TABLE 1.

Characteristics of studies included

Study, year	Participating countries	Primary target population	Inclusion/exclusion criteria	No of women with CL ≤25 mm/fetuses or infants		Intervention	Co-interventions	Primary outcome
				Vaginal progesterone group	Placebo group
Fonseca, 130 2007	United Kingdom, Chile, Brazil, Greece	Women with a short cervix	Inclusion: women with a singleton or twin pregnancy and a sonographic cervical length of 15 mm or less. Exclusion: major fetal abnormalities, painful regular uterine contractions, a history of ruptured membranes, and a cervical cerclage.	125/136	125/138	Vaginal progesterone capsule (200 mg/day) or placebo from 24 to 33 6/7 weeks of gestation	Cervical cerclage (1 in vaginal progesterone group [0.8%] and 0 [0.0%] in placebo group)	Spontaneous preterm birth <34 weeks
O’Brien, 142 2007	United States, South Africa, India, Czech Republic, Chile, El Salvador	Women with a history of spontaneous preterm birth	Inclusion: women with a singleton pregnancy, gestational age between 16 0/7 and 22 6/7 weeks, 18–45 years of age, and a history of spontaneous singleton preterm birth at between 20 and 35 weeks of gestation in the immediately preceding pregnancy. Exclusion: planned cervical cerclage, history of adverse reaction to progesterone, treatment with progesterone within 4 weeks before enrolment, treatment for a seizure disorder, a psychiatric illness or chronic hypertension at the time of enrolment, history of acute or chronic congestive heart failure, renal failure, uncontrolled diabetes mellitus, active liver disorder, HIV infection with a CD4 count of <350 cells/mm3 and requiring multiple antiviral agents, placenta previa, history or suspicion of breast or genital tract malignancy, history or suspicion of thromboembolic disease, Müllerian duct anomaly, major fetal anomaly or chromosomal disorder, or multifetal gestation.	12/12	19/19	Vaginal progesterone gel (90 mg/day) or placebo from 18–22 to 37 0/7 weeks of gestation, rupture of membranes or preterm delivery, whichever occurred first.	No	Preterm birth <33 weeks
Cetingoz,135 2006	Turkey	Women at high risk of preterm birth	Inclusion: women with a least one previous spontaneous preterm birth, uterine malformation or twin pregnancy. Exclusion: in-place or planned cervical cerclage, serious fetal anomalies	9/14	6/8	Vaginal progesterone suppository (100 mg/day) or placebo from 24 to 34 weeks of gestation.	No	Preterm birth <37 weeks
Hassan,132 2011	United States, Republic of Belarus, Chile, Czech Republic, India, Israel, Italy, Russia, South Africa, Ukraine	Women with a short cervix	Inclusion: women with a singleton pregnancy, gestational age between 19 0/7 and 23 6/7 weeks, transvaginal sonographic cervical length between 10 and 20 mm, and without signs or symptoms of preterm labor. Exclusion: planned cerclage, acute cervical dilation, allergic reaction to progesterone, current or recent progestogen treatment within the previous four weeks, chronic medical conditions that would interfere with study participation or evaluation of the treatment, major fetal anomaly or known chromosomal abnormality, uterine anatomic malformation, vaginal bleeding, known or suspected clinical chorioamnionitis.	235/235	223/223	Vaginal progesterone gel (90 mg/day) or placebo from 20–23 to 36 6/7 weeks of gestation, rupture of membranes or preterm delivery, whichever occurred first.	Emergency cervical cerclage (10 in vaginal progesterone group [4.3%] and 6 [2.7%] in placebo group)	Preterm birth <33 weeks
Rode,133 2011	Denmark, Austria	Women with a twin pregnancy	Inclusion: women with a diamniotic twin pregnancy and chorionicity assessed by ultrasound before 16 weeks of gestation. Exclusion: higher order multiple pregnancies, age <18 years, known allergy to progesterone or peanuts as the active treatment contained peanut oil, history of hormone- associated thromboembolic disorders, rupture of membranes, pregnancies treated for or with signs of twin-to-twin transfusion syndrome, intentional fetal reduction, known major structural or chromosomal fetal abnormality, known or suspected malignancy in genitals or breasts, known liver disease.	7/14	14/28	Vaginal progesterone pessary (200 mg/day) or placebo from 20– 23 6/7 to 33 6/7 weeks of gestation.	Cervical cerclage (2 in vaginal progesterone group [28.6%] and 2 [14.3%] in placebo group)	Preterm birth <34 weeks