What Is the Embryo's Special Status in the Clinic?

The first session of the 2024 PET (Progress Educational Trust) Annual Conference – '40 Years after the Warnock Report: What Is the Embryo's Special Status?' – was chaired by Sarah Norcross, director of PET. This session was entitled 'What Is the Embryo's Special Status in the Clinic?', and explored clinical perspectives on the human embryo.

Professor Anneke Lucassen, director of the Centre for Personalised Medicine at the University of Oxford, gave an inspiring opening presentation – 'Embryo Genomes: What Is Meaningful Knowledge?' – which took us back to the basics of the human genome.

She discussed how exciting the future of genetics is, and suggested that the nature of personalised medical care may change substantially if genomic technology is applied appropriately. For an individual with a disease or with a family with a disorder, assessing the genome can give clues to the genetic contribution or indeed help to make a diagnosis.

Polygenic risk scores may help to pick out target populations for health advice in relation to more common disorders. However, Professor Lucassen cautioned us that diagnosis is different from screening or prediction, and argued that polygenic scores are of no value in assessing embryos for future health or any other characteristic.

Professor Lucassen concluded that while genetic testing can be invaluable in personalising care for individuals where diagnosis of disease is possible, the widespread expectation that sequencing the genome of a healthy individual (or embryo) can predict health, disease or any other attribute is misplaced. The predictive power of whole genome sequencing is not much different from tossing a coin, she said, explaining that knowing the whole genome sequence of an embryo does not add meaningfully to information about that embryo, and does not distinguish one embryo from another in a helpful way.

Dr Raj Mathur, consultant in reproductive medicine at St Mary's Hospital and at Manchester Fertility, gave the second presentation – 'Storing Up Trouble: Clinical, Ethical and Regulatory Implications of Prolonged Embryo Storage'. He began by discussing the benefits of embryo storage, in particular observing that current practice is safe and successful, and has allowed big improvements in cumulative pregnancy rates – reducing risks of ovarian hyperstimulation syndrome and risks from multiple pregnancy, while helping with fertility preservation.

However, while increasing numbers of embryos are being cryopreserved, the success of treatment with those embryos is also increasing and this is resulting in a stockpile of unused embryos. Dr Mathur described risks arising from this situation. There are logistical challenges in terms of the space and specialist monitoring required, plus moving, auditing and inventory. Moreover, there are significant consent requirements and challenges pertaining to embryo storage, and these constitute regulatory risk for patients and clinics.

It is estimated that there are half a million embryos currently stored in the UK (and many more worldwide). Most embryos are now stored as vitrified blastocysts, with excellent chances for successful transfer during assisted reproduction. These embryos are usually stored in labelled straws in containers within large tanks of liquid nitrogen, requiring specialist premises and management. Dr Mathur hopes that in future, scaled-up storage centres will be automated to mitigate some of the attendant risks.

Informed consent for all eventualities is extremely complex, including asking patients who store embryos for instructions in the event of their incapacity. Dr Mathur explained that this can be a very difficult scenario for someone to contemplate during the course of fertility treatment. It is equally difficult to contemplate other aspects of the use or disposal of embryos in storage, particularly in the event of death of one partner. Obtaining meaningful informed consent in advance, to deal with such eventualities, is not always straightforward.

Fertility patients exhibit a range of attitudes to the status of their embryos, morally and emotionally. Some adopt a pragmatic attitude to decisions about embryo use and disposal, while others find it particularly challenging to choose to allow embryos to perish, and experience grief. Dr Mathur explained that around the world, religious or quasi-religious disposal ceremonies or so-called compassionate transfers are offered to help. However, he noted that paradoxically, patients who feel deeper attachment to embryos may be less likely to donate them to others to 'give them life'.

Dr Valerie Shaikly, founding partner at Fertility Genetics, gave the third presentation – 'Barriers to Benevolence: Navigating the Challenges of Donating Embryos to Research'.

She explained that if the option to donate embryos to research was more widely available, then this would help to mitigate some of the issues raised by Dr Mathur, reducing the number of unused embryos in storage while improving scientific knowledge of human development.

Dr Shaikly explained that although the ability to donate to research already exists in the UK, the opportunity to do so is rarely available to patients, with only one in five clinics offering the service. Couples or individuals with embryos in storage are likely to be contacted on an annual basis by a clinic, to confirm their instructions for ongoing storage or to offer alternatives. This contact is often linked to ongoing billing for storage, which is usually self-funded. Options can include continuing storage, allowing embryos to perish, donating embryos for use in training or research, or donating embryos to others for use in treatment. These annual decisions can be difficult for patients, not least because of financial considerations and because some patients find the idea of allowing embryos to perish overwhelming.

Fertility patients interested in donating their embryos for research sometimes contact licensed research centres directly, explained Dr Shaikly. She pointed out, however, that fertility clinics may not be willing to facilitate transfer. The necessary process of consent is also complex, and this can be a barrier.

Dr Shaikly explored how donating embryos for research could be made easier, and suggested that a starting point could be improving the information available on the website of the Human Fertilisation and Embryology Authority (HFEA). She also explained that, ideally, a national research embryo bank would be established, increasing the number of embryos available for research work (see BioNews 1219, 1243 and 1268). Ad hoc arrangements for transferring embryos from clinics to research centres are logistically and financially difficult, but bulk movement of embryos for research to and from a central store would be more practical.

Finally, Dr Shaikly argued that permissions for research collaboration are currently too restrictive. The HFEA could improve the situation by providing research registration alongside centre registration, and making research priorities a focus of inspection.

The final presentation – 'Managing Embryo Disposition: Policies, Practices and Challenges' – was given by Dr Aisling Ahlström, scientific director at Livio in Gothernburg, Sweden. She described the experience of dealing with the different national requirements of four Nordic countries, highlighting that embryo freeze-thaw survival is now 95 percent, and duration of storage is no longer considered an adverse factor.

Dr Ahlström discussed laboratory issues relating to longer-term embryo storage, including available space and continuity/compatibility of IT inheritance, with administrative systems needing to be maintained and updated without error. She also highlighted that freezing technologies, including equipment, have changed over the years and differ between labs. This can make transporting embryos problematic. Finally, Dr Ahlström discussed the hazards of complex informed consent forms, and the fact that patients may be completing these while their focus is elsewhere.

Dr Ahlström had experience of centres in Sweden, Norway, Denmark and Iceland, and discussed cross-border working. She explained that cross-border movement of embryos was often motivated by different local regulatory requirements, such as differences between the permitted age of female patients or the permitted duration of storage. She recognised that patients had different attitudes and wanted different choices, but acknowledged that cross-border working can make it difficult to have continual personal dialogue.

Rounding off her presentation, Dr Ahlström called for proactive policymaking, standardisation of good practice and the consideration of external providers of storage facilities.

The Q&A session that followed was stimulating and varied, with many contributors expressing sympathy for patients' dilemmas and clinics' challenges. There were questions about the management of expectations in relation to the use and disposal of unused embryos, and the need for counselling. Finally, there was a reminder that prediction from embryo screening is limited not just by technology, but by biology.

PET would like to thank the sponsor of this session (the British Fertility Society) and the other sponsors of its conference (the Anne McLaren Memorial Trust Fund, Burgess Mee, the European Society of Human Reproduction and Embryology, Born Donor Bank, Merck, Ovoria Egg Bank, Theramex, TMRW Life Sciences and the Institute of Medical Ethics).