Research Projects

Site:  Northwestern University

Principal Investigators: Paul Arntson, PhD; Marla Clayman, MPH, PhD; and Kathleen Galvin, PhD

Overview

This project explores how families facing a child’s cancer diagnosis decide whether or not to pursue fertility preservation treatments and the role that others, such as health care practitioners and religious counselors, play in this decision. The overall aim of this research is to gain a nuanced understanding of how families facing a child’s medical crisis communicate to make health care decisions and to develop a shared decision-making model that will facilitate informed choice in the clinical setting.

Objectives

• Understand how families, patients, and health care providers make “informed choices” about fertility preservation options when a young woman has been diagnosed with cancer.
• Construct a functional shared decision-making model for families, patients, and health care providers to use in making informed choices about fertility issues for young women diagnosed with cancer.
• Develop, utilize, and evaluate multiple formats of a shared decision-making model for families, patients, and health care providers that can be used in the clinical setting to help them make informed choices about fertility preservation options before cancer treatment.

Indices of Scholarship 

• Conduct in-depth interviews with parents of young women and girls diagnosed with cancer when they were a minor to learn about what they knew regarding the potential effects of cancer treatment on fertility and how they arrived at decisions regarding fertility preservation options. These interviews will also explore who they turned to for advice and information, how they determined what they needed to know in order to make a decision, how their values were incorporated into a decision, and how they weighted information received in arriving at a decision.  Depending on the age of the patient and parental consent, interviews will also be conducted with daughters.
• Conduct interviews with a representative group of health care providers to assess how they share information regarding cancer and fertility that aid in shaping the decision-making process
• Develop and pilot test a model of shared decision-making where informed choice is the goal.  Once the model has been tested, design multiple formats (print, CD-ROM, interactive Web site) of this model to be used as decision aids in family education programs and as practical aids in the clinical setting.

Consortium Support and Impact

This project draws on other parts of the Oncofertility Consortium in developing a social science inquiry that is informed by scientific innovation and insight.  It relies on clinical and medical perspectives and advances and application of oncofertility technology (see Follice Cryopreservation, Bioengineering Primate Follicles, and Human Follicle Maturation In Vitro) to develop surveys, focus group guidelines, and interviews while serving as an integrated link to interdisciplinary biomedical research in ovarian follicle harvesting, cryopreservation, maturation, and fertilization.  Insights regarding the psychosocial impact of infertility on the lives of cancer patients and their families will be applied to the training, education, and advocacy mission of the Consortium.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and RL1HD058296.

Site:  Northwestern University

Principal Investigator:  Teresa K. Woodruff, PhD

Rationale

The overarching purpose of the Oncofertility Consortium is to address the fertility threat posed by today’s highly effective cancer treatments in young men, women, and children and to serve as an authoritative voice for research, clinical practice, and training at the intersection of oncology, pediatrics, reproductive science and medicine, biomechanics, material science, mathematics, social science, bioethics, religion, policy research, reproductive health law, cognitive and learning science in a new discipline called oncofertility.

The development of this new discipline requires experts from a variety of fields in the creation of a common language and mechanisms to support communication and collaboration between Consortium members.

The interdisciplinary approach of the Oncofertility Consortium to the issue of fertility management after cancer is rather unique. Solving the distinct needs of cancer survivors is a complicated task that requires consistent collaboration and exchanges of ideas, successes and failures across a wide variety of specialties. Thus, the group must maintain its ability to cross disciplines in order to solve problems, continue developing solutions, and translate this progress into direct patient benfits . The work of the Administrative Core is as much about keeping the vision of the ultimate scope of the project in front of the individuals and groups involved and facilitating interaction among them as it is about traditional administrative governance.

The objectives of this program are to:

• Enable the interdisciplinary group and provide members with a strong, unified vision.
• Reduce barriers, encourage research, solve problems, maintain documents, and provide a robust intellectual environment with shared vision and an altruistic approach to credit and results.
• Ensure that administrative barriers do not interrupt the flow of intellectual energy and that the new ideas and data that are created at the boundaries of traditional disciplines are continuously fed back into the system.

Initial funding of this research was supported by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant 5UL1DE019587.  Funding continues under the Center for Reproductive Health After Disease (P50HD076188) from the National Institutes of Health National Center for Translational Research in Reproduction and Infertility (NCTRI)

Site:  Northwestern University and University of California, San Diego

Principal Investigators: David Dranove, PhD and Andrew Sfekas, PhD

Overview

This project is an economic analysis that weighs the costs and benefits of possible infertility and fertility preservation treatments in young adult women and parents with young children.

Objectives

• Understand the economic factors, decision-making rules, and risk-benefits analyses of  accessing fertility conserving options when the outcomes (e.g., survival and infertility) are not known.
• Estimate the value of child bearing to 2 distinct populations: women of childbearing age (defined as 18-25) and parents of young girls (aged 5 to 17).

Indices of Scholarship 

• Develop, validate, and implement a 4-stage survey to measure the direct medical costs as well as the indirect costs of choosing to pursue fertility preservation measures
• Following standard methods in cost-benefit analysis, evaluate the estimated value of child bearing using the concept of willingness to pay
• Based on variance in treatment costs and success rates outside of a clinical trial, construct a “break even” curve to depict the increase in probability of conception necessary to make treatment worthwhile at a particular cost

Consortium Support and Impact

This project draws on other parts of the Oncofertility Consortium in developing a social science inquiry that is informed by scientific innovation and insight.  It relies on clinical and medical perspectives and advances and application of oncofertility technology (see Follice Cryopreservation, Bioengineering Primate Follicles, and Human Follicle Maturation In Vitro) to develop surveys, focus group guidelines, and interviews while serving as an integrated link to interdisciplinary biomedical research in ovarian follicle harvesting, cryopreservation, maturation, and fertilization.  Insights regarding the psychosocial impact of infertility on the lives of cancer patients and their families will be applied to the training, education, and advocacy mission of the Consortium.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and RL1HD058296.

Site:  Northwestern University

Principal Investigator:  Lonnie D. Shea, PhD

Rationale

For folliculogenesis to properly occur, it is essential to maintain the intimate physiological connections between the oocyte and surrounding somatic cells. To recapitulate the 3-dimensionality of the ovary and maintain the appropriate size, shape, and architecture of the ovarian follicle while providing the necessary stimuli to direct cellular responses, a synthetic scaffold must serve as an in vitro mimic of the in vivo ovarian microenvironment.

Previous work has demonstrated that the hydrogel alginate phenocopies the in vivo ovarian environment by maintaining follicular architecture and permitting combinations of diffusible, insoluble, and mechanical signals to influence the development of the follicle.  Using this scaffold, murine ovarian follicles have been successfully matured in vitro to yield high-quality oocytes that were fertilized and used for the birth of live, viable offspring.

The application of biomaterials and tissue engineering to reproductive biology provides an enabling technology that is central to the Oncofertility Consortium®.  The work of the biomaterials core directly supports the work of other Consortium members; in particular, growth of large nonhuman primate and human follicles that may have different requirements from mouse follicles, maintaining follicle architecture and facilitating handling during cryopreservation, and promoting engraftment and survival of primate follicles following autotransplantation of ovarian tissue.

The objectives of this project are to:

• Provide biomaterial support to the Oncofertility Consortium®
• Identify biomaterial properties and culture conditions to maximize primate follicle growth and transfer knowledge to appropriate projects
• Develop novel biomaterials that can be used to minimize tissue cryoinjury
• Engineer drug-releasing hydrogels to optimize ovarian cortical strip transplants

Key Experiments

• Assess the mechanical influence of the ovarian stroma on follicle development using the alginate culture system
• Perform thermal analysis and polymer molecular weight measurements before and after follicle cryopreservation to identify optimal alginate properties and cooling procedures for maximum survival of individual follicles and cortical strips
• Subcutaneously implant alginate hydrogels with immobilized ECM and angiogenic factors into the abdomen of mice and analyze cellular infiltration, identify cell types, and quantify blood vessel growth (vascularization) to gauge host tissue engraftment

Consortium Support and Impact

The Biomaterials Core provides critical service, support, and training to the other Oncofertility Consortium® projects.  The exchange of biomaterials, development of techniques, training, and constant communication are central to the Core’s mission.  In addition, there is reciprocal interaction as results from the individual projects feed into the Core to further optimize 3-D culture systems.

Publications

Shikanov A, Smoith R M., Xu M, Woodruff T K., Shea L D. Hydrogel Network Design Using Multifunctional Macromers to Coordinate Tissue Maturation in Ovarian Follicle Culture. Biomaterials. 2011. April; 32(10): 2524-31.

Silber S J., Woodruff T K., Shea D L. To Transplant or Not to Transplant – That is the Question. Cancer Treatment and Research. 2010; 156: 41-54. PMID: 20811824.

Smith, R M., Woodruff T K., Shea L D. Designing Follicle-Environment Interactions with Biomaterials. Cancer Treatment and Research. 2010; 156: 11-24. PMID 20811822.

Weiss MS, Peñalver Bernabé B, Bellis AD, Broadbelt LJ, Jeruss JS, Shea LD. Dynamic, large-scale profiling of transcription factor activity from live cells in 3D culture. PLoS One. 2010 Nov 17;5(11):e14026.PMID: 21103341

Shikanov A, Xu M, Woodruff TK, Shea LD. Interpenetrating Fibrin–Alginate Matrices For In Vitro Ovarian Follicle Development. Biomaterials Vol. 29 5476-85 Oct 30, 2009

West-Farrell ER, Xu M, Gomberg MA, Chow YH, Woodruff TK, and Shea LD. The Mouse Follicle Microenvironment Regulates Antrum Formation and Steroid Production: Alterations in Gene Expression Profiles. Biology of Reproduction, 80, 432–439, 2009.

Xu M, Banc A, Woodruff TK, Shea LD. Secondary Follicle Growth and Oocyte Maturation by Culture in Alginate Hydrogel Following Cryopreservation of the Ovary or Individual Follicles. Biotechnology and Bioengineering, Vol. 103, No. 2, June, 2009.

West-Farrell ER, Xu M, Woodruff TK, Shea LD. Physical Properties of Alginate Hydrogels and Their Effects On In Vitro Follicle Development. Biomaterials Vol 30 4439-48 Oct 2007.

Woodruff TK and Shea LD. The Role of the Extracellular Matrix in Ovarian Follicle Development. Reprod Sci. Vol 14 No 8 Suppl 6-10 Dec 2007

Xu M, PhD, Woodruff TK, and Shea LD. Bioengineering and the Ovarian Follicle. Cancer Treat Res. 2007;138:75-82.

Berkholtz CB, Lai BE, Woodruff TK, Shea LD. Distribution of Extracellular Matrix Proteins Type I Collagen, Type IV Collagen, Fibronectin, and Laminin In Mouse Folliculogenesis. Histochem Cell Biol Vol 126 No 5 583-92 Nov 2006.

Kreeger PK, Deck JW, Woodruff TK, and Shea LD. The In Vitro Regulation Of Ovarian Follicle Development Using Alginate-Extracellular Matrix Gels. Biomaterials Vol 27 No 5 714-23 2006.

Kreeger PK, Fernandes NN, Woodruff TK, and Shea LD. Regulation of Mouse Follicle Development by Follicle-Stimulating Hormone in a Three-Dimensional In Vitro Culture System Is Dependent on Follicle Stage and Dose. Biology of Reproduction Vol 73 No 5 942-50 June 29 2005.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and PL1EB008542.

Site:  Northwestern University

Investigators:  Teresa Woodruff, PhD; Ellen Wartella, PhD, and Eric Patrick

The Education and Outreach Core of the SCCPIR Center for Reproductive Health After Disease provides Reproductive and Endocrine Awareness to Diverse Communities. It creates a process to communicates the research activities and emerging data of the Center to two important audiences:

• The clinicians who treat patients diagnosed with diseases or undergoing treatments that threaten their future reproductive health, and
• The public, who should have a general understanding of their own reproductive and endocrine health and the risk of disease-related or iatrogenic reproductive dysfunction.

For Clinicians and Researchers

The Education and Outreach Core conveys information to the clinical community regarding the reproductive and endocrine damage caused by specific diseases and treatments. To disseminate clinical information and emerging Center research findings to providers across the United States, the Core hosts quarterly Virtual Grand Rounds, through which attendees can view and listen to experts in the fields of disease, reproduction, endocrinology, and fertility preservation and interact with presenters in real time. Many fertility providers and health care clinicians have detailed questions regarding how to implement a comprehensive fertility preservation program, thus the Core hosts Clinic 101, an annual small-group training course, to give providers the resources and tools to develop their own fertility preservation and endocrine health program or to strengthen their existing program.

For the Public

A solid understanding of reproductive biology is important to ensure that all people can make fully informed decisions about their future reproductive health. Thus, public education is a critical function of the Core to disseminate information to male and female patients, their partners, and their parents. In addition, outreach to children and teenagers is necessary to provide them with a basic understanding of reproductive biology, and a basis for conceptualizing advanced reproductive and endocrine concepts as the future researchers, clinicians, and patients of tomorrow. To ensure these concepts are taught to young people, the core is developing animated video training modules targeted to young boys and girls. By providing reproductive education and outreach to this diverse set of stakeholders—providers, patients, partners, parents, and the public—we can be assured that, together with their physicians, patients and the public will have the ability to make complex decisions about their reproductive and endocrine health that will affect the rest of their lives.

Read about the Oncofertility Consortium’s previous education project: Learning Modules in Oncofertility

Site:  Northwestern University

Principal Investigator:  Lonnie D. Shea, PhD

Rationale

Compared to their age-matched peers, the five-year relative survival rate of cancer patients is now at 68%, improved from 50% thirty years ago. At least one in 250 women of reproductive age are cancer survivors. Today, 90% of these young women will be cured of their cancer. Unfortunately, the chemotherapies that save their life are fertility-threatening; in particular, alkylating agents and platinum-based drugs are highly associated with post-treatment infertility as they cause DNA damage to the oocytes that comprise the ovarian reserve.

Most young women with cancer are highly interested in trying to preserve their fertility so they might have children in the future. The cryopreservation and autotransplantation of ovarian tissue is emerging as a powerful approach for preserving fertility for patients that are losing ovarian function. Ovarian tissue transplantation has preserved fertility (at least 22 live births to date); however, for cancer patients, transplantation may not be possible due to the risk of re-seeding disease.

The objectives of this project are to:

• Refine the procedures for follicle isolation to enable large-scale recovery of primordial follicles, and subsequently investigate the engraftment and function by transplanted follicles within a range of biomaterials.
• Investigate strategies to modulate the initial recruitment of follicles that would deplete the ovarian reserve, and thereby enhance the duration of graft function.
• Investigate the transplantation of follicles from post-pubertal animals, and determine the contribution of age and obesity of the recipient on the engraftment and function of transplanted follicles.
• Investigate the transplantation of ovarian follicles from mice with metastatic disease, which simulates the clinical situation of re-seeding cancer cells.

Read about Dr. Shea’s previous project: The Oncofertility Consortium Biomaterials Core

Site: Oregon National Primate Research Center

Principal Investigator: Mary B. Zelinski, PhD

Co-Investigator: Richard R. Yeoman, PhD

Rationale

While fertility preservation for males has been available for several decades using sperm cryopreservation, attempts to similarly preserve mature female oocytes and ovarian tissue have been more challenging.  Tissue damage during the freezing and thawing process has the potential to irreversibly disrupt the 3-dimensional structure of the follicle necessary for the development of a fully viable mature oocyte. The goal of this research is to provide the direction necessary by testing existing technologies that represent the state-of-the-art in cryopreservation of ovarian tissue samples in nonhuman primates.  In addition, novel methods that will improve tissue viability after thaw as well as minimize operator time and effort will be developed.

Experimental endpoints include successful in vitro maturation of follicles, fertilization of resulting mature oocytes, embryo development and establishment of pregnancy.  After rigorous testing in nonhuman primates, the findings will be rapidly applied to the cryopreservation of human ovarian tissue in order to expand fertility preservation options for women at the time of diagnosis of cancer and other serious diseases.

The objectives of this project are to:

• Compare two methods of ovarian tissue cryopreservation (slow freeze vs. vitrification) in the nonhuman primate, and assess follicle and oocyte viability in all stages of follicle maturity
• Assess the fertilization and embryonic potential of primate oocytes derived from cryopreserved ovarian tissue and cumulus-oocyte complexes
• Adapt new cryo-technology under development around the globe to the nonhuman primate model

Key Experiments

• Compare vitrification to slow freeze methods in rhesus monkey ovarian tissue by assessing a) histology of tissue preservation; b) in follicle maturation (IFM), i.e., isolation of individual secondary follicles to monitor survival, growth and functional characteristics using the encapsulated 3-dimensional (3D) culture system recently established in the nonhuman primate; and c) isolation of the matured oocyte and assessment of fertilization, early embryonic development, and ultimately production of live offspring.
• Compare vitrification to slow freeze methods in cumulus–oocyte complexes (COCs) derived from small antral follicles in rhesus monkey ovarian tissue and assessing oocyte maturation in vitro, fertilization, early embryonic development and ultimately production of live offspring.
• Develop novel cryopreservation methods based on cutting-edge technologies derived from the cryobiology field (i.e., novel cryoprotectants) in rhesus monkey ovarian tissue and COCs
• Test methods for transporting ovarian tissues (currently used for tissue transplantation) rapidly between sites for optimal preservation of morphology and function

Consortium Support and Impact
The successful execution of this project and eventual application of preservation technology will require close collaboration with other members of the Oncofertility Consortium. Specifically, the project requires close cooperation with the team working to improve methods to mature primate follicles in vitro and the Biomaterials Core. In addition, a primary goal of the National Physicians Cooperative is to ultimately translate the results of these studies to the preservation of human ovarian tissue and follicles. While the human application of methods to cryopreserve and recover ovarian tissue will fill a significant need in fertility preservation in women, it is also expected to lead to new social, legal, and ethical concerns that will impact how patients and physicians discuss infertility (see Social Science and Oncofertility), particularly with regard to pediatric cancer patients.  Education of patients and physicians and training of oncofertility specialists also be necessary to ensure that cutting-edge procedures associated with follicle removal and storage become part of routine cancer care worldwide

Publications 

Ting AY, Yeoman RR, Lawson MS, Zelinski MB. In vitro development of secondary follicles from cryopreserved rhesus macaque ovarian tissue after slow-rate freeze or vitrification. Hum Reprod. 2011 Jun 24.

Xu J, Lawson MS, Yeoman RR, Pau KY, Barrett SL, Zelinski MB, Stouffer RL. Secondary follicle growth and oocyte maturation during encapsulated three-dimensional culture in rhesus monkeys: effects of gonadotrophins, oxygen and fetuin. Hum Reprod. 2011 Feb 28.

Jin, S, Lei, L, Shea, LD, Zelinski, MB, Stouffer, RL, and Woodruff, TK. Markers of growth and development in primate primordial follicles are preserved after slow cryopreservation. Fertility and Sterility, 2010.

Peluffo MC, Barrett SL, Stouffer RL, Hennebold JD, Zelinski MB. Cumulus-Oocyte Complexes from Small Antral Follicles During the Early Follicular Phase of Menstrual Cycles in Rhesus Monkeys Yield Oocytes That Reinitiate Meiosis and Fertilize In vitro. Biol Reprod 83:525-532, 2010.  PMID  20519694.

Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK, and Zelinski MB. Current achievements and future research directions in ovarian tissue culture, in vitro follico development and transplantation: implications for fertility preservation. Human Reproduction Update, 2010.

Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK, and Zelinski MB. Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation (Chinese excerpt). Human Reproduction Update, Vol.16, No.4 pp. 395–414, 2010.

Xu J, Bernuci MP, Lawson MS, Yeoman RR, Fisher TE, Zelinski MB, Stouffer RL. Survival, growth, and maturation of secondary follicles from prepubertal, young and older adult, rhesus monkeys during encapsulated three-dimensional (3D) culture: effects of gonadotropins and insulin. Reproduction, Aug. 2010. PMID  20729335

Xu M, West-Farrell ER, Stouffer RL, Shea LD, Woodruff TK, and Zelinski MB. Encapsulated Three-Dimensional Culture Supports Development of Nonhuman Primate Secondary Follicles. Biology of Reproduction. (3):587-94 Sep.8, 2009

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and RL1HD058293.

Fertility preservation technologies raise a variety of ethical, social, and legal challenges and concerns. This section of the website is devoted to those working in the humanities who research these issues from disciplines such as bioethics, history, literature, philosophy, religions, law, and the arts. Humanists have been involved in the Oncofertility Consortium since its inception, providing parallel scholarship to accompany scientific and technological developments, proving an integral part of the Oncofertility Consortium team.

The Oncofertility Consortium recognizes that society is always in flux, and thus understands that humanities research is continually evolving.  If you are a humanist interested in pursuing a novel research aim related to oncofertility or have questions or comment about our existing research project, please contact us.

Principal Investigator:  Kemi Jona, PhD

Development of an Oncofertility Curriculum for high school girls.

The Oncofertility Saturday Academy was founded in 2007 to expose high school students to laboratory and medical science research in the fields of cancer, fertility, and oncofertility. The keystone educational program of the Women’s Health Science Program, the program educates students at four locations around the country: Chicago, IL; San Diego, CA; Phildadelphia, PA; and Oregon (with a fifth in development in Denver, CO).

The programs include laboratory learning experiences in mouse ovary dissections, ovarian follicle encapsulation, DNA analysis, immunohistochemistry, in vitro fertilization, and developmental processes of sea urchins and frogs. Clinical learning experiences include performing breast and pelvic exams on simulation models, operating the daVinci surgical robot under the supervision of surgeons, and performing embryology techniques. In addition, bioethicists facilitate and guide the high school students to apply an ethical framework to discuss the various perspectives connected to the field of oncofertility.

Learn more about OSA in Chicago

Learn more about OSA in San Diego

Publications

Faurot M, Woodruff TK. The Oncofertility Saturday Academy: A Paradigm to Expand the Educational Opportunities and Ambitions of High School Girls. Cancer Treatment and Research. 2010; 156; 321-44. PMID: 20811845.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and RL5CA133836.

Site:  Northwestern University

Principal Investigator:  Teresa Woodruff, PhD

Rationale

Life-preserving strategies in the face of a cancer diagnosis, including radiation, surgery, and chemotherapy, can compromise nearly all aspects of the female reproductive axis resulting in infertility, subfertility, or premature menopause. In addition, several conditions and disease states can have a similar consequence.

Fortunately for females, the ovary has the potential for diverse fertility preservation options ranging from standard (i.e. IVF, ICSI, embryo banking) to investigational (ovarian tissue cryopreservation, ovarian transplant).

In vitro follicle growth is another emerging technology that has tremendous promise for a subset of individuals who have blood-borne malignancies, cannot tolerate supraphysiological hormone levels, can not delay treatment, or do not have a sperm donor. Tremendous success has been achieved in performing IVFG in the mouse to the degree that live births have been achieved using gametes derived from nearly all methods attempted to date. The translation of this technology to large mammalian species, however, has not been trivial due to significant differences in factors such as follicle size, development, metabolic requirements, and physical niche.

The objectives of this project are to:

• In this project, we will develop “smart” biomaterials that will provide human follicles with the ability to self-regulate their physical environment as they grow to terminal stages of development. We anticipate that such an environment will maintain the coordinated growth of the oocyte and its companion granulosa cells, which is required for optimal endocrine function and gamete quality.
• We will also develop new non-invasive endocrine measures of follicle health that, through a precise algorithm, could be used in association with conventional steroid and peptide assays to predict the maturity of individual follicles.
• Follicles developed to the right stage of maturity will contain the highest quality gamete, and we will use innovative nanonewton force measurements to quantitatively understand the mechanisms by which a chromosomally normal egg is generated both in vivo and in vitro during meiosis.

These experiments have broad implications on human health as a chromosomally normal egg is a fundamental pre-requisite to create a healthy offspring. Our aims are based on experiments that integrate three model organisms – mouse, cow, and human – and span multiple disciplines – reproductive medicine, cell and molecular biology, bioengineering, and biophysics. This union will allow us to advance our understanding of human reproductive biology in a quantitative way, and at the same time provide key insights into the possible clinical translation of in vitro follicle culture systems to preserve fertility in young patients with cancer or other reproductive disorders.

Read about Dr. Woodruff’s previous project: Preservation and Growth of Human Follicles

Site:  Northwestern University

Rationale

The five-year relative survival rate of cancer patients has improved from 50 to 68% in the last thirty years. The survival rate of pediatric cancers has reached 80%, and the NCI predicts that 1 out of every 250 adults will be a survivor of childhood cancer by 2015. As the number of cancer survivors increases, so does the concern for their quality of life post-treatment.

One of the most serious problems associated with radiation and chemotherapy is the off-target effect on germ cells. For young women, this is a particularly serious concern because the immature oocytes that comprise the ovarian reserve are highly sensitive to chemo/radiation therapies.

Since the ovarian reserve represents ALL the follicles available for future fertility as well as endocrine function, the loss of immature oocytes and subsequent sex steroid deficiency have significant physical and psychological consequences. The goal of this project is to better understand the mechanisms associated with survival and death of immature oocytes caused by cancer treatments, and in doing so, identify “neo-adjuvant” medical approaches for preserving fully functional ovaries in young women undergoing treatment.

The overall hypothesis of this proposal is that the balance between survival and death of oocytes in primordial and primary follicles is controlled by the interaction between p53 family members, and thus the p53 family members are targets for fertoprotective agents.

The objectives of this project are to:

• Elucidate the mechanism through which p53 family members are activated by chemotherapy.
• Dissect the molecular pathways involved in the death of immature oocytes by applying in vitro culture and subrenal grafting of mouse ovaries to genetically engineered mouse models.

The results of these proposed studies will be critically important for understanding the mechanisms that underlie physiologic and iatrogenic follicle death and may reveal new strategies for protecting the fertility of young women diagnosed with cancer.

For more information, please visit Oncofertility Professional Engagement Network.

As the field of oncofertility continues to advance, the Oncofertility Consortium seeks to support various high-risk, high-gain initiatives in order to facilitate the launch of early-stage ideas into future grant-funded projects. Applications for pilot projects are evaluated each year, with only a few awarded with financial support and access to Oncofertility Consortium resources. A total of 8 pilot projects have been backed by the Oncofertility Consortium, with additional projects planned each year.

Funded Projects, Current and Past:

1. Improving Tamoxifen Adherence by Addressing Fertility Concerns
2. A Novel Approach to Assess Direct and Estradiol-Mediated Effects of Ovulation Induction Regimens and Breast Cancer Development
3. The Male Perspective: Survey for Preservation of Adolescent Reproduction
4. Oncofertility Communication Initiative: Assessing the Short Documentary Format for Oncofertility Communications
5. Development of Blood Spot Assays for Long-term Longitudinal Studies of Reproductive Status of Cancer Survivors
6. Deriving Oocytes from Embryonic Stem Cells
7. The Effects of GDF9 Levels on TZP Reorganization and Oocyte Competence in Growing Follicles Cultured in Alginate
8. Identification of Developmental Markers and Culture Environments
9. Role of GDF-9 in Human Folliculogenesis
10. Does Gleevac Block Programmed Cell Death in Primary and Primordial Mouse Follicles Via the p63 Pathway?
11. Gene Expression in Small Antral Follicles Derived in Vivo and From Encapsulated 3-Dimensional Culture in Macaques
12. Comparing Infertility and Cancer Research, Development and Social Understandings
13. The Road to Adulthood: How Do Young Adults Make Health and Fertility-Related Decisions

______________________________________

1. Improving Tamoxifen Adherance by Addressing Fertility Concerns

Site: Northwestern University
Principal Investigator: Jacqueline S. Jeruss, MD, PhD

Study Description

The study objective is to evaluate physician- and patient-level factors, including fertility, concerns that affect adherence to tamoxifen for young women diagnosed with breast cancer. An estimated 23,000 women under age 45 are diagnosed with breast cancer annually, of whom roughly 70% have estrogen-receptor positive (ER+) breast cancer. For these women, a 5-year course of daily tamoxifen results in a 47% reduction in annual recurrence risk and a 26% reduction in annual mortality. Despite such substantial benefits, adherence and persistence are low: 20% of patients fail to reach the optimal adherence threshold during the first year of treatment, and at 5 years, up to 50% of patients have discontinued treatment. Young women consistently have been shown to have lower rates of adherence to hormonal therapy when compared to women between the ages of 50-70. It is necessary to address both clinician and patient barriers to tamoxifen adherence. We hypothesize that, for young breast cancer patients, a unique set of patient- and provider-level factors, including fertility concerns, contributes to the poor tamoxifen adherence observed in this patient population.

2. A Novel Approach to Assess Direct and Estradiol-Mediated Effects of Ovulation Induction Regimens and Breast Cancer Development

Site: Northwestern University
Principal Investigator: Jacqueline S. Jeruss, MD, PhD

Study Description

The major goal of this project is to determine if ovulation induction through medical intervention causes breast epithelial cells to progress to neoplasia, either directly by inducing proliferation or indirectly by increasing stromal angiogenesis in a 3-dimensional culture system. In addition, investigators are determining if prior infertility treatment increases the risk of breast cancer in a cohort of women with BRCA 1/2 mutations or a family history of breast cancer.

Progress and Results

Clomiphene, commonly used as a treatment for infertility, acts by blocking the estrogen receptor (ER), though it has been hypothesized that this drug also effects cell proliferation in vitro by estrogen independent mechanisms. To analyze the effects of clomiphene treatment on breast cancer development we used 3 well-established breast cancer cell lines. MCF-10A cells, which approximate normal immortalized mammary epithelium and are ER negative, showed a slight increase in colony area in response to estrogen and a slight increase in colony number in response to clomiphene during 10 days of treatment. MCF-7 cells, which are estrogen receptor (ER) positive and well-differentiated breast cancer cells, showed a significant increase in colony area in response to estrogen treatment and a slight increase in colony number in response to clomiphene. HCC 1937 cells, which are ER negative and harbor a BRCA1 mutation, showed a slight increase in colony number n response to estrogen. Proliferation assays, 3D culture, and cell cycle analysis studies are in progress to determine the response of these cells to clomiphene, FSH, estradiol, and hCG. We will also use a mouse model with mammary epithelial hyperplasia to assess how infertility treatment affects the progression of hyperplasia to malignancy. Lastly, we continue to accrue BRCA 1/2 carriers or patients with a strong family history of breast cancer to determine the risk of developing breast cancer following infertility treatment. Publications from this and related research from Dr. Jeruss are:

Jeruss J S. Discussing Fertility Preservation with Breast Cancer Patients. Cancer Treatment and Research. 2010; 156: 461-6. PMID: 20811855.

Jeruss JS, Mittendorf EA, Tucker SL, Gonzalez-Angulo AM, Buchholz TA, Sahin AA, Cormier JN, Buzdar AU, Hortobagyi GN, Hunt KK. Staging of breast cancer in the neoadjuvant setting. Cancer Res. 2008 Aug 15;68(16):6477-81. PMID: 18701468.

Weiss MS, Peñalver Bernabé B, Bellis AD, Broadbelt LJ, Jeruss JS, Shea LD. Dynamic, large-scale profiling of transcription factor activity from live cells in 3D culture. PLoS One. 2010 Nov 17;5(11):e14026. PMID: 21103341.

3. The Male Perspective: Survey for Preservation of Adolescent Reproduction

Site: Northwestern University
Principal Investigator: Robert Brannigan, MD

Study Description

Understanding and overcoming the barriers to fertility preservation is essential to optimize the reproductive health of young cancer patients. The overall aim of this project is to develop and execute a national survey (Survey for Preservation of Adolescent Reproduction, SPARE) of pediatric oncologists to assess perspectives on fertility preservation in both pre-pubertal (age 1-12) and pubertal (age 13-18) cancer patients, including willingness to discuss fertility, knowledge of current fertility preservation methods, and awareness of the American Society of Clinical Oncology published fertility preservation recommendations (ASCOR) regarding sperm cryopreservation strategies and referral to a fertility specialist. Through SPARE, we sought to obtain post-ASCOR data from pediatric oncology specialists nationwide.

Progress and Results

A total of 209 respondents, primarily consisting of pediatric oncologists, responded to the SPARE survey, providing data on both male and female pediatric oncology fertility preservation knowledge, attitudes, and practices. Our work on SPARE revealed that fertility preservation in both male and female adolescents is hampered by a lack of knowledge among treating physicians of the American Society for Clinical Oncology recommendations on this topic, as well as numerous barriers to the delivery of fertility preservation case. This project also provided insight into the gender disparity that exists in the approach that clinicians utilize in treating male and female adolescents. We conclude that pediatric oncologists are strongly motivated to preserve fertility in male pediatric cancer patients but barriers to semen preservation and referral to fertility specialists exist. Additional promotion of the ASCO fertility preservation recommendations is essential to optimize reproductive health of young cancer patients. This pilot project sucessfully resulted in a publication, as follows:

Köhler TS, Kondapalli LA, Shah A, Chan S, Woodruff TK. Results from the survey for preservation of adolescent reproduction (SPARE) study: gender disparity in delivery of fertility preservation message to adolescents with cancer. Brannigan RE. J Assist Reprod Genet. 2010 Nov 26.

4. Oncofertility Communication Initiative: Assessing the Short Documentary Format for Oncofertility Communications

Site: Northwestern University
Principal Investigator: Barbara O’Keefe, PhD
Co-Investigator: Sean Zehnder, PhD

Study Description

Video portrayals of cancer patients offer special opportunities to shape the way audiences think about issues related to a diagnosis  of cancer. We hypothesize that video portrayals of patients that dramatize their maturation into complex, multidimensional human beings will lead audiences of all types to cognize other cancer patients in more complex, multidimensional, and historicized ways, and that this broader framing will in turn change decision-making. The purpose of this project is to pilot both (a) the use of short documentary films for increasing the salience of fertility issues in decision-making about cancer treatment (oncofertility) and (b) methods for designing, disseminating, and evaluating messages about oncofertility. A long-term goal is to use the knowledge gained via this pilot to build a sustained research and development program on oncofertility communications.

Progress and Results

The first part of our pilot project was to produce three short documentaries about cancer survivors and their issues they have faced related to having biological children. Two Chicago-based professional videographers were hired and helped to produce a high definition video that portrays individual patient experiences with cancer. These videos tells to story of three unique cancer survivors: Gayle, a survivor of adult cancer who opted to participate in a new research protocol with the hope of one day being able to conceive another child; Wesley, a marathoner and business man who was diagnosed with Hodgkin’s Lymphoma as a young man; and Connie, a survivor of childhood cancer who is now struggling with infertility caused by her cancer treatment. These videos will help to develop evidence-based guidelines for web communication with patients and others and assist in the promotion of information about oncofertility. View the videos.

5. Development of Blood Spot Assays for Long-term Longitudinal Studies of Reproductive Status of Cancer Survivors

Site: Northwestern University
Principal Investigator: Teresa K. Woodruff, PhD
Co- Investigators: Clarisa Gracia, MD, Laxmi Kondapalli, MD, and Thomas McDade, PhD

Study Description

The blood spot assay is a method for collecting samples for hormone measurements. Dried blood spot (DBS) samples, which are collected by a minimally invasive finger prick, require little collection time, no post-collection processing, have low biohazard risk, and facilitate sample storage and transport.  In this pilot project, DBS assays will be developed to measure markers of reproductive function (inhibin B, AMH, and FSH).  These hormone profiles can then be used to assess reproductive potential in cancer patients. The aims of this project are to:

• Validate measurements of inhibin B, AMH and FSH in media and dried blood spots
• Assess inhibin B, AMH and FSH in pools of serum samples collected from early follicular phase, mid follicular phase and luteal phase
• Assess inhibin B, AMH and FSH in blood spots taken during one complete menstrual cycle and compare the results to a serum-based assay

Progress and Results

We have developed an enzyme immunoassay protocol for AMH using DBS derived from finger stick whole blood samples, and are currently working to improve the assay sensitivity. We have also begun collecting a set of 100 matched plasma/dried blood spot samples from menstruating reproductive aged women at the University of Pennsylvania. These samples will allow us to compare results obtained from DBS with gold-standard clinical methods using serum/plasma from venipuncture.  Using Bland-Altman plots and regression analyses, we will inspect for agreement and bias across the assay range and generate a conversion formula for calculating plasma equivalents based on DBS results.

6. Deriving Oocytes from Embryonic Stem Cells

Site: Oregon National Primate Research Center
Principal Investigator: Shoukhrat M. Matalipov, PhD
Co-Investigator: Mary B. Zelinski, PhD
Postdoctoral Fellow: Araceli Valle Prieto

Project Description

Recent research suggests that embryonic stem cells (ESCs) could serve as a source of viable gametes, since ESCs can proliferate indefinitely in an undifferentiated pluripotent state and, when allowed, can differentiate into any cell type of an adult body. The goal of this proposal is to evaluate the potential of monkey ESCs to contribute to the female germ line lineage and to explore the feasibility of deriving functional oocytes suitable for use in assisted reproductive technologies (ARTs). We hypothesize that primate ESCs derived by somatic cell nuclear transfer can form female germ cells and gametes upon spontaneous or directed differentiation.  In this pilot project, we propose:

• To develop optimal culture conditions for directed differentiation of monkey ESCs to the female germ cell lineage
• To evaluate three-dimensional (3-D) culture for directed differentiation of monkey ESC-derived follicles to functional oocytes.

Progress and Results

We have developed genetically tagged monkey ESCs under the control of germ cell-specific promoters that will allow us to detect and select early germ cells upon induced differentiation.

7. The Effects of GDF9 Levels on TZP Reorganization and Oocyte Competence in Growing Follicles Cultured in Alginate

Site: Northwestern University
Principal Investigator: Teresa K. Woodruff, PhD
Co-Investigators: Susan L. Barrett, MS, PhD

Project Description

Small secondary ovarian follicles are capable of growing in a 3D alginate matrix to generate fertilizable eggs that can give rise to live offspring in mice. Though this system has been proven successful, the percentage of competent oocytes generated from each pool of cultured follicles remains low. It is known that somatic cell-oocyte interactions, namely via transzonal projections (TZPs), are necessary for proper follicle growth and oocyte development, and that these interactions can be compromised during prolonged follicle culture. Studies have also indicated that GDF9, an oocyte maternal-effect gene, plays a role in maintaining these physical connections between somatic cells and the oocyte. The goals of this pilot study are 1) to evaluate the organization and maintenance of TZPs in growing follicles cultured in our 3D alginate system in mice, primates, and humans and 2) to determine if higher levels of secreted GDF9 correlate with well-organized somatic cell-oocyte interactions, successful follicle growth, and oocyte competency. These studies will elucidate if all follicles have the potential to become dominant follicles producing competent oocytes.

8. Identification of Developmental Markers and Culture Environments

Site: Northwestern University
Principal Investigators: Lonnie Shea, PhD, and Linda Broadbelt, PhD

Project Description

In developing cultures systems for growing follicles, there are at least two significant challenges: i) determining if follicles are developing appropriately within the culture environment, and ii) providing key factors at the appropriate time to promote follicle growth and maturation.  In this pilot project, we will analyze microarray data obtained from mouse ovarian follicles at different stages to identify factors that vary in expression levels between stages and can, therefore, be used as markers of growth progression.  We will also use bioinformatics tools to identify key biological pathways that are active during the transition between the multiple follicle stages.  This analysis will assist us in identifying factors that could be added to the culture medium to promote follicle growth at specific stages.  Results from these studies will be translated to the culture of nonhuman primate and human follicles.  The strategy developed in this proposal will provide a foundation for identifying environments that maximize the growth and development of immature follicles and will identify mechanisms through which the environment influences follicle maturation.

9. Role of GDF-9 in Human Folliculogenesis

Site: University of California, San Diego
Principal Investigator: Shunichi Shimasaki, PhD
Co-Investigator: Heidi Cook-Andersen, PhD

Project Description:

Genetic studies in female mice and ewes have demonstrated that the oocyte-specific growth and differentiation factor-9 (GDF-9) regulates female fertility. In humans, a high incidence of mutations in the GDF-9 gene has been found in women with premature ovarian failure (POF) and mothers of dizygotic (DZ) twins. In addition, GDF-9 mRNA levels are reduced in growing human oocytes in polycystic ovary syndrome (PCOS) and PCO ovaries from primordial follicle recruitment through the small Graafian follicle stage. Despite these important clinical observations, almost nothing is known about the mechanism by which GDF-9 controls ovarian function in women. In this pilot project, we will use our purified recombinant human GDF-9 (rhGDF-9) to determine the biological function of the rhGDF-9 in follicle growth and development in human ovaries. We will also determine the biological function of the mutant GDF-9 proteins described in POF women and mothers of DZ twins. The results of these studies will provide the first insight into understanding the molecular and cellular mechanisms of how ovarian function in women is governed physiologically by GDF-9 during reproductive years.

10. Does Gleevac Block Programmed Cell Death in Primary and Primordial Mouse Follicles Via the p63 Pathway?

Site: Northwestern University, Feinberg School of Medicine
Principal Investigator: Teresa K. Woodruff, PhD
Co-Investigator: Takeshi Kurita, PhD, Lonnie D. Shea, PhD, So-Youn Kim, PhD

11. Gene Expression in Small Antral Follicles Derived in Vivo and From Encapsulated 3-Dimensional Culture in Macaques

Site: Oregon National Primate Research Center
Principal Investigator: Mary B. Zelinski, PhD
Co-Investigators: Richard L. Stouffer, PhD, and Jing Xu, PhD

12. Comparing Infertility and Cancer Research, Development and Social Understandings

Site: Northwestern University, Center for Bioethics
Co-Investigator: Lisa Campo-Engelstein, PhD, and Sarah Rodriguez, PhD

13. The Road to Adulthood: How Do Young Adults Make Health and Fertility-Related Decisions

Site: Northwestern University, Feinberg School of Medicine
Principal Investigator: Karrie Snyder, PhD

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and UL1DE019587.

Site:  University of Pennsylvania

Principal Investigator:  Christos Coutifaris, MD, PhD

Rationale

In recent years, cancer diagnosis has changed, in many cases, from a death sentence to a disease with many survivors.  Aggressive cancer treatments, although successful with respect to survival, may result in damage or loss of oocytes and impairment or loss of fertility.  The purpose of the Oncofertility Consortium is to address the issue of fertility preservation in cancer patients with sufficiently trained physician-scientists who will implement the research and clinical agenda required to treat their patients with new and emerging technologies.

This multidisciplinary force of oncofertility specialists, specifically equipped to cope with the fertility concerns of patients with cancer, represents a new discipline in the field of Women’s Health.  Long-term success will depend on how well the development of this global workforce is orchestrated, supported, and focused.  It is the intent of this project to train and educate the first generation of oncofertility specialists in research related directly to the reproductive needs of the cancer patient and survivor.  Education and training programs will facilitate the development of the oncofertility discipline that exists at the intersection of oncology, pediatrics, reproductive science and medicine, biomechanics, material science, mathematics, social science, bioethics, religion, policy research, reproductive health, law, and cognitive and learning science.

Specifically, this program will train and fund both NRSA eligible and non-NRSA eligible trainees through 2 different NIH grant mechanisms.  Oncofertility training will merge entirely with the clinical and education objectives of the fellowship training program, Reproductive Endocrinology and Infertility (REI).  Therefore, the likely source of oncofertility specialists will come directly from within the ranks of the REI subspecialty fellowships for advance training after completion of a residency in Obstetrics and Gynecology.

The objectives of this program are to:

• Expand the training of oncofertility specialists within REI programs across the nation through a rigorous educational, laboratory-based, and research curriculum.
• Seek federal funding for additional training dedicated to laboratory work and research related to oncofertility.

Indices of Scholarship 

• Train fellows in cellular and molecular approaches to reproductive biology relevant to oncofertility and the responsible conduct of research
• Require the completion of additional didactic training and an online educational module
• Provide clinical exposure to adult and pediatric oncology patients who face the prospect of fertility loss or compromise
• Participate in an academic enrichment program consisting of seminars, lecture series, journal clubs, conferences, and retreats geared towards a comprehension of the interdisciplinary nature of oncofertility

Trainees To Date

• Dr. Monica Mainigi trained at Northwestern in the isolation and culture of early and secondary mouse follicles. The objectives of her research entitled “Developmental Competence of the Mammalian Oocyte: Studies Utilizing an in vitro Model of Follicular Maturation” were (1) To compare the nuclear and developmental competence of oocytes grown at physiologic oxygen (5%) versus atmospheric oxygen (20%) in a three dimensional follicle system, (2) to investigate to effect of in vitro follicle culture on gene expression in the fully grown oocyte and (3) to determine if the culture of immature follicles in vitro leads to disruption of events necessary for successful oocyte activation and fertilization.
• Dr. Fanzhen Hong trained at the University of Pennsylvania in the isolation and culture of early and secondary mouse follicles. Dr. Hong’s main laboratory training initiative was to gain expertise in the isolation and culture of mouse preantral follicles and participate in all the didactic initiatives of the Division of Reproductive Endocrinology and Infertility. Arrangements are currently being made between our program and her University to provide the necessary guidance for setting up a clinical Oncofertility program in the Province of Shandong in China.
• Dr. Shiying Jin trained and gained expertise in the isolation and culture of early secondary mouse follicles at Northwestern University. Dr. Jin’s focus during the training period was to gain expertise in the isolation and culture of mouse preantral (early secondary) follicles and initiate studies to optimize the cryopreservation and in vitro culture system for the culture of human follicles.
• Dr. Jayon Kim is training at the University of North Carolina, Chapel Hill with Dr. Jennifer E. Mersereau. Dr. Kim is involved in a variety of studies including trials evaluating the efficacy of oocyte cryopreservation; the complex relationships between BRCA mutations, breast cancer, and reproductive hormones, and more. Read one of her recently published papers.
• Additional trainees will be accepted annually as the program continues

Consortium Support and Impact

This project will draw on the biomedical and clinical research of the Oncofertility Consortium.  Fellows will be trained in cryopreservation techniques and storage, follicle growth research in primates, the effects of cancer treatment on women’s reproductive capacities and the growth and maturation of human follicles, and tissue engineering applications.  Each fellow will be expected to receive instruction in bio-psychosocial science, bioethics and religion, and reproductive health policy and law related to oncofertility.  Online Resources will provide additional information to those being trained to ensure the optimal educational environment.  Currently, there are 3 projects (see Fertility Measures After Cancer and Pilot Project Program) funded through the Consortium and being led by members of the first generation of oncofertility specialists, who use and provide feedback on the education and training program.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and TL1CA133837/RL9CA133838.

Site:  Northwestern University

Principal Investigators: Linda Emanuel, PhD, MD; Sherman Elias, MD; Laurie Zoloth, PhD; and Dorothy Roberts, JD

Overview

This project evaluates the ethical and legal issues surrounding the use of reproductive technologies in cancer patients, with a special emphasis on the implications for pediatric patients and their families.

Objectives

• A critical assessment of the ethical, religious, and legal constraints associated with the application of advanced fertility opportunities to young women and girls facing fertility-threatening diseases.
• An evaluation of the existing norms of pediatric decision-making for the young child and family who will make such decisions on their behalf, and the implications for medical practice and health care policy.
• An assessment and consideration of the competing moral appeals that arise in connection with the long-term uses of this research.

Indices of Scholarship 

• Meet with leaders from religion, law, psychology, social science, political science, and biomedical policy to identify all the major issues raised by the advanced fertility options in this project
• Based on the issues identified, conduct a comprehensive literature review that will result in a manuscript to set out the issues, identify arguments, and highlight the areas in need of further deliberation
• For each key issue, identify real and hypothetical, but realistic, cases for analysis of: (1) medical risks and benefits; (2) how best to communicate with patients and families on issues of oncofertility; (3) economic considerations; (4) ethical options; and (5) decision-making approaches for clinicians, patients, and families
• Reconvene at a mini-symposium to discuss positions, fill gaps, and collectively author a consensus paper that will provide direction and make recommendations regarding the professionally-guided ethical norms of practice for advanced reproductive oncofertility technology. Articles, notes, and presentations from the Center for Bioethics, Science and Society’s Oncofertility Summit are available in the Virtual Library.

Consortium Support and Impact

This project draws on other parts of the Oncofertility Consortium in developing a social science inquiry that is informed by scientific innovation and insight.  It relies on clinical and medical perspectives and advances and application of oncofertility technology (see Follice Cryopreservation, Bioengineering Primate Follicles, and Human Follicle Maturation In Vitro) to develop surveys, focus group guidelines, and interviews while serving as an integrated link to interdisciplinary biomedical research in ovarian follicle harvesting, cryopreservation, maturation, and fertilization.  Insights regarding the psychosocial impact of infertility on the lives of cancer patients and their families will be applied to the training, education, and advocacy mission of the Consortium.

Publications

Backhus LE and Zoloth L. Today’s Research, Tomorrows Cures: The Ethical Implications of Oncofertility. 2007.

Zoloth L, Backhus LE and Woodruff TK. Waiting to be Born: The Ethical Implications of the Generation of “NUBorn” and “NUAge” Mice from Pre-Pubertal Ovarian Tissue. The American Journal of Bioethics, 8:6,21 — 29, 2008.

Zoloth L, Backhus LE Woodruff TK, Henning A, and Raucher M.  Like/As: Metaphor and Meaning in Bioethics Narrative. The American Journal of Bioethics, 8(6): W3-W5, 2008.

Dolin G,. Roberts DE, Rodriguez LM, Woodruff TK.  Medical hope, legal pitfalls: Potential legal issues in the emerging field of oncofertility. Santa Clara L. Rev. 2009.

Zoloth, L. Jewish Perspectives on Oncofertility: The Complexities of Tradition. Cancer Treatment and Research. 2010; 156: 307-17. PMID: 20811844.

Zoloth, L. Final Thoughts. Cancer Treatment and Research. 2010; 156: 487-9. PMID: 20811861.

Zoloth, L and Henning A. Bioethics and Oncofertility: Arguments and Insights from Religious Traditions. Cancer Treatment and Research. 2010; 156: 261-78. PMID: 20811840.

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and RL1HD058296.