Women With Preterm Premature Rupture of the Membranes Do Not Benefit From Weekly Progesterone

Progesterone and preterm birth prevention: translating clinical trials data into clinical practice

“…While the exact mechanism of action of progestogens in preventing preterm birth is unknown, several possibilities have been proposed. (Table 1) (9)(10)(11)(12)(13)(14)(15)(16)(17) In general, the evidence seems to favor 2 mechanisms: an anti-inflammatory effect that counteracts the inflammatory process leading to PTB, and a local increase in progesterone in gestational tissues that counteracts the functional decrease in progesterone leading to PTB. (Table 1) (9)(10)(11)(12)(13)(14)(15)(16)(17) Regarding safety, several studies failed to detect any long term effect from the intrauterine exposure of the fetus to pharmacologic progestogens, even when given in the first trimester.…”

“…Algorithm for use of progestogens in prevention of preterm birth in clinical care Table 1 Proposed mechanisms of action reported for progestogens to prevent preterm birth [9][10][11][12][13][14][15][16][17] Mechanisms Stimulate transcription of ZEB1 and ZEB2, which inhibit connexin 43 ( a gap-junction protein that helps synchronize contractile activity) and the oxytocin-receptor gene Decrease prostaglandin synthesis, infection-mediated cytokine production (antiinflammatory effects) by the fetal membranes/placenta Changes in progesterone receptor (PR)-A and PR-B expression (decreased PR-A/PR-B ratio keeps uterus quiescent) Membrane-bound PR in myometrium Progesterone receptors, when stimulated by progesterone, help selected gene promotion, or prevent the binding of other factors Interfere with cortisol-mediated regulation of placental gene expression Non-genomic pathways Reduce cervical stromal degradation in the cervix Alter barrier to ascending inflammation/infection in the cervix Reduce contraction frequency in the myometrium Attenuate response to hemorrhage/inflammation in the decidua Alter estrogen synthesis in the fetal membranes/placenta Alter fetal endocrine-mediated effects ZEB1 and ZEB2, zinc finger E-box binding homeobox proteins 1 and 2. …”

Progestins and Preterm Birth

“…Overall 75% deliver within one week after rupture, but approximately 15% may extend gestation for several weeks (ACOG #1, 1998;Lieman et al, 2005). Briery et al (Briery et al, 2011) randomized women with PPROM at 20-30 weeks' gestation with fetus in cephalic presentation to receive weekly 17OHP-C (n=33) or placebo (n=36) in an attempt to prolong the pregnancy. The report showed that there was no difference in GA at the time of delivery or the interval between randomization and delivery between the 2 groups.…”

Prevention of Preterm Birth Redux: Progesterone Works

“…Schuit et al [9] showed that the administration of 17P in patient with twins was not helpful in reducing neonatal mortality or morbidity. Briery et al [10] demonstrated that weekly 17P was not of assistance in prolonging pregnancy or decreasing neonatal morbidity in research subjects who had preterm premature rupture of membranes. In contrast, vaginal progesterone used in patients with a short cervix has demonstrated a reduction in preterm births as well as composite neonatal morbidity [11].…”