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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Linked Research project Grant (RL1)
Project #
5RL1HD058295-03
Application #
7649510
Study Section
Special Emphasis Panel (ZRR1-SRC (99))
Program Officer
Lamar, Charisee A
Project Start
2007-09-30
Project End
2012-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$426,149
Indirect Cost
Name
Northwestern University at Chicago
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Kim, So-Youn; Ebbert, Katherine; Cordeiro, Marilia H et al. (2015) Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles. Endocrinology 156:1464-76
Jiao, Ze-Xu; Xu, Min; Woodruff, Teresa K (2014) Age-related increase in aneuploidy and alteration of gene expression in mouse first polar bodies. J Assist Reprod Genet 31:731-7
Xu, Jing; Xu, Min; Bernuci, Marcelo P et al. (2013) Primate follicular development and oocyte maturation in vitro. Adv Exp Med Biol 761:43-67
Telfer, Evelyn E; Zelinski, Mary B (2013) Ovarian follicle culture: advances and challenges for human and nonhuman primates. Fertil Steril 99:1523-33
Ting, A Y; Yeoman, R R; Campos, J R et al. (2013) Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system. Hum Reprod 28:1267-79
Woodruff, Teresa K (2013) From the bench to bedside to babies: translational medicine made possible by funding multidisciplinary team science. J Assist Reprod Genet 30:1249-53
Jiao, Ze-Xu; Woodruff, Teresa K (2013) Detection and quantification of maternal-effect gene transcripts in mouse second polar bodies: potential markers of embryo developmental competence. Fertil Steril 99:2055-61
Ahn, Richard W; Barrett, Susan L; Raja, Meera R et al. (2013) Nano-encapsulation of arsenic trioxide enhances efficacy against murine lymphoma model while minimizing its impact on ovarian reserve in vitro and in vivo. PLoS One 8:e58491
Kim, S-Y; Cordeiro, M H; Serna, V A et al. (2013) Rescue of platinum-damaged oocytes from programmed cell death through inactivation of the p53 family signaling network. Cell Death Differ 20:987-97

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