J Assist Reprod Genet

Isotretinoin may enable motile sperm recovery in severe male infertility

September 22, 2025

Study details: This single-center, prospective, repeated measures study enrolled 30 infertile men with nonobstructive azoospermia (NOA) or intermittent cryptozoospermia. Most had prior testicular sperm retrieval. Participants received oral isotretinoin 20 mg twice daily for 3 to 9 months, with serial metabolic and semen analyses. Primary endpoint: appearance of reliable motile ejaculated sperm suitable for in vitro fertilization by intracytoplasmic sperm injection (IVF-ICSI).

Results: Of 30 participants (87% azoospermic, 13% cryptozoospermic), 11 (37%) developed reliable motile ejaculated sperm. Response was highest (54%) in men with maturation arrest on biopsy. Side effects were consistent with isotretinoin’s known profile: dry skin/chapped lips (100%), irritability (47%), and lipid changes (17%).

Clinical impact: Isotretinoin may stimulate de novo sperm production in a subset of men with severe infertility, potentially avoiding surgical sperm retrieval. Further studies are needed to optimize dosing, identify responders, and assess long-term safety.

Source:

Jessup CM, et al. (2025, July 19). J Assist Reprod Genet. Treatment with isotretinoin can improve de novo sperm production in nonobstructive azoospermia or cryptozoospermia. https://pubmed.ncbi.nlm.nih.gov/40681858/