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Pioneering the science of hope

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Six years ago a revolutionary technique to restore fertility in women rendered infertile by cancer treatments brought the prospect of life into the darkest of times. Its success - decades in the making - is paving the way to even more breakthroughs.

In 2016 something unprecedented happened. A 33-year-old woman from Edinburgh gave birth to a healthy baby boy.

What set this mother and son apart from the rest of the maternity ward was that she was the first woman in the UK to gave birth after having a section of her ovary re-implanted. Eleven years earlier in a bid to preserve her fertility, she had part of her ovary removed as she underwent the harsh treatment against the cancer in her body. Now cancer-free, she was at last a mother. Since then, more than 200 other children around the world owe their existence to this revolutionary technique.

Developed at the University of Edinburgh, it has opened up other ways for giving people with cancer – even children – the chance to become parents later in life. In doing so, researchers are helping to restore patients’ hopes as well as their bodies.

Until recently, the only option for women to preserve their fertility while undergoing cancer treatment was to freeze and store their eggs and at a later date try to conceive through in vitro fertilisation (IVF) – a common medical procedure where scientists fertilise eggs with sperm outside the body.

But this process is not without its difficulties. Women are required to undertake cycles of hormone injections to stimulate the production of mature eggs, which can cause side effects such as mood swings, nausea, and fatigue. Ovarian stimulation can also mean delaying vital cancer treatment, and there is no guarantee the collected eggs will be viable when a woman wants to use them in the future. Freezing eggs also does nothing to overcome another significant impact of cancer treatment, premature menopause. Nor is it an option for children and adolescents who have not yet reached puberty.

This is where University of Edinburgh scientists come in.

A revolutionary alternative

Nearly three decades after Edinburgh scientists first experimented with transplanting ovarian tissue in sheep, the technique is fast becoming a viable alternative for female cancer patients as young as one-year-old to not only recover their fertility after treatment but also prevent premature menopause.

Professor Evelyn Telfer receives her CBE
Professor Evelyn Telfer receives her CBE

“Women are born with millions of immature eggs, called oocytes, held in a kind of stasis, waiting to grow. There are so many that the female body will only ovulate 0.1 per cent of them during its reproductive lifetime, with the rest destined to die,” says Evelyn Telfer, Professor of Reproductive Biology, who received a CBE (Commander of the Order of the British Empire) in 2021 for services to female reproductive biology.

“Oocyte numbers naturally decline throughout a woman’s lifetime until they reach menopause when they stop having periods and can no longer become pregnant naturally. However, treatments such as chemotherapy and certain genetic conditions can accelerate the process. By removing and storing a small part of a woman’s ovarian tissue before this happens and transplanting it back into their body later, we can enable them to conceive a baby naturally and delay early menopause. This technique also offers girls who undergo cancer treatment before puberty hope of having a biological child in the future.”

The shoulders of giants

Professor Telfer completed her PhD under the supervision of Professor Roger Gosden, who pioneered ovarian transplantation alongside the late Professor David Baird in the early 1990s. In the years since, she has dedicated her research career to continuing this tradition. “With every piece of work, you feel you’re standing on the shoulders of giants,” she says.

Professor Telfer’s research with Professor of Reproductive Science Richard Anderson on ovarian development and close collaboration with clinicians has facilitated the clinical application of the ovarian transplantation technique. The first UK baby born through ovarian transplantation in 2016 was the result of decades of work by Telfer and Anderson’s research groups and by Edinburgh colleagues. It is an effort that continues today through improving tissue storage, thawing and re-implantation methods to optimise the chances of fertility restoration.

In building on this remarkable legacy another Edinburgh researcher, Professor of Developmental Endocrinology and Honorary Consultant Paediatric Endocrinologist Rod Mitchell and a team of cancer doctors, surgeons and researchers, including Consultant Paediatric Oncologist and Honorary Professor Hamish Wallace, launched the UK’s first fertility preservation service for pre-pubertal boys in 2015.

“Whereas women are born with all of their eggs, men don’t begin to make sperm until they go through puberty. So, while it’s well established for an adult male cancer patient to freeze a sample of their sperm, until recently, there was no way for male children and adolescents to preserve their fertility,” explains Professor Mitchell. “By collecting a biopsy of testicular tissue before a young male undergoes treatment, we can preserve cells necessary to make sperm and transplant them back to the patient once they recover and reach reproductive age.”

Although still in its infancy, more than 2,000 boys worldwide have already had their testicular tissue frozen. As these donors reach adulthood, the reproductive science community expects the first transplant back into a patient to take place within the next few years.

The science of hope

Now, Professor Telfer and colleagues have developed a new technology that could revolutionise human fertility once again. After more than a decade of dedicated research to perfect a method of stimulating ovarian tissue and growing immature eggs outside the body, they have begun trials in sheep to test its safety. This in vitro growth (IVG) technology could also pave the way to developing new eggs from stem cells in the lab.

“The major limitation of the current method of collecting ovarian tissue is that it cannot always be transplanted back to the patient as it can contain the very cancer cells they have overcome,” Professor Telfer says. “Growing immature eggs from these biopsies outside of the body could offer cancer patients the hope of carrying children. It could also offer women with fertility challenges an alternative to conventional IVF and would particularly benefit pre-pubertal girls whose only option is currently transplantation.”

Dr Rod Mitchell removing a rack of clinical human tissue from the liquid nitrogen cryostorage tank.
Professor Rod Mitchell removing a rack of clinical human tissue from the liquid nitrogen cryostorage tank

Additionally, this technology could enable transgender people who have undergone gender reassignment and had their ovaries or testicles removed to have a child using their eggs or sperm. However, Professors Telfer and Mitchell stress that the science is still highly experimental, and there may be people for whom it will not work, even when it is eventually proven safe and effective.

“It may be impossible to use this technology to help people who have conditions associated with abnormal development of female or male reproductive tissues, for example,” Professor Mitchell cautions. “Nonetheless, in the future – although we cannot say for certain how distant – we hope that stem cell research may enable us to produce reproductive cells from other types of cells in the body to support even more people to have biological children. But for now, we have an ethical responsibility to be realistic about where the science is and how we can clinically apply it.”

The weight of responsibility

The moral magnitude of this innovative work is never far from Professor Telfer’s mind either. “The fact that clinics are now offering young, healthy women the opportunity to store their ovarian tissue with the idea of transplanting it back in their mid to late 40s to delay the menopause is troubling.”

“It’s also really tough to tell family members, particularly parents of young cancer patients, that they must consent to us disposing of the tissue samples or donating them to research if the patient passes away”, Professor Mitchell continues. “But it is the legal and ethically right thing to do.”

Still, the Professors agree that these challenging situations pale into insignificance compared to the joy and sense of purpose they gain from helping people. Summing up how she feels about her work, Professor Telfer is emphatic. “I love it,” she says. “Seeing people and the impact our research can have on their lives gets to you on a deeply human level.”

“The conversations I have with cancer patients and their families, especially parents of children, about fertility preservation might be the most positive talks they have during such a difficult and devastating time,” Professor Mitchell adds. “I wake up each morning thinking about the day when we’ll have the solution to help even more children who otherwise could not become biological parents in the future.”

Picture credits: baby – iStock; cryopreservation – Morsa Images/Getty;