In recent years, there have been an increasing number of studies on T. vaginalis infection, and accumulating studies have reported a correlation between T. vaginalis infection and infertility. In this work, we first selected four articles on the incidence of T. vaginalis infection among patients with infertility [6, 14–16]. Data regarding the incidence of T. vaginalis infection in the infertile and healthy (people with normal reproductive function) groups were extracted for a meta-analysis, and a forest plot and funnel plot were generated. The combined effect size of the forest group was determined to be z = 2.19 and p = 0.03, which indicates that the data on the incidence of T. vaginalis infection in those two groups are statistically significant. The incidence of T. vaginalis infection in the infertile group was lower than that in the healthy group, indicating that infertility has negative effects on T. vaginalis infection. The distribution symmetry of the funnel plot of studies was poor, indicating publication bias. In addition, only a small number of articles were included in this study, which may also result in bias and is a limitation of the results. In the meta-analysis, some interfering factors may have also led to a higher incidence of T. vaginalis infection in the control group, resulting in deviation in the conclusion of the analysis. These interfering factors mainly include (1) discrepancies in education level and living conditions; (2) subjects with infertility in the experimental group may also have other infections, including Mycoplasma, Chlamydia, and other pathogens, that could cause infertility, leading to a lower incidence of T. vaginalis infection in the experimental group, which would affect the final results; (3) the composition of the control group is complex, as it includes both healthy people and patients with urinary tract infections and other diseases, and patients with these disease may be more vulnerable to T. vaginalis infection. Therefore, the conclusions in this section cannot confirm the correlation between T. vaginalis infection and infertility, and qualified epidemiological data are required to reveal this correlation.
In addition, one article on the incidence of infertility among patients with T. vaginalis infection was included . In this study, people with T. vaginalis infection were assigned to the experimental group, and people without T. vaginalis infection were assigned as the control group. Comparing the incidence of infertility between the two groups showed that the incidence of infertility in the experimental group was higher, indicating T. vaginalis infection has a promoting effect on the incidence of infertility. However, such articles are scarce, which may have caused deviations in our conclusions. Therefore, further studies are needed including epidemiological investigations of the incidence of infertility among people with T. vaginalis infection.
Several review articles on the correlation between T. vaginalis and infertility were selected. Consulting these articles revealed the significant impacts of T. vaginalis infection on the function of the human reproductive system. Many of the review articles stated that T. vaginalis infection can result in infertility, while one article did not clarify the correlation between T. vaginalis infection and infertility . Upon reading and summarizing these articles, we discovered that T. vaginalis infection in female patients mainly causes inflammation of the reproductive tract [18, 19] and changes in the vaginal environment ; these disturbances can injure the reproductive tract mucosa, fallopian tubes, or pelvic cavity [18, 21, 22], which may result in a decrease or loss of reproductive function, leading to infertility. The major reason that T. vaginalis infection leads to infertility in male patients is that T. vaginalis itself or the induced inflammatory response can impair sperm cells, causing a decrease in cell viability or death of sperm cells [12, 21–26], which may result in a decrease or loss of reproductive function, leading to infertility.
We also collected and analyzed research articles on the pathogenesis of T. vaginalis-induced infertility. The collective results indicate that there are three main pathogenic mechanisms underlying infertility caused by T. vaginalis infection. First, T. vaginalis impairs sperm quality, resulting in male infertility. T. vaginalis trophozoites can adhere to sperm cells through glycoproteins, thereby enclosing and phagocytizing sperm cells . Rotation of the attached T. vaginalis trophozoites can also interfere with the horizontal movement of sperm , affecting their ability to combine with an egg cell. In addition, the proteins or metabolites secreted by T. vaginalis may kill sperm cells or significantly diminish their viability and affect semen quality by increasing sperm viscosity and the quantity of fragments or by destroying the sperm membrane [31, 32]. Proteins secreted by T. vaginalis can also damage the integrity of the sperm membrane and acrosome , thereby impacting male reproductive function.
Second, the immune response triggered by T. vaginalis infection has negative impacts on female reproductive function. T. vaginalis infection is the most common cause of fallopian tube inflammation among female patients . The inflammation initiated by the adhesion of T. vaginalis to the vagina can injury uterine epithelial cells , which can trigger inflammation of fallopian tubes. T. vaginalis-induced genital tract inflammation also increase the risk of infection by other pathogens. For instance, T. vaginalis infection increases susceptibility to Mycoplasma and Chlamydia , thereby impairing reproductive function. Infection with T. vaginalis may also lead to pelvic inflammation , which affects female reproductive function. The inflammatory response induced by T. vaginalis can cause neutrophilia through serine protease-dependent pathogenesis. Therefore, contact between neutrophils and sperm cells leads to sperm phagocytosis and death . In infertile females with T. vaginalis infection, the levels of C3 and C4 were decreased, while the levels of IgA and serum prolactin in vaginal secretions were increased , which may also be important in the pathogenesis of female infertility caused by T. vaginalis infection.
Third, T. vaginalis impairs ovum quality, resulting in infertility. Metabolites of T. vaginalis, such as enzymes [28, 35], may damage oocytes and consequently reduce the probability of conception, which can lead to infertility in severe cases. High quantities of T. vaginalis trophozoites may also block the fallopian tubes , causing problems with ovulation, thereby impacting female reproductive function and leading to infertility. As the molecular mechanisms of infertility caused by T. vaginalis remains are not yet clear, further investigations are required.