Drug therapy for preterm birth: Results of the international multicenter open-label Mystery study


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Abstract

Objective. To improve obstetric outcomes by reducing the rates of preterm birth (before 34.0 weeks of gestation) through the prophylactic use of natural progesterone at a dose of 200 mg daily vaginally at 19-34 weeks’ gestation in women at high risk for preterm birth compared with its population-based rate in this category of pregnant women. To improve neonatal outcomes and to correspondingly reduce total neonatal mortality and morbidity rates compared to population-based rates. Subjects and methods. The international multicenter open-label clinical trial was conducted to study the efficacy of vaginal progesterone in the prevention of preterm birth (Phase III), by involving asymptomatic women, women with singleton pregnancy, with ultrasound signs of cervical shortening (10 to 25 mm) at 18-236/7 weeks’ gestation (Group I; n = 110) and/or having a history of preterm birth (Group II; n = 110). The women were daily given vaginal Utrogestan from 18-236/7 to 336/7 weeks’ gestation or spontaneous termination of pregnancy. Results. The study demonstrated a statistically significant reduction in preterm birth rates at < 34 weeks’ gestation to 5.5% (95 CI 2.6-11.5) (P = 0.003) in women with a sonographic short cervix uteri and to 6.4% (95% CI3.1-12.6) (P = 0.0028) in pregnant women with a history of preterm birth - 5.9% (95% CI 3.5-9.9) (P = 0.000013) as compared to the rates given in the literature. Conclusion. The findings have led to the conclusion that 200-mg micronized vaginal progesterone capsules are effective in reducing the risk of miscarriage at less than 34 weeks of gestation in pregnant women with no clinical signs of threatened abortion, but with premature birth or preterm amniorrhea before 37 weeks of pregnancy in their history or with a short cervix identified by transvaginal ultrasound at 18-20 weeks.

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About the authors

Zulfiya S. Khodzhaeva

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: z_khodzhaeva@oparina4.ru
MD, PhD, Senior Researcher

Svetlana V. Dembovskaya

Grodno Regional Clinical Perinatal Center

Email: grodnookrd@tut.by
deputy chief medical officer for the organizational and methodical work

Yulia E. Dobrokhotova

N.I. Pirogov Russian National Research Medical University

Email: pr.dobrohotova@mail.ru
MD, Professor, Head of Department of Obstetrics and Gynecology, Medical Faculty

Lali G. Sichinava

N.I. Pirogov Russian National Research Medical University

Professor, Department of Obstetrics and Gynecology

Alexander Mikhaylovich Yuzko

Bukovina Center for Reproductive Medicine

Email: Uarm.kiev@gmail.com
head of the Department of Obstetrics and Gynecology

Larisa Ivanovna Maltseva

Kazan State Medical Academy

Head of Obstetrics and Gynecology Department One

Olga Fedorovna Serova

Moscow Regional Perinatal Center

head physician

Igor O. Makarov

I.M. Sechenov First Moscow State Medical University

Professor, head of the Department of Obstetrics and Gynecology

Elsa N. Akhmadeeva

Bashkir State Medical University

Head of the Department of Obstetrics and Gynecology

Nadine Vasil'evna Bashmakova

Ural Research Institute of Maternal and Infant Care

director

Roman G. Shmakov

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: r_shmakov@oparina4.ru
MD, chief medical

Natalia I. Klimenchenko

Research Center of Obstetrics, Gynecology, and Perinatology

Email: n_klimenchenko@oparina4.ru
PhD, the head of the 1st department of pathology of pregnancy obstetric

Kamilla T. Muminova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: kamika9l@mail.ru
Junior Researcher

Oleg B. Talibov

A.I. Evdokimov Moscow State University of Medicine and Dentistry

associate professor of the department of therapy, clinical pharmacology and ambulance

Gennady T. Sukhikh

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
MD, PhD, director

References

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  6. O’Brien J.M., Adair C.D., Lewis D.F., Hall D.R., DeFranco E.A., Fusey S. et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet. Gynecol. 2007; 30(5): 687-96.
  7. O’Brien J.M., DeFranco E.A., Adair C.D., Lewis D.F., Hall D.R., How H. et al. Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, doubleblind, placebo-controlled trial. Ultrasound Obstet. Gynecol. 2009; 34(6): 653-9.
  8. DeFranco E.A., O’Brien J.M., Adair C.D., Lewis D.F., Hall D.R., Fusey S. et al. Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet. Gynecol. 2007; 30(5): 697-705.
  9. Hassan S.S., Romero R., Vidyadhari D., Fusey S., Baxter J.K., Khandelwal M. et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, doubleblind, placebo-controlled trial. Ultrasound Obstet. Gynecol. 2011; 38(1): 18-31.
  10. Romero R., Nicolaides K., Conde-Agudelo A., Tabor A., O’Brien J.M., Cetingoz E. et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and meta-analysis of individual patient data. Am. J. Obstet. Gynecol. 2012; 206(2): 124. e1-19.

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