Does isotretinoin (Accutane) affect long-term fertility?

From the Guidelines

Isotretinoin (Accutane) does not appear to affect long-term fertility in either men or women, as there is no evidence suggesting that past isotretinoin use impacts future fertility or reproductive outcomes once the medication has been stopped. While men taking isotretinoin may experience temporary changes in sperm parameters during treatment, these effects are reversible after discontinuation of the medication 1. For women, the primary concern with isotretinoin is its high teratogenic potential, meaning it can cause severe birth defects if pregnancy occurs during treatment or shortly after, but this does not translate to permanent damage to reproductive organs or fertility potential 1.

Key points to consider:

• Temporary changes in sperm parameters in men are reversible after stopping the medication.
• No evidence suggests past isotretinoin use affects future fertility or reproductive outcomes in women once the medication is stopped.
• Isotretinoin is highly teratogenic, necessitating strict pregnancy prevention measures for women of childbearing potential, including two forms of contraception and regular pregnancy testing during treatment and for one month after stopping the medication.
• The teratogenic effects are related to the drug's ability to interfere with embryonic development but do not imply permanent damage to fertility potential.

Given the potential for temporary side effects and the necessity of strict pregnancy prevention, it is crucial for individuals considering isotretinoin treatment to discuss their concerns and questions with their dermatologist or healthcare provider to make an informed decision. This discussion should include the potential temporary effects on fertility, the importance of pregnancy prevention, and the lack of evidence suggesting long-term fertility issues 1.

From the FDA Drug Label

In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of isotretinoin of 2,8, or 32 mg/kg/day (0.3,1.3, or 5. 3 times the recommended clinical dose of 1 mg/kg/day, respectively, after normalization for total body surface area). In studies of 66 men, 30 of whom were patients with nodular acne under treatment with oral isotretinoin, no significant changes were noted in the count or motility of spermatozoa in the ejaculate In a study of 50 men (ages 17 to 32 years) receiving isotretinoin therapy for nodular acne, no significant effects were seen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose.

Isotretinoin and Long-Term Fertility:

• The available data from studies in rats and men suggest that isotretinoin does not have a significant impact on gonadal function or fertility.
• Key findings include:
  • No adverse effects on fertility in rats at dosages up to 5.3 times the recommended clinical dose.
  • No significant changes in sperm count or motility in men treated with isotretinoin.
  • No significant effects on ejaculate volume, sperm count, or sperm morphology in men receiving isotretinoin therapy. Based on the available evidence from the FDA drug label 2 and 2, it appears that isotretinoin does not affect long-term fertility.

From the Research

Isotretinoin and Long-Term Fertility

• The effect of isotretinoin (Accutane) on long-term fertility is a topic of interest due to its teratogenic properties and widespread use in treating severe acne.
• Studies have shown that isotretinoin can have a negative impact on ovarian reserve, which is an indicator of female fertility 3.
• However, research suggests that the deteriorative effects of systemic isotretinoin treatment on ovarian reserve diminish over time, with mean anti-Mullerian hormone (AMH), ovarian volume (OV), and antral follicle count (AFC) values returning to similar levels as before treatment after 12 months 3.
• It is essential for women of reproductive age to use effective contraception while taking isotretinoin to prevent exposed pregnancies, which can result in major birth defects 4, 5, 6.
• Compliance with pregnancy prevention programs, such as the Dutch Pregnancy Prevention Programme, is crucial to minimize the risk of isotretinoin-exposed pregnancies, but studies have shown that concomitant use of isotretinoin and contraceptives is often too low 7.

Key Findings

• Isotretinoin can affect ovarian reserve, but the effects may diminish over time 3.
• Effective contraception is essential for women of reproductive age taking isotretinoin to prevent exposed pregnancies 4, 5, 6.
• Compliance with pregnancy prevention programs is crucial, but often inadequate 7.
• Reserving isotretinoin prescribing to specialists may improve adherence to pregnancy prevention programs 7.

Implications

• Women of reproductive age should be aware of the potential risks of isotretinoin on fertility and take necessary precautions to prevent exposed pregnancies.
• Healthcare providers should emphasize the importance of effective contraception and compliance with pregnancy prevention programs when prescribing isotretinoin.
• Further research is needed to fully understand the long-term effects of isotretinoin on fertility and to develop effective strategies for minimizing the risk of isotretinoin-exposed pregnancies.