Fertility care in the era of commercial direct-to-consumer home DNA kits: issues to ponder

Abstract

Recently, we have witnessed a shift in the nature of genetic testing. What was once solely in the hands of the scientific community is now easily accessible to anyone. Commercial companies such as Veritas Genetics, Ancestry, and 23andMe offer cheap direct-to-consumer home DNA kits that are branded as a “health and ancestry service.” These tests are gaining in popularity, and it is estimated that since their marketing, over 30 million people worldwide have provided their DNA samples. The implications of this new genetic era are diverse, ranging from the individuals personal health assessment, to family genealogy and ancestry, and the complexity of establishing an enormous population-based genetic database. Unique implications of commercial DNA tests on fertility patients and heath care providers, such as in the case of gamete donation, are important to acknowledge and have implications for reproductive care.

Our understanding of the human genome is no less than revolutionary and has had an immense influence on many aspects of the medical field, from the diagnosis and treatment of diseases to illness prevention. Understanding the genetic root of different diseases permits early diagnosis and treatment of many conditions. A comprehensive genomic profile of malignant tumors may help us match cancer patients to personalized targeted treatment, based on genomic alterations in their DNA. Technologies such as chromosomal microarrays (CMA) and next-generation sequencing (NGS) have permitted the identification of genetic defects in many disorders and syndromes that previously escaped detection. Preimplantation genetic testing (PGT) based on these technologies have permitted prevention of disorders causing significant morbidity and mortality. Modern genetic databases can also be harnessed for the benefit of forensic science. Genetic databases, including those held by commercial companies and genealogy databases have recently been used to solve several “cold cases” of horrendous crimes, bringing to justice rapists and murderers decades after committing their wrongdoings [1–4]. The identification of the culprits is possible by linking DNA samples from the crime scene, with relatives of the culprits who are in the database and building a genetic cross matching accordingly.

Nowadays, the power of genetic testing has become easily available to anyone with a keyboard and as little as 100$. Companies such as Veritas Genetics, Ancestry, and 23andMe offer direct-to-consumer home DNA kits that are branded as a “health and ancestry service.” These kits are gaining in popularity, and sales are skyrocketing particularly during the holiday periods, when they are promoted as the perfect Christmas and New Year’s gift and are often discounted. Since the marketing of commercial DNA kits started, it is estimated that over 30 million people around the world have provided their DNA samples. While some people are merely interested in finding more about their ancestry and genealogy, others seek to learn more about their health predispositions or disease carrier status. Genetic testing companies are providing consumers with an unprecedented level of access to their personal genome and only seldom are the individuals taking the test aware of possible implications of it on themselves, their families, and society as a whole. Someone being tested may uncover that his or her biological origin is different than anticipated. The lay press is filled with stories of people discovering their father is not their biological parent or that they have half siblings they did not know about [5–8].

As for the diagnosis of disease carrier status and risk of health conditions, the interpretation and practical implications for individuals can be challenging tasks even for well experienced geneticists [9–11]. Commercial companies encourage consumers to consult with a genetic counselor prior to and after testing, but they do not mandate it. It is up to the consumer to decide whether to pursue such counseling. 23andMe for instance links their consumers to the relevant National Associations of Genetic Counselors, while Veritas Genetics offer their own team of genetic counselors [12].

A different aspect of the growing popularity of direct-to-consumers tests relates to the development of an enormous genetic database containing the genome of tens of millions of people worldwide. While promising consumers confidentiality, privacy risks are not yet fully understood. As in any other large database, hacking is always a concern. On June 2018 “MyHeritage” posted on their website an announcement reporting a breach in their database [13]. Although the information breached contained email addresses alone and neither family trees nor DNA were exposed, this breach emphasized the vulnerability of such sources containing delicate information. But illegal activity is not the only privacy concern. Commercial companies themselves state that their confidentiality policy is subjected to possible changes [14–16], and questions remain as to the right of law enforcement and the federal government to force these companies to share genetic data. Another troubling question is what would happen if insurance companies gain knowledge to such sensitive personal information, which might even be extrapolated indirectly through results of relatives in the databases.

Trying to cover all questions and concerns arising from the new commercial direct-to-consumer kits is far beyond the scope of a single discussion. As fertility doctors, we would like to question what possible implications do these commercial genetic tests have on our discipline.

1. “Who is my father/mother?” Is the era of anonymous gamete donation over?

Since the 1970s, when sperm banks became popular, gamete donors were almost always anonymous and most sperm donors were promised anonymity. Nowadays, more professionals speak in favor of disclosure. This approach is reflected by the ASRM committee opinion from 2013 that supports disclosure about the facts of embryo and gamete (sperm or oocyte) donation to children. That said, the committee opinion also emphasized the complexity of the subject, and that a consensus has yet to be reached [17]. From both the donor and recipient perspectives, some still prefer the comfort of anonymity, whether for emotional or cultural reasons or the fear of being legally responsible. While in the past, anonymity could be promised, with the emergence of readily available and cheap DNA testing, that promise can likely, no longer be maintained. Today, many donor conceived children seeking for their biological parent through genetic relatives matching based on these DNA database. There are numerous stories of adults finding their biological father. Others have discovered that they have dozens of genetic half siblings [5, 7, 18]. There are also many stories of individuals, who when taking these commercial tests have discovered that their biological parent was not who they thought to be and that in fact they were conceived via sperm donation [5, 7, 8]. In reality, in North America as well as in many European countries, almost anyone can be linked to other family members on the basis of genetic findings and the current databases. It is not necessarily for a donor to be listed on the database to be recognized; as long as some of the donor’s relatives are listed, the donor-conceived individuals can cross match their DNA with those relatives and create a match tree leading to the donor [19]. Some countries such as Australia and the UK have changed their regulations of gamete donation and banned anonymous donation all together [20]. Considering the simplicity of tracking a donor, it is likely that even in countries that allow it, the era of anonymous donation is over [21]^. As fertility doctors or managers of gamete banks, we have got to acknowledge the current genetic landscape and are obliged to consult patients that are seeking gamete donation as well as potential donors accordingly. Consideration should also be given to donors who were promised anonymity in the past who now can likely be found.

2. “Who is my father?” Intentional and unintentional swaps

There are several stories published in the media of embryo or sperm mix-ups that were discovered by DNA testing of the children conceived after their parents presented with a suspicion of a mix-up [22, 23]. More disturbing are a number of stories of deliberate swaps of sperm samples. Such stories include that of an Ontario fertility doctor who had fathered more than 12 children by replacing donor or husband’s sperm with his own, without the knowledge or consent of his patients [7]. In the same manner, a fertility doctor from Indianapolis, and a Dutch physician, were each proven by DNA testing to have fathered 50 children, the latter estimated to have fathered as many as 200 children without the knowledge of his patients [8, 18]. These cases of blatant misconduct were all revealed after individuals chose to use commercial DNA kits. It should also be noted that in all these cases, the “mix-ups” were not detected by linking to the genetic progenitor but by relatives of that progenitor in commercial databases. Published cases all took place in the 1970–1980s. Since that time, as the field of assisted reproductive treatment developed, strict guidelines for human embryology and andrology laboratories were published by the American Society for Reproductive Medicine (ASRM), emphasizing the importance of sample recognition and identification [24]. This is also highlighted in the World Health Organization (WHO) guideline for the examination and processing of human semen [25].

“Fertility fraud”: a new legal terminology

On October 2019, the ASRM published an update on “fertility fraud” legislation [7]. Currently, several states in the USA including California, Indiana, and Texas have bills criminalizing fertility fraud. These bills are the direct consequence of the aforementioned cases of physicians substituting a donor or husband’s sperm with their own without an explicit consent from their patients. Texas legislators determined that doctors, who perform procedures using reproductive material from a donor that the patient did not consent to, can be charged with sexual assault. The fact that legislators find it necessary to define such misconducts as a distinct felony is important however, also troubling, as patient-doctors trust is fundamental to our practice. Due to these cases, the trust our patients bestow upon us may be affected.

3. Counseling about genetic testing and communication of genetic test results

As some of our patients could also choose to take direct-to-consumer tests, questions may rise regarding their general health and the possible implications of the results on their offspring. The American College of Obstetricians and Gynecologists (ACOG) has issued committee opinions addressing this issue [9, 11]. It highlights the complexity of interpreting genetic results in the unique context of each patient, and recommends the involvement of a health care provider with knowledge of genetics in the ordering and interpreting of appropriate genetic tests. Clearly, patients may come to us confused about results discovered on commercial tests. Luckily, we can refer to genetic counselors when indicated, and use our compassion to minimize their fears.

In their committee opinion, the ACOG also comments on the lack of sufficient oversight of the commercial companies. The same concern is shared by the federal trade commission that in accordance with the Food and Drug Administration (FDA) and the Center for Disease Control and Prevention (CDC), who have stated that some of the tests may lack scientific validity [10]. In general, direct-to-consumer tests for non-medical, general wellness, or low risk medical purposes are not reviewed by the FDA before they are offered. Although, some of the tests have received marketing authorization by them [26]. The ACOG recommendation that “direct-to-consumer genetic testing should be discouraged because of the potential harm of a misinterpreted or inaccurate result” may be justified. Nonetheless, a recommendation as such seems anachronistic in the direct-to-consumer aggressive marketing era, thus it is our responsibility to be familiar and updated with the existing tests and their limitations.

One question that remains is related to legal responsibility, if two prospective parents are found to be carrier for a recessive disease on a commercial test. They then do not identify this significance and do not see a counselor for explanation of these results. They subsequently deliver an affected child. Should the obstetrician or reproductive endocrinologist have screened the patients for having taken the test? Likely, our medical history should include whether such tests were taken, and a request for the results should be performed.

In conclusion, commercial DNA kits that are inexpensive and easily available are here to stay. The healthcare community is no longer the sole mediator between individuals and their genetic information. This change in landscape requires us to always be on top of the genetic testing revolution and to be able to offer advice to our patients about the findings they may receive. It also reminds us that in our unique filed of work, helping people create life is of great importance to humbly recognize our limitations and possible pitfalls. Commercial DNA tests and what they sometimes unexpectedly reveal emphasize the importance of strict adherence to protocols for handling reproductive material. Moreover, it puts into question the relevance and feasibility of anonymous gamete donation and mandates us to adjust our practice to the changing reality.