Cancer Related Male Infertility
With modern treatment protocols, many cancers have excellent prognoses. Because of this, efforts are being made to not only treat the cancer, but also address long-term concerns, such as future family planning.
Cancer-related fertility problems include effects related to the malignancy itself, and the effects of treatments, such as chemotherapy, radiation and surgery on the testicles. Most cancers are treated with a variety of therapies.
The two primary functions of the testicles are to produce sperm and testosterone. Because the sperm producing cells in the testicles are exquisitely sensitive to the effects of cancer treatments, sperm production can easily decrease with cancer treatments. The effects are generally dose dependent and can cause a low sperm count (oligospermia) or no sperm at all (azoospermia). These effects may be permanent or temporary, and may result in genetically abnormal sperm precursors. Contraception/abstinence is recommended during treatment. Although little data is published about how long it takes for sperm cells to recover following treatment, contraception/abstinence is suggested for 24 months.
The testicular cells that produce testosterone are less likely to be affected. Low testosterone levels can secondarily affect male fertility by altering libido, erectile function and sexual satisfaction.
It is important that patients undergo a discussion of fertility preservation options prior to the start of cancer treatments. In this way, they may have the option of having a family after their cancer has been treated.
The toxicity of chemotherapeutic agents depends on the type of cancer treated, agent used, dosage administered, dosing interval and other agents used simultaneously. No chemotherapeutic agent can be considered truly without risk. Therapies are typically categorized according to how toxic they are to the testicles.
- Alkylating agents (cyclophosphamide, chlorambucil, mustine, ifosfamide)
- Nitrogen mustard derivatives (busulfan, melphalan)
- MOPP regimen (nitrogen-mustard, oncovin (vincristine), procarbazine, prednisone)
- BEP (bleomycin, etoposide, cisplatin)
- ABVD (adriamycin, bleomycin, vinblastine, dacarbazine)
- Topoisomerase inhibitors
- Vinca alkaloids (vincristine, vinblastine)
Cisplatin is a mainstay in the treatment of malignancies seen in men of reproductive age, including testicular cancers and lymphomas. Low doses of cisplatin may hurt the testicles and lower sperm counts, and high doses may severely suppress sperm production. Post-treatment paternity also varies significantly according to treatment, with 80% of men being successful in achieving a live birth after surgery alone, 73% after low-dose cisplatin-based chemotherapy and 42% after high-dose cisplatin.
Radiation therapy (either directly to the testis or through scatter exposure) can damage the testicles. The sperm producing cells are more sensitive than the testosterone producing cells. Damage is dependent on total radiation dose received, radiation field, as well as the dosing schedule. However, very low doses have been shown to result in temporary azoospermia, and moderate doses in permanent azoospermia. Prepubertal boys are more sensitive than adults. Total body irradiation prior to stem cell transplantation is particularly toxic due to the high radiation doses required, and causes permanent gonadal failure in approximately 80% of men.
Surgery alone does not usually impact sperm production. However, abdominal or pelvic surgery for cancer may impair sexual or reproductive function. An obvious example is removal of a testicle, for testicular cancer. Others include damage to the nerves or accessary structures responsible for erections or ejaculation. Efforts have been made to technically minimize these risks, but at times they are unavoidable.
Because of these effects, it is crucial that male cancer patients undergo a discussion of fertility preservation options prior to the start of cancer treatments. Cryopreservation of sperm prior to treatment is oftentimes recommended, as it provides “insurance” for the preservation of post-treatment fertility. Traditionally, the banking of 3 semen samples is recommended. However, some cancers are themselves associated with abnormal sperm, thus there is no guarantee that the stored samples will be completely normal. Sperm banking is only an option for post-pubertal males. In pre-pubertal males, no clinically proven methods are available and all options are considered experimental.