Alpha-Lipoic Acid Supplementation for Male Partner of Couples with Recurrent Pregnancy Loss: A Post hoc analysis in Clinical Trial

Document Type : Original Article


1 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

2 Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

3 Isfahan Fertility and Infertility Center, Isfahan, Iran

4 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

5 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran


Background: Increased sperm DNA damage is known as one of the causes of recurrent pregnancy loss(RPL) which can be due to increased levels of oxidative stress. In this study, the effect of alpha-lipoic acid (ALA) as an antioxidant soluble in water and fat was investigated on sperm parameters and sperm function tests in couples with a history of RPL.

Materials and Methods: In this preliminary study, a total of 37 patients (n=12 and n=25 for placebo and ALA groups, respectively) were considered. Men with high sperm DNA damage were treated with ALA (600 mg/day) or placebo for 80 days. Semen samples were acquired from the participants before initiation and after completion of the medication course and assessed regarding conventional sperm parameters, DNA damage/integrity, intracellular oxidative stress, lipid peroxidation, and seminal antioxidant characteristics. Individuals were further followed up for twelve months for pregnancy occurrence and outcomes. Finally, after excluding patients with no history of RPL, the data was analyzed.

Results: No statistically significant difference was observed between the baseline measures except for seminal volume. However, after the intervention, the mean sperm DNA damage (TUNEL), nuclear protamine deficiency, and persisted histones were significantly lower in the ALA group than placebo receivers (p<0.05). We noticed a decrease in the mean levels of seminal total antioxidant capacity (p=0.03), malondialdehyde (p=0.02), and SCSA-assayed sperm DNA damage (p=0.004) as well as an increase in mean sperm total motility (p=0.04) after treatment with ALA. In addition, the mean of nuclear protamine deficiency and remnant histone content were declined post-ALA therapy (p=0.003 and 0.002, respectively). Regarding post-medication pregnancy loss, no statistically significant difference was observed between the two groups (p=0.15).

Conclusions: ALA-therapy attenuates sperm DNA damage and lipid peroxidation while enhancing sperm total motility and chromatin compaction in the male partner of couples with RPL.


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