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    World J Mens Health. 2024;42:e9. Forthcoming. English.
    Published online Jan 02, 2024.
    https://doi.org/10.5534/wjmh.230106
    Copyright © 2024 Korean Society for Sexual Medicine and Andrology
    Original Article

    Effects of Physical Activity on Fertility Parameters: A Meta-Analysis of Randomized Controlled Trials

    Arturo Lo Giudice,1 Maria Giovanna Asmundo,1 Sebastiano Cimino,1 Giuseppe Morgia,1 Andrea Cocci,2 Marco Falcone,3 Ioannis Sokolakis,4 Paolo Capogrosso,5 Afonso Morgado,6 Giorgio Ivan Russo,1 and on behalf of the EAU-YAU Sexual and Reproductive Health Group
      • 1Department of Surgery, Urology Section, University of Catania, Catania, Italy.
      • 2Department of Urology, University of Florence, Florence, Italy.
      • 3Urology Section, University of Turin, Molinette Hospital, Turin, Italy.
      • 4Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany.
      • 5Department of Urology, University of Insubria, Insubria, Italy.
      • 6Department of Urology, Centro Hospitalar Universitário São João, Porto, Portugal.
    • Correspondence to: Giorgio Ivan Russo. Department of Surgery, University of Catania, Via Santa Sofia 78, Catania 95123, Italy. Tel/Fax: +39-0953782710, Email: giorgioivan.russo@unict.it
    Received April 13, 2023; Revised July 19, 2023; Accepted August 10, 2023.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Purpose

    Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed.

    Materials and Methods

    The search terms included: “Assisted reproduction therapies,” “fertility,” “semen parameters,” “sperm parameters,” and “physical activity.” This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014–2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias.

    Results

    The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01).

    Conclusions

    We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility.

    Keywords
    Exercise; Fertility; Oligospermia; Reproductive techniques; Semen analysis

    INTRODUCTION

    Physical activity has been shown to have both positive and negative effects on fertility parameters [1] while moderate physical activity has been associated with improved sperm quality, including increased sperm count and motility [2]. In fact, an increase in adiposity may adversely affect male fertility due to its metabolic and hormonal effects [3].

    In a recent systematic review and meta-analysis of observational studies, authors reported that sperm count was lower in class II and class III obesity categories (−0.66; p<0.001, and −0.20; p=0.001, respectively) if compared to non-obese patients [1].

    Since infertility occurs as a result of different metabolic conditions, the underlying mechanisms could be better investigated from a multidisciplinary perspective. It is important to note that the relationship between physical activity and fertility is complex and it may depend on the individual’s exercise habits, overall health, and underlying medical conditions.

    In fact, sedentary lifestyle behaviors not only impact general wellness but also fertility parameters by accelerating aging-processes. A study conducted by Sharqawi et al [4] reported that patients with longer telomere length (16/84 vs. 7/91; p=0.04) are the ones who train most; contrarily those who practice less physical activity are reported to have shorter telomeres. Consequently, sperm motility was negatively correlated with telomeres length (0.588; p=0.002).

    However, evidence about the role of exercise on fertility and sperm parameters have never been summarized due to discordant results and heterogeneity of findings.

    Based on these premises, the aim of this paper is to perform a systematic review of randomized clinical trials with metanalysis to assess if physical activity may have a positive impact.

    MATERIALS AND METHODS

    1. Literature search

    This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines [5] and it was registered on PROSPERO (CRD42023384471). We performed a systematic literature search of PubMed, EMBASE and Scopus using Medical Subject Headings (MeSH) indexes, keyword searches, and publication types. The research was limited to English articles. The search terms included: “Assisted reproduction therapies,” “fertility,” “semen parameters,” “sperm parameters,” and “physical activity”. Relevant articles identified in the reference lists of the selected manuscripts have been included, too. Eligible studies included published journal articles that provided quantitative data on the association between physical activity and sperm concentration, semen volume, total motility, total sperm count, morphology (normal forms), pregnancies rate and live birth rate.

    2. Data extraction

    Three reviewers applied eligibility criteria and selected studies for inclusion in this systematic review. Two reviewers (ALG, MGA) independently screened records for inclusion; one reviewer (GIR) checked for final inclusion or exclusion and resolved disagreements. Decisions have been recorded in an excel sheet reporting principal data of the studies included (Authors, year, DOI). A single reviewer (MGA) performed data extraction using an excel sheets master format and a single reviewer (ALG) checked extracted data that are suitable for analysis. A Third reviewer (GIR) checked for final inclusion or exclusion and resolved disagreements. The following data were extracted from selected paper: authors of the study, source, year of publication, type of study design. Moreover, patients from selected studies were divided into expose and control group; for each category sperm concentration at baseline and at follow-up, semen volume at baseline and at follow-up, total motility at baseline and at follow-up, total sperm count at baseline and at follow-up, morphology (percentage of normal sperm morphology) at baseline and at follow-up, total pregnancies rate at follow-up, live birth rate at follow-up were reported. All data will be collected and managed with an excel spreadsheet and the software Review Manager (RevMan, Version 5.4; The Cochrane Collaboration, 2020).

    3. Risk of bias assessment

    Two reviewers (MGA and ALG) assessed the risk of bias before the outcome’s extraction; the following characteristics have been assessed: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcomes assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias). Cochrane risk of bias tool had been applied to accomplish the task. In conclusion, the third reviewer (GIR) solved any disagreement between reviewers’ judgements.

    4. Data analysis

    Semen parameters, sperm concentration, semen volume, total sperm motility, total sperm count, sperm morphology (percentage of normal sperm morphology) had been reported at baseline and follow-up time as mean with standard deviation for both groups. The number of patients in groups have been reported as continuous variable. Data about total pregnancies rate and live birth rate at follow-up have been reported as dichotomous variable of total events within patients’ groups. Also in this case, the number of patients belonging to the different groups have been reported as continuous variable. Statistical heterogeneity has been explored using χ2 test for continuous or dichotomous variable. The outcomes about sperm concentration, semen volume, total sperm motility, total sperm count, morphology (percentage of normal sperm morphology) have been reported as a standard mean difference between the values at follow-up in physical activity and controls group. The outcomes about total pregnancies rate and live birth rate have been reported as a risk difference (RD) between the ratio of total events to total patients in physical activity group and controls group.

    RESULTS

    1. Characteristics of the studies

    A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014–2022) have been included in the meta-analysis (Supplement Fig. 1) [2, 6, 7, 8, 9, 10]. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias (Supplement Fig. 2).

    The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the meta-analysis. Parameters investigated were semen quality parameters (i.e., sperm concentration, semen volume, total sperm motility, total sperm count, sperm morphology) and pregnancy and live births rates. In particular, a total of 340 patients have been enrolled in the three studies investigating semen quality [2, 6, 7] while a total of 1,297 patients have been enrolled in the studies investigating pregnancy rate and live births rate [8, 9, 10]. A total of two references that studied sperm concentration parameters in a sample of 280 total patients were included [2, 6]; three studies investigated semen volume and total motility parameters among a 340 patients-sample [2, 6, 7]; two studies enrolling 99 patients assessed total sperm count [2, 7]; two more articles investigated normal sperm forms among 323 participants [6, 7]; finally, three studies enrolling a total of 1,297 patients investigated pregnancy rate and live births rate [8, 9, 10]. Characteristics of the studies included in the meta-analysis are listed in Table 1. The qualities of these studies were all satisfactory according to the previously specified criterion.

    Table 1
    Characteristics of the studies included in the meta-analysis

    2. Analysis

    Standard mean difference (SMD) (IV, Fixed, 95% confidence interval [CI]) analysis has been performed to investigate on the association between physical activity and sperm concentration, semen volume, total motility, total sperm count and normal forms. RD (IV, Fixed, 95% CI) analysis has been performed to investigate on the association between physical activity and total pregnancies rate and live birth rate.

    We revealed that the association between physical activity and sperm concentration is statistically significant (Z=2.37; p=0.02) with a SMD of 0.28 (95% CI 0.05–0.52); heterogeneity between studies was 0% (chi2=0.16, df=1; p=0.69) (Fig. 1).

    Fig. 1
    Forest plot of sperm concentration and physical activity. SD: standard deviation, CI: confidence interval.

    We also evidenced that the association between physical activity and total motility is statistically significant (Z=5.62; p<0.00001), with a SMD of 0.63 (95% CI 0.41–0.85); heterogeneity between studies was 60% (chi2=4.99, df=2; p=0.08) (Fig. 2).

    Fig. 2
    Forest plot of total motility and physical activity. SD: standard deviation, CI: confidence interval.

    We demonstrated that the association between physical activity and total sperm count is statistically significant (Z=2.83; p<0.005), with a SMD of 0.62 (95% CI 0.19–1.05); heterogeneity between studies was 0% (chi2=0.00, df=1; p=0.99) (Fig. 3).

    Fig. 3
    Forest plot of total sperm count and physical activity. SD: standard deviation, CI: confidence interval.

    The association between physical activity and normal forms is also statistically significant (Z=4.93; p<0.00001), with a SMD of 0.56 (95% CI 0.34–0.78); heterogeneity between studies was 75% (chi2=4.01, df=1; p=0.05) (Fig. 4).

    Fig. 4
    Forest plot of normal forms and physical activity. SD: standard deviation, CI: confidence interval.

    The association between physical activity and semen volume is not statistically significant (Z=1.37; p=0.17), with a SMD of 0.15 (95% CI 0.06–0.36); heterogeneity between studies was 0% (chi2=1.04, df=2; p=0.60). Regarding physical activity and total pregnancies rate, our results proved that a statistically significant association existed (Z=27.91; p<0.00001), with a RD of 0.50 (95% CI 0.46–0.53); heterogeneity between studies was 99% (chi2=233.09, df=2; p=0.00001) (Fig. 5).

    Fig. 5
    Forest plot of total pregnancies and physical activity. SD: standard deviation, CI: confidence interval.

    Moreover, we found that the association between physical activity and live births rate is statistically significant (Z=7.97; p<0.00001), with a RD of 0.71 (95% CI 0.54–0.89); heterogeneity between studies was 75% (chi2=8.22, df=2; p=0.02) (Fig. 6).

    Fig. 6
    Forest plot of live birth and physical activity. SD: standard deviation, CI: confidence interval.

    DISCUSSION

    Herein our data suggested that physical activity significantly influenced semen parameters and pregnancy outcome in infertile patients. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01). However, no relevant connection between exercise and semen volume has been documented.

    Previous studies have reported that obesity has a detrimental impact on male fertility [11, 12]. In more details, Salas-Huetos et al [1] reported that overweight and obesity were linked with lower sperm quality like semen volume, sperm count and concentration, sperm vitality, total motility, and normal morphology and underweight was linked with reduced normal sperm morphology.

    Augmented adiposity may negatively impact on sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones [3, 13]. In fact, disrupted hypothalamic-pituitary-gonadal axis negatively influences spermatogenesis process and, therefore, fertility. Overabundance of adipose tissue impacts on hormonal profile leading to altered testosterone/estrogen ratio and insulin, sex-hormone-binding globulin, leptin, inhibin B level; all these components play a pivotal role on testosterone level and consequent impaired spermatogenesis [14]. In addition, Jia et al [15] revealed the increment of apoptosis of spermatogenic cells in their “obesity group rats”. Moreover, according to Garolla et al [16], dysregulated metabolic pathways may promote apoptosis among spermatogenic cells via overexpression and overactivation of pro-apoptotic factors as Bax. Furthermore, a recent study found that apoptosis of testicular spermatogenic cells is one of the major causes of male subfertility [17]. Moreover, obesity and dyslipidemia are reported to challenge sperm function through the activation of oxidative stress and proinflammatory signaling among testicular cells [18]. Based on these premises, a relation between weights loss and improvement of semen quality seems consistent.

    According to these findings and due to the multiple influence of different metabolic conditions, a multidisciplinary approach seems the most appropriate to investigate the underlying connections between body weight and semen quality. Focusing on the role of exercise on sperm characteristics, a great heterogeneity of results had been registered.

    Literature evidenced that recreational physical activity has a positive or neutral effect on semen quality while highly intense training may lead to worsen parameters [19]. Several studies reported that relevant modification of semen parameters may occur according to the type, duration and intensity of the training performed.

    In an animal study conducted by Silva et al [20], the impact of physical exercise on testicular function and antioxidant capacity were evaluated. Testicular mitochondrial adaptation has also been investigated in animal model performing intense training. Authors demonstrated that higher level of serum testosterone in older exercised animal if compared with the sedentary ones. Moreover, they benefited from augmented mitochondrial antioxidant capacity and increased levels of antioxidant enzymes (super oxide dismutase [SOD] 1 and SOD 2) that lead to an improved capacity to recover from cellular stress.

    Before concluding we would like to underline some limitation. Included studies were not homogeneous and performed physical activity was different among groups analyzed. Moreover, we did not account on other putative risk factors related to health (i.e. diabetes, smoking, etc.) or also genetic characters (i.e. related genes). Moreover, studies weight is sometimes very different in plot and these could influence final results, included studies numbers were small and had high heterogeneity in forest plot, however a leave one out meta-analysis or an individuation of potential outliers can’t be performed due to the small number of studies included and for these reasons other clinical studies are necessary to confirm the findings of this meta-analysis; next step could be the investigation of the effect of physical activities on genomic in male infertility. Finally, studies did not report data on markers of oxidative stress that may justify these findings.

    On the other hand, strengths of the present meta-analysis are the inclusion of randomized controlled trials and full assessment of male infertility.

    CONCLUSIONS

    We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility. Further studies may be warranted to confirm and strengthen our findings.

    Supplementary Materials

    Supplementary materials can be found via https://doi.org/10.5534/wjmh.230106.

    Supplement Fig. 1

    Study selection flow chart.

    Click here to view.(70K, pdf)

    Supplement Fig. 2

    Risk of bias assessment.

    Click here to view.(70K, pdf)

    Notes

    Conflict of Interest:The authors have nothing to disclose.

    Funding:None.

    Author Contribution:

    • Conceptualization: ALG, GIR.

    • Methodology: GIR.

    • Validation: SC, GM, AC.

    • Formal analysis: MF, IS, PC, AM.

    • Investigation: ALG.

    • Data curation: ALG.

    • Writing - original draft preparation: ALG.

    • Writing - review and editing: MGA.

    • Visualization: SC.

    • Supervision: GIR.

    • Project administration: GIR.

    • All authors have read and agreed to the published version of the manuscript.

    Acknowledgements

    None.

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