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.

 

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

Eligibility Criteria

Search Methods

Data Collection and Validity Assessment

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

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 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.