Effectiveness of Exercise Training on Male Factor Infertility: A Systematic Review and Network Meta-analysis.

CONTEXT: Mounting evidence from the literature suggests that different types of training interventions can be successful at improving several aspects of male reproductive function in both fertile and infertile populations. OBJECTIVE: The aim of this study was to evaluate the effectiveness of exercise training on male factor infertility and seminal markers of inflammation. DATA SOURCES: We searched PubMed, CISCOM, Springer, Elsevier Science, Cochrane Central Register of Controlled Trials, Scopus, PEDro, Ovid (Medline, EMBASE, PsycINFO), Sport Discus, Orbis, CINAHL, Web of Science, ProQuest, and the ClinicalTrials.gov registry for randomized controlled trials (RCTs) that analyzed the impacts of selected types of exercise interventions on markers of male reproductive function and reproductive performance. STUDY SELECTION: A total of 336 records were identified, of which we included 7 trials reporting on 2641 fertile and infertile men in the systematic review and network meta-analysis. LEVEL OF EVIDENCE: Level 1 (because this is a systematic review of RCTs). DATA EXTRACTION: The data included the study design, participant characteristics, inclusion and exclusion, intervention characteristics, outcome measures, and the main results of the study. RESULTS: The results of network meta-analysis showed that, compared with a nonintervention control group, the top-ranking interventions for pregnancy rate were for combined aerobic and resistance training (CET) (relative risk [RR] = 27.81), moderate-intensity continuous training (MICT) (RR = 26.67), resistance training (RT) (RR = 12.54), high-intensity continuous training (HICT) (RR = 5.55), and high-intensity interval training (HIIT) (RR = 4.63). While the top-ranking interventions for live birth rate were for MICT (RR = 10.05), RT (RR = 4.92), HIIT (RR = 4.38), CET (RR = 2.20), and HICT (RR = 1.55). Also, with the following order of effectiveness, 5 training strategies were significantly better at improving semen quality parameters (CET > MICT > HICT > RT > HIIT), seminal markers of oxidative stress (CET > MICT > HIIT > HICT > RT), seminal markers of inflammation (CET > MICT > HIIT > RT > HICT), as well as measures of body composition and VO2max (CET > HICT > MICT > HIIT > RT). CONCLUSION: The review recommends that the intervention with the highest probability of being the best approach out of all available options for improving the male factor infertility was for CET.

COVID-19 and male reproductive function: a prospective, longitudinal cohort study.

The existing evidence suggests that the human reproductive system may be potentially vulnerable to COVID-19 infection. However, little is known about the virus-host interaction of COVID-19 in sperm cells. We are the first to address the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19. In a prospective longitudinal cohort study, seminal ACE2 activity, markers of inflammation and oxidative stress, apoptotic variables, and semen quality parameters were evaluated at 10-day intervals for a maximum follow-up time of 60 days among male patients with laboratory-confirmed COVID-19 (n = 84) and healthy controls (CON; n = 105). At the baseline and the subsequent follow-ups, the COVID-19 group revealed significantly higher levels of seminal plasma ACE2 enzymatic activity, IL-1ß, IL-6, IL-8, IL-10, TGF-ß, TNF-α, IFN-α, IFN-γ, ROS, caspase-8, caspase-9, and caspase-3 activity as well as lower levels of SOD activity than those in the CON group (P < 0.05). These perturbations tended to persist over time and were correlated with significant impairments in semen volume, progressive motility, sperm morphology, sperm concentration, and the number of spermatozoa. We provide the direct experimental evidence that the male reproductive system could be targeted and damaged by the COVID-19 infection. These findings go beyond our current understanding of the disease, suggesting that the reproductive function of the patients recovering from the disease should be precisely followed and evaluated to detect and avoid more serious reproductive problems in the future, as they may develop a transient state of male subfertility like those with oligoasthenoteratozoospermia.

Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects.

This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o2max). After 1 wk, the same subjects, as their own control, participated in a nonfasting trial (NFA-T) in which they performed an exercise trial of the same duration and intensity. Blood samples were taken before, immediately after, and 1 h after each exercise bout and analyzed for several immunological and metabolic markers. At baseline, fasting subjects showed lower levels of T cell apoptosis, lymphocyte-proliferative responses, IL-6, monocyte chemoattractant protein-1 (MCP-1), insulin, and leptin (P < 0.05) as well as higher levels of neutrophil oxidative burst and thiobarbituric acid reactive substances (TBARS) than those in the NFA-T (P < 0.05). After the exercise protocol, fasted subjects revealed higher T cell apoptosis, neutrophil oxidative burst, TBARS, TNFα, and MCP-1 levels as well as lower levels of lymphocyte-proliferative response, IL-6, insulin, and leptin than those in the NFA-T (P < 0.05). Short-term fasting aggravates perturbations in markers of immune function, and inflammation was induced by an acute moderate-intensity exercise protocol.

High-intensity interval training modulates male factor infertility through anti-inflammatory and antioxidative mechanisms in infertile men: A randomized controlled trial.

The effects of 24 weeks of high-intensity interval training (HIIT) on markers of male reproductive function in infertile patients were studied. Infertile men (n = 441) were randomized to exercise (EX, n = 221) or non-exercise (NON-EX, n = 220) group. Patients in the EX group performed an interval training (1:1 work:rest ratio) 3 times per week at 75-95% of maximal oxygen consumption, for 24 weeks (VO2max). Markers of inflammation and oxidative stress in the seminal plasma, as well as semen parameters, sperm DNA fragmentation and rates of pregnancy, were measured at baseline, on weeks 12, 24; and 7 and 30 days thereafter during the recovery period. The intervention resulted in decreased seminal levels of proinflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) and markers of oxidative stress (ROS, MDA, and 8-isoprostane) (P < 0.05). The concentrations of seminal antioxidants were unaltered with HIIT intervention. These changes further coincide with promising developments in semen parameters, sperm DNA integrity and rates of pregnancy (P < 0.05). This may indicate that HIIT induced beneficial effects on markers of male reproductive function through decreased oxidative damage and proinflammatory status. Findings highlight the possibility that HIIT may be an effective intervention for male factor infertility and support the need for further human studies.

Effects of Aerobic, Resistance, and Combined Exercise on Markers of Male Reproduction in Healthy Human Subjects: A Randomized Controlled Trial.

Hajizadeh Maleki, B, Tartibian, B, and Chehrazi, M. Effects of aerobic, resistance, and combined exercise on markers of male reproduction in healthy human subjects: a randomized controlled trial. J Strength Cond Res 33(4): 1130-1145, 2019-The effects of moderate intensity treadmill exercise training (MI), resistance training (RT), and combined treadmill + resistance training (CT) on markers of male reproductive function including seminal markers of oxidative stress and inflammation, and semen quality and sperm DNA integrity were evaluated in healthy human subjects. A total of 376 healthy sedentary male volunteers (aged 25-40) were screened and 282 were randomized into 4 treatment groups: MI (n = 71), RT (n = 71), CT (n = 71), and nonexercise (NON-EX, n = 70) groups for an experimental period of 24 weeks. After the intervention, compared with the NON-EX group, all 3 MI, RT, and CT exercise modalities showed significantly reduced body mass, fat percent, waist circumference, reactive oxygen species, interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α and improved maximal oxygen uptake (V[Combining Dot Above]O2max), progressive motility, sperm morphology, sperm concentration and sperm DNA integrity, as indicated by a decrease of percentage of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling-positive sperm cells (p ≤ 0.05). Body mass index, semen volume, number of spermatozoa, superoxide dismutase, catalase, total antioxidant capacity, malondialdehyde, and 8-isoprostane improved significantly in the MI and CT groups (p ≤ 0.05) but not significantly in the RT group (p > 0.05). In summary, all 3 MI, RT, and CT interventions attenuate seminal markers of inflammation and oxidative stress and improve body composition, semen quality parameters, and sperm DNA integrity in the studied population. In respect to all the aspects studied, those men who took part in MI intervention had the best results. Considering the seminological parameters, however, CT had a synergistic effect and was superior over the other interventions used.

Resistance exercise modulates male factor infertility through anti-inflammatory and antioxidative mechanisms in infertile men: A RCT.

AIMS: Inflammation and oxidative stress appear to be involved in the pathogenesis of male factor infertility. Exercise training has been shown to strengthen antioxidant defenceses and attenuate inflammation across body fluids, organs and tissues. However, the effect of resistance exercise training upon male factor infertility is unknown. Our aim was to investigate the effects of resistance exercise training on markers of male reproduction and reproductive performance in infertile patients. MAIN METHODS: This study evaluated the changes in seminal oxidative stress status, inflammatory biomarkers, semen parameters, sperm DNA integrity and pregnancy rate following 24 weeks of resistance exercise in infertile patients. A total of 1228 sedentary infertile patient (aged 25-40 years) were screened and 430 were randomized to exercise (EX, n = 216) and non-exercise (NON-EX, n = 214) groups. Semen samples were taken before, 12 and 24 weeks as well as 7 and 30 days during recovery. KEY FINDINGS: Exercise intervention favorably attenuated inflammation as indicated by seminal cytokines (IL-1ß, IL-6, IL-8 and TNF-α), oxidative stress (SOD, MDA and 8-isoprostane) and enhanced antioxidants (SOD and catalase) (P < 0.05), and these changes correlate with favorable improvements in semen parameters, sperm DNA integrity and pregnancy rate in this cohort of infertile patients (P < 0.05). SIGNIFICANCE: Taken together, resistance exercise training improves markers of male reproduction and reproductive performance through inflammatory and oxidative stress mechanisms in infertile patients.

Low-to-moderate intensity aerobic exercise training modulates irritable bowel syndrome through antioxidative and inflammatory mechanisms in women: Results of a randomized controlled trial.

Our aim was to explore the putative beneficial effects of low-to-moderate intensity exercise training program in patients with irritable bowel syndrome (IBS). This study evaluated the changes in blood oxidative stress status, inflammatory biomarkers and IBS severity symptoms following 24 weeks of moderate aerobic exercise in sedentary IBS patients. A total of 109 female volunteers (aged 18-41 yrs) who fulfilled Rome III criteria for the diagnosis of IBS were screened and 60 were randomized to exercise (EX, n = 30) and non-exercise (NON-EX, n = 30) groups. Exercise intervention favorably attenuated inflammation as indicated by plasma cytokines (IL-1ß, IL-6, IL-8, IL-10 and TNF-α), adenosine deaminase, oxidative stress (XO, MDA and NO) and enhanced antioxidants (SOD, CAT and GSH-Px) (P < .05), and these alterations correlate with promising improvements in IBS symptoms (P < .05). Taken together, low-to-moderate intensity exercise training program attenuates symptoms in IBS. Symptom improvement was associated with a reversal of the ratio of anti- to pro-inflammatory cytokines as well as facilitating blood redox homeostasis, suggesting an immune- and redox modulating function for exercise training.

Combined aerobic and resistance exercise training for improving reproductive function in infertile men: a randomized controlled trial.

This randomized controlled trial was conducted to examine the effects of 24 weeks of combined aerobic and resistance exercise training on seminal markers of inflammation and oxidative stress as well as markers of male reproductive function and reproductive performance in infertile patients. Of a total of 1296 infertile patients (aged 25-40 years) who were screened, 556 were randomly assigned to exercise (n = 278) and nonexercise (n = 278) groups. Semen samples were taken before and at 12 and 24 weeks as well as 7 and 30 days post-intervention. The training program reduced seminal proinflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor alpha) and markers of oxidative stress (reactive oxygen species, malondialdehyde, and 8-isoprostane) (P < 0.05). Additional improvements were also achieved in seminal antioxidant defense system (superoxide dismutase, catalase, and total antioxidant capacity) (P < 0.05). Training-induced changes in inflammation and oxidative stress status correlated with favorable improvements in semen parameters, sperm DNA integrity, and pregnancy rate (P < 0.05). In conclusion, these results support the evidence for the favorable effects of combined aerobic and resistance exercise training in male factor infertility.

Moderate aerobic exercise training for improving reproductive function in infertile patients: A randomized controlled trial.

This study investigated for the first time the changes in seminal markers of inflammation, oxidative stress status, semen parameters, sperm DNA integrity as well as pregnancy rate following 24weeks of moderate aerobic exercise in infertile patients. A total of 1026 sedentary men (aged 25-40years) attending the infertility clinic with history of more than one year of infertility, were screened and 419 were randomized to either exercise (EX, n=210) or non-exercise (NON-EX, n=209) groups. Exercise training favorably attenuated seminal markers of both inflammation (IL-1ß, IL-6, IL-8, and TNF-α) and oxidative stress (ROS, MDA, 8-Isoprostane) as well as enhanced antioxidant defense system (SOD, catalase and TAC) (P<0.05). These changes correlate with favorable improvements in semen parameters, sperm DNA integrity and pregnancy rate (P<0.05). The results provide information about the effectiveness of moderate aerobic exercise training as a treatment option for male factor infertility. The 4-week detraining period was not enough to reverse all benefits promoted by exercise intervention.

The effects of three different exercise modalities on markers of male reproduction in healthy subjects: a randomized controlled trial.

The aim of this study was to investigate the effects of moderate-intensity continuous training (MICT), high-intensity continuous training (HICT) and high-intensity interval training (HIIT) on markers of male reproduction including seminal markers of oxidative stress and inflammation as well as semen quality and sperm DNA integrity in healthy human subjects. A total of 397 healthy male volunteers were screened and 280 were randomly assigned to one of the MICT (n = 70), HICT (n = 70), HIIT (n = 70) and non-exercise (NON-EX, n = 70) groups. Subjects had inflammatory markers (IL-1ß, IL-6, IL-8 and TNF-α), oxidants (ROS, MDA and 8-isoprostane), antioxidants (SOD, catalase and TAC), semen parameters and sperm DNA damage measured at baseline (T1), the end of week 12 (T2), the end of week 24 (T3), and 7 (T4) and 30 days (T5) after training. Chronic MICT, HICT and HIIT attenuated seminal markers of oxidative stress and inflammation with different kinetics for the three types of exercise (P < 0.05), and these changes were correlated with favorable improvements in semen quality parameters and sperm DNA integrity (P < 0.05). MICT was superior to HICT and HIIT in the improvements of markers of male reproductive function (P < 0.05). In conclusion, different exercise modalities favorably affect markers of male reproduction with different kinetics, suggesting intensity-, duration- and type-dependent adaptations to exercise training in healthy human subjects.

A randomized controlled trial examining the effects of 16 weeks of moderate-to-intensive cycling and honey supplementation on lymphocyte oxidative DNA damage and cytokine changes in male road cyclists.

The aim of this study was to investigate whether honey supplementation (70g, ninety minutes before each training session) attenuates changes in lymphocyte counts, DNA damage, cytokines, antioxidative and peroxidative biomarkers following moderate-to-intensive exercise training in male road cyclists. Healthy nonprofessional cyclists (n=24, aged 17-26years) were randomly assigned to exercise+supplement (EX+S, n=12) and exercise (EX, n=12) groups for an experimental period of 16weeks. Moderate-to-intensive exercise training increased lymphocytes DNA damage, cytokines and peroxidative biomarkers as well as decreased antioxidative biomarkers in the EX group. These changes were significantly attenuated in the EX+S group. Furthermore, for both groups the observed changes in peroxidative and antioxidative biomarkers could be correlated positively and negatively, respectively, with lymphocyte DNA damage and cytokines. Findings suggest that honey attenuates oxidative stress and lymphocyte DNA damage after exercise, activities that are most likely attributable to its high antioxidant capacity.

Long-term Low-to-Intensive Cycling Training: Impact on Semen Parameters and Seminal Cytokines.

OBJECTIVE: To examine the effects of long-term low-to-intensive cycling training on seminal cytokines and semen parameters in male road cyclists. DESIGN: Repeated measures design. SETTING: The Exercise Physiology Laboratory of the Urmia University. PARTICIPANTS: Twenty-four healthy nonprofessional male road cyclists (23.1 ± 6.2 years) participated in this study. INTERVENTIONS: All subjects participated in a 16-week low-to-intensive cycling training. The semen samples were collected, respectively, at baseline (T1), immediately (T2), 12 (T3), and 24 (T4) hours after the last training session in week 8; immediately (T5), 12 (T6), and 24 (T7) hours after the last training session in week 16; as well as 7 (T8) and 30 (T9) days after the last training session in week 16. MAIN OUTCOME MEASURES: Semen volume, sperm motility, sperm morphology, sperm concentration, and number of spermatozoa as well as seminal interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α in seminal plasma from male road cyclists. RESULTS: The levels of seminal IL-1ß, IL-6, and IL-8 increased (P < 0.008) and remained high after 30 days of recovery. Semen volume, sperm motility, sperm morphology, sperm concentration, and number of spermatozoa decreased (P < 0.008). All of the above-mentioned variables (with the exception of semen volume, sperm motility, and sperm concentration) remained low after 30 days of recovery (P < 0.008). CONCLUSIONS: A 16-week low-to-intensive cycling training may have deleterious consequences for spermatozoa and hence may have an impact on male fertility among cyclists. CLINICAL RELEVANCE: Given that exercise can affect reproductive system among male cyclists, hence cyclists may routinely employ sufficient rest after their training sessions to ensure that the sperm healthy parameters and seminal immunological profiles have properly recovered from the last training sessions.

Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study.

BACKGROUND: Evidence indicates that dietary fats and physical activity influence bone health. The purpose of this study was to examine the effects of long-term aerobic exercise and omega-3 (N-3) supplementation on serum inflammatory markers, bone mineral density (BMD), and bone biomarkers in post-menopausal women. METHODS: Seventy-nine healthy sedentary post-menopausal women aged 58-78 years participated in this study. Subjects were randomized to one of 4 groups: exercise + supplement (E+S, n = 21), exercise (E, n = 20), supplement (S, n = 20), and control (Con, n = 18) groups. The subjects in the E+S and E groups performed aerobic exercise training (walking and jogging) up to 65% of HRmax, three times a week for 24 weeks. Subjects in the E+S and S groups consumed 1000 mg/d N-3 for 24 weeks. The lumbar spine (L2-L4) and femoral neck BMD, serum tumor necrosis factor (TNF) α, interleukin (IL) 6, prostaglandin (PG) E2, estrogen, osteocalcin, 1, 25-dihydroxyvitamin D3 (1, 25 Vit D), C-telopeptide (CTX), parathyroid hormone (PTH) and calcitonin (CT) were measured at baseline, the end of week 12 and 24. RESULTS: Serum estrogen, osteocalcin, 1, 25 Vit D, CT, L2-L4 and femoral neck BMD measures increased (P < 0.05) and the serum CTX, PTH, TNF-α, IL-6, and PGE2 decreased (P < 0.05) in E + S group after the 24 wk intervention but not in the E or S intervention groups. L2-L4 and femoral neck BMD, estrogen, osteocalcin, and CT were negatively (P < 0.05) correlated with TNF-α and PGE2. PTH and CT were correlated positively and negatively with IL-6, respectively (P < 0.05). CONCLUSIONS: The present study demonstrates that long-term aerobic exercise training plus N-3 supplementation have a synergistic effect in attenuating inflammation and augmenting BMD in post-menopausal osteoporosis.