Sexually Transmitted Disease and Male Infertility: A Systematic Review

doi:10.1016/j.euf.2016.08.002

European Urology Focus

Volume 2, Issue 4, October 2016, Pages 383-393

https://doi.org/10.1016/j.euf.2016.08.002 Get rights and content

Abstract

Context

Theoretically, sexually transmitted diseases (STDs) have the potential to disrupt male fertility; however, the topic remains controversial.

Objective

To describe the possible association between STDs and male infertility and to explore possible pathophysiologic mechanisms.

Evidence acquisition

We performed a systematic literature review in accordance with the PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched for articles published before January 1, 2016, using the MeSH terms for a variety of STDs and infertility. The search was restricted to human studies performed in men and published in English. Studies were included if they contained original data on a possible association or a cause-and-effect relationship between STD and male infertility. Studies were considered only if they included an appropriate control group and/or comprehensive laboratory data. Due to heterogeneity in the literature, a qualitative analysis was performed.

Evidence synthesis

Relevant studies on Chlamydia trachomatis, genital mycoplasmas, Neisseria gonorrhoeae, Trichomonas vaginalis, and viral infections were identified. For all pathogens, the studies were contradictory and generally of limited quality. In studies confirming an association, there was a tendency for authors to perform multiple analyses without appropriate corrections and to subsequently focus solely on outcomes that seemed to suggest a positive association; however, the body of literature that does not confirm an association between STDs and male infertility is also of inadequate quality. The data regarding possible pathophysiologic mechanisms are inconclusive.

Conclusions

There may be an association between STDs and male infertility of unknown genesis and possibly with different pathogenic mechanisms for different pathogens. Alternatively, some STDs may cause male infertility, whereas others may not; however, there is hardly a strong correlation. High-quality studies of the subject are needed.

Patient summary

Sexually transmitted diseases may cause male infertility through unknown mechanisms; however, from the available research, we cannot be sure that there is an association, and more studies are needed.

Introduction

Infertility is defined as the inability of a couple to achieve pregnancy despite unprotected intercourse for a period of >12 mo [1]. Approximately 15% of all couples are infertile, and it is estimated that a male factor plays a role in about half of the cases [2]. The components of male reproductive function include hormonal regulation of the hypothalamic–pituitary–gonadal axis, complete spermatogenesis, and unobstructed normal sperm transport and storage. Theoretically, sexually transmitted diseases (STDs) have the potential to disrupt several of these steps. Nevertheless, the main focus in studied STD-induced infertility tends to be on the female partner. This review aimed to describe the possible association between various STDs and male infertility. In addition, possible mechanisms by which STDs may influence male fertility have been explored and discussed.

Section snippets

Evidence acquisition

We performed a systematic literature review in accordance with the PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched for articles published before January 1, 2016, using the MeSH terms for a variety of STDs and infertility (Fig. 1). The search was restricted to human studies performed in men and published in English. Studies were included if they contained original data on a possible association or a cause-and-effect relationship between STD and male infertility. To

Evidence synthesis

Studies investigating STDs and fertility status and/or semen quality are summarized in Table 1, Table 2, Table 3, Table 4 according to pathogenic agents. The studies are further described in the text. Studies investigating possible causative links between STDs and infertility are described in the text only.

Conclusions

The available literature exploring a possible association between STDs and male infertility is of limited quality, and the results are contradictory. Studies confirming an association more frequently tended to have significant drawbacks. There was a tendency for authors to perform multiple analyses without appropriate corrections and to subsequently focus solely on outcomes that seemed to suggest a positive association; however, the body of literature that does not confirm an association

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Cited by (43)

A systematic review of the correlation between Trichomonas vaginalis infection and infertility
2022, Acta Tropica
Citation Excerpt :
Upon reading and summarizing these articles, we discovered that T. vaginalis infection in female patients mainly causes inflammation of the reproductive tract (Fichorova, 2009; Tsevat et al., 2017) and changes in the vaginal environment (Menezes et al., 2016), and these disturbances can injure the reproductive tract mucosa, fallopian tubes, or pelvic cavity (Mielczarek and Blaszkowska, 2016; Shiadeh et al., 2016; Tsevat et al., 2017), which may result in a decrease or loss of reproductive function, leading to infertility. The major reason that T. vaginalis infection leads to infertility in male patients is that T. vaginalis itself or the induced inflammatory response can impair sperm cells, causing a decrease in cell viability or death of sperm cells (Fode et al., 2016; Gimenes et al., 2014b; La Vignera et al., 2011; Martinez-Garcia et al., 1996; Mielczarek and Blaszkowska, 2016; Roh et al., 2015; Shiadeh et al., 2016), which may result in a decrease or loss of reproductive function, leading to infertility. We also collected and analyzed research articles on the pathogenesis of T. vaginalis-induced infertility.
Trichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate.
In this work, we consulted 205 relevant articles, which were classified into three categories: epidemiological investigations (100), review articles (43), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups. Review and research articles were used to summarize the pathogenesis of infertility caused by T. vaginalis.
The results indicated that rate of T. vaginalis infection in the infertile group was significantly higher than that in the fertile group. Moreover, the epidemiological surveys showed that the infertility rates of population infected with T. vaginalis were significantly higher than that of population without T. vaginalis infection. Nine out of ten (90%) related review articles stated that T. vaginalis infection causes infertility, and the review and research articles indicated the main pathogenic mechanisms of infertility caused by T. vaginalis were as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function.
Our results confirm that there is a correlation between T. vaginalis infection and infertility, and T. vaginalis infection can lead to infertility. The study provides a foundation for further investigations into its pathogenesis.
Hormonal and nonhormonal treatment of male infertility
2022, Management of Infertility: A Practical Approach
The causes and management of male infertility can be broadly classified by the position of the defect in the hypothalamo-pituitary-gonadal axis. However a significant portion of male infertility is unexplained and thus termed idiopathic infertility. Hormonal replacement is an established treatment for infertility associated with hypothalamo-pituitary dysfunction. The management of testicular failure involves surgical sperm removal and assisted reproductive technology. In specialist centers, hormonal stimulation is used to increase the success rate of surgical sperm retrieval; the evidence for this is conflicting. Idiopathic male infertility poses a clinical challenge. It is being increasingly understood that reactive oxygen species may play an important role in the etiology of idiopathic infertility. As such lifestyle modification and antioxidant therapy show promise.
European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2021 Update on Male Infertility
2021, European Urology
Citation Excerpt :
Contemporary data on the effects of symptomatic and asymptomatic infections and their treatment on sperm function are conflicting [146–149] and further well-designed studies are needed. A systematic review evaluating the association between sexually transmitted infections and male infertility observed that the current literature is contradictory, the evidence is of poor quality, and the data pertaining to potential pathophysiological mechanisms are limited [150]. WHO defines leucocytospermia as ≥1 × 106 peroxidase-positive white blood cells/ml ejaculate and this is often used as a surrogate marker for potential infection [21].
The European Association of Urology (EAU) has updated its guidelines on sexual and reproductive health for 2021.
To present a summary of the 2021 version of the EAU guidelines on sexual and reproductive health, including advances and areas of controversy in male infertility.
The panel performed a comprehensive literature review of novel data up to January 2021. The guidelines were updated and a strength rating for each recommendation was included that was based either on a systematic review of the literature or consensus opinion from the expert panel, where applicable.
The male partner in infertile couples should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors causing fertility impairment. Infertile men are at a higher risk of harbouring and developing other diseases including malignancy and cardiovascular disease and should be screened for potential modifiable risk factors, such as hypogonadism. Sperm DNA fragmentation testing has emerged as a novel biomarker that can identify infertile men and provide information on the outcomes from assisted reproductive techniques. The role of hormone stimulation therapy in hypergonadotropic hypogonadal or eugonadal patients is controversial and is not recommended outside of clinical trials. Furthermore, there is insufficient evidence to support the widespread use of other empirical treatments and surgical interventions in clinical practice (such as antioxidants and surgical sperm retrieval in men without azoospermia). There is low-quality evidence to support the routine use of testicular fine-needle mapping as an alternative diagnostic and predictive tool before testicular sperm extraction (TESE) in men with nonobstructive azoospermia (NOA), and either conventional or microdissection TESE remains the surgical modality of choice for men with NOA.
All infertile men should undergo a comprehensive urological assessment to identify and treat any modifiable risk factors. Increasing data indicate that infertile men are at higher risk of cardiovascular mortality and of developing cancers and should be screened and counselled accordingly. There is low-quality evidence supporting the use of empirical treatments and interventions currently used in clinical practice; the efficacy of these therapies needs to be validated in large-scale randomised controlled trials.
Approximately 50% of infertility will be due to problems with the male partner. Therefore, all infertile men should be assessed by a specialist with the expertise to not only help optimise their fertility but also because they are at higher risk of developing cardiovascular disease and cancer long term and therefore require appropriate counselling and management. There are many treatments and interventions for male infertility that have not been validated in high-quality studies and caution should be applied to their use in routine clinical practice.
Semen infections in men with primary infertility in the real-life setting
2020, Fertility and Sterility
Citation Excerpt :
In this context, most studies investigating a possible association between semen infection and consequent male infertility yielded conflicting findings, despite having been generally rated as of limited quality. Therefore, the real impact of a positive semen culture on fertility outcomes is far from elucidated (21). The aim of this cross-sectional, real-life study was to investigate the prevalence of and the association between the presence of semen infection (any) and sperm parameters in a cohort of white European men seeking first medical help for a couple’s primary infertility.
To study the impact of asymptomatic semen infections on seminal parameters in men presenting for primary couple’s infertility.
Cross-sectional study.
Academic center.
Socio-demographic, clinical, and laboratory data from 1689 infertile men were analyzed.
Semen analysis was based on 2010 World Health Organization reference criteria. Each patient underwent semen culture test to identify common urogenital pathogens. Infections by Mycoplasma, Ureaplasma, and Chlamydia spp. were evaluated through a real time polymerase chain reaction platform. Descriptive statistics and linear and logistic regression models were used to test the association between semen infections and clinical, seminal, and hormonal parameters.
Prevalence of asymptomatic semen infection and impact of semen infection on sperm parameters.
Of 1689 men, 354 (21.0%) had an asymptomatic positive semen culture. Ureaplasma urealyticum (37.6%) was the most frequent single pathogen, followed by Enterobacteriaceae (any type; 24.8%), other pathogens (20.3%), Chlamydia trachomatis (3.4%) and Mycoplasma spp (3.4%). Positive semen cultures were associated with lower sperm concentrations (P<0.001) and progressive motility (P<.001). These latter findings were mostly particular to men with infections caused by Ureaplasma urealyticum compared with negative semen cultures. A positive semen culture was both univariably (P<.001) and multivariably (P=.04) associated with a lower sperm concentration.
One out of five men presenting for a couple’s primary infertility had asymptomatic semen infections, which were significantly associated with impaired sperm concentration. These observations point out the importance of an accurate investigation of semen infection in the everyday clinical practice diagnostic workup of infertile men.
Infecciones de semen en hombres con infertilidad primaria en el entorno de la vida real
Estudiar el impacto de las infecciones asintomáticas de semen sobre los parámetros seminales en hombres de parejas con infertilidad primaria.
Estudio transversal.
Centro académico.
El análisis de semen se basó en los criterios de referencia de la Organización Mundial de Salud de 2010. Cada paciente se sometió a una prueba de cultivo de semen para identificar patógenos urogenitales comunes. Infecciones por Mycoplasma, Ureaplasma y Chlamydia spp. fueron evaluadas a través de la reacción en cadena de la polimerasa a tiempo real. La estadística descriptiva y los modelos de regresión lineal y logística se utilizaron para testar la asociación entre infecciones de semen y parámetros clínicas, seminales y hormonales.
Prevalencia de infección de semen asintomática e impacto de la infección de semen en los parámetros del esperma.
De los 1689 hombres, 354 (21,0%) tuvieron un cultivo de semen asintomático positivo. Ureaplasma urealyticum (37,6%) fue el patógeno más frecuente, seguido de Enterobacteriaceae (cualquier tipo; 24,8%), otros patógenos (20,3%), Chlamydia trachomatis (3,4%) y Mucoplasma spp (3,4%). Los cultivos positivos de semen fueron asociados con concentraciones más bajas de esperma (P<0,001) y motilidad progresiva (p<0,001). Estos hallazgos fueron principalmente particulares en hombres con infecciones causadas por Ureaplasma urealyticum comparado con cultivos de semen negativos. Un cultivo de semen positivo fue asociado univariablemente (P<0,001) y multivariablemente (P<0,001) con una menor concentración de semen.
Uno de cada cinco hombres que se presentaron por infertilidad primaria con su pareja tenía infecciones de semen asintomáticas, las cuales fueron significativamente asociadas con una concentración de esperma deteriorada. Estas observaciones señalan la importancia de una investigación precisa de la infección de semen en el diagnóstico de práctica clínica habitual de hombres infértiles.
Recommendation on screening for chlamydia and gonorrhea in primary care for individuals not known to be at high risk
2021, CMAJ
Recommendation on screening for chlamydia and gonorrhea in primary care for individuals not known to be at high risk
2021, CMAJ

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Review – AndrologySexually Transmitted Disease and Male Infertility: A Systematic Review

Abstract

Context

Objective

Evidence acquisition

Evidence synthesis

Conclusions

Patient summary

Introduction

Section snippets

Evidence acquisition

Evidence synthesis

Conclusions

Fertil Steril

Fertil Steril

Eur Urol

Diagn Microbiol Infect Dis

Urology

FEMS Microbiol Lett

Fertil Steril

Urology

J Urol

Fertil Steril

Fertil Steril

Fertil Steril

Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach

Fertil Steril

The relationship of Chlamydia trachomatis infection and male infertility

Am J Public Health

Chlamydiae in the ejaculate: their influence on the quality and morphology of sperm

Acta Obstet Gynecol Scand

Detection of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in infertile Bulgarian men with multiplex real-time polymerase chain reaction

APMIS

Effect of human papillomavirus and Chlamydia trachomatis co-infection on sperm quality in young heterosexual men with chronic prostatitis-related symptoms

BJU Int

Chlamydia trachomatis infection as a problem among male partners of infertile couples

Andrologia

Prevalence of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum infections and seminal quality in infertile and fertile men in Kuwait

J Androl

Reproductive tract complications associated with Chlamydia trachomatis infection in US Air Force males within 4 years of testing

Sex Transm Dis

Association between Chlamydia trachomatis antibodies and subfertility in the Northern Finland Birth Cohort 1966 (NFBC 1966), at the age of 31 years

Epidemiol Infect

Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31

Am J Reprod Immunol

Prevalence of genital chlamydia and mycoplasma infection in couples attending a male infertility clinic

Eur J Epidemiol

Review – Andrology
Sexually Transmitted Disease and Male Infertility: A Systematic Review