On average, 21,997 cases of cancer are diagnosed yearly among UK women aged between 25 and 49. Therapy involves surgery, radiotherapy or chemotherapy, each potentially resulting in infertility through either uterine or ovarian factors. To date, no effective method to prevent this significant impact on fertility has been discovered.
Fertility cryopreservation using egg or ovarian tissue freezing is not always possible because of the urgency of the life-saving intervention. Furthermore, many oncologists prefer not to delay treatment in the face of an aggressive cancer and, in many cases, it is the patient's choice to proceed with the treatment rather than delay. In cases where chemotherapy is used, particularly alkylating agents, the risk of ovarian insufficiency after treatment is high.
Ovarian insufficiency is usually irreversible, and methods that can undo this process have not been investigated. This is why a recent study in mice (see BioNews 825), which raises the possibility of restoring ovarian function after chemotherapy, could trigger hope for the millions of women worldwide with ovarian insufficiency after cancer therapy or from other causes.
The authors of this study used laboratory mice in three intervention groups: controls (receiving no chemotherapy and only water injections in their ovaries), a second group who received chemotherapy in the abdominal cavity and saline injected into their ovaries, and the treatment group who received chemotherapy along with human bone marrow stem cells injected into their ovaries.
The Egyptian authors showed that mice that received the adult stem cells recovered from the state of ovarian insufficiency and had follicles present in their ovaries, with an increase in the ovarian-reserve hormone anti-Müllerian hormone, suggesting growing follicles were present in the ovaries and a return to normal function.
In addition to helping women who have undergone cancer treatment, ovarian follicle development after stem-cell injection could also have a positive impact on ovarian ageing and help with many of the debilitating postmenopausal conditions like osteoporosis and heart disease.
As a proof of principle, this research is groundbreaking. But before creating hype of a cure for ovarian ageing and insufficiency due to cancer-adjuvant therapy, the medical community has a duty to deliver evidence from human studies.
Hopeful as these findings may be, medical research on mice does not always translate into similar results in humans. Furthermore, data on safety in mice and the impact upon the health of one or two generations must be explored prior to human studies.
There are other issues raised by this research. We must make a clear difference between the intent of restoring hormonal ovarian function (e.g. to protect against osteoporosis and heart disease) or reproductive ovarian function, or both.
From a fertility perspective, questions remain about the lifespan and quality of newly formed follicles and corresponding eggs. Are the newly created follicles capable of producing mature eggs that can be fertilised? Whether the resulting children are healthy and what consequences present in the next generation must be the focus of any future research. How long the effects of one stem-cell injection last, and whether these cells can travel to other organs, also remain to be explored.
What remains is the need for the scientific community not to stifle the excitement of a new discovery, but to consider carefully the risks and the opportunities that it might bring to millions of women worldwide.
Acknowledging that patient and potential future offspring well-being come first, well-designed research in humans could answer many of the above questions while providing the opportunity for the long-term follow-up of women and their children.
If proven to work in humans, this technology could allow us to restore ovarian function as we also cure cancer. It will bring hope where none existed before. Is this not what medical science is for?
Sources and References
Mohamed SA, et al. Human bone marrow mesenchymal stem cells therapy restores ovarian functions and reverses infertility in a preclinical model of chemotherapy induced premature ovarian failure.