Risks of genetic damage in offspring conceived using spermatozoa produced during chemotherapy or radiotherapy

Background Men who have just started cytotoxic therapy for cancer are uncertain and concerned about whether spermatozoa collected or pregnancies occurring during therapy might be transmitting genetic damage to offspring. There are no comprehensive guidelines on the risks of different doses of the various cytotoxic, and usually genotoxic, antineoplastic agents. Objectives To develop a schema showing the risks of mutagenic damage when spermatozoa, exposed to various genotoxic agents during spermatogenesis, are collected or used to produce a pregnancy. Materials and methods A comprehensive literature review was performed updating the data on genetic and epigenetic effects of genotoxic agents on animal and human spermatozoa exposed during spermatogenic development. Results Relevant data on human spermatozoa and offspring are extremely limited, but there are extensive genetic studies in experimental animals that define sensitivities for specific drugs and times. The animal data were extrapolated to humans based on the stage when the cells were exposed and the relative kinetics of spermatogenesis and were consistent with the limited human data. In humans, alkylating agents and radiation should already induce a high risk of mutations in spermatozoa produced within 1 or 2 weeks after initiation of therapy. Topoisomerase II inhibitors and possibly microtubule inhibitors produce the greatest risk at weeks 5-7 of therapy. Nucleoside analogs, antimetabolites, and bleomycin exert their mutagenic effects on spermatozoa collected at 7-10 weeks of therapy. Discussion and conclusions A schema showing the time from initiation of therapy at which specific antineoplastic agents can cause significant levels of genetic damage in conceptuses and live offspring was developed. The estimates and methods for computing the level of such risk from an individual patient's treatment regimen will enable patients and counselors to make informed decisions on the use of spermatozoa or continuation of a pregnancy.