In 2006 alone, nearly 55,000 women either prior to or in their reproductive age range are expected to bediagnosed with cancer. For females undergoing radio- or chemotherapy for cancer treatment, iatrogenicdamage to the ovaries is common, often resulting in infertility. Significant advances in treatment during thepast few decades have improved the survival significantly among individuals diagnosed with cancer; the 5-year relative survival rate for all cancers diagnosed between 1995 and 2001 is 65%. It has been estimatedthat; by 2010, 1 in 250 people in the adult population will be cancer survivors. The remarkable success ofimproved cancer therapy has generated a significant societal need: namely, the development of effectivemeans to preserve the fertility of individuals undergoing such therapies. Currently, all forms of female fertilitypreservation are considered experimental. Cryopreservation of cells and tissues is an interplay of as manyas 8-12 factors, most of which interact. By establishing a clear understanding of the underlying fundamentalcryobiological characteristics of the cells or tissues, we can develop mathematical models that enable us todesign optimal methods. The overall goal of R01A under the auspices of the Oncofertility Consortium is todevelop improved methods to cryopreserve primate oocvtes. immature follicles and ovarian tissue, basedupon sound, fundamental crvobiological principles. We propose the following specific aims for this project:(1) develop and empirically test an optimized method for cryopreserving rhesus and human in vitro maturedoocytes; (2): develop and empirically test an optimized method for cryopreserving rhesus and humanimmature follicles; (3): develop and empirically test an optimized method for cryopreserving rhesus andhuman ovarian cortical tissue. We are proposing a series of experiments to determine the tolerance of cellscrucial for female fertility to several stresses associated with Cryopreservation including changes intemperature, osmolality, and cryoprotective agents. In addition, we are proposing experiments designed tounderstand biophysical characteristics of oocytes, follicles, and ovarian tissue, such as the permeability ofthe cells to cryoprotectants and the intracellular ice formation characteristics of whole ovarian tissue pieces.Used in conjunction with the tolerances of the cells to the stresses as described above, the resultinginformation will allow the development of theoretically-optimal Cryopreservation procedures. We will testthese procedures using in vitro maturation, fertilization, and development as experimental endpoints. We willinitially conduct all of the experiments using rhesus macaque oocytes, follicles and ovarian tissue. As newknowledge is gained from this approach and improved methods for Cryopreservation are developed, we willapply these developments to human oocytes, follicles and ovarian tissue working with the R01B in nonhumanprimates, R01C human follicles and in conjuction with each of the training and social scienceprograms (R01D, R25, T90/R90, K01).
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