Restoring Male Fertility After Childhood Cancer

BRUSSELS — The reimplantation of testicular tissue in patients unable to produce sperm after undergoing cancer treatment in childhood has received approval from the ethics committee at the Free University of Brussels, known as the VUB (Vrije Universiteit Brussel).

Cancer treatments like chemotherapy and radiation can affect fertility in patients. In those old enough to have started producing sperm, specimens can be collected before treatment and frozen for use in future IVF treatments. In prepubescent children, however, this is obviously not an option.

Medscape’s MediQuality spoke with Goosens to find out more about her work.

MediQuality: Could you tell us about the preservation of fertility in young children?

Goossens: Our research group has developed, together with Brussels University Hospital, a protocol for the storage of testicular tissue in a special bank. The hospital is currently storing specimens from about 130 patients who underwent cancer treatment during childhood, and an increasing number of centers around the world are following in our footsteps. Testicular tissue from more than 1000 boys has been collected and stored around the world.

MediQuality: What technique are you using?

Goossens: Before applying anything in a clinical setting, we conducted 15 to 20 years of research on animal models. We’ve looked at various ways of reimplanting cells. Initially, we focused on the transplantation of spermatogenesis precursor cells in a suspension that was then injected into the seminiferous tubules to enable them to start producing sperm. Then, around 2010, we moved to another technique, which involved transplanting tissue samples into the testicles. This proved to be much more effective. In animal models, these tissue fragments consistently made it possible to obtain sperm. Since then, other sites suitable for tissue reimplantation were identified, such as the scrotum.

MediQuality: What role is Belgium playing in this field?

Goossens : Brussels University Hospital first stored a patient’s testicular tissue back in 2002. The idea came from research carried out in mice in the 1990s, in which stem cells were transplanted from a fertile mouse to an infertile mouse to study spermatogenesis. Herman Tournaye, MD, PhD, director of the Center for Reproductive Medicine at Brussels University Hospital, who was leading our research group at the time, had the idea to apply this approach to the preservation of fertility, and it proved effective. Other European centers quickly followed suit. This method is also being studied in other parts of the world, particularly in Australia, Israel, and the United States. But Europe is still at the forefront of research in this field and our group is playing a pioneering role.”

MediQuality: What do we know about the effects of cancer treatments on the fertility of young children?

Goossens: When we started our research, around 20 years ago, we only really knew about the effects of chemotherapy and radiation therapy on adult male fertility. After cancer treatment, spermatogenesis often ended completely in these patients. Little was known about the impact on future fertility in young children, and it’s only now that we’re seeing the first data, often 20 years after treatment. What we’re seeing is that fertility recovers spontaneously in some people but not others. There are still very few publications available, and those that do exist often use very recent data from small-scale studies. So more in-depth research is needed now more than ever, but that depends on funding.

MediQuality: How is this research funded?

Goossens: It’s supported by the Research Foundation – Flanders (Fonds Wetenschappelijk Onderzoek – Vlaanderen, or FWO). To determine which projects receive funding, the FWO calls on the patient committee of Stand Up To Cancer (Kom op tegen Kanker). We’ve also received support from the European Union through the Marie Skłodowska-Curie Actions International Training Network “GROWSPERM”, which ran from 2014 to 2018, as part of a collaboration with the main European centers that is still ongoing. Funding for fertility research is never straightforward because it’s not a priority in Europe. It’s always easier when we can make a connection with cancer treatment.

MediQuality: What did the ethics committee’s approval process entail?

Goossens: After success in earlier studies, the ethics committee approved the research group’s proposal to reimplant previously collected and frozen testicular tissue in patients, which should make it possible for the patient to develop sperm cells that can be used in fertility treatments.

Because this will be the first time this type of transplant is performed, we had to submit an application to the ethics committee and set up a clinical trial. It’s a complex application that took us a long time. However, once it was submitted and reviewed, we didn’t have to wait too long for the approval.

MediQuality: When do you expect to conduct the first transplantation?

Goossens: The research group is expecting to perform the first transplant very soon; around ten patients have already undergone fertility testing. Some were found to have sperm and will therefore be able to attempt IVF. Others are infertile, but they aren’t necessarily wanting to start a family. We’re hoping that somehow these young adults might become fertile without treatment, but if that isn’t the case, we’re here to help.

MediQuality: What message would you like to share?

Goossens: It’s very important that primary care physicians and oncologists inform young cancer patients and their parents of the risks associated with cancer treatments and that they refer them to a fertility center.

You can find more information about the work of Goossens’ group and work being conducted at other European centers on the Human Reproduction Open website.

This article originally appeared in French on MediQuality from Medscape.

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