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

written by: niknak•edited by: Emma Lloyd•updated: 9/27/2010

Some chemotherapy drugs are mutagenic i.e cause DNA damage. If mutagenic changes occur in sperm, there is a theoretical risk of increased birth defects from paternal exposure to chemotherapy. This article summarizes current medical and scientific opinion on chemotherapy and male fertility issues.

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    Chemotherapy and Fertility

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

    Infertility can be a side-effect of chemotherapy, but many patients regaintheir fertility after treatment. There are concerns that therapy may induce germ-line mutations that increase therisks of birth defects in future offspring. Commonly used doses of chemotherapy drugsare in the range known to be mutagenic in experimental animals and several chemotherapies induce chromosomalabnormalities 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.

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    Human Studies on Congenital Defects and Chemotherapy

    Human studies evaluating birth defects from paternal exposure to chemotherapy have found littleevidence of increased chromosomal abnormalities or genetic diseases. Althoughthese findings are reassuring, some researchers working in this field think the data haslimitations:

    • The studies include patients who received both mutagenicand nonmutagenic agents with broad differences in drug regimens,doses and exposure time.
    • These studies involved small numbers ofchildren born to cancer survivors and the criteria measured were not always the same.
    • Most parents involvedwere 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 survivorstreated with specific chemotherapy drugs.

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    Animal Studies

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

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

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    References

    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.