Comparison of the frequency of preterm births in patients treated with oral versus intramuscular progesterone with history of previous preterm birth

Khadija Shahzad, Hafiza Ateeqa Mubarak Ali, Urooj Anwar, Ayesha Haroon


Background: Globally, it has proven that preterm birth is associated with perinatal mortality to the extent of >75%, and >50% of perinatal and long term morbidity. Oral progesterone are easy to take but are less effective because of first pass hepatic metabolism leading to variable plasma levels while intramuscular progesterone carries the risk of swelling and bruising at injection site. The aim was to find out frequency of preterm birth in patients treated with oral versus intramuscular progesterone.

Methods: Randomized controlled trial conducted in the department of obstetrics and gynecology, Sir Ganga Ram hospital Lahore, Pakistan conducted from 5 October 2017 to 4 April 2018. This study involved 530 pregnant women with history of at least 1 previous preterm delivery presenting in antenatal clinic between 16-20 weeks of gestation. Group I received oral progesterone 10 mg tablet duphaston BD from 20 weeks till 37 weeks. Group II received intramuscular progesterone injection proluton depot 250 mg IM weekly from 16-20 weeks till 37 weeks.

Results: The mean age of the patients was 27.52±4.57 years while the mean gestational age was 17.39±1.38 weeks. 47.5% of the patients were para 2 followed by para 3 (32.3%) and para 1 (20.2%). The mean gestational age at delivery was significantly higher among intramuscular group (36.14±2.23 versus 35.07±2.97 weeks; p=0.000). The frequency of preterm delivery was significantly lower in intramuscular group (24.9% versus 39.6%; p=0.000) as compared to oral group.

Conclusions: Frequency of preterm delivery was significantly lower in patients treated with intramuscular progesterone (24.9% versus 39.6%; p=0.000) as compared to oral progesterone.


Preterm delivery, Oral progesterone, Intramuscular progesterone

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Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):261-9.

Natarajan G, Shankaran S. Short- and Long-Term Outcomes of Moderate and Late Preterm Infants. Am J Perinatol. 2016;33(3):305-17.

Harrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med. 2016;21(2):74-9.

Ganchimeg T, Ota E, Morisaki N, Laopaiboon M, Lumbiganon P, Zhang J, et al. Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization multicountry study. BJOG. 2014;120(1):40-8.

Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010;88(1):31-8.

Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller A, et al. Born too soon: the global epidemiology of 15 million preterm births. Reproduct Health. 2013;10(2).

Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincenzo Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012;206(5):376-86.

Committee on Practice Bulletins-Obstetrics, The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol. 2012;120(4):964-73.

How HY, Sibai BM. Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety. Ther Clin Risk Manag. 2009;5(1):55-64.

Romero R, Yeo L, Chaemsaithong P, Chaiworapongsa T, Hassan SS. Progesterone to prevent spontaneous preterm birth. Semin Fetal Neonatal Med. 2014;19(1):15-26.

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348(24):2379-85.

Saghafi N, Khadem N, Mohajeri T, Shakeri MT. Efficacy of 17α-hydroxyprogesterone caproate in prevention of preterm delivery. J Obstet Gynaecol Res. 2011;37(10):1342-5.

Winer N, Bretelle F, Senat MV, Bohec C, Deruelle P, Perrotin F, et al. Alpha-hydroxyprogesterone caproate does not prolong pregnancy or reduce the rate of preterm birth in women at high risk for preterm delivery and a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2015;212(4):1-10.

Senat MV, Porcher R, Winer N, Vayssière C, Deruelle P, Capelle M, et al. Prevention of preterm delivery by 17 alpha-hydroxyprogesterone caproate in asymptomatic twin pregnancies with a short cervix: a randomized controlled trial. Am J Obstet Gynecol. 2013;208(3):1-8.

Rozenberg P, Chauveaud A, Deruelle P, Mantel A, Azimi S, Porcher R, et al. Prevention of preterm delivery after successful tocolysis in preterm labor by 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial. Res Obstet. 2020.

Facchinetti F, Paganelli S, Comitini G, Dante G, Volpe A. Cervical length changes during preterm cervical ripening: effects of 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 2007;196(5):1-4.

Nigar A, Hakim S, Mohsin Z. Role of 17 α hydroxy: progesterone caproate (17OHPC) in the prevention of preterm labor. J Obstet Gynecol. 2012;62(4):398-400.

Rai P, Rajaram S, Goel N, Gopalakrishnan RA, Agarwal R, Mehta S. Oral micronized progesterone for prevention of preterm birth. Int J Gynecol Obstet. 2009;104(1):40-3.

Maher MA, Abdelaziz A, Ellaithy M, Bazeed MF. Prevention of preterm birth: a randomized trial of vaginal compared with intramuscular progesterone. Acta Obstet Gynecol Scand. 2013;92(2):215-22.

Bafghi AS, Bahrami E, Sekhavat L. Comparative study of vaginal versus intramuscular progesterone in the prevention of preterm delivery: a randomized clinical trial. Electron Physician. 2015;7(6):1301-9.

Elimian A, Smith K, Williams M, Knudtson E, Goodman JR, Escobedo MB. A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent preterm birth. Int J Gynaecol Obstet. 2016;134(2):169-72.

Saccone G, Khalifeh A, Elimian A, Bahrami E, Chaman-Ara K, Bahrami MA, et al. Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2017;49(3):315-21.

Glover MM, McKenna DS, Downing CM, Smith DB, Croom CS, Sonek JD. A randomized trial of micronized progesterone for the prevention of recurrent preterm birth. Am J Perinatol. 2011;28(5):377-81.

Hameed AAE. Vaginal versus intramuscular progesterone in the prevention of preterm labor and their effect on uterine and fetal blood flow. Middle East Fert Soc J. 2011;17(3):163-9.

Berghella V, Figueroa D, Szychowski JM, Owen J, Hankins GDV, Iams JD, et al. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010;202(4):351.

Choudhary M, Suneja A, Vaid NB, Guleria K, Faridi M. Maintenance tocolysis with oral micronized progesterone for prevention of preterm birth after arrested preterm labor. Int J Gynaecol Obstet. 2014;126(1):60-3.

Grobman WA, Thom EA, Spong CY, Iams JD, Saade GR, Mercer BM, et al. 17: alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012;207(5):390.

Lucovnik M, Kuon RJ, Chambliss LR, Maner WL, Shi S, Shi L, et al. Progestin treatment for the prevention of preterm birth. Acta Obstet Gynecol Scand. 2011;90(10):1057-69.