Table 1.

Characteristics of studies included in the systematic review

Study	Country	Primary target population	Inclusion and exclusion criteria	Women with CL ≤ 25 mm (n)	Intervention	Primary outcome measure
Fonseca (2007)48	UK, Chile, Brazil, Greece	Women with short cervix	Inclusion: women with singleton or twin gestation and transvaginal sonographic CL ≤ 15 mm Exclusion: major fetal abnormality, painful regular uterine contractions, history of ruptured membranes or cervical cerclage	226	Vaginal progesterone capsule (200 mg/day) or placebo from 24 to 33 + 6 weeks	Spontaneous PTB < 34 weeks
O'Brien (2007)49	USA, South Africa, India, Czech Republic, Chile, El Salvador	Women with history of spontaneous PTB	Inclusion: women with singleton gestation between 16 + 0 and 22 + 6 weeks and history of spontaneous singleton PTB at 20–35 weeks in immediately preceding pregnancy Exclusion: planned cervical cerclage, history of adverse reaction to progesterone, treatment with progesterone within 4 weeks before enrollment, treatment for seizure disorder, psychiatric illness or chronic hypertension at time of enrollment, history of acute or chronic congestive heart failure, renal failure, uncontrolled diabetes mellitus, active liver disorder, HIV infection with CD4 count < 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 multiple gestation	31	Vaginal progesterone gel (90 mg/day) or placebo from 18–22 to 37 + 0 weeks, rupture of membranes or preterm delivery, whichever occurred first	PTB ≤ 32 + 0 weeks
Cetingoz (2011)50	Turkey	Women at high risk of PTB	Inclusion: women with at least one previous spontaneous PTB, uterine malformation or twin gestation Exclusion: in‐place or planned cervical cerclage or serious fetal anomaly	8	Vaginal progesterone suppository (100 mg/day) or placebo from 24 to 34 weeks	PTB < 37 weeks
Hassan (2011)51	USA, Republic of Belarus, Chile, Czech Republic, India, Israel, Italy, Russia, South Africa, Ukraine	Women with short cervix	Inclusion: women with singleton gestation between 19 + 0 and 23 + 6 weeks, transvaginal sonographic CL of 10–20 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 previous 4 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	458	Vaginal progesterone gel (90 mg/day) or placebo from 20–23 + 6 to 36 + 6 weeks, rupture of membranes or preterm delivery, whichever occurred first	PTB < 33 weeks
OPPTIMUM (2016)44	UK, Sweden	Women at high risk of PTB	Inclusion: women with singleton gestation and (1) previous spontaneous PTB ≤ 34 + 0 weeks; or (2) transvaginal sonographic CL ≤ 25 mm at 18–24 weeks; or (3) positive cervicovaginal fetal fibronectin test at 22–24 weeks plus history of previous PTB or second‐trimester loss, PPROM or cervical procedure to treat abnormal smear Exclusion: congenital structural or chromosomal fetal anomaly, known sensitivity, contraindications or intolerance to progesterone or any excipient, rupture of fetal membranes at time of recruitment or prescription or ingestion of medication known to interact with progesterone	251	Vaginal progesterone capsule (200 mg/day) or placebo from 22–24 to 34 weeks, or delivery	PTB ≤ 34 + 0 weeks or fetal death, composite outcome of neonatal death, bronchopulmonary dysplasia or brain injury assessed by neurosonography, and Bayley‐III cognitive composite score at 2 years of age

CL, cervical length; HIV, human immunodeficiency virus; PPROM, preterm prelabor rupture of the membranes; PTB, preterm birth.