Prevention of Preterm Birth with Progesterone

Abstract

Gestational age at birth is a critical factor for perinatal and adulthood outcomes, and even for transgenerational conditions’ effects. Preterm birth (PTB) (prematurity) is still the main determinant for infant mortality and morbidity leading cause of infant morbidity and mortality. Unfortunately, preterm birth (PTB) is a relevant public health issue worldwide and the global PTB rate is around 11%. The premature activation of labor is underlined by complex mechanisms, with a multifactorial origin influenced by numerous known and probably unknown triggers. The possible mechanisms involved in a too early labor activation have been partially explained, and involve chemokines, receptors, and imbalanced inflammatory paths. Strategies for the early detection and prevention of this obstetric condition were proposed in clinical settings with interesting results. Progesterone has been demonstrated to have a key role in PTB prevention, showing several positive effects, such as lower prostaglandin synthesis, the inhibition of cervical stromal degradation, modulating the inflammatory response, reducing gap junction formation, and decreasing myometrial activation. The available scientific knowledge, data and recommendations address multiple current areas of debate regarding the use of progesterone in multifetal gestation, including different formulations, doses and routes of administration and its safety profile in pregnancy.

Vaginal Nanoformulations for the Management of Preterm Birth

“…The most successful drug therapy to prevent PTB is vaginal progesterone, which is administered off-label to women who have had a PTB before and are therefore at risk for delivering preterm. Vaginal progesterone, however, has only a modest effect on the incidence of PTB [15]. As far as tocolytics, magnesium sulfate, indomethacin and nifedipine, which are the three most often used, only postpone PTB for approximately 48 hours [94], which allows time for the administration of antenatal corticosteroids for the promotion of lung maturity but does prolong gestation long enough to significantly effect neonatal or long-term outcomes.…”

“…The role of progesterone in maintaining pregnancy cannot be overstated. Although many hormones are important regulators of physiological processes during pregnancy, only progesterone can sustain reproductive structures that support fetal development until term in mammals [15]. Questions about the positive effects that progesterone has in the prevention of preterm birth may not extend to the variety of risk phenotypes for spontaneous premature conclusion of pregnancy [16].…”

Vaginal Nanoformulations for the Management of Preterm Birth

“…The role of progesterone in maintaining pregnancy cannot be overstated. Although many hormones are important regulators of physiological processes during pregnancy, only progesterone can sustain reproductive structures that support fetal development until term in mammals [ 16 ]. Questions about the positive effects that progesterone has in the prevention of PTB may not extend to the variety of risk phenotypes for spontaneous premature conclusion of pregnancy [ 17 ].…”

“…This effect is accomplished by changing the resting potential of smooth muscle cells via suppressing the calcium–calmodulin–myosin light chain kinase system [ 20 , 21 ]. In pregnant rats, progesterone blocks inflammatory changes in cervix structure and collagenolysis before PTB [ 16 ]. In both rats and mice, specific progesterone receptor agonists or antagonists regulate cervix remodeling associated with prevention or promotion of PTB, respectively [ 22 , 23 ].…”

Pessary or progesterone to prevent preterm birth in women with short cervical length: protocol of the 4–6 year follow-up of a randomised controlled trial (Quadruple-P)

“…[2][3][4][5][6][7] Progesterone promotes uterine quiescence by a range of actions including inhibition of prostaglandin activity, reduction of contraction associated proteins and decreasing oxytocin receptors. 8 In addition, it inhibits cervical ripening by regulating the extracellular matrix metabolism. 9 These range of actions result in its effectiveness to prevent PTB.…”