11 April 2016
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.