HFEA Chair, Julia Chain, on what genomics mean for fertility treatment

Expanded carrier screening

Casting our minds back to the first session of the day and we started with expanded carrier screening, or ECS.

There is currently no national guidance in the UK specific to ECS and, to date, it has played a relatively minor role in fertility treatment as we do not require UK fertility clinics to carry out this type of screening – nor are gamete donors required to have it.

Several of today’s speakers mooted the question as to whether ECS should be used more widely. As Dr Heidi Mertes put it, just because it’s possible, this does not generate a “moral duty” to rule out all possible genetic “defects” in future children. And there are also risks to consider, including the one flagged by Professor Jackson Kirman Brown: that it only serves to reduce the pool of available donors.

PGT-A as an add-on

Moving on to PGT-A as an add-on. In the USA, use of PGT-A has become almost routine, and here in the UK it’s on the up as well - with our National Patient Survey 2024 finding that the use of PGT-A has nearly doubled from 7% in 2021 to 13% in 2024.

There’s no doubt that the topic of PGT-A has always been, and continues to be, a polarising one that sparks many a debate. Advocates argue that it increases the chance of a pregnancy, while critics worry that it leads to too many embryos being discarded that would otherwise lead to a pregnancy.

From our perspective, we classify PGT-A as an add-on, not because we are intrinsically opposed to its use, but because it is not an essential element of fertility treatment.

Our rating system has five ratings that indicate whether a treatment add-on is effective at improving treatment outcomes for someone undergoing fertility treatment, according to high-quality evidence from studies and RCTs – such as the ones Professor Karen Sermon highlighted in her presentation earlier.

As a reminder, our expert committee has assessed PGT-A as:

• Red for improving the chances of having a baby. Red means there are potential safety concerns and/or, on balance, findings from moderate/high quality evidence shows that this add-on may reduce treatment effectiveness.
• Green for reducing the chances of miscarriage for most fertility patients. Green means that, on balance, findings from high quality evidence shows this add-on is effective at improving the treatment outcome. However, reducing the chance of miscarriage may not necessarily increase the chances of having a baby.
• Grey for these outcomes in older women. This is because there is insufficient evidence investigating the effectiveness of using PGT-A in older women.

PGT

Staying with the subject of pre-implantation genetic testing for Alan Handyside’s keynote speech on its origins – which was truly fascinating.

What struck me is the speed of development in recent years, technology is fast-moving, and test are now more accurate, less expensive, and quicker than they were previously. Even the name has changed to reflect its progress – what we used to call PGD is now known as PGT-M or PGT-SR.

As a result of these advances, fertility treatment today not only offers a growing number of different family types the option to have their own much-wanted child, it also provides a way for families to avoid passing on serious inherited illnesses.

As many of you will know, the use of PGT here in the UK is overseen by us at the HFEA, after Parliament decided that an embryo can only be tested if the reason for testing satisfies one of the permitted purposes, one of which is whether it carries a serious inherited illness. There’s where our Statutory Approvals Committee (SAC) comes in.

SAC’s job is to decide whether an inherited illness passes that test and can be added to our approved list of conditions. Such is the demand for testing new genetic variants that SAC meets every month to consider applications – with our list currently sitting at more than 1,900 approved serious inherited conditions, and some of them are incredibly rare.

Every time a condition is approved it’s a success story for UK fertility treatment, as it represents a chance that a family will avoid passing on a serious inherited condition to a newborn baby.

However, there is a challenge to face as the legal framework for PGT sits increasingly awkwardly with the way testing is going. The law, written back in 1990, was written for a world in which different technologies were employed to look for chromosomal rearrangements and single gene disorders, now the same technology can be used to look for both, today, testing is often carried out by means of whole genome sequencing. This raises some initial questions: can additional findings be sought, what to do with any additional findings and, also, in what way can a patient give informed consent to a test of many conditions? These are questions we’re receiving more and more regularly from our licensed clinics and we’re planning to publish guidance next year.

Polygenic risk scores/ Pre-implantation genetic testing for polygenic disease (PGT-P)

PGT-P is another genetic test that’s increasingly being offered in the USA and marks a fundamental break with previous testing technologies in both its methods and intended use. The main difference I want to highlight is that PGT-P is not the search for the presence of a condition, but instead the assessment of its likelihood – often through the supposed interplay of different findings, with its biggest supporters claiming it can identify embryos that are likely to lead to people with a higher IQ, for example.

This raises all sorts of issues that we don’t have time to delve back into now, but I feel were well-debated by our speakers today, but let me simply say that PGT-P is unlawful for use in the UK, as it cannot be used to identify a particular risk and therefore does not meet a permitted purpose for testing set out in the Human Fertilisation and Embryology Act.

Current evidence suggests that PGT-P is not sufficiently advanced for application in embryo testing, with scores giving information relevant to populations rather than individuals. Making healthy lifestyle choices is likely to have a bigger impact on preventing disease than relying on these genetic scores. Screening embryos using PGT-P is also likely to reduce the number of embryos available for transfer and so reducing the chance of having a healthy baby. This is because embryos that would have been healthy at birth may be excluded due to a perceived increased risk of disease which may never develop.

Licensed clinics in the UK are responsible for testing based on what is permitted in the HFE Act and, therefore, should not offer such testing.

Donor conception and genomics

It may be hard to believe that it’s been ten years since the UK became the first country in the world to licence mitochondrial donation treatment to avoid passing the condition to children.

Fast forward to July this year and we welcomed the wonderful news that mitochondrial donation treatment has led to eight babies being born. For the first time, families with severe inherited mitochondrial illness have the possibility of a healthy child - although it’s still early days.

However, it’s worth remembering that only people who are at a very high risk of passing a serious mitochondrial disease onto their children are eligible for this treatment in the UK. The HFEA will continue to oversee the safe use of mitochondrial donation treatment and assess each application as families come through the programme.

Finally, we ended with Debbie Kennett’s presentation on donor anonymity and I want to say that I very much recognise the picture she painted. The easy availability of direct-to-consumer DNA testing has, put bluntly, driven a coach and horses through our notions of anonymity and undermines the integrity of the current legislative framework.

That’s why we included a recommendation in our 2023 proposals to modernise fertility law to enable families to access identifiable information about their donor from the birth of their child. However, any change to the law is a decision for Government and, ultimately, Parliament and should uphold the existing principles already set out.

Conclusion

So, what does genomics mean for fertility treatment?

I think it’s clear from today’s event that developments in genomics and our understanding of serious conditions is already having an impact on some aspects of fertility treatment – from the eight healthy babies born from mitochondrial donation treatment through to the 1,900+ serious inherited conditions that have been licensed by our SAC so far, as well as the ongoing conversations around donor anonymity and the law.

As scientific advances continue to be made, that impact is only likely to grow, and it’s down to us to wrestle with the policy choices that will follow as a result. I, for one, look forward to that debate.