Oral isotretinoin as a strategy to boost male reproductive health

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Created On: 21/11/2025

Retinoic acid (RA), vitamin A metabolite, is critical for spermatogenesis. Men with infertility often exhibit diminished intratesticular RA levels.

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Key take away

Oral isotretinoin boosts the production of reliably motile ejaculated sperm in a subset of men with nonobstructive azoospermia or cryptozoospermia.

Background

Retinoic acid (RA), vitamin A metabolite, is critical for spermatogenesis. Men with infertility often exhibit diminished intratesticular RA levels. Early studies suggest RA supplementation can enhance sperm counts in oligospermic men and induce sperm production in nonobstructive azoospermia (NOA). This study evaluated whether oral isotretinoin could stimulate spermatogenesis in men with NOA or cryptozoospermia.

Method

In this single-center, prospective study, infertile men battling NOA or cryptozoospermia received isotretinoin (20 mg twice daily) for 3–9 months, with serial metabolic and semen assessments. Participants included men of all infertility etiologies, including those with prior testicular sperm retrieval. The primary endpoint was achieving consistently motile ejaculated sperm suitable for in vitro fertilization by intracytoplasmic sperm injection (IVF-ICSI).

Result

Among 30 men treated, 4 (13%) were reported to be intermittently cryptozoospermic and 26 (87%) were reported to be azoospermic. Most azoospermic men (92%) illustrated prior testicular procedures; 23% exhibited a history of cryptozoospermia. Overall, 11/30 men (37%) produced reliably motile ejaculated sperm during therapy. Histology revealed the highest response (54%) among men with maturation arrest. Reported adverse effects encompassed altered cholesterol (17%), dry skin/chapped lips (100%), irritability (47%), and rash (13%).

Conclusion

Intratesticular RA deficiency may underlie certain forms of severe male infertility. Oral isotretinoin can restore sperm generation in NOA or cryptozoospermia, potentially minimizing the need for invasive sperm retrieval procedures.