Background: An advanced cancer diagnosis at a reproductive age can disrupt expectations of a normal lifecycle and rob patients of the opportunity for parenthood. Cancer often presents with little warning and can compromise reproductive functioning directly or indirectly via treatments. This Fast Fact reviews the psycho-social, logistical, and ethical concerns regarding reproduction for patients facing advanced cancer. Certain content may be applicable for patients with other life-limiting illnesses; however, there is less available published evidence to guide fertility planning for non-cancer illnesses.

Importance of fertility counseling: Although multiple professional organizations recommend fertility counseling at diagnosis for any person of reproductive-age diagnosed with cancer, many patients do not recall receiving adequate fertility counseling and report unmet informational needs (1). These unaddressed concerns have been associated with psychologic distress (2,3). Conversely, those who received timely fertility counseling experienced less regret, better coping, and better quality of life (4,5). Barriers to fertility counseling include clinician uncertainty about who should provide the counseling, perceived lack of training in leading these discussions, cost of preservation, and worry about the appropriateness of the topic (6,7). To navigate these barriers, consider the following learning pearls: 

• Surveys suggest that patients feel it is the primary cancer clinicians’ responsibility to initiate fertility counseling and make appropriate referrals to fertility specialists (7,8).
• Initial fertility counseling should occur at or shortly after diagnosis and should be focused on whether to pursue fertility preservation (7). This is a psychosocially complex issue, especially for terminal illnesses given that the patient may not survive to co-parent. Palliative care specialists, social workers, chaplains, psychologists, and/or nurses can be helpful with these discussions.
• Patients should specify in writing what they would want to happen to any stored genetic material posthumously and inform designated proxies or guardians of their reproductive intentions (9,10).
• Providers should not assume that all patients with terminal diagnoses have decreased fertility, or that all desire to preserve their fertility. Some patients may wish to utilize contraceptive methods to prevent unwanted pregnancy. Of note, certain contraceptive methods are contraindicated depending on the patient’s risk of VTE, cancer type, and other comorbidities. The Centers for Disease Control’s Summary Chart of U.S. Medical Eligibility Criteria for Contraceptive Use is a helpful resource for choosing appropriate contraceptive methods (11).

Effect of cancer treatment on fertility:  

• The American Cancer Society has online educational resources for men and women specific to fertility in the context of cancer diagnosis and treatment (12).
• Radiation is teratogenic and therefore cancer clinicians aim to avoid it during pregnancy. If it cannot be avoided, fetal and infertility risk depends largely on the radiation dose and anatomic location, with direct exposure of reproductive organs or the pituitary gland carrying the greatest infertility risk (13).
• Most oncologic surgeries can be safely performed during pregnancy with minimal risk to the mother or fetus, though surgery involving pelvic organs is more likely to harm fertility or a pregnancy (13).
• Bone marrow transplants usually lead to temporary or permanent infertility; hence, fertility preservation, if desired, should be completed prior to transplantation.
• Most chemotherapeutic agents are pregnancy category Cor D meaning they pose potential risks to normal fetal development (14). The severity of this risk varies by agent and timing. The greatest risk to the fetus occurs during the first trimester, when organogenesis is occurring. Therefore, chemotherapy may be delayed if appropriate (13). Patients with a first trimester pregnancy who require urgent chemotherapy may be advised to consider pregnancy termination (13). Chemotherapy agents can be detected in semen and vaginal secretions, though it is unknown how long they persist and how much of a risk this poses to sexual partners (15). Patients receiving chemotherapy are often advised to use barrier protections such as condoms to protect their partners from exposure.
• There are limited data on immunotherapy and its effect on fertility and fetal development.

Fertility preservation options:  Fertility preservation generally involves referral to a reproductive endocrinologist, ob-gyn, urologist, and/or fertility center as options have become varied, complex, and effective. Considerations when choosing a preservation method include the patient’s state of health, treatment regimen, age, partner status, and the cost of the procedures and associated storage of genetic material, which are often not covered by insurance. Most preservation methods now can be completed within days to weeks. For females, options include cryopreservation of oocytes, embryos, or ovarian tissue, as well as ovarian transplantation, suppression, shielding, or transposition. For males, options include sperm banking or retrieval, testicular tissue cryopreservation (still experimental), and gonadal shielding.  Alternatively, surrogates, gamete donors, and adoption can be considered.

Ethical and legal concerns:  What happens to stored sperm, oocytes or embryos after a patient’s death is ethically and legally complex. Laws and policies governing the custody and use of genetic material vary by country, state and institution. Ideally, patients have specified in writing their reproductive intentions (9,10). Use of gametes stored prior to the patient’s death without the patient’s written consent may be allowed in certain cases, however (9). If the patient did not store genetic material, posthumous gamete retrieval has been described, though few medical centers currently have policies governing this (16). An ethics committee for the American Society for Reproductive Medicine has stated that post-mortem retrieval and use of gametes and embryos is “ethically justifiable” when there is written consent from the deceased person(9). Without written consent, they caution health care centers to consider such requests only if initiated by the surviving spouse or partner (9).

References:

1. Benedict C, Thom B, N Friedman D et al. Young Adult Female Cancer Survivors’ Unmet Information Needs and Reproductive Concerns Contribute to Decisional Conflict Regarding Posttreatment Fertility Preservation. Cancer. 2016;122(13):2101-9.
2. Wenzel L, Dogan-Ates A, Habbal R et al. Defining and measuring reproductive concerns of female cancer survivors. J Natl Cancer Inst Monogr. 2005;(34):94-8.
3. Logan S, Perz J, Ussher JM, Peate M, Anazodo A. Systematic review of fertility-related psychological distress in cancer patients: Information on an improved model of care. Psycho-oncology. 2019;28(1):22-30.
4. Letourneau JM, Ebbel EE, Katz PP et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012;118(6):1710-7.
5. Despande NA, Braun IM, Meyer FL. Impact of fertility preservation counseling and treatment on psychological outcomes among women with cancer: A systematic review. Cancer. 2015;121(22):3938-47.
6. King L, Quinn GP, Vadaparampil ST et al. Oncology Nurses’ Perceptions of Barriers to Discussion of Fertility Preservation with Patients with Cancer. Clinical Journal of Oncology Nursing. 2008;12(3):467-76.
7. Taylor J and Ott M. Fertility Preservation after a Cancer Diagnosis: A Systematic Review of Adolescents’, Parents’, and Providers’ Perspectives, Experiences, and Preferences. J Pediatr Adolesc Gynecol. 2016;29(6):585–598.
8. Stein DM, Victorson DE, Choy JT et al. Fertility Preservation Preferences and Perspectives Among Adult Male Survivors of Pediatric Cancer and Their Parents. Journal of Adolescent and Young Adult Oncology. 2014;3(2):75-82.
9. Ethics Committee of the American Society for Reproductive Medicine. Posthumous Retrieval and Use of Gametes or Embryos: An Ethics Committee Opinion. Fertility and Sterility. 2018;110(1):45-49. 
10. American College of Obstetricians and Gynecologists Committee on Ethics. ACOG Committee Opinion No. 617: End-of-Life Decision Making. 2015. https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Ethics/End-of-Life-Decision-Making?IsMobileSet=false. Accessed June 2, 2019.
11. Centers for Disease Control and Prevention. Summary Chart of U.S. Medical Eligibility Criteria for Contraceptive Use. Accessed online 25 July, 2019. <https://www.cdc.gov/reproductivehealth/contraception/pdf/summary-chart-us-medical-eligibility-criteria_508tagged.pdf>.
12. American Cancer Society. Accessed online 31 July, 2019. <https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects.html>.
13. Hepner A, Negrini D, Azeka Hase E et al. Cancer During Pregnancy: The Oncologist Overview. World Journal of Oncology. 2019;10(1):28-34.
14. Leslie KK, Koil C, Rayburn WF. Chemotherapeutic Drugs in Pregnancy. Obstetrics and Gynecology Clinics of North America. 2005;32:627-640.
15. Memorial Sloan Kettering Cancer Center. Sexual Activity During Cancer Treatment: Information for Women. Accessed online 25 July, 2019. <https://www.mskcc.org/cancer-care/patient-education/sexual-activity-during-treatment-information-women#consider-steps-to-avoid-exposing-your-partner-to-chemotherapy-and-other-anticancer-medications>.
16. Waler N, Clavijo R, Brackett NL, Lynne CM, Ramasamy R. Policy on Posthumous Sperm Retrieval: Survey of 75 Major Academic Medical Centers. Urology. 2018;113:45-51.

Author affiliations: Massachusetts General Hospital, Boston, MA.

Conflicts of Interest: The authors have no conflicts of interest to disclose.

Version History:  originally edited by Sean Marks MD; first electronically published in September 2019