Donor Conception and Genomics: Sperm, Eggs, Embryos, Mitochondria

The fifth session of the 2025 PET (Progress Educational Trust) Annual Conference – 'Donor Conception and Genomics: Sperm, Eggs, Embryos, Mitochondria' – brought together clinical, scientific and ethical perspectives on the relationship between genomics and donor conception. It was chaired by Professor Karen Sermon – former chair of the European Society of Human Reproduction and Embryology (ESHRE) – who had given a presentation at another conference session earlier in the day (see BioNews 1320a).

The opening presentation – 'How Far Is Too Far? Navigating Reasonable Limits in Genetic Screening of Gamete Donors' – was given by Professor Stéphane Viville, founder of the Genetics of Infertility Unit at the University Hospitals of Strasbourg, France. Professor Viville explored the medical foundations and ethical dilemmas of gamete donation, beginning with the following definitions of key concepts.

• Donor conception is where a child is conceived with donated sperm and/or donated eggs, or where a child results from the transfer of a donated embryo. (The presentation that followed explored the additional possibility of conveiving a child with donated mitochondria.)
• Genetic conditions arise from a person's DNA, and – depending on the condition – can be inherited in different ways from one's parents (and/or from a donor, if a person is donor-conceived)
• Expanded carrier screening (ECS) is an approach to testing in which prospective parents (and/or gamete donors) are tested prior to conception, to check whether they (unknowingly) carry gene variants that could potentially lead to ill health in future children (see BioNews 1320b).

Professor Viville proceeded to discuss Mackenzie's Mission, a national carrier screening study in Australia, which evaluated the feasibility, acceptability, and outcomes of ECS. The largest study of its kind, it enrolled more than 10,000 couples and tested 1300 genes covering roughly 750 conditions. The study identified 1.9 percent of couples as being at risk of having an affected child, rising to 21.7 percent in consanguineous couples. 

Turning to donor screening, Professor Viville observed that donors already undergo extensive testing for infectious diseases (among other things). He argued that ECS could be a way to enhance donor-recipient matching and improve informed decisionmaking, but emphasised that screening can never eliminate all residual risk, and that the welfare of future children must remain a central concern.

Professor Viville concluded by highlighting the ethical challenges involved in screening donors, discussing the importance of nondirective offers, informed consent and proportionality. He said that overly broad screening risks coercion, psychological harm and unrealistic expectations of there being such a thing as a perfect donor.

The second speaker was Professor Dagan Wells, director of Juno Genetics and professor of reproductive genetics at the University of Oxford. His presentation was entitled 'Mitochondrial Replacement Therapies for Avoidance of Disease and Treatment of Infertility', and focused on the different ways that mitochondrial donation can address either mitochondrial disease or infertility.

Mitochondria are tiny structures that exist in almost all the cells in a human body, and that contain their own DNA in the form of a circular chromosome. There are multiple copies of this circular chromosome within each individual mitochondrion, and there can be hundreds or even thousands of mitochondria within a single human cell.

Professor Wells explained that inherited mutations in mitochondrial DNA (mtDNA) can cause debilitating, maternally inherited conditions for which there is no treatment. While preimplantation genetic testing for mitochondrial disorders can help to avoid this in certain circumstances, it is not always a reliable approach, and there are some situations where it cannot help at all. Professor Wells provided an overview of this year's news that eight healthy children with donated mitochondria had been born in the UK (see BioNews 1298a, 1298b, 1310 and 1313).

Professor Wells then proceeded to discuss the use of mitochondrial donation as an experimental treatment for (certain forms of) infertility, including a pilot study with promising results that he had conducted together with colleagues in Greece, Spain and the USA (see BioNews 984 and 995). Later in the day, Julia Chain – chair of the UK fertility regulator, the Human Fertilisation and Embryology Authority (HFEA) – reminded us that this particular application of mitochondrial donation is not currently permitted within the UK (see BioNews 1320c).

The next two presentations had a greater focus upon ethical and societal implications. The third presentation – entitled 'Donor Conception and Genomics: Ethical Questions in Day-to-Day Practice' – was delivered by Professor Michael Parker, director of the Ethox Centre and of the Global Health Bioethics Network.

Professor Parker began by presenting us with various case studies, which illustrated the ethical and regulatory complexity of genetic testing in relation to donor conception. In one instance, a woman diagnosed with breast cancer discovered that she carried a paternally inherited BRCA mutation (meaning that she had always been at elevated risk of breast cancer), and then discovered subsequently that her father (from whom she may have inherited the mutation) had been a sperm donor. The case raised difficult questions about anonymity, recontacting donors and responsibilities to genetic relatives.

Professor Parker then focused on a case concerning a child conceived via egg donation, who developed serious health problems and was eligible for genomic trio testing. Such testing required a DNA sample from the egg donor, who had previously declined to consent to be recontacted for genetic findings or future research. The fertility clinic therefore refused to contact her, leaving the child and the parents without access to potentially valuable diagnostic information.

Professor Parker explored whether the donor's original decision not to be recontacted applied to this unanticipated situation, and also whether the potential seriousness of harm to the child could justify overriding that decision in any case. The matter went to court, where Mrs Justice Theis said in her judgment that the clinic was permitted – but not obliged – to contact the donor. In the end, the donor was indeed contacted, and agreed to provide a DNA sample. Professor Parker highlighted how this outcome exposed certain weaknesses in the system, and underscored the need for clearer guidance.

Such cases are explored regularly by the GenEthics Forum, a national forum – founded by Professor Parker and colleagues – that discusses ethical and practical problems encountered in the working lives of UK genetics practitioners. Professor Parker concluded by discussing some of the key lessons he had learned, from more than two decades of working with the Forum.

• Ethical problems are rarely resolved by law alone.
• Ethical judgement is a core part of genetic and reproductive medicine.
• Ethical judgement is best developed through discussion, communication and shared professional experience. 

The session's final presentation was by genetic genealogist Debbie Kennett, and was entitled 'Does Consumer DNA Testing Spell the End of Donor Anonymity?'.

Kennett examined the rapid growth of direct-to-consumer genetic testing, which has all but ended the possibility of anonymous gamete donation. Companies that host databases containing tens of millions of users enable various parties involved in donor conception – donors, donor-conceived people, and the genetic half-siblings of donor-conceived people – to identify one another, without one another's knowledge or consent.

Kennett discussed high-profile podcasts, Netflix docuseries and other media coverage from recent years, which have brought this situation to widespread public attention (see BioNews 1048, 1075, 1124, 1146, 1147, 1210, 1215, 1228, 1257 and 1260). She explained that even if someone has not consented to join a genetic testing service, or to be included on a database, there are still ways that they can be identified via genetic testing (see BioNews 849, 939, 1002, 1003 and 1009).

Modern tests can distinguish between maternal and paternal ancestry, estimate the degree and nature of relatedness between two people, and provide highly detailed results. While current databases are skewed towards populations in Europe and the USA, coverage continues to expand globally.

A lively question-and-answer session followed the four presentations. One question prompted Kennett to clarify that mitochondrial DNA testing can be used to trace maternal ancestry, while Y chromosome testing can be used to trace paternal ancestry. Other questions concerned how donor-conceived people can come to terms with knowing little about their biological origins, and – conversely – how donors who thought they had donated anonymously can come to terms with the possibility that they (and/or their own children) might be identified, and contacted, by donor-conceived relatives.

Professor Parker noted that there are no easy answers to such questions, and Kennett emphasised an important distinction – people may have a right to knowledge about their biological relatives, but that does not mean they have a right to a relationship with those relatives.  Overall, the session highlighted how genomics and donor conception are reshaping one another in profound and often irreversible ways. This is creating new possibilities, while also giving rise to ethical challenges that deserve collective reflection. 

---

PET would like to thank the sponsors of this session (ESHRE) and the other sponsors of its conference (the British Fertility Society, PRECAS, Remaking Fertility, the Adelphi Genetics Forum, the Anne McLaren Memorial Trust Fund, Born Donor Bank, CooperSurgical, Ferring Pharmaceuticals, Merck, Salve, Theramex, Xytex, Juno Genetics and the Institute of Medical Ethics).