Treatment of infertility in men with pathospermia associated with oxidative stress


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Introduction. Oxidative stress considered to be the main cause of male infertility. Surgical treatment of varicocele and elimination of the inflammatory process in the male accessory glands can help reduce the level of oxidative stress, however, in most cases, antioxidant therapy is additionally prescribed. Currently, much attention is paid to regulatory peptides as a component of antioxidant therapy due to their antioxidant, anti-inflammatory and immunomodulatory properties.

Aim. To evaluate the efficiency of a complex of antimicrobial peptides and cytokines Superlymph® for the treatment of male infertility associated with oxidative stress.

Materials and methods. A total of 30 patients with elevated levels of reactive oxygen species were recruited in the open, prospective, multicenter study. Ejaculate analysis (WHO-2010), MAR-test, sperm DNA damage testing and reactive oxygen species measurement were performed. All patients received Superlymph® 25 IU/day for 60 days. Antibiotics and vitamin D were also prescribed if indicated. In addition, 12 patients took dietary supplements with antioxidant action. Laboratory tests were repeated after the completion of treatment.

Results. Superlymph® therapy led to an improvement in standard semen parameters as well as decrease in sperm DNA fragmentation and oxidative stress. At the end of treatment, a significant increase in the sperm concentration was observed (46.8 [30; 87] vs. 62 [43–89], p=0.002). After treatment, there was also an increase in the median of sperm cells with normal morphology (3 [1; 7] vs. 4.5 [2; 9], p=0.002). The median sperm DNA fragmentation was lower compared to baseline, but this difference did not reach significant level (19 [14; 26] vs. 15 [10.5; 19.5], p=0.06). A significant decrease in the level of oxidative stress both in patients who took Superlymph® as monotherapy (43 [27; 51] vs. 33 [22; 44], p=0.005), and as part of combination therapy with other antioxidants (31 [22; 54] vs. 21 [12; 36], p=0.009) was also observed.

Conclusion. Superlymph® contributes to the improvement of standard ejaculate parameters as well as decrease in the level of sperm DNA fragmentation and oxidative stress.

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Sobre autores

V. Vinogradov

Peoples’ Friendship University of Russia; Scientific and Practical Center of Reproductive and Regenerative Medicine

Autor responsável pela correspondência
Email: ivvinogradov@mail.ru
ORCID ID: 0000-0001-7469-3952

Ph.D., MD, professor of the Department of Urology and Operative Nephrology with a course of oncourology

Rússia, Moscow; Moscow

M. Gabliya

Scientific and Practical Center of Reproductive and Regenerative Medicine

Email: ivvinogradov@mail.ru
ORCID ID: 0000-0002-8176-2597

andrologist

Rússia, Moscow

D. Rogozin

South Ural State Medical University

Email: ivvinogradov@mail.ru

Ph.D., Department of General and Pediatric surgery

Rússia, Chelyabinsk

O. Tazhetdinov

Krasnodar Medical and Biological Center Ltd

Email: ivvinogradov@mail.ru
ORCID ID: 0000-0001-6162-1554

Ph.D.

Rússia, Krasnodar

E. Novikova

Regional Medical Diagnostic Center; Federal Research Center for Fundamental and Translational Medicine

Email: ivvinogradov@mail.ru
ORCID ID: 0000-0003-4723-0666

Ph.D., Chief researcher of the Endocrinologic Laboratory; urologist and andrologist

Rússia, Novosibirsk; Novosibirsk

D. Fateev

Medical Center for Diagnostics and Prevention Plus

Email: ivvinogradov@mail.ru

Ph.D., urologist and andrologist

Rússia, Yaroslavl

Yu. Olefir

I.M. Sechenov First Moscow State Medical University

Email: ivvinogradov@mail.ru
ORCID ID: 0000-0001-7652-4642

Ph.D., MD, professor

Rússia, Moscow

G. Estevesh

Peoples’ Friendship University of Russia

Email: ivvinogradov@mail.ru
ORCID ID: 0000-0002-0830-6405

Ph.D. student of the Department of Urology and Operative Nephrology with a course of oncourology

Rússia, Moscow

Bibliografia

  1. World Health Organization (WHO) WHO laboratory manual for the examination and processing of human semen, sixth edition. Geneva: World Health Organization; 2021.
  2. Agarwal A., Parekh N., Panner Selvam M.K., Henkel R., Shah R., Homa S.T., et al. Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37:296–312.
  3. Dutta S., Majzoub A., Agarwal A. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J Urol. 2019 Apr 24;17(2):8797. doi: 10.1080/2090598X.2019.1599624. PMID: 31285919; PMCID: PMC6600059.
  4. Beygi Z., Forouhari S., Mahmoudi E., Hayat S.M.G., Nourimand F. Role of Oxidative Stress and Antioxidant Supplementation in Male Fertility. Curr Mol Med. 2021;21(4):265–282. doi: 10.2174/1566524020999200831123553. PMID: 32867638.
  5. Male Infertility Gudeline EAU 2022.
  6. Zaitsev V.G., Ostrovsky O.V., Zakrevsky V.I. The relationship between the chemical structure and the target of action, as the basis for the classification of direct-acting antioxidants. Experimental clinical pharmacology. 2003;66(4):66–70.
  7. Male infertility. Clinical recommendations of the Russian Federation, 2021.
  8. Pushkar D.Yu., Kupriyanov Yu.A., Bernikov A.N., Gamidov S.I., etc. Evaluation of the safety and efficacy of the drug based on regulatory polypeptides of testes PPR-001. Urologiia. 2021;6:100–108.
  9. Tyuzikov I.A., Grekov E.A., Smirnov A.V. Local cytokinotherapy in the complex treatment of chronic prostatitis. Effective pharmacotherapy. 2022;3:26–38.

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2. Fig.1. Change in sperm concentration. Dynamics of sperm concentration (median and interquartile distance) before and after therapy with Superlymph

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3. Fig.2. Change in progressive sperm motility. Dynamics of progressive sperm motility (%, median and interquartile distance) before and after therapy with Superlymph

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4. Fig.3. Changes in the morphology of spermatozoa. Dynamics of the proportion of normal spermatozoa morphology (%, median and interquartile distance) before and after therapy with Superlymph

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5. Fig.4. Change in sperm DNA fragmentation. Dynamics of sperm DNA fragmentation index (%, median and interquartile distance) before and after therapy with Superlymph

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6. Fig.5. Change in the level of ROS. Changes in the level of oxidative stress in the ejaculate (Rlu/sec, median and interquartile distance) before and after therapy with Superlymph

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7. Fig.6. Changes in the level of ROS depending on the concomitant intake of antioxidants. Changes in the level of oxidative stress in the ejaculate (Rlu/sec, median and interquartile distance) before and after therapy with Superlymph. A) Superlymph in monotherapy; C) Superlymph in combination with antioxidants

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