The impact of Chlamydia infection on semen parameters and male fertility: A systematic review and meta-analysis

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This systematic review and meta-analysis compared semen parameters of Chlamydia (+) males with Chlamydia (-) males. Method The databases MEDLINE, Embase and PubMed were searched for relevant studies. Results Sixteen studies were included with more than 3000 patients. Chlamydia infection negatively impacted on sperm concentration (DM -3.33, 95% CI: -6.54 to -0.12; P = 0.04; I 2 = 30%) and progressive motility (DM -1.62, 95% CI: -3.04 to -0.20; P = 0.03; I 2 = 14%) in infertile males. Semen volume, sperm normal morphology, sperm vitality and semen pH may not be associated with Chlamydia infection in infertile males. Chlamydia infection may influence semen volume with combining with region factor (DM -0.87, 95% CI: -1.29 to -0.44; P < 0.0001; I 2 = 33%). Discussion and conclusions: Chlamydia infection deteriorates infertile males’ reproductive function. These finds induce us to consider Chlamydia’s contribution to males’ reproductive dysfunction, and the treatment of Chlamydia whether protect males’ reproductive function should be studied in the future. semen parameters male fertility reproductive function Chlamydia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction It’s reported that 8–12% of couples are troubled by infertility all over the world 1 . Infertility is defined as inability to conceive after 12 months of trying, and male factors are estimated to contribute to 30–50% of infertility. Infertility or impaired fertility can be caused by testicular dysfunction, endocrine disorders, lifestyle factors (such as tobacco and obesity), congenital anatomical abnormality, gonadal toxic exposure, aging, and other factors 2 . In the meanwhile, C Keck et al . reported that urogenital tract infection can also cause infertility 3 . Chlamydia infection is one of the most prevalent bacterial sexually transmitted disease (STD). Chronic prostatitis can be caused by Chlamydia, and prostatitis has been proven associated with decreased sperm concentration, altered sperm morphology, and lower inducibility of the acrosome reaction 4 . Some of these studies reported Chlamydia would lead to semen parameters abnormality, while the rest of these studies hold opposite attitude. For example, Ahmadi et al. conducted a case-control study and emphasized that the semen parameters of asymptomatic males with Chlamydia infection will turn better if being treated 5 . In this aspect, the impact of Chlamydia on reproduction is controversial, more investigations are still needed to determine the efficacy and prognosis of antibiotics treatment for patients with Chlamydia infection 6 . These contradictory results leave us puzzled about the effects of Chlamydia infection on male fertility with a lack of clarity. Thus, it is of great significance to clarify whether Chlamydia infection impact infertility and semen parameters. Many health conditions can affect male fertility, which underscore the need for a thorough evaluation of patients to identify treatable or reversible lifestyle factors or medical conditions 7 . The evaluation of male infertility includes a detailed history, focused physical examination, and selective laboratory tests 2 . Semen analysis is still the cornerstone for evaluating male infertility 7 . The fundamental examinations of semen analysis include sperm concentration, motility, and morphology, while initial macroscopic examinations include appearance, volume, consistency and pH 8 . Thus, the aim of this meta-analysis is to concentrate on the effect of Chlamydia infection on infertility, regarding sperm concentration, sperm morphology, and other semen parameters. Search strategy We searched the studies on November 15,2023 in MEDLINE, Embase and PubMed, without language limits and also searched the gray literature for meta-analysis. The following is our keywords: (Chlamydia OR Chlamydia trachomatis OR Chlamydia muridarum) AND (semen parameters OR Sperm concentration OR sperm Morphology OR sperm Motility OR seminal fluid Volume OR seminal fluid pH). The exclusion criteria were as follows: 1. The population has characteristics that are significantly worse than the general population, such as soldiers, people with normal fertility and so on. 2.The evaluation of semen quality in this paper is a range value rather than a specific value. 3.Studies reporting only on bacteriospermia without analyzing the impact on semen parameters or the association with male infertility. In our study, we excluded studies based on mentioned criteria for some consideration. Firstly, some special crowds may have unique characteristics, for example, immunity of soldiers may be greater. Secondly, the clear values of semen parameters are crucial for meta-analysis, which is not provided by some studies. Last, some studies reported bacteriospermia without analyzing the impact on semen parameters or the association with male infertility. Outcomes measures: The main outcome measure is the semen parameters of males infected with Chlamydia. Evidence Synthesis 16 studies (Table 1) were included into this meta-analysis, with more than 3000 subjects 9 – 24 . The studies which were excluded from this research is shown in the PRISMA flowchart (Fig. 1 ). The systematic review was registered with PROSPERO (ID number CRD42024503506). Parts of excluded studies revealed their findings with range value, while some studies just reported whether their statistics were in normal range or not. Some studies were considered as low-quality research, which didn’t explain which group some of these data belong to, and these were excluded. Those data can’t be involved in to conclude the mean value and SD. Two study chose two ways to determine Chlamydia infection, and reported all statistics corresponding to each method(PCR and ELISA) 12 , 17 . Concerning about that the method to determine Chlamydia infection will affect the latest result, we collected in the meta-analysis only the data which is from the group that use the method of PCR. Two studies comprehensively argued the impact of Chlamydia infection on males, which includes fertile males, infertile males with previous Chlamydia infection and without previous infection 11 , 14 . We collected the latter two patterns, but abandoned the data of fertile males for a lack of the same crowd to explore if the factor, fertile/infertile, will make an effort to semen parameters with Chlamydia infection 14 . The data extracted were collected in Microsoft 365(Microsoft Corporation, Redmond, CA, USA), and the analysis was conducted by review manager (5.3, The Cochrane Collaboration,). The process of collecting data was exerted by two independent reviewers, to ensure accuracy and consistency. For each semen parameters, we calculated the mean difference and the corresponding confidence interval. The choice of fixed effect model and random effect model is up to I 2 or p, Q-test (when I 2 ≥ 50% or p < 0.10,Q-test). Whether latest result is meaningful depends on the relationship between invalid line and the diamond. Data were kept in forms we designed before. Two reviewers independently screened titles and abstracts of all articles searched by the search strategies. All potentially relevant reports were retrieved in full and assessed by one reviewer. The statistics were collected, and the bias-comments were done by two reviewers independently via Newcastle-Ottawa Scale. Any disagreements during the selection process were resolved by consensus. This meta-analysis collected data for exploring the influence Chlamydia has on the various semen parameters. In this study, the semen parameters which include semen volume (ml), semen sperm concentrations (million/ml), progressive motility (%), normal morphology (%), sperm vitality (%) and semen pH are argued. The studies included in this systematic review use various methods to identify males whether were infected by Chlamydia or not. The methods consist of blood culture (n = 1), PCR (n = 5), ELISA (n = 3) and serology (n = 3). More that, the rest of studies adopted multiple methods to diagnose Chlamydia infection, and two studies reported corresponding statistics in each method (PCR and serology), partial literature didn’t distinguish the statistics (is mixed) from which detection group. Results Semen volume The data of 13 studies were extracted to compare semen volume between Chlamydia (+) and Chlamydia (-), analyzed using a random effects model (Fig. 2 ). The result revealed that semen volume of Chlamydia (+) group didn’t be more than Chlamydia (-) group (Difference in means − 0.22, 95% CI: -0.50 to 0.06; P = 0.12; I 2 = 64%). And we did a subgroup analysis by various settlements (Fig. 3 ). The meta-analysis revealed that, based on continuous data (mean +/- SD), semen volume of Chlamydia (+) group in Iran is significantly more than Chlamydia (-) group (Difference in means − 0.87, 95% CI: -1.29 to -0.44; P < 0.0001; I 2 = 33%) 9,17,18 . sperm concentration The data of 16 studies were extracted to compare sperm concentration of Chlamydia (+) males with Chlamydia (-), analyzed using a fixed effects model (Fig. 4 ). The forest plot revealed the mean sperm concentration of Chlamydia (-) group is significantly more than Chlamydia (+) group (Difference in means − 3.33, 95% CI: -6.54 to -0.12; P = 0.04; I 2 = 30%). Sperm progressive motility The data of 15 studies were extracted to compare sperm progressive motility of Chlamydia(+) group with Chlamydia(-), by utilizing a fixed effects model (Fig. 5 ). The meta-analysis was conducted on these studies that provided continuous data (mean +/- SD) which revealed that Chlamydia (-) group had a significantly better rate of progressive motility compared with Chlamydia (+) (Difference in means − 1.62, 95% CI: -3.04 to -0.20; P = 0.03; I 2 = 14%). Sperm normal morphology The data of 13 studies were extracted to compare sperm normal morphology of Chlamydia (+) with Chlamydia (-), analyzed using a fixed effects model (Fig. 6 ). The forest plot revealed that There is no difference between two groups (Difference in means 0.00, 95% CI: -0.66 to 0.66; P = 0.99; I 2 = 49%). Sperm vitality The data of 6 studies were extracted to compare sperm vitality of Chlamydia (+) group with Chlamydia (-) group, analyzed using a fixed effects model (Fig. 7 ). And the meta-analysis of the pooled data found that statistics have no sense (Difference in means − 0.05, 95% CI: -2.85 to 1.85; P = 0.68; I 2 = 11%). Semen pH The data of 8 studies were extracted to compare semen pH of Chlamydia (+) group with Chlamydia (-) group, analyzed using fixed effects model (Fig. 8 ). The forest plot revealed that data didn’t reach statistically significantly (Difference in means − 0.03, 95% CI: -0.06 to 0.01; P = 0.13; I 2 = 0%). Discussion To determine the Chlamydia infection whether would have an impact on semen parameters or not, this meta-analysis collected and evaluated such objects (semen volume, sperm concentration, progressive motility, normal morphology, vitality, and pH) in Case-control studies. Our meta-analysis of more than 3000 patients by including 16 studies, indicates that, Chlamydia infection will deteriorate infertile males’ sperm concentration and sperm progressive motility. But the rest of parameters decreasing is not associated with Chlamydia infection in infertile males. As the crucial factors of males’ reproductive function, sperm concentration and sperm progressive motility are usually utilized to analyze males’ semen quality. Overall, Chlamydia infection will decrease semen quality and damage males’ reproductive function. According to previous studies, the males’ reproductive function might be influenced by many kinds of pathogens. In addition to pathogens’ direct impairment, there are also other indirect factors such as inflammation, fever leading to sperm quality worsen. Meanwhile, we also found that the CI of semen volume trended to achieve the threshold (judging roughly by the forest plot). By subgroup analysis, we found that region as an influencing factor is associated with semen volume changing. The region factor may affect volume by influencing population characteristics or ethnic groups. Nevertheless, we found that there is no significant difference between Chlamydia (+) and Chlamydia (-) in the pH, sperm vitality and sperm normal morphology. This might be because Chlamydia infection mainly affects spermatogenic function of testis, but pH of semen is mainly influenced by the prostate gland and seminal vesicles, while mean sperm vitality rates of two groups are nearly the same. Compared to a prior meta-analysis, we improved the result 26 . When the prior reported that Chlamydia infection won’t affect semen parameters which including sperm concentration and sperm progressive motility, our new meta-analysis denied it. Compared with the prior, an important strength of our study is that the number of included studies are 16, much more and with more participants. Furthermore, we analyzed more subgroups in terms of sources of samples and characteristics of population by utilizing previous collected data, we have actively reduced research waste. Although those new subgroup analysis didn’t support positive results. We also made our finding more believable. But we still have limitations. We all know that there are many factors that can cause a decline in reproductive system function, such as varicocele, primary hypogonadism, cryptorchidism, obstructive azoospermia, history of vasectomy, and a history of receiving radiation or chemotherapy. Literature also reported that infection is an important contributing factor to the damage in reproductive function. In our studies searched, we found that some studies explicitly excluded patients with a history of the aforementioned conditions or partial conditions, while others did not. This resulted in heterogeneity in the characteristics of the included populations. (as men defined merely as infertility status may have a history of these diseases contributing to their infertility as well). We also conducted subgroup analyses in terms of the literature that performed exclusion on populations with a history of aforementioned diseases. We still didn’t find positive result. But considering one of these studies have significant publication bias, we excluded it 25 . We suggest that future research should establish more uniform inclusion and exclusion criteria for patients with a history of diseases, to help us further investigate the impact of Chlamydia infection on infertile men and make results more believable. What’s more, the included studies didn’t provide details on the timing of infection occurrence and the course of infection, which should be given more attention. Due to the particularity of this disease, we can’t conduct randomized controlled trials, and thus, it’s hard to accurately determine the specific time of getting infected and the development of the disease. Nevertheless, it takes time from infection occurrence to potentially affect reproduction function. And this leads to this part being hard to standardize. Meanwhile, we found that the most patients reported in these literature who performed semen analysis usually seek medical advice for infertility symptoms rather than infection symptoms, even partial patients are asymptomatic. This suggests that patients likely consist of both long-term asymptomatic carriers and short-term infection cases, and the progression of this disease takes time. In our discussion, the site of infection is also considered as a factor, because Chlamydia infection in elsewhere will lead to serum anti-Chlamydia antibodies positive. Additionally, we differentiated between urine and semen samples for PCR testing to reduce the impact of the infection site on the results in subgroup analysis. However, we didn’t find positive results. This condition possibly due to contamination of semen samples with urethral secretions during collection, but we were unable to eliminate this impact. Puncture as an invasive method is not recommended to reduce this impact. In addition, as we all know, the immune system will produce antibodies when get infected. As the IgG antibodies increase, which will persist in serum for a long period, The IgM antibodies will decline in a short-term after their production. Meanwhile, we found that when semen PCR positive and serum anti-Chlamydia IgG as diagnostic criteria respectively, significant differences in semen parameters were observed between the PCR group and IgG group in two studies 9 , 13 . Nevertheless, partial studies didn’t differentiate patients with detection methods. This suggests that the method of Chlamydia detection has an impact on the result. Considering what mentioned above, we should realize that Chlamydia infection really have an influence on males’ reproductive function. And this would guide us to consider Chlamydia infection as a factor affecting males’ fertility. Our study population are infertile males, and evidence of the impact of Chlamydia infection on normal reproductive function males in long term is still lacking. In the future, we should start with above orientation, taking to explore appropriate treatment for males of Chlamydia infection and evaluate efficacy, to diminish damage of males’ reproductive function from Chlamydia infection. Conclusion This meta-analysis determined Chlamydia infection really deteriorates infertile males’ reproductive function and decreases both sperm concentration and sperm progressive motility. Decreasing of sperm normal morphology, sperm vitality and semen pH are not associated with Chlamydia infection in infertile males. But Chlamydia infection may influence semen volume with combining with region factor Abbreviations CI, confidence interval; MD, mean difference; STD, sexually transmitted disease Declarations Conflict of interest statement The authors declare that they have no competing interests, be it financial, personal or professional. Funding information This work was supported by the National Natural Science Foundation of China [No. 82071632], and the Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0069]. Acknowledgment I would like to thank my supervisor, Shengde Wu, for his guidance through each stage of the process. Meanwhile I’d like to thank Chengjun Yu, who always offers me help and advises me to learn more information. Author’s Contribution Yuanzhi Song took part in all stages of this research involving searching studies, collecting data, analyzing data and editing article. Chengjun Yu offered guidance for Yuanzhi Song in all stages. Wuhong Weng searched studies and collected data. Maolin Liu, Hao Yan and Miao Sun helped Yuanzhi Song to analyse data. Shengde Wu* guided Yuanzhi Song through each stage of the process. Data availability Data openly available in a public repository Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests Not applicable. References Ombelet W, Cooke I, Dyer S, Serour G, Devroey P. Infertility and the Provision of Infertility Medical Services in Developing Countries. Hum Reprod Update. 2008;14(6):605–21. https://doi.org/10.1093/humupd/dmn042 . Eisenberg ML, Esteves SC, Lamb DJ, Hotaling JM, Giwercman A, Hwang K, Cheng Y-S. Male Infertility Nat Rev Dis Primer. 2023;9(1):49. https://doi.org/10.1038/s41572-023-00459-w . Keck C, Gerber-Schäfer C, Clad A, Wilhelm C, Breckwoldt M. Seminal Tract Infections: Impact on Male Fertility and Treatment Options. Hum Reprod Update. 1998;4(6):891–903. https://doi.org/10.1093/humupd/4.6.891 . 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Characteristics of included studies Study Year published Country Study design Recruitment Chlamydia(+) Chlamydia(-) Outcomes Guidelines for semen analysis Patients Patients Ahmadi K et al. 2023 Iran Case control 2016-2017 5 39 semen volume, sperm concentration, motility, morphology, pH WHO2021 Ammar-Keskes L et al. 1998 Tunisia Case control 1996 37 60 semen volume, sperm concentration, motility, morphology, vitality Unclear Auroux MR et al. 1987 France Case control Unclear 15 39 semen volume, sperm concentration, motility, vitality, pH Unclear Auroux MR et al. 1987 France Case control Unclear 15 13 semen volume, sperm concentration, motility, vitality, pH Unclear Chen L et al. 2020 China Case control 2017-2019 17 309 semen volume, sperm concentration, motility, morphology, pH WHO2010 de Barbeyrac B et al. 2006 France Cohort study 1998-2001 40 191 semen volume, sperm concentration, motility, morphology Unclear Gregoriou O et al. 1989 Greece Case control Unclear 21 63 semen volume, sperm concentration, motility, vitality, pH WHO1980 Gregoriou O et al. 1989 Greece Case control Unclear 19 17 semen volume, sperm concentration, motility, vitality, pH WHO1980 Hosseinzadeh S et al. 2004 UK Case control Unclear 31 611 semen volume, sperm concentration, motility, morphology, pH WHO1999 López-Hurtado M et al. 2018 Mexico Case control Unclear 37 79 semen volume, sperm concentration, morphology, vitality, pH WHO2010 Marvast L et al. 2016 Iran Case control 2009-2010 11 239 semen volume, sperm concentration, motility, morphology, pH WHO1999 Moosavian M et al. 2019 Iran Case control 2016-2017 5 17 semen volume, sperm concentration, motility, morphology, pH Unclear Nagy B et al. 1989 Hungary Case control Unclear 26 158 sperm concentration, motility, morphology WHO1980 Rybar R et al. 2012 Czech Republic Case control Unclear 38 173 semen volume, sperm concentration, motility, morphology, vitality WHO2010 Segnini A et al. 2003 Venezuela Case control Unclear 25 27 semen volume, sperm concentration, motility, morphology WHO1992 Sellami H et al. 2014 Tunisia Case control Unclear 13 57 sperm concentration, motility, vitality WHO1999 Veznik Z et al. 2004 Czech Republic Case control Unclear 136 491 semen volume, sperm concentration, motility, morphology WHO1999 Vigil P et al. 2002 Chile Case control Unclear 42 42 sperm concentration, motility, morphology WHO1992 Additional Declarations No competing interests reported. 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Urology, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengjun","middleName":"","lastName":"Yu","suffix":""},{"id":318989483,"identity":"a24b8362-06b7-454a-b418-c199606be85e","order_by":2,"name":"Wuhong Weng","email":"","orcid":"","institution":"The First Clinic College, Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wuhong","middleName":"","lastName":"Weng","suffix":""},{"id":318989484,"identity":"e4d67c2a-d94c-4a0c-bf56-0d08dc7119c4","order_by":3,"name":"Maolin Liu","email":"","orcid":"","institution":"Department of Urology, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Maolin","middleName":"","lastName":"Liu","suffix":""},{"id":318989485,"identity":"cee0115d-435b-43a1-a648-601fb1143337","order_by":4,"name":"Hao Yan","email":"","orcid":"","institution":"Department of Urology, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Yan","suffix":""},{"id":318989487,"identity":"122af3af-ef2e-4da5-b133-60185f89d667","order_by":5,"name":"Miao Sun","email":"","orcid":"","institution":"Department of Urology, Children’s Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Miao","middleName":"","lastName":"Sun","suffix":""},{"id":318989488,"identity":"1fe922e6-ddcf-41ef-b60e-fccb15d56ce3","order_by":6,"name":"Shengde Wu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABL0lEQVRIiWNgGAWjYDACCRDBBsTsPVAuO1wugYAWnjNgrgQDM9FaJHKgfEJa5Gc3H3v4pcwmccPNtwcf/txhUcffzMD44W3OYQZ+9hwDhp87MLQY3DmWbixzLi1xw+28ZGPeMxISEocZmCXnbjvMINnzxoCx9wymFokcM2nJtsO5G24DGYxtQL8cZmBj5gVqMbiRY8DM2IbpsBn534Ba/uduuHnGTPInUIs8TIs9Di0MN3LYJD+2HcjdcIPHTIIXqMUAbosEdi0GN9LMpBnOJdfPPJNjDPKL5MbDjM1Av6TzSJx5VnCwF5vDkp9J/iizM+Y7fsYQGGJ1/HLHmw9+eLvNWo6/PXnjg59YHAYEzDwwFmMDlASKgAUPYNUAVPIDVQsDVP0oGAWjYBSMAggAAJZqaV11i9VZAAAAAElFTkSuQmCC","orcid":"","institution":"Chongqing Key Laboratory of Structural BirthDefect and Reconstruction, Chongqing, China","correspondingAuthor":true,"prefix":"","firstName":"Shengde","middleName":"","lastName":"Wu","suffix":""}],"badges":[],"createdAt":"2024-06-07 07:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4544403/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4544403/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60196557,"identity":"28c515fb-452b-4057-aff5-e5d97a01935b","added_by":"auto","created_at":"2024-07-13 01:46:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24595,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flowchart\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/c5f4b4a1147f7e90660441d2.png"},{"id":60197062,"identity":"c238e335-d25d-476b-88c7-87a549ea39b7","added_by":"auto","created_at":"2024-07-13 01:54:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108042,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing semen volume of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/fc40b3d8deb18194cf8eba65.png"},{"id":60196562,"identity":"3554617f-815a-4149-af42-65bf7f907fc7","added_by":"auto","created_at":"2024-07-13 01:46:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51519,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing semen volume of Chlamydia (+) and Chlamydia (-) in Iran\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/222af297451e0e91de208bc6.png"},{"id":60197983,"identity":"ee2c8f7d-5eab-49fe-8155-f66ac5be2c92","added_by":"auto","created_at":"2024-07-13 02:02:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":127235,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing sperm concentration of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/efafb67e06dc8173647af4aa.png"},{"id":60196564,"identity":"074c1d6b-fc74-4194-b28f-2da3a701cf1e","added_by":"auto","created_at":"2024-07-13 01:46:25","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":122544,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing sperm progressive motility of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/4c6ebea0fba180b220701a6a.png"},{"id":60196558,"identity":"8a987fc3-177e-46a0-930e-49370add1f14","added_by":"auto","created_at":"2024-07-13 01:46:24","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":18966,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing sperm normal morphology of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/7f0affbe6a48c408a0ae7820.png"},{"id":60196560,"identity":"dd3e6e60-1136-4289-9d92-5162956c7b6d","added_by":"auto","created_at":"2024-07-13 01:46:24","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":76618,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing sperm vitality of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/3969778a9bc48099c1c5d8f2.png"},{"id":60197064,"identity":"08235fe7-39c8-4c5d-bdfc-8fe3dc62458c","added_by":"auto","created_at":"2024-07-13 01:54:24","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":82440,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing semen pH of Chlamydia (+) and Chlamydia (-)\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/1092bab8fbbe36cced7c5bc7.png"},{"id":60292252,"identity":"25b80f7d-7f8c-4579-87d4-453398704a26","added_by":"auto","created_at":"2024-07-15 09:03:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":983070,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4544403/v1/eb1fb6d0-5855-4438-a17a-f4fb6e070cb9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The impact of Chlamydia infection on semen parameters and male fertility: A systematic review and meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIt\u0026rsquo;s reported that 8\u0026ndash;12% of couples are troubled by infertility all over the world\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Infertility is defined as inability to conceive after 12 months of trying, and male factors are estimated to contribute to 30\u0026ndash;50% of infertility. Infertility or impaired fertility can be caused by testicular dysfunction, endocrine disorders, lifestyle factors (such as tobacco and obesity), congenital anatomical abnormality, gonadal toxic exposure, aging, and other factors\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. In the meanwhile, C Keck \u003cem\u003eet al\u003c/em\u003e. reported that urogenital tract infection can also cause infertility\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Chlamydia infection is one of the most prevalent bacterial sexually transmitted disease (STD). Chronic prostatitis can be caused by Chlamydia, and prostatitis has been proven associated with decreased sperm concentration, altered sperm morphology, and lower inducibility of the acrosome reaction\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Some of these studies reported Chlamydia would lead to semen parameters abnormality, while the rest of these studies hold opposite attitude. For example, Ahmadi \u003cem\u003eet al.\u003c/em\u003e conducted a case-control study and emphasized that the semen parameters of asymptomatic males with Chlamydia infection will turn better if being treated\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In this aspect, the impact of Chlamydia on reproduction is controversial, more investigations are still needed to determine the efficacy and prognosis of antibiotics treatment for patients with Chlamydia infection\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. These contradictory results leave us puzzled about the effects of Chlamydia infection on male fertility with a lack of clarity. Thus, it is of great significance to clarify whether Chlamydia infection impact infertility and semen parameters.\u003c/p\u003e \u003cp\u003eMany health conditions can affect male fertility, which underscore the need for a thorough evaluation of patients to identify treatable or reversible lifestyle factors or medical conditions\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The evaluation of male infertility includes a detailed history, focused physical examination, and selective laboratory tests\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Semen analysis is still the cornerstone for evaluating male infertility\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The fundamental examinations of semen analysis include sperm concentration, motility, and morphology, while initial macroscopic examinations include appearance, volume, consistency and pH\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThus, the aim of this meta-analysis is to concentrate on the effect of Chlamydia infection on infertility, regarding sperm concentration, sperm morphology, and other semen parameters.\u003c/p\u003e"},{"header":"Search strategy","content":"\u003cp\u003eWe searched the studies on November 15,2023 in MEDLINE, Embase and PubMed, without language limits and also searched the gray literature for meta-analysis. The following is our keywords: (Chlamydia OR Chlamydia trachomatis OR Chlamydia muridarum) AND (semen parameters OR Sperm concentration OR sperm Morphology OR sperm Motility OR seminal fluid Volume OR seminal fluid pH).\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: 1. The population has characteristics that are significantly worse than the general population, such as soldiers, people with normal fertility and so on. 2.The evaluation of semen quality in this paper is a range value rather than a specific value. 3.Studies reporting only on bacteriospermia without analyzing the impact on semen parameters or the association with male infertility.\u003c/p\u003e \u003cp\u003eIn our study, we excluded studies based on mentioned criteria for some consideration. Firstly, some special crowds may have unique characteristics, for example, immunity of soldiers may be greater. Secondly, the clear values of semen parameters are crucial for meta-analysis, which is not provided by some studies. Last, some studies reported bacteriospermia without analyzing the impact on semen parameters or the association with male infertility.\u003c/p\u003e \u003cp\u003eOutcomes measures: The main outcome measure is the semen parameters of males infected with Chlamydia.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEvidence Synthesis\u003c/h2\u003e \u003cp\u003e16 studies (Table\u0026nbsp;1) were included into this meta-analysis, with more than 3000 subjects\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. The studies which were excluded from this research is shown in the PRISMA flowchart (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The systematic review was registered with PROSPERO (ID number CRD42024503506). Parts of excluded studies revealed their findings with range value, while some studies just reported whether their statistics were in normal range or not. Some studies were considered as low-quality research, which didn\u0026rsquo;t explain which group some of these data belong to, and these were excluded. Those data can\u0026rsquo;t be involved in to conclude the mean value and SD. Two study chose two ways to determine Chlamydia infection, and reported all statistics corresponding to each method(PCR and ELISA)\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Concerning about that the method to determine Chlamydia infection will affect the latest result, we collected in the meta-analysis only the data which is from the group that use the method of PCR. Two studies comprehensively argued the impact of Chlamydia infection on males, which includes fertile males, infertile males with previous Chlamydia infection and without previous infection\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. We collected the latter two patterns, but abandoned the data of fertile males for a lack of the same crowd to explore if the factor, fertile/infertile, will make an effort to semen parameters with Chlamydia infection\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe data extracted were collected in Microsoft 365(Microsoft Corporation, Redmond, CA, USA), and the analysis was conducted by review manager (5.3, The Cochrane Collaboration,). The process of collecting data was exerted by two independent reviewers, to ensure accuracy and consistency. For each semen parameters, we calculated the mean difference and the corresponding confidence interval. The choice of fixed effect model and random effect model is up to I\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e or p, Q-test (when I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026ge;\u0026thinsp;50% or p\u0026thinsp;\u0026lt;\u0026thinsp;0.10,Q-test). Whether latest result is meaningful depends on the relationship between invalid line and the diamond. Data were kept in forms we designed before.\u003c/p\u003e \u003cp\u003eTwo reviewers independently screened titles and abstracts of all articles searched by the search strategies. All potentially relevant reports were retrieved in full and assessed by one reviewer. The statistics were collected, and the bias-comments were done by two reviewers independently via Newcastle-Ottawa Scale. Any disagreements during the selection process were resolved by consensus.\u003c/p\u003e \u003cp\u003eThis meta-analysis collected data for exploring the influence Chlamydia has on the various semen parameters. In this study, the semen parameters which include semen volume (ml), semen sperm concentrations (million/ml), progressive motility (%), normal morphology (%), sperm vitality (%) and semen pH are argued.\u003c/p\u003e \u003cp\u003eThe studies included in this systematic review use various methods to identify males whether were infected by Chlamydia or not. The methods consist of blood culture (n\u0026thinsp;=\u0026thinsp;1), PCR (n\u0026thinsp;=\u0026thinsp;5), ELISA (n\u0026thinsp;=\u0026thinsp;3) and serology (n\u0026thinsp;=\u0026thinsp;3). More that, the rest of studies adopted multiple methods to diagnose Chlamydia infection, and two studies reported corresponding statistics in each method (PCR and serology), partial literature didn\u0026rsquo;t distinguish the statistics (is mixed) from which detection group.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSemen volume\u003c/h2\u003e \u003cp\u003eThe data of 13 studies were extracted to compare semen volume between Chlamydia (+) and Chlamydia (-), analyzed using a random effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The result revealed that semen volume of Chlamydia (+) group didn\u0026rsquo;t be more than Chlamydia (-) group (Difference in means \u0026minus;\u0026thinsp;0.22, 95% CI: -0.50 to 0.06; P\u0026thinsp;=\u0026thinsp;0.12; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;64%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAnd we did a subgroup analysis by various settlements (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The meta-analysis revealed that, based on continuous data (mean +/- SD), semen volume of Chlamydia (+) group in Iran is significantly more than Chlamydia (-) group (Difference in means \u0026minus;\u0026thinsp;0.87, 95% CI: -1.29 to -0.44; P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;33%)\u003csup\u003e9,17,18\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003esperm concentration\u003c/h2\u003e \u003cp\u003eThe data of 16 studies were extracted to compare sperm concentration of Chlamydia (+) males with Chlamydia (-), analyzed using a fixed effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The forest plot revealed the mean sperm concentration of Chlamydia (-) group is significantly more than Chlamydia (+) group (Difference in means \u0026minus;\u0026thinsp;3.33, 95% CI: -6.54 to -0.12; P\u0026thinsp;=\u0026thinsp;0.04; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;30%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSperm progressive motility\u003c/h2\u003e \u003cp\u003eThe data of 15 studies were extracted to compare sperm progressive motility of Chlamydia(+) group with Chlamydia(-), by utilizing a fixed effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The meta-analysis was conducted on these studies that provided continuous data (mean +/- SD) which revealed that Chlamydia (-) group had a significantly better rate of progressive motility compared with Chlamydia (+) (Difference in means \u0026minus;\u0026thinsp;1.62, 95% CI: -3.04 to -0.20; P\u0026thinsp;=\u0026thinsp;0.03; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;14%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSperm normal morphology\u003c/h2\u003e \u003cp\u003eThe data of 13 studies were extracted to compare sperm normal morphology of Chlamydia (+) with Chlamydia (-), analyzed using a fixed effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The forest plot revealed that There is no difference between two groups (Difference in means 0.00, 95% CI: -0.66 to 0.66; P\u0026thinsp;=\u0026thinsp;0.99; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;49%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eSperm vitality\u003c/h2\u003e \u003cp\u003eThe data of 6 studies were extracted to compare sperm vitality of Chlamydia (+) group with Chlamydia (-) group, analyzed using a fixed effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). And the meta-analysis of the pooled data found that statistics have no sense (Difference in means \u0026minus;\u0026thinsp;0.05, 95% CI: -2.85 to 1.85; P\u0026thinsp;=\u0026thinsp;0.68; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;11%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eSemen pH\u003c/h2\u003e \u003cp\u003eThe data of 8 studies were extracted to compare semen pH of Chlamydia (+) group with Chlamydia (-) group, analyzed using fixed effects model (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). The forest plot revealed that data didn\u0026rsquo;t reach statistically significantly (Difference in means \u0026minus;\u0026thinsp;0.03, 95% CI: -0.06 to 0.01; P\u0026thinsp;=\u0026thinsp;0.13; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo determine the Chlamydia infection whether would have an impact on semen parameters or not, this meta-analysis collected and evaluated such objects (semen volume, sperm concentration, progressive motility, normal morphology, vitality, and pH) in Case-control studies. Our meta-analysis of more than 3000 patients by including 16 studies, indicates that, Chlamydia infection will deteriorate infertile males\u0026rsquo; sperm concentration and sperm progressive motility. But the rest of parameters decreasing is not associated with Chlamydia infection in infertile males.\u003c/p\u003e \u003cp\u003eAs the crucial factors of males\u0026rsquo; reproductive function, sperm concentration and sperm progressive motility are usually utilized to analyze males\u0026rsquo; semen quality. Overall, Chlamydia infection will decrease semen quality and damage males\u0026rsquo; reproductive function. According to previous studies, the males\u0026rsquo; reproductive function might be influenced by many kinds of pathogens. In addition to pathogens\u0026rsquo; direct impairment, there are also other indirect factors such as inflammation, fever leading to sperm quality worsen. Meanwhile, we also found that the CI of semen volume trended to achieve the threshold (judging roughly by the forest plot). By subgroup analysis, we found that region as an influencing factor is associated with semen volume changing. The region factor may affect volume by influencing population characteristics or ethnic groups.\u003c/p\u003e \u003cp\u003eNevertheless, we found that there is no significant difference between Chlamydia (+) and Chlamydia (-) in the pH, sperm vitality and sperm normal morphology. This might be because Chlamydia infection mainly affects spermatogenic function of testis, but pH of semen is mainly influenced by the prostate gland and seminal vesicles, while mean sperm vitality rates of two groups are nearly the same.\u003c/p\u003e \u003cp\u003eCompared to a prior meta-analysis, we improved the result\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. When the prior reported that Chlamydia infection won\u0026rsquo;t affect semen parameters which including sperm concentration and sperm progressive motility, our new meta-analysis denied it. Compared with the prior, an important strength of our study is that the number of included studies are 16, much more and with more participants. Furthermore, we analyzed more subgroups in terms of sources of samples and characteristics of population by utilizing previous collected data, we have actively reduced research waste. Although those new subgroup analysis didn\u0026rsquo;t support positive results. We also made our finding more believable.\u003c/p\u003e \u003cp\u003eBut we still have limitations. We all know that there are many factors that can cause a decline in reproductive system function, such as varicocele, primary hypogonadism, cryptorchidism, obstructive azoospermia, history of vasectomy, and a history of receiving radiation or chemotherapy. Literature also reported that infection is an important contributing factor to the damage in reproductive function. In our studies searched, we found that some studies explicitly excluded patients with a history of the aforementioned conditions or partial conditions, while others did not. This resulted in heterogeneity in the characteristics of the included populations. (as men defined merely as infertility status may have a history of these diseases contributing to their infertility as well). We also conducted subgroup analyses in terms of the literature that performed exclusion on populations with a history of aforementioned diseases. We still didn\u0026rsquo;t find positive result. But considering one of these studies have significant publication bias, we excluded it\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. We suggest that future research should establish more uniform inclusion and exclusion criteria for patients with a history of diseases, to help us further investigate the impact of Chlamydia infection on infertile men and make results more believable.\u003c/p\u003e \u003cp\u003eWhat\u0026rsquo;s more, the included studies didn\u0026rsquo;t provide details on the timing of infection occurrence and the course of infection, which should be given more attention. Due to the particularity of this disease, we can\u0026rsquo;t conduct randomized controlled trials, and thus, it\u0026rsquo;s hard to accurately determine the specific time of getting infected and the development of the disease. Nevertheless, it takes time from infection occurrence to potentially affect reproduction function. And this leads to this part being hard to standardize. Meanwhile, we found that the most patients reported in these literature who performed semen analysis usually seek medical advice for infertility symptoms rather than infection symptoms, even partial patients are asymptomatic. This suggests that patients likely consist of both long-term asymptomatic carriers and short-term infection cases, and the progression of this disease takes time. In our discussion, the site of infection is also considered as a factor, because Chlamydia infection in elsewhere will lead to serum anti-Chlamydia antibodies positive. Additionally, we differentiated between urine and semen samples for PCR testing to reduce the impact of the infection site on the results in subgroup analysis. However, we didn\u0026rsquo;t find positive results. This condition possibly due to contamination of semen samples with urethral secretions during collection, but we were unable to eliminate this impact. Puncture as an invasive method is not recommended to reduce this impact.\u003c/p\u003e \u003cp\u003eIn addition, as we all know, the immune system will produce antibodies when get infected. As the IgG antibodies increase, which will persist in serum for a long period, The IgM antibodies will decline in a short-term after their production. Meanwhile, we found that when semen PCR positive and serum anti-Chlamydia IgG as diagnostic criteria respectively, significant differences in semen parameters were observed between the PCR group and IgG group in two studies\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Nevertheless, partial studies didn\u0026rsquo;t differentiate patients with detection methods. This suggests that the method of Chlamydia detection has an impact on the result.\u003c/p\u003e \u003cp\u003eConsidering what mentioned above, we should realize that Chlamydia infection really have an influence on males\u0026rsquo; reproductive function. And this would guide us to consider Chlamydia infection as a factor affecting males\u0026rsquo; fertility. Our study population are infertile males, and evidence of the impact of Chlamydia infection on normal reproductive function males in long term is still lacking. In the future, we should start with above orientation, taking to explore appropriate treatment for males of Chlamydia infection and evaluate efficacy, to diminish damage of males\u0026rsquo; reproductive function from Chlamydia infection.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis meta-analysis determined Chlamydia infection really deteriorates infertile males\u0026rsquo; reproductive function and decreases both sperm concentration and sperm progressive motility. Decreasing of sperm normal morphology, sperm vitality and semen pH are not associated with Chlamydia infection in infertile males. But Chlamydia infection may influence semen volume with combining with region factor\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCI, confidence interval; MD, mean difference; STD, sexually transmitted disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests, be it financial, personal or professional.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China [No. 82071632], and the Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0069].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI would like to thank my supervisor, Shengde Wu, for his guidance through each stage of the process. Meanwhile I\u0026rsquo;d like to thank Chengjun Yu, who always offers me help and advises me to learn more information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuanzhi Song took part in all stages of this research involving searching studies, collecting data, analyzing data and editing article. Chengjun Yu offered guidance for Yuanzhi Song in all stages. Wuhong Weng searched studies and collected data.\u0026nbsp;Maolin Liu, Hao Yan and Miao Sun helped Yuanzhi Song to analyse data. Shengde Wu* guided Yuanzhi Song through each stage of the process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData openly available in a public repository\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOmbelet W, Cooke I, Dyer S, Serour G, Devroey P. Infertility and the Provision of Infertility Medical Services in Developing Countries. 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Chlamydia Trachomatis Infection in Male Partners of Infertile Couples: Incidence and Sperm Function. ANDROLOGIA. 2002;34(3):155\u0026ndash;61. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1046/j.1439-0272.2002.00472.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1439-0272.2002.00472.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEzzEl-Din AM, Gaber HD, Kamal DT. Chlamydia Trachomatis Infection: Its Relation to Semen Parameters and Sperm DNA Integrity. Egypt J Immunol. 2021;28(4):290\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarahani L, Tharakan T, Yap T, Ramsay JW, Jayasena CN, Minhas S. The Semen Microbiome and Its Impact on Sperm Function and Male Fertility: A Systematic Review and Meta-Analysis. Andrology. 2021;9(1):115\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/andr.12886\u003c/span\u003e\u003cspan address=\"10.1111/andr.12886\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eCharacteristics of included studies\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\" rowspan=\"2\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\" rowspan=\"2\"\u003e\n \u003cp\u003eYear published\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\" rowspan=\"2\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\" rowspan=\"2\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\" rowspan=\"2\"\u003e\n \u003cp\u003eRecruitment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eChlamydia(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003eChlamydia(-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\" rowspan=\"2\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\" rowspan=\"2\"\u003e\n \u003cp\u003eGuidelines for semen analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.444444444444443%\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"80.55555555555556%\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eAhmadi K et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2016-2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO2021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eAmmar-Keskes L et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eTunisia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, vitality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eAuroux MR et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, vitality, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eAuroux MR et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, vitality, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eChen L et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2017-2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO2010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003ede Barbeyrac B et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1998-2001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eGregoriou O et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eGreece\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, vitality, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1980\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eGregoriou O et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eGreece\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, vitality, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1980\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eHosseinzadeh S et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eL\u0026oacute;pez-Hurtado M et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eMexico\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, morphology, vitality, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO2010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eMarvast L et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2009-2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eMoosavian M et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2016-2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, pH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eNagy B et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eHungary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esperm concentration, motility, morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1980\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eRybar R et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eCzech Republic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology, vitality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO2010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eSegnini A et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eVenezuela\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1992\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eSellami H et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eTunisia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esperm concentration, motility, vitality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eVeznik Z et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eCzech Republic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esemen volume, sperm concentration, motility, morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003eVigil P et al.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e2002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003eChile\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eCase control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003esperm concentration, motility, morphology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003eWHO1992\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.421052631578947%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.473684210526315%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.368421052631579%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.526315789473685%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.842105263157894%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.2631578947368425%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"semen parameters, male fertility, reproductive function, Chlamydia","lastPublishedDoi":"10.21203/rs.3.rs-4544403/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4544403/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and objective:\u003c/h2\u003e \u003cp\u003eThere has been no consensus regarding whether Chlamydia impacts on males\u0026rsquo; reproductive function. This systematic review and meta-analysis compared semen parameters of Chlamydia (+) males with Chlamydia (-) males.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThe databases MEDLINE, Embase and PubMed were searched for relevant studies.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSixteen studies were included with more than 3000 patients. Chlamydia infection negatively impacted on sperm concentration (DM -3.33, 95% CI: -6.54 to -0.12; P\u0026thinsp;=\u0026thinsp;0.04; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;30%) and progressive motility (DM -1.62, 95% CI: -3.04 to -0.20; P\u0026thinsp;=\u0026thinsp;0.03; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;14%) in infertile males. Semen volume, sperm normal morphology, sperm vitality and semen pH may not be associated with Chlamydia infection in infertile males. Chlamydia infection may influence semen volume with combining with region factor (DM -0.87, 95% CI: -1.29 to -0.44; P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;33%).\u003c/p\u003e\u003ch2\u003eDiscussion and conclusions:\u003c/h2\u003e \u003cp\u003eChlamydia infection deteriorates infertile males\u0026rsquo; reproductive function. These finds induce us to consider Chlamydia\u0026rsquo;s contribution to males\u0026rsquo; reproductive dysfunction, and the treatment of Chlamydia whether protect males\u0026rsquo; reproductive function should be studied in the future.\u003c/p\u003e","manuscriptTitle":"The impact of Chlamydia infection on semen parameters and male fertility: A systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-13 01:46:19","doi":"10.21203/rs.3.rs-4544403/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b356b898-95a5-426b-9fb6-190568f12631","owner":[],"postedDate":"July 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-15T08:54:59+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-13 01:46:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4544403","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4544403","identity":"rs-4544403","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}