The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Towards the development of novel oncofertility strategies for female cancer patients (#90)

Michael J Bertoldo 1 2
  1. Fertility and Research Centre, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia
  2. Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

Whilst chemotherapy can be life-saving for cancer patients it commonly results in infertility. In vitro fertilisation (IVF) offers patients the best chance of a successful pregnancy, however, IVF is not suitable for many patients such as girls. Although alternative treatments such as ovarian tissue cryopreservation exist, they have poor outcomes. Therefore, with improving cancer survival rates there is an urgent need for new medical options to protect the fertility of females before cancer treatment. I have established a 3-tiered research program whereby we are: 1)enhancing the efficiency of oocyte in vitro maturation (IVM); 2)improving transplanted ovarian tissue quality of and; 3)developing methods to protect the ovary in situ –the “holy grail” of oncofertility. Through our work, evidence has emerged that nicotinamide adenine dinucleotide (NAD+) plays a critical role in maintaining female fertility and protecting the ovary against the damaging effects of chemotherapy. By manipulating NAD+ metabolism during IVM, we are unravelling the contribution of NAD+ to oocyte developmental competence. We have demonstrated that the NAD+ precursor nicotinamide mononucleotide (NMN) as an adjuvant to IVM, increases oocyte quality following IVM and IVF. Using mouse-to-mouse ovarian tissue transplants we revealed positive effects of systemic NMN administration on follicle development within grafted tissue. Finally, to protect the ovary during chemotherapy, our results demonstrate a clear protective effect of the NAD+ precursor NMN when administered systemically. However, we are cognisant that while NMN protects the ovary from chemotherapy it may also have the potentially undesirable effect of also protecting the cancer from chemotherapy. To circumvent this issue we are developing and assessing the efficacy of hydrogels to deliver NMN locally to the ovary. These findings illuminate the key role of NAD+ actions in fertility and chemoprotection in the ovary, as well as providing novel avenues of basic research for translation into the clinic.