Can alpha‑lipoic acid (ALA) be used as an adjunct therapy to improve pregnancy rates in women with infertility due to oxidative stress, polycystic ovary syndrome, or endometriosis, and what is the appropriate dosage and safety profile?

Alpha-Lipoic Acid in Female Infertility

Based on current evidence, alpha-lipoic acid (ALA) cannot be recommended as a standard treatment for female infertility, as there are no high-quality randomized controlled trials demonstrating improved live birth rates or pregnancy outcomes. While preliminary research suggests potential benefits in specific contexts like obesity-related infertility and PCOS, the evidence remains insufficient to support routine clinical use.

Evidence Quality and Limitations

The available evidence for ALA in female infertility suffers from the same methodological problems that plague antioxidant research in reproductive medicine:

• No guideline-level recommendations exist for ALA specifically in female infertility from major reproductive medicine societies 1
• The 2025 European Association of Urology guidelines on male infertility note that antioxidant therapy evidence is "still conflicting," with a Cochrane review showing that when high-risk-of-bias studies were removed, increases in live birth rates were no longer apparent 1
• Similar conclusions apply to female infertility: a Cochrane review of 48 antioxidant studies found only 7 reported clinical pregnancy rates and only 4 reported live births, with low-quality evidence and insufficient data on adverse effects 2

Specific Clinical Contexts Where ALA Shows Preliminary Promise

Obesity-Related Infertility

• A 2020 study in obese infertile women showed that 800 mg ALA daily plus 2 g myo-inositol for 2 months before ovarian stimulation improved antioxidant capacity in follicular fluid and pregnancy rates approached those of normal-weight women 3
• The supplemented obese group showed significantly higher antioxidant levels compared to unsupplemented controls, with improved mitochondrial function markers in granulosa cells 3
• Dosage tested: 800 mg ALA daily combined with 2 g myo-inositol for at least 2 months prior to assisted reproductive technology 3

Polycystic Ovary Syndrome (PCOS)

• ALA's effects in PCOS appear limited to metabolic parameters (insulin resistance) rather than reproductive outcomes 4
• A 2022 review concluded that "ALA does not seem to influence significantly reproductive hormones" and that "ALA usefulness in improving inositol activity still awaits convincingly confirmation" 4
• Clinical implication: ALA should not be recommended for routine PCOS management, even when combined with myo-inositol, due to lack of reliable evidence 4

Endometriosis

• The American College of Obstetricians and Gynecologists recommends combining vitamins C and E (not ALA specifically) with first-line hormonal treatment for pain management in endometriosis, but this is for symptom control, not fertility improvement 2, 5
• The American Academy of Family Physicians explicitly states that medical treatment of endometriosis, including antioxidants, does not improve future fertility 5
• ALA combined with N-acetyl cysteine and bromelain has been studied for endometriosis-related pain, but not for fertility outcomes 6

Theoretical Mechanisms vs. Clinical Reality

While ALA demonstrates multiple beneficial properties in laboratory and preliminary studies:

• Antioxidant effects: Reduces oxidative stress, which affects oocyte quality and embryo development 7, 8
• Anti-inflammatory action: Decreases pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) that may impair reproduction 7
• Metabolic effects: Improves insulin sensitivity, potentially beneficial in PCOS and obesity 4, 6

However, these mechanistic benefits have not translated into proven improvements in the outcomes that matter most: live births and healthy pregnancies 1, 2.

Safety Profile

• ALA appears generally safe in the doses studied (400-800 mg daily) for short-term use (2-3 months) 3, 6
• No significant adverse effects were reported in the available female fertility studies 8, 3
• However, long-term safety data in pregnancy planning and early pregnancy remain limited 6

Evidence-Based Recommendations for Clinical Practice

Instead of ALA supplementation, prioritize interventions with proven fertility benefits:

• Weight optimization: Achieve BMI 18.5-25 kg/m² through caloric balance and exercise, which has established benefits for fertility 1
• Smoking cessation: Strong evidence supports negative effects on fertility 1
• Dietary modification: Increase fruits, vegetables, whole grains, and healthy fats while reducing refined carbohydrates and saturated fats 2
• Standard fertility treatments: Focus on evidence-based interventions appropriate to the specific cause of infertility 1

Critical Pitfalls to Avoid

• Do not delay proven fertility treatments while attempting ALA supplementation, as age-related fertility decline continues 1
• Do not use ALA as monotherapy for any fertility condition—if used at all, it should only be adjunctive to standard care 4
• Do not assume antioxidant benefits in male infertility translate to female infertility—the evidence bases are separate and both insufficient 1
• Beware of supplement interactions: ALA inhibits cytochrome P450 enzymes, which could theoretically affect fertility medication metabolism, though this has not been studied in reproductive contexts 9

When ALA Might Be Considered (Off-Label, Shared Decision-Making)

If a patient with obesity-related infertility undergoing IVF requests ALA after standard interventions:

• Consider: 800 mg ALA daily plus 2 g myo-inositol for 2 months before ovarian stimulation, based on the single positive preliminary study 3
• Counsel clearly: This is not standard of care, evidence is preliminary, and it should not replace weight loss efforts or delay proven treatments 3, 4
• Monitor: Ensure no delays in pursuing definitive fertility treatment while attempting supplementation 1

The fundamental problem remains: until large, well-designed randomized placebo-controlled trials with primary outcomes of live births are conducted, ALA cannot be recommended as an evidence-based fertility treatment 1.