Accumulating evidence has shown that progesterone supplementation in the second and third
trimester of pregnancy significantly reduces risk of preterm delivery in high-risk singleton pregnancies.
As early as the 1950s, Arpad Csapo [15] suggested that progesterone supplementation couldpotentially help maintain human pregnancy until term. The first larger study to investigate the effect of
progesterone treatment for prevention of preterm delivery was carried out by Papiernik–Berkhauer in
1970 [16]. Since then, several studies have been conducted, and it is now quite well-established that
progesterone treatment prevents preterm delivery in women with singleton pregnancies and a short
cervix at 23 weeks of gestation [17–20], a history of previous preterm delivery, or both [21–25]. A
recent individual patient data meta-analysis concluded that vaginal progesterone treatment (90–
200 mg/day) reduces risk of delivery before 33 weeks of gestation by about 45% in women with
singleton pregnancies and a short cervix at 20–23 weeks’ gestation [20]. Risk of composite neonatal
morbidity and mortality was reduced with a RR of 0.6 (95% CI 0.4 to 0.8). Another meta-analysis
showed that, in women with a history of previous preterm delivery, the relative risk of delivery
before 32 weeks of gestation is 0.6 (95% CI 0.5 to 0.8), with a corresponding statistically significant
reduction in perinatal complications [26].