Use of prostaglandin E2 to ripen the cervix of the mare prior to induction of parturition

Eleven light-breed pregnant mares (335 to 347 d gestaton) were used to evaluate the use of prostaglandin E2 as a cervical ripening agent prior to induction of parturition during the months of April and May. Six hours prior to induction, each mare's cervix was examined per vagina for softness and dilation. Each mare was then assigned to 1 of 2 treatment groups: Group PGE mares (n = 7) received 2.0 to 2.5 mg prostaglandin E2 deposited intracervically; Group SAL mares (n = 4) received 0.5 mL of sterile NaCl deposited intracervically. Six hours later, the mares were readied for parturition by wrapping the tail, scrubbing and rinsing the perineum and udder, and examining the cervix as previously described. Each mare was then administered 15 U, i.v. oxytocin at 15-min intervals until the chorioallantois ruptured. Intervals from initial oxytocin injection until rupture of the chorioallantois, from initial oxytocin injection until delivery of the foal, from delivery of the foal until the foal stood unassisted, and from delivery of the foal until the foal suckled were recorded. Mean cervical dilation immediately prior to induction of parturition tended to be greater in Group PGE mares (3.9 +/- 1.7 cm) than in Group SAL mares (1.9 +/- 1.9 cm; P = 0.10). Mean change in cervical dilation over the 6-h period prior to induction (3.4 +/- 1.9 cm vs 1.5 +/- 2.1 cm), mean number of injections of oxytocin required until the chorioallantois ruptured (1.9 +/- 0.7 vs 2.5 +/- 1.0), and mean intervals from initial injection of oxytocin to rupture of the chorioallantois (20 +/- 10 min vs 28 +/- 19 min) and delivery of the foal (28 +/- 7 min vs 34 +/- 22 min) were not different between Group PGE and SAL mares, respectively (P > 0.10). The proportion of foals that stood within 1 h of birth also did not differ between Group PGE foals (6/7; 86%) and Group SAL foals (3/4; 75%; Chi-square = 0.17; P > 0.10). The proportion of foals that nursed within 2 h of birth was higher in Group PGE foals (6/7; 86%) than in Group SAL foals (1/4; 25%; Chi-square = 4.02; P < 0.05). Premature separation requiring manual rupture of the chorioallantois at the vulvar labia occurred in 1 Group PGE mare (cervical dilation of 1.5 cm at time of induction) and 1 Group SAL mare (cervix closed and firm at time of induction). Foals born from the 2 mares with premature placental separation had the longest intervals from initial oxytocin injection to delivery, delivery to ability to stand unassisted, and delivery to suckling within their respective treatment groups. In summary, it appears that cervical ripening prior to induction of parturition favors shorter deliveries and foal vigor. Intracervical administration of prostaglandin E2 may prove useful for ripening the cervix of the mare prior to induction of parturition. Further studies are indicated to determine optimal dosage and method of administration of prostaglandin E2.     

Uterine priming with oral prostaglandin E2 prior to elective induction with oxytocin.

Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E2 or a placebo. Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.     

Uterine priming with oral prostaglandin E2 prior to elective induction with oxytocin

Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E₂ or a placebo. Oral PGE₂ was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.     

Cervical ripening prior to induction of labor (intracervical application of a PG E2 viscous gel).

In 38 pregnant patients at term with unfavorable cervices labor induction was initiated with PG-E2 after a preceding intracervical application of 0.1, 0.2 or 0.3 mg PG-E2 in 1 ml viscous gel. The mean Bishop score improved from 3.36 to 7.0 in an average time of 2 h 37 min. The cervical diameter increased from 14 mm to 22.7 mm. 31 patients delivered their babies spontaneously, while 7 patients were delivered by cesarean section due to cervical dystocia and delayed labor. Fetal outcome was normal in all cases, with an average Apgar score of 8.7 and an average pH-value in the umbilical artery of 7.245. The study indicates that local application of PG-E2 induces cervical dilatation, and is of particular use in patients presenting a low Bishop score. A possible local effect of PG E2 is discussed.     

A comparison of buccal (oromucosal) and oral prostaglandin E2 for the elective induction of labor

In 100 clinically-normal women, labor was induced at term by low amniotomy and PGE2. The drug was administered by either the oral or the oromucosal route, the same incremental dose scheme (initial dose of 0.5 mg; hourly increment of 0.5 mg until adequate uterine stimulation or a maximum single dose of 3.0 mg) being applied.Both routes of administration had comparable efficacy and were equally safe. The incidence of abnormal monitoring findings (uterine hypertonus, transient bradycardia and dips II during the first stage; late decelerations, progressive and transient bradycardia during the second stage of labor) and of low Apgar scores was similar. Acid-base and lactate-pyruvate equilibria in mother and fetus were not influenced by the route of drug administration in parous women. In nulliparae treated with PGE2 by the oromucosal route, higher values were found for the fetal-maternal difference in excess lactate than in those given oral PGE2; however, this is probably of little clinical importance.     

控释前列腺素E2-普贝生用于足月妊娠引产的疗效观察

目的:探讨控释前列腺素E2栓剂普贝生用于足月妊娠引产的有效性及安全可行性.方法:将本院2008年12月2009年4月有引产指征的足月妊娠孕妇140例随机分成两组,研究组以普贝生用药,对照组行催产素静滴引产,比较两组产妇Bishop评分、引产费用、临产时间、破膜时间、分娩时间、总产程时间、分娩情况和结局以及新生儿体重及评分.结果:普贝生组用于足月妊娠引产效果明显优于对照组(P＜0.01),研究组用药至临产时间显著短于对照组(P＜0.01),引产成功率高于对照组,对母婴影响无显著差别.结论:普贝生是一种安全有效方便实惠的新型引产药物,对母婴没有明显不良影响,可在,临床上应用.     

A comparison of buccal (oromucosal) and oral prostaglandin E2 for the elective induction of labor.

In 100 clinically-normal women, labor was induced at term by low amniotomy and PGE2. The drug was administered by either the oral or the oromucosal route, the same incremental dose scheme (initial dose of 0.5 mg; hourly increment of 0.5 mg until adequate uterine stimulation or a maximum single dose of 3.0 mg) being applied. Both routes of administration had comparable efficacy and were equally safe. The incidence of abnormal monitoring findings (uterine hypertonus, transient bradycardia and dips II during the first stage; late decelerations, progressive and transient bradycardia during the second stage of labor) and of low Apgar scores were similar. Acid-base and lactate-pyruvate equilibria in mother and fetus were not influenced by the route of drug administration in parous women. In nulliparae treated with PGE2 by the oromucosal route, higher values were found for the fetal-maternal difference in excess lactate than in those given oral PGE2; however, this is probably of little clinical importance.     

Comparative study of oestradiol and prostaglandin E2 vaginal gel for ripening the unfavourable cervix before induction of labour.

Oestradiol 150 mg and prostaglandin E2 (PGE2) 4 mg suspended in viscous gel and applied intravaginally were compared with regard to ripening the unfavourable cervix of patients randomly allocated to two study groups. In primigravidae no significant difference was observed in the efficacy of the two substances. Some multiparous patients, however, had considerably more uterine sensitivity to PGE2 quickly developed decelerative cardiotocographic tracings after insertion of the gel. In the group given oestradiol there was a significant absence of uterine activity after gel application. The findings suggest that oestradiol applied vaginally is a safe, comfortable, cheap, and equally effective alternative to PGE2 for ripening the cervix, without the disadvantages of uterine stimulation frequently encountered with PGE2.     

Single extra-amniotic injection of prostaglandin E2 in viscous gel to induce mid-trimester abortion.

In a preliminary study a single extra-amniotic injection of 1.5 mg of prostaglandin E-2 incorporated into an aqueous viscous gel was given to 24 patients aborted within 24 hours, and the mean induction-abortion interval (plus or minus S.E. of mean) was 13.5 plus or minus 1.5 hours. Vomiting occurred in seven patients, and transient severe uterine cramps, pallor, nausea, and shivering occurred in one patient immediately after injection. Complete abortion occurred in 20patients. A delay in the time taken to abort seemed to be associated with an immediate and rapid rise in uterine tone after the injection which required prompt analgesia; this probably reflected rapid decidual absorption and dissolution of the prostaglandins away from their site of action. The degree of distention of the catheter-retaining balloon did not influence abortion times.     

Clinical experiences with a new gel for intracervical application of prostaglandin E2 before therapeutic abortion or induction of term labor

A new gel for intracervical application of prostaglandin E₂ (PGE₂) has been elaborated and evaluated. The main component of the gel is a cross-linked starch polymer to which prostaglandins can be added and preserved for long-term storage (> 12 months).In a double blind study, 20 patients requiring legal abortion in late first trimester were given gel containing 0.25 mg PGE₂ or gel without PGE₂. The gel was applied within the cervical canal. In all patients receiving PGE₂-gel, a rapid ripening of the cervix occurred which facilitated the subsequent dilatation and evacuation. In patients receiving gel without PGE₂ cervix did not ripen. In a subsequent open study, 30 patients were treated with PGE₂-gel before therapeutic abortion. The same degree of cervical ripening was registered as for the patients receiving PGE₂-gel in the double blind study.In 50 patients at term, intracervical application of 3 ml gel containing 0.50 mg PGE₂ induced labor in 27 cases, i.e. 54 per cent of the patients. In the remaining undelivered women, a prominent cervical ripening occurred within 24 hours. No side effects of the treatment were observed.We conclude the new PGE₂-gel to be a promising future alternative in the treatment of patients with an unfavorable cervix, prior to surgical evacuation of the uterus in late first trimester abortion, as well as before induction of labor at term.     

Cervical ripening prior to induction of labor (intracervical application of a PG E2 viscous gel)

In 38 pregnant patients at term with unfavorable cervices labor induction was initiated with PG-E₂ after a preceding intracervical application of 0.1, 0.2 or 0.3 mg PG-E₂ in 1 ml viscous gel. The mean Bishop score improved from 3.36 to 7.0 in an average time of 2 h 37 min. The cervical diameter increased from 14 mm to 22.7 mm. 31 patients delivered their babies spontaneously, while 7 patients were delivered by cesarean section due to cervical dystocia and delayed labor. Fetal outcome was normal in all cases, with an average Apgar score of 8.7 and an average pH-value in the umbilical artery of 7.245. The study indicates that local application of PG-E₂ induces cervical dilatation, and is of particular use in patients presenting a low Bishop score. A possible local effect of PG E₂ is discussed.     

Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2.

A group of 84 women at 39-43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E2. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE2 and 85.7% of those treated with 0.4 mg PGE2. The mean Apgar scores in the three groups were the same. The mean total dose of PGE2 were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE2 is an effective and acceptable method of inducing labor at term.     

控释前列腺素E2^-普贝生用于足月妊娠引产的疗效观察

目的：探讨控释前列腺素E2栓剂普贝生用于足月妊娠引产的有效性及安全可行性。方法：将本院2008年12月2009年4月有引产指征的足月妊娠孕妇140例随机分成两组,研究组以普贝生用药,对照组行催产素静滴引产,比较两组产妇Bishop评分、引产费用、临产时间、破膜时间、分娩时间、总产程时间、分娩情况和结局以及新生儿体重及评分。结果：普贝生组用于足月妊娠引产效果明显优于对照组（P〈0.01）,研究组用药至临产时间显著短于对照组（P〈0.01）,引产成功率高于对照组,对母婴影响无显著差别。结论：普贝生是一种安全有效方便实惠的新型引产药物,对母婴没有明显不良影响,可在临床上应用。     

In vitro response of prostaglandin E2 receptor (EP3) in the term pregnant rat uterus and cervix to misoprostol

We examined and compared the in vitro effects of misoprostol (synthetic prostaglandin E1 (PGE1) analogue) on prostaglandin E2 (PGE2) secretion and EP3 receptor mRNA expression in the pregnant rat myometrium and cervix at 19 days gestation. Myometrial and cervical tissue samples were exposed to media with or without misoprostol (50 or 100 pg/ml) and incubated for 15 and 30 min, and 1, 3, 6, 12, and 24 h. Media and tissue samples were collected for quantification of PGE2 and mRNA expression of rEP3alpha and rEP3beta receptor, respectively. PGE2 secretion increased (P < or = 0.05) in the myometrium exposed to 50 and 100 pg/ml misoprostol. Cervical PGE2 secretion increased following exposure to the 100 pg/ml dose only. In the myometrium, 50 and 100 pg/ml misoprostol induced elevations in rEP3alpha and rEP3beta receptor mRNA expression. rEP3alpha and rEP3beta receptor mRNA expression in the cervix was not different from controls. These data demonstrate that the EP3 receptor is differentially expressed in the myometrium and cervix in response to misoprostol. This may account for the ability of misoprostol to stimulate the myometrium when administered for cervical ripening.     

Immunolocalization of adipocytes and prostaglandin E2 and its four receptor proteins EP1, EP2, EP3, and EP4 in the caprine cervix during spontaneous term labor

The mechanisms of cervical ripening and dilation in mammals remain obscure. Information is lacking about the localization of prostaglandin E(2) (PGE(2))-producing cells and PGE(2) receptors (EP) in intrapartum cervix and whether cervical dilation at parturition is an active process. To reveal these mechanisms, immunolocalization of EP1-EP4 (official gene symbols PTGER1-PTGER4) and PGE(2)-producing cells in caprine cervix during nonpregnancy, pregnancy, and parturition was assayed by immunohistochemistry (IHC); the mRNA expression levels of PTGS2, PTGER2 (EP2), and PTGER4 (EP4) were determined using quantitative PCR; and the existence of adipocytes in the cervix at various stages was demonstrated with Oil Red O staining and IHC of perilipin A. The results suggested that in intrapartum caprine cervix staining of the PGE(2) was observed in the overall tissues, for example, blood vessels, canal or glandular epithelia, serosa, circular and longitudinal muscles, and stroma in addition to adipocytes; EP2 was detectable in all the tissues other than glandular epithelia; EP4 was strongly expressed in all the tissues other than serosa; EP1 was detected mainly in arterioles and canal or glandular epithelia; and EP3 was poorly expressed only in stroma, canal epithelia, and circular muscles. Little or no expression of EP2, EP3, and EP4 as well as PGE(2) in all cervical tissues was observed during nonpregnancy and pregnancy except for the strong expression of EP1 in canal or glandular epithelia during pregnancy. The mRNA expression levels of PTGS2, PTGER2, and PTGER4 were significantly higher in intrapartum than nonpregnant and midpregnant cervices (P < 0.01). Adipocytes appear only in the intrapartum cervix. These results support the concept that PGE(2) modulates specific functions in various anatomical structures of the caprine cervix at labor and the appearance of adipocytes at labor is likely related to caprine cervical dilation.     

Intestinal lipid alterations occur prior to antibody-induced prostaglandin E2 production in a mouse model of ischemia/reperfusion

Ischemia/reperfusion (IR) induced injury results in significant tissue damage in wild-type, but not antibody-deficient, Rag-1^−/− mice. However, Rag-1^−/− mice sustain intestinal damage after administration of wild-type antibodies or naturally occurring, specific anti-phospholipid related monoclonal antibodies, suggesting involvement of a lipid antigen. We hypothesized that IR initiates metabolism of cellular lipids, resulting in production of an antigen recognized by anti-phospholipid antibodies. At multiple time points after Sham or IR treatment, lipids extracted from mouse jejunal sections were analyzed by electrospray ionization triple quadrupole mass spectrometry. Within 15 min of reperfusion, IR induced significantly more lysophosphatidylcholine (lysoPC), lysophosphatidylglycerol (lysoPG) and free arachidonic acid (AA) production than Sham treatment. While lysoPC, lysoPG, and free AA levels were similar in C57Bl/6 (wild-type) and Rag-1^−/− mice, IR led to Cox-2 activation and prostaglandin E₂ (PGE₂) production in wild-type, but not in the antibody-deficient, Rag-1^−/− mice. Administration of wild-type antibodies to Rag-1^−/− mice restored PGE₂ production and intestinal damage. These data indicate that IR-induced intestinal damage requires antibodies for Cox-2 stimulated PGE₂ production but not for production of lysoPC and free AA.     

Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2

A group of 84 women at 39 – 43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E₂. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE₂ and 85.7% of those treated with 0.4 mg PGE₂. The mean Apgar scores in the three groups were the same. The mean total dose of PGE₂ were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE₂ is an effective and acceptable method of inducing labor at term.     

Changes in the plasma prostaglandin F2 alpha metabolite before and during spontaneous labor and labor induced by amniotomy, oxytocin and prostaglandin E2

To elucidate the role of endogenous prostaglandin F2 alpha in spontaneous and induced labor, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were determined before the onset of labor, at onset of labor, during active labor, at the crowning of the fetal head, and 1 and 2 hours after delivery. Patients in spontaneous labor and labor induced by amniotomy, oxytocin, and prostaglandin E2 were studied. The levels of plasma PGFM in patients who entered spontaneous labor fell 2 to 3 weeks before delivery, whereas those in the induced labor group did not change until the time of induction. Although the levels of PGFM rose gradually with the progress of labor in all cases, the levels in the spontaneous labor were significantly lower in each stage than in the corresponding stage of induced labor. These results suggest that endogenous prostaglandin F2 alpha (PGF2 alpha) production decreases 2-3 weeks prior to the spontaneous onset of labor and is increased again as labor progresses, that the patterns of PGF2 alpha production are similar to each other during spontaneous labor and labor induced by various methods. Therefore, it is felt that endogenous PGF2 alpha may participate in the progress of all kinds of labor.