Immunogenetics of Chlamydia trachomatis infections: genetic profiling of subfertility patients to assess tubal pathology

Chlamydia trachomatis (CT) infections are the world leading cause of blindness (trachoma) and the most prevalent sexually transmitted disease, strongly associated with pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. Twin study-based findings of members of the EpiGenChlamydia Consortium identified a 40% human genetic predisposition to CT infections. The Consortium structured transnational research to such degree that comparative genomics and genetic epidemiology on large numbers of unrelated individuals can be performed to identify genetic markers used for patient profiling.

           Subfertility poses an enormous burden on healthcare and society throughout the world. Indeed, worldwide 15% of couples trying to conceive suffer from subfertility. The condition is  generally described as a failure to conceive after one year of unprotected, regular sexual intercourse. Approximately half of the couples suffering from subfertility will conceive spontaneously, or after simple treatment. The other half needs more complex treatment, such as in vitro fertilization (IVF) or other assisted reproduction procedures.

           There are several causes of subfertility, among those: ovulation disorders, male linked subfertility factors, tubal damage, unexplained subfertility, and other causes, such as endometriosis and fibroids. In women, one of the major causes of subfertility is tubal pathology, with a prevalence of around 30%. Further, in all of cases of tubal pathology, C. trachomatis is the single most common cause for infertility.

          The reference standard for diagnosing tubal pathology in subfertile women is laparoscopy performed usually after a CT IgG positive antibody test, only positive in 50-60% of women with tubal pathology. Despite its effectiveness, laparoscopy is costly, invasive and has a low positive predictive value. Therefore there is a unmet medical need for better diagnosing tubal pathology in women with subfertility, a need which could potentially be met by adding genetic profiling to current diagnostic approaches.