Screening donors: New challenges in the UK fertility landscape

Considerable discussion has recently taken place in the UK around the management of gamete donation, including the possibility of identifying gamete donors to recipients at the birth of any offspring and questions about the compensation of donors (see BioNews 1208). However, there has been little attention given to the new dilemmas arising from the use of donated gametes which have been screened using expanded carrier screening (ECS).

ECS is a reproductive genomic test, used prior to conception, that can identify whether a potential parent or donor carries any of the hundreds of genetic mutations associated with recessive genetic conditions. When used in gamete donation, it can facilitate 'matching' of donors and recipients on the basis of their test results to reduce the risk of the future offspring being affected by a recessive monogenic condition. For example, if a donor is found to be a carrier, they would not be used for a recipient who is also a carrier for that same condition, which is estimated to happen in two percent of cases. However, crucially, the same donor could be used for a different recipient – who is not a carrier for the same condition – without any risks of transmission to the offspring.

The use of ECS is increasing in a context characterised by growing attention on the potential transmission of genetic conditions, especially after a few cases where a genetic condition was transmitted from donor to offspring have been highlighted in the media. Because it can test for a large number of rare mutations in people with no known disorders, ECS has the potential to transform current practice and give rise to new and ethically sensitive questions for recipients, clinicians and donors.

While UK fertility clinics rarely use ECS to screen gamete donors recruited in the UK, many gametes offered in both NHS and private clinics are imported from banks in Europe and the USA, where donors – especially sperm donors – are often screened using ECS. This means that when a patient selects (or is matched with) a donor from one of these banks, the clinicians treating them in the UK may be aware of the donor's carrier status and need to decide what to do with this information. This becomes especially significant when the selected donor is identified as a carrier of a recessive disorder, something that can happen relatively frequently: across the whole population, the average person carries two to three genetic variants for recessive genetic conditions. A recent study conducted at a US sperm bank shows that 45 percent of donors appear to be a carrier of one or more recessive disorders (Lynch, 2024).

Therefore, even if UK fertility clinics do not use or offer ECS themselves, if they hold this information about screened gametes that they import, they will have to deal with its potential implications, ie, what they should do, and cannot do, when a gamete donor is a carrier of a potentially severe recessive heritable disorder.

Can they allow the recipient to use this donor? Are they obliged to inform the recipient about the potential risks of transmission, possibly prompting them to reject that donor? If they do not tell, whose responsibility is if the future child ends up developing the condition? Should the recipient be tested too and if so, who should pay for the test and provide counselling? And what happens if the recipient does not want to take the test? These are just some of the novel and important questions clinicians are increasingly facing in their practice, and that have arisen in the PRECAS study we are currently conducting on the use of ECS in the UK.

Little guidance or regulation exists in the UK on the use of ECS tests, or how to manage positive screening results. The HFEA's 2023 Code of Practice requires clinics to test donors only for recessive conditions known to be prevalent in their ethnic background, explain them to the recipient, and mitigate the risk. The Code of Practice further refers to professional guidance published by the British Fertility Society; the most recent version of which supports that requirement without discussing extended testing or its implications. The question of how to deal with a donor carrying a recessive disorder thus remains in a grey zone, where it advised against but not strictly forbidden, leaving clinicians often confused or uncomfortable about what to do.

Through the interviews the PRECAS team has conducted with key stakeholders in the field, it has become apparent that this lack of clarity and the resulting uncertainty for clinicians have led to a variety of practices emerging in clinics. For instance, some clinics, out of concern about not fully understanding what is permitted, have chosen to cease using ECS-screened donors altogether or have requested that banks provide gametes that have not been tested. Others opt not to discuss this information with recipients, fearing it may alarm recipients or limit their choice of donors. Additionally, many clinics are concerned about not having the appropriate counselling services in place to inform recipients about the test and its outcomes, in a context where specialised genetic counsellors are already low in numbers.

On the other hand, an increasing number of clinics are embracing this new feature of gamete donation by offering the recipient the option to undertake a 'match' test, which specifically tests for the genetic variant the donor carries, if the need should arise. Usually, this ends up being paid for by the recipient, either directly or indirectly. Practices also vary in the NHS with at least one clinic offering a match test to the recipient if the condition is relatively frequent among the general population.

However clinics proceed with testing for recipients, counselling may then be provided by the clinic or the genetic testing company if the recipient is a carrier for the same condition as the donor. More often, recipients are simply advised to choose a different donor. All in all, it is striking to observe both the diversity of responses to the availability of ECS results in practice and the lack of awareness and communication about these issues between fertility centres.

This situation also introduces new complexities and questions for recipients who become aware of the possibility of accessing additional health information about potential donors and need to interpret and possibly act upon it. Recipients may not necessarily understand what being a carrier means and may immediately reject a donor who carries a mutation.

They may also face a dilemma if they need to pay extra fees for a carrier match test, which could ultimately lead them to choose another donor. Several stakeholders told us that, because of the cost and in order to access fertility treatment quickly, some recipients of donated sperm declined match tests from donors with known positive results or did not want to discuss the donor's ECS results, choosing to accept liability for the potential risk. Counselling thus appears to be of utmost importance, not only to assist recipients with decision-making but also to ensure that they understand the scope of the test and its implications, including the fact that, while it may reduce transmission risk, this risk reduction is marginal and does not guarantee a healthy child.

The important questions, tensions and needs that appear around the use of gametes tested with ECS point to the need for debate, guidance and regulation which offer a clear and consistent roadmap for clinicians and recipients. The question of whether carrier-positive donors can be used or not, and in which circumstances, must be specified, alongside clarifying responsibilities in case of disorder transmission.

It is also important to carefully consider the implications of such decisions and ensure that measures are taken to minimise the impact. This could mean, for example, taking action to ensure appropriate provision of genetic counselling, minimise the cost of match testing for recipients, and maintain a sufficient and diverse supply of gametes. This would guarantee that recipients can access high-quality gamete donation and are properly informed about their options and implications.

In a world where understanding and uses of genetic medicine are progressing rapidly, these issues need to be addressed in a timely way to ensure consistent good practice across the UK.