Preimplantation Genetic Testing: Barriers to Access

In its first online event of the year, PET (the Progress Educational Trust), with the support of the D'Oyly Carte Charitable Trust, brought together experts to discuss access to and funding for preimplantation genetic testing (PGT). The wide-ranging presentations covered the medical, legal and practical challenges that families seeking PGT may encounter, and potential solutions.

PET director Sarah Norcross provided some historical context and key definitions to help attendees navigate the 'acronym soup' in the field, starting with PGT for monogenic conditions (PGT-M) and PGT for chromosomal structural rearrangements (PGT-SR). Both involve the use of IVF, with subsequent genetic testing and selection of embryos to avoid genetic conditions that could jeopardise a pregnancy or affect the health of a future child.

The first pregnancies following PGT were reported in the journal Nature in 1990. The timing of this announcement – a week ahead of the free vote in the House of Commons on the Human Fertilisation and Embryology (HFE) Bill – was no coincidence. The bill to regulate the use of assisted reproduction technologies in the UK, including provision for PGT, was passed with a substantial majority.

PGT is licensed by the Human Fertilisation and Embryology Authority (HFEA), which to date has approved the use of PGT-M for around 1900 monogenic conditions. Although PGT is authorised for use by the NHS and not subjected to the same 'postcode lottery' as IVF treatment, there are still accessibility issues due to its limited availability across the UK (see BioNews 1234).

The first speaker was Charlotte Tomlinson, consultant general genetic counsellor and clinical genetics PGT lead at Guy's Hospital, London. She explained that PGT involves genetic testing of a few cells removed from an IVF embryo at the blastocyst stage for presence of monogenic or chromosomal conditions. Tomlinson shared the experience of a patient who underwent PGT-M to avoid passing on the X-linked condition Duchenne muscular dystrophy, one of several case studies discussed on the hospital's website.

Tomlinson described the patient journey for couples seeking PGT-M. This starts with an appointment with a genetic counsellor, to discuss reproductive options and eligibility for NHS-funded PGT treatment. Following referral to a PGT centre, couples are assessed to establish whether genetic testing can identify the mutation responsible. In addition a licence may need to be sought from the HFEA if the condition has not been tested for previously. The couple then undergo IVF treatment, and any embryos that reach the blastocyst stage after 5-6 days are tested. Genetic testing can take up to four months, during which time the embryos are kept in frozen storage, with any embryo identified as not having the mutation being eligible for transfer.

Tomlinson emphasised the importance of support from fertility counsellors and a patient support group throughout the process. She finished by outlining the current referral criteria for couples in England seeking NHS-funded PGT-M or PGT-SR. These criteria were last published in 2014, with an update promised in 2018 but still not forthcoming.

The next speaker was Dr Melanie Nana, a clinical research fellow at King's College London and obstetric medicine fellow at St Thomas' Hospital, London. Many women who undergo PGT are themselves affected by a genetic condition, and Dr Nana's talk focused on the management of such patients, with care ideally starting in the preconception period. She presented data from the MBRRACE-UK report (see BioNews 1100 and 1220), which found that more than 50 percent of women who died during pregnancy in 2020-2022 had a pre-existing medical condition. The report also found that in over half of these cases, improvements in care may have made a difference to their outcomes.

Dr Nana highlighted the opportunity for pre-pregnancy counselling during the PGT patient journey, to discuss risks with couples and maximise the chances of having 'a healthy baby born as close to term as possible'. She presented the case of a woman with dilated cardiomyopathy, a condition in which the left ventricle of the heart is enlarged and the heart muscle weakened. A causal genetic mutation had been identified in this patient that could be tested for using PGT. However, as the patient was at significant risk of cardiovascular complications during pregnancy, the team also needed to assess whether she could safely carry a baby conceived in this way as cardiac output increases by 50 percent during pregnancy. The patient opted for PGT followed by surrogacy.

Other prospective PGT patients commonly referred to Dr Nana and her team are those living with Marfan syndrome and cystic fibrosis. In both cases, pre-pregnancy counselling is essential for assessing individual risks of a pregnancy to both mother and baby.

Professor Frances Flinter, trustee at PET and emeritus professor of clinical genetics at King's College London, started her talk by explaining her role as chair of the Statutory Approvals Committee (SAC) of the HFEA. The SAC decides which monogenic conditions are tested for using PGT-M, meeting every month to considering applications for any conditions not yet licensed on an individual basis.

The HFEA grants licences for conditions that comply with certain legal criteria, related to their risk of transmission and seriousness. A list of all monogenic conditions either licensed for PGT-M or under consideration is available on the authority's website. Once licensed by the HFEA, any centre can offer PGT-M for that condition. In contrast, conditions caused by chromosomal structural rearrangements are licensed together as one group, so centres do not have to make individual applications on behalf of couples seeking to undergo PGT-SR.

Professor Flinter highlighted that couples often have direct experience of a condition for which they are seeking PGT-M, perhaps because they are living with it themselves, or have an affected child. She described the detail required for each application form that centres applying for PGT-M licences are required to submit. The centres are also responsible for providing counselling for couples, to discuss their reproductive options as well as the current treatment options available for the condition.

The next speaker was Nick Meade, director of policy at Genetic Alliance UK, an umbrella charity that supports people living with genetic, rare and undiagnosed conditions. Over the last 25 years, only 268 of more than 3000 potential new medicines have been approved and marketed in the EU, with just 104 of these approved for children. Meade explained that while existing treatments such as bone marrow transplants are available for some conditions, the burden and risk of these are often high.

Genetic Alliance UK believes that PGT is often the most appropriate intervention, for people living with rare genetic conditions for which a genetic test is available. Meade described the process for generating the evidence that Genetic Alliance UK provides to the HFEA, to assist with licensing decisions. This involves reaching out to the relevant patient community with a survey and demonstrating the impact of the condition, through quotes from people affected by the same symptoms.

Since 2009, Genetic Alliance UK has submitted 618 statements to the SAC committee. Meade shared, with permission, an example survey response: 'I strongly would not wish my baby to have the limiting condition that I have had... I do not want my child to be judged, to not be able to live independently or follow their dreams due to the restrictions of this condition.'

He concluded by considering the different ways in which the severity of a condition can be felt, including its family and social impact.

The final panel speaker was Diana Perry, founder and chief executive of the Ectodermal Dysplasia Society and mother of two children with ectodermal dysplasia. She provided an overview of barriers to accessing PGT-M from the family's point of view, starting with cost. A single cycle of PGT-M in a private setting can exceed £12,000. The NHS provides up to three cycles of IVF with PGT-M for certain conditions, although if the first attempts are unsuccessful, families are often required to self-fund additional cycles.

Another barrier is geographical location. In 2020 there were 37 PGT-M clinics in London and 24 in the South East of England. However, there were only seven each in Yorkshire, the Humber and the North East, and very few in the South West of England. Travel, accommodation costs and time off work all increase the financial burden on families seeking treatment. Perry explained that the complexity of some genetic conditions can also impact access. For example, the group of ectodermal dysplasia conditions includes more than 180 syndromes, with only 31 licensed for PGT-M. For X-linked hypohidrotic ectodermal dysplasia (XLHED), the testing process can take years, causing additional anxiety for families waiting to proceed with treatment.

For one family seeking PGT-M to avoid passing on XLHED, their journey began in 2022 with a GP referral to NHS genetic services. A year after joining the waiting list, the family received an appointment in January 2024. Testing to confirm the diagnosis took another year, and the family are now on the waiting list for a PGT-M clinic.

Perry called for reforms in genetic healthcare services to reduce waiting times, streamline diagnostic processes and expand access to PGT-M clinics to address increasing demand. She also described promising results for a new in-utero protein therapy in development for XLHED, offering hope and a potential alternative to PGT-M. Perry concluded her talk with a call to action for the NHS to transform its approach, from managing symptoms to eradicating conditions. She emphasised that 'families are not just patients but key stakeholders in pushing forward this evolution of care'.

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PET is grateful to the D'Oyly Carte Charitable Trust for supporting this event.