Sperm DNA Fragmentation In Men Research Articles

The paternal clock: Uncovering the consequences of advanced paternal age on sperm DNA fragmentation

The objective of the study was to investigate the relationship between advanced paternal age and sperm DNA fragmentation (SDF) levels, specifically identifying the age at which a significant increase in SDF occurs. This is a retrospective cohort study involving 4250 consecutive semen samples from patients presenting for infertility evaluation. Patients were stratified into seven age groups: < 26 (n = 36; 0.8 %), 26–30 (n = 500; 11.8 %), 31–35 (n = 1269; 29.9 %), 36–40 (n = 1268; 29.8 %), 41–45 (n = 732; 17.2 %), 46–50 (n = 304; 7.2 %), > 50 (n = 141; 3.3 %). The main outcome measures included comparing mean SDF levels throughout different age groups and assessing the prevalence of normal, intermediate, and high SDF among the age groups. A positive correlation was observed between paternal age and SDF (r = 0.17, p < 0.001). SDF remained relatively constant until the age of 35 but increased significantly beyond age 35. Mean SDF levels in the older age groups (36–40, 41–45, 46–50, and >50 years) were significantly higher than in the younger age groups (<26, 26–30, and 31–35 years) (p < 0.001). The prevalence of normal SDF was highest among the younger age groups, whereas the prevalence of high SDF was highest among the older age groups. Interestingly, the prevalence of intermediate SDF was relatively constant throughout the age groups (ranging between 29.8 % to 37.2 %). The increase in SDF after the age of 35 highlights the importance of considering male age in infertility evaluations. Assessing SDF in men over the age of 35 is crucial in couples seeking to conceive.

Антиоксидантная терапия в коррекции ДНК-фрагментации сперматозоидов.

Introduction. The progressive deterioration of reproductive function, observed throughout the world in recent decades, is an extremely alarming trend, while the incidence of male infertility is increasing. The universal pathogenetic mechanism of spermatogenesis disorders, which underlies almost all forms of male infertility, is oxidative stress of sperm. It has various manifestations, the essence of which, as a rule, boils down to the formation of mitochondrial dysfunction and fragmentation of sperm DNA. It has been found that consuming antioxidants and microelements helps increase the chances of conception for subfertile couples, and also reduces the risk of reproductive losses. Of greatest and justifiable interest are medicinal complexes designed to reduce the level of oxidative stress and sperm DNA fragmentation. The purpose of the study was to evaluate the effect of antioxidant therapy on the degree of sperm DNA fragmentation in men suffering from infertility. Materials and methods. The study involved 42 men aged 25 to 37 years with an established diagnosis of male infertility who were treated at the Center for Family Health and Reproduction. The patients were divided into 2 groups, comparable according to the main criteria assessed. Patients in the control group (12 people, 29%) received standard antioxidant therapy. Patients of the main group (30 people, 71%) received the BESTFertil-DHA® complex. The course of treatment for patients in both groups was 3 months. Control examinations were carried out at 1.5 and 3 months from the start of therapy. Spermogram data and assessment of the degree of DNA fragmentation in sperm using the SCD (Sperm chromatin dispersion test) method were used as the main criterion for assessing the effectiveness of therapy. Results. After three months of taking BESTFertil-DHA®, in 16 patients (53%), the degree of sperm DNA fragmentation decreased to less than 15%. Against this background, 5 couples became pregnant naturally, and 4 couples became pregnant as a result of the in vitro fertilization procedure. The average level of sperm DNA fragmentation was less than 13% (p &lt; 0.05). A decrease in the level of DNA fragmentation was noted in 53% of patients after 1.5 months of taking BESTFertil-DHA®, which is especially important when preparing patients for assisted reproductive technology programs. In patients taking BESTFertil-DHA®, the total progressive motility of spermatozoa «A+B» increased by 28%, and the concentration of spermatozoa in 1 ml of ejaculate – by 61%. In the control group, the degree of sperm DNA fragmentation did not undergo statistically significant changes during treatment. Conclusion. BESTFertil-DHA® statistically significantly helps to reduce the degree of DNA fragmentation in sperm, increase the number of actively motile forms of sperm and reduce the degree of teratozoospermia.

Evaluation of the effect of the antioxidant complex “BESTFertil-DHA” on spermogram parameters and the index of sperm DNA fragmentation in men from infertile couples with metabolic syndrome

Introduction.Antioxidant therapy is the optimal type of treatment for idiopathic male infertility due to the good ratio of efficacy and safety. Considering that oxidative stress is one of the pathogenetic links in sperm DNA damage, antioxidant drugs can also reduce the DNA fragmentation index. Men who are overweight or severely obese have a high risk of sexual dysfunction and reproductive disorders. Antioxidant therapy plays a leading role in infertility associated with metabolic syndrome. The main active ingredients in «BESTFertil-DHA» are L-carnitine, eicosapentaenoic and docosahexaenoic acids, the action of which is complemented by other components, which makes the use of the complex attractive in combination with male infertility and metabolic syndrome. However, it is unknown how well they work with a combination of these pathological conditions.Aim.Is to evaluate the effectiveness of administration of Russian complex «BESTFertil-DHA» on spermogram parameters and the index of sperm DNA fragmentation in men from infertile couples with metabolic syndrome.Materials and methods.The study included 60 patients divided into cohort A- 26 patients with metabolic syndrome, cohort B- 34 patients without metabolic syndrome. All patients received «BESTFertil-DHA». All patients underwent a spermogram, an analysis for the fermentation of sperm DNA, blood for sex hormones, markers of metabolic syndrome on the first visit, and on the 2nd visit after therapy.Results.In cohort A, significant results were observed in terms of weight, BMI, C-reactive protein level, and HOMA-IR index. There is a significant improvement in the parameters of the spermogram, a decrease in the index of fragmentation of sperm DNA, a decrease in estradiol, normalization of the T/E2 index. In cohort B, changes in weight, BMI and a number of spermological parameters were observed, there were no changes in metabolic and endocrine parameters.Conclusion.Combined antioxidant therapy in the form of a complex of nutrients «BESTFertil-DHA» effectively reduces the index of fragmentation of sperm DNA and leads to normalization of spermogram parameters, both in the general cohort of patients and among men with metabolic syndrome. Moreover, in the latter, the «BESTFertilDHA» complex in combination with measures to reduce body weight gives additional therapeutic effects, affecting carbohydrate metabolism, aromatization of testosterone and the severity of systemic inflammation.

Seminal Oxidative Stress and Sperm DNA Fragmentation in Men from Couples with Infertility or Unexplained Recurrent Pregnancy Loss

(1) Background: This case–control study examined whether men from couples with unexplained recurrent pregnancy loss (RPL) or infertility exhibited higher seminal oxidative stress (OS) and sperm DNA fragmentation (SDF) compared to fertile controls. (2) Methods: The study included 30 participants from each group: unexplained RPL, unexplained infertility, and proven fertility. Data were collected at Aalborg University Hospital tertiary RPL and fertility treatment clinics (Aalborg, Denmark), excluding couples with mixed conditions for homogeneity. Semen samples were analyzed using computer-aided sperm analysis (CASA) for concentration, motility, and morphology. SDF was assessed via a CASA-based sperm chromatin dispersion test. OS was measured as static oxidation-reduction potential (sORP). (3) Results: The results showed no significant OS differences between groups. The RPL group had significantly lower SDF levels than the control group. A significant positive correlation between SDF and OS was observed in the infertility group. Overall, this study did not find significant differences in OS levels between men from couples with unexplained RPL or infertility and fertile controls, while SDF levels were lower in the RPL group compared to controls. (4) Conclusion: In conclusion, despite the existing literature suggesting that OS and SDF are negative prognostic factors, our findings suggest they may not be reliable diagnostic markers for RPL and infertility.

Self-reported occupational exposure and its association with sperm DNA fragmentation in infertile men

Background/Aim: Sperm quality has experienced a decline in recent years, with this issue being particularly pronounced in industrialized nations, suggesting a potential link to occupational exposures. Evaluating sperm DNA fragmentation can yield valuable insights into male fertility, although its association with occupational exposures remains less well-established. Our study aimed to investigate the relationship between self-reported occupational exposures and sperm DNA fragmentation in infertile men. Methods: This retrospective cohort study involved 391 infertile men who sought fertility treatment at a university clinic between 2017 and 2020. A brief questionnaire was administered to collect data on patients’ demographic characteristics, medical history, occupation, and exposure types. In this comparative study, patients were categorized into two groups based on their occupational exposures (the unexposed and exposed groups). The exposed group was further sub-grouped according to their specific exposure types, which included cement, solvents, metals, pesticides, mechanical vibration, and heat. The primary outcome in this study was assessed using the terminal deoxynucleotidyl transferase-mediated nick end-labeling test (TUNEL), with results expressed as the sperm DNA fragmentation index (DFI). Results: Patients in the exposed group exhibited a significantly higher sperm DFI compared to those in the unexposed group (14 [17] vs. 8 [9], P&lt;0.001). After accounting for potential confounding factors, our results demonstrated that several occupational exposure factors significantly increased the risk of elevated sperm DFI (&gt;15%) levels, including solvents (odds ratio (OR)=8.2, 95% confidence interval (CI)=3.6–18.5, P&lt;0.001), metals (OR=2.2, 95% CI=1.0–4.7, P=0.048), pesticides (OR=14.6, 95% CI=1.6–130.7, P=0.016), mechanical vibration (OR=2.6, 95% CI=1.5–4.6, P&lt;0.001), and heat (OR=6.4, 95% CI=1.7–23.5, P=0.005). Conclusion: The findings of our study corroborate earlier research suggesting that occupational exposures may have adverse effects on sperm DNA fragmentation in men. The identification and management of such exposures as part of routine clinical practice could offer a complementary approach to enhancing infertility treatment outcomes.

Effects of cigarette smoking on semen quality, reproductive hormone levels, metabolic profile, zinc and sperm DNA fragmentation in men: results from a population-based study.

Cigarette smoking seems to have a negative impact on men's reproductive health, but our knowledge of its effects on the reproductive function of Russian men is still very limited. The purpose of this study was to evaluate the effect of cigarette smoking on semen quality, including sperm DNA fragmentation, hormonal, zinc and metabolic status in young men from the general multi-ethnic Russian population (n=1,222, median age 23 years) and to find out the ethno-specific effects of smoking by comparing male groups of different ethnicity. Each participant filled out a standardized questionnaire, provided one blood and semen sample. Semen parameters, serum reproductive hormones, lipids, glucose, uric acid and seminal zinc were analyzed. Participants were classified as smokers (n=450) and non-smokers (n=772), and smokers were stratified into moderate (≤10 cigarettes/day) and heavy (>10 cigarettes/day) smokers. In the entire study population, heavy smokers were characterized by a decrease in semen volume, total sperm count, sperm concentration and motility, and an increase in sperm DNA fragmentation and teratozoospermia compared with non-smokers (p<0.05). There was also a reduction in the serum and seminal zinc level as well as an impairment in metabolic health in smokers compared with non-smokers (p<0.05). No significant differences between smokers and non-smokers were found for serum levels of LH, FSH, inhibin B, testosterone and estradiol. In the second part of our study, the most numerous ethnic groups of Slavs (n=654), Buryats (n=191), and Yakuts (n=125) were selected from the entire study population. Among three ethnic groups, the smoking intensity was higher in Slavs than in Buryats or Yakuts suggesting a greater tobacco addiction in Slavs than in Asians. A decrease in semen parameters and seminal zinc levels, and an increase in sperm DNA fragmentation and teratozoospermia was observed only in smoking Slavs (p<0.05); moderate decrease in testosterone and increase in triglyceride levels were revealed in smoking Yakuts (p<0.05), but no significant changes were detected in smoking Buryats. We concluded that cigarette smoking has an ethno-specific effect on male reproductive function, probably due to the different activity of the seminal antioxidant system, which is yet to be elucidated.

Combined treatment of idiopathic male infertility using low-intensity laser therapy and complex prostate peptides: single-centre experience

Introduction. The study of effective and safe combined methods of conservative treatment of idiopathic male infertility is of great interest.Objective. To evaluate the effectiveness of the combined use of low-level laser therapy (LLLT) in the infrared (IR) spectrum and bioregulatory therapy with complex prostate peptides on the semen parameters and sperm DNA fragmentation (SDNAF) in men with idiopathic infertility.Materials &amp; methods. The study is based on the results of examination and treatment of 97 men with idiopathic infertility. Prior to the start of treatment, all patients were divided into three groups by randomization. Patients in group 1 (n = 34) underwent a course of LLLT in the IR spectrum consisting of 10 procedures q.o.d. Patients in group 2 (n = 31) were prescribed complex prostate peptides Supp. Prostatilen® AC (30 + 180 mg) PR q.h.s. FXD, with a repeat of the course of treatment after 5 days. Patients in group 3 (n = 32) underwent combined treatment: LLLT sessions in the IR spectrum (10 procedures q.o.d.) and a course of Supp. Prostatilen® AC (30 + 180 mg) PR q.h.s. FXD, with a repeat of the course of treatment with peptides according to the same scheme after 5 days. Control examination of patients in all groups was carried out two months after the end of treatment.Results. As a result of treatment of patients in groups 1, 2, and 3, a significant improvement in the main semen parameters, a decrease in the grade of pathological SDNAF, an increase in serum total and free testosterone concentration (p &lt; 0.05) were observed. A comparative statistical analysis of the results obtained in three groups of patients showed that the combined treatment of patients of group 3, who were prescribed a course of LLLT in combination with complex prostate peptides Supp. Prostatilen® AC, was significantly more effective in improving concentration (p &lt; 0.01) and progressive sperm motility (p &lt; 0.01), as well as a decrease in the grade of pathological SDNAF (p &lt; 0.05), than in groups 1 and 2.Conclusion. Combined therapy that includes complex prostate peptides and LLLT in the IR spectrum improves the main semen parameters and reduces the grade of pathological SDNAF in men with idiopathic infertility.

Sperm DNA fragmentation in men vaccinated with Gam-COVID-Vac (Sputnik V)

Aim. To perform comparative analysis of sperm characteristics and DNA fragmentation in men vaccinated with GamCOVID-Vac (Sputnik V) and unvaccinated men.Materials and methods. Characteristics ofsemen analysis and DNA fragmentation index in ejaculate samples of 122 men, 28 of whom were vaccinated with Gam-COVID-Vac (Sputnik V), were analyzed. Study participants did not have history of coronavirus infection COVID-19. Vaccinated patients were divided into 2 groups: group 1 (n = 10) included patients for whom the time between full vaccination (2 doses of the vaccine) and ejaculate sampling was shorter than 75 days; and the group 2 (n = 18) included patients for whom the time between vaccination and ejaculate sampling was longer than 75 days. Unvaccinated men comprised the control group (group 3, n = 94). Standard semen analysis was performed in accordance with the accepted laboratory guidelines of the World Health Organization (2010). DNA fragmentation was evaluated using fluorescent labelling of single- and double-strand DNA breaks (TUNEL).Results. Totalsperm countin the group 1 was 265 ± 75 million, in the group 2 – 355 ± 67 million, in the group 3 – 304 ± 26 million. Progressive motile (PR)sperm in the group 1was 18.5 ± 1.9 %, in the group 2 – 23.2 ± 3.0 %, in the group 3 – 18.2 ± 1.1 %. Normal sperm morphology in the group 1 was 4.0 ± 0.5 %, in the group 2 – 5.8 ± 0.9 %, in the group 3 – 4.1 ± 0.3 %. The best ejaculate quality was observed in patients of the group 2, however, no statistically significant differences in semen analysis characteristics between the groups were found. Percentage of sperm with fragmented DNA (DNA fragmentation index, DFI) in the group 1 varied between 4.6 and 31.4 %, in the group 2 between 0.8 and 36.5 %, in the group 3 (control) between 1.3 and 39.8 %. Mean number of germ cells with DNA breaksin the group 1 (12.5 ± 2.4 %) was higher than in the group 2 (10.9 ± 2.0 %) and control group (10.5 ± 0.7 %), but with no statistical significance. Percentage of patients with DNA fragmentation index above the reference value (≤15 %) in the groups 1, 2 and 3 was 20, 22 and 18 % respectively. In 3 of 6 patients with increased DFI in the groups 1 and 2, this value was above the reference level even before vaccination.Conclusion. No significant effect of vaccination with Sputnik V on sperm DNA fragmentation level in men was observed.

Variability in Sperm DNA Fragmentation in Men with Mild/Unexplained Subfertility in a Prospective Longitudinal Intrauterine Insemination Trial.

The biological variability of semen and sperm DNA fragmentation (SDF) parameters in a longitudinal intrauterine insemination (IUI) trial over multiple IUI cycles was investigated. A TUNEL assay was used for SDF testing, both before and after density gradient centrifugation. A significant age effect was observed: while semen parameters deteriorated with advancing age, on average, higher SDF values were observed for older males. There was quite some variability observed for both semen and SDF variables. Using fertile threshold values, three patient categories were distinguished: those with a high SDF in all samples, those with low SDF in all samples and those who fluctuated between high and low during the whole IUI trial. Density gradient centrifugation increases SDF. However, the three patient categories react differently after semen processing. A large percentage of those with high SDF retain their high SDF even after gradient centrifugation. The SDF fluctuaters react with a high SDF after gradient centrifugation. The low SDF category, on the contrary, distributes itself evenly between the three categories after gradient centrifugation. SDF testing after semen processing might be indispensable for therapeutic purposes, probably influencing medical decision-making. In order to isolate fluctuaters, a second SDF testing might be advocated in certain cases. SDF after semen processing is indispensable for therapeutic management.

Oxidative Stress Markers and Sperm DNA Fragmentation in Men Recovered from COVID-19.

SARS-CoV-2 negatively affects semen characteristics, impairs various biochemical processes in seminal fluid and within spermatogenic cells ultimately leading to male fertility decline. However, the distinct mechanisms, in particular, the role of oxidative stress on the consequences of coronavirus infection, have not been well investigated, which is the purpose of the present study. The standard semen parameters, its pro- and antioxidant system state, as well as the level of sperm DNA fragmentation, were assessed in 17 semen samples of men five months after the coronavirus infection and in 22 age-matched control patients. We determined that the DNA fragmentation rate negatively correlated with the period after coronavirus recovery, as well as seminal fluid superoxide dismutase activity and uric acid level. It was demonstrated that COVID-19 is not always associated with increased DNA fragmentation, allowing them to be considered as two independent factors. Thus, the most significant changes were noted in the samples of men after COVID-19 and abnormal TUNEL results: increased round cell number, decreased seminal fluid’s nitrotyrosine level, and total antioxidant capacity and Zn, as well as an increased 8-hydroxy-2′-deoxyguanosine level within spermatozoa. The data obtained indicate that increased DNA fragmentation and diminished semen quality in men can be the result of an imbalance in semen pro- and antioxidant components after COVID-19.

Subclinical Hypothyroidism and Sperm DNA Fragmentation: A Cross-sectional Study of 5401 Men Seeking Infertility Care.

Our previous study showed that paternal subclinical hypothyroidism (SCH) had a detrimental effect on the clinical outcomes of assisted reproductive technologies. However, it remains to be determined whether paternal SCH affects sperm DNA integrity. To investigate the association between SCH and sperm DNA fragmentation in men seeking infertility care. This cross-sectional study included 4983 men with euthyroidism and 418 men with SCH seeking infertility treatment in a tertiary care academic medical center between January 2017 and December 2021. The outcome measures were the absolute DNA fragmentation index (DFI) and the risk of abnormal DFI (defined as DFI ≥ 25% or ≥ 30%). The mean (SD) age of men with euthyroidism and men with SCH was 34.20 (5.97) and 35.35 (6.48) years, respectively (P < 0.001). The difference in DFI was not statistically significant (adjusted mean: 19.7% vs 18.9% in the SCH and euthyroidism groups, respectively; P = 0.07) after confounder adjustment. A DFI ≥25% was significantly more frequent in men with SCH (20.57%) than in men with euthyroidism (14.49%) after confounder adjustment [odds ratio (OR) 1.43 (95% CI 1.09-1.88)]. DFI ≥ 30% was also significantly more common in men with SCH (11.72%) than in men with euthyroidism [6.74%; OR 1.84 (95% CI 1.34-2.52)]. In addition, thyroid-stimulating hormone concentration was significantly associated with an increased risk of having a DFI ≥25% (P < 0.001) or ≥30% (P = 0.011). SCH was significantly associated with an increased risk of an abnormal DFI.

The effect of different seasons on the rate of sperm DNA fragmentation in men

The effect of different seasons on the rate of sperm DNA fragmentation in men

Impaired semen quality, an increase of sperm morphological defects and DNA fragmentation associated with environmental pollution in urban population of young men from Western Siberia, Russia.

Poor sperm morphology and an elevated DNA fragmentation level are considered to be related to spermiogenesis malfunctions as a result of genetic mutations and effects of environmental factors, including industrial pollution. Standardized cross-sectional population studies of sperm morphology defects and sperm DNA fragmentation, especially in regions with increased environmental pollution may be helpful to investigate an influence of industrial pollution and other population-related factors on spermiogenesis process. The aim of present study was to estimate an influence industrial pollution on sperm morphogenesis and sperm DNA fragmentation in men from the general population of the Western Siberia. The Novosibirsk and Kemerovo cities are located to same climatic conditions in Western Siberia but the Kemerovo city is characterized by increased environmental pollution especially by particulate matter (PM). The male volunteers living in Novosibirsk (n = 278) and Kemerovo (n = 258) were enrolled. Percentages of sperm morphological defects are counted after staining native ejaculate smears by Diff-Quick kits. DNA fragmentation was estimated by a SCSA technique. The residents of Kemerovo were characterized by lowered sperm count and sperm motility, elevated DNA fragmentation, poor sperm morphology and increased incidence of morphological effects of head (pyriform, elongated, round, abnormal acrosome and vacuolated chromatine), asymmetrical neck insertion and excess residual cytoplasm. Moreover, elevated DNA fragmentation was associated with lowered sperm count, sperm motility and increased percentages of several sperm morphology defects, with the place of residence affecting the relationships between conventional semen parameters, sperm morphology and DNA fragmentations. Our study suggests that excessive sperm head elongation and impaired acrosome formation can contribute to sperm morphology deterioration in men from polluted areas. Regional features in the relationships between sperm morphology, sperm count and DNA fragmentation were shown, suggesting an importance of studying sperm morphology pattern in men from different regions.

STUDY OF SPERM DNA FRAGMENTATION IN MALE PARTNERS OF INFERTILE COUPLES

Background: Infertility affects 15% couples of reproductive age in those 35% with male factor. Semen analysis is cornerstone to evaluate male factor infertility. Sperm chromatine dispersion test is light weight and fast test Normal sperm creates sperm halo. If sperm DNA fragments exceeds 30% sperm quality is significantly reduced. Aim: To study the Role of DNA fragmentation in male partner of infertile couple. Results: The mean age of cases was 31.71 years and that of control was 32.63 years with majority of cases (43.3%) were in age group 31-35 years and controls were (56.7%) in age group 25-30 years. The age difference was statistically non-significant as p-value is greater than 0.05. The mean BMI in cases was 22.9 kg/m2 and that of control was 24.5 kg/m2 with majority of cases (73.33%) and controls (53.3%) had BMI between 18.5-24.9 kg/m2. The difference was statistically non-significant. Here in cases 56.7% were tobacco chewer followed by 30% were smoker, 26.7% were alcoholic, 6.7% had other habits and 1% had no personal history. In control 33.33% were tobacco chewer followed by 23.3% were smoker, 6.7% were alcoholic and 36.7% had no personal history. In cases 83.3% had DFI greater than equal to 30 and 16.7% had DFI less than 30. In control 20% had DFI greater than equal to 30 and 80% had DFI less than 30. The mean DFI in cases was 37.26 and that of control was 23.64. The difference was statistically significant Conclusion: Sperm DNA integrity measurement is more reproducible and more objective than conventional parameters. Our study indicates that the levels of sperm DNA fragmentation in men with subnormal semen parameters were significantly higher compared to the levels in men with normal semen parameters. SDI may reveal a hidden abnormality of sperm nuclear DNA in infertile men classified as idiopathic based on apparently normal standard sperm parameters. This test has an important diagnostic and prognostic value in the evaluation of male infertility, particularly in relation to assisted reproductive technologies. Keywords: DNA fragmentation, DFI

Bariatric Surgery Impact on Reproductive Hormones, Semen Analysis, and Sperm DNA Fragmentation in Men with Severe Obesity: Prospective Study

Growing evidence in the literature suggests that obesity is capable of altering reproductive hormone levels and male fertility. Effects on classic semen parameters and sperm DNA fragmentation (SDF), however, have not been properly established. Additionally, the impact of bariatric surgery (BS) on those parameters is still controversial. In Phase 1, 42 patients with obesity and 32 fertile controls were submitted to reproductive hormone evaluation, semen analysis, and SDF testing. In Phase 2, patients with obesity were submitted to BS or clinical follow-up and were invited to 6-month revaluation. Phase 1: Men with obesity have higher levels of estradiol, LH, and FSH and lower levels of total testosterone (TT) when compared with eutrophic fertile men. Additionally, they present worse semen parameters, with reduction in ejaculated volume and sperm concentration, worse sperm motility and morphology, and higher SDF. Phase 2: 32 patients returned to revaluation. Eighteen were submitted to BS (group S) and 14 were not submitted to any specific therapeutic regimen (group NS). In group S, TT more than doubled after surgery (294.5 to 604ng/dL, p < 0.0001). Worsening of sperm concentration and total ejaculated sperm count were also noticed, and 2 patients became azoospermic after BS. SDF, however, improved after the procedure. No changes in the variables studied were observed in non-operated patients. In this prospective study, we have found that BS results in improvements in reproductive hormone levels and SDF after 6-month follow-up. Sperm concentration, however, reduced after the procedure.

Sperm DNA fragmentation in men of different age

The study objective is to analyze the content of spermatozoa with single and double-stranded DNA breaks in different age groups.Materials and methods. The level of DNA fragmentation was studied in 300 ejaculate samples obtained from 266 sub- or infertile men. The group 1 included 150 samples obtained from 131 patients under the age of 45 (21–44 years), the group 2 included 150 samples obtained from 135 patients above the age of 45 (45–68 years). Mean ages were 34.8 ± 3.9 and 48.6 ± 3.1 years, respectively. The number of sperm with fragmented DNA was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method on ejaculate smears. The number of spermatozoa with &gt;15 % of fragmented DNA was considered elevated. Standard semen analysis was performed in 117 and 97 men from the groups 1 and 2, respectively.Results. The number of sperm with fragmented DNA varied in ejaculated samples from 1.5 to 64.5 %. Mean number of sperm with DNA breaks in the group 1 (12.0 ± 6.0 %) was significantly lower than in the group 2 (16.1 ± 8.3 %, p &lt;0.05). Mean sperm count in the ejaculate of the group 1 (267.0 ± 198.7 million) was significantly higher than in the group 2 (201.0 ± 162.9 million, p = 0.02).Conclusion. We revealed that in men over the age of 45 years, the percentage of spermatozoa with DNA fragmentation is higher than in men under 45 years of age, it may indirectly indicate an increased level of reactive oxygen species in the seminal plasma in older patients.

The risk of sperm demage in men with the combined effect of endocrine disruptors

Background: The most frequent ultrastructural change in sperm cells is nuclear DNA fragmentation. Many authors believe that DNA damage to sperm cells can serve as a diagnostic marker of a negative paternal effect in the pre-implantation period of human development. A number of studies have shown a direct correlation between the high percentage of sperm DNA damage and the frequency of spontaneous abortions. On the other hand, it is known that the damaging effect of endocrine disruptors, for example, triclosan and bisphenol A, is based on their ability to induce oxidative stress, which is considered as one of the factors in cell DNA damage.&#x0D; Aims: to assess the risk of sperm DNA fragmentation in men with the combined effect of bisphenol A, triclosan and 4-nonylphenol in seminal fluid.&#x0D; Materials and methods: 84 samples of seminal fluid of men with normo-and patozoospermia were studied. The concentration of bisphenol A, triclosan and 4-nonylphenol in gas was determined by gas chromatography with mass spectrometry (GC-MS). The comparison groups were divided according to the degree of DNA fragmentation of spermatozoa into two groups: the 1st group of patients with DNA fragmentation of spermatozoa 15% (n=18) and the 2nd group 15% (n=29). The spermiological study was carried out according to the WHO recommendations (2010) taking into account the assessment of the number of spermatozoa, their motility and morphology, as well as the degree of fragmentation of the sperm DNA.&#x0D; Results: Bisphenol A was found in 100% of the ejaculate samples with a median concentration of 0.150 ng/ml. Triclosan and 4-nonylphenol were detected in 84.3 and 98.1% of ejaculate samples with a median concentration of 0.11 and 0.16 ng/ml respectively. Comparison groups were statistically significantly distinguished by the concentration of bisphenol A and triclosan p=0.014; p0.001 respectively. Triclosan with an increase in concentration in seminal fluid by 0.1 ng/ml increased the chance of development of the degree of DNA fragmentation 15% by 2.9 times. The odds ratio of bisphenol A and 4-nonylphenol to DNA damage was not statistically significant. The prognostic model of the joint effect of endocrine disruptors on DNA damage, constructed using multiple logistic regression analysis, was also found to be statistically significant only with respect to the effect of triclosan.&#x0D; Conclusions: The risk of damage to sperm DNA in men is primarily associated with the effect of triclosan in seminal fluid. At the same time, it is necessary to assume the absence of a synergistic effect of bisphenol A, triclosan and 4-nonylphenol on the DNA damage of spermatozoa in men.

Двойное слепое рандомизированное плацебо-контролируемое исследование эффективности и безопасности комплекса ацетил-L-карнитина, L-карнитина фумарата и альфа-липоевой кислоты (СпермАктин® Форте) в лечении мужского бесплодия

Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest.To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility.A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants.In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively.The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.

Двойное слепое рандомизированное плацебо-контролируемое исследование эффективности и безопасности комплекса ацетил-L-карнитина, L-карнитина фумарата и альфа-липоевой кислоты (СпермАктин® Форте) в лечении мужского бесплодия

Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest. To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility. A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants. In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively. The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.

Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial.

Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets.Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test.Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis.Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function.Trial Registration: EUDRACT Number 2010-020196-23. Registred 14 April 2011.