Oncofertility Publications

Abstract

Increases in the number of adult cancer survivors and other issues have forced the oncology community to examine, evaluate, and alter the cancer care paradigm. Pediatric oncologists are grappling with the task of transitioning a growing population of adult survivors of childhood cancer to adult medicine, while oncologists caring for adult cancer survivors are seeking models of follow-up care that are acceptable to patients and providers. Workforce and access-to-care issues suggest that primary care providers will see more cancer survivors in their practices across time, although it is unclear how prepared they are for this task. Translational research is needed to develop evidence-based clinical care and survivorship care plans. A broad picture of the evolving field of adult cancer survivorship is presented. The recent focus on young adult survivors of childhood cancer, an overview of translational research needed to inform the physical and psychosocial care of cancer survivors, and the roles of primary and specialty care providers managing this population is examined. Finally, an overview of evolving treatment summary and care plan initiatives is presented.

Jacobs LA, Palmer SC, Schwartz LA, DeMichele A, Mao JJ, Carver J, Gracia C, Hill-Kayser CE, Metz JM, Hampshire MK, Vachani C, Pucci D, Meadows AT. CA Cancer J Clin. 2009 Nov-Dec;59(6):391-410.

Abstract

BACKGROUND:
In late reproductive-aged breast cancer survivors, there is a need for real-time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age-matched control women and determined the association between these hormones and postchemotherapy menstrual pattern.

METHODS:
Breast cancer patients (n = 127) with American Joint Committee on Cancer stage I to III disease who were premenopausal at diagnosis were enrolled postchemotherapy and observed. The primary endpoint was chemotherapy-related amenorrhea (CRA) (> or = 12 months of amenorrhea after chemotherapy). Matched pair analyses compared AMH, inhibin B, and follicle-stimulating hormone (FSH) levels between cancer and age-matched control subjects. Associations between hormones, CRA status, and change in CRA status over time were assessed.

RESULTS:
The median age of the patients at chemotherapy was 43.2 years (range, 26.7-57.8 years). At enrollment, median follow-up since chemotherapy was 2.1 years, and 55% of subjects had CRA. Compared with age-matched controls, cancer subjects had significantly lower AMH (P = .004) and inhibin B (P < .001) and higher FSH (P < .001). AMH (P = .002) and inhibin B (P = .001) were found to be significantly associated with risk of CRA, even after controlling for FSH. AMH was significantly lower (P = .03) and FSH was significantly higher (P = .04) in menstruating subjects who developed subsequent CRA.

CONCLUSIONS:
AMH and inhibin B are 2 additional measures of postchemotherapy ovarian function in late reproductive-aged breast cancer survivors. With further research and validation, these hormones may supplement limited current tools for assessing and predicting postchemotherapy ovarian function.

Su HI, Sammel MD, Green J, Velders L, Stankiewicz C, Matro J, Freeman EW, Gracia CR, Demichele A. Cancer. 2009 Nov 13.

Abstract

BACKGROUND:
Female cancer patients are offered ‘banking’ of gametes before starting fertility-threatening cancer therapy. Transplants of fresh and frozen ovarian tissue between healthy fertile and infertile women have demonstrated the utility of the tissue banked for restoration of endocrine and fertility function. Additional methods, like follicle culture and isolated follicle transplantation, are in development. METHODS Specialist reproductive medicine scientists and clinicians with complementary expertise in ovarian tissue culture and transplantation presented relevant published literature in their field of expertise and also unpublished promising data for discussion. As the major aims were to identify the current gaps prohibiting advancement, to share technical experience and to orient new research, contributors were allowed to provide their opinioned expert views on future research. RESULTS Normal healthy children have been born in cancer survivors after orthotopic transplantation of their cryopreserved ovarian tissue. Longevity of the graft might be optimized by using new vitrification techniques and by promoting rapid revascularization of the graft. For the in vitro culture of follicles, a successive battery of culture methods including the use of defined media, growth factors and three-dimensional extracellular matrix support might overcome growth arrest of the follicles. Molecular methods and immunoassay can evaluate stage of maturation and guide adequate differentiation. Large animals, including non-human primates, are essential working models. CONCLUSIONS Experiments on ovarian tissue from non-human primate models and from consenting fertile and infertile patients benefit from a multidisciplinary approach. The new discipline of oncofertility requires professionalization, multidisciplinarity and mobilization of funding for basic and translational research.

J. Smitz, M.M. Dolmans, J. Donnez, J.E. Fortune, O. Hovatta, K. Jewgenow, H.M. Picton, C. Plancha, L.D. Shea, R.L. Stouffer, E.E. Telfer, T.K. Woodruff, and M.B. Zelinski. Human Reproduction Update, 2010.

Nieman CL, Kinahan KE, Yount SE, Rosenbloom SK, Yost KJ, Hahn EA, Volpe T, Dilley KJ, Zoloth L, Woodruff TK. Cancer Treat Res. 2007;138:201-17. Review. No abstract available. PMID: 18080667

Abstract

OBJECTIVE:
To characterize the early experience of a clinical program designed to provide strategies for fertility preservation to female cancer patients about to undergo chemotherapy or radiation therapy.

DESIGN:
Retrospective chart review; case-control study.

SETTING:
Academic medical center.

PATIENT(S):
Sixty-five female cancer patients and 57 age-matched infertility patients.

INTERVENTION:
Enrollment in a program for fertility preservation.

MAIN OUTCOME MEASURE(S):
Choice of active participation, fertility preservation option selection, clinical outcomes of patients undergoing oocyte retrieval, attitudes regarding embryo disposition.

RESULT(S):
Of 65 patients referred to the program, 18 declined to undergo embryo, oocyte, or tissue cryopreservation. Six were found not to be eligible for medical reasons. Of the remaining 41 patients, 35 chose to cryopreserve embryos, four chose to cryopreserve oocytes, and two chose to undergo ovarian tissue freezing. Fewer oocytes were recovered from the embryo cryopreservation group when compared with an age-matched control group, but the mean number of zygotes generated was similar. Attitudes regarding embryo disposition were different between the two groups. No serious clinical sequelae resulted from participation.

CONCLUSION(S):
Fertility preservation techniques employing available technology may provide safe and practical options to female cancer patients facing chemotherapy or radiation therapy. A significant number of otherwise appropriate participants decline active management. Cancer patients display different attitudes regarding embryo disposition when compared with infertility patients without cancer.

Susan C. Klock, John X. Zhang, and Ralph R. Kazer; Fertility and Sterility, In Press 2009

“Fertility preservation treatments can be expensive; cost and the lack of insurance coverage are often the major reasons given by oncologists for why they do not provide information on fertility preservation options to their patients. One method of ensuring people in their reproductive years or children who are diagnosed with cancer have access to and insurance coverage for FPT is to legally treat them as a distinct group from people diagnosed with infertility.”

Basco D, Campo-Engelstein L, and Rodriguez, S. Journal of Law, Medicine, and Ethics.

Abstract

OPINION STATEMENT:
Breast cancer effects nearly 200,000 American women each year, with 9% of these women still in their childbearing years. For this subset of future survivors, the issue of fertility may be a significant quality-of-life concern. Both the causes and treatments for infertility in young breast cancer patients must be thoroughly understood by the multidisciplinary team caring for these women in order for the caregivers to be effective advocates for their patients. Radiation, cytotoxic chemotherapy, and hormonal therapy all effect ovarian function to greater or lesser degrees, with the incidence of permanent post-treatment amenorrhea following systemic treatment for breast cancer in women age 50 or younger estimated as between 33% and 76%. The science of fertility preservation continues to experience significant advances in terms of the success of oocyte, embryo, and ovarian tissue preservation, and it is crucial that physicians and patients are aware of the available fertility preservation options. The optimal time to address the possibility of treatment-related infertility and strategies to combat this with younger patients is prior to treatment, rather than after cancer therapy has begun, and a full knowledge of the available technologies is a prerequisite for an informed discussion. Causes of ovarian suppression and options for treatment, including consideration of preimplantation genetic diagnosis and alternative parenting approaches are also discussed to assist the clinician caring for young patients with cancer.

Hulvat MC, Jeruss JS. Curr Treat Options Oncol. 2009 Dec;10(5-6):308-17. Review.

Co-editors Clarisa Gracia and Teresa K. Woodruff

Forward by Roger A. Lobo, MD

Part I: Fertility Risks for Cancer Patients

1. Gonadotoxicity of Cancer Therapies in Pediatric and Reproductive-Age Females by Jennifer Levine
2. Gonadotoxicity of Cancer Therapies in Pediatric and Reproductive-Age Males by Jill P. Ginsberg

Part II: Options for Preserving Fertility

1. Fertility Preservation in Males by Robert Brannigan
2. Embryo and Oocyte Banking by Lynn M. Westphal and Jamie A.M. Massie
3. Ovarian Tissue Cryopreservation and Transplantation by Laxmi Kondapalli, MD, MS
4. The Role of In Vitro Maturation in Fertility Preservation by Peter S. Uzelac, Greg L. Christiansen, and Steven T. Nakajima
5. Mitigating the Risk: The Role of Ovarian Transposition and Medical Suppression by Jaime M. Knopman and Nicole Noyes

Part III: Care of the Oncofertility Patient

1. The Birds and the Bees and the Bank: Talking With Families About Future Fertility Amidst a Cancer Diagnosis by Gwendolyn P. Quinn, Caprice A. Knapp, and Devin Murphy
2. Addressing the Three Most Frequently Asked Questions of a Bioethicist in an Oncofertility Setting by Lisa Campo-Engelstein
3. Pregnancy in Cancer Survivors and Patients by Eileen Wang
4. Communication Between Oncofertility Providers and Patients by Jennifer Mersereau

Part IV: Oncofertility in Clinical Practice

1. Setting up an Oncofertility Program by H. Irene Su, Lindsay Ray, and R. Jeffery Chang
2. Patient Navigation and Coordination of Care for the Oncofertility Patient: A Practical Guide by Kristin Smith, Brenda Efymow, and Clarisa Gracia
3. Preparing an Interdisciplinary Workforce in Oncofertility – A suggested educational and research training program by Christos Coutifaris

Part V: Clinical Cases in Oncofertility and Resources

1. Clinical Cases in Oncofertility by Clarisa Gracia

Appendices – Oncofertility Resources for the Clinician by Kate E. Waimey

1. Appendix A. Sample IRB Protocol: Ovarian Tissue Freezing For Fertility Preservation In Women Facing a Fertility Threatening Medical Diagnosis Or Treatment Regimen
2. Appendix B. Sample Consent Form: Ovarian Tissue Freezing For Fertility Preservation In Adult Women Facing A Fertility Threatening Medical Diagnosis Or Treatment Regimen
3. Appendix C. Sample IRB Protocol: Oocyte Banking For Fertility Preservation In Women Facing A Fertility Threatening Medical Diagnosis Or Treatment Regimen
4. Appendix D. Sample Consent Form: Oocyte Banking For Fertility Preservation In Women Facing A Fertility Threatening Medical Diagnosis Or Treatment Regimen
5. Appendix E. Letter Template: Provider Letter of Medical Necessity for Fertility Preservation Procedures
6. Appendix F. Letter Template: Patient Letter of Appeal for Fertility Preservation Procedures Template
7. Appendix G. Updating or Establishing Your FDA Registration

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.

Gracia, C R. Cancer and Treatment Research. 2010; 156: 3-9. PMID: 20811821.

PURPOSE:
Diminished reproductive capacity is a devastating consequence of life-sparing therapies for childhood malignancy. In 2006, the American Society of Clinical Oncology (ASCO) published fertility preservation recommendations (ASCOR) emphasizing the importance of early discussion and intervention for fertility preservation strategies. Using the Survey for Preservation of Adolescent REproduction (SPARE), we sought to determine fertility preservation attitudes and practice patterns post-ASCOR from pediatric oncology specialists nationwide.

MATERIALS and METHODS:
The SPARE survey consists of 22 questions assessing pediatric oncology specialists’ attitudes and practice patterns toward fertility preservation. Broad perspectives on fertility preservation, including a willingness to discuss fertility, knowledge of current fertility preservation methods and awareness of ASCOR, were assessed.

RESULTS:
The majority of respondents acknowledged that fertility threats are a major concern for them and agreed that all pubertal cancer patients should be offered a fertility consultation, but only 46% reported they refer male pubertal cancer patients to a fertility specialist prior to cancer treatment >50% of the time, and only 12% reported they refer female pubertal cancer patients to a fertility specialist prior to cancer treatment > 50% of the time. While 44% of respondents were familiar with the 2006 ASCOR, only 39% of those utilized them to guide decision-making in greater than half of their patients.

CONCLUSION:
Our study demonstrates pediatric oncologists’ motivation to preserve fertility in pediatric cancer patients; however, barriers to both gamete cryopreservation and referral to fertility specialists persist. Female pubertal patients are referred to fertility preservation specialists with much less frequency than are male pubertal patients, highlighting a disparity.

Köhler TS, Kondapalli LA, Shah A, Chan S, Woodruff TK, Brannigan RE. J Assist Reprod Genet. 2010 Nov 26.

Abstract

OBJECTIVE:
To articulate the need for a new approach to primary ovarian insufficiency. The condition, also known as premature menopause or premature ovarian failure, is defined by the presence of menopausal-level serum gonadotropins in association with irregular menses in adolescent girls or women younger than 40 years. It can be iatrogenic as related to cancer therapy or may arise spontaneously, either alone or as part of a host of ultrarare syndromes. In a large percentage of spontaneous cases no pathogenic mechanism can be identified.

DESIGN:
Literature review and consensus building at a multidisciplinary scientific workshop.

CONCLUSION(S):
There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of primary ovarian insufficiency. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about the condition. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency.

Amber R. Cooper, MD, Valerie L. Baker, MD, Evelina W. Sterling, PhD, Mary E. Ryan, MLS, Teresa K. Woodruff, PhD, and Lawrence M. Nelson, MD. Fertility and Sterility, 2010.

Trainer, J.; The American Brain Cancer Foundation Fertility Preservation March 24, 2009

Abstract

PURPOSE:
Oncofertility, an emerging discipline at the intersection of cancer and fertility, strives to give cancer patients options when they are confronting potential infertility as a consequence of cancer treatment. Fertility preservation decisions must be made before treatment begins, adding stress to the decision-making process.

METHODS:
Healthcare providers need to be aware of the intricacies involved in oncofertility decision making, and the often tight time line that patients face when making these decisions. Cancer patient’s perspectives may also change, as the dual burden of a cancer diagnosis and potential infertility can cause great flux in emotions.

RESULTS:
A provider-facing decision tree was created to enhance patient decision-making capacities and outline the multiple potential intervention points.

CONCLUSIONS:
Decision trees, which highlight the important decision points during which providers can approach patients, can be a useful tool to help providers in counseling patients on fertility preservation.

Shauna L. Gardino, Jacqueline S. Jeruss, Teresa K. Woodruff. J Assit Reprod Genet, 2010.