To achieve pregnancy, men with azoospermia must currently undergo a testicular procedure to retrieve sperm for intracytoplasmic sperm injection (ICSI). However, sperm are successfully retrieved only ~50% of the time. Recently, isotretinoin administration has been investigated as a means of increasing sperm production in azoospermic men. This review explains the rationale for isotretinoin use and will update readers on the results from early studies of isotretinoin treatment of male infertility.
Pilot studies suggest that isotretinoin treatment for 3-6 months may improve sperm production to the point of reliable ejaculated sperm in up to one quarter of men with azoospermia. Notably, response rates differ by histological sub-type, with 25-40% of men with maturation arrest exhibiting improvement, while men with Sertoli-cell only syndrome do not appear to benefit. A recent case series found that in men with cryptozoospermia, sperm production can be stimulated to levels that allow for ICSI using ejaculated samples in about half of men, thus obviating the need for testicular sperm retrieval procedures.
Isotretinoin therapy may improve sperm production in a subset of men with severe infertility. A fuller understanding of which men will benefit from isotretinoin will require larger studies.
Current opinion in urology. 2026 Jul 08 [Epub ahead of print]
John K Amory, Molly Jessup, Paul J Turek
Department of Medicine, University of Washington, Seattle, Washington, USA., The Turek Clinic, San Francisco, California, USA.