Outcomes of the second half of pregnancy in patients with recurrent pregnancy loss (results of multicenter study of TRISTAN-2)
Objective. To assess obstetric and neonatal outcomes of the second half of pregnancy (after 22 weeks) in women with a habitual miscarriage who received or did not receive periconceptional care and therapy with micronized progesterone (a pharmaceutical product of Utrogestan) in the framework of TRISTAN-2 multicenter study.Saveleva G.M., Aksenenko V.A., Andreeva M.D., Bazina M.I., Bashmakova N.V., Borovkova I.V., Bryuhina E.V., Bushtyireva I.O., Volkov V.G., Gurev D.L., Dankova I.V., Dobrohotova Yu.E., Egorova A.T., Ivanova T.V., Konstantinova O.D., Korotkih I.N., Kravchenko E.N., Kramarskiy V.A., Kuleshov V.M., Lebedenko E.Yu., Maltseva L.I., Manuhin I.B., Martirosyan S.V., Mihelson A.F., Olina A.A., Pashov A.I., Rogozhina I.E., Sahautdinova I.V., Selihova M.S., Serova O.F., Sinchihin S.P., Sichinava L.G., Tapilskaya N.I., Tshay V.B., Yarmolinskaya M.I.
Materials and methods. A total of 743 women who are 22–24 weeks pregnant and diagnosed with habitual miscarriage (2 or more consecutive interruptions of pregnancy in anamnesis) took part in the study. All patients included in TRISTAN-2 study, previously participated in TRISTAN-1 study (TRISTAN-2 study is a continuation of TRISTAN-1 patients’ observation). Of these, 369 patients in Group 1 received periconceptional care with micronized progesterone before conception in the luteal phase of their menstrual cycle and during the first half of pregnancy (intravaginally 200–400 mg / day), 374 patients in Group 2 started taking micronized progesterone only after the clinical confirmation of pregnancy and during the first half of pregnancy (intravaginally 200–400 mg / day). All patients underwent micronized progesterone therapy in the second half of pregnancy (intravaginally 200–400 mg / day) with the appropriate indications described in the instructions for the medical use of Utrogestan). The monitoring of patients in both groups was carried out in late pregnancy (starting from 22 weeks 0 days before discharge from the hospital after delivery). The study collected data on the course of the current pregnancy and its outcomes: gestational age at the time of delivery, neonatal outcomes, use of additional medications, complications and hospitalizations during pregnancy, adverse events on the part of the mother and/or fetus/child during the whole period of observation. All medical procedures performed as part of the study were routine and used in everyday clinical practice. Statistical analysis of the collected data was carried out using IBM SPSS 23 software.
Results. The main criterion for the therapy effectiveness was the frequency of preterm delivery before 34 full weeks of pregnancy. In Group 1 (patients who underwent periconceptional therapy with micronized progesterone), the incidence of preterm delivery was 8.9% (2.0% of preterm deliveries in the period of ≤33+6 weeks), in Group 2 (patients who started taking micronized progesterone only after the clinical confirmation of pregnancy) the incidence was 9.6% (1.7% of preterm deliveries in the period of ≤33+6 weeks) p> 0,05, which corresponds to the general population level in the world. Very early (before 28 weeks) and early
(28-30+6 weeks) premature births in the groups were not observed. On this basis, it can be concluded that the use of micronized progesterone in accordance with approved indications is an effective tool for the prevention of preterm delivery in patients at risk of a habitual miscarriage, regardless of previous periconceptional therapy. The frequency and nature of adverse events were statistically comparable in the groups (p> 0.05).
Conclusion. The presented results of the study prove the efficacy and safety of the use of micronized progesterone (the pharmaceutical product of Utrogestan) in accordance with the recorded indications in late pregnancy with a habitual miscarriage.
Keywords
habitual abortion
habitual miscarriage
micronized progesterone
preterm delivery
Utrogestan
periconceptional care
References
1. Манухин И.Б., Силаев К.А., Вученович Ю.Д. Влияние современной методики дородовой психопрофилактической подготовки беременных и альтернативных способов вагинального родоразрешения на течение и исход родов. Акушерство и гинекология. 2018; 2: 115-9. [Manukhin I.B., Silaev K.A., Vuchenovich U.D. Influence of modern methods of prenatal psychoprophylactic preparation of pregnant women and alternative methods of vaginal delivery on the course and outcome of labor. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (2): 115-9. (in Russian)] https://dx.doi.org/10.18565/aig.2018.2.115-119
2. Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil. Steril. 2013; 99(1): 63.
3. Савельева Г.М., Сухих Г.Т., Серов В.Н., Радзинский В.Е., ред. Акушерство. Национальное руководство. 2-е изд. М.: ГЭОТАР-Медиа; 2015: 189-98. [Savelyeva G.M., Sukhikh G.T., Serov V.N., Radzinsky V.E., ed. Obstetrics. National guideline. 2nd ed. Moscow: GEOTAR-Media; 2015: 189-98. (in Russian)]
4. Ismail A.M., Abbas A.M., Ali M.K., Amin A.F. Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. J. Matern. Fetal Neonatal Med. 2018; 31(3): 388-94.
5. Stephenson M.D., McQueen D., Winter M., Kliman H.J. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss. Fertil. Steril. 2016; 107(3): 684-90.
6. Савельева Г.М., Аксененко В.А., Андреева М.Д., Базина М.И., Башмакова Н.В., Боровкова Л.В., Брюхина Е.В., Буштырева И.О., Волков В.Г., Гурьев Д.Л., Данькова И.В., Доброхотова Ю.Э., Егорова А.Т., Иванова Т.В., Константинова О.Д., Коротких И.Н., Кравченко Е.Н., Крамарский В.А., Кулешов В.М., Лебеденко Е.Ю., Мальцева Л.И., Манухин И.Б., Мартиросян С.В., Михельсон А.Ф., Олина А.А., Пашов А.И., Рогожина Е.И., Сахаутдинова И.В., Селихова М.С., Серова О.Ф., Синчихин С.П., Сичинава Л.Г., Тапильская Н.И., Цхай В.Б., Ярмолинская М.И. Терапия привычного выкидыша микронизированым прогестероном (результаты многоцентрового исследования ТРИСТАН-1). Акушерство и гинекология. 2017; 11: 44-55. [Saveleva G.M., Aksenenko V.A., Andreeva M.D., Bazina M.I., Bashmakova N.V., Borovkova I.V., Bryuhina E.V., Bushtyireva I.O., Volkov V.G., Gurev D.L., Dankova I.V., Dobrohotova Yu.E., Egorova A.T., Ivanova T.V., Konstantinova O.D., Korotkih I.N., Kravchenko E.N., Kramarskiy V.A., Kuleshov V.M., Lebedenko E.Yu., Maltseva L.I., Manuhin I.B., Martirosyan S.V., Mihelson A.F., Olina A.A., Pashov A.I., Rogozhina I.E., Sahautdinova I.V., Selihova M.S., Serova O.F., Sinchihin S.P., Sichinava L.G., Tapilskaya N.I., Tshay V.B., Yarmolinskaya M.I. Micronized progesterone therapy of recurrent pregnancy loss (results of multicenter Tristan-1 study). Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2017; (11): 44-55. (in Russian)] https://dx.doi.org/10.18565/aig.2017.11.44-55
7. Coomarasamy A., Williams H., Truchanowicz E., Seed P.T., Small R., Quenby S. et al. A Randomized trial of progesterone in women with recurrent miscarriages. N. Engl. J. Med. 2015; 373(22): 2141-8.
8. Howard J.A. Carp, ed. Recurrent pregnancy loss: causes, controversies, and treatment. 2nd ed. CRC Press; 2014: 339-49.
9. Hughes N., Hamilton E.F., Tulandi T. Obstetric outcome in women after multiple spontaneous abortions. J. Reprod. Med. 1991; 36(3): 165-6.
10. Jivraj S., Anstie B., Cheong Y.C., Fairlie F.M., Laird S.M., Li T.C. Obstetric and neonatal outcome in women with a history of recurrent miscarriage: A cohort study. Hum. Reprod. 2001; 16(1): 102-6.
11. Thom D.H., Nelson L.M., Vaughan T.L. Spontaneous miscarriage and subsequent adverse birth outcomes. Am. J. Obstet. Gynecol. 1992; 166(1, Pt1): 111-6.
12. Sheiner E., Levy A., Katz M., Mazor M. Pregnancy outcome following recurrent spontaneous abortions. Eur. J. Obstet. Gynecol. Reprod. Biol. 2005;118(1): 61-5.
13. Ходжаева З.С., Дембовская С.В., Доброхотова Ю.Э., Сичинава Л.Г., Юзько А.М., Мальцева Л.И., Серова О.Ф., Макаров И.О., Ахмадеева Э.Н., Башмакова Н.В., Шмаков Р.Г., Клименченко Н.И., Муминова К.Т., Талибов О.Б., Сухих Г.Т. Медикаментозная профилактика преждевременных родов (результаты международного многоцентрового открытого исследования МИСТЕРИ). Акушерство и гинекология. 2016; 8: 37-43. [Khodzhaeva Z.S., Dembovskaya S.V., Dobrokhotova Yu.E., Sichinava L.G., Yuzko A.M., Maltseva L.I., Serova O.F., Makarov I.O., Akhmadeeva E.N., Bashmakova N.V., Shmakov R.G., Klimenchenko N.I., Muminova K.T., Talibov O.B., Sukhikh G.T.. Drug therapy for preterm birth: Results of the international multicenter open-label Mystery study. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2016; (8): 37-43. (in Russian)] http://dx.doi.org/10.18565/aig.2016.8.37-43
14. Reginald P.W., Beard R.W., Chapple J., Forbes P.B., Liddell H.S., Mowbray J.F., Underwood J.L. Outcome of pregnancies progressing beyond 28 weeks gestation in women with a history of recurrent miscarriage. Br. J. Obstet. Gynaecol. 1987; 94(7): 643-8.
15. Romero R., Nicolaides K.H., Conde-Agudelo A., O’Brien J.M., Cetingoz E., Da Fonseca E. et al. Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta-analysis including data from the OPPTIMUM study. Ultrasound Obstet. Gynecol. 2016; 48(3): 308-17.
Received 08.06.2018
Accepted 22.06.2018
About the Authors
Savelyeva, Galina M., Doctor of Medicine, Professor, academician of the Russian Academy of Sciences, Department of Obstetrics and Gynecology, N.I. PirogovRussian National Research Medical University. 117997, Russia, Moscow, Ostrovityanova str. 1 Tel.: +74954329897. E-mail: agpf-gms@rambler.ru
Aksenenko, Viktor A., Doctor of Medicine, professor, Department of Obstetrics and Gynecology, Stavropol State Medical University.
355017, Russia, Stavropol, Mira str. 310. Tel.: +79624026899. E-mail: aksenenko.vic@yandex.ru
Andreeva, Margarita D., Doctor of Medicine, Professor, department of obstetrics, gynecology and perinatology, Faculty of advanced training and professional retraining
of specialists. Kuban state medical university. 350063, Russia, Krasnodar, Sedina St., 4. E‑mail: andreeva_md@mail.ru.
Bazina, Marina I., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Krasnoyarsk State Medical University named after prof. V.F. Voyno-Yasenetskii. 660034, Russia, Krasnoyarsk, Krasnoyarskiy rabochiy pr. 170
Bashmakova, Nadezda V,, Doctor of Medicine, Professor, Director of Ural Research Institute of Maternity and Child Care, Ministry of Health of Russia.
620028, Russia, Ekaterinburg, Repina str. 1. Tel.: +73433718768. E-mail: dr@niiomm.ru
Borovkova, Lyudmila V., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Nizhniy Novgorod State Medical Academy.
603950, Russia, Nizhniy Novgorod, Minin and Pozharskiy Square, 10/1. Tel. +79519137727. E-mail: BorovcovaLV@yandex.ru
Bryukhina, Elena V., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology South-Ural State Medical University.
454080, Russia, Chelyabinsk, Vorovskogo str. 64. E-mail: elena-bruhina@rambler.ru
Bushtyreva, Irina O., Doctor of Medicine, Professor, the Head of the Department of Obstetrics, Gynecology and Reproduction № 4, Rostov State Medical University,
Ministry of Health of Russia; leading researcher, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
344022, Russia, Rostov-on-Don, Nakhichevan lane 29. Tel.: +7928770972. E-mail: kio4@mail.ru
Volkov, Valeriy G., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Tula State Medical Institute.
300012, Russia, Tula, pr. Lenina, 92. E-mail: valvol@yandex.ru
Gurev, Dmitriy L., assistant professor, Department of Obstetrics and Gynecology Yaroslavl State Medical Academy, Yaroslavl, Russia, Chief Obstetrician-Gynecologist
of the Department of Health and Pharmacy of the Yaroslavl Region. 150003, Yaroslavl, Z. Kosmodemyanskoy, 9. Tel. +74852729279. E-mail: d_guriev@mail.ru
Dankova, Irina, candidate of medical science, senior researcher, Research Department of Preservation of Reproductive Function, Ural Research Institute
for Maternity and Infancy. 620028, Russia, Yekaterinburg, Repina str. 1
Dobrokhotova, Yuliya E., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, N.I. Pirogov Russian National Research Medical University,
Ministry of Health of Russia. 117997, Russia, Moscow, Ostrovityanova str. 1. Tel.: +74952374033. E-mail: pr.dobrohotova@mail.ru
Egorova, Antonina T., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Krasnoyarsk State Medical University named
after prof. V.F. Voyno-Yasenetskii. 660034, Russia, Krasnoyarsk, Krasnoyarskiy rabochiy pr. 170
Ivanova, Tatyana V., assistant professor Department of Obstetrics and Gynecology, Siberian State Medical University.
634050, Russia, Tomsk, Moskovskiy trakt, 2. Tel.: +73822530423. E-mail: office@ssmu.ru
Konstantinova, Olga D., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Orenburg State Medical University.
460000, Russia, Orenburg, Sovetskaya str. 6. Tel.: +73532520612. E-mail: const55@mail.ru
Korotkih, Irina N., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Voronezh State Medical University.
394036, Russia, Voronezh, Studencheskaya str. 10. E-mail: korotkikh_1950@mail.ru
Kravchenko, Elena N., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Omsk State Medical University.
644099, Russia, Omsk, Lenina str. 12. E-mail: kravchenko.en@mail.ru
Kramarskiy, Vladimir A., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Irkutsk State Medical University.
664000, Russia, Irkutsk, Krasnogo Vosstaniya, 1. E-mail: kramarskye@mail.ru
Kuleshov, Vitaliy M., Doctor of Medicine, Professor of the Department of Obstetrics and Gynecology, Novosibirsk State Medical University.
630091, Russia, Novosibirsk, Krasnyiy prospekt, 52. Tel.: +73833410436. E-mail: kuleshov_vm@mail.ru
Lebedenko, Elizaveta Yu., Doctor of Medicine, Professor of the Department of Obstetrics and Gynecology, Rostov State Medical University.
344022, Russia, Rostov-on-Don, per. Nahichevanskiy, 29. Tel.: 8 (863) 252-24-65. E-mail: Lebedenko08@mail.ru
Maltseva, Larisa I., Doctor of Medicine, Professor, Department of obstetrics and gynecology № 1, Kazan State Medical Academy.
420012, Russia, Kazan, Mushtari str. 11. Tel.: +78432333487. E-mail: laramalc@mail.ru
Manukhin, Igor B., Honored Doctor of Russia, Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Medical Faculty, Moscow State University
of Medicine and Dentistry, Ministry of Health of Russia. 127473, Russia, Moscow, Delegatskaya str. 20, bld. 1. Tel.: +74991782831. E-mail: mgmsugyn@mail.ru
Martirosyan, Sergey V., candidate of medical science, chief doctor of the regional perinatal center.
620000, Russia, Ekaterinburg, Serafimyi Deryabinoy, 32k2. E-mail: smart.75@list.ru
Mihelson, Aleksandr F., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Rostov State Medical University.
344022, Russia, Rostov-on-Don, per. Nahichevanskiy, 29. Tel: +78632522465
Olina, Anna A., Doctor of Medicine, Professor of the Department of Obstetrics and Gynecology, Academician E.A. Wagner Perm State Medical University,
Ministry of Health of Russia. 614000, Russia, Perm, Petropavlovskaya str. 26. Tel.: +73422364472. E-mail: olina29@mail.ru
Pashov, Aleksandr I., Doctor of Medicine, Professor of the Department of Obstetrics and Gynecology, Baltic State University named after Immanuel Kant.
236000, Russia, Kaliningrad, Aleksandra Nevskogo, 14. E-mail: pachov@mail.ru
Rogozhina, Irina E., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Saratov State Medical University.
410012, Russia, Saratov, Bolshaya Kazachya, 112. E-mail: itg.r@yandex.ru
Sahautdinova, Indira V., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Bashkir State Medical University.
450000, Russia, Ufa, Lenina str. 3. Tel.: +73472721160. E-mail: bgmu.ag@yandex.ru
Selikhova, Marina, Doctor of Medicine, professor of the department of obstetrics and gynecology, Volgograd State Medical University.
400131, Russia, Volgograd, Pavshih boytsov sq. 1. Tel.: +78442417002. E-mail: selichovamarina@yandex.ru
Serova, Olga F., Doctor of Medicine, professor, chief physician of the Moscow Regional Perinatal Center. 143900, Russia, Moscow Region, Balashikha, sh. Enthusiasts, 12
Sinchihin, Sergey., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, Astrakhan State Medical University.
414000, Russia, Astrakhan, Bakinskaya, 121. E-mail: Doc_sinchihin@rambler.ru
Sichinava, Lali G., Doctor of Medicine, Professor, Department of Obstetrics and Gynecology, N.I. Pirogov Russian National Research Medical University.
117997, Russia, Moscow, Ostrovityanova str. 1
Tapilskaya, Natalia I., Doctor of Medicine, Professor of the Department of Obstetrics and Gynecology, St Petersburg State Pediatric Medical University; leading scientific member ART department, D.O. Ott Scientific Research Institute of Obstetrics, Gynecology and Reproduction. Russia, St. Petersburg, Mendeleevskaya line, 3
Tskhay, Vitaliy B., Doctor of Medicine, Professor, Department of Perinatology, Obstetrics and Gynecology Medical Faculty, V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University. 660022, Russia, Krasnoyarsk, P. Geleznyaka str. 1. Tel.: +79232872134. E-mail: tchai@yandex.ru
Yarmolinskaya, Maria, Doctor of Medicine, Leading researcher of the Department of Reproduction Endocrinology, D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology; Professor in the Department of obstetrics and gynecology № 2, North-Western Federal Medical Research Center, Ministry of Health of Russia.
199034, Russia, Saint-Petersburg, Mendeleevskaya line 154. Tel.: +78123289849. E-mail: m.yarmolinskaya@gmail.com
For citations: Saveleva G.M., Aksenenko V.A., Andreeva M.D., Bazina M.I., Bashmakova N.V., Borovkova I.V., Bryuhina E.V., Bushtyireva I.O., Volkov V.G., Gurev D.L., Dankova I.V., Dobrohotova Yu.E., Egorova A.T., Ivanova T.V., Konstantinova O.D., Korotkih I.N., Kravchenko E.N., Kramarskiy V.A., Kuleshov V.M., Lebedenko E.Yu., Maltseva L.I., Manuhin I.B., Martirosyan S.V., Mihelson A.F., Olina A.A., Pashov A.I., Rogozhina I.E., Sahautdinova I.V., Selihova M.S., Serova O.F., Sinchihin S.P., Sichinava L.G., Tapilskaya N.I., Tshay V.B., Yarmolinskaya M.I. Outcomes of the second half of pregnancy in patients with recurrent pregnancy loss (results of multicenter study of TRISTAN-2). Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (8): 111-21. (in Russian)
https://dx.doi.org/10.18565/aig.2018.8.111-121
Similar Articles
