Ten years ago, the phrase 'families after cancer1 for most women would have been an oxymoron if contemplated at all. Today, due to the impressive rise in young female cancer survivors, this is not only a well-used phrase, but also an issue that women increasingly want addressed. As the lexicon is being established, the boundaries are expanding to encompass the fertility needs of childhood cancer survivors for whom fertility-conserving options are limited. The role of the emerging oncofertility specialist is to navigate through the available options and provide individualized counseling to patients. To provide this kind of authoritative information to women in different age brackets, with different treatment regimens, it is necessary to evaluate the reproductive axis and its response to cancer treatment in a rigorous manner. The ability to recruit patients through the large National Physicians Cooperative (P30B) will provide sufficient power to correlate treatment and outcome data in a comprehensive and thorough manner. In Specific Aim 1, we will develop combinatorial analytical methods and a predictive algorithm to assess the Risk of Impending Premature Ovarian Failure (RIPOF, pronounced rip off) in young women treated with chemotherapeutics for their cancers. These data will improve information exchange between the provider and the patient about the risk and timeframe of impending premature ovarian failure. We will also use the established murine ovarian culture system to test a broad panel of chemotherapeutics and establish endpoints that can be used to rapidly assess the likely fertility impact of any new or existing drugs that are introduced into the oncologists' arsenal (Specific Aim 2). Therefore, the relative toxicity of new chemotherapeutic agents on in vitro follicle survival and maturation (in vitro risk, IVR) will be investigated. Finally, the major goal of the project is to develop methods to grow immature human ovarian follicles into the mature, fertilizable stage (Specific Aim 3). We will translate recent breakthroughs at the interface of material science and reproductive biology into clinically-proven technology that can provide additional fertility options to those who may lose fertility due to cancer treatment.