Friday, May 2. Parenthood After Cancer Treatment: Discussing Fertility With Your Patients. Clinical Lecture 8 9:30 am Arena

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1 Clinical Lecture 8 9:30 am Arena Parenthood After Cancer Treatment: Discussing Fertility With Your Patients Oncology nurses should play an active role in teaching patients about how cancer and its treatment affect fertility. Join ONS Clinical Award winner Joanne Kelvin, RN, MSN, AOCN, for an empowering presentation on what you need to know. You ll learn about the biologic effects of treatment on reproductive health, options for preserving fertility before treatment and building a family afterward, and resources for educating patients, including when to refer someone to a reproductive specialist. You ll come away with new oncology nursing strategies and an increased awareness of the updated American Society of Clinical Oncology guidelines about fertility preservation. Content Area: Clinical Practice Content Level: Intermediate Coordinator/Speaker: Joanne Kelvin, RN, AOCN Clinical Nurse Specialist Memorial Sloan-Kettering Cancer Center New York, NY kelvinj@mskcc.org Full Disclosure: Nothing to Disclose Objectives: At the end of this session, participants will be able to: 1. Explain effects of cancer treatment on reproductive health. 2. Discuss options for patients to preserve fertility before treatment and build a family after treatment. 3. Describe strategies to communicate with patients about fertility and family building. Content Outline: I. Effects of treatment on reproductive health A. Males (impaired sperm production, impaired sperm transport, pituitary gland dysfunction) B. Females (depletion of ovarian follicles, uterine damage, pituitary gland dysfunction) II. Fertility preservation before treatment A. Options for males (sperm banking, electroejaculation, testicular sperm extraction, and gonadal shielding) B. Options for females (embryo/oocyte cryopreservation, ovarian tissue cryopreservation, ovarian transposition, ovarian suppression, alternative treatment) C. Options for children (ovarian/testicular tissue cryopreservation) III. Family building after treatment A. Options for men to have a biologic child (natural conception, frozen sperm, testicular sperm extraction) B. Options for women to have a biologic child (natural conception, frozen embryos/oocytes, ovarian stimulation with in vitro fertilization) C. Alternative options (donor sperm/oocytes/embryos, surrogacy/gestational carrier, adoption) IV. Strategies for discussing fertility with patients A. Introducing the topic B. Explaining risks and options C. Making referrals D. Recognizing associated social, cultural, religious, and ethical issues E. Supporting patients around decision-making Bibliography: Guidelines American Society of Reproductive Medicine. (2013a). Fertility preservation and reproduction in patients facing gonadotoxic therapies. Fertility and Sterility (0nline). doi: /j.fertnstert American Society of Reproductive Medicine. (2013b). Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: A committee opinion. Fertility and Sterility (0nline). doi: /j.fertnstert Coccia, P., Altman, J., Bhatia, S., Borinstein, S.C., Flynn, J., George, S.,... Shead, D.A. (2012). Adolescent and young adult oncology. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 10(9), Fallat, M.E., Hutter, J., American Academy of Pediatrics Committee on Bioethics, American Academy of Pediatrics Section on Hematology/Oncology, & American Academy of Pediatrics Section on Surgery.. (2008). Preservation of fertility in pediatric and adolescent patients with cancer. Pediatrics, 121(5), e1461-e1469. Loren, A.W., Mangu, P.B., Beck, L.N., Brennan, L., Magdalinski, A.J., Partridge, A.H.,... Oktay, K. (2013). Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. Journal of Clinical Oncology, 31(19), Males Choy, J.T., & Brannigan, R.E. (2013). The determination of reproductive safety in men during and after cancer treatment. Fertility and Sterility, 100(5),

2 Howell, S., & Shalet, S. (2005). Spermatogenesis after cancer treatment: Damage and recovery. Journal of the National Cancer Institute. Monographs, 2005(34), Hwang, K., Ridgeway, A., & Lamb, D.J. (2013). Spermatogenesis. In J.P. Mulhall, L.D. Applegarth, R.D. Oates, & P.N. Schlegel (Eds.), Fertility Preservation in Male Cancer Patients. Cambridge University Press. Katz, D.J., Kolon, T.F., Feldman, D.R., & Mulhall, J.P. (2013). Fertility preservation strategies for male patients with cancer. Nature Reviews. Urology, 10(8), Samplaski, M.K., & Sabanegh Jr., E.S. (2013). The semen analysis. In J.P. Mulhall, L.D. Applegarth, R.D. Oates, & P.N. Schlegel (Eds.), Fertility Preservation in Male Cancer Patients. Cambridge University Press. Females Bedaiwy, M.A., Abou-Setta, A.M., Desai, N., Hurd, W., Starks, D., El-Nashar, S.A.,... Falcone, T. (2011). Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: A systematic review and meta-analysis. Fertility and Sterility, 95(3), , e Ben-Aharon, I., Gafter-Gvili, A., Leibovici, L., & Stemmer, S.M. (2010). Pharmacological interventions for fertility preservation during chemotherapy: A systematic review and meta-analysis. Breast Cancer Research and Treatment, 122(3), Ben-Aharon, I., & Shalgi, R. (2012). What lies behind chemotherapy-induced ovarian toxicity? Reproduction, 144(2), Donnez, J., Jadoul, P., Squifflet, J., Van Langendonckt, A., Donnez, O., Van Eyck, A.S.,... Dolmans, M.M. (2010). Ovarian tissue cryopreservation and transplantation in cancer patients. Best Practice and Research. Clinical Obstetrics and Gynaecology, 24(1), Gracia, C.R., Sammel, M.D., Freeman, E., Prewitt, M., Carlson, C., Ray, A.,... Ginsberg, J.P. (2012). Impact of cancer therapies on ovarian reserve. Fertility and Sterility, 97(1), , e131. Hoffman, B.L. (2012). Reproductive endocrinology. In B.L. Hoffman, J.O. Schorge, J.I. Schaffer, L.M. Halvorson, K.D. Bradshaw, F.G. Cunningham, & L.E. Calver (Eds.), Williams Gynecology (2nd ed.). McGraw-Hill. Lawrenz, B., Henes, M., Neunhoeffer, E., Fehm, T., Huebner, S., Kanz, L.,... Mayer, F. (2012). Pregnancy after successful cancer treatment: What needs to be considered? Onkologie, 35(3), Meirow, D., Biederman, H., Anderson, R.A., & Wallace, W.H.B. (2010). Toxicity of chemotherapy and radiation on female reproduction. Clinical Obstetrics and Gynecology, 53(4), Morgan, S., Anderson, R.A., Gourley, C., Wallace, W.H., & Spears, N. (2012). How do chemotherapeutic agents damage the ovary? Human Reproduction Update, 18(5), Noyes, N., Melzer, K., Druckenmiller, S., Fino, M.E., Smith, M., & Knopman, J.M. (2013). Experiences in fertility preservation: Lessons learned to ensure that fertility and reproductive autonomy remain options for cancer survivors. Journal of Assisted Reproduction and Genetics, 30(10), Oktem, O., & Oktay, K. (2008). The ovary: anatomy and function throughout human life. Ann N Y Acad Sci, 1127, 1-9. Reddy, J., & Oktay, K. (2012). Ovarian stimulation and fertility preservation with the use of aromatase inhibitors in women with breast cancer. Fertility and Sterility, 98(6), Rodriguez-Wallberg, K.A., & Oktay, K. (2012). Options on fertility preservation in female cancer patients. Cancer Treatment Reviews, 38(5), Westphal, L., & Massie, J. (2012). Embryo and oocyte banking. In C. Garcia & T.K. Woodruff (Eds.), Oncofertility Medical Practice: Clinical Issues and Implementation. New York: Springer. Wo, J.Y., & Viswanathan, A.N. (2009). Impact of radiotherapy on fertility, pregnancy, and neonatal outcomes in female cancer patients. International Journal of Radiation Oncology*Biology*Physics, 73(5),

3 MALES Basics of Reproductive Biology Effects of Cancer Treatment Fertility Preservation before Treatment Fertility Effects of Treatment Impaired sperm production Depletion of stem cells and developing sperm Recovery Oligospermia Azoospermia Impaired sperm transport Injury to pelvic ducts/blood vessels/nerves erectile/ejaculatory dysfunction Pituitary gland dysfunction Disruption of hypothalamic-pituitary-gonadal axis Howell & Shallet 2005; Meistrich 2009 Fertility Preservation Options Sperm Cryopreservation (Banking) Cryopreservation Reduction of Toxicity Semen collected, analyzed, placed in vials, frozen, and stored for possible future use Post-Pubertal Sperm banking Electroejaculation Testicular sperm extraction Pre-Pubertal Testicular tissue Gonadal shielding Sperm Bank Collection Manual stimulation 3 collections Abstain 2-5 days Electroejaculation EEJ If patient is unable to collect manually Testicular Sperm Extraction TESE If patient is azoospermic Katz et al 2013; Trost & Brannigan 2012 Testicular Tissue Cryopreservation Investigational Pre-pubertal boys Tissue biopsied, frozen, and stored for potential future use Tissue reimplantation no live births to date Concern about re-implanting cancer cells In vitro maturation no live births to date Gonadal Shielding During pelvic/inguinal field radiation With IMRT to minimize testicular dose Recommend sperm banking before treatment Available only at select centers Katz et al 2013; Trost & Brannigan 2012 Katz et al 2013; Trost & Brannigan

4 FEMALES Basics of Reproductive Biology Effects of Cancer Treatment Fertility Preservation before Treatment Fertility Effects of Treatment Depletion of ovarian follicle pool (oocytes) Premature ovarian failure infertility, menopause Narrowed window of reproductive opportunity Gonadotoxic therapy # Follicles Menopause Age (years) Fertility Effects of Treatment Fertility Preservation Options Uterine damage Vascular changes, endometrial injury inability to support embryo implantation Myometrial fibrosis inability to accommodate a growing fetus Pituitary gland dysfunction Disruption of hypothalamic-pituitary-gonadal axis Cryopreservation Post-Pubertal Embryos Oocytes Ovarian tissue Reduction of Toxicity Ovarian transposition Ovarian suppression Ben-Aharon & Shalgi 2012; Gracia et al 2012; Meirow et al 2010; Morgan et al 2012; Wo & Viswanathan 2009 Pre-Pubertal Ovarian tissue Alternative treatment Embryo Cryopreservation Oocyte Cryopreservation Ovarian stimulation Oocyte retrieval In vitro fertilization Cryopreservation Ovarian stimulation Oocyte retrieval In vitro fertilization Cryopreservation ASRM 2013; Rodriguez-Wallberg & Oktay 2012; Westphal & Massie 2012 ASRM 2013; Rodriguez-Wallberg & Oktay 2012; Westphal & Massie

5 Embryo/Oocyte Cryopreservation Medical Concerns Delay in treatment Estrogen Specific medical risks ASRM 2013; Noyes 2013; Rodriguez-Wallberg & Oktay 2012; Westphal & Massie 2012 Ovarian Tissue Cryopreservation Investigational Post-pubertal, can not delay treatment Pre-pubertal girls Ovary resected, cortex dissected, frozen, and stored for potential future use Tissue reimplantation ~30 live births to date Concern about re-implanting cancer cells In vitro maturation no live births to date Available at selected centers Donnez et al 2010 Ovarian Transposition Prior to pelvic/inguinal field radiation With IMRT to minimize ovarian & uterine dose Also consider embryo/oocyte cryopreservation If IVF needed in the future patient will need transabdominal retrieval Does not protect the uterus Ovarian Suppression GnRH agonist (leuprolide) To prevent recruitment of follicles, potentially protecting them from effects of chemotherapy Initiated 2-4 weeks before starting chemotherapy, continued monthly throughout treatment Investigational - studied primarily in breast cancer and lymphoma with conflicting results Bedaiwy et al 2011; Ben-Aharon et al 2010 Alternative Treatment For Select Patients Early stage cervical cancer Radical Trachelectomy BUILDING A FAMILY AFTER TREATMENT Evaluation of Fertility Family Building Options Rectal cancer No pelvic radiation Non-gonadotoxic chemotherapy regimen 5

6 Evaluation of Fertility Evaluation of Male Fertility It is impossible to predict with certainty who will be affected permanently Timing of evaluation is a consideration Men can recover sperm production years later Females may initially be fertile but lose fertility at a young age Schedule evaluation 12 months or longer after completion of treatment Semen analysis (WHO criteria, 2010) Volume Sperm count Hormonal analysis FSH, LH, Testosterone 1.5 ( ) ml 39 (33-46) million/ejaculate Sperm concentration 15 (12 16) million/ml Progressive motility 32 (31 34)% Vitality 58 (55 63)% Samplaski & Sabanegh 2013 Evaluation of Female Fertility Fertility Preservation After Treatment Reproductive Endocrinologist Transvaginal ultrasound Ovarian antral follicle count Hormonal analysis Anti-Mullerian Hormone (AMH) Follicle Stimulating Hormone (FSH) Estradiol An option to consider for: Adolescent and young adult females Did not undergo egg freezing before treatment Menstruating regularly, but are at risk for premature ovarian failure Not yet ready to start a family Natural Conception Pregnancy Considerations Wait at least 1-2 years Time allows for Clearance of damaged gametes Recovery from treatment Pass time of greatest risk for recurrence/relapse Ability to carry a pregnancy Hysterectomy High dose pelvic RT Safety of carrying a pregnancy Late effects of treatment Risk of recurrence Patients with metastatic disease Consider referral to a Maternal Fetal Medicine Specialist or Cardiologist Choy & Brannigan 2013, Lawrenz et al 2012; Nangia et al

7 Family Building Options for Men Family Building Options for Women Biologic Child Biologic Child Thawed Sperm TESE Thawed Embryos Thawed Eggs Retrieval of Fresh Eggs IUI or IVF +/- ICSI IVF +/- ICSI IVF +/- ICSI Natural Conception Embryo Transfer Natural Conception Embryo Transfer Surrogacy Alternative Family Building Options For women who cannot carry a pregnancy Traditional Surrogate Insemination of surrogate to create the embryo Surrogate is birth mother AND biologic mother Significant legal risks Gestational Carrier IVF to create embryo transferred into carrier s uterus Carrier is birth mother but NOT biologic mother Favored approach Not Able to Have a Biologic Child Donor Sperm/ Eggs/Embryos Adoption/ Foster Parenting Child-Free Living Donor Gametes and Embryos Finding gametes and embryos Sperm sperm banks Eggs fertility center or egg donor agency Embryos embryo donor agency Few government requirements for testing/screening No oversight to ensure compliance with standards Consider recommendations from fertility center or reproductive attorney Adoption Domestic versus international Attorney versus agency (private or public) Issues for patients who have had cancer Cancer-free for a period of time May require medical letter International adoptions generally more restrictive; regulations vary widely and change frequently 7

8 COMMUNICATING ABOUT FERTILITY Parenthood After Cancer TReatment Prepare Assess Consider Teach Refer Prepare Reflect on Your patient population How fertility is currently addressed Your personal assumptions or biases Prepare Identify reproductive specialists in your area Males Sperm banks: state licensure/fda registration Society for Male Reproduction and Urology Females American Society for Reproductive Medicine Society for Assisted Reproductive Technology Prepare Identify resources for patients Informational brochures and/or web sites Cancer.net, SaveMyFertility, MyOncofertility Financial LiveSTRONG/Fertility, HeartBeat Prepare Collaborate with physician colleagues on how to integrate fertility discussion into practice Clarify impact of frequently used treatments Discuss safety of fertility preservation based on various patient situations Establish the optimal timing for the discussion Define roles and responsibilities Assess Relationship status Prior children Desire for children in the future Awareness of treatment-related fertility risks Awareness of fertility preservation options 8

9 Consider Factors related to planned treatment Risk of impaired fertility Consider future treatment as well Factors related to disease Safety of delaying treatment Safety of undergoing fertility preservation Factors that may influence decisionmaking Teach Discuss early enough that patient has time to act on the information Integrate into teaching about other treatment side effects Be direct, honest, and matter of fact Keep intent in mind Be respectful and nonjudgmental Consider the unique needs of adolescents Teach Explain risks Explain fertility preservation options Keep it simple ASCO guidelines - key discussion points listed in section on communication Refer For patients who are interested in learning more or who already know they want to pursue fertility preservation Facilitate scheduling the appointment Consider coordination needs of complex patients Clarify timing to plan start of treatment Loren et al 2013 Summary It is our responsibility to ensure patients are informed of their treatment-related fertility risks and of their options to preserve fertility before cancer treatment. Interested patients should be referred to appropriate reproductive specialists. A systematic approach to communicating about fertility can help nurses better address these issues. 9