Male fertility and effect of cancer treatment.
Infertility is defined as the failure to achieve pregnancy after more than one year of regular sexual intercourse without contraception. As is the case with women, fertility in men is contingent on a normal anatomy and normal functioning of the gonads. The testicles produce sperm and sex hormones, including testosterone, under the control of gonadotropins. Sperm production starts at puberty. Men produce sperm from stem cells throughout their adult lives in a continuous cycle that takes about 70 days
Infertility in men with cancer may be caused by the disease itself and/or by surgery, chemotherapy and radiation treatment (table 1)
(2). With testicular cancer and Hodgkin’s lymphoma, sperm quality may deteriorate and the sperm may suffer DNA damage even before the cancer treatment starts (3). Transient infertility induced by various types of cytostatics may last for several years after the completion of treatment. Permanent infertility occurs most commonly after high doses of cytostatics treatment (alkylating cytostatics), after radiation of the testicles with doses of > 1.2 Gy and after full body radiation prior to haematopoietic stem cell transplantation (4). Chemotherapy and radiation therapy affect both the sterol cells and the lending cells in the testicles, but the germinal epithelium is more prone to cell damage than the lending cells, so that infertility is a more frequent side effect than endocrine hypogonadism. Radiation treatment of the central nervous system with doses of ≥ 40 Gy can result in hypogonadotropic hypogonadism. Cancer treatment can damage the nerves and blood supply of the pelvis, which can cause problems with ejaculation and/or erection.
Risk of azoospermia due to cancer treatment (2)
Full body radiation
Irradiation of testicles ≥ 2.5, Gy men, ≥ 6 Gy prepubertal boys
Alkylating chemotherapy (including cyclophosphamide ≥ 7.5 g/m²
High-dose melphalan chemotherapy with stem cell support (HMAS)
Protocols for treating lymphoma that contain procarbazine: BEACOPP¹, cyclophosphamide, vincristine, procarbazine, prednisone-dacarbazine (COPP), nitrogen mustard, vincristine, procarbazine, prednisone (MOPP)
Radiation of the brain ≥ 40 Gy
Bleomycin, etoposide, cisplatin (BEP) with testicular cancer
Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)
Carboplatin < 2 g/m²
Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD)
Vincristine, etoposide, prednisone, doxorubicin, (OEPA)
Irradiation of testicles 0.2 – 0.7 Gy
In some men, there has been a documented decline in normal testicular function after radiation treatment and various types of chemotherapy several years after treatment has finished, depending on the dose and type of treatment (Table 1). As with women, protection of the gonads during radiation treatment is therefore standard practice. With boys, some serious benign diseases, for example aplastic anaemia, thalassaemia, sickle cell anaemia, Langherhans cell histiocytosis, haemophagocytic lymphohistiocytosis, Wegener’s granulomatosis and Klinefelter’s syndrome, may also result in infertility due to the disease itself or to gonadotoxic treatment of the underlying disease. Fertility-preserving treatment may also be relevant for these patients, but at present it is only offered to those who are receiving gonadotoxic treatment for their underlying disease.
In Norway, all fertility treatment is regulated by the Biotechnology Act
(5). Fertility preservation is an important topic for many young cancer survivors (6). Several studies have demonstrated that failing to discuss the negative effects of cancer treatment can result in greater emotional stress and a poorer quality of life after remission (7).
Fertility-preserving treatment should always be considered for boys and young men who are going to undergo cancer treatment
(8) and patients must receive clear information about the possible side effects of the therapy, including fertility-related topics. Figures 1 and 2 provide an overview of fertility-preserving treatment for boys and young men.
Figure 1 Schematic overview of fertility-preserving methods for prepubertal boys and men who do not produce semen samples
Figure 2 Schematic overview of fertility-preserving methods for adult men who produce semen samples