Farname Inc. in collaboration with Iranian Society of Gynecology Oncology

Document Type : Original Research Article

Authors

1 Department of Obstetrics and Gynecology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Department of Obstetrics and Gynecology, Baqiyatallah University of Medical Sciences, Tehran, Iran

Abstract

Background & Objective: The association of Trichomonas vaginalis (T. vaginalis) and infertility is controversial. There is a doubt regarding the relation between T. vaginalis infection and female infertility. This study is the first meta-analysis that investigated the association between T. vaginalis infection and risk of female infertility.
Materials & Methods: Web of Science, PubMed and Scopus were searched using appropriate keywords as major international electronic bibliographic databases up to January 2020. Q-test and I2 statistic were used for evaluating heterogeneity between studies as well as Begg's and Egger's tests for exploring publication. Results were reported by pooled odds ratio (OR) estimate from individual studies by choosing random-effects model.
Results: In total, 650 articles were obtained by initial search until January 2020 with 9779 women. Results of the pooled OR estimates showed a significant association between T. vaginalis and infertility in adjusted studies (OR=1.95; 95% CI: 1.46, 2.43). Based on Begg's and Egger's tests, there was no evidence of publication bias (P < /i>=0.532 and P < /i>=0.896, respectively).
Conclusion: There was a significant association between T. vaginalis and female infertility. However, more evidence is necessary to prove the potential association of T. vaginalis with an increased risk of female infertility.

Keywords

Main Subjects

Introduction
 


Sexually transmitted diseases (STDs) are usually considered the leading cause of infertility worldwide. About 70% of all pelvic inflammatory disease (PID) lead to tubal damage (1). The Trichomonas vaginalis (T. vaginalis) is one of STDs and has a worldwide distribution (2). T. vaginalis is categorized as the leading non-viral STDs in the world (3). This infection is one of the parasites considered as the major public health concern (4). According to the reports of the world Health Organization (WHO), protozoa T. vaginalis involves more than a half of all STDs worldwide which are curable. The studies have reported that T. vaginalis is in relation with endometritis, salpingitis and PID (5).
High prevalence of T. vaginalis in women, and its association with severe adversarial reproductive results has made this infection a major health challenge in the world (6). El-Shazly et al. showed that the rate of T. vaginalis among infertile women is considerably higher than fertile women (7). However, the relation between T. vaginalis and infertility is controversial. In some studies a trend exists between T. vaginalis and infertility risk (8-10) while others do not show such an association (2, 11-13).
Up to now, no meta-analysis has been performed to investigate the association between T. vaginalis infection and the risk of infertility. Literature search showed an adequate reports regarding T. vaginalis infection and the risk of infertility worldwide. Therefore the present meta-analysis was designed to assess whether T. vaginalis can cause infertility in females.


 

 
Materials and Methods

We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as a guideline to conduct this study (14).

Eligibility Criteria
The association between T. vaginalis and infertility in observational studies were included with no restriction on age, primary or secondary infertility, race, country, year, and study language. In the present study we considered T. vaginalis as exposure and infertility as the outcome.
Search Methods
Scopus, PubMed and Web of Science were searched as the three major relevant international databases by relevant keywords to assess the association between of T. vaginalis and infertility from inception to January 2020. The keywords searched were (trichomonas vaginalis, trichomonas vaginitis, trichomoniasis vaginalis or trichomoniasis vaginitis) and (infertile or infertility). The references of relevant articles were also searched manually.
Data Collection and Validity Assessment
Articles were determined and relevant data were extracted by two of the researchers independently (ZS and NH). Disagreements between them were fixed by negotiation to reach to a consensus. Two authors separately extracted variables of interest from each study which was included first author, the setting of the study, publication year and country, number of patients, age, diagnostic modality for T. vaginalis, infertility, odds ratio (OR).
Quality of the selected studies was assessed by the Newcastle Ottawa Statement Manual (NOS) instrument (15). A set of items included in this measure. They were selection, comparability, exposure, and outcome. If a study obtained seven star-items or higher was considered as high-quality and the rest were considered low-quality investigations.
Assessing Heterogeneity Among Studies and Publication Bias

The heterogeneity among studies was assessed by Q-test and I2 test (16). Also we used Funnel plot as the graphical scale and the Begg's and Egger's tests (17) to determine possible publication bias, and the random effect model was used to estimate the relation between T. vaginalis and infertility (18). For controlling risk factors of infertility (smoking, age, race, contraceptive use and number of pregnancies), meta-analysis was performed by two ways including crude and adjusted form. Data was analyzed by Stata 14 at 0.05 significant level.


 

Results
A total of 650 studies were collected for the study up to January 2020 and 105 duplicate articles in the mentioned databases were excluded. In continue by evaluating the titles, 511 studies were dropped. In the second assessment, 25 were excluded based on studying the full article. Finally, 9 studies included in the final analysis (Figure 1). Of these nine selected studies, six were case-control (1, 2, 7, 8, 10, 12) and three were cross-sectional (9, 19, 20). There was no cohort study in this meta-analysis.
 
 Figure 1. Flow diagram of choosing the relevant studies
Figure 1. Flow diagram of choosing the relevant studies
Effects of Exposure
In this study, the relation between T. vaginalis and risk of female infertility was assessed in Figure 2. Results of the adjusted OR estimates indicating a significant relation between the T. vaginalis and the risk of infertility (OR=1.95; 95% CI: 1.46, 2.43). However results of the crude estimate was not significant (OR=0.55; 95% CI: 0.10, 1.00). The results in adjusted and crude studies were homogenous.
Subgroup analysis was performed based on design of the studies. Results of the OR estimates showed a significant association between T. vaginalis and infertility in case-control studies (OR=1.50; 95% CI: 1.08, 1.93) while in cross-sectional studies, the observed association was not significant (OR=1.79; 95% CI: - 0.15, 3.74).
Publication Bias
 Based on the Begg's and Egger's tests, there was no evidence of publication bias (P=0.532 and P=0.896, respectively) and studies were nearly symmetrical (Figure 3).
Quality of the Studies
  According to the NOS scale, of included studies seven studies were high- quality and two low-quality.
 
Figure 2. Forest plot of the association between trichomonas vaginalis and infertility
Figure 2. Forest plot of the association between trichomonas vaginalis and infertility

Figure 3. Funnel plot of the association between trichomonas vaginalis and infertility
Figure 3. Funnel plot of the association between trichomonas vaginalis and infertility
 
 
Table 1. Characteristics of the included studies to the meta-analysis
1st author, year Country Design Sample Diagnosis method age Estimate Adjustment Quality
Sherman et al., 1987 USA Case-control 1312 Medical records 20-39 OR Adjusted High
Grodstein et al., 1993 USA Case-control 3833 Not reported No data OR Adjusted High
Okonofua et al., 1995 Nigeria Case-control 178 Under microscope 27.8 OR Crude Low
Kildea et al., 2000 Australia Cross-sectional 342 Medical records 30.4 OR Adjusted High
El-shazly et al., 2001 Egypt Case-control 280   No data OR Crude High
Adamson et al., 2011 India Case-control 1923 Culture 25.9 OR Crude Low
Kaya et al., 2015 Turkey Case-control 51 CPLM 31.1 OR Crude High
Rostami, 2017 Iran Cross-sectional 420 Culture 33.74 OR Crude High
Klinger, 2006 Tanzania Cross-sectional 1440 M-PCR 20-44 OR Adjusted High
OR: Odds Ratio, author: Author
 
Table 2. The subgroup analysis according the study design
Subgroups Studies
No. of studies OR (95% CI) I2
Case-control studies 6 1.50(1.08, 1.93) 0.0%
Cross-sectional studies 3 1.45(-0.15, 3.74) 84.4%
OR: Odds Ratio, CI: confidence interval
 

 

 

Discussion

 

To our knowledge, this was the first meta-analysis in the world to assess the association of T. vaginalis and infertility in females. Based on this evidences, T. vaginalis in females is a risk factor for infertility. There was no cohort study in this meta-analysis. In subgroup analysis, there was a significant association between T. vaginalis and infertility in case-control studies.
Many microorganisms including bacteria, parasites, viruses and yeasts can be involved in female reproductive and lead to infertility (21). T. vaginalis is identified in nearly 3.15% of asymptomatic admitted women in infertility clinics (21). Some studies have shown that tubal infertility is nearly twofold as high in women who showed a history of T. vaginalis compared to women without infection (8, 10).
T. vaginalis in females might play a main role in preterm labor, and low birth weight in pregnancy. T. vaginalis is also is in relation with cervical intraepithelial neoplastic and atypical pelvic inflammatory disease and these complications can lead to infertility in women (21).
T. vaginalis can decrease the complement elements and elevate the IgA level in serum prolactin and vaginal discharge (22). According to these results, screening and treatment of T. vaginalis seems necessary to control STDs and female infertility.
In the current study, there were some limitations. (a) In some studies only the unadjusted OR were reported. However for controlling known risk factors of infertility we used the adjusted form in this meta-analysis. However, this might introduce information bias and limitation in our results. (b) Some studies did not distinguish primary and secondary infertility and cause of infertility (tubal, ovulation, etc). Therefore, we could not perform subgroup analysis for them.  Despite these limitations, the findings show that T. vaginalis is a risk factor for female infertility in adjusted studies with 9779 participants.

 

 
Conclusion

T. vaginalis is a risk factor for female infertility in adjusted studies with 9779 participants. More studies are needed to assess the potential association of T. vaginalis with an increased risk of female infertility.

 

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

 

Conflicts of Interest

The authors declare no conflict of interest.
 

 
1. Adamson PC, Krupp K, Freeman AH, Klausner JD, Reingold AL, Madhivanan P. Prevalence & correlates of primary infertility among young women in Mysore, India. Indian J Med Res. 2011;134(10):440-6.
2. Kaya OA, Silfeler DB, Kurt RK, Gozukara I, Yengil E, Bayramoglu N. Investigation of the presence of Trichomonas vaginalis in infertile Turkish women. Asian Biomed. 2015;9(5):659-63. [DOI:10.5372/1905-7415.0905.437]
3. World Health Organization. Prevalence and incidence of selected sexually transmitted infections, Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and Trichomonas vaginalis: methods and results used by the WHO to generate 2005 estimates. 2011.
4. Mielczarek E, Blaszkowska J. Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure. Infection. 2016;44(4):447-58. [DOI:10.1007/s15010-015-0860-0] [PMID]
5. Tsevat DG, Wiesenfeld HC, Parks C, Peipert JF. Sexually transmitted diseases and infertility. Am J Obstet Gynecol. 2017;216(1):1-9. [DOI:10.1016/j.ajog.2016.08.008] [PMID] [PMCID]
6. Simhan HN, Anderson BL, Krohn MA, Heine RP, de Tejada BM, Landers DV, et al. Host immune consequences of asymptomatic Trichomonas vaginalis infection in pregnancy. Am J Obstet Gynecol. 2007;196(1):59.e1-.e5. [DOI:10.1016/j.ajog.2006.08.035] [PMID]
7. El-Shazly A, El-Naggar H, Soliman M, El-Negeri M, El-Nemr H, Handousa A, et al. A study on Trichomoniasis vaginalis and female infertility. J Egypt Soc Parasitol. 2001;31(2):545-53.
8. Grodstein F, Goldman MB, Cramer DW. Relation of tubal infertility to history of sexually transmitted diseases. Am J Epidemiol. 1993;137(5):577-84. [DOI:10.1093/oxfordjournals.aje.a116711] [PMID]
9. Kildea S, Bowden FJ. Reproductive health, infertility and sexually transmitted infections in Indigenous women in a remote community in the Northern Territory. Aust N Z J Public Health. 2000;24(4):382-6. [DOI:10.1111/j.1467-842X.2000.tb01598.x] [PMID]
10. Sherman KJ, Daling JR, Weiss NS. Sexually transmitted diseases and tubal infertility. Sex Transm Dis. 1987;14(1):12-6. https://doi.org/10.1097/00007435-198701000-00003 [DOI:10.1097/OLQ.0000000000001292] [PMID]
11. El-Shazly AM, El-Naggar HM, Soliman M, El-Negeri M, El-Nemr HE, Handousa AE, et al. A study on Trichomoniasis vaginalis and female infertility. J Egypt Soc Parasitol. 2001;31(2):545-53.
12. Okonofua FE, Ako-Nai KA, Dighitoghi MD. Lower genital tract infections in infertile Nigerian women compared with controls. Genitourin Med. 1995;71(3):163-8. [DOI:10.1136/sti.71.3.163] [PMID] [PMCID]
13. Sherman KJ, Daling JR, Stergachis A, Weiss NS, Foy HM, Wang SP, et al. Sexually transmitted diseases and tubal pregnancy. Sex Transm Dis. 1990;17(3):115-21. [DOI:10.1097/00007435-199007000-00001] [PMID]
14. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9. [DOI:10.7326/0003-4819-151-4-200908180-00135] [PMID]
15. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses Ontario: Ottawa Hospital Research Institute; 2009 [Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
16. Higgins JPT, Thompson SG, Deeks JJ, Altman D. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-60. [DOI:10.1136/bmj.327.7414.557] [PMID] [PMCID]
17. Begg CB, Mazumdar M. Operating characteristics of a rank cor relation test for publication bias. Biometrics. 1994;50(4):1088-101. [DOI:10.2307/2533446]
18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-88. [DOI:10.1016/0197-2456(86)90046-2]
19. Klinger EV, Kapiga SH, Sam NE, Aboud S, Chen C-Y, Ballard RC, et al. A Community-based study of risk factors for Trichomonas vaginalis infection among women and their male partners in Moshi urban district, northern Tanzania. Sex Transm Dis. 2006;33(12):712-8. [DOI:10.1097/01.olq.0000222667.42207.08] [PMID]
20. Rostami MN, Rashidi BH, Habibi A, Nazari R, Dolati M. Genital infections and reproductive complications associated with Trichomonas vaginalis, Neisseria gonorrhoeae, and Streptococcus agalactiae in women of Qom, central Iran. Int J Reprod Biomed. 2017;15(6):357. [DOI:10.29252/ijrm.15.6.357]
21. Nourollahpour Shiadeh M, Niyyati M, Fallahi S, Rostami A. Human parasitic protozoan infection to infertility: a systematic review. Parasitol Res. 2016;115(2):469-77. [DOI:10.1007/s00436-015-4827-y] [PMID]
22. el-Sharkawy IM, Hamza SM, el-Sayed MK. Correlation between trichomoniasis vaginalis and female infertility. J Egypt Soc Parasitol. 2000;30(1):287-94.