Hyperandrogenism as a risk factor for isthmic-cervical insufficiency

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Abstract

Objective: To assess the association of isthmic-cervical insufficiency (ICI) with hyperandrogenism (HA).

Materials and methods: A prospective cohort controlled study was performed (the study period was 2014–2019). The clinical base was Maternity Hospital One, Branch, L.A. Vorokhobov City Clinical Hospital Sixty-Seven (Moscow). The study involved 98 women, including 63 with ICI (a study group) and 35 without ICI (a control group). HA was evaluated by high-performance liquid chromatography according to the steroid profile and quantitative determination of urinary steroids. The data were statistically analyzed using the programs of Microsoft Excel 2007, Statistica 12.0. The association of HA with ICI was assessed.

Results: Regardless of the presence of HA, ICI is associated with the factors of a compromised reproductive history (the number of pregnancies, р=0.00008; the term of premature birth (р=0.04); with the frequency of miscarriage (р<0.001); with the experience in using cerclage (р=0.49); with the pregestational weight exceeding the norm (OR=4.16; 95% CI, 1.32–13.31)). ICI is associated with HA (OR=3.48; 95% CI, 1.37–8.84). HA in the women with ICI is associated with an earlier age at menarche (р=0.01) and an older age during the current pregnancy (p=0.002).

The gestational risk factors of HA-associated ICI are shown to be the absence of progesterone therapy in the preconception period/the first trimester of pregnancy (ОR=10.23; 95% CI. 1.12–93.35); the greater frequency of threatening spontaneous abortion (SA) (OR=5.38; 95% CI 1.83–15.79); that of imminent SA (p=0.01); the length of the cervix is 10 mm or less; ICI totals more than 6 scores; the significantly earlier gestational period in the diagnosis of ICI (19 weeks or less).

Conclusion: The asymptomatic onset of ICI cannot implement modern prevention, limits the possibilities of medical management. Prescribing progesterones to woman with HA in the preconceptional period/the first trimester of pregnancy should be considered as a measure for the prevention of ICI.

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About the authors

Sergey A. Levakov

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Author for correspondence.
Email: levakoff@yandex.ru

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology of the N.V. Sklifosovsky Institute of Clinical Medicine

Russian Federation, Moscow

Artur V. Mokh

Perinatal Center, M.P. Konchalovsky City Clinical Hospital, Moscow City Healthcare Department

Email: mohar2205@mail.ru

Head of the Maternity Department

Russian Federation, Moscow

References

  1. ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency. American College of Obstetricians and Gynecologists. Obstet. Gynecol. 2014; 123(2, Pt 1): 372-9. https://dx.doi.org/10.1097/ 01.AOG.0000443276.68274.cc.
  2. Информационное письмо МАРС по клиническим рекомендациям «Истмико-цервикальная недостаточность» [Текст]: Направлены письмом Минздрава России от 28 декабря 2018 года №15-4/10/2-7991. М.: Редакция журнала StatusPraesens; 2019. 52c. [MARS Informational letter on clinical recommendations " Isthmic-cervical insufficiency»: Sent by letter of the Ministry of health of the Russian Federation dated 28 December 2018 no 15-4/10/2-7991. Moscow: Editorial office of StatusPraesens; 2019. 52p. (in Russian)].
  3. Brown R., Gagnon R., Delisle M.F. No. 373-сervical insufficiency and cervical cerclage. J. Obstet. Gynaecol. Can. 2019; 41(2): 233-47. https://dx.doi.org/10.1016/j.jogc.2018.08.009.
  4. South Australian Perinatal Practice Guidelines. Cervical Insufficiency and Cerclage. 2017. 13 р.
  5. Diagnosis and Management of Cervical Insufficiency GLM0055. Maternity Guidelines Group Christchurch Women’s Hospital. New Zealand. 2017. 8 р.
  6. Шалина Р.И. Коррекция истмико-цервикальной недостаточности. Акушерство и гинекология: новости, мнения, обучение. 2015; 1(7): 40-3. [Shalina R.I. Correction of isthmic-cervical insufficiency. Obstetrics and Gynecology: News, Opinions, Training. 2015; 1(7): 40-3. (in Russian)].
  7. Луценко Л.А. Надпочечниковые гиперандрогении: мультидисциплинарный подход к решению проблемы. Международный эндокринологический журнал. 2016; 8: 29-34. [Lutsenko L.A. Adrenal hyperandrogenism: a multidisciplinary approach to solving the problem. International Journal of Endocrinology. 2016; (8): 29-34. (in Russian)].
  8. Доброхотова Ю.Э., Рагимова З.Э., Ильина И.Ю., Ибрагимова Д.М. Гиперандрогения и репродуктивное здоровье женщины. М.: ГЭОТАР-Медиа; 2015. 140c. [Dobrokhotova Yu.E., Ragimova Z.E., Ilyina I.Yu., Ibragimova D.M. Hyperandrogenism and reproductive health of women. Moscow: GEOTAR-Media; 2015. 140p. (in Russian)].
  9. Mossa F., Latham K.E., Ireland J.J., Veiga-Lopez A. Undernutrition and hyperandrogenism during pregnancy: Role in programming of cardiovascular disease and infertility. Mol. Reprod. Dev. 2019; 86(9): 1255-64. https://dx.doi.org/10.1002/mrd.23239.
  10. Makieva S., Saunders P.T.K., Norman J.E. Androgens in pregnancy: roles in parturition. Hum. Reprod. Update. 2014; 20: 542-59.
  11. Fornes R., Maliqueo M., Hu M., Hadi L., Jimenez-Andrade J.M., Ebefors K. et al. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams. Sci. Rep. 2017; 7(1): 8066. https://dx.doi.org/10.1038/s41598-017-08559-w.
  12. Kumar S., Gordon G., Abbott D., Mishra J. Androgens in maternal vascular and placental function: implications for preeclampsia pathogenesis. Reproduction. 2018; 156(5): R155-67.
  13. Sherman S.B., Sarsour N., Salehi M., Schroering A., Mell B., Joe B., Hill J.W. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes. 2018; 9(5): 400-21. https://dx.doi.org/10.1080/19490976. 2018.1441664.
  14. Semeniuk L.M., Likhachov V.K., Yuzvenko T.Y., Dobrovolska L.М., Makarov O.G. Risk markers of reproductive loss in women with hyperandrogenism. Wiad. Lek. 2018; 71(8): 1550-3.
  15. Hu M., Zhang Y., Guo X., Jia W., Liu G., Zhang J. et al. Hyperandrogenism and insulin resistance induce gravid uterine defects in association with mitochondrial dysfunction and aberrant reactive oxygen species production. Am. J. Physiol. Endocrinol. Metab. 2019; 316(5): E794-E809. https://dx.doi.org/10.1152/ajpendo.00359.2018.
  16. Hakim Ch., Padmanabhan V., Vyas A.K. Gestational hyperandrogenism in developmental pro-gramming. Endocrinology. 2017; 158(2): 199-212. https://dx.doi.org/10.1210/en.2016-1801.
  17. Синдром поликистозных яичников в репродуктивном возрасте (современные подходы к диагностике и лечению). Клинические рекомендации (Протокол лечения). М.; 2015. 22с. [Polycystic ovary syndrome in reproductive age (modern approaches to diagnosis and treatment). Clinical guidelines (Treatment Protocol). Moscow; 2015. 22p. (in Russian)].
  18. Johnson T., Kaplan L., Ouyang P., Rizza R. National Institutes of Health Evidence-Based Methodology Workshop on Polycystic Ovary syndrome. National Institutes of Health Bethesda: National Institutes of Health; 2012: 1-14.
  19. Cheng J., Wu H., Liu H., Li H., Zhu H., Zhou Y. et al. Exposure of hyperandrogen during pregnancy causes depression- and anxiety-like behaviors, and reduced hippocampal neurogenesis in rat offspring. Front. Neurosci. 2019; 13: 436. https://dx.doi.org/10.3389/fnins.2019.00436.
  20. Адамян Л.В., Андреева Е.Н., Абсатарова Ю.С., Григорян О.Р., Дедов И.И., Мельниченко Г.А., Сутурина Л.В., Филиппов О.С., Шереметьева Е.В., Чернуха Г.Е., Ярмолинская М.И. Клинические рекомендации «Синдром поликистозных яичников». Проблемы эндокринологии. 2022; 68(2): 112-27. [Adamyan L.V., Andreeva E.N., Absatarova Yu.S., Grigoryan O.R., Dedov I.I., Melnichenko G.A., Suturina L.V., Filippov O.S., Sheremetyeva E.V., Chernukha G.E., Yarmolinskaya M.I. Clinical guidelines «Polycystic Ovary syndrome». Problems of Endocrinology. 2022; 68(2): 112-27.(in Russian)].
  21. Zawadski J.K., Dunaif A. Diagnostic criteria for Polycystic Ovary syndrome: towards a rational approach. In: Dunaif A., Givens J.R., Haseltine F.P., Merriam G.R., eds. Polycystic Ovary syndrome. Boston: Blackwell Scientific Publications; 1992: 377-84.
  22. International evidence-based guideline for the assessment and management of Polycystic Ovary Syndrome (PCOS). 2018. Available at: https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS_Evidence-Based-Guidelines_20181009.pdf Accessed 10 June 2020.
  23. Айламазян Э.К., Кулаков В.И., Радзинский В.Е., Савельева Г.М., ред. Акушерство. Национальное руководство. М.: ГЭОТАР-Медиа; 2014. 1200 с. [Ailamazyan A.K., Kulakov V.I., Radzinsky V.E., Saveleva G.M., ed. Obstetrics: National guidance. Moscow: GEOTAR-Media; 2014. 1200p. (in Russian)].
  24. Леваков С.А., Габитова Н.А. Система гемостаза у беременных с гиперандрогенией. Лечение и профилактика. 2015; 2: 20-3. [Levakov S.A., Gabitova N.A. Hemostasis system in pregnant women with hyperandrogenism. Treatment and Prevention. 2015; (2): 20-3. (in Russian)].
  25. Мельниченко Г.А., Трошина Е.А., Молашенко Н.В., Сазонова А.И., Ужегова Ж.А. Клинические рекомендации Российской ассоциации эндокринологов по диагностике и лечебно-профилактическим мероприятиям при врожденной дисфункции коры надпочечников у пациентов во взрослом возрасте. Consilium Medicum. 2016; 4: 8-19. [Melnichenko G.A., Troshina E.A., Molashenko N.V., Sazonova A.I., Uzhegova Z.A. Russian Association of Endocrinologists clinical practice guidelinesfor diagnosis, treatment and preventive measures in congenital adrenal hyperplasia due to 21-hydroxylase deficiency patients in adulthood. Consilium Medicum. 2016; (4): 8-19. (in Russian)].
  26. Меликова А.В. Гиперандрогения: мифы и реальность. Эффективная фармакотерапия. 2018; 3: 40-5. [Melikova A.V. Hyperandrogenism: mythsandreality. Effective Pharmacotherapy. 2018; (3): 40-5. (in Russian)].
  27. Malinowski A.K., Sen J., Sermer M. Hyperreactio luteinalis: maternal and fetal effects. J. Obstet. Gynaecol. Can. 2015; 37(8): 715-23. https://dx.doi.org/10.1016/S1701-2163(15)30176-6.
  28. Yang C., Wang H., Zou Y., Cui W., Yang J., Li T., Li C., Jiang J. Hyperreactio luteinalis after delivery: a case report and literature review. Int. J. Clin. Exp. Med. 2015; 8(4): 6346-8.
  29. Palomba S., de Wilde M.A., Falbo A., Koster M.P., La Sala G.B., Fauser B.C. Pregnancy complications in women with polycystic ovary syndrome. Hum. Reprod. Update. 2015; 21(5): 575-92. https://dx.doi.org/10.1093/humupd/dmv029.
  30. Stangler Herodež Š., Fijavž L., Zagradišnik B., Kokalj Vokač N. Detection of mutations in the CYP21A2 gene: genotype-phenotype correlation in Slovenian couples with conceiving problems. Balkan J. Med. Genet. 2016 ; 18(2): 25-32.
  31. Edell H., Shearkhani O., Rahmani M.R., Kung R.C. Incidentally found hyperreactioluteinalis in pregnancy. Radiol. Case Rep. 2018; 13(6): 1220-3. https://dx.doi.org/10.1016/j.radcr.2018.08.022.
  32. Wei D.M., Zhang Z.Z., Wang Z., Li P., Wang J.F., Liu Y.J. et al. Effect of hyperandrogenism on obstetric complications of singleton pregnancy from in vitro fertilization in women with polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2018; 53(1): 18-22. (in Chinese). https://dx.doi.org/10.3760/cma.j.issn.0529-567X.2018.01.005.
  33. Gomes L.G., Bachega T.A.S.S., Mendonca B.B. Classic congenital adrenal hyperplasia and its impact on reproduction. Fertil. Steril. 2019; 111(1): 7-12. https://dx.doi.org/10.1016/j.fertnstert.2018.11.037.
  34. Kocova M., Anastasovska V., Bitovska I. The impact of CYP21A2 (P30L/I172N) genotype on female fertility in one family. Eur. J. Med. Res. 2019; 24: 21. https://dx.doi.org/10.1186/s40001-019-0379-4.
  35. Thurston L., Abbara A., Dhillo W.S. Investigation and management of subfertility. J. Clin. Pathol. 2019; 72(9): 579-87. https://dx.doi.org/10.1136/jclinpath-2018-205579.
  36. Schwandner A., Zámečník M., Kaščák P. Hyperreactio luteinalis - two accidental findings during cesarean section. Ceska Gynekol. 2019; 84(6): 439-42.
  37. Wang Y., Gu X., Tao L., Zhao Y. Co-morbidity of cervical incompetence with polycystic ovarian syndrome (PCOS) negatively impacts prognosis: A retrospective analysis of 178 patients. BMC Pregnancy Childbirth. 2016; 16(1): 308.
  38. Kandeel M.S., Sanad Z.F., Sayyed T.M., Elyazid Elmenawy S.A. The effect of body mass index on cervical characteristics and on the length of gestation in low-risk pregnancies. Menoufia Med. J. 2014; 27 :518-23.
  39. Prodromidou A., Frountzas M., Perrea D., Vlachos G.D., Pergialiotis V. The impact of obesity on cervical cerclage efficacy: A systematic review of the literature. J. Neonatal. Perinatal. Med. 2016; 9(1): 59-65. https://dx.doi.org/10.3233/NPM-16915058.
  40. Zaher Y.A., Al-Kholy A.F. Cervicovaginal inflammatory cytokines, obesity and inter-pregnancy interval negatively affect pregnancy duration in pregnant women at high-risk for recurrent spontaneous preterm birth. Adv. Reprod. Sci. 2019; 7: 125-37. https://dx.doi.org/10.4236/arsci.2019.74014.
  41. Venkatesh K.K., Cantonwine D.E., Zera C., Arjona M., Smith N.A., Robinson J.N., McElrath T.F. Is there an association between body mass index and cervical length? Implications for obesity and cervical length management in pregnancy. Am. J. Perinatol. 2017; 34(6): 568-75. https://dx.doi.org/10.1055/s-0036-1594242.
  42. Иловайская И.А. Влияние ожирения у женщин на фертильность и вынашивание беременности. РМЖ. 2016; 1: 32-7. [Ilovaiskaya I.A. Influence of obesity in women on fertility and pregnancy. Russian Medical Journal. 2016; (1): 32-7. (in Russian)].
  43. Радынова С.Б., Иванова Е.А. Осложнение беременности и родов у женщин с ожирением. Современные проблемы науки и образования. 2018; 5: 45. [Radynova S.B., Ivanova E.A. Complication of pregnancy and childbirth in women with obesity. Modern problems of science and education. 2018; (5): 45. (in Russian)].
  44. Радзинский В.Е., Фукс А.М., ред. Акушерство. Учебник. М.: ГОЭТАР-Медиа; 2016. 1040с. [RadzinskyV.E., FuksA.M., eds. Obstetrics. Textbook. Moscow: GOETAR-Media; 2016. 1040p. (in Russian)].
  45. Жабченко И.А., Коваленко Т.Н., Сюдмак О.Р. Пути минимизации акушерских рисков у беременных с ожирением. Охрана материнства и детства. 2016; 2: 69-75. [Zhabchenko I.A., Kovalenko T.N., Sudmak O.R. The ways of obstetrical risks minimization in pregnant women with obesity. Protection of Motherhood and Childhood. 2016; (2): 69-75. (in Russian)].
  46. Доброхотова Ю.Э., Боровкова Е.И., Залесская С.А., Нагайцева Е.А., Раба Д.П. Диагностика и тактика ведения пациенток с истмико-цервикальной недостаточностью. Гинекология. 2018; 2: 41-5. [Dobrokhotova Yu.E., Borovkova E.I., Zalesskaya S.A., Nagaitseva E.A., Raba D.P. Diagnosis and management of patients with isthmic-cervical insufficiency. Gynecology. 2018; (2): 41-5. (in Russian)].
  47. Белова И.С., Хащенко Е.П., Уварова Е.В. Современные аспекты роли инсулинорезистентности, системного воспаления и оксидативного стресса в патогенезе гиперандрогении и нарушений фолликулогенеза у пациенток с синдромом поликистозных яичников. Акушерство и гинекология. 2021; 5: 55-63. [Belova I.S., Khashchenko E.P., Uvarova E.V. Current aspects of the role of insulin resistance, systemic inflammation, and oxidative stress in the pathogenesis of hyperandrogenism and abnormal folliculogenesis in patients with polycystic ovary syndrome. Obstetrics and Gynecology. 2021; (5): 55-63. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.5.55-63.
  48. Чернуха Г.Е., Найдукова А.А., Каприна Е.К., Донников А.Е. Молекулярно-генетические предикторы формирования синдрома поликистозных яичников и его андрогенных фенотипов. Акушерство и гинекология. 2021; 4: 120-7. [Chernukha G.E., Naidukova A.A., Kaprina E.K., Donnikov A.E. Molecular genetic predictors of polycystic ovary syndrome and its androgenic phenotypes. Obstetrics and Gynecology. 2021; (4): 120-7. (in Russian)]. https://dx.doi.org/10.18565/aig.2021.4.120-127.

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