4. Legislative barriers could slow down the development and introduction of IVG

Legislation relating to human reproduction varies widely across jurisdictions and there are a number of current barriers to the development and introduction of IVG.

To understand how human germ cells originate, and to confirm the similarity of laboratory-made gametes to those produced in the human body, it is necessary to research the early stages of human embryo development. However, there are various restrictions on embryo research that are prohibiting scientific progress with IVG.

In countries such as Austria, Germany, Italy and Turkey, there is an outright ban on embryo research. In Canada, Japan, the Netherlands and Spain, while embryo research is allowed, it is illegal to create an embryo for this purpose – only donated IVF embryos can be used, leading to a scarcity of high-quality embryos for research.

In many jurisdictions where embryo research is permitted, a 14-day limit on the cultivation of the embryos applies. It is around the 14-day mark that gastrulation starts. Gastrulation is a critical stage in human embryo development where the primary cell layers are formed and the process of developing organs and tissues begins, including germ cell specification. As a result of the 14-day limit, scientists in many countries cannot investigate germline development. There have been calls to extend the limit to 28-days – the Health Council of the Netherlands, for example, recently made a recommendation to this effect – but so far there haven’t been any changes to the law in those countries that have adopted the 14-day rule.

In response, scientists have been developing Stem Cell Based Embryo Models (SCBEMs), embryo-like structures that mimic the processes that occur in early human embryo development, to investigate, amongst other things, germline development. However, these models raise their own ethical and regulatory issues, which led the International Society for Stem Cell Research (ISSCR) to publish a statement on research with these entities in 2023.

In some countries, IVG is prohibited for use in human reproduction under current legislation. This is the case in the UK because, while IVG is not specifically mentioned, Section 3 of the Human Fertilisation and Embryology Act (as amended in 2008) has definitions of ‘permitted’ sperm, eggs and embryos that exclude IVD gametes and embryos created from those gametes. Only ‘permitted’ embryos and gametes can be lawfully placed in a woman. In other countries, IVG is not accounted for at all in current legislation.

There is also a question of whether the definitions of legal parenthood, in different jurisdictions, will be able to accommodate the new forms of biological family that IVG could enable, and whether bans on surrogacy (for example, in Italy, France, Germany and Norway) will need to be reviewed to ensure equitable access to the benefits of IVG. These bans, for example, could disproportionately disadvantage male same-sex couples who will need to use a surrogate in order to make use of IVG to create their own genetically-related child.

There is, then, an urgent need to review current frameworks to ensure that they are capable of dealing with anticipated developments in IVG technology. Failure to do so could have negative effects such as an increase in patients travelling for treatment to countries where reproductive services are underregulated.

5. IVG raises ethical issues

As with the introduction of any new reproductive biotechnology, IVG raises a number of ethical challenges.

One of the core issues is how to determine when IVG is sufficiently safe for use in the human reproductive context, who should decide this, and how they should decide. Even with extensive pre-clinical and clinical trials, no new technology is ever going to be completely risk-free and so a decision needs to be made about what constitutes an acceptable level of risk and how this acceptability is determined. For example, is it determined comparatively (is the risk higher than in natural reproduction or other alternative ways of becoming a parent?); by delineating an acceptable risk threshold (if the risk is not higher than X% then it is deemed safe); or by proportionality (do the risks/disadvantages outweigh the benefits?)? And what if future users of IVG are prepared to accept a higher level of risk so that they can have a genetically-related child?

There are also risks beyond practical questions of clinical safety, such as the potential for IVG to be misused. Specific concerns include the possibility of using IVG to bring about gamete theft, unwitting parenthood, or inappropriate uses of selective reproduction or genetic modification. The latter is a particularly live issue because, while a combination of genome editing and IVG could potentially avoid some of the off-target effects that are created during cell transformation, it could also enable the extensive genome editing of germ cells for non-medical reasons.

If IVG is, at some point, deemed safe for clinical use, it could have both a medical benefit (enabling those with certain types of infertility to have a genetically-related child); and a social benefit (democratising reproduction to enable groups that were previously excluded from having a genetically-related child to do so). However, this raises a series of further questions. Which uses of the technology should be permitted and why? Who should have access to treatment and how will this be determined? How will it be funded? There are justifiable concerns that access to IVG will be inequitable either because the costs will be prohibitive or because certain groups will be purposely excluded from accessing the technology.

The status of the IVG-created embryo and the welfare of children born using IVG also merits consideration. Are there any moral differences between an IVG embryo, an IVF embryo and an embryo created through biological reproduction and, if so, what are they? Is a child born using IVG any different from a child born via IVF or unassisted conception, and do they have a right to know that they were conceived using IVG and about the origins of the IVD gametes used?

Finally, there is the issue of whether it is right to privilege genetic-relatedness over other types of parent-child relationship and what this could mean for those who choose alternative routes to parenthood, such as donor gametes or adoption. Might the introduction of IVG call into doubt the choices of those who decide that they do not prefer genetically-related offspring?

Tackling the complex ethical challenges raised by IVG requires a plurality of perspectives and it is important that there are opportunities for policy-makers, regulators, academics, scientists and potential users of the technology to be involved in the debate. IVG should not be used for human reproduction until these pressing issues have been properly considered.

6. Engaging with the public about IVG is vital

There is currently a lack of public awareness about IVG research, although some groups have been consulted as part of smaller public engagement initiatives in the Netherlands, UK and US. Anecdotal evidence from these suggests that there is sympathy and support for IVG in some contexts (e.g. as an alternative for infertile couples) but not in others (e.g. for post-menopausal women); and that it is seen as a potentially positive alternative to existing interventions such as egg retrieval and gamete donation.

More work needs to be done to inform people about IVG because if it does become available for use in human reproduction, it could have far-reaching social implications. It is vitally important to engage with the public, to ensure that they are heard, can learn enough so that they can contribute in a meaningful way, and are actively involved in decision-making processes. This is key if there is going to be public trust in the science of IVG and in the regulatory frameworks that will oversee its introduction.

This blog is based on discussions that took place at the IVG Ethics and Policy Symposium on 3rd and 4th June 2024 in Leiden, the Netherlands. The Future of Human Reproduction team would like to thank the panel chairs, speakers and participants for their insightful and thought-provoking contributions.

The Symposium was funded by the UKRI QR Policy Support Fund at Lancaster University.

The full Symposium programme can be found here: IVG Symposium Schedule.