RICERCHE

THE SPERM PARAMETERS DYNAMICS IN THE TREATMENT OF

IDIOPATHIC MALE INFERTILITY WITH NOVOFERTIL

M.I. Boyko, I.S. Chornokulskyi, O.N. Boyko, Ballara Giovanni, Ye.V. Zarubin
State Scientific Institution “Scientific and Practical Centre of
Preventive and Clinical Medicine” of the State Administration, Ukraine
O.O. Bogomolets National Medical University, Ukraine
ASL of the province of Novara, Italy
Androcenter Clinic, Ukraine
Journal «Medical aspects of man’s health», Volume 3 (22), 2016

Abstract
Up to 75% of male infertility cases have the established and scientifically proven etiology. The role of oxidative stress that leads to disruption of the integrity of the DNA nucleus and sperm motility, as an explanation of the causes of male infertility. This paper evaluates the clinical efficacy of antioxidant and metabolic therapy with “Novofertil®.” The results show significant improvement of sperm parameters and men fertility potential.

Study objective
To study the dynamic pattern of sperm analysis parameters in the treatment of idiopathic male infertility with Novofertil® product.

Materials and method
Selection of test material.
In implementing this study, analysis was carried out on sperm samples of a total of 62 men who sought medical advice due to infertility at the Scientific and Practical Centre of Preventive and Clinical Medicine, which is the clinical site of the Department of Urology at O.O. Bogomolets National Medical University (Ukraine), “Androcenter clinic (Ukraine) and the city hospital of Novara (Italy). All patients were of reproductive age (26 to 38 years) with a history of infertility within a couple for ≥1 year. The patients over the 12-week period were receiving the drug Novofertil® (Salix, Italy), 1 capsule twice a day.

Conclusions

  1. The therapy with a complex of antioxidants and metabolites of the Novofertil® product leads to the improved quantitative (sperm concentration increase by more than twice) and qualitative (approximately one-third increase in the progressive motility and normal morphology indicators) sperm parameters.
  2. The minimum treatment course of the Novofertyl® product is 3 months that covers the full cycle of spermatogenesis, produce a statistically significant improvement in the male fertility indicators and likely contributes to the onset of pregnancy in female partners of patients. In the absence of clinical effect, the treatment should be continued.
  3. The therapy with Novofertil® is recommended to patients with idiopathic infertility, high levels of DNA fragmentation, oligo-, astheno- and teratozoospermia, or in combination of the above conditions, as well as in preparation for ART cycles as monotherapy and in combination with other agents that improve the male fertility potential.

PROBLEMS OF ІDІOPATHIC MALE INFERTILITY

Gorpinchenko І.І., Nurіmanov K.R., Poroshina T.V., Savchenko V.S., Drannik G.M.
The Institute of Urology of the National Academy of Medical Sciences of Ukraine
HEALTH OF MAN, Ukrainian scientific-practical journal
May 2016, Volume 1 (56), p. 133-137

Objective
To assess association of semen, cytokines TNF-α and TGF-β1 indices, as well as the antioxidant properties of the ejaculate in male idiopathic infertility, as well as the dynamics of fertility under influence of antioxidant agents.

Materials and Methods
Thirty-two male patients, age range 18-45 years, with idiopathic infertility were included in the study. The dynamics of sperm parameters (including its antioxidant properties – NBT-test) and ejaculate cytokines (TNF-α, TGF- β1) under the influence of Novofertil (1 caps. 2 times/day) administered for 6 months was studied.

Results
The data obtained revealed statistically significant (p<0.05) increase in the sperm motility and in the number of live sperm. Statistically significant associations were established between NBT test indices and sperm motility, NBT test indices and number of live spermatozoids. No immunological deviations in the dynamic were found.

Conclusion
The antioxidant agents proved their efficacy in idiopathic male infertility treatment.

ROLE OF VITAMIN D DEFICIENCY IN MALE FERTILITY

K. Waud, S. Bocca
The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA, USA
Fertility and Sterility
February 2015, Volume 103, Issue 2, Supplement, Page e39

Background
Vitamin D deficiency is associated with suboptimal health. Data from the 2001-2004 National Health and Nutrition Examination Survey showed that nearly 75% of Americans have vitamin D insufficiency. In addition to maintenance of bone health, vitamin D also has a role in cell differentiation and inhibition of cell growth. Studies of human male reproductive tract revealed presence of the vitamin D receptor suggesting that vitamin D is important for spermatogenesis. Few clinical studies published to date address the possible association between vitamin D deficiency and male infertility.

MICRONUTRIENTS INTAKE IS ASSOCIATED WITH IMPROVED SPERM DNA QUALITY IN OLDER MEN

Thomas E. Schmid, Ph.D., Brenda Eskenazi, Ph.D., Francesco Marchetti, Ph.D., Suzanne Young, M.P.H., Rosana H. Weldon, Ph.D., Adolf Baumgartner, Ph.D., Diana Anderson, Ph.D., Andrew J. Wyrobek, Ph.D.
Fertility and Sterility
November 2012, Volume 98, Issue 5, Pages 1130–1137.e1

Objective
To investigate whether lifestyle factors such as increased dietary intake of micronutrients reduce the risks of sperm DNA damage, and whether older men benefit more than younger men.
Design
Cross-sectional study design with equalized assignments into age groups.
Setting
National laboratory and university.
Patient(s)
Nonclinical group of 22–80-year-old nonsmoking men (n = 80) who reported no fertility problems.
Main Outcome Measure(s)
Sperm DNA damage measured by alkaline and neutral DNA electrophoresis (i.e., sperm Comet assay).
Result(s)
Sociodemographics, occupational exposures, medical and reproductive histories, and lifestyle habits were determined by questionnaire. The average daily dietary and supplement intake of micronutrients (vitamin C, vitamin E, b-carotene, zinc, and folate) was determined using the 100-item Modified Block Food Frequency Questionnaire (FFQ). Men with the highest intake of vitamin C had approximately 16% less sperm DNA damage (alkaline sperm Comet) than men with the lowest intake, with similar findings for vitamin E, folate, and zinc (but not β-carotene). Older men (>44 years) with the highest vitamin C intake had approximately 20% less sperm DNA damage compared with older men with the lowest intake, with similar findings for vitamin E and zinc. The older men with the highest intake of these micronutrients showed levels of sperm damage that were similar to those of the younger men. However, younger men (<44 years) did not benefit from higher intakes of the micronutrients surveyed.
Conclusion(s)
Men with higher dietary and supplement intake of certain micronutrients and antioxidants (vitamin C, vitamin E, and folate) may produce sperm with less DNA damage, especially among older men. This raises the broader question of how lifestyle factors, including higher intakes of antioxidants and micronutrients, might protect somatic as well as germ cells against age-associated genomic damage.

SELENIUM IN REPRODUCTIVE HEALTH
Hiten D. Mistry, PhD, Fiona Broughton Pipkin, DPhil, FRCOG ad eundem, Christopher W.G. Redman, MD, FCRP, FRCOG, Lucilla Poston, PhD, FRCOG ad eundem
American Journal of Obstetrics Gynecology
January 2012, Volume 206, Issue 1, Pages 21–30

Selenium is an essential trace element of importance to human biology and health. Increasing evidence suggests that this mineral plays an important role in normal growth and reproduction in animals and humans, and selenium supplementation is now recommended as part of public health policy in geographical areas with severe selenium deficiency in soil. This review addresses the biological functions of selenium followed by a detailed review of associations between selenium status and reproductive health. In many countries, selenium dietary intake falls below the recommended nutrient intakes and is inadequate to support maximal expression of the selenoenzymes. Numerous reports implicate selenium deficiency in several reproductive and obstetric complications including male and female infertility, miscarriage, preeclampsia, fetal growth restriction, preterm labor, gestational diabetes, and obstetric cholestasis.

IMPROVEMENT OF SPERM QUALITY AFTER MICRONUTRIENT SUPPLEMENTATION
Martin Imhof, Jakob Lackner, Markus Lipovac, Peter Chedraui, Claus Riedl
European e-Journal of Clinical Nutrition and Metabolism
February 2012, Volume 7, Issue 1, Pages e50–e53

Summary

Background & aims
Nearly 50% of male infertility is idiopathic and to date there still is no proven therapy. We evaluated the effect of a non prescription nutraceutical containing eight micronutrients on sperm quality in males with idiopathic sub-fertility.

Methods
This open comparative pilot study was carried out at the Fertility Center IMI, Vienna, Austria. A total of 132 sub-fertile males (active treatment group) were invited to participate and take two daily capsules of the active compound for a three month period between the first and the follow-up semen analysis. Each capsule contained L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 and folic acid. Sub-fertile men receiving no active treatment served as controls (n = 73). Main outcome measure was the standardized semen analysis.

Results
All parameters evaluated by semen analysis significantly increased after 3 months of treatment with the active compound. Median ejaculatory volume, sperm cell density, sperm motility (progressive and total) and normal morphology rate increased by 33.3%, 215.5%, 83.1%, 36.4% and 23.0%, respectively. These increments were significantly higher than those observed among controls. In the active treatment group no side effects were encountered and a total of 34 pregnancies were reported after 6 months follow-up whereas 11 were reported in the control group.

Conclusion
Semen analysis significantly improved in sub-fertile men after treatment with an active micronutrient compound, leading to pregnancies without any adverse effects.

LOW FOLATE IN SEMINAL PLASMA IS ASSOCIATED WITH INCREASED SPERM DNA DAMAGE
Jolanda C. Boxmeer, M.D., Marij Smit, M.D., Elaine Utomo, M.D., Johannes C. Romijn, Ph.D., Marinus J.C. Eijkemans, Ph.D., Jan Lindemans, Ph.D., Joop S.E. Laven, Ph.D., Nick S. Macklon, Ph.D., Eric A.P. Steegers, Ph.D., Regine P.M. Steegers-Theunissen, Ph.D.
Fertility and Sterility
August 2009, Volume 92, Issue 2, Pages 548–556

Objective
To determine associations between vitamin B status, homocysteine (tHcy), semen parameters, and sperm DNA damage.

Design
Observational study.

Setting
A tertiary referral fertility clinic.

Patient(s)
Two hundred fifty-one men of couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, with subgroups of fertile (n = 70) and subfertile men (n = 63) defined according to semen concentration and proven fertility.

Main Outcome Measure(s)
The DNA fragmentation index (DFI) as marker of sperm DNA damage determined using the sperm chromatin structure assay (SCSA), and semen parameters assessed according to World Health Organization criteria; tHcy, folate, cobalamin, and pyridoxine concentrations determined in seminal plasma and blood.

Results
In the total group of fertile and subfertile men, all biomarkers in blood were statistically significantly correlated with those in seminal plasma. No correlation was found between the biomarkers in blood and the semen parameters. In seminal plasma, both tHcy and cobalamin positively correlated with sperm count. Folate, cobalamin, and pyridoxine were inversely correlated with ejaculate volume. In fertile men, seminal plasma folate showed an inverse correlation with the DNA fragmentation index.

Conclusion(s)
Our study emphasizes the importance of B-vitamin status in spermatogenesis in humans. We found that low folate concentration in the seminal plasma of a subgroup of fertile men was associated with increased levels of sperm DNA damage. This may suggest that low folate concentrations in the microenvironment of spermatozoa may be detrimental for sperm DNA stability. High concentrations of sperm DNA damage are associated with poor sperm cell motility and morphology.

ZINC LEVELS IN SEMINAL PLASMA ARE ASSOCIATED WITH SPERM QUALITY IN FERTILE AND INFERTILE MEN
Abasalt Hosseinzadeh Colagar, Eisa Tahmasbpour Marzony, Mohammad Javad Chaichi
Nutrition Research
February 2009, Volume 29, Issue 2, Pages 82–88

Abstract
Zinc has antioxidative properties and plays an important role in scavenging reactive oxygen species. We hypothesized that in the absence of Zn, the possibility of increased oxidative damage exists that would contribute to poor sperm quality. Therefore, measurement of seminal Zn in the seminal plasma of males with a history of subfertility or idiopathic infertility is necessary and can be helpful in fertility assessment. The primary objective of the present study was to assess the relationship between Zn levels in seminal plasma with sperm quality in fertile and infertile men. Semen samples were provided by fertile (smoker [n = 17], nonsmoker [n = 19]) and infertile men (smoker [n = 15], nonsmoker [n = 21]). After semen analysis, concentrations of Zn, Mg, Ca, Na, and K in the seminal plasma of all groups were determined by atomic absorption spectroscopy. Element concentrations in seminal plasma of all groups were in the order Na > K > Ca > Zn > Mg. Fertile subjects, smoker or not, demonstrated significantly higher seminal Zn levels than any infertile group (P < .001). A trend was observed for a lower Zn levels in seminal plasma of smokers compared with nonsmokers. Seminal Zn in fertile and infertile (smokers or nonsmokers) males correlated significantly with sperm count (P < .01) and normal morphology of sperm (P < .001). There was a significantly positive correlation between seminal Zn with Ca (P < .01) and K (P < .01) levels in all specimens. In conclusion, poor Zn nutrition may be an important risk factor for low quality of sperm and idiopathic male infertility.

EFFECTS OF FOLIC ACID AND ZINC SULFATE ON MALE FACTOR SUBFERTILITY: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL
Wai Yee Wong, M.D, Ph.D., Hans M.W.M Merkus, M.D., Ph.D., Chris M.G Thomas, Ph.D., Roelof Menkveld, Ph.D., Gerhard A Zielhuis, Ph.D., Régine P.M Steegers-Theunissen, M.D., Ph.D.
Fertility and Sterility
March 2002, Volume 77, Issue 3, Pages 491–498

Abstract

Objective: To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.

Design: Double-blind, placebo-controlled interventional study.

Setting: Two outpatient fertility clinics and nine midwifery practices in The Netherlands.

Participant(s): One hundred eight fertile and 103 subfertile men.

Intervention(s): Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg.

Main Outcome Measure(s): Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men.

Result(s): Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Preintervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.

Conclusion(s): Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health.

Antioxidant treatment of patients with excretory-toxic infertility as a result of chronic abacterial prostatitis

K.R. Nurimanov, V.S. Savchenko, T.V. Poroshina, E.A. Nedogonova, G.N. Drannik

The Institute of Urology of the National Academy of Medical Sciences of Ukraine
HEALTH OF MAN, Ukrainian scientific-practical journal
December 2016, Volume 4 (59), p. 95-98

Chronic abacterіal prostatitis – difficult and widespread disease, which increases the efficiency of treatment – a problem of modern andrology.

The objective: to study the changes of prostatitis symptoms, comorbid mental disorders and subfertility under the influence of combined treatment.

Patients and methods. The 32 patients with chronic abacterial prostatitis aged 18 to 45 years.

To assess the symptoms of chronic prostatitis using questionnaire NIH-CPSI. Psychological symptoms was studied using that Hospital anxiety depression scale. The concentrations of cytokines in the ejaculate was determined by ELISA. Patients received rectal electrostimulation (10 sessions a day, two courses with an interval of 6 weeks), and functional food supplement Novofertil (2 capsules twice a day for 3 months).

Results. Under the influence of the treatment showed a significant reduction in the symptoms of chronic prostatitis, anxiety and depression, a statistically significant (p<0,05) reduction in the concentration of IL-1b and an increase in the concentration of TGF-b1 in the ejaculate. Increasing of the total number of spermatozoa, the content moving, living and morphologically normal sperm was observed.

Conclusion. The combination of physical therapy and antioxidant complex Novofertil is effective in the treatment of patients with excretory-toxic infertility as a result of chronic abacterial prostatitis.