March 22, 2019

expert reaction to study looking at fertility preservation, sperm production and birth of live young in macaques

Research published in Science describes how sperm isolated from frozen testicular tissue and grafted back into castrated Rhesus macaques was used to give birth to a healthy macaque baby. The results offer a proof of principle that preserved testicular tissue could aid with fertility concerns of cancer survivors.

Prof Simon Fishel, Founder and President and Head of R&D, and Professor of Human Reproduction, CARE Fertility, said:

“This is truly exciting research!  It particularly excites me personally as it was in 1997 that my colleague, Dr Irfan Aslam, and I took testicular tissue that was removed from a 3-year old boy suffering from mucopolysaccharidosis VI, prior to his chemotherapy, prepared and cryopreserved that tissue for potential use.  This research brings that dream ever closer.

Does the press release accurately reflect the science?

“Yes.

Is this good quality research?  Are the conclusions backed up by solid data?

“A study that concludes with an apparently normal offspring is in itself enough evidence to merit an encouraging if not an exceptional achievement.  Where this differs, for example, in studies that generate gametogenesis in vitro is the full developmental proclivity of the gametes in the outcome of normal offspring, thus indeed providing hope for future clinical therapy.

How does this work fit with the existing evidence?

“It provides further and leading evidence of the opportunity to take immature testicular tissue and, following an autograft, generate fully-formed and fertile spermatozoa.

Have the authors accounted for confounders?

“Hardly relevant in this kind of study, although further studies are needed, for example when dealing with intact testes rather than castrated animals, but this is indeed pointed out by the authors.

Are there important limitations to be aware of?

“As above, plus the animal’s further development, health and its own fertility is important.  To date, complete spermatogenesis has not yet been achieved in humans in the few studies, but this study encouraged continued research to bring this about.

What are the implications in the real world?

“The preservation of fertility for prepubertal boys may yet be realised.

Is there any overspeculation?

“No.”

Dr Rod Mitchell, Reader and Lead for Male Fertility Preservation, MRC Centre for Reproductive Health, University of Edinburgh, said:

“This study represents a major step towards developing treatments for restoring fertility potential in boys facing sterilising cancer treatment.

“Since 2016, we have been freezing and storing testicular tissue in boys at high risk of future infertility as a result of their cancer treatment.  This study provides proof-of-principle for restoring fertility potential in these boys when they reach adulthood.

“This is the first primate study to show that prepubertal testicular tissue can be successfully removed, cryopreserved and re-transplanted, resulting in the development of sperm that can generate a livebirth.

“Whilst translation of this approach into humans will require carefully conducted clinical studies, for young boys currently having their testicular tissue cryopreserved these results provide genuine optimism for their future fertility.”

Prof Daniel Brison, Professor of Clinical Embryology, University of Manchester, said:

“This study represents an important proof of concept showing for the first time in a primate model that cryopreserved testicular tissue from prepubertal boys may in the future be regrafted and give rise to live young.  The study is limited by the fact that only one animal was born, and more extensive pre-clinical studies are now required to address the long term health of individuals conceived by this method.

“Nevertheless this is an exciting and important breakthrough; here at St Mary’s Hospital in Manchester we have been freezing sperm for cancer patients for more than 40 years, and new treatments for young boys are urgently needed.”

Prof Allan Pacey, Professor of Andrology at the University of Sheffield, said:

“This is a really excellent study which takes us one step closer to being able to preserve (and later restore) the fertility of pre-pubertal boys who need to be treated with chemotherapy or radiotherapy for diseases like cancer.

“At present, we are only able to preserve male fertility by freezing sperm, and therefore this isn’t an option for boys younger than about 13 years old because they have not yet gone through puberty and started making any.

“Although many men who were treated for cancer as boys are still fertile, and are able to have their children without medical assistance, there are many that are not and this can be a source of great sadness for them and their partners.

“Currently, the only option available to men who were made infertile through cancer treatment at a young age, and who don’t have any stored sperm, is for them to either use donor sperm, or to adopt, or remain childless.

“This study is a great step forward, but it is important to remember that before we could attempt to use it in humans, further research would be needed to show that it is safe and that it works in the same kind of way.  This, I think, is still a number of years away.”

‘Autologous grafting of cryopreserved prepubertal rhesus testis produces sperm and offspring’ by Adetunji P. Fayomi et al. was published in Science at 18:00 UK time on Thursday 21 March 2019.

Declared interests

Dr Rod Mitchell: “Dr Mitchell is currently leading a research project on fertility preservation in prepubertal boys, involving cryopreservation of testicular tissue prior to cancer treatment.”

Prof Daniel Brison: “I supervise PhD students and receive academic grant funding from NIHR and MRC in the general area of fertility research including human embryo development.   I have no commercial interests.”

None others received.