Introduction. Chlamydia trachomatis is an established cause of tubal factor infertility; however its role in male fertility is not as clear. We sought to determine the prevalence of Chlamydia in infertile men and evaluate its impact on male reproductive potential. Materials and Methods. We compared the incidence of Chlamydia in our infertile male population with that reported in the literature. We then reviewed the impact of Chlamydia infection on male fertility. Results. The incidence of Chlamydia infection in our population of infertile men was 0.3%. There is considerable variability in the reported incidence, likely due to variation in the population studied, and detection technique. The optimal testing method and sample are presently unclear. The effect of Chlamydia on male reproductive function is also variable in the literature, but appears to be relatively minimal and may be related primarily to sperm DNA fragmentation or female partner transmission. Conclusions. The prevalence of Chlamydia in the infertile male population is low and routine testing is not supported by the literature. For high-risk infertile men, nucleic acid testing of urine +/？ semen is the most sensitive method to detect Chlamydia. A validated testing system for semen needs to be developed, so that a standardized methodology can be recommended. In this way the full implications of Chlamydia on male fertility can be elucidated. 1. Introduction Chlamydia trachomatis (C. trachomatis) is the most prevalent sexually transmitted disease in the world and a common cause of pathology in both men and women, causing urethritis, epididymitis, prostatitis, cervicitis, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility . While there are regional differences in the prevalence, it remains a common cause of genitourinary pathology in both men and women. In women C. trachomatis is a well-established cause of tubal factor infertility. In men it is a known common genitourinary pathogen, and electron microscopy has clearly demonstrated that C. trachomatis attach to spermatozoa [2–5], both on the surface and in the nucleus ; however its role in male fertility (sperm function, pregnancy rates, and live birth rates) is not clear. As the etiology of approximately 55% of male factor infertility is unknown, it is possible that Chlamydia is contributory in some of these cases. In our study in a Canadian clinic, we identified a very low prevalence of Chlamydia in the infertile male population of only 0.3% . This is the largest study of the prevalence of C.
K. Purvis and E. Christiansen, “Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility,” International Journal of Andrology, vol. 16, no. 1, pp. 1–13, 1993.
W. J. Hellstrom, J. Schachter, R. L. Sweet, and R. D. McClure, “Is there a role for Chlamydia trachomatis and genital mycoplasma in male infertility?” Fertility and Sterility, vol. 48, no. 2, pp. 337–339, 1987.
P. Vigil, P. Morales, A. Tapia, R. Riquelme, and A. M. Salgado, “Chlamydia trachomatis infection in male partners of infertile couples: incidence and sperm function,” Andrologia, vol. 34, no. 3, pp. 155–161, 2002.
T. Domes, K. C. Lo, E. D. Grober, J. B. Mullen, T. Mazzulli, and K. Jarvi, “The utility and cost of Chlamydia trachomatis and Neisseria gonorrhoeae screening of a male infertility population,” Fertility and Sterility, vol. 97, no. 2, pp. 299–305, 2012.
B. Nagy, G. Corradi, Z. Vajda, R. Gimes, and S. Csomor, “The occurrence of Chlamydia trachomatis in the semen of men participating in an IVF programme,” Human Reproduction, vol. 4, no. 1, pp. 54–56, 1989.
S. S. Witkin, J. Jeremias, J. A. Grifo, and W. J. Ledger, “Detection of Chlamydia trachomatis in semen by the polymerase chain reaction in male members of infertile couples,” American Journal of Obstetrics and Gynecology, vol. 168, no. 5, pp. 1457–1462, 1993.
M. G. Munoz and S. S. Witkin, “Autoimmunity to spermatozoa, asymptomatic Chlamydia trachomatis genital tract infection and γδ T lymphocytes in seminal fluid from the male partners of couples with unexplained infertility,” Human Reproduction, vol. 10, no. 5, pp. 1070–1074, 1995.
W. Eggert-Kruse, S. Pohl, H. Naher, W. Tilgen, and B. Runnebaum, “Microbial colonization and sperm-mucus interaction: results in 1000 infertile couples,” Human Reproduction, vol. 7, no. 5, pp. 612–620, 1992.
Z. Samra, Y. Soffer, and M. Pansky, “Prevalence of genital chlamydia and mycoplasma infection in couples attending a male infertility clinic,” European Journal of Epidemiology, vol. 10, no. 1, pp. 69–73, 1994.
S. Dieterle, J. B. Mahony, K. E. Luinstra, and W. Stibbe, “Chlamydial immunoglobulin IgG and IgA antibodies in serum and semen are not associated with the presence of Chlamydia trachomatis DNA or rRNA in semen from male partners of infertile couples,” Human Reproduction, vol. 10, no. 2, pp. 315–319, 1995.
W. Eggert-Kruse, N. Buhlinger-Gopfarth, G. Rohr, et al., “Antibodies to Chlamydia trachomatis in semen and relationship with parameters of male fertility,” Human Reproduction, vol. 11, no. 7, pp. 1408–1417, 1996.
M. S. Bornman, T. N. Ramuthaga, M. F. Mahomed, A. S. Greeff, H. H. Crewe-Brown, and S. Reif, “Chlamydial infection in asymptomatic infertile men attending an andrology clinic,” Archives of Andrology, vol. 41, no. 3, pp. 203–208, 1998.
R. Levy, M.-P. Layani-Milon, S. Giscard D'Estaing et al., “Screening for Chlamydia trachomatis and Ureaplasma urealyticum infection in semen from asymptomatic male partners of infertile couples prior to in vitro fertilisation,” International Journal of Andrology, vol. 22, no. 2, pp. 113–118, 1999.
F. R. Ochsendorf, K. ？zdemir, H. Rabenau et al., “Chlamydia trachomatis and male infertility: chlamydia-IgA antibodies in seminal plasma are C. trachomatis specific and associated with an inflammatory response,” Journal of the European Academy of Dermatology and Venereology, vol. 12, no. 2, pp. 143–152, 1999.
B. Habermann and W. Krause, “Altered sperm function or sperm antibodies are not associated with chlamydial antibodies in infertile men with leucocytospermia,” Journal of the European Academy of Dermatology and Venereology, vol. 12, no. 1, pp. 25–29, 1999.
S. Penna Videau, J. Cermeno Vivas, and N. Salazar, “IgA antibodies to Chlamydia trachomatis and seminal parameters in asymptomatic infertile males,” Archives of Andrology, vol. 46, no. 3, pp. 189–195, 2001.
J. Mania-Pramanik, J. Gokral, and P. K. Meherji, “Chlamydia trachomatis infection among asymptomatic males in an infertility clinic,” Indian Journal of Dermatology, Venereology and Leprology, vol. 67, no. 5, pp. 242–245, 2001.
R. Gdoura, F. Daoudi, F. Bouzid et al., “Detection of Chlamydia trachomatis in semen and urethral specimens from male members of infertile couples in Tunisia,” European Journal of Contraception and Reproductive Health Care, vol. 6, no. 1, pp. 14–20, 2001.
A. Idahl, J. Boman, U. Kumlin, and J. I. Olofsson, “Demonstration of Chlamydia trachomatis IgG antibodies in the male partner of the infertile couple is correlated with a reduced likelihood of achieving pregnancy,” Human Reproduction, vol. 19, no. 5, pp. 1121–1126, 2004.
F. Hamdad-Daoudi, J. Petit, and F. Eb, “Assessment of Chlamydia trachomatis infection in asymptomatic male partners of infertile couples,” Journal of Medical Microbiology, vol. 53, part 10, pp. 985–990, 2004.
B. de Barbeyrac, A. Papaxanthos-Roche, C. Mathieu et al., “Chlamydia trachomatis in subfertile couples undergoing an in vitro fertilization program: a prospective study,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 129, no. 1, pp. 46–53, 2006.
R. Gdoura, W. Kchaou, L. Ammar-Keskes et al., “Assessment of Chlamydia trachomatis, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, and Mycoplasma genitalium in semen and first void urine specimens of asymptomatic male partners of infertile couples,” Journal of Andrology, vol. 29, no. 2, pp. 198–206, 2008.
P. Joki-Korpela, N. Sahrakorpi, M. Halttunen, H. Surcel, J. Paavonen, and A. Tiitinen, “The role of Chlamydia trachomatis infection in male infertility,” Fertility and Sterility, vol. 91, supplement 4, pp. 1448–1450, 2009.
W. Eggert-Kruse, M. Weltin, and T. Strowitzki, “Are chlamydial lipopolysaccachide-directed antibodies in seminal plasma or serum clinically significant during investigation of male infertility?” Urology, vol. 77, no. 5, pp. 1101–1106, 2011.
R. Rybar, P. Prinosilova, V. Kopecka, et al., “The effect of bacterial contamination of semen on sperm chromatin integrity and standard semen parameters in men from infertile couples,” Andrologia, vol. 44, supplement 1, pp. 410–418, 2012.
S. D. Datta, E. Torrone, D. Kruszon-Moran et al., “Chlamydia trachomatis trends in the united states among persons 14 to 39 Years of Age, 1999-2008,” Sexually Transmitted Diseases, vol. 39, no. 2, pp. 92–96, 2012.
H. ？hman, A. Tiitinen, M. Halttunen, M. Lehtinen, J. Paavonen, and H.-M. Surcel, “Cytokine polymorphisms and severity of tubal damage in women with chlamydia-associated infertility,” Journal of Infectious Diseases, vol. 199, no. 9, pp. 1353–1359, 2009.
S. L. Gottlieb, D. H. Martin, F. Xu, G. I. Byrne, and R. C. Brunham, “Summary: the natural history and immunobiology of Chlamydia trachomatis genital infection and implications for chlamydia control,” Journal of Infectious Diseases, vol. 201, supplement 2, pp. S190–S204, 2010.
I. M. Linhares and S. S. Witkin, “Immunopathogenic consequences of Chlamydia trachomatis 60？kDa heat shock protein expression in the female reproductive tract,” Cell Stress and Chaperones, vol. 15, no. 5, pp. 467–473, 2010.
A. Hjelholt, G. Christiansen, T. G. Johannesson, H. J. Ingerslev, and S. Birkelund, “Tubal factor infertility is associated with antibodies against Chlamydia trachomatis heat shock protein 60 (HSP60) but not human HSP60,” Human Reproduction, vol. 26, no. 8, pp. 2069–2076, 2011.
M. Chernesky, S. Castriciano, J. Sellors et al., “Detection of Chlamydia trachomatis antigens in urine as an alternative to swabs and cultures,” Journal of Infectious Diseases, vol. 161, no. 1, pp. 124–126, 1990.
A. Eley, S. Hosseinzadeh, H. Hakimi, I. Geary, and A. A. Pacey, “Apoptosis of ejaculated human sperm is induced by co-incubation with Chlamydia trachomatis lipopolysaccharide,” Human Reproduction, vol. 20, no. 9, pp. 2601–2607, 2005.
R. Peeling and J. Embree, “Screening for sexually transmitted infection pathogens in semen samples,” The Canadian Journal of Infectious Diseases & Medical Microbiology, vol. 16, no. 2, pp. 73–76, 2005.
G. Gallegos-Avila, M. Ortega-Martínez, B. Ramos-González, R. Tijerina-Menchaca, J. Ancer-Rodríguez, and G. Jaramillo-Rangel, “Ultrastructural findings in semen samples of infertile men infected with Chlamydia trachomatis and mycoplasmas,” Fertility and Sterility, vol. 91, no. 3, pp. 915–919, 2009.
H. Wolff, U. Neubert, M. Volkenandt et al., “Detection of Chlamydia trachomatis in semen by antibody-enzyme immunoassay compared with polymerase chain reaction, antigen-enzyme immunoassay, and urethral cell culture,” Fertility and Sterility, vol. 62, no. 6, pp. 1250–1254, 1994.
K. H. Tjiam, B. Y. van Heijst, A. A. Polak-Vogelzang, et al., “Sexually communicable micro-organisms in human semen samples to be used for artificial insemination by donor,” Genitourinary Medicine, vol. 63, no. 2, pp. 116–118, 1987.
M. Puolakkainen, E. Vesterinen, E. Purola, P. Saikku, and J. Paavonen, “Persistence of chlamydial antibodies after pelvic inflammatory disease,” Journal of Clinical Microbiology, vol. 23, no. 5, pp. 924–928, 1986.
A. K. Rodgers, J. Wang, Y. Zhang, et al., “Association of tubal factor infertility with elevated antibodies to Chlamydia trachomatis caseinolytic protease P,” American Journal of Obstetrics & Gynecology, vol. 203, no. 5, pp. 494.e7–494.e14, 2010.
C. Campanella, A. Marino Gammazza, L. Mularoni, F. Cappello, G. Zummo, and V. Di Felice, “A comparative analysis of the products of GROEL-1 gene from Chlamydia trachomatis serovar D and the HSP60 var1 transcript from Homo sapiens suggests a possible autoimmune response,” International Journal of Immunogenetics, vol. 36, no. 1, pp. 73–78, 2009.
A. Idahl, L. Abramsson, U. Kumlin, J. A. Liljeqvist, and J. I. Olofsson, “Male serum Chlamydia trachomatis IgA and IgG, but not heat shock protein 60 IgG, correlates with negatively affected semen characteristics and lower pregnancy rates in the infertile couple,” International Journal of Andrology, vol. 30, no. 2, pp. 99–107, 2007.
Y. Pannekoek, S. M. Westenberg, P. P. Eijk et al., “Assessment of Chlamydia trachomatis infection of semen specimens by ligase chain reaction,” Journal of Medical Microbiology, vol. 52, part 9, pp. 777–779, 2003.
W. Weidner, E. Floren, O. Zimmermann, D. Thiele, and M. Ludwig, “Chlamydial antibodies in semen: search for, “silent” chlamydial infections in asymptomatic andrological patients,” Infection, vol. 24, no. 4, pp. 309–313, 1996.
J. Friberg, E. Confino, M. Suarez, and N. Gleicher, “Chlamydia trachomatis attached to spermatozoa recovered from the peritoneal cavity of patients with salpingitis,” Journal of Reproductive Medicine for the Obstetrician and Gynecologist, vol. 32, no. 2, pp. 120–122, 1987.
H. Wolff, U. Neubert, M. Zebhauser, G. Bezold, H. C. Korting, and M. Meurer, “Chlamydia trachomatis induces an inflammatory response in the male genital tract and is associated with altered semen quality,” Fertility and Sterility, vol. 55, no. 5, pp. 1017–1019, 1991.
R. Bollmann, S. Engel, D. Sagert, and U. B. Gobel, “Investigations on the detection of Chlamydia trachomatis infections in infertile male outpatients,” Andrologia, vol. 30, supplement 1, pp. 23–27, 1998.
J. P. MacKern-Oberti, R. D. Motrich, M. L. Breser et al., “Male rodent genital tract infection with chlamydia muridarum: persistence in the prostate gland that triggers self-immune reactions in genetically susceptible hosts,” Journal of Urology, vol. 186, no. 3, pp. 1100–1106, 2011.
S. Mazzoli, T. Cai, P. Addonisio, A. Bechi, N. Mondaini, and R. Bartoletti, “Chlamydia trachomatis infection is related to poor semen quality in young prostatitis patients,” European Urology, vol. 57, no. 4, pp. 708–714, 2010.
G. A. Greendale, S. T. Haas, K. Holbrook, B. Walsh, J. Schachter, and R. S. Phillips, “The relationship of Chlamydia trachomatis infection and male infertility,” American Journal of Public Health, vol. 83, no. 7, pp. 996–1001, 1993.
A. J. Stephens, M. Aubuchon, and D. J. Schust, “Antichlamydial antibodies, human fertility, and pregnancy wastage,” Infectious Diseases in Obstetrics and Gynecology, vol. 2011, Article ID 525182, 9 pages, 2011.
G. Gallegos, B. Ramos, R. Santiso, V. Goyanes, J. Gosálvez, and J. L. Fernández, “Sperm DNA fragmentation in infertile men with genitourinary infection by Chlamydia trachomatis and Mycoplasma,” Fertility and Sterility, vol. 90, no. 2, pp. 328–334, 2008.
I. Günyeli, F. Abike, I. Dünder et al., “Chlamydia, Mycoplasma and Ureaplasma infections in infertile couples and effects of these infections on fertility,” Archives of Gynecology and Obstetrics, vol. 283, no. 2, pp. 379–385, 2011.
R. D. Motrich, C. Cuffini, J. P. Mackern Oberti, M. Maccioni, and V. E. Rivero, “Chlamydia trachomatis occurrence and its impact on sperm quality in chronic prostatitis patients,” Journal of Infection, vol. 53, no. 3, pp. 175–183, 2006.
S. S. Witkin, I. Kligman, and A. M. Bongiovanni, “Relationship between an asymptomatic male genital tract exposure to Chlamydia trachomatis and an autoimmune response to spermatozoa,” Human Reproduction, vol. 10, no. 11, pp. 2952–2955, 1995.
S. S. Witkin, K. M. Sultan, G. S. Neal, J. Jeremias, J. A. Grifo, and Z. Rosenwaks, “Unsuspected Chlamydia trachomatis infection and in vitro fertilization outcome,” American Journal of Obstetrics and Gynecology, vol. 171, no. 5, pp. 1208–1214, 1994.
L. Karinen, A. Pouta, A.-L. Hartikainen et al., “Association between Chlamydia trachomatis antibodies and subfertility in the Northern Finland Birth Cohort 1966 (NFBC 1966), at the age of 31 years,” Epidemiology and Infection, vol. 132, no. 5, pp. 977–984, 2004.
L. Karinen, A. Pouta, A.-L. Hartikainen et al., “Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31,” American Journal of Reproductive Immunology, vol. 52, no. 5, pp. 291–297, 2004.
S. Hosseinzadeh, I. A. Brewis, A. Eley, and A. A. Pacey, “Co-incubation of human spermatozoa with Chlamydia trachomatis serovar E causes premature sperm death,” Human Reproduction, vol. 16, no. 2, pp. 293–299, 2001.
S. Hosseinzadeh, A. A. Pacey, and A. Eley, “Chlamydia trachomatis-induced death of human spermatozoa is caused primarily by lipopolysaccharide,” Journal of Medical Microbiology, vol. 52, no. 3, pp. 193–200, 2003.
K. Urata, H. Narahara, Y. Tanaka, T. Egashira, F. Takayama, and I. Miyakawa, “Effect of endotoxin-induced reactive oxygen species on sperm motility,” Fertility and Sterility, vol. 76, no. 1, pp. 163–166, 2001.
D. P. Evenson, L. K. Jost, D. Marshall et al., “Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic,” Human Reproduction, vol. 14, no. 4, pp. 1039–1049, 1999.
M. Spano, J. P. Bonde, H. I. Hjollund, H. A. Kolstad, E. Cordelli, and G. Leter, “Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team,” Fertility and Sterility, vol. 73, no. 1, pp. 43–50, 2000.
A. J. C. van den Brule, D. J. Hemrika, J. M. M. Walboomers et al., “Detection of Chlamydia trachomatis in semen of artificial insemination donors by the polymerase chain reaction,” Fertility and Sterility, vol. 59, no. 5, pp. 1098–1104, 1993.
N. Al-Mously, N. A. Cross, A. Eley, and A. A. Pacey, “Real-time polymerase chain reaction shows that density centrifugation does not always remove Chlamydia trachomatis from human semen,” Fertility and Sterility, vol. 92, no. 5, pp. 1606–1615, 2009.
S. Jakus, A. Neuer, S. Dieterle, A. M. Bongiovanni, and S. S. Witkin, “Antibody to the Chlamydia trachomatis 60kDa heat shock protein in follicular fluid and in vitro fertilization outcome,” American Journal of Reproductive Immunology, vol. 59, no. 2, pp. 85–89, 2008.
I. Sziller, P. Fedorcsák, Z. Csapó et al., “Circulating antibodies to a conserved epitope of the Chlamydia trachomatis 60-kDa heat shock protein is associated with decreased spontaneous fertility rate in ectopic pregnant women treated by salpingectomy,” American Journal of Reproductive Immunology, vol. 59, no. 2, pp. 99–104, 2008.
Royal College of Obstetricians and Gynaecologists Evidence-based Clinical Guidelines, “Guideline Summary No. 3: the management of infertility in secondary care,” BJU International, vol. 83, no. 6, pp. 641–645, 1999.
Male Infertility Best Practice Policy Committee of the American Urological Association and Practice Committee of the American Society for Reproductive Medicine, “Report on optimal evaluation of the infertile male,” Fertility and Sterility, vol. 86, supplement 1, no. 5, pp. S202–S209, 2006.
D. S. Meyers, H. Halvorson, and S. Luckhaupt, “Screening for chlamydial infection: an evidence update for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, vol. 147, no. 2, pp. 135–142, 2007.
K. Owusu-Edusei Jr., M. K. Bohm, H. W. Chesson, and C. K. Kent, “Chlamydia screening and pelvic inflammatory disease. Insights from exploratory time-series analyses,” American Journal of Preventive Medicine, vol. 38, no. 6, pp. 652–657, 2010.
B. Andersen, I. Van Valkengoed, I. Sokolowski, J. K. M？ller, L. ？stergaard, and F. Olesen, “Impact of intensified testing for urogenital Chlamydia trachomatis infections: a randomised study with 9-year follow-up,” Sexually Transmitted Infections, vol. 87, no. 2, pp. 156–161, 2011.
D. R. Blake, N. Maldeis, M. R. Barnes, A. Hardick, T. C. Quinn, and C. A. Gaydos, “Cost-effectiveness of screening strategies for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease clinic setting,” Sexually Transmitted Diseases, vol. 35, no. 7, pp. 649–655, 2008.
B. Andersen, P. O. Eidner, D. Hagensen, S. Lomborg, and G. Hoff, “Opportunities screening of young men for urogenital Chlamydia trachomatis infection in general practice,” Scandinavian Journal of Infectious Diseases, vol. 37, no. 1, pp. 35–39, 2005.
R. L. Nevin, E. E. Shuping, K. D. Frick, J. C. Gaydos, and C. A. Gaydos, “Cost and effectiveness of chlamydia screening among male military recruits: Markov modeling of complications averted through notification of prior female partners,” Sexually Transmitted Diseases, vol. 35, no. 8, pp. 705–713, 2008.