The Use of Ellagic Acid and Annona Muricata Improves Semen Quality in Men with High-Risk Papillomavirus Infection

Background: Few data are currently available on the treatment of patients with HPV infection. In particular, there is no agreement on the use of antioxidants in these patients. Ellagic acid and annona muricata appear to improve HPV clearance in infected women. However, it is presently unknown whether they could enhance the clearance of HPV infection in infertile male patients. Aim: To evaluate the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with documented papillomavirus (HPV) infection, and on the frequency of HPV DNA detection in seminal fluid after treatment. In addition, anti-sperm antibodies and the percentage of spermatozoa with fragmented DNA were evaluated. Materials and methods: This was a retrospective case-control study including patients attending our center for infertility. Fifty selected patients who were positive for high risk (HR)-HPV with available semen analysis results were consecutively enrolled. Patients were classified into two groups, according to the clinician’s decision to either administer ellagic acid 100 mg and annona muricata 100 mg (combined tablet formulation) for a period of three months (Group A; 25 patients), or to re-evaluate HPV DNA after a period of active surveillance only (protected sexual intercourse) (Group B; 25 patients). Results: Group A patients had a mean age of 31.0 ± 11.0 years, while Group B was 33.0 ± 8.0 years old (p > 0.05). After three months of treatment with ellagic acid and annona muricata, all conventional seminal parameters improved more significantly in Group A than in Group B patients: sperm concentration = 45 mil/mL vs. 20 mil/mL (p < 0.05); sperm progressive motility = 45% vs. 18% (p < 0.05); and normal sperm morphology = 18% vs. 6% (p < 0.05). After the treatment, the frequency of persistence of HPV DNA in the seminal fluid was significantly lower in Group A patients compared to those in Group B (12/25 = 48% vs. 22/25 = 88%; p < 0.05). Finally, after 3 months, Group A showed a significant reduction in anti-sperm antibodies and in the percentage of spermatozoa with fragmented DNA. Conclusion: The results of this study demonstrate, for the first time, the effects of a commercially available combined compound containing ellagic acid and annona muricata on semen quality in patients with HR-HPV infection, and that this therapy is also associated with a significant reduction in the persistence of HPV DNA in the seminal fluid.