Oncofertility in the 21st Century: The Impact of Mutagenic Chemotherapy Exposure on Gamete Preservation

Abstract

Cancer treatment-related infertility concerns are heavily intertwined to the impact of utilized agents on hormonal and gonadal function, and resultant decreased gonadal reserve or premature gonadal failure. While recommendations for germ cell preservation are primarily focused on causal infertility, they do not account for prior chemotherapeutic exposures that may potentially result in genetic mutation, possibly leading to birth defects. This investigational analysis is offered to enhance recognition of those agents and exposures which should be identified during oncofertility assessment and preclude gamete preservation. An original analysis examining the documented pharmacokinetics and mutagenic toxicities of conventional chemotherapy was conducted, with results then compared to administration rates of such agents over a 23-week period. Of the investigated agents (and related metabolites), a substantial 54% were found to be of mutagenic capability; analysis of the agent distribution pattern demonstrated mutagenic exposures within more than one-third of the treated child-bearing population, an age bracket representing 27% of the total study patient population. As the capability to alter the DNA of oocytes and sperm is present for greater than half of conventional chemotherapies, determination of prior exposures to mutagenic chemotherapeutics should be undertaken. If exposure is confirmed, preclusion of gamete preservation may be warranted secondary to possible increased risk of genetic mutation potentially leading to birth defects, both physical and mental. Identification of such exposures in reproductive-age cancer patients, as well as the need to assess newly developed oncologic agents for mutagenic/clastogenic potential fundamentally changes the current approach to fertility preservation.