Micronized progesterone therapy of recurrent pregnancy loss (results of multicenter TRISTAN-1 study)

Galina Mihaylovna Saveleva; Савельева Галина Михайловна; Viktor Alekseevich Aksenenko; Аксененко Виктор Алексеевич; Margarita Darchoevna Andreeva; Андреева Маргарита Дарчоевна; Marina Ivanovna Bazina; Базина Марина Ивановна; Nadezda Vasilievna Bashmakova; Башмакова Надежда Васильевна; Lyudmila Vasilevna Borovkova; Боровкова Людмила Васильевна; Elena Vladimirovna Bryuhina; Брюхина Елена Владимировна; Irina Olegovna Bushtyireva; Буштырева Ирина Олеговна; Valeriy Georgievich Volkov; Волков Валерий Георгиевич; Dmitriy Lvovich Gurev; Гурьев Дмитрий Львович; I. V Dankova; Данькова Ирина Владимировна; Yuliya E. Dobrohotova; Доброхотова Юлия Эдуардовна; Antonina Timofeevna Egorova; Егорова Антонина Тимофеевна; Tatyana Vasilevna Ivanova; Иванова Татьяна Васильевна; Olga Dmitrievna Konstantinova; Константинова Ольга Дмитриевна; Irina Nikolaevna Korotkih; Коротких Ирина Николаевна; Elena Nikolaevna Kravchenko; Кравченко Елена Николаевна; Vladimir Aleksandrovich Kramarskiy; Крамарский Владимир Александрович; Vitaliy Mihaylovich Kuleshov; Кулешов Виталий Михайлович; Elizaveta Yurevna Lebedenko; Лебеденко Елизавета Юрьевна; Larisa Ivanovna Maltseva; Мальцева Лариса Ивановна; Igor Borisovich Manuhin; Манухин Игорь Борисович; Sergey Valerevich Martirosyan; Мартиросян Сергей Валерьевич; Aleksandr Feliksovich Mihelson; Михельсон Александр Феликсович; Anna Aleksandrovna Olina; Олина Анна Александровна; Aleksandr Ivanovich Pashov; Пашов Александр Иванович; Irina Evgenevna Rogozhina; Рогожина Ирина Евгеньевна; Indira Venerovna Sahautdinova; Сахаутдинова Индира Венеровна; Marina Sergeevna Selihova; Селихова Марина Сергеевна; Olga Fedorovna Serova; Серова Ольга Федоровна; Sergey Petrovich Sinchihin; Синчихин Сергей Петрович; Lali Grigorevna Sichinava; Сичинава Лали Григорьевна; Natalia Igorevna Tapilskaya; Тапильская Наталья Игоревна; Vitaliy Borisovich Tshay; Цхай Виталий Борисович; Maria Igorevna Yarmolinskaya; Ярмолинская Мария Игоревна

doi:10.18565/aig.2017.11.44-55

Micronized progesterone therapy of recurrent pregnancy loss (results of multicenter TRISTAN-1 study)

Authors: Saveleva G.M.¹, Aksenenko V.A.², Andreeva M.D.³, Bazina M.I.⁴, Bashmakova N.V.⁵, Borovkova L.V.⁶, Bryuhina E.V.⁷, Bushtyireva I.O.⁸^,9, Volkov V.G.¹⁰, Gurev D.L.¹¹, Dankova I.V¹², Dobrohotova Y.E.¹, Egorova A.T.⁴, Ivanova T.V.¹³, Konstantinova O.D.¹⁴, Korotkih I.N.¹⁵, Kravchenko E.N.¹⁶, Kramarskiy V.A.¹⁷, Kuleshov V.M.¹⁸, Lebedenko E.Y.⁸, Maltseva L.I.¹⁹, Manuhin I.B.²⁰, Martirosyan S.V.²¹, Mihelson A.F.⁸, Olina A.A.²², Pashov A.I.²³, Rogozhina I.E.²⁴, Sahautdinova I.V.²⁵, Selihova M.S.²⁶, Serova O.F.²⁷, Sinchihin S.P.²⁸, Sichinava L.G.¹, Tapilskaya N.I.²⁹, Tshay V.B.³⁰, Yarmolinskaya M.I.³¹^,32
Affiliations:
1. N.I. Pirogov Russian National Research Medical University
2. Stavropol State Medical University
3. Kuban state medical university
4. Krasnoyarsk State Medical University named after prof. V.F. Voyno-Yasenetskii
5. Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia
6. Nizhniy Novgorod State Medical Academy
7. South-Ural State Medical University
8. Rostov State Medical University
9. Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
10. Tula State Medical Institute
11. Yaroslavl State Medical Academy
12. Ural Research Institute for Maternity and Infancy
13. Siberian State Medical University
14. Orenburg State Medical University
15. Voronezh State Medical University
16. Omsk State Medical University
17. Irkutsk State Medical University
18. Novosibirsk State Medical University
19. Kazan State Medical Academy
20. Moscow State University of Medicine and Dentistry
21. Regional perinatal center, Ekaterinburg
22. Academician E.A. Wagner Perm State Medical University
23. Baltic State University named after Immanuel Kant
24. Saratov State Medical University
25. Bashkir State Medical University
26. Volgograd State Medical University
27. Moscow Regional Perinatal Center
28. Astrakhan State Medical University
29. St Petersburg State Pediatric Medical University
30. V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University
31. D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
32. North-Western Federal Medical Research Center, Ministry of Health of Russia
Issue: No 11 (2017)
Pages: 44-55
Section: Articles
URL: https://journals.eco-vector.com/0300-9092/article/view/248064
DOI: https://doi.org/10.18565/aig.2017.11.44-55
ID: 248064

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Subject and methods. The study involved 800 women with recurrent pregnancy loss (2 or more consecutive interruptions of pregnancy in history). 383 patients in group 1 started taking micronized progesterone from pregravid preparation before conception during luteal phase of menstrual cycle and during pregnancy (intravaginally 200- 400 mg per day), 417 pregnant women (group 2) started taking micronized progesterone only after clinical confirmation of pregnancy, from 8 weeks 0 days (intravaginally 200-400 mg per day). Observation of patients of both groups continued in the first half of pregnancy from 8 weeks 0 days until 22 weeks and 0 days of gestation. Current pregnancies were observed during the study: the use of additional drugs, the presence of complications, hospitalizations and their duration, as well as adverse events that occur in patients throughout the observation period. All performed medical research and procedures in the study were routine, used in everyday clinical practice. The statistical analysis of the data was performed using IBM SPSS 23. Results. The main criterion for the therapy effectiveness was prolongation of current pregnancy from 8 weeks 0 days up to 22 weeks 0 days. In group 1 (who had micronized progesterone pregravid preparation), the frequency of pregnancy loss was 2.3%, while in group 2 (who start taking micronized progesterone only after clinical confirmation of pregnancy) - 7.7% (p <0.001). The analysis of the obtained data showed effectiveness and safety of micronized progesterone administration from pregravid stage for the therapy of recurrent pregnancy loss. It can be concluded that the relative risk of interruption of pregnancy decreases with the use of micronized progesterone during pregravid preparation and during pregnancy compared with the use of micronized progesterone only after clinical confirmation of gestation (from 8 weeks 0 days), RR = 0.306 (95% CI 0.148-0.633), p < 0.001. The frequency and nature of adverse events in the groups was statistically comparable (p> 0.05). Conclusion. Results of the study demonstrate effectiveness and safety of micronized progesterone (Utrogestan) administration during pregravid preparation and during pregnancy up to 22 weeks 0 days of gestation in case of recurrent pregnancy loss. The use of micronized progesterone after clinical confirmation of pregnancy (from 8 weeks 0 days) is less effective.

Keywords

recurrent pregnancy loss, habitual miscarriage, micronized progesterone, Utrozestan, pregravid preparation

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Micronized progesterone therapy of recurrent pregnancy loss (results of multicenter TRISTAN-1 study)

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