Oncofertility Publications

By Co-editors Teresa K. Woodruff, Laurie Zoloth, Lisa Campo-Engelstein, and Sarah Rodriguez

Part I: The Science and Technology of Oncofertility

1. Reproductive Health After Cancer by Clarisa Garcia
2. Designing Follicle-Environment Interactions with Biomaterials by Rachel M. Smith, Teresa K. Woodruff, and Lonnie D. Shea
3. Gamete Preservation by Susan L. Barrett and Teresa K. Woodruff
4. To Transplant or Not to Transplant – That is the Question by Sherman J. Silber, Teresa K. Woodurff and Lonnie D. Shea
5. Clinical Cases in Oncofertility by Laxmi A. Kondapalli, Fanzhen Hong, and Clarisa R. Gracia
6. Cancer Genetics: Risks and Mechanisms of Cancer in Women with Inherited Susceptibility to Epithelial Ovarian Cancer by Lee Shulman and Jeffrey Dungan
7. Protecting and Extending the Fertility Options for Female Wildlife and Endangered Mammals by Pierre Comizzoli, David Wildt, and Nucharin Songsasen

Part II: Historical and Legal Perspectives

1. Placing the History of Oncofertility by Sarah Rodriguez
2. Medical Hope, Legal Pitfalls: Potential Legal Issues in the Emerging Field of Oncofertility by Gregory Dolin, Dorothy E. Roberts, Teresa K. Woodruff, and Lina M. Rodriguez
3. Domestic and International Surrogacy Laws: Implications for Cancer Survivors by Kiran Sreenivas and Lisa Campo-Engelstein
4. Adoption After Cancer: Adoption Agency Perspectives on the Potential to Parent Post-Cancer by Shauna Gardino, Andrew Russell, and Teresa K. Woodruff

Part III: Clinical and Theoretical Ethics

1. Ovarian Tissue Cryopreservation and Bioethical Discourse by Christina L.H. Traina
2. The Lessons of Oncofertility for Assisted Reproduction by Adrienne Asch
3. Morally Justifying Oncofertility Research by Carolyn McLeod
4. Ethical Dilemmas in Oncofertility: An Exploration of Three Clinical Scenarios by Clarisa R. Gracia, Jorge J.E. Gracia, and Shasha Chen
5. Participation in Investigational Fertility Preservation Research: A Feminist Ethics Approach by Michelle L. McGowan
6. Reproductive “Choice” and Egg Freezing by Angel Petropanagos
7. The Impact of Infertility: Why ART Should Be a Higher Priority for Women in the Global South by Amanda Fleetwood and Lisa Campo-Engelstein
8. Oncofertility and Informed Consent: Addressing Beliefs, Values and Future Decision Making by Felicia Cohn

Part IV: Religious Perspectives

1. Bioethics and Oncofertility: Arguments and Insights from Religious Traditions by Laurie Zoloth and Alyssa A. Hennings
2. Sacred Bodies: Considering Resistance to Oncofertility in Muslim Communities by Rumee Ahmed
3. Unlikely Motherhood in the Qur’an: Oncofertility as Devotion by Ayesha S. Chaudry
4. Technology and Wholeness: Oncofertility and Catholic Tradition by Paul Lauritzen
5. Jewish Perspectives on Oncofertility: The Complexities of Tradition by Laurie Zoloth

Part V: Ramifications for Education and Economics

1. The Oncofertility Saturday Academy: A Paradigm to Expand the Educational Opportunities and Ambitions of High School Girls by Megan Faurot and Teresa K. Woodruff
2. MyOncofertility.org: A Web-Based Patient Education Resource Supporting Decision Making Under Severe Emotional and Cognitive Overload by Kemi Jona and Adam Gerber
3. Anticipating Ovarian Tissue Cryopreservation in the Health-care Marketplace: A Willingness to Pay Assessment by Shauna L. Gardino, Andrew Sfekas, and David Dranove
4. Perspectives on Oncofertility from Demography and Economics by Rosalind King
5. For the Sake of Consistency and Fairness: Why Insurance Companies Should Cover Fertility Preservation Treatment for Iatrogenic Infertility by Lisa Campo-Engelstein

Part VI: Repercussions of Oncofertility for Patients and their Families

1. Health Care Provider Perspectives on Fertility Preservation for Cancer Patients by Caprice A. Knapp and Gwen P. Quinn
2. Counseling and Consenting Women with Cancer on their Oncofertility Options: A Clinical Perspective by Emily S. Jungheim, Kenneth R. Carson, and Douglas Brown
3. The Fertility-Related Treatment Choices of Cancer Patients: Cancer-Related Infertility and Family Dynamics by Karrie Ann Synder, May Kyaw Thazin, William B. Pearse, and Mehwish Moinuddin
4. Whose Future Is It? Ethical Family Decision Making About Daughters’ Treatment in the Oncofertility Context by Marla L. Clayman and Kathleen M. Galvin
5. Choosing Life when Facing Death: Understanding Fertility Preservation Decision-Making for Cancer Patients by Shauna L. Gardino and Linda L. Emanuel

Part VII: Health Care Provider Stories and Final Thoughts

1. Discussing Fertility Preservation with Breast Cancer Patients by Jackie S. Jeruss
2. Warning: Google can be Hazardous to Your Health: Fertility Preservation Is an Important Part of Cancer Care by Jennifer Hirschfield-Cytron
3. The Role of a Patient Navigator in Fertility Preservation by Jill Scott-Trainer
4. Judaism and Reproductive Technology by Sherman J. Silber
5. Reading Between the Lines of Cancer & Fertility: A Provider’s Story by Leonard S. Sender
6. A Rewarding Experience for a Pediatric Urologist by Margarett Shnorhavorian
7. Final Thoughts by Laurie Zoloth

Abstract

BACKGROUND:
This study sought to determine the prevalence of distribution of fertility preservation (FP) materials, source of the materials, and providers’ perceived relevance of the materials among a sample of US oncologists.

METHODS:
A 53‐item survey was administered via mail and the Web to a stratified sample of oncologists from the American Medical Association Masterfile. This study represents a subset of results, reporting on three survey items.

RESULTS:
Among the 511 oncologists (32% response rate), only 13.5% (n = 69) reported ‘always or often’ giving their patients educational materials about FP. Among those who reported ever distributing materials, 39.5% used American Cancer Society materials, 11.0% used Fertile Hope, 6.4% used Lance Armstrong Foundation, and 11.8% used ‘other’. Among those who provided materials, only 27.4% believe the FP materials they provide are ‘relevant to patient’s specific cancer diagnosis’.

CONCLUSION:
There is need to improve oncologists’ distribution of FP educational materials to patients with cancer.

Traina C L. Cancer Treatment and Research. 2010; 156: 173-80. PMID: 20811832.

McGowan, M L. Cancer Treatment and Research. 2010; 156: 209-21. PMID: 20811836.

Abstract

OPINION STATEMENT:
With improving survival rates for pediatric and young adult cancer patients, considerations regarding the long-term effects of therapy have become more important. Cancer therapies are known to pose reproductive risks, though the effects may be unpredictable. All at-risk patients should have a discussion about potential treatment-related infertility before the onset of cancer therapy, and should be offered appropriate fertility preservation options. Embryo and sperm cryopreservation are considered standard therapy, though oocyte cryopreservation is gaining acceptance. Ovarian tissue cryopreservation, while still experimental, is showing great promise. It is the only option currently available to prepubertal girls. No fertility preservation options exist for prepubertal boys though some institutions may offer experimental testicular tissue cryopreservation.

Dillon KE, Gracia CR. Curr Treat Options Oncol. 2012 Mar 16. PMID: 22422325

Berkowitz-King, R. Cancer Treatment and Research. 2010; 156: 371-9. PMID: 20811848.

Abstract

Transforming growth factor-beta (TGFbeta) homologues form a diverse superfamily that arose early in animal evolution and control cellular function through membrane-spanning, conserved serine-threonine kinases (RII and RI receptors). Activin and inhibin are related dimers within the TGFbeta superfamily that share a common beta-subunit. The evolution of the inhibin alpha-subunit created the only antagonist within the TGFbeta superfamily and the only member known to act as an endocrine hormone. This hormone introduced a new level of complexity and control to vertebrate reproductive function. The novel functions of the inhibin alpha-subunit appear to reflect specific insertion-deletion changes within the inhibin beta-subunit that occurred during evolution. Using phylogenomic analysis, we correlated specific insertions with the acquisition of distinct functions that underlie the phenotypic complexity of vertebrate reproductive processes. This phylogenomic approach presents a new way of understanding the structure-function relationships between inhibin, activin, and the larger TGFbeta superfamily.

Jie Zhu, Edward L. Braun, Satomi Kohno, Monica Antenos, Eugene Y. Xu, Robert W. Cook, S. Jack Lin, Brandon C. Moore, Louis J. Guillette, Jr., Theodore S. Jardetzky, Teresa K. Woodruff. PLoS One, Volume 5, Issue 3, March 2010.

Abstract

The mechanical properties and density of natural and synthetic extracellular matrices are known to affect cellular processes and regulate tissue formation. In this report, these factors were independently investigated for their role in ovarian follicle development. The matrix composition was controlled through decreasing the solids concentration or the molar mass of the encapsulating biomaterial, alginate. Decreasing matrix stiffness and solids concentration enhanced follicle growth and coordinated differentiation of the follicle cell types, as evidenced by antral cavity formation, theca cell differentiation, oocyte maturation, and relative hormone production levels. While a stiff environment favored high progesterone and androgen secretion, decreasing alginate stiffness resulted in estrogen production which exceeded progesterone and androgen accumulation. These studies reveal, for the first time, a direct link between the biomechanical environment and follicle function, and suggest a novel non-hormonal mechanism regulating follicle development.

Erin R. West, Min Xu, Teresa K. Woodruff, Lonnie D. Shea; Biomaterials Vol 30 4439-48 Oct 2007

Summary

Both medical and non-medical factors have equally contributed to the emerging field of oncofertility. It is a microcosm of the medical, cultural and personal that shapes this field including, but not limited to: changes in cancer research, survival rates and treatment; cancer as a publicly acknowledged diagnosis; and a growing cultural acceptance of assisted reproductive technologies (ART). Taking a closer look at this history will help both patients and practitioners be more receptive to the overlapping issue that influence the field of oncofertility in the future.

Rodriguez S. Cancer Treatment and Research. 2010; 156: 103-10. PMID: 2081128

Abstract

Posthumous reproduction is an issue fraught with legal, ethical, religious, and moral debate. The involvement of the hospice and palliative care community in this debate may be peripheral due to the fact that other health care professionals would be actually delivering the services. However, the hospice and palliative care community are more likely to treat patients considering posthumous reproduction as they near the end of their lives. This article provides the hospice and palliative care community with a review of the medical, ethical, and legal considerations associated with posthumous reproduction. Having knowledge of these issues, and a list of available resources, will be useful if hospice and palliative care staff find themselves facing a patient or family that is considering posthumous reproduction.

Knapp C, Quinn G, Bower B, Zoloth L. J Palliat Med. 2011 Aug;14(8):895-8. Epub 2011 Jun 28. PMID: 21711126

Abstract

More than half of the primordial follicles that are formed by Day 6 of postnatal life in the mouse will be eliminated from the ovary by the time of puberty. Apoptosis, a form of programmed cell death, is one mechanism by which these follicles could be actively lost. To investigate whether apoptosis is responsible for the loss of primordial follicles, follicular atresia was examined during the prepubertal period, when follicles die and are cleared from the ovary at an extremely high rate. Four hallmarks of classical apoptosis were measured in follicles present in prepubertal ovaries. The primordial follicle cohort was not positively associated with nuclear condensation or cell shrinkage, activation of caspase 3, cleavage of poly(ADP ribose) polymerase 1 (PARP1), or fragmentation of DNA. These data are consistent with a nonapoptotic pathway that is responsible for small follicle death.

Candace M. Tingen, Sarah K. Bristol-Gould, Sarah E. Kiesewetter, Jason Tyler Wellington, Lonnie Shea, and Teresa K. Woodruff; Biology Reproduction Vol 81 No 1 16-25 July 2009

The unique duality involved in confronting a life-threatening diagnosis while simultaneously considering the deeply human desire to have a child presents a struggle both for patients with cancer and for clinicians. Yet with improved survival rates among young patients with cancer, recent bench to-bedside translation of new techniques to preserve fertility, and increased awareness of choices for the preservation of fertility, options for family planning are now being offered to patients who have received a diagnosis of cancer. Concerns about fertility are similar for men and women; however, their opportunities for intervention differ considerably. This review describes current and emerging options for the preservation of fertility in patients with cancer and provides a conceptual framework for managing concerns about fertility at the time of diagnosis.

Jacqueline S. Jeruss and Teresa K. Woodruff; New England J. Med. Vol 360 No 9 902-911 Feb 26 2009.

Woodruff TK. Preserving fertility during cancer treatment. Nat Med. 2009 Oct;15(10):1124-5.

Chemotherapy can save the lives of many individuals with cancer. Unfortunately, it usually cause infertility after treatment, posing a concern for these people who will face a lifetime condition that considerably limits the quality of their lives. Advances in the field of oncofertility have brought hope to cancer survivors who long to plan a family; however, standard approaches only rely on cryopreservation of sperms and eggs before treatment and do not prevent infertility. In ‘Bedside to Bench’, Min Xu, Mary Ellen Pavone and Teresa Woodruff examine a study where individuals treated with gonadotropin-releasing hormone (GnRH) agonists before cancer therapy showed a decreased risk of infertility. How these agonists work to suppress and protect ovarian function and increase fertility in women after treatment is still unclear and begs further investigation at the bench.

Comizzoli P, Songsasen N, Wildt D E. Cancer Treatment and Research. 2010; 156: 87-100. PMID: 20811827.

Abstract

Background Breast cancer is the most common cancer in women younger than age 50 years. Cancer treatments in younger women may cause premature menopause, infertility, and negative psychosocial effects. In this systematic review, we examined three key domains of functioning that are particularly relevant for younger breast cancer survivors: health-related quality of life (QOL), menopausal symptoms and fertility concerns, and behavioral health outcomes. Methods We conducted a literature review using PubMed and secondary sources and examined 840 articles published between January 1990 and July 2010. Inclusion criteria for articles were 1) published in English after 1989; 2) exclusively analyzed female breast cancer survivors aged 50 years or younger or premenopausal at diagnosis, with baseline characteristics and/or quantitative or descriptive analyses for this age group; 3) investigated QOL (health-related QOL including physical functioning and mental health, depression, and anxiety), menopause- or fertility-related concerns, and weight gain or physical activity-related behavioral health outcomes. Data were extracted using a standardized table collecting the purpose, design, population, and results of each study. Extracted data were reviewed for accuracy by two investigators and presented as descriptive tables. Results A total of 28 articles met the inclusion criteria (15 cross-sectional studies, eight longitudinal studies, and five randomized trials). Regarding data review, no discordance between investigators was noted. Standardized measures of QOL and depressive symptoms identified worse outcomes as being more frequent or severe in breast cancer survivors aged 50 years or younger when compared with the general age-matched population of women without cancer and to older women (aged >50 years) with breast cancer. Concerns about premature menopause, menopausal symptoms, and infertility were common in younger women (aged ≤50 years) and had a role in the level of distress after treatment. Weight gain and physical inactivity were common health outcomes in younger women. Conclusions Younger women with breast cancer were found to experience distinct psychosocial and menopause-related concerns, weight gain, and physical inactivity. A need for more longitudinal research, including efforts at intervention to manage these symptoms and adverse health outcomes, remains.

Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. J Natl Cancer Inst. 2012 Mar 7;104(5):386-405. Epub 2012 Jan 23, PMID: 22271773

Sender L S. Cancer Treatment and Research. 2010; 156: 481-4. PMID: 20811859.

Abstract

The developmental requirements of ovarian follicles are dependent on the maturation stage of the follicle; in particular, elegant studies with genetic models have indicated that FSH is required for antral, but not preantral, follicle growth and maturation. To elucidate further the role of FSH and other regulatory molecules in preantral follicle development, in vitro culture systems are needed. We employed a biomaterials-based approach to follicle culture, in which follicles were encapsulated within matrices that were tailored to the specific developmental needs of the follicle. This three-dimensional system was used to examine the impact of increasing doses of FSH on follicle development for two-layered secondary (100-130 microm; two layers of granulosa cells surrounding the oocyte) and multilayered secondary (150-180 microm, several layers of granulosa cells surrounding the oocyte) follicles isolated from mice. Two-layered secondary follicles were FSH responsive when cultured in alginate-collagen I matrices, exhibiting FSH dose-dependent increases in follicle growth, lactate production, and steroid secretion. Multilayered secondary follicles were FSH dependent, with follicle survival, growth, steroid secretion, metabolism, and oocyte maturation all regulated by FSH. However, doses greater than 25 mIU/ml of FSH negatively impacted multilayered secondary follicle development (reduced follicle survival). The present results indicate that the hormonal and environmental needs of the follicular complex change during the maturation process. The culture system can be adapted to each stage of development, which will be especially critical for translation to human follicles that have a longer developmental period.

Pamela K. Kreeger, Nisha N. Fernandes, Teresa K. Woodruff, and Lonnie D. Shea; Biology of Reproduction Vol 73 No 5 942-50 June 29 2005