CHLAMYDIA TRACHOMATIS, THE WORST ENEMY OF FEMALE FERTILITY

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Sexually transmitted infections (STIs) have a huge impact on communities; they are associated with morbidity and mortality in individuals and also with increased public health expenditure due to their direct effect on fertility, the pregnancy process and carcinogenesis. Chlamydia infection is one of the most common curable sexually transmitted diseases worldwide, caused by Chlamydia trachomatis. Chlamydia trachomatis is a gram-negative, obligate intracellular parasite bacterium belonging to the family Chlamydiaceae, which can have specific infective potential for epithelial cells of the male and female reproductive tract. Chlamydia trachomatis infections represent the most widespread sexually transmitted infection caused by bacteria globally, with 131 million new cases per year. In symptomatic cases, men may present with urethritis or, less commonly, epididymitis while women, in addition to yellowish vaginal discharge, spontaneous bleeding, pain during intercourse or urination and pelvic pain, may experience pelvic inflammatory disease (PID). However, most women and 50% of affected men do not present many identifiable clinical symptoms, as the infection goes unnoticed. Unfortunately, there is a high percentage of asymptomatic infections, up to 70% in women. For these reasons, the majority of infected individuals do not seek treatment, not only endangering the health of their sexual partners, but also worsening their condition, as the persistent presence of the pathogen evokes a chronic immune response, leading to an increased production of genital immune mediators, such as interleukin IL-6 and interferon gamma, which increases the number of destroyed epithelial cells. This process is especially dangerous for women, as the manifestations and consequences are more detrimental to their reproductive health than for men. In women, CT can ascend from the lower genital tract and thus affect the uterus giving cervicitis and endometritis, the ovaries and fallopian tubes causing salpingitis, scarring and occlusions, as well as causing pelvic inflammatory disease. The literature shows that approximately 20% of women with lower genital tract Chlamydia infection will develop PID, almost 100% will develop chronic pelvic pain, 2% will experience adverse pregnancy outcomes (chromosomal abnormalities, miscarriages congenital malformations and stillbirth) and 3% infertility, probably due to scar formation and fallopian tube occlusion, whose tubular damage associated with chlamydia infection is mainly due to the persistence of such infections rather than single acute episodes. A consensus among physicians on this topic has not yet been reached, but a recent systematic review of the literature points out that there is an important association between previous chlamydia infection and female infertility. Evidence of tubal damage is highly suggestive of reduced fertility as a secondary consequence of this parasitic infection, but further studies on possible molecular causes are needed. Pelvic inflammatory disease is a chronic condition that leads to the development of fibrotic tissue and adhesion syndrome, resulting in several adverse reproductive health outcomes, including ectopic pregnancy and infertility. Although there are still controversial findings on reproductive complications due to infection, chlamydia PID remains the most important preventable cause of infertility and adverse reproductive health outcomes. As for the treatment of the infection, as such it is based on the use of antibiotic therapy. Chlamydia Trachomatis responds to the use of antibiotics listed in the British Association for Sexual Health and HIV guidelines, such as tetracyclines (doxycyline, minocycline), macrolides such as azithromycin, clarithromycin or erythromycin, others belonging to other classes such as clindamycin, ofloxacin, amoxicillin. In general, in cases of uncomplicated genital infection, the guidelines point out that doxycycline is the most effective treatment and should be used as first-line therapy, the others being alternative options to be used in the event of contraindication to the drug, resistance or other reasons. The first-line choices also include azithromycin, whose antibiotic activity ensures that bacterial growth is blocked due to its affinity for bacterial ribosomes; it also has an immunomodulatory effect that controls the inflammatory process. Doxycycline, on the other hand, belongs to the tetracycline class of antibiotics, which exhibit biological activity against bacteria through inhibition of protein synthesis. As with all infections susceptible to antibiotic therapy, the risk of drug resistance and reinfection exists for Chlamydia trachomatis infection. Against this background, there is an urgent need to make progress in the development of therapeutic weapons against the infection, and it would be reasonable to make Chlamydia screening via vagino-cervical swabs part of routine infertility investigation, despite the fact that to date methods of detecting the bacterial agent still give false negatives. In the future, the key to controlling CT infection will have to focus on public health intervention by screening the population of asymptomatic individuals to prevent transmission of the infection and treat patients appropriately in a timely manner and, why not, focus on the development of a vaccine.

 

 

References

Casper D J den Heijer, et al. Chlamydia trachomatis and the Risk of Pelvic Inflammatory Disease, Ectopic Pregnancy, and Female Infertility: A Retrospective Cohort Study Among Primary Care Patients. Clin Infect Dis. 2019 Oct 15;69(9):1517-1525. doi: 10.1093/cid/ciz429.

Laura Gazal Passos, et al. The Correlation between Chlamydia Trachomatis and Female Infertility: A Systematic Review. Rev Bras Gynecol Obstet . 2022 Jun;44(6):614-620. doi: 10.1055/s-0042-1748023. Epub 2022 May 16.

Oluwaseyi Isaiah Odelola, et al. Chlamydia trachomatis seropositivity among women with tubal factor infertility and fertile controls: a comparative study. Pan Afr Med J. 2023; 44: 178. Published online 2023 Apr 14. doi: 10.11604/pamj.2023.44.178.29443

Rafaela Rodrigues, et al. Therapeutic Options for Chlamydia trachomatis Infection: Present and Future. Antibiotics (Basel). 2022 Nov 16;11(11):1634. doi: 10.3390/antibiotics11111634.