Fertility treatment regulation and embryo research

The case for change 

Informed consent is one of the most important principles in healthcare. It is central to fertility treatment and clinic staff are required by law to obtain properly informed written consent from their patients before they store or use their sperm, eggs, or embryos.

The law relating to consent in fertility treatment is complex, particularly in cases involving donation or surrogacy. Consent to fertility treatment involves more than one person, and needs patients to consider potentially challenging scenarios, including making decisions about what might happen in the future to their gametes and any embryos in the event of their death (or mental incapacity). The conversation between clinic and patient is therefore crucial in ensuring consent is appropriately informed. 

When consent is taken well the current rules provide certainty for all involved. But those rules are complex and both clinics and patients report difficulties with obtaining properly informed consent. In some cases, poorly taken fertility consents have had to be resolved by the courts which can be upsetting, time consuming and expensive.

This survey is an opportunity to consider whether there are ways of streamlining consent without giving rise to greater costs to the patient or compromising on certainty for all involved in treatment.

It is also an opportunity to seek views on ways in which fertility patient data can better be shared among medical professionals to ensure safer care and to improve the provision of embryos for research.

Consent to research

Patients who do not use all their embryos for their own treatment have the option to donate them to specific research projects. Donated embryos are crucial to enable scientists to do research, including the development of new treatments that may help fertility patients.

Current situation

The Act currently requires consent to the use of embryos in research to be donated to specific named projects. This makes it difficult to use research embryos efficiently through initiatives like research embryo banking.

Issues 

Ensuring that there are enough suitable embryos available for research

Some patients will not want to donate embryos that they do not use in treatment to research.  Others may place a lot of importance on being able to do so. Because the current system means any embryos donated have to be suited to the needs of the specific project(s) that their clinic has links to, not all embryos will be suitable, or, some clinics may not have links to any projects for embryo donation.

There is also considerable variation in embryo donation consent rates at clinics, which suggests that while some clinics may be actively promoting research projects to patients, others may not be discussing the option of research donation with patients fully. This may be in part because not every clinic has links to an actively recruiting research project, or to any research project. Overall, these factors can mean that licensed and ethically-approved research projects may lack access to a timely supply of suitable embryos, and that patients who would like to donate their embryos to research are not always able to do so.

Proposals for change

A generic consent to research option should be introduced

Allowing for broader generic consent to research would enable patients to donate to a research bank to store embryos, whether or not their clinic is currently linked to any research projects itself. The research embryo bank could then allocate the stored embryos to a suitable research project(s) when needed, in line with the patients’ consent given to the research embryo bank. This could improve the timely supply of available embryos for research projects and allow more patients who wish to do so to support research. It would make it easier for patients whose clinics do not have links with research projects to donate their embryos to research if they wish to do so.

Some patients will welcome the opportunity to donate embryos to any research project. Others would only want to donate to a project that resonates with them personally. Patients should continue to be allowed to donate their embryos directly to specific research projects only if that is their preference.

The case for change

The Act has provided a robust but flexible framework that has helped to generate public trust in a sometimes-contested area of scientific and clinical work. Regulation has in turn created conditions where innovation can more easily flourish.

However, demand for new treatments continues. Patients’ expectations of treatment possibilities have risen, partly due to the increase in self-funded treatment and the internet enabling wider access to information. 

The link between fertility treatments and advances in genetics and genomics offers hope for families affected by serious genetic conditions. In future these may present prospective parents with new reproductive options.

Global research in these areas continues at pace and is now (in places) pushing against, or going beyond, the boundaries of what would be legally permitted in the UK. That alone does not mean that the Act should be changed to accommodate such new scientific developments, but it does suggest that the Act should be future proofed so that it is better able to respond and adapt to innovation. 

How regulation can best support innovation

Changes in the practice of the regulation of new technologies could support the earlier introduction of innovation in the fertility sector.

Current situation

Regulating emerging techniques or technologies, or new uses of established techniques or technologies, requires a balance to be struck between what is written in law and what is subject to regulatory discretion. At present, the law is ambiguous as to the circumstances in which the HFEA is able to approve new processes for use in a clinic, especially where more clinical evidence may be required to establish their efficacy.

Issues 

The authorisation of licences for novel processes for use in treatment risks making the barrier to entry too high

Currently, the HFEA must assess whether a novel process is “necessary or desirable” prior to authorisation for use in treatment. But as with any new development, the scientific data alone cannot be conclusive without clinical evidence. Where clinical evidence is not yet available (for example, from trials in other jurisdictions), it can be hard for the HFEA to determine whether a process will achieve the stated aims in practice such as to make it ‘desirable’. It would benefit patients if the law explicitly provided for the HFEA to pilot novel processes for a trial period, with appropriate controls and conditions available to the HFEA, if the initial promise is not demonstrated in practice.

Proposals for change

That the Act better encourages innovation

One way of enabling this approach is through the use of trials or regulatory ‘sandboxes’, which are a flexible approach to regulation increasingly used by regulators to encourage innovation while minimising risks. Sandboxes have been described as ‘controlled experiments in which new products, services, or ways of doing things can be placed into a real-world environment’. Sandboxes allow regulators to place conditions on those conducting a newly approved process (or a process which is being assessed for approval), to ensure that it is only used in a limited, specific, monitored setting. Sandboxes build in review points to examine risk, allowing for regulatory intervention if a new process is not shown to be sufficiently safe and effective in practice. The sandbox rules usually involve working within what are effectively research principles, but as determined by the regulator, rather than being formally regulated as research. 

An express statutory power to establish regulatory sandboxes, with a lower evidential threshold than is currently required for the full approval of a novel process, could provide the HFEA with greater flexibility to authorise relevant licensed centres to pilot innovative processes.  This would be subject to effective safeguards, including specific restrictions, monitoring and reporting requirements,  post-authorisation controls and, where appropriate, express mechanisms to swiftly amend, suspend or revoke the relevant authorisation. 

Sandboxes would not be appropriate for all innovations, for example those presenting unacceptable safety risks to patients.

Improving the HFEA’s ability to handle rapidly changing developments in science

The Act sets out several significant limitations on scientific research and possible future assisted reproductive technologies. At present, the entire Act would need to be re-opened to enable certain research or new treatment and it may be possible to design a new model that is more flexible but better maintains the social consensus over time.

Current situation

The restrictions in the Act reflect the social consensus when it was written. Over 30 years on, there may be a case for re-examining elements of that consensus, or recasting the Act so that it is better able to adapt to scientific developments over time.

Issues 

The regulation of certain scientific advances in the Act means that our rules can be slow to adapt, to the detriment of patients

At present the entire Act needs to be re-opened to accommodate some developments in research or clinical practice. The pressure on parliamentary time inevitably means that such change happens rarely, which can restrict the development of novel research and new clinical techniques for use in assisted reproduction. The greater use of secondary legislation in these areas could combine parliamentary oversight with greater flexibility. The aim would be an adaptable regulatory mechanism that could command public support while allowing treatment and research advances to be considered in a more timely way.

Scientific advances are creating new 'categories' of cells such as in vitro-derived gametes, embryo-like entities, and stem-cell based embryo models which are outside the regulatory categories of the Act

The Act currently specifies that research involving gametes and embryos is regulated by the HFEA. However, these new categories of cells, despite their biological similarity to in vivo-derived gametes or embryos, are not currently regulated by the Act. These entities are becoming increasingly similar to bona fide human gametes and embryos, and research on these could offer significant benefits. It may be necessary to consider whether the Act needs to be revised to include these entities, or whether these biological cells should fall under the remit of other regulators. Without a flexible regime, the potential future use of any such developments for patient benefit could be limited, even when the advances in the field establish that their use is ethical and safe.

The Act places limits on the use of human or admixed embryos in research which are now being challenged by scientific developments

At present the Act limits the use of human or admixed embryos in research to 14 days or the appearance of a primitive streak (if earlier). It is now increasingly possible for researchers to keep embryos alive beyond 14 days. If this were permitted in the UK for research purposes, it would lead to improved understanding of early embryo development and the possibility of new or improved treatments. There is a window of very early pregnancy between 14 – 28 days of embryo development which is not currently well understood by any existing permissible route. Increasing the 14-day rule would allow scientists a valuable insight into embryonic development and the study of disease processes, such as miscarriage and the development of congenital abnormalities. Extending this limit has been proposed by some international organisations. For example, the International Society for Stem Cell Research recently proposed guidelines to remove the 14-day limit on embryo research, and replace this with strict case-by-case oversight of any research past 14 days where justified, and after extensive public engagement.

In order to ensure that such a change could be dealt with in a timely, and flexible, manner a new mechanism could be put into law to allow for parliamentary consideration of the 14-day rule in the future, outside of reopening the HFE Act. This could be similar to the regulation making power written into the HFE Act in 2008 that required positive approval of the resulting statutory instrument of the Mitochondrial Regulations of 2015.

The Act does not permit interventions in the nuclear DNA of gametes or embryos for use in reproduction

At present there are significant safety, efficacy, and ethical issues raised by the application of nuclear germline genome editing in treatment. However, in future these issues might be resolved and the technique could have the potential to be offered in treatment to avoid passing on heritable conditions in certain defined circumstances. Amending the Act to specify a principle that in limited instances germline genome editing techniques could be used, subject to further parliamentary approval of regulations setting out principles for what such acceptable uses might be, would be one way forward.

Proposals for change

That the Act is ‘future proofed’

This survey is not the place to resolve whether the current restrictions should change, but whether, given the pace of scientific development in the field, the Act should be ‘future proofed’ so that it could become more accommodating of potential new developments that offer patient benefit. Any change in the regulation of these advances would require wider public debate prior to parliamentary amendment.