Is There an Increased Risk of Birth Defects From Paternal Exposure to Chemotherapy?

The search for better cancer treatment has produced chemotherapy drugs which significantly increase survival among certain cancer patients. Over 70% of patients now survive childhood cancer and this percentage is still improving.

Infertility can be a side-effect of chemotherapy, but many patients regain their fertility after treatment. There are concerns that therapy may induce germ-line mutations that increase the risks of birth defects in future offspring. Commonly used doses of chemotherapy drugs are in the range known to be mutagenic in experimental animals and several chemotherapies induce chromosomal abnormalities in the sperm of treated patients.

Storage of sperm prior to treatment is an option for many patients, but it must be done before any chemotherapy has been received. Even sperm harvested immediately after the start of therapy could have DNA damage, and hence affect the health of future offspring.

Human studies evaluating birth defects from paternal exposure to chemotherapy have found little evidence of increased chromosomal abnormalities or genetic diseases. Although these findings are reassuring, some researchers working in this field think the data has limitations:

• The studies include patients who received both mutagenic and nonmutagenic agents with broad differences in drug regimens, doses and exposure time.
• These studies involved small numbers of children born to cancer survivors and the criteria measured were not always the same.
• Most parents involved were treated as children and therefore became fathers a long time after treatment. This data is unlikely to be reflective of patients treated as young adults who have offspring shortly after they have recovered from chemotherapy .

These variables have made it difficult to calculate reliable risks for survivors treated with specific chemotherapy drugs.

• Rodent experiments assessing birth defects from paternal exposure to chemotherapy suggest that the link is complex.
• Direct measurements of chromosomal abnormalities in the sperm of mice have shown that some agents are more damaging to sperm cells than others. This is also affected by the dose.
• The risk of producing chromosomally defective sperm is highest in the first few weeks after chemotherapy. This risk appears to decrease with time.

The extent to which paternal exposures to chemotherapy drugs contribute to human infertility and pregnancy loss is unknown. What is well-established however is the risk from occupational exposure to toxic substances. Epidemiological data show that occupations involving exposure to metals, combustion products, solvents or pesticides (e.g.welder, painter, mechanic, firefighter) are linked to increased male infertility and adverse reproductive outcomes.

Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies. A.Wyrobek A, T.Schmid, F.Marchetti Journal of the National Cancer Institute, 2005 Vol 34 P31-5.

Advances in male-mediated developmental toxicity. Edited by B.Robaire & B.Hales. Advances in Experimental Medicine and Biology 2003, Vol 518, P1–300.