2658-6533Научные результаты биомедицинских исследований2658-653310.18413/2658-6533-2021-7-4-0-92587Клиническая медицина<strong>Микробиом влагалища при нарушениях менструального цикла (обзор)</strong><strong>Vaginal microbiome in patients with menstrual cycle disorders (review)</strong>ЛебедеваОльга ПетровнаLebedevaOlga P.safonova2@yandex.ruГрязноваМария ВладимировнаGryaznovaMariya V.mariya-vg@mail.ruКозаренкоОлеся НиколаевнаKozarenkoOlesya N.ivashovao2@yandex.ruСыромятниковМихаил ЮрьевичSyromyatnikovMikhail Y.mihan.vrn@mail.ruПоповВасилий НиколаевичPopovVasily N.pvn@bio.vsu.ru20217400

Актуальность: В последние два десятилетия, благодаря использованию некультуральных методов исследования, накоплены новые данные об особенностях микробиома женских половых путей. Однако, причины, определяющие преобладание тех или иных микроорганизмов и формирование типа микробиома, окончательно не определены. Наибольшие изменения влагалищного микробиома происходят в ответ на гормональные влияния. Цель исследования: Оценить роль нарушений менструального цикла в формировании микробиома влагалища. Материалы и методы: Выполнен обзор литературы, посвященный роли нарушений менструального цикла в формировании влагалищного микробиома, по данным публикаций в базах данных EBSCO, Pubmed, Scopus, Google Academy, ResearchGate, Elibrary за последние 20 лет. Результаты: Представлены данные о роли микробиома человека в патогенезе соматических заболеваний. Даны основные характеристики влагалищного микробиома, представлена его классификация, описаны основные функции Lactobacillus&nbsp; spp. в женском репродуктивном тракте и их влияние на местную иммунореактивность. Описаны особенности влагалищного микробиома в течение нормального менструального цикла и у пациенток с его нарушениями. Заключение: Несмотря на критическую значимость микробиома женских половых путей для репродукции человека, данные о роли нарушений менструального цикла в формировании микробиома являются единичными и посвящены в основном исследованию влагалищного микробиома при синдроме поликистозных яичников (СПКЯ). Данные о роли гиперпролактинемии, врожденной дисфункции коры надпочечников и других причин нарушений менструального цикла в формировании влагалищного микробиома в литературе отсутствуют. Это диктует необходимость дальнейших исследований микробима у пациенток с нарушениями менструального цикла различного генеза, а также разработки методов коррекции выявленных нарушений.

Background:&nbsp;In the last two decades, because of the usage of non-cultural methods, new data on the female genital tract microbiome have been accumulated. However, the causes determining the predominance of certain microorganisms, and, consequently, the formation of microbiome composition, have not been finally determined. The major changes in the microbiome of the reproductive tract of women occur in response to the influence of hormones. The aim of the study:&nbsp;To assess the influence of menstrual cycle disorders on the vaginal microbiome composition. Materials and methods:&nbsp;The articles describing the role of menstrual cycle disorders in the formation of the vaginal microbiome composition, published over the past 20 years and deposited in the Pubmed, Google Academy, Scopus, Elibrary, ResearchGate, and EBSCO databases, were analyzed. Results:&nbsp;The data on the role of the human microbiome in the pathogenesis of somatic diseases are presented. The main characteristics of the vaginal microbiome are given, its classification is presented, the main functions of Lactobacillus in the female reproductive tract and their influence on local immunity are discussed. The vaginal microbiome during the normal menstrual cycle and in patients with menstrual cycle disorders is described. Conclusion:&nbsp;Despite the critical importance of the female genital tract microbiome for human reproduction, data on the role of menstrual cycle disorders in the formation of the microbiome are sporadic and are mainly concerned with the vaginal microbiome in polycystic ovary syndrome (PCOS). There are no data on the role of hyperprolactinemia, congenital adrenal hyperplasia, and other causes of menstrual cycle disorders in vaginal microbiome formation. Further studies of the microbiome in patients with menstrual cycle disorders, as well as its correction, are needed.

микробиом влагалищаменструальный циклнарушения менструального цикласиндром поликистозных яичников (СПКЯ)лактобактериигарднерелламикоплазмапревотеллаТолл-подобные рецепторы (TLR)vaginal microbiomemenstrual cyclemenstrual cycle disorderspolycystic ovary syndrome (PCOS)LactobacillusGardnerellaMycoplasmaPrevotellaToll-like receptors (TLRs)Список литературыHuttenhower C, Gevers D, Knight R, et al. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207-14. DOI: https://doi.org/10.1038/nature11234Larsen OFA, Claassen E. The mechanistic link between health and gut microbiota diversity. Scientific Reports. 2018;8(1):1-5. DOI: https://doi.org/10.1038/s41598-018-20141-6Sung J, Kim S, Cabatbat JJT, et al. Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis. Nature Communications. 2017;8(1):1-12. DOI: https://doi.org/10.1038/ncomms15393Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low gut microbiota diversity in early infancy precedes asthma at school age. Clinical and Experimental Allergy. 2014;44(6):842-50. DOI: https://doi.org/10.1111/cea.12253Wang M, Karlsson C, Olsson C, et al. Reduced diversity in the early fecal microbiota of infants with atopic eczema. Journal of Allergy and Clinical Immunology. 2008;121(1):129-34. DOI: https://doi.org/10.1016/j.jaci.2007.09.011Reiger M, Schwierzeck V, Traidl-Hoffmann C. [Atopic eczema and microbiome]. Hautarzt. 2019;70(6):407-15. DOI: 10.1007/s00105-019-4424-6Szari S, Quinn JA. Supporting a Healthy Microbiome for the Primary Prevention of Eczema. Clinical Reviews in Allergy and Immunology. 2019;57(2):286-93. DOI: https://doi.org/10.1007/s12016-019-08758-5Bisgaard H, Li N, Bonnelykke K, et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. Journal of Allergy and Clinical Immunology. 2011;128(3):646-652.e1-5. DOI: https://doi.org/10.1016/j.jaci.2011.04.060Karlsson F, Tremaroli V, Nielsen J, et al. Assessing the human gut microbiota in metabolic diseases. Diabetes. 2013;62(10):3341-9. DOI: https://doi.org/10.2337/db13-0844Castaner O, Goday A, Park Y-M, et al. The Gut Microbiome Profile in Obesity: A Systematic Review. International Journal of Endocrinology. 2018;2018:e4095789. DOI: https://doi.org/10.1155/2018/4095789Maruvada P, Leone V, Kaplan LM, et al. The Human Microbiome and Obesity: Moving beyond Associations. Cell Host and Microbe. 2017;22(5):589-99. DOI: https://doi.org/10.1016/j.chom.2017.10.005Ferreira CM, Vieira AT, Vinolo MAR, et al. The central role of the gut microbiota in chronic inflammatory diseases. Journal of Immunology Research. 2014;2014:689492. DOI: https://doi.org/10.1155/2014/689492Kau AL, Ahern PP, Griffin NW, et al. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327-36. DOI: 10.1038/nature10213Lakhan SE, Kirchgessner A. Gut inflammation in chronic fatigue syndrome. Nutrition and Metabolism. 2010;7:79. DOI: https://doi.org/10.1186/1743-7075-7-79Peirce JM, Alvi&ntilde;a K. The role of inflammation and the gut microbiome in depression and anxiety. Journal of Neuroscience Research. 2019;97(10):1223-41. DOI: https://doi.org/10.1002/jnr.24476Foster JA, McVey Neufeld K-A. Gut&ndash;brain axis: how the microbiome influences anxiety and depression. Trends in Neurosciences. 2013;36(5):305-12. DOI: https://doi.org/10.1016/j.tins.2013.01.005Lach G, Schellekens H, Dinan TG, et al. Anxiety, Depression, and the Microbiome: A Role for Gut Peptides. Neurotherapeutics. 2018;15(1):36-59. DOI: https://doi.org/10.1007/s13311-017-0585-0Gopalakrishnan V, Helmink BA, Spencer CN, et al. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell. 2018;33(4):570-80. DOI: https://doi.org/10.1016/j.ccell.2018.03.015Spanogiannopoulos P, Bess EN, Carmody RN, et al. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nature Reviews Microbiology. 2016;14(5):273-87. DOI: https://doi.org/10.1038/nrmicro.2016.17Hickey RJ, Zhou X, Pierson JD, et al. Understanding vaginal microbiome complexity from an ecological perspective. Translational Research. 2012;160(4):267-82. DOI: https://doi.org/10.1016/j.trsl.2012.02.008Kamińska D, Gajecka M. Is the role of human female reproductive tract microbiota underestimated? Beneficial Microbes. 2017;8(3):327-43. DOI: https://doi.org/10.3920/BM2015.0174van de Wijgert JHHM, Jespers V. The global health impact of vaginal dysbiosis. Research in Microbiology. 2017;168(9-10):859-64. DOI: https://doi.org/10.1016/j.resmic.2017.02.003Manning R, James CP, Smith MC, et al. Predictive value of cervical cytokine, antimicrobial and microflora levels for pre-term birth in high-risk women. Scientific Reports. 2019;9(1):11246. DOI: https://doi.org/10.1038/s41598-019-47756-7Лобанова ЕН, Комзин КВ, Соловьева МИ, и др. Особенности микробиоценоза влагалища при различных клинических вариантах невынашивания беременности. Акушерство, Гинекология и Репродукция. 2019;13(1):13-19. DOI: https://doi.org/10.17749/2313-7347.2019.13.1.013-019Brown RG, Marchesi JR, Lee YS, et al. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Medicine. 2018;16(1):9. DOI: https://doi.org/10.1186/s12916-017-0999-xBridwell RE, Carius BM, Long B, et al. Sepsis in Pregnancy: Recognition and Resuscitation. Western Journal of Emergency Medicine. 2019;20(5):822-32. DOI: https://doi.org/10.5811/westjem.2019.6.43369Яковчук ЕК, Сулима АН, Рыбалка АН, и др. Хронический эндометрит: современное состояние проблемы, основные аспекты патогенеза, влияние на репродуктивную функцию. . DOI: https://doi.org/10.17116/rosakush201616537-41Воропаева ЕЕ, Казачков ЕЛ, Медведев БИ, и др. Структурные особенности эндометрия у женщин с невынашиванием беременности ранних сроков, ассоциированным с хроническим эндометритом. . 2009;(6):332-338.Brown J. Surgical gynaecological infections [Internet]. O&amp;G Magazine. 2019 [cited 2021 May 5]. Available from: https://www.ogmagazine.org.au/21/4-21/surgical-gynaecological-infections/Soper DE. Bacterial vaginosis and surgical site infections. American Journal of Obstetrics and Gynecology. 2020;222(3):219-23. DOI: https://doi.org/10.1016/j.ajog.2019.09.002Onderdonk AB, Delaney ML, Fichorova RN. The Human Microbiome during Bacterial Vaginosis. Clinical Microbiology Reviews. 2016;29(2):223-38. DOI: https://doi.org/10.1128/CMR.00075-15Greenbaum S, Greenbaum G, Moran-Gilad J, et al. Ecological dynamics of the vaginal microbiome in relation to health and disease. American Journal of Obstetrics and Gynecology. 2019;220(4):324-35. DOI: https://doi.org/10.1016/j.ajog.2018.11.1089Rukhliada NN, Bren AK. Abnormal vaginal microflora as a risk factor for reproductive loss. Global Reproduction. 2020;3:15-18.Smith SB, Ravel J. The vaginal microbiota, host defence and reproductive physiology. The Journal of Physiology. 2017;595(2):451-63. DOI: https://doi.org/10.1113/JP271694Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences. 2011;108(Supplement 1):4680-7. DOI: https://doi.org/10.1073/pnas.1002611107Gajer P, Brotman RM, Bai G, et al. Temporal dynamics of the human vaginal microbiota. Science Translational Medicine. 2012;4(132):132ra52-132ra52. DOI: https://doi.org/10.1126/scitranslmed.3003605Aiyar A, Quayle AJ, Buckner LR, et al. Influence of the tryptophan-indole-IFN&gamma; axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections. Frontiers in Cellular and Infection Microbiology. 2014;4:72. DOI: https://doi.org/10.3389/fcimb.2014.00072Pyles RB, Vincent KL, Baum MM, et al. Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures. PLoS ONE. 2014;9(3):e93419. DOI: https://doi.org/10.1371/journal.pone.0093419Anahtar MN, Byrne EH, Doherty KE, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity. 2015;42(5):965-76. DOI: https://doi.org/10.1016/j.immuni.2015.04.019Moreno I, Simon C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reproductive Medicine and Biology. 2019;18(1):40-50. DOI: https://doi.org/10.1002/rmb2.12249Moreno I, Codo&ntilde;er FM, Vilella F, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. American Journal of Obstetrics and Gynecology. 2016;215(6):684-703. DOI: https://doi.org/10.1016/j.ajog.2016.09.075Macklaim JM, Fernandes AD, Di Bella JM, et al. Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis. Microbiome. 2013;1(1):1-11. DOI: https://doi.org/10.1186/2049-2618-1-12van Houdt R, Ma B, Bruisten SM, et al. Lactobacillus iners-dominated vaginal microbiota is associated with increased susceptibility to Chlamydia trachomatis infection in Dutch women: a case&ndash;control study. Sexually Transmitted Infections. 2018;94(2):117-23. DOI: http://dx.doi.org/10.1136/sextrans-2017-053133Mls J, Str&aacute;n&iacute;k J, Kacerovskỳ M. Lactobacillus iners-dominated vaginal microbiota in pregnancy. Ceska Gynekologie. 2019;84(6):463-7.Song SD, Acharya KD, Zhu JE, et al. Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise. mSphere. 2020;5(4). DOI: https://doi.org/10.1128/mSphere.00593-20Moosa Y, Kwon D, De Oliveira T, et al. Determinants of vaginal microbiota composition. Frontiers in Cellular and Infection Microbiology. 2020;10. DOI: https://doi.org/10.3389/fcimb.2020.00467Agostinis C, Mangogna A, Bossi F, et al. Uterine immunity and microbiota: a shifting paradigm. Frontiers in Immunology. 2019;10:2387. DOI: https://doi.org/10.3389/fimmu.2019.02387Hickey RJ, Zhou X, Settles ML, et al. Vaginal Microbiota of Adolescent Girls Prior to the Onset of Menarche Resemble Those of Reproductive-Age Women. mBio. 2015;6(2):e00097-15. DOI: https://doi.org/10.1128/mBio.00097-15Murphy K, Keller M, Anastos K, et al. Impact of reproductive aging on the vaginal microbiome and soluble immune mediators in women living with and at-risk for HIV infection. PLoS ONE. 2019;14:e0216049. DOI: https://doi.org/10.1371/journal.pone.0216049Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome. Maturitas. 2016;91:42-50. DOI: https://doi.org/10.1016/j.maturitas.2016.05.015Bastianelli C, Farris M, Bianchi P, et al. The effect of different contraceptive methods on the vaginal microbiome. Expert Review of Clinical Pharmacology. 2021;14(7):1-16. DOI: https://doi.org/10.1080/17512433.2021.1917373Lebedeva OP, Kalutsky PV. Anti-infectious defense of vagina during use of low-dose monophasic contraceptives. Zhurnal mikrobiologii, &egrave;pidemiologii i immunobiologii. 2007;(1):67-9.Maldonado-Barrag&aacute;n A, Caballero-Guerrero B, Mart&iacute;n V, et al. Purification and genetic characterization of gassericin E, a novel co-culture inducible bacteriocin from Lactobacillus gasseri EV1461 isolated from the vagina of a healthy woman. BMC Microbiology. 2016;16(1):37. DOI: https://doi.org/10.1186/s12866-016-0663-1Кира ЕФ, Молчанов ОЛ, Семенова КЕ. Биологическая роль молочной кислоты в обеспечении стабильности микроэкосистемы влагалища. Акушерство и гинекология. 2014;12:31-36.Кира ЕФ, Душкина ЕА, Бадикова НС. Биологическая роль кислотности влагалища. Механизмы стабильности и методы коррекции. Акушерство и гинекология. 2013;3:102-106.Селихова МС, Солтыс ПА, Смольянинов АА. Воспалительные заболевания органов малого таза: современные акценты проблемы: монография. Волгоград: Волгоградский государственный медицинский университет; 2020.Солтыс ПА, Селихова МС. Микробиом репродуктивного тракта женщины и воспалительные заболевания органов малого таза. Якутский Медицинский Журнал. 2020;1(69):95-8. DOI: https://doi.org/10.25789/YMJ.2020.69.23Кира ЕФ, Прилепская ВН, Костава МН, и др. Современные подходы к выбору препарата локального действия в терапии бактериального вагиноза. Акушерство и гинекология. 2012;7:60-67.Spurbeck RR, Arvidson CG. Lactobacilli at the front line of defense against vaginally acquired infections. Future Microbiology. 2011;6(5):567-82. DOI: https://doi.org/10.2217/fmb.11.36Lebedeva OP, Pakhomov SP, Ivashova ON, et al. Expression of TLR 1-10 and caspase-3 alfa in human endometrium at women with early miscarriages. Giornale Italiano di Ostetricia e Ginecologia. 2013;35(1):270-1.Aboussahoud W, Aflatoonian R, Bruce C, et al. Expression and function of Toll-like receptors in human endometrial epithelial cell lines. Journal of Reproductive Immunology. 2010;84(1):41-51. DOI: https://doi.org/10.1016/j.jri.2009.09.008Rose WA, McGowin CL, Spagnuolo RA, et al. Commensal Bacteria Modulate Innate Immune Responses of Vaginal Epithelial Cell Multilayer Cultures. PLoS ONE. 2012;7(3):e32728. DOI: https://doi.org/10.1371/journal.pone.0032728Krause M, Wheeler TL, Snyder TE, et al. Local Effects of Vaginally Administered Estrogen Therapy: A Review. Journal of Pelvic Medicine and Surgery. 2009;15(3):105-14. DOI: https://doi.org/10.1097/SPV.0b013e3181ab4804Mirmonsef P, Hotton AL, Gilbert D, et al. Glycogen Levels in Undiluted Genital Fluid and Their Relationship to Vaginal pH, Estrogen, and Progesterone. PLoS ONE. 2016;11(4):e0153553. DOI: https://doi.org/10.1371/journal.pone.0153553Miller L, Patton DL, Meier A, et al. Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstetrics and Gynecology. 2000;96(3):431-9. DOI: https://doi.org/10.1016/S0029-7844(00)00906-6Kaur H, Merchant M, Haque MM, Mande SS. Crosstalk Between Female Gonadal Hormones and Vaginal Microbiota Across Various Phases of Women&rsquo;s Gynecological Lifecycle. Frontiers in Microbiology. 2020;11:551. DOI: https://doi.org/10.3389/fmicb.2020.00551Brotman RM, Shardell MD, Gajer P, et al. Association between the vaginal microbiota, menopause status and signs of vulvovaginal atrophy. Menopause. 2014;21(5):450-8. DOI: https://doi.org/10.1097/GME.0b013e3182a4690bChaban B, Links MG, Jayaprakash TP, et al. Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome. 2014;2(1):23. DOI: https://doi.org/10.1186/2049-2618-2-23Romero R, Hassan SS, Gajer P, et al. The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome. 2014;2(1):18. DOI: https://doi.org/10.1186/2049-2618-2-18Eschenbach DA, Thwin SS, Patton DL, et al. Influence of the Normal Menstrual Cycle on Vaginal Tissue, Discharge, and Microflora. Clinical Infectious Diseases. 2000;30(6):901-7. DOI: https://doi.org/10.1086/313818Morison L, Ekpo G, West B, et al. Bacterial vaginosis in relation to menstrual cycle, menstrual protection method, and sexual intercourse in rural Gambian women. Sexually Transmitted Infections. 2005;81(3):242-7. DOI: http://dx.doi.org/10.1136/sti.2004.011684Roberts SA, Brabin L, Diallo S, et al. Mucosal lactoferrin response to genital tract infections is associated with iron and nutritional biomarkers in young Burkinab&eacute; women. European Journal of Clinical Nutrition. 2019;73(11):1464-72. DOI: https://doi.org/10.1038/s41430-019-0444-7Goodarzi MO, Dumesic DA, Chazenbalk G, et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nature Reviews Endocrinology. 2011;7(4):219-31. DOI: https://doi.org/10.1038/nrendo.2010.217Lindheim L, Bashir M, M&uuml;nzker J, et al. The salivary microbiome in polycystic ovary syndrome (PCOS) and its association with disease-related parameters: a pilot study. Frontiers in Microbiology. 2016;7:1270. DOI: https://doi.org/10.3389/fmicb.2016.01270Lindheim L, Bashir M, M&uuml;nzker J, et al. Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): a pilot study. PLoS ONE. 2017;12(1):e0168390. DOI: https://doi.org/10.1371/journal.pone.0168390Thackray VG. Sex, microbes, and polycystic ovary syndrome. Trends in Endocrinology and Metabolism. 2019;30(1):54-65. DOI: https://doi.org/10.1016/j.tem.2018.11.001Torres PJ, Siakowska M, Banaszewska B, et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. Journal of Clinical Endocrinology and Metabolism. 2018;103(4):1502-11. DOI: https://doi.org/10.1210/jc.2017-02153Chu W, Han Q, Xu J, et al. Metagenomic analysis identified microbiome alterations and pathological association between intestinal microbiota and polycystic ovary syndrome. Fertility and Sterility. 2020;113(6):1286-98. DOI: https://doi.org/10.1016/j.fertnstert.2020.01.027Kriebs A. IL-22 links gut microbiota to PCOS. Nature Reviews Endocrinology. 2019;15(10):565-565. DOI: https://doi.org/10.1038/s41574-019-0255-xRotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and Sterility. 2004;81(1):19-25. DOI: https://doi.org/10.1016/j.fertnstert.2003.10.004Tu Y, Zheng G, Ding G, et al. Comparative Analysis of Lower Genital Tract Microbiome Between PCOS and Healthy Women. Frontiers in Physiology. 2020;11:1108. DOI: https://doi.org/10.3389/fphys.2020.01108Zhang J, Sun Z, Jiang S, et al. Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis [Internet]. mSystems. 2019 Apr 30 [cited 2021 Apr 8];4(2). Available from: https://msystems.asm.org/content/4/2/e00017-19. doi:10.1128/mSystems.00017-19Garc&iacute;a AG, Trevi&ntilde;o MVU, S&aacute;nchez DCV, et al. Diagnostic accuracy of triglyceride/glucose and triglyceride/HDL index as predictors for insulin resistance in children with and without obesity. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 2019;13(4):2329-34. DOI: https://doi.org/10.1016/j.dsx.2019.05.020Радзинский ВЕ, Оразмурадов АА, Оразмурадова ЛД, и др. Беременность ранних сроков. От прегравидарной подготовки к здоровой гестации. 3-е издание. Москва: Общество с ограниченной ответственностью &laquo;Meдиaбюpo Cтaтyс пpeзeнс&raquo;; 2018.Радзинский ВЕ, Ордиянц ИМ, Добрецова ТА. Эндометрий в огне. Острое и хроническое воспаление эндометрия: от новых взглядов к новым стратегиям.StatusPraesens. Гинекология, акушерство, бесплодный брак. 2016;2(31):126-132.Соловьева АВ, Герасимова ОП, Ермоленко КС, и др. Состояние биоценоза у беременных женщин с привычным невынашиванием в анамнезе. Акушерство и гинекология. 2018;10:106-111. DOI: https://doi.org/10.18565/aig.2018.10.106-111Torcia MG. Interplay among Vaginal Microbiome, Immune Response and Sexually Transmitted Viral Infections. International Journal of Molecular Sciences. 2019;20(2):266. DOI: https://doi.org/10.3390/ijms20020266Tsonis O, Gkrozou F, Harrison E, et al. Female genital tract microbiota affecting the risk of preterm birth: What do we know so far? A review. European Journal of Obstetrics, Gynecology and Reproductive Biology. 2020;245:168-73. DOI: https://doi.org/10.1016/j.ejogrb.2019.02.003