A case of secretory azoospermia: is valganciclovir responsible?

Valganciclovir, the prodrug of ganciclovir, is an antiviral agent targeting herpes viruses. It is indicated for the prophylaxis or treatment of cytomegalovirus infections in immunocompromised patients. Pre-clinical studies state ganciclovir as a mutagenic, teratogenic, reprotoxic drug that can rarely alter male fertility.

Mr S. had experienced primo-secondary infertility with his partner for 12 months. He had no significant medical history aside from exertional asthma and achieved semen analysis at age 33, revealing normal sperm concentration (110 million/mL, 383 million/ejaculate) with normal progressive motility (50%). One month after, during a trail race, he reported malignant exertional hyperthermia (41.7°C) leading to multi-organ failure and coma and requiring intensive care and an emergency hepatic transplant. Post-transplant, anti-rejection therapy was started including tacrolimus, mycophenolate mofetil, co-trimoxazole, and valganciclovir. Six months after the transplant, he undertook sperm cryopreservation. Repeated semen analysis confirmed azoospermia. Semen analysis 12 weeks after discontinuation of valganciclovir showed rare motile sperm, allowing cryopreservation. Subsequent analyses showed significant improvement, with concentration reaching 10.1 M/mL 14 weeks later and 70 M/mL 24 weeks later, allowing ICSI with fresh sperm. This resulted in a successful pregnancy and live birth.

We report a case of azoospermia observed after valganciclovir treatment. Based on a review of the literature, the azoospermia observed in this patient could be attributed to valganciclovir. However, alternative explanations such as fever or infectious complications cannot be ruled out. Valganciclovir is reprotoxic and should be replaced with an alternative drug in men planning to conceive.