Treatment with isotretinoin can improve de novo sperm production in nonobstructive azoospermia or cryptozoospermia.

Purpose: Retinoic acid (RA), a metabolite of vitamin A, is required for mammalian spermatogenesis. Clinically, intratesticular RA concentrations are lower in infertile men. In pilot studies, RA treatment is associated with increased ejaculated sperm counts in men with oligospermia and with de novo ejaculated sperm in nonobstructive azoospermia (NOA). We evaluated whether oral isotretinoin could improve sperm production in men with NOA and cryptozoospermia.

Methods: Single-center, prospective, repeated measures analysis of infertile men with NOA or cryptozoospermia who received isotretinoin (20 mg twice daily) and had metabolic and semen evaluations over 3-9 months. All etiologies of infertility were included, as were subjects with prior sperm retrieval procedures. The primary endpoint was attaining reliable motile ejaculated sperm for IVF-ICSI.

Results: Among n = 30 consecutive men undergoing isotretinoin treatment, 26 (87%) were azoospermic and 4 (13%) were intermittently cryptozoospermic. Among azoospermic men, 24 (92%) had prior testicular procedures and 6 (23%) had a history of cryptozoospermia. Overall, 11/30 (37%) of patients developed reliable, motile ejaculated sperm counts with treatment. When evaluating biopsy histology, those with maturation arrest patterns had the highest response (6/11 or 54%) to therapy. Side effects included 30 (100%) men with dry skin/chapped lips, 4 (13%) rashes, 14 (47%) irritability, and 5 (17%) with altered cholesterol panels.

Conclusion: Intratesticular retinoic acid deficiency may underlie some forms of severe male factor infertility. Treatment with isotretinoin increases sperm production in some men with NOA or cryptozoospermia to the point of obviating the need for testicular sperm retrieval procedures.