Call for Stricter Regulations on Sperm Donation Following Genetic Health Risks

Recent findings concerning a sperm donor who unknowingly carried a cancer-linked genetic variant have prompted experts to advocate for more stringent regulations surrounding sperm donation. This alarming case highlights the challenges faced in the regulation of gamete donations across Europe.

At the European Society of Human Genetics annual conference, Dr. Edwige Kasper, a researcher specializing in genetic cancer predisposition at Rouen University Hospital, emphasized that the lack of cohesive cross-border regulations can lead to the misuse of gametes, raising concerns about inbreeding and the spread of hereditary diseases.

In late 2023, Dr. Kasper's laboratory was alerted by a French clinician regarding a patient who had received a notification from a European sperm bank. The notice warned of a 'variant of unknown significance' discovered in the TP53 gene in nearly half of the donor's sperm samples. The TP53 gene is crucial for producing a protein that suppresses tumors, preventing cells from growing uncontrollably.

The notification stated that while the donor was reported to be in good health, there was a potential risk for his biological children to develop Li-Fraumeni syndrome, a rare genetic disorder that increases the likelihood of various cancers. Tragically, some children conceived with this donor's gametes had already been diagnosed with leukemia and non-Hodgkin's lymphoma, leading to a halt in the use of his sperm.

Dr. Kasper conducted a thorough analysis of the genetic variant through population databases and functional tests, concluding that it was likely cancer-causing and that the children born from this donor should undergo genetic counseling.

Following discussions with French networks, the alarming cases were presented at a 2024 meeting of the European Reference Network focused on genetic tumor risk syndromes. Concurrently, geneticists and pediatric specialists across Europe began investigating similar cases, leading to the testing of 67 children from 46 families in eight countries, with the variant identified in 23 of these children and cancer diagnoses confirmed in ten.

Li-Fraumeni syndrome, associated with mutations in the TP53 gene, is one of the most severe inherited cancer predispositions, characterized by a wide range of tumors developing at an early age. Children affected by this syndrome, born between 2008 and 2015, are now under close observation to catch any early signs of cancer.

The monitoring protocol is extensive, including whole-body MRI scans, brain MRI scans, abdominal ultrasounds, and specialist clinical examinations. Although this approach can be heavy and stressful for those involved, it has proven effective in enabling early tumor detection, which significantly improves survival chances.

Dr. Kasper noted that while the genetic variant in question may have been undetectable in 2008 when the donor began contributing sperm, there are many areas for improvement in the regulatory framework. She mentioned that some fertility clinics have withheld information regarding the genetic variant from families, opting instead to conduct tests in their own laboratories. This lack of uniform regulation across Europe presents significant challenges.

Currently, sperm donation laws vary significantly from one European country to another. Private sperm banks often restrict a single donor's contributions to a limited number of families worldwide. For instance, French law limits the number of births per donor to ten, while in Germany and Denmark, the cap can be set at 15 births. In the UK, a donor may be used for up to 12 families. Such discrepancies could result in a considerable number of births stemming from a single donor across European borders.

Dr. Kasper advises parents in France to pursue medically assisted reproduction within the country, where donation is anonymous, voluntary, and without cost. This system may address the gap between parental demands and resource availability more safely.

In France, gamete donation is closely medically supervised for both donors and recipients. Any suspected genetic disorders must be reported and investigated immediately. Each donor is limited to a maximum of ten births nationally, and the import or export of gametes requires approval from the Agence de la Biomédecine.

Dr. Kasper cautioned that although this specific case is rare, similar situations could arise in the future, noting that gonadal mosaicism has previously been documented in sperm donors concerning neurofibromatosis type 1. She calls for comprehensive regulatory measures at the European level to prevent future occurrences and to establish limits on the number of offspring conceived from a single donor.

Professor Alexandre Reymond, chair of the conference, underscored the necessity for broader oversight, stating that while current assisted reproduction legislations do not extend across borders, the lessons learned in one country can benefit future parents globally.