A widely used acne medication may offer new hope for men with severe infertility, according to a small study that suggests isotretinoin could stimulate sperm production in patients with extremely low or absent sperm counts.
The research, published in July in the Journal of Assisted Reproduction and Genetics, investigated isotretinoin (commonly known as Accutane) as a potential treatment for male infertility. Currently, men with nonobstructive azoospermia or cryptozoospermia face limited options, with surgical sperm retrieval being the primary medical intervention for in vitro fertilization (IVF).
Study Design and Participants
Researchers enrolled 30 men in the study: 26 with nonobstructive azoospermia (no sperm in ejaculate due to production problems) and four with cryptozoospermia (extremely low sperm numbers). All participants received 20 milligrams of isotretinoin twice daily for at least six months, with close monitoring of blood values, hormone levels, and semen parameters throughout the treatment period.
Promising Results in Subset of Patients
Of the 30 men treated, 11 began producing motile sperm in their ejaculate, enabling them and their partners to proceed with IVF without surgical intervention. This treatment-responsive group included all four men with cryptozoospermia and seven men who previously had no detectable sperm.
For the remaining 19 men who still required surgical sperm collection, the procedure became significantly more efficient after isotretinoin treatment. Surgery time decreased from an average of 105 minutes to 63 minutes, though the study did not specify the mechanism behind this improvement.
At the time of publication, nine IVF cycles had been completed using sperm collected after isotretinoin treatment, resulting in multiple healthy embryos, ongoing pregnancies, and one live birth.
Biological Mechanism
The treatment approach is based on previous research showing that infertile men often have reduced levels of retinoic acid in their testes. This vitamin A derivative plays a crucial role in sperm development, controlling the maturation of immature germ cells into functional sperm and facilitating their release into the seminiferous tubules. Isotretinoin, which mimics natural retinoic acid, was tested as a way to stimulate this essential process.
Safety Profile and Side Effects
All 30 participants experienced side effects, with dry skin and chapped lips occurring universally. Approximately half reported irritability, while some developed rashes and elevated cholesterol and triglyceride levels. The potential for liver function changes necessitates regular blood monitoring during treatment, similar to protocols used when prescribing isotretinoin for acne.
Expert Perspectives
Dr. Justin Houman, an assistant professor of urology at Cedars-Sinai Medical Center who was not involved in the study, expressed cautious optimism about the findings. "The idea that a well-studied drug could stimulate spermatogenesis in men with severely impaired sperm production is exciting because it opens the door to a non-surgical option for men who might otherwise require invasive testicular sperm retrieval," he told Live Science.
However, Houman emphasized the preliminary nature of the research: "The study is small, preliminary, and requires replication in larger, randomized trials before we can consider it a true breakthrough."
Dr. Brian Levine, founding partner and practice director of CCRM Fertility of New York, also not involved in the study, highlighted the potential impact: "The prospect of helping a patient avoid the pain, recovery time, and emotional stress of surgery is a source of genuine excitement for me and my colleagues." He cautioned that "this is not a cure-all, and there is much more research to be done."
Current Limitations and Future Research
Researchers acknowledge several important limitations. The optimal dosage, treatment duration, and long-term safety profile of isotretinoin for male infertility remain unknown. Response rates are unpredictable, and many men may not benefit from the treatment at all.
Until larger studies provide more definitive data, Houman cautioned that isotretinoin should not be used to treat male infertility outside of clinical trials.
Future research priorities include identifying which patients are most likely to respond to treatment, optimizing dosing protocols, and determining whether the drug can improve overall sperm quality and fertility outcomes.
Implications for Male Fertility Treatment
The potential for oral medication to restore sperm production represents a significant departure from current surgical approaches. As Levine noted, such a development "would represent a monumental shift in how we approach male infertility" and "offers a new layer of hope — not just the hope of finding sperm, but the hope of restoring a natural biological function."
The research also highlights important differences between male and female reproductive biology regarding isotretinoin safety. While the drug carries severe teratogenic risks for pregnant women, requiring black box warnings and strict contraception protocols, it appears to pose no DNA damage risks to sperm or resulting offspring in men.
