Ten families and counting

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Ten Families and Counting: Time for Global Limits on Donor-Created (Half-) Siblings?
by Dr Thomas Hopkins

The latest event produced by PET (the Progress Educational Trust) focused on the issue of limits on the number of people and families, worldwide, who can be created from the sperm or eggs of the same donor.

Current practice is to limit the number of donor-created families to ten in the UK, although back in 1984 it was a ten-child limit that was originally recommended in the Warnock Report. The limit was intended originally to prevent 'inadvertent incest', and to manage the social and psychological implications of donor conception.

Sarah Norcross, director of PET, opened the event by discussing how circumstances have changed. She highlighted that the Warnock Committee did not envisage a global market for sperm donation, evolving over decades. Different countries have varying regulations and practices, which can complicate the tracking and tracing of donors. Nor was it possible, at the time of the Warnock Report, to trace donors through direct-to-consumer genetic testing.

An ability to trace genetic connections across borders necessitates a careful reevaluation of existing limits and practices. Is having dozens (or even hundreds) of half-siblings a problem?

The first speaker was Professor Jackson Kirkman-Brown, chair of the Association of Reproductive and Clinical Scientists and a professor of reproductive biology at the University of Birmingham. He opened his presentation by illustrating the scale of donor conception: 4100 donor-conceived babies are born annually in the UK, approximately 1 in every 170 births. He highlighted a tripling in children born from donor sperm between 2006 and 2019, a trend largely driven by single patients and same-sex couples seeking donor sperm.

Professor Kirkman-Brown pointed out that donor anonymity is increasingly untenable in the age of widespread genetic testing. Additionally, gametes can now be kept in storage for up to 55 years (see BioNews 1111), potentially resulting in future half-siblings with significant age gaps and related emotional and psychological impacts on children seeking donors who may be deceased.

Professor Kirkman-Brown also pointed out logistical issues, noting that travel from London to central Europe can now be quicker than travel from London to Scotland, making the utility of UK-only family limits questionable. Furthermore, over half of the sperm used in UK clinics is imported, primarily from countries like Denmark and the USA where different rules apply.

He concluded by emphasising the need for better data on the psychological impact of donor conception on children, and called for the Human Fertilisation and Embryology Authority (HFEA) to take a definitive stance and advocate for internationally policed family limits.

Next to speak was Christina Sommerlund, business development manager at Born Donor Bank. She opened her presentation by citing a paper recommending a global limit of 100 families per donor, and described how Born works to a maximum of 75 families per donor, making this very clear on its website. To ensure that this is not exceeded, Born allocates 'pregnancy slots', permitting a recipient to use the same donor for multiple children.

Sommerlund argued that sperm banks should be actively responsible, to make sure that the limits are adhered to. However, she also argued that clinics, donors and recipients share the responsibility for preventing an excessive number of families being created per donor.

She raised an interesting point, regarding the shifting definition of families to highlight the layers of complexity that need to be considered in the regulation of donor limits.  She said that the HFEA's Code of Practice now covers scenarios such as if a female same-sex couple splits up, whether both parties would be allowed to continue using the same donor sperm after separation and whether this counts as one family or two.

The third speaker Kevin Moore shared his personal experience as both a donor-conceived person and as a sperm donor. He described being part of a WhatsApp group with seven half-siblings and their donor, emphasising that finding out about their genetic relationships at different times and through various methods was a complex experience.

Some of the siblings in the group discovered their connections through genetic testing, which came as a surprise to them. Moore reflected that emotional bonds are easier to maintain when the number of siblings is relatively small, and acknowledged that larger numbers could be overwhelming emotionally, particularly when trying to maintain a level of contact with such large groups.

He pointed out the potential challenges posed by cultural and language differences among siblings from different countries, which can complicate relationship-building. Despite these challenges, he noted the rewarding aspects of having a large network of siblings, such as providing mutual support and discussing similar experiences.

The fourth speaker was Dr Astrid Indekeu, a research fellow at the Catholic University of Leuven and who has published research and commentary on kinship, psychosocial challenges and voluntary DNA databases in relation to donor-conceived half-siblings and donors.

Dr Indekeu discussed her findings concerning the psychosocial dynamics of having multiple donor family connections. This included the positive aspects of discovering similarities among donor-conceived siblings, such as shared physical traits and interests.

However, she also highlighted several challenges, including the transition from individual identities to forming a cohesive group. Regulating closeness and distance within the group, and balancing individual needs against group dynamics, are significant hurdles that need to be overcome. She asked how donor-conceived individuals transition from being strangers to forming a sense of belonging within a group. Factors such as resemblance, shared genetics, beliefs, values and humour all play a role.

Dr Indekeu quoted a participant from her research who preferred not to be forced into a group identity based solely on shared DNA, emphasising that group dynamics should evolve naturally and not through any expectation. She also raised the issue of managing expectations within growing groups, noting that some participants feel overwhelmed by the expanding number of siblings, and the realisation that maintaining contact with everyone is not possible.

She concluded by pointing out practical challenges such as language and cultural barriers, and physical distance between half-siblings in a global context. Dr Indekeu stressed that these psychosocial aspects should be actively considered, when setting limits on the number of offspring per donor.

The final presentation was from Dr Grace Halden, co-director of the Centre for Medical and Health Humanities at Birkbeck University of London. She shared her experience as a solo mother using donor sperm, and highlighted the lack of transparency regarding the exportation of sperm after a donor has reached the ten-family limit within the UK. She said that she and other donor recipients were surprised to find out that their donors' profiles had changed, to note that the donor's sperm is unavailable for further UK recipients but is still available for export (see BioNews 1222).

Dr Halden called for clearer communication about the possibility of sperm being exported to create more families after the UK limit is reached, suggesting that this information should be prominently displayed in relevant sections of donor profiles, clinic websites and FAQs. She also suggested that differences between UK limits and global limits should be raised at the point of consultation, and that the possibility of export should be mentioned every time a UK family limit comes up.

She concluded that transparency is crucial, in order for recipients to make informed decisions and manage their expectations about the potential size and distribution of their donor-conceived family network.

A lively question-and-answer session followed, underscoring the complexities and ever evolving nature of donor conception practices in the UK, and the difficulty of establishing global limits. Key themes included the need for continuous review and updates to donor limits, considering global markets and advances in practice. The speaker panel also emphasised the importance of international consensus, better data collection, and addressing the psychosocial impacts on donor-conceived children.

Overall, the event highlighted that while donor conception offers significant benefits to many families, it also presents complex challenges that require careful regulation, ongoing research into the impact on all involved, and – most importantly – regard for to the needs and wellbeing of donor-conceived people.

PET is grateful to the Association of Reproductive and Clinical Scientists for supporting this event.

The next free-to-attend online events from PET will be:

IVF Add-Ons: Building Bridges between Clinics, Regulators and Patients, taking place online next week (on Wednesday 5 June 2024) – register here.
Where Art Meets ART: Creative Exploration of Fertility Research and Treatment, taking place online on Wednesday 12 June 2024 – register here.
News
US senators propose bill to protect IVF access
by Ryan Au

Two republican senators have proposed a bill to protect IVF, after some states' abortion laws created uncertainty.

Following the Alabama Supreme Court's ruling earlier this year that embryos created via IVF are considered children (see BioNews 1228), Senator Ted Cruz of Texas and Senator Katie Britt of Alabama have introduced a bill called the IVF Protection Act that seeks to ensure no state prohibits access to IVF services.

'Families across the US are understandably worried that in vitro fertilisation is under threat', wrote Cruz and Britt in a Wall Street Journal article, adding: 'This is an opportunity to unite on a shared bipartisan commitment to life, family, and personal liberty by protecting access to IVF treatments in every corner of America'.

The issue of access to IVF has arisen following the overturning of Roe v Wade in 2022, which returned the power of regulating abortions to individual states. This triggered a wave of bans and restrictions on abortion in some states, some of which contain language affecting the legal status of human embryos.

The Alabama Supreme Court ruling caused many IVF clinics in Alabama to suspend their services out of fear of prosecution. In response, the Alabama legislature passed a new law to protect fertility clinics from criminal charges (see BioNews 1230).

A previous attempt to protect IVF at a federal level, the Access to Family Building Act introduced by
Democratic Senator Tammy Duckworth of Illinois, sought to establish a federal right to IVF and allow healthcare providers the ability to provide such care without fear of prosecution. This bill was blocked because Republicans saw it as a 'backdoor in broader abortion legislation,' Cruz explained in an interview with Bloomberg.

The proposed IVF Protection Act would not compel any person or organisation to provide IVF services but would make states ineligible to receive some federal healthcare funding if IVF access was banned. Cruz hopes that both parties can agree on this approach:

'Every senator says they support IVF,' said Cruz. 'We should be able to come together 100 to nothing to say we stand with the ability of parents who want to love their kids to bring those children into the world'.

Genetic control of the brain – comprehensive cell maps published
by Dr Paige Mumford

Fifteen studies comprehensively mapping the genes responsible for regulation of activity and development of the brain have been published.

Neurodevelopmental conditions such as autism, and mental illnesses such as schizophrenia are common, yet their underlying mechanisms are poorly understood. The PsychENCODE Consortium is a multi-institutional collaboration funded by the US National Institute of Mental Health (NIMH) aimed at understanding gene regulation's impact on brain function and dysfunction, including what occurs during neuropsychiatric diseases. It published 11 papers in 2018, and this publication of 15 new papers, represents the second phase of the project.

Dr Daniel Geschwind, senior author of one of the studies from the University of California Los Angeles, said: 'This collection of manuscripts from PsychENCODE, both individually and as a package, provides an unprecedented resource for understanding the relationship of disease risk to genetic mechanisms in the brain.'

The studies were published across Science, Science Advances, and Scientific Reports, included characterisation of donated human brain tissue across different brain regions, studied several neuropsychiatric diseases as well as the neurotypical developing human brain, and used standardised methods to create multidimensional maps of gene regulation networks.

In one study published in Science, researchers developed a transcriptomic atlas of the prefrontal cortex from individuals with and without schizophrenia and identified cell type-specific transcriptional changes associated with schizophrenia, revealing that genetic risk variants for schizophrenia predominantly target genes in cells known as excitatory neurons.

For a study on autism, researchers analysed genetic expression in the brain tissues of 66 people, 33 people with autism and 33 controls to better understand the mechanisms underpinning genetic risk factors associated with autism. They discovered known risk genes played a role in regulating transcription of genes associated with stress response in immune cells found in the brain, and synaptic gene expression. Overall they found substantial gene expression changes across 35 different cell types in the brain. Results were published in Science.

Researchers characterised molecular alterations across three different brain regions from individuals with post-traumatic stress disorder and major depressive disorder compared with control subjects, in another study published in Science. They identified brain region-specific molecular differences.

Lastly, researchers presented a new tool called PsychSCREEN, an interactive web-based platform to allow for easy visualisation of the data from diverse brain cell types in individuals with and without mental disorders generated by the PsychENCODE consortium, in a paper in Science Advances.

The director of the NIMH, Dr Joshua Gordon, said: 'These groundbreaking findings advance our understanding of where, how, and when genetic risk contributes to mental disorders such as schizophrenia, post-traumatic stress disorder, and depression... Moreover, the critical resources, shared freely, will help researchers pinpoint genetic variants that are likely to play a causal role in mental illnesses and identify potential molecular targets for new therapeutics.'

Epigenetic reprogramming aids development of human gametes in vitro
by David Cansfield

For the first time, human stem cells that were originally skin cells have been reprogrammed into early-stage sperm and egg precursors.

Published in Nature, by a team of Japanese researchers at Kyoto University, the study describes the method used to produce large quantities of early-stage sperm and egg cells from stem cells by erasing the epigenetic 'memory' that determines which genes are expressed. In future this could help people who are infertile or in same-sex couples to have a biologically-related child.

'Epigenetic reprogramming is key to making the next generation,' said developmental biologist Professor Mitinori Saitou from the Institute for the Advanced Study of Human Biology who led this research.

The team set out to bridge the gap between previous research which was able to grow mouse eggs using stem-cell-like cells generated from skin (see BioNews 1231). Crucial to the team's success was discovering that the addition of a protein called bone morphogenetic protein (BMP2) was essential to promote epigenetic reprogramming. The cells advanced one step further in their development compared to cells in cultures without added BMP2.

'The results of this research are an important milestone in clarifying the mechanism of human germ cell development and the promotion of research on the in vitro development of human germ cells,' the researchers said.

After this epigenetic reprogramming, the cells' development stopped and Professor Saitou acknowledged that there are still further steps to be taken to perfect this process. The researchers also found that in the cells the reprogramming was incomplete. This could have serious consequences if such cells were used for reproduction, highlighting the need for discussion on how to conduct this type of biomedical research safely and ethically.

'This involves many technical problems and ethical questions, and that is still a long way off. But in mice it has already been possible to fertilise an egg cell obtained in this way with a natural sperm cell,' commented Dr Arend Overeem, a stem cell biologist at the Leiden University Medical Centre who was not involved in the study (see BioNews 1104).

Understanding how eggs and sperm develop can provide researchers with insights into some causes of infertility. It also opens up possibilities for creating sperm and egg cells in a lab in future, which could significantly advance reproductive medicine and aid individuals with fertility issues.