**4. Effects of microorganisms on the Fallopian tubes**

The Fallopian tubes play an integral role in reproduction and undergo cyclical changes in morphology and ciliary activity that are dependent upon ovarian hormones (Lyons *et al.,* 2006). Recent reviews have reported that infection reduces ciliary motion and even destroys cilia within the Fallopian tubes (Lyons *et al.,* 2006; Shaw *et al.,* 2010). Reduced ciliary function can be a cause of infertility and can result in ectopic pregnancy since the embryo relies on cilia to facilitate its propulsion through the Fallopian tubes into the uterus. In addition, inflammation of the lumen of the Fallopian tubes results in tubal occlusion and tubal factor infertility. Whilst much research regarding the microflora associated with Fallopian tube damage continues to focus on sexually transmitted pathogens many other microorganisms have been associated with Fallopian tube pathology and tubal factor infertility.

#### **4.1 Bacterial vaginosis**

Bacterial vaginosis is a frequently encountered condition among women affecting from between 10 – 20% of fertile women (Holmes, 2008). Bacterial vaginosis is induced by the change from *Lactobacillus* spp. dominant vaginal flora to vaginal flora dominated by other microorganisms (Holmes, 2008). Several factors contribute to a reduction in the vaginal *Lactobacillus* spp. levels including antimicrobial treatment, hormonal imbalance, douching, use of non-barrier contraception, demographic factors − age and socioeconomic status, and the sexual history of the female − age of commencement of sexual intercourse, and number of previous sexual partners (Tibaldi *et al.,* 2009; Witkin *et al.,* 2007a). Bacterial vaginosis is a polymicrobial condition and an altered immunity hypothesis proposes that bacterial vaginosis develops as a result of the inhibition of Toll-like receptor (TLR) activation. The negative consequences of bacterial vaginosis are facilitated in part by a release and/or inadequate function of the antimicrobial plasma protein, mannose binding lectin (MBL) (Witkin *et al.,* 2007b). Microorganisms that frequently replace the normal *Lactobacillus* dominant lower genital tract flora include *Gardnerella vaginalis, Ureaplasma* spp.*, M*. *hominis, Streptococcus viridans* and anaerobic Gram-negative bacilli from the genera *Prevotella, Porphyromonas, Bacteroides, Fusobacterium* and the coccus, *Peptostreptococcus* (Biagi *et al.,* 2009; Hillier 1993). The quantification of several microorganisms, particularly *G*. *vaginalis* and *Atopobium vaginae*, allows for a molecular diagnosis of bacterial vaginosis (Menard *et al.,* 2008). Microorganisms infecting the lower genital tract can be transported to the uterus and the Fallopian tubes either by (1) ascending to cause endometritis and subsequent salpingitis or (2) transport by the

activity of tubal cilia, result in the partial or complete destruction of cilia, and alter the composition and viscosity of the tubal secretions. Within the Fallopian tube mucosa, the response to microorganisms is not uniform. Each species evokes an individual and specific response (Laufer *et al.,* 1984). For example, *E. coli* cells or lipopolysaccharide cause swelling of the ciliary tips followed by adhesions between shortened and swollen cilia in addition to shortened microvilli on non-ciliated cells (Laufer *et al.,* 1980; Laufer *et al.,* 1984). *C*. *trachomatis* infection of Fallopian tubes reveals patches of flattened cells mixed with cells with only a single elongated cilium (Patten *et al.,* 1990). The sexually transmitted pathogen, *N*. *gonorrhoeae* causes invagination in ciliated cells and loss of microvilli in non-ciliated cells

The Fallopian tubes play an integral role in reproduction and undergo cyclical changes in morphology and ciliary activity that are dependent upon ovarian hormones (Lyons *et al.,* 2006). Recent reviews have reported that infection reduces ciliary motion and even destroys cilia within the Fallopian tubes (Lyons *et al.,* 2006; Shaw *et al.,* 2010). Reduced ciliary function can be a cause of infertility and can result in ectopic pregnancy since the embryo relies on cilia to facilitate its propulsion through the Fallopian tubes into the uterus. In addition, inflammation of the lumen of the Fallopian tubes results in tubal occlusion and tubal factor infertility. Whilst much research regarding the microflora associated with Fallopian tube damage continues to focus on sexually transmitted pathogens many other microorganisms have been associated with Fallopian tube pathology and tubal factor

Bacterial vaginosis is a frequently encountered condition among women affecting from between 10 – 20% of fertile women (Holmes, 2008). Bacterial vaginosis is induced by the change from *Lactobacillus* spp. dominant vaginal flora to vaginal flora dominated by other microorganisms (Holmes, 2008). Several factors contribute to a reduction in the vaginal *Lactobacillus* spp. levels including antimicrobial treatment, hormonal imbalance, douching, use of non-barrier contraception, demographic factors − age and socioeconomic status, and the sexual history of the female − age of commencement of sexual intercourse, and number of previous sexual partners (Tibaldi *et al.,* 2009; Witkin *et al.,* 2007a). Bacterial vaginosis is a polymicrobial condition and an altered immunity hypothesis proposes that bacterial vaginosis develops as a result of the inhibition of Toll-like receptor (TLR) activation. The negative consequences of bacterial vaginosis are facilitated in part by a release and/or inadequate function of the antimicrobial plasma protein, mannose binding lectin (MBL) (Witkin *et al.,* 2007b). Microorganisms that frequently replace the normal *Lactobacillus* dominant lower genital tract flora include *Gardnerella vaginalis, Ureaplasma* spp.*, M*. *hominis, Streptococcus viridans* and anaerobic Gram-negative bacilli from the genera *Prevotella, Porphyromonas, Bacteroides, Fusobacterium* and the coccus, *Peptostreptococcus* (Biagi *et al.,* 2009; Hillier 1993). The quantification of several microorganisms, particularly *G*. *vaginalis* and *Atopobium vaginae*, allows for a molecular diagnosis of bacterial vaginosis (Menard *et al.,* 2008). Microorganisms infecting the lower genital tract can be transported to the uterus and the Fallopian tubes either by (1) ascending to cause endometritis and subsequent salpingitis or (2) transport by the

**4. Effects of microorganisms on the Fallopian tubes** 

(Draper *et al.,* 1980).

infertility.

**4.1 Bacterial vaginosis** 

lymphatic system (Brook, 2002). Bacterial vaginosis has been associated with genital and obstetric infections, including PID (Catlin, 1992; Hay *et al.,* 1992; Soper, 1994), particularly in the presence of other sexually transmitted infections (Hillier *et al.,* 1996; Wiesenfeld *et al.,* 2002) including human papilloma virus infections (Verteramo *et al.,* 2009).

Gaudoin *et al.,* (Gaudoin *et al.,* 1999) reported a strong association between bacterial vaginosis and tubal factor infertility and in a study by Wilson and colleagues (2002) it was concluded that women with tubal infertility were three times more likely to have bacterial vaginosis than women with male factor or unexplained infertility. In a retrospective analysis of a population of 952 women investigated over two years, it was recently reported that the genital discharges of asymptomatic women with infertility consisted of an overgrowth of several aerobic bacteria especially *G*. *vaginalis* (19.7%), Enterobacteriaceae or Enterococci (12.1%) and *Streptococcus agalactiae* (8.6%) noting a prevalence of *C*. *trachomatis* of only 0.5% in this cohort of women (Casari *et al.,* 2010).
