EFFECT OF MYO-INOSITOL AND ALPHA-LIPOIC ACID ON OOCYTE QUALITY IN POLYCYSTIC OVARY SYNDROME NON-OBESE WOMEN UNDERGOING IN VITRO FERTILIZATION: A PILOT STUDY.

Rago R, Marcucci I, Leto G, Caponecchia L, Salacone P, Bonanni P et al. J Biol Regul Homeost Agents. 2015 Oct 1;29(4):913-23.

Polycystic ovary syndrome (PCOS) is a common condition affecting women that impacts both metabolic health and fertility. Many women with PCOS struggle to conceive, and may undergo assisted reproductive technologies such as in vitro fertilisation (IVF). Myo-inositol is known for its insulin-sensitising properties and is commonly used by women with PCOS. Alpha-lipoic acid is a potent antioxidant and also supports metabolic function.

Study Design

This is an open, prospective study including 37 non‑obese women with PCOS who had previously undergone IVF cycles supplemented with myo-inositol 4g plus folic acid 400 mcg daily but did not achieve pregnancy. After a six‑month washout period, participants received three months of combined myo-inositol 2 g daily plus alpha-lipoic acid 800 mg daily, followed by another IVF cycle. Outcomes were compared within the same patients between their myo-inositol only and myo-inositol + alpha-lipoic acid cycles, reducing interindividual variability.

Key assessments included:

• Endocrine and metabolic parameters (body mass index, insulin levels, lipids, oral glucose tolerance test)
• Ovarian volume and reserve
• Oocyte maturation stage and morphological quality
• Embryo grading
• Fertilisation, cleavage, and pregnancy rates

Key Findings

Metabolic Improvements
Myo-inositol + alpha-lipoic acid supplementation resulted in:

• Body mass index (BMI) reduced from 22.3 at baseline to 21.2 after three months (p<0.01)
• Fasting and post‑load insulin levels reduced at three months compared to baseline, notably at 60 and 120 minutes of oral glucose tolerance test (p<0.001)
• Ovarian volume reduced from 10.9 cm³  at baseline to 9.5 cm³ at three months (p<0.001)

These effects were not observed with myo-inositol alone, suggesting that alpha-lipoic acid strengthens insulin‑sensitising and metabolic responses.

Oocyte Quality
Compared with myo-inositol alone, the combination therapy resulted in:

• Fewer immature (germinal vesicles/degenerate, not suitable for use) oocytes (p<0.001)
• A higher proportion of mature metaphase 2 (MII) oocytes (p<0.05)
• A reduction in BMI was associated with a significant improvement in oocyte maturity (p=0.01)

Embryo Development
Myo-inositol + alpha-lipoic acid cycles produced:

• More grade 1 embryos (higher quality)
• Fewer grade 2 embryos (lower quality)
• No change in fertilisation or cleavage rates

This suggests a specific improvement in embryo quality, likely due to improved cytoplasmic and nuclear maturation conditions influenced by reduced oxidative stress and improved insulin signalling.

Pregnancy Rates
Although not statistically significant, pregnancy rates showed a positive trend:

• 52% with myo-inositol + alpha-lipoic acid versus 33% with myo-inositol alone (p= 0.07)

Given the small sample size and open-label design, these outcomes are promising but preliminary.

Conclusion

This pilot study suggests that combining myo‑inositol and alpha‑lipoic acid may offer synergistic benefits for oocyte maturity, embryo quality, and metabolic parameters in non‑obese PCOS patients undergoing IVF. While the increase in pregnancy rates did not reach statistical significance, the overall trends justify further investigation through larger, randomised controlled trials.