Sirolimus-associated infertility: Case report and literature review of possible mechanisms

The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters. Herein, we report on a case of sirolimus-associated infertility in a young male heart-lung transplant recipient and provide a detailed synopsis of potential mechanisms by which sirolimus may negatively influence spermatogenesis. Testicular immunohistochemistry, the course of sex hormone and sperm quality parameters of our patient support the hypothesis that mTOR might act as an important key regulator in the reproductive system. Fortunately, due to withdrawal of sirolimus as part of the maintenance, immunosuppression improved sperm quality and sex hormone parameters could be observed. Recently, these improvements even resulted in a spontaneous pregnancy of the patient's wife more than 1 year after the drug was withdrawn. In our view, oligospermia as a possible and at least partly reversible side-effect of mTOR inhibitors has to be taken into consideration, particularly, when administrated to young male patients.