Protecting future fertility is becoming a key driver in the treatment of childhood cancers, as survival rates climb beyond 80 per cent.
“Until recently, children’s cancer treatment had been solely focused on ensuring patients’ survival,” explains fertility expert Dr Yasmin Jayasinghe.
But these days, most children and adolescents diagnosed with cancer will survive, meaning that fertility is an increasingly important consideration in their treatment.
This is especially so given the toxicity of certain types of chemotherapy, as well as the debilitating effects of other treatments such as radiotherapy, and even the surgical removal of reproductive organs.
“Fertility . . . is very meaningful to survivors,” says Dr Jayasinghe, a paediatric and adolescent gynaecologist, who heads the fertility preservation taskforce at The Royal Melbourne Hospital. “It’s now an international standard of care that fertility be discussed in all people receiving any kind of treatment that can impact on the function of the gonads.”
Yet, child cancer patients pose a unique challenge when it comes to fertility preservation. Sperm and egg collection procedures – widely available among adults – aren’t viable in pre-pubertal children.
The collection of testicular or ovarian tissue that can be frozen and stored for possible later use is the only option available to children at high risk of impaired fertility after cancer treatment.
However, such procedures are still in their infancy and are considered experimental.
“The [tissue collection] surgery itself isn’t experimental,” Dr Jayasinghe is quick to point out. “We know what to do, we know how to do it, and what the complications are. It’s low risk and unlikely to cause any major complications.
“What we don’t know is what is possible with that tissue in the future and that’s where the research is being done at the moment.”
Dr Jayasinghe says the considerable “lag time” between tissue collection in childhood and re-transplantation in adulthood is the main reason researchers lack necessary safety and efficacy data.
“At this stage I’m not aware that any child has attempted to have their tissue used in order to initiate pregnancy,” Dr Jayasinghe says. “It may be another 10, 20 or even 30 years before a young patient we see today might consider childbearing.”
Associate Professor Kate Stern, the head of fertility preservation at Melbourne IVF and The Women’s Hospital, sees research and technology advances as opening up enormous possibilities for tissue preservation.
“We are now testing the tissue and growing tissue outside the human body,” she says.
New research endeavours, such as grafting tissue onto a mouse to check for the resurfacing of cancer cells prior to reinsertion in the body, aim to reduce risk to patients.
In fact, the ‘Paediatric Adolescent and Young Adult Fertility Preservation Taskforce’ (a collaboration of experts from a range of interrelated disciplines) was established to integrate research in this emerging field.
The taskforce of fertility specialists, gynaecologists, oncologists and paediatric service providers work in conjunction with the Royal Children’s and Women’s Hospitals and aims to develop best practice for clinicians.
Currently, no national guidelines exist for clinicians regarding ethical challenges around the issue of consent, and about when or how to offer fertility support.
Dr Jayasinghe says: “We’ve developed our program so we can provide guidelines around how to approach these discussions surrounding fertility, [and make] recommendations for management, so we can provide information and support to clinicians and families.”
Professor Stern agrees that discussions surrounding fertility with children, their families and clinicians are complex but hugely important.
“It’s a vote of confidence in their future,” she says. “It’s a really important part of patient care.”
Importantly, Dr Jayasinghe describes the preservation taskforce as an “intellectual exchange” where collaboration is critical “in order to develop and track more long term data and potential success of tissue transplants leading to pregnancy.”
An embryologist working in the field also says a lack of collaboration and understanding among specialists can sometimes mean patients don’t always know their fertility options.
“It has been accepted that, in exchange for your life, you need to forego your fertility,” the embryologist says. “There are lots of things that people diagnosed with cancer don’t think of when it comes to fertility preservation options. Often, the first thing on their mind is to get immediate treatment, not the preservation of their fertility.”
To date, there has been just one reported birth worldwide from tissue preservation collected from a 14-year-old female before she completed puberty. No births have been recorded from anyone who has had tissue collected before entering puberty.
However, Dr Jayasinghe remains optimistic about a breakthrough.
“We do know that with ovarian tissue, that tissue is able to be stored, it’s able to be put back into the body, [it] has good follicle counts in children, [it] can activate if it’s given a blood supply and produce hormones, and those grafts can last for years before they run out,” she says.
Dr Jayasinghe is resolute about the importance of consistent guidelines and individual patient risk assessments.
“We try and assess the risk of the impact on fertility of the treatment,” says Dr Jayasinghe. “We look at the type of treatment that is to be administered, the dose, and the pubertal development of the young person. All of those factors contribute to the actual impact on fertility . . . and we try and estimate the impact.
“In terms of doing any kind of invasive procedure, we more often tend to do them for young patients at high risk of infertility, rather than low risk.
“The hope is that future pregnancies can occur successfully and safely from the use of frozen ovarian tissue transplants. We’re cautiously optimistic that our children will be able to have a choice in terms of using their tissue in the future.”