**8. Conclusions**

30 Ectopic Pregnancy – Modern Diagnosis and Management

microorganisms, and endometriomas have been identified as a risk factor for tubo-ovarian abscess formation (Kubota *et al.,* 1997; Lin *et al.,* 2010). Women with endometriosis appear to represent a population at increased risk of infection and subsequent tubo-ovarian abscess due to an altered local immune environment (Chen *et al.,* 2004; Lebovic *et al.,* 2001). The risk of endometriosis is also increased in women with shorter menstrual cycles and an increased menstrual flow (Halme *et al.,* 1984). Again, the retrograde menstruation of non-sterile menstrual blood into the peritoneal cavity provides a route for microbial transport. The menstrual debris may also promote continued survival and persistence of these microorganisms in the upper genital tract. Microorganisms have been detected in the endometrium of 83% of women during the post-partum period (Andrews *et al.,* 2005). However, both vaginal and endocervical cultures demonstrated low concordance with endometrial cultures (Cicinelli *et al.,* 2009). This may suggest that tropisms exist in the genital tract that can modulate microbial survival. In studies investigating women with chronic endometritis, Cicinelli *et al.,*. (Cicinelli *et al.,* 2008) reported isolation aerobic bacteria in over 73% of cases in symptomatic women but in only 5% of women without clinical evidence of endometritis. A shortcoming if their study was that they did not screen endometrial samples for the presence of anaerobes, which dominate the genital microflora. Together, these studies suggest that the endometrial cavity is not sterile, and that the presence of microorganisms does not necessarily result on overt inflammation. The possibility exists that in women with endometriosis, who have an impaired genital tract immune response, that (1) these microorganisms may replicate causing increased pathology, including tubal damage and (2) the microflora represent a stimulus for the enhanced chemotaxis of macrophages and the subsequent secretion of secondary inflammatory

Other chemical mediators have also been investigated in women with endometriosis. Inducible nitric oxide synthase, activated by cytokines and growth factors (Morris and Billiard, 1994; Nussler and Billiar, 1993), regulates embryo transport within the Fallopian tube. What is interesting is that in women with endometriosis and PID, nitric oxide levels are increased (Alpay *et al.,* 2006; Bouyer *et al.,* 2002; Sioutas *et al.,* 2008). Lipopolysaccharide was capable of *in vitro* activation of macrophages in the peritoneal fluid of women with endometriosis, increasing inducible nitric oxide synthase and nitric oxide production in these women but not in women without disease (Osborn *et al.,* 2002). If endometriosis is part of an infectious condition, then these results may be evidence of the activity f polarised macrophages in this population. A macromolecular ovum capture inhibitor, causing formation of a membrane over the fimbrial cilia, has been also detected in the peritoneal

Studies investigating ectopic pregnancy following IVF are limited however, it has been suggested that the hormonal stimulation protocol and the infertility history may also be

Hydrosalpinx is associated with decreased IVF success (Wainer *et al.,* 1997). Approximately 30% of women undergoing IVF for tubal factor infertility have hydrosalpinges (Blazar *et al.,* 1997; Murray 1997). The incidence of ectopic pregnancy was significantly higher in patients having IVF treatment for tubal factor infertility than in those diagnosed with infertility die to endometriosis or idiopathic infertility (Dubuisson *et al.,* 1991). It has been reported that

mediators identified in this condition.

**7. IVF** 

fluid from women with endometriosis (Suginami & Yano 1988).

mechanisms predisposing women to ectopic pregnancy (Chang & Suh 2010).

Infectious agents can damage biological functions of the female reproductive tract with devastating consequences. Among the most common microorganisms involved in sexually transmitted infections and interfering with female fertility are *C*. *trachomatis* and *N*. *gonorrhoeae*. These two pathogens are involved in damage to the cervix, Fallopian tubes and tubal luminal architecture in infected women. Tubo-peritoneal damage seems to be the leading cause of microbial interference with human fertility. *C. trachomatis* is considered the most important cause of tubal obstruction and PID. Screening for repeat chlamydial infections using randomised control trials and prevalence of *Chlamydia* rather than PID as an end point should provide information useful for controlling morbidity associated with these infections. Infection of the female genital tract with other bacterial organisms including *M*. *genitalium,* Ureaplasma spp., anaerobes and aerobes/microaerophiles can also affect the precise functioning of components of this site resulting in tubal occlusion and infertility. Bacterial vaginosis is strongly linked to tubal infertility as causative agents can produce ascending infections of the female upper genital tract. The role of bacterial infections particularly those caused by *C*. *trachomatis* and immune responses to these infections as causes of damage to sperm function require further investigation. Finally, continued efforts in vaccine development to control *C. trachomatis* genital infections would seem prudent to prevent sequelae of unresolved or untreated infections of the female genital tract that can have profound effects on fertility in women.
