Before looking at the effect of chemotherapy on fertility, it is important to bear in mind that the cancer itself may have an effect on male fertility. Semen analyses in untreated men with Hodgkin lymphoma have shown reduced sperm counts in up to 50% of those surveyed, as well as poor motility and an elevated number of abnormal forms. Similar findings have been found in men with untreated testicular cancer.(20) This is important as the quality of sperm donated when men are unwell (prior to treatment) may affect the success of subsequent IVF treatment.

A recent survey by Schover et al (cited in Shin et al 2005) showed that 51% of men with cancer wanted children in the future. As it is hard to predict the exact impact of chemotherapy on a man’s fertility, sperm banking should be offered to all men (who wish to maintain their reproductive potential) before they undergo surgery, chemotherapy or radiotherapy.(21)

Temporary or permanent infertility can be a common side effect of chemotherapy. Chemotherapy, through its effect on rapidly dividing cells, can cause alpasia (lack of development) of the germinal epithelium which lines the semineferous tubules reducing sperm production. This can often lead to low sperm count (oligospermia) or total absence of sperm in the semen (azoospermia).

Men with cancer often have sperm counts of below 20 million per ml (a normal count is 20–150 million per ml). However, pregnancy is still possible even with this reduced count. A reduction in the sperm count can be detected as soon as 21 days after the first course of treatment and can continue to fall for two or three months. Azoospermia has been observed about 70 days after chemotherapy.(22)

Cytotoxic drugs have little effect on the Leydig cells however and testosterone production is not noticeably affected so that there are no changes in secondary sexual characteristics.

The recovery of sperm function following chemotherapy is unpredictable. Alkylating agents damage the germinal epithelium and appear to cause the most damage to the male gonad.

The dose given and the age at which the man had treatment appear to affect the severity and duration of oligospermia or azoospermia. The greater the dose of drug, the less chance there is of regaining fertility. Barton and Waxman (1995) report a study where it was shown that recovery from oligospermia due to chlorambucil was possible if treatment was stopped before a total dose of 400mg, but that azoospermia appeared to be irreversible with total doses of 25mg/kg or greater.(23)

Even in men who recover, it may be several years following their treatment before spermatogenesis is restored; the duration of this recovery period appears to be dose-related.(6)

Effects on fertility are greater and more prolonged with combination treatment than with single agents, and are related to total dose, length of treatment and the age of the patient. The majority of research has looked at men treated for Hodgkin lymphoma and testicular cancer. Currently, the ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) combination is a regimen for Hodgkin lymphoma which is far less likely to have a long-term effect on reproductive function than the previously given MOPP.

The drugs commonly used to treat testicular cancer include etoposide, bleomycin and cisplatin. Azoospermia is almost universal after this regimen but recovery is common with between 50% and 80% of men having a normal sperm count 3–5 years after treatment.(24)

NB prednisolone, which is used in a number of treatment regimens for lymphoma and leukaemia, is also associated with reversible oligospermia.

In men, the use of TBI usually causes infertility but with normal testosterone levels. If a booster dose of radiotherapy is given to the testes (so that total doses are greater than 20Gy), testosterone levels may be reduced and supplement therapy required. There have been reports of recovered fertility in men who were treated with cyclophosphamide and single-fraction TBI.(19)

Without TBI, recovery of fertility following a high-dose treatment is variable, although it is not so likely as with women. Age at treatment with BMT in men does not appear to be related to recovery of gonadal function.(19)