Cochrane for Clinicians

Putting Evidence into Practice

Treatment of Threatened Miscarriage with Progestogens


Am Fam Physician. 2019 Sep 1;100(5):279-280.

Clinical Question

Are progestogens a safe and effective treatment option for patients with threatened miscarriage?

Evidence-Based Answer

Progestogens reduce the risk of miscarriage when compared with placebo in patients with threatened miscarriage (number needed to treat [NNT] = 10.) Use of progestogens poses no significant risks to mother or baby.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Miscarriage occurs in 15% to 20% of pregnancies and is associated with significant physical and psychological morbidity. Threatened miscarriage is defined as any vaginal bleeding, with or without abdominal pain, with a closed cervix and a viable fetus inside the uterine cavity. Effective treatment options to increase the chance of a successful pregnancy are lacking. Bed rest, pelvic rest, vitamins, uterine relaxants, and administration of beta subunit of human chorionic gonadotropin are not recommended.2 Progesterone has physiologic roles in maintaining pregnancy by inducing changes in the endometrium, suppressing uterine contractions, and modulating the maternal immune system. Progestogens—medications that mimic the activity of progesterone—are therefore a rational therapeutic option to treat threatened miscarriage. Early studies had less rigorous methodology, so the authors of this Cochrane review sought to evaluate progestogen using newer data.1

This Cochrane review included seven randomized controlled trials and 696 patients from lower middle- to high-income countries, although none of the trials took place in North America.1 Three of these trials investigated oral progestogens and four trials evaluated vaginal progesterone. The authors assessed the body of evidence to be of moderate quality for the primary outcome of miscarriage vs. successful pregnancy, mainly because of limitations in study design. For example, only three of the seven studies were deemed to be at low risk of selection bias. The authors analyzed only studies that included pregnant women at 23 weeks of gestation or less, presenting with a concern of threatened miscarriage, and in which the viability of the pregnancy had been confirmed before starting treatment. Secondary outcomes were maternal (pain, preterm birth) and fetal (preterm birth, stillbirth, neonatal death, congenital abnormalities, low birth weight, or any other adverse neonatal outcomes reported). Maternal pain was reported in two trials; one double-blind, randomized, placebo-controlled trial included 50 patients and demonstrated significantly decreased maternal pain with use of progesterone. The other single-blind, randomized trial included 60 patients and demonstrated no pain relief with progesterone vs. no treatment.

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Outcomes of Progesterone vs. Placebo or No Treatment for Threatened Miscarriage

Outcomes of pregnancyProbable outcome with placebo or no treatmentProbable outcome with progesterone treatment (95% CI)NNT (95% CI)Participants (studies)Quality of evidence


242 per 1,000

138 per 1,000 (102 to 189)

10 (8 to 19)

696 (7)


Preterm birth

91 per 1,000

84 per 1,000 (49 to 142)


588 (5)


Congenital abnormalities

13 per 1,000

9 per 1,000 (1 to 62)


337 (2)

Very low

NA =

Author disclosure: No relevant financial affiliations.


1. Wahabi HA, Fayed AA, Esmaeil SA, et al. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018;(8):CD005943.

2. Committee on Practice Bulletins—Gynecology. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015;125(5):1258–1267.

3. The National Institute for Health and Care Excellence. Pain and bleeding in early pregnancy: assessment and initial management of ectopic pregnancy and miscarriage in the first trimester. June 2012. Accessed October 4, 2018.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, Assistant Medical Editor.

A collection of Cochrane for Clinicians published in AFP is available at



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