GynecologyGynecology2079-56962079-5831Consilium Medicum28335Research ArticleSubclinical inflammatory diseases of the pelvic organs: chronic endometritisTapilskayaN I-KarpeevS A-KuznetsovaI Vms_smith@list.ru1502201416110410909042020Copyright © 2014, Consilium Medicum2014The economic costs of treating infertility using assisted reproductive technologies are a burden even for advanced Western countries.In infertility patients with long and unsuccessfully treatment history, where all available methods, including assisted reproductive technology are present, chronic endometritis is diagnosed in 60% of cases. Overview of research on chronic endometritis, suggests that endometrium contaminated by microorganisms with confirmed subclinical inflammation is the cause of the reduction in fertility. Identification of a microbial agent in endometritis in routine outpatient practice is not mandatory, as the international experience, including research with a high level of evidence proves the expediency of empirical therapy, based on the minimum clinical criteria, because, otherwise, the consequences for the reproductive system may be irreparable. Preventive antibiotic therapy in patients with pre-conception infertility and recurrent miscarriage is an effective way of preventing reproductive losses. Josamycin is the drug of choice for these conditions due to broad-spectrum, high efficacy against intracellular agents and anaerobic microbiota, favorable safety profile, as well as additional systemic anti-inflammatory and immunomodulatory effects.endometritischronic endometritisinflammatory diseases of the pelvic organsjosamycinэндометритхронический эндометритвоспалительные заболевания органов малого тазаджозамицин[Гущин А.Е., Бурцев О.А., Рыжих П.Г. и др. Мониторинг лечения пациентов с инфекцией, вызванной Mycoplasma genitalium, с помощью методов ПЦР и НАСБД в реальном времени. Клин. дерматология и венерология. 2009; 4: 58-63.][Радзинский В.Е. Репродуктивная инфектология XXI века. Status Praesens. 2013; 16 (5): 33-6.][Радзинский В.Е., Димитрова В.И., Майскова И.Ю. Неразвивающаяся беременность. М.: ГЭОТАР-Медиа, 2009.][Aagaard K, Petrosino J, Keitel W et al. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. J FASEB J 2013; 27 (3): 1012-22.][Amsden G.W. Anti - inflammatory effects of macrolides - an underappreciated benefit in the treatment of community - acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 2005; 55 (1): 10-21.][Antoine T.E, Park P.J, Shukla D. Glycoprotein targeted therapeutics: a new era of anti - herpes simplex virus-1 therapeutics. Rev Med Virol 2013; 23 (3): 194-208.][Baston-Büst D.M, Götte M, Janni W et al. Syndecan-1 knock - down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns. Reprod Biol Endocrinol 2010; 8: 133.][Christoffersen M, Woodward E, Bojesen A.M et al. Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis. BMC Vet Res 2012; 8: 41.][Cicinelli E, Ballini A, Marinaccio M et al. Microbiological findings in endometrial specimen: our experience. Arch Gynecol Obstet 2012; 285 (5): 1325-9.][Cicinelli E, De Ziegler D, Nicoletti R et al. Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril 2008; 89 (3): 677-84.][Cicinelli E, De Ziegler D, Nicoletti R et al. Poor reliability of vaginal and endocervical cultures for evaluating microbiology of endometrial cavity in women with chronic endometritis. Gynecol Obstet Invest 2009; 68 (2): 108-15.][Cicinelli E, Tinelli R, Lepera A et al. Correspondence between hysteroscopic and histologic findings in women with chronic endometritis. Acta Obstet Gynecol Scand 2010; 89 (8): 1061-5.][Dewi F.N, Wood C.E, Lampe J.W et al. Endogenous and exogenous equol are antiestrogenic in reproductive tissues of apolipoprotein e - null mice. J Nutr 2012; 142 (10): 1829-35.][De Francesco M.A, Caracciolo S, Bonfanti C, Manca N. Incidence and antibiotic susceptibility of Mycoplasma hominis and Ureaplasma urealyticum isolated in Brescia, Italy, over 7 years. J Infect Chemother 2013; 19 (4): 621-7.][Di Pietro C, Cicinelli E, Guglielmino M.R et al. Altered transcriptional regulation of cytokines, growth factors, and apoptotic proteins in the endometrium of infertile women with chronic endometritis. Am J Reprod Immunol 2013; 69 (5): 509-17.][Donath E, Chaudhry A, Hernandez-Aya L.F, Lit L. A meta - analysis on the prophylactic use of macrolide antibiotics for the prevention of disease exacerbations in patients with Chronic Obstructive Pulmonary Disease. Respir Med 2013; 107 (9): 1385-92.][Espinoza J, Erez O, Romero R. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. Am J Obstet Gynecol 2006; 194 (3): 630-7.][Haggerty C.L. Evidence for a role of Mycoplasma genitalium in pelvic inflammatory disease. Curr Opin Infect Dis 2008; 21 (1): 65-9.][Hillier S.L, Rabe L.K, Meyn L et al. Endometrial Gardnerella vaginalis and Atopobium Vaginea are associated with histologic endometritis among women with clinically diagnosed pelvic inflammatory disease (PID). Sex Transm Infect 2013; 89 (1): A36.][Horner P, Blee K, Adams E. Time to manage Mycoplasma genitalium as an STI: but not with azithromycin 1g! Curr Opin Infect Dis 2014; 27 (1): 68-74.][Johnston-Mac Ananny E.B, Hartnett J, Engmann L.L et al. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril 2010; 93 (2): 437-41.][Kanoh S, Rubin B.K. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev 2010; 23 (3): 590-615.][Karasneh G.A, Ali M, Shukla D. An important role for syndecan-1 in herpes simplex virus type-1 induced cell - to - cell fusion and virus spread. PLoS One 2011; 6 (9): e25252.][Khan S, Tøndervik A, Sletta H et al. Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics. Antimicrob Agents Chemother 2012; 56 (10): 5134-41.][Leli C, Mencacci A, Bombaci J.C et al. Prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in a population of Italian and immigrant outpatients. Infez Med 2012; 20 (2): 82-7.][Munro M.G, Critchley H.O, Broder M.S, Fraser I.S. FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011; 113 (1): 3-13.][Ortega E, Escobar M.A, Gaforio J.J et al. Modification of phagocytosis and cytokine production in peritoneal and splenic murine cells by erythromycin A, azithromycin and josamycin. J Antimicrob Chemother 2004; 53 (2): 367-70.][Rockx B, Winegar R, Freiberg A.N. Recent progress in henipavirus research: molecular biology, genetic diversity, animal models. Antiviral Res 2012; 95 (2): 135-49.][Silva M.J, Florêncio G.L, Gabiatti J.R et al. Perinatal morbidity and mortality associated with chlamydial infection: a meta - analysis study. Braz J Infect Dis 2011; 15 (6): 533-9.][Swidsinski A, Verstraelen H, Loening-Baucke V et al. Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis. PLoS One 2013; 8 (1): e53997.][Teng Y.H, Aquino R.S, Park P.W. Molecular functions of syndecan-1 in disease. Matrix Biol 2012; 31 (1): 3-16.][Tortorella C, Piazzolla G, Matteo M et al. Interleukin-6, interleukin-1β,and tumor necrosis factor α in menstrual effluents as biomarkers of chronic endometritis. Fertil Steril 2013; 101 (1): 242-7.][Wiesenfeld H.C, Hillier S.L, Meyn L.A et al. Subclinical pelvic inflammatory diseaseand infertility. Obstet Gynecol 2012; 120: 37-43.][Yoshii N, Hamatani T, Inagaki N et al. Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity. Reprod Biol]