patient population. As a medical community, we must advocate for full financial coverage for those with HBOC who wish to access PGT-M as a component of preventive care for future generations, and as a measure of both reproductive and genomic justice.