Comparative efficacy of oral versus vaginal micronized progesterone in the prolongation of preterm labour: a prospective comparative study

Preeti Kanal; Neha Gupta; Hema J. Shobhane; Smriti Agnihotri

doi:10.18203/2320-1770.ijrcog20262102

Authors

Preeti Kanal Department of Obstetrics and Gynecology, Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India
Neha Gupta Department of Obstetrics and Gynecology, Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India
Hema J. Shobhane Department of Obstetrics and Gynecology, Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India
Smriti Agnihotri Department of Health Sciences Education and Pathology, University of Illinois College of Medicine, Peoria, Illinois

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20262102

Keywords:

Vaginal progesterone, Preterm labour, Preterm birth prevention, Oral progesterone, Gestation prolongation, Micronized progesterone

Abstract

Background: Preterm labour is a leading cause of neonatal morbidity and mortality worldwide. Progesterone supplementation is an established strategy for preterm birth prevention; however, the optimal route of administration- oral or vaginal- remains debated, particularly regarding gestation prolongation. Objective was to compare the efficacy of oral versus vaginal micronized progesterone (200 mg daily) in prolonging gestation in women presenting with preterm labour.

Methods: A prospective comparative study was conducted at Maharani Laxmi Bai Medical College, Jhansi, from May 2025 to April 2026. One hundred pregnant women with preterm labour (24-36+6 weeks) were randomised to oral micronized progesterone 200 mg daily (group A, n=50) or vaginal micronized progesterone 200 mg daily (group B, n=50). Primary outcomes were mean prolongation of gestation (days) and mean gestational age at delivery (weeks).

Results: Both groups were comparable at baseline. The vaginal progesterone group demonstrated significantly greater mean gestation prolongation (20.14±4.58 versus 11.38±2.82 days; p=0.0001) and higher mean gestational age at delivery (35.81±1.09 versus 33.88±1.84 weeks; p=0.001). Deliveries at 33-36+6 weeks were more frequent in the vaginal group (94% versus 74%; p=0.02). Very preterm deliveries (24-29 weeks) occurred only in the oral group (2%).

Conclusions: Vaginal micronized progesterone is significantly more effective than oral progesterone in prolonging gestation in preterm labour, attributable to enhanced uterine bioavailability via the first uterine pass effect. It should be the preferred route in clinical management of preterm labour.

References

Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10(Suppl 1):S2.

Cao G, Liu J, Li M. Global, regional, and national incidence and mortality of neonatal preterm birth, 1990–2019. JAMA Pediatr. 2022;176(8):787-96.

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

Blencowe H, Lee AC, Cousens S, Bahalim A, Narwal R, Zhong N, et al. Preterm birth–associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013;74(1):17-34.

Norwitz ER, Caughey AB. Progesterone supplementation and the prevention of preterm birth. Rev Obstet Gynecol. 2011;4(2):60-72.

Velez Edwards DR, Likis FE, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ, et al. Progestogens for preterm birth prevention: a systematic review and meta-analysis by drug route. Arch Gynecol Obstet. 2013;287(6):1059-66.

Jarde A, Lutsiv O, Beyene J, McDonald SD. Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis. Obstet Gynecol Surv. 2019;74(9):545-7.

Care A, Nevitt SJ, Medley N, Donegan S, Good L, Hampson L, et al. Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis. BMJ. 2022;376.

Ashoush S, Elkady OS, Al-Hawwary G, Othman A. The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: a randomized controlled trial. Acta Obstet Gynecol Scand. 2017;96(12):1460-6.

Srisutham K, Wuttikonsammakit P, Chamnan P. Efficacy of vaginal and oral progesterone after tocolytic therapy in threatened preterm labor: a 3-arm parallel-group randomized controlled trial. J Med Assoc Thai. 2021;104(5):705-11.

Iqbal SZ, Hanif S, Nisa ZU, Shabbir A, Anwar K, Afridi N. Comparison of the effectiveness of oral progesterone and micronized progesterone pessary in reducing the spontaneous preterm birth incidences. Pak J Med Health Sci. 2023;17(2):395-7.

Deshpande HG, Dhedia RA, Katakdhond S. A comparative study of oral 400 mg natural micronized progesterone versus vaginal 400 mg natural micronized progesterone in threatened preterm labour and perinatal neonatal outcomes. J Neonat Surg. 2025;14:46.

Abdelaziz MH. Oral versus vaginal progesterone in preterm labor. Evid Based Womens Health J. 2018;8(1):141-9.