Donor limits and genetic risk: Separating fact from perception

There are many reasons to limit the number of children per donor, but protecting donor-conceived persons from genetic conditions is not one of them. 

The sperm from a donor with a serious cancer risk was used to conceive more than 190 children across Europe (see BioNews 1291 and 1319). As discussed at a recent event produced by PET (the Progress Educational Trust), about one third of the tested children carry the disease-causing variant, and 12 children have already developed cancer before the age of 15 (see BioNews 1345 and 1352a). Although the scale and severity of this case is exceptional, the fact that donors pass on disease-causing variants to donor-conceived children is not.

Our recent research shows that all Belgian fertility clinics deal with cases where it is suspected that a donor may have passed on a pathogenic variant (an 'error' in their DNA) to donor-conceived persons. The clinics reported an average of nine reports per 100 children born. Sometimes these concerns prove unfounded, but in rare cases, such as this one, the consequences can be severe.

In the search for ways to prevent such events from happening again, two measures have been advocated: more thorough screening of donors and further limits on the number of children per donor.

Ten families per donor

In the UK, a legal maximum of ten families per donor applies. One family can consist of one or more children. However, donated gametes frequently travel across borders, as many European countries rely on Danish sperm banks. This means the number of families per donor can exceed national limits, as happened in the case described above.

In Belgium, moreover, not even the national limit was respected because samples from the same donor were supplied to different clinics. This remained unnoticed as the legally required central register was only established in 2024. Had this register been introduced as planned in 2007, the impact of this case would have been much smaller.

Following this, there has been a push to better enforce national limits and to cap the number of families – and thus children – on a wider scale. This approach is advocated by the European Society of Human Reproduction and Embryology (ESHRE) in a recent position statement. As explained by Professor Lucy Frith at the PET event (and in BioNews 1352b), such limits may have psychosocial benefits for donor-conceived persons, support more meaningful contact between donor siblings and donors, reduce feelings of commodification, and reflect preferences expressed by representatives of donor-conceived persons.

Limiting the number of children

Many people – both lay people and professionals – appear to think that limiting the number of offspring per donor would reduce the number of donor-conceived children born with genetic conditions, making donor conception safer. While this sounds intuitively plausible, it is unfortunately a statistically flawed conclusion.

All donors carry pathogenic variants, just like everyone else. Not all variants are equally severe, and many can remain unexpressed and thus undetected for generations. A stricter limit on families per donor means that a wider range of conditions may appear among donor-conceived persons, because different donors carry different variants, but it does not mean that fewer donor-conceived people will have a genetic condition.

This can be compared to the fear of flying versus driving. Air travel is statistically safer than travelling by car, but as the consequences of a single plane crash are more catastrophic than the consequences of a single car crash, air travel appears more dangerous. Similarly, a single severe pathogenic variant in a donor whose donations were widely used (like the TP53 case) has a much more catastrophic impact than if the same cancer risk had been passed on to only one or two children through other forms of reproduction.

Arguing that fewer donor-conceived persons will be affected by severe genetic conditions when there are fewer children per donor is like arguing that air travel can be made safer by dividing the same number of travellers across more planes. While each individual crash would affect fewer people, the overall number of casualties would not necessarily change.  

There is one important nuance to consider. If no additional donors are recruited, limits on the number of children per donor would reduce the total number of donor-conceived persons, and therefore also the absolute number of donor-conceived children born with genetic conditions. However, this argument can hardly be taken seriously. We would also not claim that the best way to reduce the number of children being born with congenital conditions is abstinence.  

Reducing risks

So what can we do to reduce the risks? First, it is important to recognise that the chance of a donor passing on a pathogenic variant is already significantly lower than a parent passing on a pathogenic variant in most other forms of reproduction. This is because candidate donors undergo family history assessments and DNA screening for common variants, such as those linked to cystic fibrosis or spinal muscular atrophy. Donors with increased risks are refused.

Screening donors for all possible genetic risk may sound attractive, but as we have previously argued here and here, because all people carry pathogenic variants, this would mean that no donor would be approved. Moreover, many variants remain unknown. In the recent case, the donor's variant was rare, and at the time of the donation in 2008, it was not known to increase cancer risk. The donor was healthy, and the variant could not have been detected because it was only present in some sperm cells rather than in blood, for example.

For such cases, it is important that risks are not only detected before donation but that parents of donor children report suspected genetic conditions to the fertility centre where they received treatment. This allows further use of sperm from that donor to be restricted, if necessary, and enables other families with children from the same donor to be informed. In this way, conditions can be identified and treated quickly.

In conclusion, while there are valid arguments for limiting the number of families per donor, preventing genetic conditions in donor-conceived persons is not one of them. Donor conception is already relatively safe in terms of inherited genetic risk, and it can become safer through robust reporting systems and by restricting the use of sperm from donors with known severe pathogenic variants.