Infectious Diseases

ISSN: 2374-4235 (Print) 2374-4243 (Online) Journal homepage: http://www.tandfonline.com/loi/infd20

Association of Chlamydia trachomatis with

infertility and clinical manifestations: a systematic
review and meta-analysis of case-control studies

Mohammad Hossein Ahmadi, Akbar Mirsalehian & Abbas Bahador

To cite this article: Mohammad Hossein Ahmadi, Akbar Mirsalehian & Abbas Bahador
(2016): Association of Chlamydia trachomatis with infertility and clinical manifestations:
a systematic review and meta-analysis of case-control studies, Infectious Diseases, DOI:
10.3109/23744235.2016.1160421

To link to this article: http://dx.doi.org/10.3109/23744235.2016.1160421

Published online: 11 Apr 2016.

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 INFECTIOUS DISEASES, 2016
http://dx.doi.org/10.3109/23744235.2016.1160421

ORIGINAL ARTICLE

Association of Chlamydia trachomatis with infertility and clinical manifestations: a

systematic review and meta-analysis of case-control studies
Mohammad Hossein Ahmadi, Akbar Mirsalehian and Abbas Bahador
Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

ABSTRACT ARTICLE HISTORY

Background Chlamydia trachomatis is one of the sexually transmitted pathogens causing reproductive Received 28 November 2015
health-threatening diseases worldwide. However, its role in infertility, particularly in asymptomatic indi- Revised 24 February 2016
viduals, is not yet definitely determined. Methods For the study, electronic databases were searched Accepted 25 February 2016
using the following keywords; ‘Chlamydia trachomatis’, ‘prevalence’, ‘frequency’, ‘fertile’, ‘infertile’, ‘case’, Published online 6 April 2016
‘control’, ‘symptomatic’ and ‘asymptomatic’. Finally, after some exclusions, 34 studies (19 fertile–infertile KEYWORDS
and 15 symptomatic–asymptomatic) from different countries were included in the study and meta-ana- Chlamydia trachomatis;
Downloaded by [RMIT University Library] at 00:15 12 April 2016

lysis was performed on the data collected. Results Odds ratios (ORs) for urogenital C. trachomatis preva- infertility; clinical
lence in males in the fertile–infertile group, for infertile and fertile individuals, ranged from 1.3–3.7 and manifestations; meta-
in females from 1.04–4.8, and the overall OR for both genders was 2.2 (95% CI). In the symptomatic– analysis
asymptomatic group, the overall OR in males and females was 4.9 (95% CI ¼ 1.1–21.7) and 3.3 (95%
CI ¼ 1.7–6.3), respectively. In all of the analyses, there were high levels of heterogeneity (I2 >50%,
p-value <0.05) and, except for the females in the symptomatic–asymptomatic group, neither Egger’s
tests nor Begg’s tests were statistically significant for publication bias. Conclusions C. trachomatis can
impact on the potential for fertility and cause clinical manifestations and complications in both males
and females. Thus, national programmes for adequate diagnosis, screening and treatment of infected
individuals, particularly asymptomatic ones, seem to be necessary.

Introduction women and to compare the prevalence of this bacterium

Chlamydia trachomatis is one of the most common pathogens
causing sexually transmitted infections (STIs),[1] including
infections threatening fertility such as non- and post-gono-
coccal urethritis, epididymitis and prostatitis in males [2] and
cervicitis, salpingitis, pelvic inflammatory disease (PID), ectopic
pregnancy and adverse pregnancy outcomes in females.[3,4]
However, a characteristic feature of C. trachomatis genital
tract infections is chronicity and persistence with asymptom-
atic or only mildly symptomatic infections, which may lead to
severe complications and infertility in males and females.[5]
Up to two-thirds of women and 50% of men who are
infected are asymptomatic.[6] However, the impact of infec-
tions due to this bacterium, particularly asymptomatic ones,
on the potential for fertility, especially in men, is still contro-
versial.[2,3,7,8]. Many studies have been conducted to deter-
mine the prevalence or frequency of urogenital C. trachomatis
in fertile and infertile individuals. Some are case-control sur-
veys that have investigated the frequency of the bacterium in
fertile–infertile or symptomatic–asymptomatic individuals and
reported different and controversial data. A systematic review
and meta-analysis of these reported data can help to better
evaluate the aetiologic role of this bacterium in male and
female infertility or clinical manifestations.
The present study was designed to investigate whether
C. trachomatis infections can cause infertility in men and
among symptomatic patients (having pathologies including
genitourinary tract infections, ectopic pregnancy, miscarriage,
leukocytospermia, cervical or vulvar cancer and pre-term
birth) and asymptomatic individuals by calculating Odds
Ratios, using a systematic review and meta-analysis according
to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement.[9]
Methods
Search strategies
Electronic databases, including OVID databases, PubMed,
Web of Science, Scopus, MEDLINE, EMBASE, Cochrane Library,
and Google Scholar, were searched for case-control studies
reporting the prevalence rates of C. trachomatis in case (infer-
tile/symptomatic individuals) and control (fertile/asymptom-
atic individuals) groups from January 1990 to April 2015. The
search was restricted to original articles throughout the
world, published in English using the following keywords
with the help of Boolean operators (AND, OR): ‘Chlamydia’,
‘Chlamydia trachomatis’, ‘C. trachomatis’, ‘prevalence’, ‘fre-
quency’, ‘epidemiology’, ‘fertile’, ‘infertile’, ‘fertility’, ‘infertility’,
‘case’, ‘control’, ‘case-control’, ‘symptomatic’ and ‘asymptom-
atic’. References from reviewed articles were also searched for
more information.

CONTACT Dr A. Bahador abahador@tums.ac.ir, ab.bahador@gmail.com Department of Microbiology, School of Medicine, Tehran University of Medical
Sciences, Keshavarz Blvd, 100 Poursina Ave., Tehran, Iran. Postal code: 14167-53955
ß 2016 Society for Scandinavian Journal of Infectious Diseases
 2 M. H. AHMADI ET AL.

Study selection articles published between 1992–2015 were included in the

Included studies were all original articles presenting case–
control studies on the prevalence of urogenital C. trachomatis
in infertile/symptomatic and fertile/asymptomatic individuals
in males and females in which the diagnostic methods were
molecular amplification techniques such as polymerase chain
reaction (PCR), plasmid-based PCR, real-time PCR, PCR-restric-
tion fragment length polymorphism (PCR-RFLP) and multiplex
PCR. Excluded were studies that: (1) did not have a control
group or were not case-control studies; (2) used detection
methods other than nucleic acid amplification techniques
(NAAT) including culture or serological methods, such as
enzyme-linked immunosorbent assay (ELISA) or immunofluor-
escence (IF); and (3) studied chlamydial infections in organs
other than the genitourinary tract. Review articles, congress
abstracts, studies reported in languages other than English,
meta-analyses or systematic reviews, experimental animal
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final analyses (Figure 1 and Table 1).
Of these 34 case-control studies, 19 (10 in females and
nine in men) studied fertile-infertile/sub-fertile individuals and
15 (10 in females, four in men and one in both genders)
investigated the prevalence of C. trachomatis in symptom-
atic–asymptomatic individuals. Symptomatic individuals were
patients with genitourinary tract infections, ectopic pregnan-
cies, miscarriages, leukocytospermia, cervical or vulvar cancer
and pre-term birth and asymptomatic ones were healthy
people.
For ease of analysis, the included studies were divided into
two groups: fertile–infertile group and symptomatic–asymp-
tomatic group. The most commonly collected samples in
females in both groups were first void urine and endocervical
swabs but also other samples (cervico-vaginal swabs or
scrapes, fallopian tube tissue and endometrial or ovarian core
biopsies). The most common samples in males in both groups

studies, duplicate publications of the same study and articles were semen, first void urine and, to a lesser extent, urethral
available only in abstract form were also excluded. swabs. Eight reports studied other agents in addition to C.
trachomatis such as Neisseria gonorrhoeae, mycoplasma spp.,
Gardnerella vaginalis, cytomegalovirus, herpes simplex virus
Data extraction
and human papillomavirus, simultaneously.
Variables extracted from each study included first author’s
name, year of publication, study setting, geographical location
(country), participants, gender, specimen type, number of
patients investigated, type of detection method, and number
of positive samples in cases (infertile/symptomatic patients)
and controls (fertile/asymptomatic individuals). The articles
were reviewed and relevant data were extracted by two
authors independently. Disagreements between reviewers
were discussed to obtain consensus.

Statistical analysis
Data was analysed using Comprehensive Meta-Analysis
Software Version 2.0 (Biostat, Englewood, NJ). Odds ratios
were reported with 95% confidence intervals (CIs) for case
(infertile/symptomatic) and control (fertile/asymptomatic)
groups. Cochrane Q-statistic test and I2 test were performed
to estimate heterogeneity between studies and the random
effect model was chosen to estimate the average prevalence
because of its conservative summary estimate and because in
all calculations, I2 was above 50%. To assess possible publica-
tion bias, a funnel plot, Begg’s rank correlation and Egger’s
weighted regression methods were used. Two-tailed p < 0.05
was considered indicative of a significant publication bias.
The relative weight for each study was calculated.

Results
A total of 232 articles were collected for the study. In the first
screening, 81 articles were excluded on the basis of title
evaluation. In the second assessment, 79 were excluded
because they were not case-control studies, reported chla-
mydia infections in organs other than the genitourinary tract,
or were review articles. Finally, after full-text evaluation, 38 Figure 1. Flow chart of the literature search, systematic review and study selec-
studies were excluded due to detection methods. Thirty-four tion. * Articles studied other Chlamydial infections than urogenital.
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Table 1. Studies included in meta-analysis after final evaluation.

Events Characteristics,
Total number Events rate (%) disease,
Mean age of participants number (95% CI) complication
Reference Pub. Year Country Sex Sample Case Control Case Control Case Control Case Control Case Control
Mahony et al. [10] 1992 Canada M FVU ND ND 91 592 31 9 34.1 1.5 symptomatic asymptomatic
Lan et al. [11] 1995 Netherlands F Cervical scrapes and 42.5 23.5 734 393 58 36 7.9 9.2 symptomatic asymptomatic
cervix brushes
Ombelet et al. [12] 1997 Belgium M Semen 30.6 30.5 143 144 11 6 7.7 4.2 subfertile fertile
Gopalkrishna et al. [13] 2000 India F Endocervical swabs or scrapes 27.2 28 50 30 25 1 50 3.3 STI healthy
Barlow et al. [14] 2001 UK & India F Endometrial, fallopian tube and 29.7 39.5 14 50 10 15 71.4 30 infertile fertile
ovarian core biopsy
Barlow et al. [14] 2001 UK & India F Endometrial, fallopian tube and 31.1 39.5 33 50 21 15 63.6 30 ectopic healthy
ovarian core biopsy pregnancy
Awwad et al. [15] 2003 Jordan M FVU 34 35 70 61 4 0 5.7 0 symptomatic asymptomatic
F FVU 23 30 60 39 2 0 3.3 0 symptomatic asymptomatic

Das et al. [16] 2006 India F FVU 35 35 50 50 7 2 14 4 symptomatic asymptomatic

Bezold et al. [17] 2007 US M Semen 38.5 38.5 132 108 3 3 2.3 2.8 with LCS without LCS
Kwasniewska et al. (a) [18] 2007 Poland F Paraffin sections 44.9 45.9 520 50 135 4 26 8 cervical cancer normal cervical
tissue
Kwasniewska et al. (b) [18] 2007 Poland F Paraffin sections 60.5 45.9 46 46 3 1 6.5 2.2 vulvar cancer normal epithe-
lial tissue
Al-Ramahi et al. [19] 2008 Jordan F Endocervical swab 31.2 34.2 152 146 6 1 3.9 0.7 infertile fertile
Siemer et al. [20] 2008 Ghana F FVU ND ND 191 248 3 6 1.6 2.4 infertile Healthy
pregnant
Feky et al. [21] 2009 Egypt M Semen 30.8 33.1 75 25 23 0 30.7 0 infertile fertile
Ouzounova- Raykova et al. [8] 2009 Bulgaria M Urethral swab 31 30 60 40 5 1 8.3 2.5 infertile fertile
Jenab et al. [22] 2009 Iran F Endocervical swab 37.5 37.5 58 22 11 6 19 27.3 symptomatic asymptomatic
Çalışkan et al. [23] 2010 Turkey M Semen 34 34.5 144 31 12 3 8.3 9.7 infertile fertile
Muvunyi et al. [24] 2011 Rwanda F Vaginal swab 33 33 303 312 10 12 3.3 3.8 subfertile fertile
Baud et al. (a) [25] 2011 Switzerland F Placenta and endocervical swab 33.3 31.5 125 261 5 2 4 0.8 miscarriage healthy
Siam et al. [26] 2012 Egypt F FVU 30.2 30.1 90 80 4 6 4.4 7.5 infertile fertile
Al-Sweih et al. [27] 2012 Kuwait M Semen ND ND 127 188 5 7 3.9 3.7 infertile fertile
Okoror et al. [28] 2012 Nigeria M Semen 43 43 666 666 417 225 62.6 33.8 low sperm normal sperm
count count
Mania-Pramanik et al. [29] 2012 India F Endocervical and vaginal swab 26 30 264 102 49 2 18.6 2 infertile fertile
Fatholahzadeh et al. (a) [30] 2012 Iran F FVU 32.5 32.5 130 130 27 12 20.8 9.2 symptomatic asymptomatic
Naderi et al. [31] 2012 Iran F Fallopian tube tissue 31.2 31.2 42 87 5 0 11.9 0 ectopic healthy
pregnancy
Rashidi et al. [32] 2013 Iran F FVU 29.9 26.9 234 223 29 19 12.4 8.5 infertile fertile
Tomusiak et al. [33] 2013 Poland F Cervico-vaginal swab and FVU 30 30 101 60 0 2 0 3.3 infertile fertile
Abusarah et al. [34] 2013 Jordan M Semen and FVU 33 32 93 70 4 1 4.3 1.4 infertile fertile
Yeganeh et al. [35] 2013 Iran M FVU 33.5 33.4 100 100 20 4 20 4 symptomatic asymptomatic
Fathollahzadeh et al. (b) [36] 2013 Iran M FVU 34 34 100 100 11 6 11 6 symptomatic asymptomatic
Marashi et al. [37] 2014 Iran F Endocervical swab 24.3 25.2 150 200 48 13 32 6.5 infertile fertile
Liu et al. [1] 2014 China M Semen ND ND 621 615 16 14 2.6 2.3 infertile fertile
Al-Marzoqi et al. [38] 2014 Iraq M Semen 34 34 77 77 18 4 23.4 5.2 antheno- normo-spermic
spermic
Alfarraj et al. [39] 2015 Saudi Arabia F endocervical swab 32.5 34.1 100 100 8 1 8 1 infertile fertile
Baud et al. (b) [40] 2015 Switzerland F endocervical swab and 32.4 31.5 146 261 14 4 9.6 1.5 preterm birth healthy
placenta samples
INFECTIOUS DISEASES

M, males; F, females; FVU, first void urine; ND, not determined; STI, sexually transmitted infections; LCS, leukocytospermia.
3
 4 M. H. AHMADI ET AL.
Included studies were carried out in 20 different countries,
eight in Asia, six in Europe, four in Africa and two in North
America (Table 1).
In the fertile–infertile group, the mean age for infertile and
fertile males was 33.8 years and 33.9 years, respectively, and
for females 29.6 years and 31.4 years, respectively. Three stud-
ies did not report the ages of participants or age-stratified
data. In the symptomatic–asymptomatic group, the mean age
for infertile and fertile males was 35 years and 35.2 years,
respectively, and for females 36.2 years and 34.6 years,
respectively. One study did not report the ages of partici-
pants. Most studies had no useful information on patients’
education and/or occupation.
The numbers of participants (sample sizes) for males in the
fertile–infertile group varied from 60–666 infertile and 25–666
fertile, and for females from 14–303 infertile and 50–312 fer-
tile individuals. In the symptomatic–asymptomatic group,
numbers for males ranged from 70–132 symptomatic and
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61–592 asymptomatic and for females from 33–734 symptom-
atic and 22–393 asymptomatic ones. The average prevalence
of urogenital C. trachomatis in infertile males and females in
the fertile–infertile group was 16.8% (95% CI ¼ 2.6–62.6%)
and 15.6% (95% CI ¼ 0–71.4%), respectively, and in fertile
males and females it was 7% (95% CI ¼ 0–33.8%) and 6.6%
(95% CI ¼ 0.7–30%), respectively. In the symptomatic–asymp-
tomatic group, the average prevalence of the bacterium in
symptomatic males and females was 14.6% (95% CI ¼ 2.3–
34.1%) and 20.6% (95% CI ¼ 4–63.6%), respectively, and in
asymptomatic males and females 2.9% (95% CI ¼ 0–6%) and
8.5% (95% CI ¼ 0–30%), respectively.
Odds ratios (ORs) for urogenital C. trachomatis prevalence
in males in the fertile–infertile group for infertile and fertile
individuals ranged from 1.3–3.7 and the overall OR was 2.2
(95% CI) (Figure 2a). The overall OR in females in this group
was also 2.2 (95% CI ¼ 1.04–4.8) (Figure 2b). In the symptom-
atic–asymptomatic group, the overall OR in males and
females was 4.9 (95% CI ¼ 1.1–21.7) and 3.3 (95% CI ¼ 1.7–
6.3), respectively. Figure 2(c and d) shows the forest plots of
meta- analyses of C. trachomatis prevalence in the symptom-
atic–asymptomatic group for symptomatic and asymptomatic
males and females, respectively.
In all of the analyses, there were high levels of heterogen-
eity (I2 > 50%, p-value < 0.05) and, except for the females in
the symptomatic–asymptomatic group (Egger’s test: two-
tailed p ¼ 0.014), no evidence of publication bias was
observed. Neither Egger’s tests nor Begg’s tests showed sig-
nificant publication bias (Table 2). Figure 3 shows the funnel
plots of all analyses and there is no evidence of publication
bias (Figure 3a–c), except in females in the symptomatic-
asymptomatic group (Figure 3d).
Discussion
Being an obligate intracellular pathogen, the hallmark of C.
trachomatis urogenital tract infection is its chronicity and per-
sistence, resulting in silent and asymptomatic infections. The
combination of silent disease and frequency of infections
makes chlamydial disease a serious health concern in some
countries. Furthermore, asymptomatic or mildly symptomatic
individuals may not seek medical attention and, therefore,
develop complications, or unknowingly transmit the organism
to their partner(s).[5]. However, the assumption that the infec-
tions, particularly asymptomatic ones, can lead to infertility,
especially in males, is still controversial.[2,3,7,8] Thus, this sys-
tematic review and meta-analysis was performed to investi-
gate the relationship between this bacterium and infertility or
clinical manifestations and complications in males and
females. As men and women are distinct populations with dif-
ferent prevalences, the data for each gender was analysed
separately in the present study.
According to the forest plot meta-analysis of males in the
fertile–infertile group, the overall OR was 2.2 (95% CI ¼ 1.3–
3.7), and the overall p-value was 0.003 (below 0.05), indicating
that urogenital C. trachomatis prevalence was significantly
higher in the case group (infertile men) compared with the
control group (fertile men). This indicates that the bacterium
can play a role in male infertility (Figure 2a). Similarly, in the
analysis of females in this group, the overall OR was 2.2 (95%
CI ¼ 1.04–4.8) and the overall p-value was 0.04, which sug-
gests a role in female infertility as well (Figure 2b).
In meta-analysis of the symptomatic–asymptomatic group,
the prevalence of urogenital C. trachomatis in both males and
females was significantly higher in the case group (symptom-
atic individuals) compared with the control group (asymptom-
atic people). The corresponding forest plots are shown in
Figure 2(c and d). The overall OR and p-value in males were
4.9 (95% CI ¼ 1.1–21.7) and 0.03, respectively, and in females
3.3 (95% CI ¼ 1.7–6.3) and < 0.001, respectively. This implies
that urogenital C. trachomatis is associated with clinical mani-
festations and complications such as urogenital infections,
miscarriage, ectopic pregnancy, cervical cancer and vulvar
cancer in females and leukocytospermia and genitourinary
tract infections in males.
One limitation of the present study was that many studies
from different countries had to be excluded from the analyses
because their methods of detection were culture or serology
(ELISA and IF), which have lower sensitivity and specificity in
comparison with molecular techniques.[41] This may suggest
some participation bias in the generalisation of the meta-ana-
lysis results. Furthermore, the collected samples were dissimi-
lar and the number of cases and controls in the included
studies. The relative weight for each study was calculated and
reported to overcome this limitation. Another problem in the
current study was that the number of included studies in
males in both the fertile–infertile and the symptomatic–
asymptomatic groups was fewer than 10 and insufficient for a
good meta-analysis and an accurate conclusion. However, as
previously mentioned, this topic is still controversial and fur-
ther case–control studies as well as randomised, controlled
clinical trials are needed for accurate conclusions and general-
isation of results.
Our results showed that the overall prevalence of urogeni-
tal C. trachomatis varied in different countries with different
geographical locations. This is consistent with the World
Health Organisation’s report in 2005, which suggests that
101 million chlamydial infections are detected annually
worldwide.[42] The variability in prevalence rates reported in
 INFECTIOUS DISEASES 5
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Figure 2. Forest plots of the meta-analysis of C. trachomatis prevalence in the fertile–infertile group for men (a) and women (b) and in the symptomatic–asymptom-
atic group for men (c) and women (d).

different countries is perhaps due to a variation in social pop- treatment and control programmes, particularly in some of
ulations, differences in detection methods, types of samples the developing countries. However, increasing rates of mainly
studied, sample sizes, hygiene issues, socio-economic status, asymptomatic C. trachomatis infections worldwide and the
age of participants and absence of regular screening, adverse long-term consequences resulting from these
 6 M. H. AHMADI ET AL.

Table 2. Meta analysis results for study groups of included surveys.

Begg’s test*
Overall effects p-value (two-
(random, 95% CI) Heterogeneity test tailed)
Number of Egger’s test**
Study group included studies Sex odds ratio p-value I2 (%) p-value a b p-value (two-tailed)
Fertile–infertile 9 M 2.2 (1.3–3.7) 0.003 54.7 0.02 0.68 0.75 0.44
10 F 2.2 (1.04–4.8) 0.04 76 < 0.001 0.93 1.00 0.85
Symptomatic–asymptomatic 5 M 4.9 (1.1–21.7) 0.03 85.6 < 0.001 1.00 1.00 0.39
12 F 3.3 (1.7–6.3) < 0.001 71.9 < 0.001 0.68 0.73 0.01
M, male; F, female; a, Kendall’s tau without continuity correction; b, Kendall’s tau with continuity correction.
*Begg and Mazumdar rank correlation;
**Egger’s regression intercept.
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Figure 3. Funnel plots of the meta-analysis of C. trachomatis prevalence in the fertile–infertile group for men (a) and women (b); and in the symptomatic–asymptom-
atic group for men and women (c and d, respectively). Publication bias was only observed in females in the symptomatic–asymptomatic group (d).

infections denote the urgent need to develop an efficient Disclosure statement

and safe vaccine against this pathogen.[43]
This systematic review and meta-analysis, which to our
knowledge is the first such study in the world, showed that
C. trachomatis can impact on the potential for fertility and
cause clinical manifestations and complications in both
males and females. This highlights the necessity of national
programmes for adequate diagnosis of and screening for
genitourinary tract infections due to this bacterium, particu-
larly asymptomatic infections, and for treatment of infected
individuals (including sexual partners) to control STIs and
prevent consequent complications, reduce the carrier rate
and maintain reproductive health and the potential for
fertility.
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of the
paper.
References
[1] Liu J, Wang Q, Ji X, et al. Prevalence of Ureaplasma urealyticum,
Mycoplasma hominis, Chlamydia trachomatis infections, and
semen quality in infertile and fertile men in China. Urology.
2014;83:795–799.
[2] Gallegos G, Ramos B, Santiso R, et al. Sperm DNA fragmentation
in infertile men with genitourinary infection by Chlamydia tracho-
matis and Mycoplasma. Fertil Steril. 2008;90:328–334.

[3] Eley A, Pacey AA, Galdiero M, et al. Can Chlamydia trachomatis dir-
ectly damage your sperm? Lancet Infect Dis. 2005;5:53–57.
[4] Baud D, Regan L, Greub G. Emerging role of Chlamydia and
Chlamydia-like organisms in adverse pregnancy outcomes. Curr
Opin Infect Dis. 2008;2:70–76.
[5] Kalayoglu MV, Byrne GI. The genus Chlamydia—medical. The
Prokaryotes: Springer, 2006. pp 741–754.
[6] Gonzales G, Munoz G, Sanchez R, et al. Update on the impact of
Chlamydia trachomatis infection on male fertility. Andrologia.
2004;36:1–23.
[7] Gdoura R, Keskes-Ammar L, Bouzid F, et al. Chlamydia trachomatis
and male infertility in Tunisia. Eur J Contracept Reprod Health
Care. 2001;6:102–107.
[8] Ouzounova-Raykova V, Ouzounova I, Mitov I. Chlamydia trachoma-
tis infection as a problem among male partners of infertile cou-
ples. Andrologia. 2009;41:14–19.
[9] Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for
systematic reviews and meta-analyses: the PRISMA statement. Ann
Intern Med. 2009;151:264–269.
[10] Mahony JB, Luinstra KE, Sellors JW, et al. Confirmatory polymerase
chain reaction testing for Chlamydia trachomatis in first-void urine
from asymptomatic and symptomatic men. J Clin Microbiol.
Downloaded by [RMIT University Library] at 00:15 12 April 2016
1992;30:2241–2245.
[11] Lan J, Melgers I, Meijer C, et al. Prevalence and serovar distribution
of asymptomatic cervical Chlamydia trachomatis infections as
determined by highly sensitive PCR. J Clin Microbiol.
1995;33:3194–3197.
[12] Ombelet W, Bosmans E, Janssen M, et al. Semen parameters in a
fertile versus subfertile population: a need for change in the inter-
pretation of semen testing. Hum Reprod. 1997;12:987–993.
[13] Gopalkrishna V, Aggarwal N, Malhotra V, et al. Chlamydia tracho-
matis and human papillomavirus infection in Indian women with
sexually transmitted diseases and cervical precancerous and can-
cerous lesions. Clin Microbiol Infect. 2000;6:88–93.
[14] Barlow R, Cooke I, Odukoya O, et al. The prevalence of Chlamydia
trachomatis in fresh tissue specimens from patients with ectopic
pregnancy or tubal factor infertility as determined by PCR and in-
situ hybridisation. J Med Microbiol. 2001;50:902–908.
[15] Awwad ZM, Al-Amarat AA, Shehabi AA. Prevalence of genital chla-
mydial infection in symptomatic and asymptomatic Jordanian
patients. Int J Infect Dis. 2003;7:206–209.
[16] Das V, Agarwal M, Agarwal J, et al. Prevalence of genital
Chlamydia trachomatis by first void urine polymerase chain reac-
tion test in women attending out patient clinic. J Obstet Gynaecol
India. 2006;56:511–513.
[17] Bezold G, Politch JA, Kiviat NB, et al. Prevalence of sexually trans-
missible pathogens in semen from asymptomatic male infertility
patients with and without leukocytospermia. Fertil Steril.
2007;87:1087–1097.
[18] Kwasniewska A, Skoczynski M, Korobowicz E, et al. Prevalence of
Chlamydia trachomatis in cervical and vulvar carcinoma of the
Lublin Region patients. Bull Vet Inst Pulawy. 2007;51:357–360.
[19] Al Ramahi M, Mahafzah A, Saleh S, et al. Prevalence of Chlamydia
trachomatis infection in infertile women at a university hospital in
Jordan. East Mediterr Health J. 2008;14:1148–1154.
[20] Siemer J, Theile O, Larbi Y, et al. Chlamydia trachomatis infection
as a risk factor for infertility among women in Ghana, West Africa.
Am J Trop Med Hyg. 2008;78:323–327.
[21] Feky MAE, Hassan EAS, El AME, et al. Chlamydia trachomatis:
Methods of Identification and Impact on Semen Quality. Egypt J
Immunol. 2009;16:49–59.
[22] Jenab A, Golbang N, Golbang P, et al. Diagnostic value of PCR and
ELISA for Chlamydia trachomatis in a group of asymptomatic
and symptomatic women in Isfahan, Iran. Int J Fertil Steril.
2009;2:193–198.
[23] Çalışkan T, Koçak _I, Kırdar S, et al. Human papillomavirus and
Chlamydia trachomatis in semen samples of asymptomatic fertile
and infertile men: prevalence and relation between semen param-
eters and IL-18 levels. Turk J Urol. 2010;36:143–148.
INFECTIOUS DISEASES 7
[24] Muvunyi CM, Dhont N, Verhelst R, et al. Chlamydia trachomatis
infection in fertile and subfertile women in Rwanda: prevalence
and diagnostic significance of IgG and IgA antibodies testing.
Hum Reprod. 2011;26:3319–3326.
[25] Baud D, Goy G, Jaton K, et al. Role of Chlamydia trachomatis in
miscarriage. Emerg Infect Dis. 2011;17:1630–1635.
[26] Siam EM, Hefzy EM. The relationship between antisperm antibod-
ies prevalence and genital Chlamydia trachomatis infection in
women with unexplained infertility. Middle East Fertil Soc J.
2012;17:93–100.
[27] Al-Sweih NA, Al-Fadli AH, Omu AE, et al. Prevalence of Chlamydia
trachomatis, Mycoplasma hominis, Mycoplasma genitalium, and
Ureaplasma urealyticum infections and seminal quality in infertile
and fertile men in Kuwait. J Androl. 2012;33:1323–1329.
[28] Okoror L. High prevalence of Chlamydia trachomatis in the sperm
of males with low sperm count in Nigeria. J Med Microb Diagn.
2012;1:1–5.
[29] Mania-Pramanik J, Kerkar S, Sonawane S, et al. Current Chlamydia
trachomatis infection, a major cause of infertility. J Reprod Infertil.
2012;13:204–210.
[30] Fatholahzadeh B, Bahador A, Hasanabad MH, et al. Comparative
screening of Chlamydia trachomatis infection in women popula-
tion in Tehran, Iran. Iran Red Crescent Med J. 2012;14:289–293.
[31] Naderi T, Kazerani F, Bahraminpoor A. Comparison of chlamydia
infection prevalence between patients with and without ectopic
pregnancy using the PCR method. Ginekol Pol. 2012;83:819–821.
[32] Rashidi BH, Chamani-Tabriz L, Haghollahi F, et al. Effects of
Chlamydia trachomatis infection on fertility; a case-control study. J
Reprod Infertil. 2013;14:67–72.
[33] Tomusiak A, Heczko PB, Janeczko J, et al. Bacterial infections of
the lower genital tract in fertile and infertile women from the
southeastern Poland. Ginekol Pol. 2013;84:352–358.
[34] Abusarah EA, Awwad ZM, Charvalos E, et al. Molecular detection
of potential sexually transmitted pathogens in semen and urine
specimens of infertile and fertile males. Diagn Microbiol Infect Dis.
2013;77:283–286.
[35] Yeganeh O, Jeddi-Tehrani M, Yaghmaie F, et al. A survey on the
prevalence of Chlamydia trachomatis and Mycoplasma genitalium
infections in symptomatic and asymptomatic men referring to
Urology Clinic of Labbafinejad Hospital, Tehran, Iran. Iran Red
Crescent Med J. 2013;15:340–344.
[36] Fathollahzadeh B, Bahador A, Majnooni A, et al. Screening of
Chlamydia trachomatis infection in men, is it necessary in Iran?
Jundishapur J Microbiol. 2013;6:1–3.
[37] Marashi SMA, Moulana Z, Fooladi AAI, et al. Comparison of genital
Chlamydia trachomatis infection incidence between women with
infertility and healthy women in Iran using PCR and immunofluor-
escence methods. Jundishapur J Microbiol. 2014;7:1–4.
[38] Al-Marzoqi AH, Al-Taee M, Ahmed K. Cytokine profiles among
asthenospermic men with Chlamydia trachomatis infections: con-
centrations and significance of multiplex seminal fluid cytokine
and other immunologic factors. Int J Adv Biol Res. 2014;5:103–108.
[39] Alfarraj DA, Somily AM, Alssum RM, et al. The prevalence of
Chlamydia trachomatis infection among Saudi women attending
the infertility clinic in Central Saudi Arabia. Saudi Med J.
2015;36:61–66.
[40] Baud D, Goy G, Vasilevsky S, et al. Roles of bovine Waddlia chon-
drophila and Chlamydia trachomatis in human preterm birth. New
Microbes New Infect. 2015;3:41–45.
[41] El Qouqa IA, Shubair ME, Al Jarousha AM, et al. Prevalence of
Chlamydia trachomatis among women attending gynecology and
infertility clinics in Gaza, Palestine. Int J Infect Dis. 2009;13:334–
341.
[42] Rowley J, Toskin I, Ndowa F. Global incidence and prevalence of
selected curable sexually transmitted infections – 2008. World
Health Organization, 2012.
[43] Vasilevsky S, Greub G, Nardelli-Haefliger D, et al. Genital Chlamydia
trachomatis: understanding the roles of innate and adaptive
immunity in vaccine research. Clin Microbiol Rev. 2014;27:346–370.