Fertility After Treatment for Cancer

Male Infertility

Cancer treatment can also result in male infertility by causing death of spermatogonia or stem spermatogonia.² Transient infertility is common as a result of treatment with chemotherapies and radiation therapies because differentiating spermatogonia are rapidly dividing; exposure to such agents substantially reduces spermatocyte numbers several weeks following treatment initiation and until the process of spermatogenesis can begin again. This process can take up to 12 weeks after chemotherapy discontinuation to resume.

Many alkylating agents, cisplatin, and nitrosoureas are toxic to stem spermatogonia and can result in permanent infertility, depending on the doses used and other agents that may be used in the regimens.²

Non-Chemotherapy Effects on Fertility

There is little evidence on the effect of targeted therapies on male infertility; most existing studies have only been conducted in rodents.² These studies primarily suggest that targeted agents have little or no effect on spermatogenesis, except for the use of imatinib during puberty, which is when adult spermatogonia and Leydig cells are developing. Similarly, few studies have evaluated the effect of targeted therapies on female fertility.⁴ Endocrine therapy may transiently cause infertility and bevacizumab may cause ovarian failure, likely due to its antiangiogenic effects.^4,5

There are no known studies on the effect of immune checkpoint inhibitors on male or female fertility.⁶

Fertility Preservation

The ASCO guideline provides recommendations for fertility preservation for adults and children.³ Patients who are interested or uncertain about their interest in fertility should be referred to a reproductive specialist before treatment is initiated to discuss their fertility preservation options. Some patients may also benefit from a referral to a psychosocial provider to help cope with distress regarding potential loss of fertility.

For adult men, the ASCO guideline states that sperm cryopreservation is recommended for postpubertal men before the initiation of treatment because there is a higher risk of genetic damage in sperm during active cancer treatment.³ Testicular tissue cryopreservation and reimplantation of the human testicular graft should only be done as part of a clinical trial or experimental protocol. Hormonal therapy does not preserve fertility in men.

There are several fertility preservation approaches that can be used among women. ASCO indicates that embryo and unfertilized oocyte cryopreservation and ovarian tissue cryopreservation for future transplantation are established options. Ovarian transposition, particularly for women undergoing pelvic irradiation, is another option, but is not always successful. For women with gynecologic malignancies, conservative surgery may spare fertility, but is dependent on the stage of a patient’s disease. There are conflicting data regarding the practice of ovarian suppression through use of gonadotropin-releasing hormone (GnRH) or other agents; therefore, ASCO recommends employing this approach only when established approaches are not feasible, particularly in young women with breast cancer.

Postpubertal children can achieve fertility preservation using the same approached that are established for adults.³ For prepubertal children, however, ASCO states that the only options are ovarian or testicular cryopreservation, and these methods are still considered investigational.

Conclusions

Cancer treatment can cause transient or permanent infertility in both men and women, and is dependent on the treatment regimen used. There are several fertility preservation approaches available for postpubertal patients.

References

1. Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol. 2016;12:2333-2344.
2. Meistrich ML. The effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil Steril. 2013;100(5). doi: 10.1016/j.fertnstert.2013.08.010
3. 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.
4. American Cancer Society. How cancer treatments can affect fertility in women. https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/fertility-and-women-with-cancer/how-cancer-treatments-affect-fertility.html. Updated June 28, 2017. Accessed December 12, 2018.
5. Imai A, Ichigo S, Matsunami K, Takagi H, Kawabata I. Ovarian function following targeted anti-angiogenic therapy with bevacizumab. Mol Clin Oncol. 2017;6(6):807-810.
6. Sood A, Cole D, Abdollah F, et al. Endocrine, sexual function, and infertility side effects of immune checkpoint inhibitor therapy for genitourinary cancers. Curr Urol Rep. 2018;19(9):68.