Prostaglandins have been used for induction of labour since the 1960s. Initial work focused on prostaglandin F2a as prostaglandin E2 was considered unsuitable for a number of reasons. With the development of alternative routes of administration, comparisons were made between various formulations of vaginal prostaglandins. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology.
To determine the effects of vaginal prostaglandins E2 and F2a for third trimester cervical ripening or induction of labour in comparison with placebo/no treatment or other vaginal prostaglandins (except misoprostol).
The Cochrane Pregnancy and Childbirth Group trials register (May 2003) and bibliographies of relevant papers.
Clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods.
A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction.
In total, 101 studies were considered: 43 excluded and 57 (10,039 women) included. One study is awaiting assessment. Vaginal prostaglandin E2 compared with placebo or no treatment reduced the likelihood of vaginal delivery not being achieved within 24 hours (18% versus 99%, relative risk (RR) 0.19, 95% confidence interval (CI) 0.14 to 0.25, 2 trials, 384 women), there was no evidence of a difference between caesarean section rates although the risk of uterine hyperstimulation with fetal heart rate changes was increased (4.6% versus 0.51%, RR 4.14, 95% CI 1.93 to 8.90, 13 trials, 1203 women). Comparison of vaginal prostaglandin F2a with placebo showed similar caesarean section rates but the cervical score was more likely to be improved (15% versus 60%, RR 0.25, 95% CI 0.13 to 0.49, 5 trials, 467 women), and the risk of oxytocin augmentation reduced (53.9% versus 89.1%, RR 0.60, 95% CI 0.43 to 0.84, 11 trials, 1265 women) with the use of vaginal PGF2a. There were insufficient data to make meaningful conclusions for the comparison of vaginal PGE2 and PGF2a.PGE2 tablet, gel and pessary appear to be as efficacious as each other. Lower dose regimens, as defined in the review, appear as efficacious as higher dose regimens.
The primary aim of this review was to examine the efficacy of vaginal prostaglandin E2 and F2a. This is reflected by an increase in successful vaginal delivery rates in 24 hours, no increase in operative delivery rates and significant improvements in cervical favourability within 24 to 48 hours. Further research is needed to quantify the cost-analysis of induction of labour with vaginal prostaglandins, with special attention to different methods of administration.
"Upregulation of PGH 2 synthase 2 occurs late in pregnancy, resulting in an increase in the synthesis of prostaglandins, particularly the PGF 2 isomers (Mijovic et al., 1999; Slater et al., 1999; Mitchell et al., 2005; Lee et al., 2008b). Activation of the F prostanoid (FP) receptor by prostaglandins stimulates cervical ripening and the initiation of labor (Kelly et al., 2003). AKR1B1 and AKR1C3 are the enzymes that form the PGF 2 isomers in humans. "
[Show abstract][Hide abstract] ABSTRACT: A better understanding of the mechanisms underlying parturition would provide an important step toward improving therapies for the prevention of preterm labor. Aldo-keto reductases (AKR) from the 1D, 1C, and 1B subfamilies likely contribute to determining the timing of parturition through metabolism of progesterone and prostaglandins. Placental AKR1D1 (human 5β reductase) likely contributes to the maintenance of pregnancy through the formation of 5β-dihydroprogesterone (DHP). AKR1C1, AKR1C2, and AKR1C3 catalyze the 20-ketosteroid and 3-ketosteroid reduction of progestins. They could therefore eliminate tocolytic progestins at term. Activation of the F prostanoid receptor by its ligands also plays a critical role in initiation of labor. AKR1C3 and AKR1B1 have prostaglandin (PG) F synthase activities that likely contribute to the initiation of labor. AKR1C3 converts PGH(2) to PGF(2α) and PGD(2) to 9α,11β-PGF(2). AKR1B1 also reduces PGH(2) to PGF(2α), but does not form 9α,11β-PGF(2). Consistent with the potential role for AKR1C3 in the initiation of parturition, indomethacin, which is a potent and isoform selective inhibitor of AKR1C3, has long been used for tocolysis.
Frontiers in Pharmacology 01/2011; 2:92. DOI:10.3389/fphar.2011.00092 · 3.80 Impact Factor
"The most common methods in hospital practice worldwide are oxytocin (combined with ARM where possible) and vaginal prostaglandins. Prostaglandins have been shown to be of benefit to reduce the need for cesarean section when the cervix is unfavorable . Prostaglandin E 2 (dinoprostone) has now become the drug of choice in well-resourced settings for cervical ripening and induction of labor, but it is expensive, unstable and requires refrigerated storage. "
[Show abstract][Hide abstract] ABSTRACT: Induction of labor is common in clinical practice. Many different medical and mechanical methods have been used, but the current gold standard is vaginal dinoprostone. Misoprostol has been used for the induction of labor since 1987. In early studies with large misoprostol doses (e.g. 200 microg) there were high rates of uterine hyperstimulation. Cochrane meta-analysis, however, shows that when used in low doses it is as effective as vaginal dinoprostone and with no excess of hyperstimulation. 25 microg vaginal misoprostol 4-hourly, 50 microg oral misoprostol 4-hourly or 20 microg oral misoprostol solution 2-hourly are all safe and effective regimens. Reports of uterine rupture in women with previous cesarean sections mean that it remains contraindicated in this group.
International Journal of Gynecology & Obstetrics 01/2008; 99 Suppl 2:S194-7. DOI:10.1016/j.ijgo.2007.09.011 · 1.54 Impact Factor
"Prostaglandin E2 (PGE2) is widely implicated for cervical ripening in clinical practice . Among the COX enzymes, regulating prostaglandin synthesis, the COX-1 form is constitutively expressed, whereas COX-2 is inducible and particularly involved in inflammatory events . "
[Show abstract][Hide abstract] ABSTRACT: Cervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR) mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NF)kappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF) are inflammatory mediators. Inducible nitric oxide synthase (iNOS) regulates the level of nitric oxide (NO) in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening.
We monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX)-1 and -2, iNOS, as well as the PAF-receptor (PAF-R) in the uterine cervix from term pregnant women (with unripe cervices) before the onset of labor (TP), immediately after parturition (PP), as compared to non-pregnant (NP), using immunohistochemistry and RT-PCR.
The GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ). Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE), stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum. No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group.
There is a decrease in GR levels in human cervix at parturition. Concomitantly there is an increase of factors such as NFkappaB, PAF-R, COX-1 and COX-2, suggesting that they may participate in the sequence of events leading to the final cervical ripening.
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