Pelvic Inflammatory DiseaseView this Special Issue
Review Article | Open Access
Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease
Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID). Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.
Mycoplasma genitalium is a genital tract microorganism [1, 2] identified in approximately 15 to 20% of young women seen in some adolescent health centers, sexually transmitted infection clinics, and emergency departments in the United States [3–6]. Concordance of M. genitalium infection [1, 2, 7, 8] as well as M. genitalium sequence type  among sexual partners suggests that this bacteria is sexually transmitted. In some populations studied, infection with M. genitalium is as common as Chlamydia trachomatis among high risk sexually active women [3, 10] and women with clinically suspected pelvic inflammatory disease (PID) . As C. trachomatis is the most common reportable bacterial infection in the United States , M. genitalium is thus a relatively common infection. M. genitalium has been associated with cervicitis [2, 12–15] and may play a role in PID, the infection and inflammation of a woman’s upper genital tract .
PID is frequent among women of childbearing age, diagnosed in approximately 8% of US women and 15% of Swedish women in their lifetime, with over one million U.S. women treated annually [17–22]. Major reproductive and gynecologic morbidities result from PID, including infertility, ectopic pregnancy, chronic pelvic pain, and recurrent PID . Although PID has a polymicrobial etiology, with C. trachomatis and/or N. gonorrhoeae isolated from approximately one-third to one half of cases [5, 24–27], many PID cases have an unidentified etiology. Although bacterial vaginosis-associated and mycoplasmal organisms have been associated with PID [4–6, 13, 25, 27–32], independent of gonococcal and chlamydial infection [4, 28], less is known about the etiology, treatment, and sequelae of nongonococcal, nonchlamydial PID. This paper reviews recent evidence for the role of M. genitalium in PID and subsequent reproductive and gynecologic outcomes.
2. Mycoplasma genitalium Lower Genital Tract Infection
M. genitalium was first identified in the early 1980s among men with nongonococcal urethritis . Because the microbe is extremely difficult to culture, only with polymerase chain reaction (PCR) technology has research into the pathogenicity of M. genitalium progressed. Numerous studies have confirmed the role of M. genitalium in acute and chronic drug-resistant nongonococcal urethritis [34–36]. In women, M. genitalium has been positively associated with cervical inflammation and clinically diagnosed cervicitis, although variable case definitions of cervicitis are responsible for some discrepancies in this literature . As C. trachomatis is a common cause of cervicitis and thus may confound this series of studies, some have excluded patients testing positive for C. trachomatis or have adjusted for it in multivariate analyses. The vast majority of these have demonstrated an independent, significant association between M. genitalium and cervicitis .
3. Mycoplasma genitalium and PID
PID typically occurs as microorganisms ascend from the lower genital tract and through the cervical os, infecting the uterus, fallopian tubes, and ovaries. Thus, cervicitis is a common antecedent of PID. Because M. genitalium is associated with cervicitis [2, 13–15], it is reasonable that it also causes nongonococcal, nonchlamydial PID. Indeed, this organism induces salpingitis in monkeys [37, 38], has been found to ascend from the lower to the upper genital tract in a mouse model , causes morphologic changes in ciliated fallopian tube cells in vitro , and has been detected in fallopian tube tissue in a woman with salpingitis . Further, M. genitalium has been shown to adhere to human spermatozoa, and therefore may potentially be carried by motile sperm to the female upper genital tract .
M. genitalium is detected by PCR frequently among women with PID, with rates ranging from 13% to 16% [4, 6, 43]. Several epidemiologic studies have associated M. genitalium with clinically suspected PID, endometritis, and adnexitis (see Table 1) [4, 6, 13, 32, 41, 43, 45]. In particular, a handful of studies have examined the relationship between M. genitalium identified by PCR and either histologically confirmed endometritis or salpingitis among a population of women with clinically suspected PID [4, 6]. In a study of 115 women presenting to a sexually transmitted disease clinic in Nairobi, Kenya, women with histologically confirmed endometritis were significantly more likely to have M. genitalium identified by PCR from the cervix and/or endometrium (16% versus 2%, ) . After excluding women with gonococcal or chlamydial infection, this study demonstrated an independent association between M. genitalium and PID . Similarly, in the PEACH study, Haggerty et al. reported that 15% (88) of 586 women with clinically suspected PID tested positive for M. genitalium in the cervix and/or endometrium by PCR. These women were more than twice as likely to have histologically confirmed endometritis at baseline (OR 2.6, 95% CI 1.5–4.6) as compared to women without M. genitalium identified at either site, and this relationship remained significant after adjustment for age, race, and gonococcal and chlamydial infection (adjusted OR 2.0, 95% CI 1.0–4.2) .
A weakness of the above investigations and a problem which challenges many PID studies are the lack of a true comparison group without signs and symptoms of PID. That is, the control groups were comprised of women with clinically suspected PID who did not have histologically confirmed endometritis. In an attempt to overcome this limitation, a few studies have been conducted with control groups comprised of women without clinically suspected PID. In a study of 53 patients with PID and 80 asymptomatic pregnant women recruited from an obstetrics and gynecology clinic, Uno et al. demonstrated a higher prevalence of M. genitalium detected by PCR among the women with PID as compared to controls (6% versus 0%) . In another study of 45 patients with clinically suspected PID and 37 control women undergoing tubal ligation, M. genitalium was detected by PCR in 13% of cases versus 0% of controls . These studies collectively demonstrate a higher prevalence of M. genitalium among PID patients as compared to external controls, but are limited by the lack of upper genital tract sampling. One study of 194 patients with clinically suspected PID and 246 asymptomatic pregnant women being screened for rubella compared the seroprevalence of M. genitalium using a lipid-associated membrane protein-enzyme immunoassay (LAMP-EIA) . Before and after adjustment for chlamydial antibodies, M. genitalium was not associated with PID (OR 1.0, 95% CI 0.6–1.7). The null association may be explained by the use of a serologic marker of M. genitalium, which measures both acute and past exposure. Thus, it may be that only current or recent M. genitalium infection is associated with current PID.
The cross-sectional nature of most M. genitalium and PID studies has made it difficult to determine whether or not the relationship is causal. However, there are a handful of prospective studies which allow for temporal assessment. Within the PEACH cohort, Haggerty et al. demonstrated that the relationship between M. genitalium and endometritis was independent and causal, since among women without concurrent N. gonorrhoeae and/or C. trachomatis, a positive endometrial PCR test for M. genitalium was associated with over a thirteenfold risk of incident endometritis, assessed histologically 30 days following a baseline evaluation of M. genitalium (adjusted RR 13.4, 2.4–75.2) . Similarly, in a nested case-control study of 2079 women presenting for pregnancy termination at Malmo University Hospital, M. genitalium was significantly associated with postabortal PID (OR 6.3, 95% CI 1.6–25.2) . Lastly, a study of 2378 sexually active female students participating in a chlamydia screening trial in London reported a positive, nonsignificant association between M. genitalium and subsequent PID (RR 2.4, 95% CI 0.7–7.5) . There are several reasons why this study’s findings are different from those by Haggerty and Bjartling. First, despite the large sample size, the study was underpowered to detect a prospective association between M. genitalium and PID. Second, PID was assessed largely by self-report and thus may suffer from misclassification bias. Further, asymptomatic PID could not be captured in this study. Additional prospective studies with active surveillance of PID using biologic markers are needed to fully understand the relationship between M. genitalium and PID.
4. Does M. genitalium Infection Result in Long-Term Reproductive Morbidity?
PID may result in long-term reproductive sequelae, including infertility, ectopic pregnancy, and chronic pelvic pain. Evidence for this comes from the Lund, Sweden cohort study (1960–1984) in which among 2,501 women with clinically suspected PID, salpingitis verified by laparoscopy was associated with infertility, ectopic pregnancy, recurrent PID, and chronic pelvic pain [23, 47]. Additionally, a number of retrospective case-control studies have shown that women with tubal occlusion are more likely to bear chlamydial or gonococcal antibodies, providing human evidence for causal links between chlamydial PID, gonococcal PID, and infertility [48–52].
Whether or not M. genitalium upper genital tract infection can result in reproductive or gynecologic sequelae is unclear. Like C. trachomatis, M. genitalium is often asymptomatic , increasing the likelihood for “silent” PID and its sequelae. Also parallel to studies of C. trachomatis, M. genitalium antibodies have been identified more frequently (22% versus 6%) among 132 women with tubal factor infertility compared to 176 women nontubal factor infertility . In a subsequent serologic investigation of M. genitalium and tubal factor infertility by the same investigator, 212 couples attending fertility clinics were examined and a strong antibody response against M. genitalium or C. trachomatis, but no sign of current or chronic infection, was found in women with TFI, indicating that previous infections caused by these microorganisms may have resulted in permanent damage and occlusion of the fallopian tubes . In another study of 51 infertility patients and 23 healthy, fertile women, M. genitalium was identified in the cervical canal by PCR among 20% of cases versus 4% of controls () . In subgroup analyses, M. genitalium was found in 29% (7 of 24) women with idiopathic infertility, and the comparison to controls was of borderline statistical significance (). Although these relationships were not statistically significant, they suggest that current infection with M. genitalium and/or permanent damage to the reproductive tract caused by chronic infection with M. genitalium may impair fertility. One study has examined the relationship between M. genitalium and reproductive morbidity among a population of women with PID. In an analysis of 586 women from the PEACH study presenting with signs and symptoms of PID, Haggerty et al. reported that rates of sequelae, including chronic pelvic pain (42%), infertility (22%), and recurrent PID (31%), were high among women testing positive for active endometrial M. genitalium by PCR at baseline . Although differences in rates of sequelae were not significantly different between women testing positive or negative for M. genitalium, there was a trend toward increased chronic pelvic pain, infertility, and recurrent PID and decreased pregnancy and live birth following M. genitalium infection. The rate of subsequent infertility among women with active endometrial M. genitalium was approximately twice as high as the rate reported from a study utilizing the 2002 National Survey of Family Growth data , suggesting that preservation of fertility may be suboptimal for women with M. genitalium upper genital tract infection.
Data examining M. genitalium and other reproductive consequences are sparse. One serologic case-control study of 82 ectopic pregnancy cases and 246 healthy pregnancy control women found no statistically significant association between ectopic pregnancy and M. genitalium antibodies . Nonsignificant trends suggesting an association between M. genitalium and ectopic pregnancy were found among a subgroup of women aged 18–30 (OR 2.0, ) and among women testing negative for C. trachomatis antibodies (OR 2.3, ) . It may be possible that reduced power in these subset analyses limited the ability to detect statistically significant associations. Further large prospective studies utilizing both serology and PCR are needed to better understand the potential reproductive sequelae of M. genitalium infection.
5. Symptoms of M. genitalium and Implications for Delayed Treatment
Although some studies have linked M. genitalium to pathologic vaginal discharge  and urethritis , several have reported that both M. genitalium [7, 58, 59] and C. trachomatis  are comparatively less symptomatic than gonococcal infection . Harboring an asymptomatic infection may increase the likelihood for delayed care and development of sequelae. In a study of 516 sexual dyads, although M. genitalium was associated with urethral discharge in men, no symptoms were diagnostic of infection in women . In addition, M. genitalium was found to be common in asymptomatic patients attending an STD clinic in the United Kingdom .
Symptoms of PID vary by microbial pathogen. For example, chlamydial salpingitis tends to exhibit more mild symptoms than gonococcal PID, despite the fact that both pathogens cause tubal damage . Short et al. found that, compared to women with gonococcal PID, those with M. genitalium-associated PID were less likely to have elevated markers of inflammation, cervicitis, elevated vaginal pH, and a high pelvic pain score . However, signs and symptoms of PID were similar between women with C. trachomatis and M. genitalium . This may indicate that, among women with PID, those infected with N. gonorrhoeae present with more overt and severe symptoms, leading to earlier treatment than women with C. trachomatis or M. genitalium . Long time to treatment is a major concern, as a case-control study nested within a landmark Scandinavian study found that delaying care for 3 or more days significantly increased the risk of impaired fertility among 443 women with PID . In a more recent study of 298 women with histologically confirmed endometritis, those with C. trachomatis monoinfection and M. genitalium monoinfection reported waiting the longest time between onset of symptoms and care seeking (12.3 and 10.9 days), while the shortest times were among women with N. gonorrhoeae monoinfection (4.6 days) and coinfection with two or more pathogens (5.6 days) . Delayed treatment of PID for 14 days or more was not significantly associated with reproductive morbidity in this study. However, rates of infertility, recurrent PID, and chronic pelvic pain were high in this cohort (17%, 20%, and 36%). Collectively, these studies may suggest that women with M. genitalium-associated PID may have low levels of chronic inflammation that can lead to reproductive damage before treatment.
6. Treatment of Upper Genital Tract M. genitalium Infection
If women with M. genitalium upper genital tract infection do seek care, they will likely be treated with one of the currently recommended CDC treatment regimens for PID including (1) ofloxacin, (2) levofloxacin, (3) ceftriaxone plus doxycycline, or (4) cefoxitin and probenecid plus doxycycline; all with optional metronidazole for full coverage against anaerobes and BV . However, some of these regimens are ineffective for the treatment of M. genitalium. In the PEACH study, Haggerty et al reported that persistence of M. genitalium was very high among women treated with cefoxitin and doxycycline for PID, with 44% of women with baseline endometrial PCR-positive specimens testing positive again 30 days following treatment . In contrast, only 2% to 4% of women in the PEACH study had persistent or recurrent gonococcal or chlamydial cervicitis when retested at 30 days . Women with M. genitalium identified in the endometrium by PCR at study enrollment were four times as likely to experience persistent endometritis and over four times as likely to experience treatment failure, defined as the presence of both endometritis and pelvic pain 30 days following treatment for PID (adjusted RR 4.6, 95% CI 1.1–20.1) . Further, M. genitalium strains resistant to tetracycline have been isolated , and M. genitalium is associated with persistent nongonococcal urethritis among men treated with tetracyclines [35, 59, 66–68] and levofloxacin [69, 70] for nongonococcal urethritis. Thus, even if women with active M. genitalium upper genital tract infection seek treatment, antibiotic resistance among M. genitalium strains may lead to persistent or recurrent infection, resulting in chronic inflammation and infection.
PID is a common disease among American women that results in frequent, serious reproductive morbidity. Most women with PID are treated with antibiotics directed toward N. gonorrhoeae and/or C. trachomatis, despite the fact that these bacterial pathogens account for only a third to a half of PID cases. Although M. genitalium has recently been recognized as a cause of nongonococcal, nonchlamydial PID, little is known about the long-term prognosis of M. genitalium upper genital tract infection.
Given the scarcity of information regarding the long-term prognosis of women infected with M. genitalium, the lack of routine testing for M. genitalium in clinical practice, and the resistance of M. genitalium to a number of PID treatment regimens, additional research on the relationships between M. genitalium, PID, and long-term reproductive sequelae is critically needed in order to shape screening and treatment guidelines. The high rate of treatment failure among women with clinically suspected PID testing positive for M. genitalium emphasizes a need for PID antibiotic regimens targeted toward M. genitalium, with the ultimate goal to prevent reproductive and gynecologic morbidity. M. genitalium has demonstrated susceptibility to macrolides, with azithromycin being the most active, and variable resistance to fluroquinolones, including ciprofloxacin [36, 71]. However, it should be noted that M. genitalium azithromycin resistance has recently been reported [72, 73]. A newer quinolone, moxiflocacin, has recently been shown to exhibit a high degree of activity against M. genitalium , and this antibiotic has also been shown to be effective for the treatment of PID . Although these promising therapies warrant further study for the treatment of PID, no highly sensitive test is widely used to diagnose M. genitalium in clinical practice. Nucleic acid amplification tests (NAATs) have been developed and tested , and they may be useful for the clinical detection of M. genitalium among PID patients. Endocervical swabs collected from patients with clinically suspected PID are already often tested for gonococcal and chlamydial infection, and thus a NAAT for M. genitalium could efficiently be added to this diagnostic screening. M. genitalium screening among patients with clinically suspected PID would allow clinicians to select treatment regimens specific for mycoplasmal PID. Additionally, commercially available testing is also critical for the identification and treatment of uncomplicated lower genital tract M. genitalium infection, in order to prevent subsequent PID and potential sequelae.
- J. Williams, B. van der Pol, B. E. Batteiger et al., “Mycoplasma genitalium symptoms and concordance in sexual dyads,” International Society for STD Research Book of Abstracts, 2007.
- L. Falk, H. Fredlund, and J. S. Jensen, “Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection,” Sexually Transmitted Infections, vol. 81, no. 1, pp. 73–78, 2005.
- J. S. Huppert, J. E. Mortensen, J. L. Reed, J. A. Kahn, K. D. Rich, and M. M. Hobbs, “Mycoplasma genitalium detected by transcription-mediated amplification is associated with Chlamydia trachomatis in adolescent women,” Sexually Transmitted Diseases, vol. 35, no. 3, pp. 250–254, 2008.
- C. L. Haggerty, P. A. Totten, S. G. Astete et al., “Failure of cefoxitin and doxycycline to eradicate endometrial Mycoplasma genitalium and the consequence for clinical cure of pelvic inflammatory disease,” Sexually Transmitted Infections, vol. 84, no. 5, pp. 338–342, 2008.
- I. Simms, K. Eastick, H. Mallinson et al., “Associations between Mycoplasma genitalium, Chlamydia trachomatis and pelvic inflammatory disease,” Journal of Clinical Pathology, vol. 56, no. 8, pp. 616–618, 2003.
- C. R. Cohen, L. E. Manhart, E. A. Bukusi et al., “Association between Mycoplasma genitalium and acute endometritis,” Lancet, vol. 359, no. 9308, pp. 765–766, 2002.
- A. K. Tosh, B. van der Pol, J. D. Fortenberry et al., “Mycoplasma genitalium among Adolescent Women and their Partners,” Journal of Adolescent Health, vol. 40, no. 5, pp. 412–417, 2007.
- A. R. Thurman, O. Musatovova, S. Perdue, R. N. Shain, J. G. Baseman, and J. B. Baseman, “Mycoplasma genitalium symptoms, concordance and treatment in high-risk sexual dyads,” International Journal of STD and AIDS, vol. 21, no. 3, pp. 177–183, 2010.
- S. V. Hjorth, E. Björnelius, P. Lidbrink et al., “Sequence-based typing of Mycoplasma genitalium reveals sexual transmission,” Journal of Clinical Microbiology, vol. 44, no. 6, pp. 2078–2083, 2006.
- C. Gaydos, N. E. Maldeis, A. Hardick, J. Hardick, and T. C. Quinn, “Mycoplasma genitalium as a contributor to the multiple etiologies of cervicitis in women attending sexually transmitted disease clinics,” Sexually Transmitted Diseases, vol. 36, no. 10, pp. 598–606, 2009.
- Centers for Disease Control and Prevention, Sexually Transmitted Disease Surveillance, 2004, U.S. Department of Health and Human Services, Atlanta, Ga, USA, 2005.
- C. L. McGowin and C. Anderson-Smits, “Mycoplasma genitalium: an emerging cause of sexually transmitted disease in women,” PLoS Pathogens, vol. 7, no. 5, pp. 1–10, 2011.
- M. Uno, T. Deguchi, H. Komeda et al., “Mycoplasma genitalium in the cervices of Japanese women,” Sexually Transmitted Diseases, vol. 24, no. 5, pp. 284–286, 1997.
- L. E. Manhart, C. W. Critchlow, K. K. Holmes et al., “Mucopurulent cervicitis and Mycoplasma genitalium,” Journal of Infectious Diseases, vol. 187, no. 4, pp. 650–657, 2003.
- J. Pépin, A. C. Labbé, N. Khonde et al., “Mycoplasma genitalium: an organism commonly associated with cervicitis among west African sex workers,” Sexually Transmitted Infections, vol. 81, no. 1, pp. 67–72, 2005.
- C. L. Haggerty and R. B. Ness, “Epidemiology, pathogenesis and treatment of pelvic inflammatory disease,” Expert Review of Anti-Infective Therapy, vol. 4, no. 2, pp. 235–247, 2006.
- E. H. Stephen and A. Chandra, “Declining estimates of infertility in the United States: 1982–2002,” Fertility and Sterility, vol. 86, no. 3, pp. 516–523, 2006.
- Centers for Disease Control and Prevention, Sexually Transmitted Disease Surveillance, 1997, Division of STD Prevention, U.S. Department of Health and Human Services, Atlanta, Ga, USA, 1998.
- A. E. Washington and P. Katz, “Cost of and payment source for pelvic inflammatory disease: trends and projections, 1983 through 2000,” Journal of the American Medical Association, vol. 266, no. 18, pp. 2565–2569, 1991.
- D. B. Rein, W. J. Kassler, K. L. Irwin, and L. Rabiee, “Direct medical cost of pelvic inflammatory disease and its sequelae: decreasing, but still substantial,” Obstetrics and Gynecology, vol. 95, no. 3, pp. 397–402, 2000.
- L. Westrom, “Decrease in incidence of women treated in hospital for acute salpingitis in Sweden,” Genitourinary Medicine, vol. 64, no. 1, pp. 59–63, 1988.
- I. Simms, P. Rogers, and A. Charlett, “The rate of diagnosis and demography of pelvic inflammatory disease in general practice: England and Wales,” International Journal of STD and AIDS, vol. 10, no. 7, pp. 448–451, 1999.
- L. Westrom, R. Joesoef, G. Reynolds, A. Hagdu, and S. E. Thompson, “Pelvic inflammatory disease and fertility: a cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results,” Sexually Transmitted Diseases, vol. 19, no. 4, pp. 185–192, 1992.
- R. B. Ness, D. E. Soper, R. L. Holley et al., “Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial,” American Journal of Obstetrics and Gynecology, vol. 186, no. 5, pp. 929–937, 2002.
- S. L. Hillier, N. B. Kiviat, S. E. Hawes et al., “Role of bacterial vaginosis-associated microorganisms in endometritis,” American Journal of Obstetrics and Gynecology, vol. 175, no. 2, pp. 435–441, 1996.
- N. B. Kiviat, P. Wolner-Hanssen, D. A. Eschenbach et al., “Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis,” American Journal of Surgical Pathology, vol. 14, no. 2, pp. 167–175, 1990.
- D. E. Soper, N. J. Brockwell, H. P. Dalton, and D. Johnson, “Observations concerning the microbial etiology of acute salpingitis,” American Journal of Obstetrics and Gynecology, vol. 170, no. 4, pp. 1008–1017, 1994.
- C. L. Haggerty, S. L. Hillier, D. C. Bass, and R. B. Ness, “Bacterial vaginosis and anaerobic bacteria are associated with endometritis,” Clinical Infectious Diseases, vol. 39, no. 7, pp. 990–995, 2004.
- J. F. Peipert, A. B. Montagno, A. S. Cooper, and C. J. Sung, “Bacterial vaginosis as a risk factor for upper genital tract infection,” American Journal of Obstetrics and Gynecology, vol. 177, no. 5, pp. 1184–1187, 1997.
- R. P. Nugent, M. A. Krohn, and S. L. Hillier, “Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation,” Journal of Clinical Microbiology, vol. 29, no. 2, pp. 297–301, 1991.
- H. C. Wiesenfeld, S. L. Hillier, M. A. Krohn et al., “Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease,” Obstetrics and Gynecology, vol. 100, no. 3, pp. 456–463, 2002.
- C. L. Haggerty, P. A. Totten, S. G. Astete, and R. B. Ness, “Mycoplasma genitalium among women with nongonococcal, nonchlamydial pelvic inflammatory disease,” Infectious Diseases in Obstetrics and Gynecology, vol. 2006, Article ID 30184, 5 pages, 2006.
- J. G. Tully, D. Taylor-Robinson, R. M. Cole, and D. L. Rose, “A newly discovered mycoplasma in the human urogenital tract,” Lancet, vol. 1, no. 8233, pp. 1288–1291, 1981.
- P. A. Totten, M. A. Schwartz, K. E. Sjörström et al., “Association of Mycoplasma genitalium with nongonococcal urethritis in heterosexual men,” Journal of Infectious Diseases, vol. 183, no. 2, pp. 269–276, 2001.
- J. S. Jensen, “Mycoplasma genitalium: a cause of non-gonococcal urethritis?” Genitourinary Medicine, vol. 70, no. 5, p. 363, 1994.
- D. Taylor-Robinson, “Mycoplasma genitalium—an up-date,” International Journal of STD and AIDS, vol. 13, no. 3, pp. 145–151, 2002.
- B. R. Moller, D. Taylor-Robinson, P. M. Furr, and E. A. Freundt, “Acute upper genital-tract disease in female monkeys provoked experimentally by Mycoplasma genitalium,” British Journal of Experimental Pathology, vol. 66, no. 4, pp. 417–426, 1985.
- D. Taylor-Robinson, P. M. Furr, J. G. Tully, M. F. Barile, and B. R. Møller, “Animal models of Mycoplasma genitalium urogenital infection,” Israel Journal of Medical Sciences, vol. 23, no. 6, pp. 561–564, 1987.
- C. L. McGowin, R. A. Spagnuolo, and R. B. Pyles, “Mycoplasma genitalium rapidly disseminates to the upper reproductive tracts and knees of female mice following vaginal inoculation,” Infection and Immunity, vol. 78, no. 2, pp. 726–736, 2010.
- A. Baczynska, P. Funch, J. Fedder, H. J. Knudsen, S. Birkelund, and G. Christiansen, “Morphology of human Fallopian tubes after infection with Mycoplasma genitalium and Mycoplasma hominis—n vitro organ culture study,” Human Reproduction, vol. 22, no. 4, pp. 968–979, 2007.
- C. R. Cohen, N. R. Mugo, S. G. Astete et al., “Detection of Mycoplasma genitalium in women with laparoscopically diagnosed acute salpingitis,” Sexually Transmitted Infections, vol. 81, no. 6, pp. 463–466, 2005.
- H. F. Svenstrup, J. Fedder, J. Abraham-Peskir, S. Birkelund, and G. Christiansen, “Mycoplasma genitalium attaches to human spermatozoa,” Human Reproduction, vol. 18, no. 10, pp. 2103–2109, 2003.
- I. Simms, J. M. Stephenson, H. Mallinson et al., “Risk factors associated with pelvic inflammatory disease,” Sexually Transmitted Infections, vol. 13, no. 18, 2002.
- M. Jurstrand, J. S. Jensen, A. Magnuson, F. Kamwendo, and H. Fredlund, “A serological study of the role of Mycoplasma genitalium in pelvic inflammatory disease and ectopic pregnancy,” Sexually Transmitted Infections, vol. 83, no. 4, pp. 319–323, 2007.
- C. Bjartling, S. Osser, and K. Persson, “The association between Mycoplasma genitalium and pelvic inflammatory disease after termination of pregnancy,” An International Journal of Obstetrics and Gynaecology, vol. 117, no. 3, pp. 361–364, 2010.
- P. Oakeshott, A. Aghaizu, P. Hay et al., “Is Mycoplasma genitalium in women the "new chlamydia?" A community-based prospective cohort study,” Clinical Infectious Diseases, vol. 51, no. 10, pp. 1160–1166, 2010.
- L. Westrom, “Effect of acute pelvic inflammatory disease on fertility,” American Journal of Obstetrics and Gynecology, vol. 121, no. 5, pp. 707–713, 1975.
- R. Punnonen, P. Terho, V. Nikkanen, and O. Meurman, “Chlamydial serology in infertile women by immunofluorescence,” Fertility and Sterility, vol. 31, no. 6, pp. 656–659, 1979.
- J. L. Kane, R. M. Woodland, and T. Forsey, “Evidence of chlamydial infection in infertile women with and without fallopian tube obstruction,” Fertility and Sterility, vol. 42, no. 6, pp. 843–848, 1984.
- A. Miettinen, P. K. Heinonen, K. Teisala, K. Hakkarainen, and R. Punnonen, “Serologic evidence for the role of Chlamydia trachomatis, Neisseria Gonorrhoeae, and Mycoplasma hominis in the etiology of tubal factor infertility and ectopic pregnancy,” Sexually Transmitted Diseases, vol. 17, no. 1, pp. 10–14, 1990.
- S. Chutivongse, M. Kozuh-Novak, J. Annus et al., “Tubal infertility: serologic relationship to past chlamydial and gonococcal infection,” Sexually Transmitted Diseases, vol. 22, no. 2, pp. 71–77, 1995.
- G. Anestad, O. Lunde, M. Moen, and K. Dalaker, “Infertility and chlamydial infection,” Fertility and Sterility, vol. 48, no. 5, pp. 787–790, 1987.
- H. F. Clausen, J. Fedder, M. Drasbek et al., “Serological investigation of Mycoplasma genitalium in infertile women,” Human Reproduction, vol. 16, no. 9, pp. 1866–1874, 2001.
- H. F. Svenstrup, J. Fedder, S. E. Kristoffersen, B. Trolle, S. Birkelund, and G. Christiansen, “Mycoplasma genitalium, Chlamydia trachomatis, and tubal factor infertility—a prospective study,” Fertility and Sterility, vol. 90, no. 3, pp. 513–520, 2008.
- J. Grześko, M. Elias, B. Maczyńska, U. Kasprzykowska, M. Tłaczała, and M. Goluda, “Occurrence of Mycoplasma genitalium in fertile and infertile women,” Fertility and Sterility, vol. 91, no. 6, pp. 2376–2380, 2009.
- J. E. Korte, J. B. Baseman, M. P. Cagle et al., “Cervicitis and genitourinary symptoms in women culture positive for Mycoplasma genitalium,” American Journal of Reproductive Immunology, vol. 55, no. 4, pp. 265–275, 2006.
- H. Moi, N. Reinton, and A. Moghaddam, “Mycoplasma genitalium in women with lower genital tract inflammation,” Sexually Transmitted Infections, vol. 85, no. 1, pp. 10–14, 2009.
- V. L. Short, P. A. Totten, R. B. Ness, S. G. Astete, S. F. Kelsey, and C. L. Haggerty, “Clinical presentation of Mycoplasma genitalium infection versus Neisseria Gonorrhoeae infection among women with pelvic inflammatory disease,” Clinical Infectious Diseases, vol. 48, no. 1, pp. 41–47, 2009.
- L. Falk, H. Fredlund, and J. S. Jensen, “Tetracycline treatment does not eradicate Mycoplasma genitalium,” Sexually Transmitted Infections, vol. 79, no. 4, pp. 318–319, 2003.
- J. Paavonen, L. Westrom, and D. Escenbah, “Pelvic inflammatory disease,” in Sexually Transmitted Diseases, K. K. Holmes, P. F. Sparling, W. E. Stamm et al., Eds., pp. 1017–1050, McGraw–Hill, New York, NY, USA, 2008.
- J. D. C. Ross, L. Brown, P. Saunders, and S. Alexander, “Mycoplasma genitalium in asymptomatic patients: implications for screening,” Sexually Transmitted Infections, vol. 85, no. 6, pp. 436–437, 2009.
- S. D. Hillis, R. Joesoef, P. A. Marchbanks, J. N. Wasserheit, W. Cates, and L. Westrom, “Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility,” American Journal of Obstetrics and Gynecology, vol. 168, no. 5, pp. 1503–1509, 1993.
- B. D. Taylor, R. B. Ness, T. Darville, and C. L. Haggerty, “Microbial correlates of delayed care for pelvic inflammatory disease,” Sexually Transmitted Diseases, vol. 38, no. 5, pp. 434–438, 2011.
- Centers for Disease Control and Prevention, “Sexually transmitted diseases treatment guidelines,” Morbidity and Mortality Weekly Report, vol. 59, pp. 1–110, 2010.
- G. E. Kenny, P. A. Young, M. C. Roberts, L. A. Manhart, and P. A. Totten, “An improved medium for growth of Mycoplasma genitalium: isolation of a tetracycline-resistant clinical strain,” ISSTDR Book of Abstracts, p. 389, 2007.
- H. Carlberg, E. Bjornelius, and J. S. Jensen, “Mycoplasma genitalium—the search for effective treatment,” International Journal of STD & AIDS, vol. 13, pp. 30–31, 2002.
- G. Johannisson, Y. Enström, G. B. Löwhagen et al., “Occurrence and treatment of Mycoplasma genitalium in patients visiting STD clinics in Sweden,” International Journal of STD and AIDS, vol. 11, no. 5, pp. 324–326, 2000.
- P. J. Horner, C. B. Gilroy, B. J. Thomas, R. O. M. Naidoo, and D. Taylor-Robinson, “Association of Mycoplasma genitalium with acute non-gonococcal urethritis,” Lancet, vol. 342, no. 8871, pp. 582–585, 1993.
- T. Deguchi, T. Yoshida, S. Yokoi et al., “Longitudinal quantitative detection by real-time PCR of Mycoplasma genitalium in first-pass urine of men with recurrent nongonococcal urethritis,” Journal of Clinical Microbiology, vol. 40, no. 10, pp. 3854–3856, 2002.
- S. I. Maeda, M. Tamaki, K. Kojima et al., “Association of Mycoplasma genitalium persistence in the urethra with recurrence of nongonococcal urethritis,” Sexually Transmitted Diseases, vol. 28, no. 8, pp. 472–476, 2001.
- P. C. T. Hannan, “Comparative susceptibilities of various AIDS-associated and human urogenital tract mycoplasmas and strains of Mycoplasma pneumoniae to 10 classes of antimicrobial agent in vitro,” Journal of Medical Microbiology, vol. 47, no. 12, pp. 1115–1122, 1998.
- C. S. Bradshaw, M. Y. Chen, and C. K. Fairley, “Persistence of Mycoplasma genitalium following azithromycin therapy,” PLoS ONE, vol. 3, no. 11, Article ID e3618, 2008.
- J. S. Jensen, C. S. Bradshaw, S. N. Tabrizi, C. K. Fairley, and R. Hamasuna, “Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance,” Clinical Infectious Diseases, vol. 47, no. 12, pp. 1546–1553, 2008.
- R. Hamasuna, Y. Osada, and J. S. Jensen, “Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5′ nuclease real-time PCR,” Antimicrobial Agents and Chemotherapy, vol. 49, no. 12, pp. 4993–4998, 2005.
- P. Judlin, Q. Liao, Z. Liu, P. Reimnitz, B. Hampel, and P. Arvis, “Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study,” An International Journal of Obstetrics and Gynaecology, vol. 117, no. 12, pp. 1475–1484, 2010.
- P. Barry, K. Ahrens, A. Roger et al., “Prevalence and incidence of Mycoplasma genitalium and Trichomonas vaginalis infections among STD clinic patients determined by transcription mediated amplification San Francisco and Denver, 2004/2005,” International Society for STD Research Book of Abstracts, 2007.
Copyright © 2011 Catherine L. Haggerty and Brandie D. Taylor. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.