**5. Conclusion**

158 Ectopic Pregnancy – Modern Diagnosis and Management

Variations in maternal activin A concentrations occurring in trophoblast diseases are believed to be part of the adaptive response of the placenta to adverse environmental

Patients with the diagnosis of ectopic pregnancy demonstrate disturbed activin A release in the placenta, which impairs the endometrium vascularization and subsequently trophoblast

Role of the endometrium which is a pivotal source of activin A is essential in the ground of implantation of ectopic pregnancy. During the secretory phase of the menstrual cycle (at the time of blastocyst implantation), activin A is present in the uterine fluid of cycling women in higher concentrations than during the proliferative phase. Activin A is a well-known regulator of the differentiation of proliferative cytotrophoblast into extravillous invasive trophoblast cells of the anchoring villi (Norwitz et al., 2001). The lack of an adequate endometrial secretion of activin A may be related to the lack of appropriate messages to the placenta for a right implantation. Additionally, activin A levels correlate with endometrial thickness. Such an increase of endometrial activin A and secretion at the time of blastocyst apposition may play an important role in embryo implantation (Caniggia et al., 1997). The probability of having an ectopic pregnancy may be estimated more precisely and more

Single activin A measurement may identify patients at risk of ectopic pregnancy with a high sensibility and specificity. Positive predictive value for ectopic pregnancy (approximately 97%) is possible when low serum activin levels are observed. These procedures may select pregnancies at higher risk of ectopic pregnancy earlier and possibly to prevent unnecessary

Additionally, activins play an important role in inflammation and are involved in the pathogenesis of inflammatory, fibrotic diseases and early scar formation. Activin A expression has been reported to increase in several inflammatory diseases, such as septicemia,

Nowadays, there is a suggestion that activin A could play an essential role in chlamydial infection. Refaat B. et al in 2009 performed a study about role of activins in the ectopic pregnancy in patients with or without Chlamydia trachomatis infection (Refaat, 2009). Infection with Chlamydia trachomatis increases the production of tumor necrosis factor alpha (TGF-α) in human cervical tissue, interleukin-1 in human fallopian tube bearing an ectopic pregnancy, and interleukin-6 in serum from women diagnosed with ectopic pregnancy. Activin A has been reported to modulate the function of B lymphocytes, which play an important role in controlling reinfection with Chlamydia trachomatis. Infection with Chlamydia trachomatis is associated with scar formation. Repeated Chlamydia trachomatis infection of pigtailed macaque fallopian tubes produces a Th1-like cytokine response

There is an increased activin A expression and its related molecules by human tubal epithelial cells in patients with the diagnosis of ectopic pregnancy. It has been suggested that tubal activins may be involved in the immune response to chlamydia-induced tubal chronic inflammation. This impairment in the activin expression by epithelial cells of fallopian tube may result in tubal pathology and subsequently may be the cause of

Increased expression of activin βA subunit and type II receptors may lead to impairment of tubal motility, an increase in tubal receptivity, and subsequently the development of ectopic pregnancy. It is said that tubal activin A, its type II receptors could be involved in the microbial-

inflammatory bowel disease, rheumatoid arthritis and asthma (Phillips et al., 2001).

conditions (Florio et al., 2001).

interventions.

implantation not in the uterus (Dimitriadis et al., 2005).

quickly if activin A measurement is performed.

associated with fibrosis and scarring.

development of ectopic pregnancy (Roan et al., 2008).

Ectopic pregnancy is really an important clinical problem. Particular aspect is referred to precise and fast diagnosis with the use of serum biomarkers. Activins and inhibins can be regarded as such biomarker candidate. So far the number of reports on the role of activins and inhibins in ectopic pregnancy diagnosis is limited.

Majority of studies on inhibin A (but the number is very limited) indicates that this substance can be consider as possible marker of ectopic pregnancy.

New biomarkers can be based on genomic technology. The attention should be paid on recent discovery the inhibin/activin beta B under-expression in the decidualized endometrium of women with tubal ectopic pregnancies. This kind of discovery can indicate that some secreted proteins associated with uterine decidualization can be useful in the diagnostic process of ectopic pregnancy.

During pregnancy, the human placenta is the main source of maternal activin A and serum concentrations of activin A progressively increase throughout pregnancy until delivery. Impaired secretion of activin A is related to trophoblast invasion and implantation. Patients with the diagnosis of ectopic pregnancy are thought to have low serum activin A concentrations.

There is no doubts that further studies on activins and inhibins in the aspect of ectopic pregnancy are required.
