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Pre-pubertal ovarian tissue preservation – are we pushing the boundaries too far?

11 April 2016
By Dr Edgar Mocanu
Treasurer, International Federation of Fertility Societies
Appeared in BioNews 846

Oncofertility services allow some women to cryopreserve oocytes, embryos or ovarian tissue in order to protect their ability to have a family when faced with malignancy and adjuvant therapy. However, to date, fertility cryopreservation had very little to offer young, pre-pubertal girls undergoing chemo- or radiotherapy for childhood cancer. 

A recent press release appears to have changed this forever. Teams from St George's Hospital in London and Rigshospitalet in Copenhagen have reported creating in vitro embryos using eggs collected from a cancer survivor's ovary, frozen at the age of eight and transplanted at the age of 21 (reported in BioNews 844). The success opens the possibility of a pregnancy in the immediate future, once the embryos are implanted. This would be a world first. 

The findings offer proof of the maturation of eggs following FSH, follicle-stimulating hormone, stimulation of ovarian tissue taken before puberty. The pre-pubertal ovary contains a large number of primordial follicles, which go on to produce egg cells, and therefore is an ideal target for cryopreservation. Even if the freeze–thaw process results in the demise of a large number of follicles, it is expected that more follicles survive from a pre-pubertal ovary compared to a post-pubertal one. The ability of this young ovarian tissue to respond to stimulation and the development of mature eggs is key to the success of this novel procedure.

So what does it mean to young girls undergoing cancer treatment? It opens a door towards using the technique of ovarian tissue preservation irrespective of age. Towards reimplantation of ovarian tissue and the possibility of achieving either a spontaneous or assisted conception via IVF, once the cancer has been cured.    

While this a significant scientific development, we must place it in the context of how it may change clinical practice. Childhood cancer represents less than one percent of all cancers diagnosed. In UK, annually, about 1600 children are diagnosed with cancer, of whom 800 are girls and 50 percent are under five years of age.  

The identification of suitable candidates for the surgical removal of ovarian tissue, particularly considering that in many malignancies the general health might require an immediate oncological intervention, could be a challenge. Furthermore, the abdominal procedure needed to remove ovarian tissue involves risks related to anaesthesia and potential risks and complications associated with the surgery. 

In these circumstances, the first question that comes to mind is whether the reported procedure could be recommended on a large scale. In other words, should all girls, irrespective of age, be offered cryopreservation of ovarian tissue once adjuvant therapy is recommended? The process encompasses many steps, namely, surgery to remove the ovarian tissue, special preparation of such tissue and cryopreservation, storage of cryopreserved material, sometimes for very long periods of time. When the decision to procreate is made, it requires thaw of tissue and further surgery to re-implant the preserved young ovarian material. 

It goes without saying that expertise in this highly specialised field (paediatric surgery to include removal and also re-implantation, laboratory cryopreservation) is in its infancy. As such, the development of expertise, for practical and financial reasons, would involve a single national centre to cater for all these cases. Would it be accessible to all in need? Unless health systems plan for adequate financial resources and clinical expertise to cater for the ever-increasing numbers, access might be limited to the chosen few.

And are we helping the family? While it is advisable to discuss with parents of children that require adjuvant therapy the potential of ovarian failure, how can we expect the already devastated parents to have to juggle so many decisions about their young girls' lives? Can they make decisions allowing young girls to undergo such surgery for a potential later benefit? If they say no, would they regret it later? Counselling sessions and the presence of trained psychologists who can help with the decision-making process should be mandatory if such services are ever established.

Finally, how can the procedure be justified? An intervention exposing a child to further risks, one that could potentially help towards, but not guarantee a pregnancy, in the circumstances of possible ovarian failure in the future? Is this overtreatment? The 82 percent survival rate after childhood cancer calls for a better understanding of what the adjuvant therapy impact is on the reproductive function of surviving girls. Newer regimes are milder, and it is possible that the ovarian failure rate will significantly decrease in the future thus reducing the need for major interventions like the ones here described.

In an attempt to keep a balanced view, nothing is more devastating than the late realisation that something could have been done earlier that to prevent childlessness later in life. While it is our duty to ensure that additional risks are not imposed on already-vulnerable children, we must keep an open mind about medical progress in the childhood fertility cryopreservation arena.

18 July 2016 - by Rebecca Carr 
A cancer patient in Edinburgh has become the first woman in the UK to have a child following a transplant of her frozen ovarian tissue...
11 July 2016 - by Dr Rosie Morley 
A two-year-old girl has become the youngest person to undergo a new technique that could preserve her fertility after chemotherapy...
27 June 2016 - by Dr Lucy Freem 
The Progress Educational Trust held its first-ever debate in Scotland – on the subject of egg freezing – which proved a lively topic of debate...
31 May 2016 - by Dr Özge Özkaya 
A majority of female cancer patients with 'uncertain' fertility status have said they were not given enough information about the risks of infertility resulting from their treatment...
21 March 2016 - by Antony Starza-Allen 
A 23-year-old woman may soon become become pregnant after receiving an implant of an ovary that had been frozen since she was eight years old...
23 November 2015 - by Dr Edgar Mocanu 
A recent study in mice raised the possibility of restoring ovarian function after chemotherapy. But before creating hype, the medical community has a duty to deliver evidence from human studies...
26 October 2015 - by Dr Nicoletta Charolidi 
A stem-cell therapy in mice shows promise for reversing infertility in women who have received cancer treatment...
12 October 2015 - by Dr Rachel Montgomery 
A Danish study has reported that ovarian tissue transplants appear to be safe and can restore fertility in women who have undergone treatment for cancer, with around one in three procedures in young women leading to live births....
15 June 2015 - by Dr Julia Hill 
A woman who has received a transplant of ovarian tissue stored when she was a child has given birth. It is believed to be the first time ovarian tissue taken from young girl has led to a successful pregnancy...
Girls with other conditions could benefit from this treatment ( - 12/04/2016)
It is worth bearing in mind that this type of research doesn't only potentially benefit girls with cancer but also those with other conditions where a girl is born with functioning ovaries but has POF at a young age, such as Turner Syndrome. Although only a small number of girls with TS are born with ovaries, their fertility could potentially be preserved this way; experimental work freezing ovarian tissue from very young girls with TS has already been carried out, although the frozen tissue has not yet been used.

TS is not a life-threatening condition so some of the other considerations raised here don't apply, or don't apply in the same way.
You make some interesting points... ( - 17/06/2016)
Interesting points made in the article. I would like to give my opinion as a mother of a  female childhood cancer survivor who is likely to become infertile as a result of her treatment.

I think we do need to press on with this research and give parents (and teenage children if they are old enough to consent to this) the option of conserving their child's fertility. If this technique were to become more "mainstream" then the ovary removal might be able to be performed at the same time as other surgical procedures such as removal of tumours from the abdomen/pelvis. If I had been given this option I would have chosen this for my child, but as I do not live near a specialist centre this would have caused too many delays for her cancer treatment. I have spoken to many parents in my position (with young children having cancer treatment that may render their daughters infertile in the future) and they are very sad that they were not offered this. You say they might need counselling to consider the option of doing/not doing this BUT already I know parents (including myself and some of my close friends) are thinking " Could I have done something to preserve my daughters fertility?" They do not know the ins and out of the procedure but they are already considering how can they give hope to their child should she survive to reproductive age.

So I don't think it is over treatment, I think the clinicians involved and the oncologists could advise on whether it is practically possible with regards to risks (depending on the health of the child at the time) and whether it would delay significantly the start of treatment of the cancer. I would hope in time, the technology for this will become more efficient and there will be more specialists around so that these treatment delays will be minimised.

I also think as childhood cancer survival rates are rising, albeit slowly, we should think about the implications of having these potential adults around who will want to live a long and fulfilling life, including the chance to have their own genetic child. Just because something like childhood cancer is rare, does not mean we should not strive to improve this technology and offer it to more families.

Thank you.

Abi Burchill. Embryologist.
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