Fertility Preservation in Patients with Cancer

Mollie Beck, PharmD
Oncology Clinical Pharmacist
Saint Elizabeth Healthcare
Edgewood, KYT

It is estimated that more than 90,000 adolescents and young adults (AYAs) aged 19 to 39 years are diagnosed with cancer each year in the United States.1 With advances in detection, treatment, and supportive care for various malignancies, long-term survival for this patient population is high—greater than 80% at 5 years.¹ This results in a growing number of cancer survivors of reproductive age. These patients may undergo a wide variety of therapies for cure, including radiation, chemotherapy, and surgery; however, the therapies may entail risks for subsequent treatment-related infertility, including azoospermia in men and premature ovarian failure in women. Alkylating agents, cranial radiation, and targeted radiation to the abdomen or pelvis pose the highest risk for infertility. The impact of cancer treatment on fertility is related to the age of the patient at the time of treatment and is dependent on the type, duration, and dose intensity of treatment. As efforts are focused on achieving the primary objective of cancer treatment—survival—reproductive health issues, including fertility preservation, may often be overlooked.

The importance of fertility to AYA survivors, however, has been well documented. In a study conducted at a large pediatric academic center, 80% of male AYAs reported a desire to have a biological child.² Another study revealed that almost 45% of male AYAs ranked fertility as one of the “top 3 life goal[s].”² Similar trends have been noted in female survivors. For example, a multi-institutional study of more than 600 AYA breast cancer patients showed that 50% of females expressed concerns about fertility at the time of diagnosis.¹ In addition, fertility concerns can negatively affect quality of life and cause significant psychological distress and depressive symptoms for survivors.³ This was demonstrated in a prospective case-control study involving hematopoietic stem cell transplant recipients, in which 55% of survivors reported that infertility had a negative impact on their emotions, relationships, and self-worth.⁴

With the aim of increasing awareness, knowledge, and opportunities related to cancer treatment and fertility, oncofertility has emerged as an interdisciplinary field intersecting oncology and reproductive medicine in order to expand fertility options for cancer survivors.⁵ In addition, clinical practice guidelines vaguely highlight the importance of fertility discussions with patients of reproductive age at the time of diagnosis. For example, the National Comprehensive Cancer Network recommends referral for fertility preservation clinics within 24 hours for all patients who are interested in pursuing fertility preservation upon diagnosis.⁶ In addition, the American Society of Clinical Oncology, the American Society for Reproductive Medicine, and the American Academy of Pediatrics have all issued recommendations (albeit brief ones) relating to education and referrals for patients interested in fertility preservation.^7,8

Despite recognition in the literature that fertility preservation can be an essential part of the treatment plan, it remains one of the most underprescribed and least implemented services provided to AYA patients with cancer.^6,9 A survey of cancer survivors revealed that 30%–40% of patients did not recall any sort of fertility discussion with their provider. In another survey, 45% of respondents reported self-initiation of the discussion.¹⁰ Furthermore, a number of patients recalled discussions of fertility impairment occurring not at diagnosis, but after treatment initiation. Although it is possible that the discussion of reproductive health was lost among the overwhelming emotions and abundance of information that accompany a new cancer diagnosis, studies of healthcare professionals suggest that infertility discussions are not routinely performed.⁷ A number of barriers have been cited and include oncologists’ lack of knowledge about fertility preservation techniques, lack of awareness of appropriate resources and referral centers, concern about potential treatment delay posed by the various preservation methods, the complexity of parental involvement in decision making and child assent, and lack of time for discussion.^7,8,11

Concerns about fertility seem to be similar for men and women; however, the options available for fertility preservation are quite different. Interestingly, sex-based differences in initiation of reproductive health discussions have been highlighted in the literature. One study showed that the majority of men had discussed fertility-related aspects of their treatment with their physician, while only half of women reported a similar discussion.¹⁰ Proposed explanations for this phenomenon include the ease and reliability of methods available for men versus those for women. Sperm banking is an effective and well-established method in which treatment delay is generally minimal. In addition, only a small amount of sperm is needed to generate a pregnancy.¹⁰ Female fertility preservation, on the other hand, is more complex, and in some cases may not be as easy or effective as sperm banking. Fertility preservation options and important considerations for men and women are summarized in Tables 1 and 2 (see PDF), respectively.

A multidisciplinary team composed of oncologists, reproductive endocrinologists, urologists, nurses, social workers, financial assistance personnel, bioethicists, psychologists, and pharmacists may be advantageous in optimizing the future reproductive health of cancer survivors. Specifically, a pharmacist may contribute through

• identification of patients of reproductive age eligible for consideration of fertility preservation
• patient education summarizing the risks associated with chemotherapy
• medication counseling and side-effect management in situations whereby pharmacotherapeutic methods are initiated
• consideration of alternative regimens whereby exposure to alkylating agents is reduced or eliminated without compromising care.

Fertility preservation and the possibility of having children are important for AYA cancer survivors. The lack of clear direction in clinical practice guidelines may contribute to the trend of documented underuse of fertility preservation in this patient population. Patients should be proactively informed and educated on the risk that cancer treatment poses to their fertility and the preservation options available. Having children may not be at the forefront of an AYA’s mind. Therefore, it may be helpful to initiate fertility discussions with a developmental perspective; for example, discussing what may be important in the present versus in the future.² In additional to the physical, emotional, and psychosocial support given during cancer treatment, addressing fertility and sexual health and function are essential to optimize cancer outcomes, particularly for AYAs.

References

1. Su HI, Lee YT, Barr R. Oncofertility: Meeting the fertility goals of adolescents and young adults with cancer. Cancer J. 2018;24(6):328-335.
2. Nahata L, Caltabellotta NM, Yeager ND, et al. Fertility perspectives and priorities among male adolescents and young adults in cancer survivorship. Pediatr Blood Cancer. 2018;65(7):e20719.
3. Gorman JR, Bailey S, Pierce JP, Su HI. How do you feel about fertility and parenthood? The voices of young female cancer survivors. J Cancer Surviv. 2012;6(2):200-209.
4. Hammond C, Abrams JR, Syrjala KL. Fertility and risk factors for elevated infertility concern in 10-year hematopoietic cell transplant survivors and case-matched controls. J Clin Oncol. 2007;25(33):3511-3517.
5. Woodruff TK. Oncofertility: a grand collaboration between reproductive medicine and oncology. Reproduction. 2015;150(3):S1-10.
6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Adolescent and Young Adult (AYA) Oncology. Version 1.2020 (July 11, 2019). Available at https://www.nccn.org/professionals/physician_gls/pdf/aya.pdf. Accessed: September 21, 2019.
7. Levine J, Canada A, Stern CJ. Fertility preservation in adolescents and young adults with cancer. J Clin Oncol. 2010;28(32):4831-4841.
8. Johnson RH, Kroon L. Optimizing fertility preservation practices for adolescent and young adult cancer patients. J Natl Compr Canc Netw. 2013;11(1):71-77.
9. Quinn GP, Block RG, Clayman ML, et al. If you did not document it, it did not happen: rates of documentation of discussion of infertility risk in adolescent and young adult oncology patients’ medical records. J Oncol Pract. 2015;11(2):137-144.
10. Armuand GM, Rodriguez-Wallberg KA, Wettergren L, et al. Sex differences in fertility-related information received by young adult cancer survivors. J Clin Oncol. 2012;30(17):2147-2153.
11. Jeruss JS, Woodruff TK. Preservation of fertility in patients with cancer. N Engl J Med. 2009;360:902-11.
12. Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994-2001.
13. De Vos M, Smitz J, Woodruff TK. Fertility preservation in women with cancer. Lancet. 2014;384(9950):1302-1310.