The seminal plasma contains natural antioxidants that act as free radical scavengers. When ROS production exceeds the natural scavenger capacity of seminal fluid, oxidative stress increases. Spermatozoa are particularly susceptible to oxidative stress. Indeed, ROS can directly damage sperm DNA. Spermatozoa cannot repair their DNA due to the scarce cytoplasmic content of enzyme systems involved in the molecular mechanisms of DNA repair. Furthermore, the plasma membrane of spermatozoa plays a key role in successful fertilization and it can be deoxidized by ROS causing an altered sperm motility. Several studies have reported that the oral administration of antioxidants is efficacious in improving conventional sperm parameters and antioxidants are widely available and relatively inexpensive compared to other therapeutic strategies used for fertility treatments.
On this account, we undertook this retrospective, single-center, real-life study to evaluate the effects of a combination of nutraceuticals with antioxidant properties in patients with male infertility.
Materials and Methods: Forty-three male patients aged 20 to 55 years were included in this study; 17 had idiopathic infertility, 13 had varicocele, 10 had testicular hypotrophy, and 3 had male accessory gland infection (MAGI). Patients were divided into 3 groups based on the assigned treatment.
- Group A: 24 patients were treated with a combination of antioxidants (Androlen®)
- Group B: 12 patients were treated with Androlen ® plus mixture of fibrinolytic molecules (Lenidase®)
- Group C: 7 patients were treated with Androlen ® plus other molecules different from those used in group B
Results: Eleven couples achieved pregnancy, five of them through natural intercourse. The remaining 32 failed to achieve pregnancy. Of the 11 pregnancies obtained, 3 occurred in group A, 5 in group B, and 3 in group C. Taking into account the diagnoses of the male partners of these couples, 4 pregnancies came from the varicocele group, 2 from the testicular hypotrophy group, 5 from patients with idiopathic infertility, and none from the MAGI group.
Regarding conventional sperm parameters, group A showed a significant increase in progressive sperm motility (12.3±7.8% vs. 16.1±8.2%) after treatment with Androlen®. In contrast, no significant improvement of these parameters was observed in groups B and C. We also found a trend towards an increase in total sperm count (71.1±68.5 mil/ml vs. 96.1±78.6 mil/ml). The results of biofunctional sperm analysis showed that the percentage of alive spermatozoa significantly increased in patients with testicular hypotrophy (60.9±8.1% vs. 76.5±6.7 %, p<0.05). In addition, an upward trend toward an increase in the percentage of spermatozoa with high mitochondrial membrane potential (66.7±19.5 % vs. 58.7±19.4 %, p=0.06) was found in patients with varicocele.
Discussion: This study was conducted to evaluate the best combination of nutraceuticals among those we use most, as well as which infertile patients could benefit most from the treatment. Patients treated with antioxidants alone showed a significant increase in progressive sperm motility, total motile sperm count, and percentage of alive spermatozoa. The improvement in sperm parameters was not found in the other treatment groups, suggesting a potential interference of other molecules with the effects of antioxidants. The treatment was effective in infertile patients with varicocele or idiopathic infertility, while patients with mild testicular hypotrophy did not benefit from this type of treatment. Testicular volume could therefore represent a useful clinical sign for deciding whether to start antioxidant treatment. Antioxidant administration did not prove to be of any effectiveness in patients with MAGI, but the number of patients included in this group is limited to draw conclusions.
The number of pregnancies was significantly higher in the groups treated with antioxidants plus fibrinolytics or in those treated with antioxidants plus other nutraceuticals, but this evidence should be taken with caution due to the different sample sizes of groups A, B, and C.
These findings are limited by the retrospective study design and the limited sample size. No cause-and-effect relationship should be derived between the observed results and the prescriptions. Nevertheless, these findings can prompt future prospective double-blinded randomized trials to understand which kind of patients can benefit more from antioxidants, as well as which antioxidant scheme is most effective.
Conclusions: Patients treated with antioxidants showed a significant increase in some sperm parameters. The addition of fibrinolytic or other nutraceuticals to antioxidants increased the number of pregnancies achieved by couples, although this conclusion must be taken with caution. Furthermore, the treatment was effective in infertile patients with varicocele or idiopathic infertility, while patients with mild testicular hypotrophy or chronic MAGI did not benefit from the treatment.
Written by: Rossella Cannarella,1,2 Ferdinando Panciera,1 Aldo E. Calogero1
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
- Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA