Effectiveness of preconceptional preparation in women with early pregnancy loss


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To evaluate the effectiveness of an integrated approach using intravaginal peloid therapy and oral dydrogesterone to improve an outcome in subsequent pregnancy in women with unexplained sporadic loss of early pregnancy. Subjects and methods. A prospective, open-label, randomized study. Randomization was conducted using the envelope technique. The study enrolled 40 reproductive-aged women after sporadic pregnancy loss at less than 12 weeks of gestation. Group 1 consisted of 20 patients who, after spontaneous abortion, received peloid therapy using a gel based on Dead Sea mud. In the third menstrual cycle after abortion, the patients were prescribed 60 ml administered as a single intravaginal injection over 60 minutes for 12 days on days 7-8 of the menstrual cycle. If the period was delayed, a pregnancy test was carried out and when its results were positive, dydrogesterone was prescribed in a daily dose of 20 mg up to 20 weeks’ gestation. After spontaneous abortion, 20 patients in Group 2 underwent traditional rehabilitation, including physiotherapy and vitamin-mineral complexes. Primary and secondary outcomes were evaluated. The primary outcomes were the levels of estradiol (E2) and progesterone (PG), the frequency of ovulatory cycles, and that of recording the full secretory phase (histological examination of the endometrium on day 24 of the fourth menstrual period). The secondary outcomes were the rate of pregnancy during a year after completing rehabilitation, the frequency of recording heartbeats at 12 weeks of gestation, and the rate of live birth.All the patients underwent general clinical and special gynecological examinations. Enzyme immunoassay was used to measure the level of E2 on days 2-5 of the menstrual period and that of PG on days 21-22 of the second and fourth menstrual ones. A test was carried out to detect ovulation. All the patients underwent endometrial biopsy, followed by histological examination, on days 23-24 of the fourth menstrual period. Results. All the patients enrolled in the study completed the planned protocol. The obtained results showed that there were no statistically significant differences in the levels of E2 and PG in the patients of the comparable groups (p>0.05). In the first menstrual period after a miscarriage, anovulation occurred in 15% and 42% of women, respectively; and the inadequate luteal phase (ILP) was observed in 55% and 42% (p=0.003). Three months after a miscarriage, anovulatory cycles were recorded in only the patients (39%) in Group 2 (p=0.008). Pipelle endometrial biopsy showed the presence of a full secretory phase and the correspondence of the endometrium to the phase of the cycle in 55.5% and 16.7% of patients, respectively (p=0.035); ILP in 38.9% and 61.1% and chronic endometritis in 16.7% and 55.5% (p=0.035). During a year after completion of rehabilitation, the occurrence of pregnancy was recorded in 17(85%) women in Group 1 and in 8 (40%) patients in Group 2 (p=0.008). Fetal heart activity was recorded in all these women at 12 weeks’ gestation. There were 16 (80%) and 7 (35%) live births, respectively (p=0.01). The absolute benefit increase (ABI) when applying the integrated approach was 45%. The relative benefit increase (RBI) was 113%. That is, to achieve pregnancy in one woman with sporadic unexplained pregnancy loss within one year, it is necessary to treat two patients in this way. The odds ratio of the probability of obtaining a positive result in the use of peloid therapy versus traditional treatment was 8.50 [1.88-38.47]. Conclusion. Thus, the comprehensive approach including intravaginal peloid therapy at the preconceptional stage and administration of dydrogesterone, when pregnancies of less than 20 weeks’ gestation is recorded, is more effective than the traditional approach and can improve outcomes of subsequent pregnancy in patients with sporadic unexplained pregnancy loss. The combined use of peloid therapy and dydrogesterone contributes to the restoration of the biphasic cycle in patients with a history of early reproductive losses, to the creation of the full secretory phase, to the lower incidence of chronic endometritis, and allows a greater than twofold increase in live birth rates.

Full Text

Restricted Access

About the authors

Natalya V. Artymuk

Kemerovo State Medical University

Email: artymuk@gmail.com
MD, professor, head of the Department of Obstetrics and Gynecology. prof. G. A. Ushakova 650056, Russia, Kemerovo, ul. Voroshilova, d.22a

Irina N. Noskova

S.M. Belyaev Kemerovo Regional Hospital

Email: irnikno@yandex.ru
candidate of medical sciences, obstetrician-gynecologist, gynecological department 650066, Russia, Kemerovo, Oktyabrsky prospekt, d. 22

Olga A. Tachkova

Kemerovo State Medical University

Email: ol.an.t@yandex.ru
candidate of medical sciences, associate professor of the Department of Hospital Therapy and Clinical Pharmacology 650056, Russia, Kemerovo, ul. Voroshilova, d.22a

References

  1. Манухин И.Б., Доброхотова Ю.Э.,Кулешов В.М.,Цхай В.Б., Тапильская Н.И., Рогожина И.Е., Волков В.Г., Буштърева И.О., Базина М.И. Лечение угрожающего выкидыша препаратами микронизированного прогестерона и дидрогестерона (результаты многоцентрового открытого проспективного сравнительного неинтервенционного исследования). Проблемы репродукции. 2018; 24(3): 34-42. https://doi.org/10.m16/repro201824334
  2. Омарпашаева М.И., Абусуева З.А., Хашаева Т.Х-М., Эседова А.Э., Магомедова М.А., Стефанян Н.А., Маммаева С.М. Сочетанное влияние низкочастотной ультразвуковой кавитации и пелоидотерапии на содержание цитокинов и состояние микробиоты половых путей после прерывания неразвивающейся беременности. Проблемы репродукции. 2018; 24(4): 102-7. https://doi.org/10.17116/repro201824041102
  3. Цуригова З.А., Эльдеова К.С., Черникина О.Г., Степанян Л.В., Синчихин С.П. Влияние пелоидотерапии на некоторые показатели местного иммунитета влагалища. Известия Самарского научного центра Российской академии наук. 2015; 17(5-2): 622-6. eLIBRARY ID: 26092441
  4. Белок/иницкая Т.Е., Фролова Н.И., Глотова Е.Ю., Герасимович Н.Б., Мальцева Т.В., Чеузова А.Н., Белозерцева Е.П., Ананьина Д.А. Эффективность интравагинальной пелоидотерапии грязями Мертвого моря у женщин с бесплодием. Практическая медицина. 2015; 6: 30.
  5. Дикке Г.Б. Применение лечебных грязей Мертвого моря у женщин с нарушением репродуктивной функции на фоне хронического эндометрита. Медицинский совет. 2016; 5: 124-7. https://doi.org/10.21518/2079-701X-2016-05-124-127
  6. Carp H.J.A. Progestogens and pregnancy loss. Climacteric. 2018; 21(4): 380-4. doi: 10.1080/13697137.2018.1436166
  7. Schindler A.E. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas. 2009; 65 (Suppl 1): S3-S11. doi: 10.1016/j.maturitas.2009.10.011.
  8. Mirza F.G., Patki A., Pexman-Fieth C. Dydrogesterone use in early pregnancy. Gynecol. Endocrinol. 2016; 32(2): 97-106. doi: 10.3109/09513590. 2015.1121982
  9. Прохоненко Н.Ф. Демографический потенциал: дополнительные аспекты. ОРГЗДРАВ: новости, мнения, обучение. Вестник ВШОУЗ. 2019; 5(2): 22-47. doi: 10.24411/2411-8621-201912002.
  10. Адамян Л.В., Артымук Н.В., Белокриницкая Т.Е., Петрухин В.А., Смольнова Т.Ю., Сутурина Л.В., Тетруашвили Н.К., Филиппов О.С., Чечнева М.А., Шмаков Р.Г. Выкидыши в ранние сроки беременности: диагностика и тактика ведения. Проблемы репродукции. 2018; 24 (S6) : 338-57.
  11. Carp H. A systematic review of dydrogesterone for the treatment of threatened miscarriage. Gynecol Endocrinol. 2012; 28(12): 983-90. doi: 10.3109/09513590.2012.702875.
  12. Lee H.J., Park T.C., Kim H.J., et al. The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and MetaAnalysis. BioMed Research International. 2017; 2017: Article ID 3616875, 10 pp. doi.org/10.1155/2017/3616875
  13. Kumar A., Begum N., Prasad S., Aggarwal S., Sharma S. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril. 2014; 102(5): 1357-63.e3. doi: 10.1016/j.fertnstert.2014.07.1251
  14. Coomarasamy A., Williams H., Truchanowicz E., Seed P.T., Small R., Quenby S., Gupta P., Dawood F, Koot Y.E., Bender A.R., Bloemenkamp K.W., Brady R., Briley A.L., Cavallaro R., Cheong Y.C., Chu J.J., Eapen A., Ewies A., Hoek A., Kaaijk E.M., Koks C.A., Li T.C., MacLean M., Mol B.W., Moore J., Ross J.A., Sharpe L., Stewart J., Vaithilingam N., Farquharson R.G., Kilby M.D., Khalaf Y., Goddijn M., Regan L., Rai R. A Randomized Trial of Progesterone in Women with Recurrent Miscarriages. N Engl J Med. 2015; 373(22): 2141-8. doi: 10.1056/NEJMoa1504927
  15. Coomarasamy A., Devall A.J., Cheed V., Harb H., Middleton L.J., Gallos I.D., Williams H., Eapen A.K., Roberts T., Ogwulu C.C., Goranitis I., Daniels J.P., Ahmed A., Bender-Atik R., Bhatia K., Bottomley C., Brewin J., Choudhary M., Crosfill F., Deb S., Duncan W.C., Ewer A., Hinshaw K., Holland T., Izzat F, Johns J., Kriedt K., Lumsden M.A., Manda P., Norman J.E., Nunes N., Overton C.E., Quenby S., Rao S., Ross J., Shahid A., Underwood M., Vaithilingam N., Watkins L., Wykes C., Horne A., Jurkovic D. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. N Engl J Med. 2019; 380(19): 1815-1824. doi: 10.1056/NEJMoa1813730.
  16. Recurrent pregnancy loss. Guideline of the European Society of Human Reproduction and Embryology 2017. [updated November 2017]. Available at: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrentpregnancy-loss.aspx.
  17. Toth B., Würfel W., Bohlmann M., Zschocke J., Rudnik-Schoneborn S., Nawroth F, Schleufiner E., Rogenhofer N., Wischmann T., von Wolff M., Hancke H., von Otte S., Kuon R., Feil K., Tempfer C. Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050). Geburtshilfe Frauenheilkd. 2019; 79(12):1278-92. doi: 10.1055/a-1017-3389
  18. Tournaye H., Sukhikh G. T., Kahler E., Griesinger G. A Phase III randomized controlled trial comparing the effi cacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in vitro fertilization. Hum Reprod. 2017; 32: 1019-27. URL: http://refhub.elsevier.com/S0015-0282(18)30289-9/sref24. 32.
  19. Griesinger G., Tournaye H. Oral dydrogesterone vs. micronized vaginal progesterone as luteal phase support in IVF: a systematic review and metaanalysis. Abstracts of the 33rd Annual Meeting of ESHRE. Geneva, 2-5 July 2017. P. i289-i90.
  20. Сухих Г.Т., Баранов И.И., Мельниченко Г.А., Башмакова Н.В., Блокилл К., Гризингер Г., Ломакина А.А., Пексман-Фейз К. Lotus I: Рандомизированное III фазы контролируемое исследование сравнения пероральной формы дидрогестерона и вагинальной формы микронизированного прогестерона для поддержки лютеиновой фазы в циклах экстракорпорального оплодотворения, фокус на субанализ российской популяции. Акушерство и гинекология. 2017; 7: 75-95. doi: 10.18565/aig.2017.7.75-95
  21. Носкова И.Н., Артымук Н.В. Эффективность преконцепционной интра-вагинальной пелоидотерапии у женщин с потерей беременности в ранние сроки. Мать и дитя в Кузбассе. 2012; S1: 113-8. eLIBRARY ID: 17683757
  22. Artymuk N.V., Kira E.F., Kondratieva T.A. Intravaginal gel prepared from Dead Sea peloid for treating luteal-phase defect. Int J Gynaecol Obstet. 2010; 108(1): 72-3. doi: 10.1016/j.ijgo.2009.08.027.
  23. Артымук Н.В., Кира Е.Ф., Кондратьева Т.А. Эффективность и безопасность интравагинального применения геля, изготовленного на основе грязи Мертвого моря у женщин с недостаточностью лютеиновой фазы. Журнал акушерства и женских болезней. 2010; 59(4): 24-9.
  24. Белокриницкая Т.Е., Фролова Н.И., Глотова Е.Ю., Герасимович Н.Б., Мальцева Т.В., Чеузова А.Н., Белозерцева Е.П., Ананьина Д.А. Эффективность интравагинальной пелоидотерапии грязями мертвого моря у женщин с бесплодием. Акушерство и гинекология. 2014; 7: 68-73.
  25. Степанян Л.В., Цуригова З.А., Кимаева А.Х., Синчихин С.П. Лечение бактериального вагиноза у женщин с привычной потерей беременности и в климактерии при применении пелоидотерапии. Таврический медико-биологический вестник. 2018; 21(2-2): 135-9.
  26. Ма/инкин И.О., Трунченко Н.В., Волчек А.В., Агеева Т.А., Никитенко Е.В., Макаров К.Ю., Кулешов В.М., Омигов В.В., Айдагулова С.В. Маркеры воспаления в нормальном и тонком эндометрии при хроническом эндометрите. Акушерство и гинекология. 2018; 2: 65-73. doi: 10.18565/aig.2018.2.65-73
  27. Кабулова И.В., Цаллагова Л.В., Майсурадзе Л.В., Пхалагов Р.П., Мирзаева Л.М. Реабилитационные мероприятия у женщин, страдающих привычным невынашиванием беременности, обусловленным истмико-цервикальной недостаточностью. Курортная медицина. 2018; 1: 65-9.
  28. Гатагажева З.М., Льянова З.А., Гатагажева М.М., Узденова З.Х. Роль эндометрия в решении вопроса бесплодия, невынашивания беременности. Дневник казанской медицинской школы. 2017; 2(16): 58-61. eLIBRARY ID: 29322825
  29. Beer A.M., Fetaj S., Lange U. Peloid therapy. An overview of the empirical status and evidence of mud therapy. Z Rheumatol. 2013; 72(6): 581-9. doi: 10.1007/s00393-013-1144-7.
  30. Min K.J., Choi H., Tae B.S., Lee M.G., Lee S.J., Hong K.D. Short-term benefits of balneotherapy for patients with chronic pelvic pain: a pilot study in Korea. J Obstet Gynaecol. 2019 Aug 28:1-6. doi: 10.1080/01443615.2019. 1631771.
  31. Hamed S., Almalty A.M., Alkhatib H.S., Al-Hashimi N.N., Hamed D. Does Salt and Mineral Content of Dead Sea Mud Affect Its Irritation Potential: A Laser Doppler Flowmetry Study. J Cosmet Sci. 2019; 70(5): 259-70.
  32. Al-Karablieh N. Antimicrobial Activity of Bacillus persicus 24-DSM Isolated from Dead Sea Mud. Open Microbiol J. 2017; 11: 372-83. doi: 10.2174/1874285801711010372

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Bionika Media