Integrative evaluation of menstrual blood biomarkers in the diagnosis of endometrial non-tumor pathology

Kachalina T.S., Motovilova T.M., Borovkova L.V., Grechkanev G.O., Ponomareva I.V., Puchkova T.N., Martyantseva I.V., Zamyslova V.P., Zinovyeva O.S., Chikalova K.I., Sirotina L.Z.

1 Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia; 2 «Sadko» Modern Technology Clinic, Nizhny Novgorod, Russia
Objective. To enhance diagnostic accuracy for endometrial competence.
Subjects and methods. A total of 96 patients with a history of reproductive failures were examined. Menstrual blood was analyzed for glutathione peroxidase-1, interleukin-6, and E-selectin, by using a monoclonal antibody-based sandwich ELISA. To determine the regulatory limit values, the material of 30 healthy women was studied. The results were assessed using the logistic regression method. A mathematical model was developed, which could determine the probability of endometrial pathology at the threshold value of the integrative indicator P ≥ 0.29.
Results. Patients with diagnostically significant P levels were observed to have signs of chronic inflammation and dystrophic changes in the endometrium. The mean probability (Pmean) of the disease was 0.59 for patients and 0.22 or healthy women. The diagnostic sensitivity and specificity of the test were 93.3 and 92.86%, respectively.
Conclusion. It is appropriate to calculate the prognostic probability of endometrial pathology, by measuring the concentration of biologically active substances in the menstrual discharge for the primary non-invasive diagnosis of endometrial non-tumor pathology.

Keywords

fertility disorders
non-invasive diagnosis
endometrial pathology
laboratory diagnosis
parameters of menstrual blood

References

  1. Зуев В.М., Калинина Е.А., Александров М.Т., Пиманчева Ю.И. Несостоятельный эндометрий в программах ЭКО: патогенез, диагностика и реабилитация. В кн.: Репродуктивные технологии сегодня и завтра. Материалы XXV Юбилейной международной конференции Российской Ассоциации Репродукции Человека. 9-12 сентября 2015 г., г. Сочи. 2015: 47-9. [Zuev V.M., Kalinina E.A., Aleksandrov M.T., Pimancheva Yu.I. Insolvent endometrium in IVF programs: pathogenesis, diagnosis and rehabilitation. In the book: Reproductive technologies today and tomorrow. Materials of the XXV Anniversary International Conference of the Russian Association of Human Reproduction. September 9-12, 2015, Sochi. 2015: 47-9.(in Russian)].
  2. Маринкин И.О., Кулешов В.М., Илизарова Н.А., Айдагулова С.В., Непомнящих Г.И. Атрофия эндометрия как проявление синдрома регенераторно-пластической недостаточности при привычном невынашивании беременности. Вестник Российского университета дружбы народов. Серия: Медицина. 2012; 5: 223-30. [Marinkin I.O., Kuleshov V.M., Ilizarova N.A., Aidagulova S.V., Nepomnyaschik G.I. Endometrial atrophy as a manifestation of the syndrome of regenerative-plastic insufficiency with habitual miscarriage. Bulletin of Peoples’ Friendship University of Russia. Series: Medicine. 2012; 5: 223-30. (in Russian)].
  3. Волкова Е.Ю., Силантьева Е.С., Корнеева И.Е. Роль физиотерапии в коррекции нарушений маточной гемодинамики у женщин с нарушением репродуктивной функции и «тонким» эндометрием. В кн.: Здоровье девочки, девушки, женщины. Материалы Всероссийской научно-практической конференции. Томск, 4-5 декабря 2012. Томск: НИИАГиП СО РАМН; 2012: 8-10. [Volkova E.Yu., Silantieva E.S., Korneeva I.E. The role of physiotherapy in the correction of uterine hemodynamic disorders in women with impaired reproductive function and «thin» endometrium. In the book: Health girls, girls, women. Materials of the All-Russian scientific-practical conference. Tomsk, December 4-5, 2012. Tomsk: NIIAGiP SB RAMS; 2012: 8-10. (in Russian)].
  4. Кузнецова И.В., Землина Н.С., Рашидов Т.Н., Коваленко М.А. Проблема тонкого эндометрия и возможные пути ее решения. Эффективная фармакотерапия. 2015; 5: 42-9. [Kuznetsova I.V., Zemlina N.S., Rashidov T.N., Kovalenko M.A. The problem of thin endometrium and possible solutions. Effective pharmacotherapy. 2015; 5: 42-9. (in Russian)].
  5. Лызикова Ю.А. Хронический эндометрит как причина нарушений репродуктивной функции у женщин. Проблемы здоровья и экологии. 2015; 3: 9-16. [Lyzikova Yu.A. Chronic endometritis as a cause of impaired reproductive function in women. Health and ecology problems. 2015; 3: 9-16. (in Russian)].
  6. Viana G.A., Cela V., Ruggiero M., Pluchino N., Genazzani A.R., Tantini C. Endometritis in infertile couples: the role of hysteroscopy and bacterial endotoxin. JBRA Assist. Reprod. 2015; 19(1): 21-3.
  7. Козырева Е.В., Давидян Л.Ю. Иммуногистохимические особенности хронического эндометрита при бесплодии и невынашивании беременности (обзор литературы). Известия высших учебных заведений. Поволжский регион. Медицинские науки. 2015; 4: 124-36. [Kozyreva Ye.V., Davidyan L YU. Immunohistochemical features of chronic endometritis with infertility and miscarriage (literature review). Proceedings of higher educational institutions. Volga region. Medical sciences. 2015; 4: 124-36.(in Russian)].
  8. Gleicher N., Kim A., Michaeli T., Lee H.J., Shohat-Tal A., Lazzaroni E., Barad D.H. A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies. Hum. Reprod. 2013; 28(1): 172-7.
  9. Cicinelli E., Matteo M., Tinelli R., Lepera A., Alfonso R., Indraccolo U. et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum. Reprod. 2015; 30(2): 323-30.
  10. Kasius A., Smit J.G., Torrance H.L., Eijkemans M.J., Mol B.W., Opmeer B.C., Broekmans F.J. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum. Reprod. Update. 2014;20(4): 530-41.
  11. Yoshii N., Hamatani T., Inagaki N., Hosaka T., Inoue O., Yamada M. et al. Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity. Reprod. Biol. Endocrinol. 2013; 11: 37.
  12. Рудакова Е.Б., ред. Внутриматочная патология: клиника, гистероскопическая диагностика и лечение. Учебно-методическое пособие. М.: МЕДпресс-информ; 2011. [Rudakova EB, ed. Intrauterine pathology: clinic, hysteroscopic diagnosis and treatment. Teaching manual. M .: MEDpress-inform; 2011. (in Russian)].
  13. Гомболевская Н.А., Марченко Л.А. Современные критерии диагностики хронического эндометрита (обзор литературы). Проблемы репродукции. 2012; 18(1): 42-6. [Modern criteria for the diagnosis of chronic endometritis (literature review). Reproduction problems. 2012; 18 (1): 42-6(in Russian)].
  14. Краснопольский В.И., Логутова Л.С., Зароченцева Н.В., Дуб Н.В., Титченко Ю.П., Овчинникова В.В., Меньшикова Н.С., Аршакян А.К., Ушакова С.В. Прегравидарная подготовка женщин с невынашиванием беременности и хроническим эндометритом. Учебное пособие. М.; 2014. [Krasnopol’skiy V.I., Logutova L.S., Zarochentseva N.V. i dr. Pregravid training of women with miscarriage and chronic endometritis. Tutorial. M .; 2014. (in Russian)].
  15. Мотовилова Т.М., Качалина Т.С., Гречканев Г.О., Боровкова Л.В., Зиновьев А.Н., Николаева О.А. Пономарева И.В., Замыслова В.П., Пучкова Т.Н., Стройкова К.И., Горхелашвили Л.З., Козлова Н.А. Определение биомаркеров в менструальной крови как возможность неинвазивной диагностики воспалительного процесса в полости матки. Медицинский альманах. 2016; 5: 88-91. [Motovilova T.M., Kachalina T.S.,
  16. Grechkanev G.O., Borovkova L.V., Zinov’yev A.N., Nikolayeva O.A., Ponomareva I.V., Zamyslova V.P., Puchkova T.N., Stroykova K.I., Gorkhelashvili L.Z., Kozlova N.A. Determination of biomarkers in menstrual blood as the possibility of non-invasive diagnosis of the inflammatory process in the uterine cavity. Medical Almanac. 2016; 5: 88-91.(in Russian)].
  17. Патент № 2587720 РФ от 17.08.2017. Зоева А.Р., Дикарева Л.В., Теплый Д.Л., Аюпова А.К. «Способ диагностики хронического эндометрита у женщин с аномальными маточными кровотечениями». Заявлено 12.08.2014; Опубликовано 20.06.2016. [Zoyeva A.R., Dikareva L.V., Teplyy D.L., Ayupova A.K. Patent RF № 0002587720 from 17.08.2017
  18. «A method for the diagnosis of chronic endometritis in women with abnormal uterine bleeding». (in Russian)].
  19. Дикарева Л.В., Аюпова А.К., Ажалилова А.Р., Уханова Ю.Ю., Джальмуханбетов Т.С. Диагностическая ценность исследования морфологии менструальных выделений в гинекологической практике. В кн.: Тезисы VI Общероссийского научно-практического семинара «Репродуктивный потенциал России: версии и контраверсии». 7-10 сентября 2013г. Сочи. 2013: 24-5. [Dikareva L.V., Ayupova A.K., Azhalilova A.R., Ukhanova Yu.Y., Dzhalmukhanbetov T.S. The diagnostic value of the study of the morphology of menstrual flow in gynecological practice. In the book: Abstracts of the VIth All-Russian Scientific and Practical Seminar «Reproductive Potential of Russia: Versions and Contraversion». September 7-10, 2013 Sochi. 2013: 24-5. (in Russian)].
  20. Tortorella C., Piazzolla G., Matteo M., Pinto V., Tinelli R., Sabb С. et al. Interleukin-6, interleukin-1β, and tumor necrosis factor in menstrual effluents as biomarkers of chronic endometritis. Fertil. Steril. 2014; 101(1): 242-7.
  21. Богданов Л.Ю. Оценка эффективности бинарных классификаторов на основе логистической регрессии методом ROC-анализа. Вестник Саратовского государственного технического университета. 2010; 2: 92-7. [Bogdanov L.Yu. Evaluating the effectiveness of binary classifiers based on logistic regression using ROC analysis. Bulletin of the Saratov State Technical University. 2010; 2: 92-7. (in Russian)].

Received 06.09.2018

Accepted 22.09.2018

About the Authors

Kachalina, Tatyana S., PhD, professor of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia, doctor of the highest qualification category, honored doctor of the Russian Federation.
603126, Russia, N.Novgorod, Rodionov str. 190, Department of Obstetrics and Gynecology. Tel.: +79519065830. E-mail: yander24@bk.ru
Motovilova, Tatyana M., PhD, associate professor of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia, doctor of the highest qualification category.
603126, Russia, N. Novgorod, Rodionov str. 190. Tel.: +79519088937. E-mail: tatyana.m.motovilova@gmail.com
Borovkova, Lyudmila V., PhD, professor, doctor of the highest qualification category, head of the Department of the Department of Obstetrics and Gynecology,
Volga Regional Research Medical University, Ministry of Health of the Russian Federation.
603126, Russia, N. Novgorod, Rodionov str. 190.
Grechkanev, Gennadiy O., PhD, professor of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation. 603126, Russia, N. Novgorod, Rodionov str. 190.
Ponomareva, Irina V., obstetrician-gynecologist of the highest qualification category, chief doctor of the Sadko Clinic of Modern Technologies LLC.
603057, Russia, N. Novgorod, Beketov str. 13. Tel.: +79519053326. E-mail: Ponomareva_irina_70@mail.ru
Puchkova, Tat’yana N., doctor of laboratory diagnostics LLC Sadko Clinic of Modern Technologies.
603057, Russia, N. Novgorod, Beketov str. 13. Tel.: +7908 7338514. E-mail: sadko.lab@yandex.ru
Martyantseva, Irina V., doctor of laboratory diagnostics LLC Sadko Clinic of Modern Technologies.
603057, Russia, N. Novgorod, Beketov str. 13. Tel.: +7960 1779585. E-mail: martyantseva1989@mail.ru
Zamyslova, Valentina P., obstetrician-gynecologist at the Health Center, correspondence postgraduate student of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation.
603126, Russia, N. Novgorod, Rodionov str. 190. Тel.: +79506224575. E-mail: zamyslowa.valentina@yandex.ru
Zinovyeva, Olga S., assistant of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation. 603126, Russia, N. Novgorod, Rodionov str. 190. Tel.: +79081538583. E-mail: zamashkina87@mail.ru
Chikalova, Kseniya I., postgraduate student of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation. 603126, Russia, N. Novgorod, Rodionov str. 190. Tel.: +79087291196. E-mail: k.stroikova@yandex.ru
Sirotina, Liya Z., resident of the Department of Obstetrics and Gynecology, Volga Regional Research Medical University, Ministry of Health of the Russian Federation.
603126, Russia, N. Novgorod, Rodionov str. 190. Tel.: +79081628760. E-mail: liya.z.sirotina@bk.ru

For citation: Kachalina T.S., Motovilova T.M., Borovkova L.V., Grechkanev G.O., Ponomareva I.V., Puchkova T.N., Martyantseva I.V., . Zamyslova V.P., Zinovyeva O.S., Chikalova K.I., Sirotina L.Z. Integrative evaluation of menstrual blood biomarkers in the diagnosis of endometrial non-tumor pathology. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2019; (3): 121-6. (in Russian)
https://dx.doi.org/10.18565/aig.2019.3.121-126

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