Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix.

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E2 the evening prior to planned induction. One group received PGE2 500 micrograms suspended in a viscous medium extra-amniotically. One group received PGE2 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE2 vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E2 in pessary form is a superior form of administration.     

Preinduction cervical priming with PGE2 vaginal film in primigravidae--a randomised, double blind, placebo controlled study

Previous reports with an 850 micrograms prostaglandin E2 film for cervical ripening before induction of labour in term pregnancy have been favourable. These studies however had no controls. The present study compares this PGE2 vaginal film with a nonmedicated similar vaginal film (placebo) for preinduction cervical ripening in primigravid women at term. A total of 69 women with modified Bishop's cervical scores 1-5 were assigned randomly to either the PGE2 group (33 women) or placebo group (36 women). Cervical score assessments were made at 12 and 24 hours after which labour was induced by amniotomy and oxytocin infusion. Although the cervical scores between placebo and PGE2 groups at 12 and 24 hours were not significantly different, the scores were marginally better with the prostaglandin film. Pregnancy outcome was satisfactory in both groups with no perinatal or maternal mortality and morbidity. The caesarean rate was 30.6% in the placebo group and 24.2% in the PGE2 group. This study emphasizes the need for a control group when studying the success of agents used for ripening the pregnant cervix at term.     

Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E₂ the evening prior to planned induction. One group received PGE₂ 500 μg suspended in a viscous medium extra-amniotically. One group received PGE₂ 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE₂ vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E₂ in pessary form is a superior form of administration.     

The PGE2 vaginal film: An alternative to conventional induction in multiparae with poor cervical scores

In a study involving 50 multiparous subjects with poor cervical scores (⪕3), induction of labour by conventional amniotomy and oxytocin was compared with preinduction cervical ripening using a single administration of prostaglandin E₂ (850ug) in a new vaginal film formulation. Indications for elective delivery, maternal characteristics and distribution of cervical scores in the two groups were similar. Significant changes in mean cervical score were achieved within 12 hours of film insertion. In this group, 11 subjects (45.8%) established labour within 12 hours and a further 8(33.3%) did so before 24 hours so that only 5 cases required amniotomy and oxytocin. Instrumental delivery was less in this group and none of these subjects required Caesarean section for a failure of induction. No adverse maternal or fetal side effects were observed. Convenience, ease of administration and stability of this new prostaglandin formulation make it a useful alternative to conventional induction of labour in the multiparous patient with a poor cervical score.     

The concurrent in vitro and in vivo release of PGE2 from a controlled-release hydrogel polymer pessary for cervical ripening

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pessary containing 10 mg prostaglandin E2 (PGE2), designed to release 0.6 mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63 mg/hr. to 1.23 mg/hr. This compared with a concomitant release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE2 release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE2 release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.     

COOK双球囊导管在足月妊娠引产中的临床研究

目的:探讨宫颈双球囊导管在足月妊娠促宫颈成熟及引产中的有效性和安全性。方法:回顾性选择符合有引产指征、单胎头位、宫颈评分6分的100例足月妊娠孕妇进行分析,其中51例采用COOK双球囊导管引产者为COOK组,49例采用小剂量缩宫素引产者为对照组,比较分析两组宫颈成熟度、引产效果、分娩方式、分娩结局、产后出血、新生儿窒息等情况。结果:100例孕妇引产指征主要是延期(过期)妊娠、羊水过少、妊娠期高血压、妊娠期糖尿病、妊娠合并甲减等。COOK组51例促宫颈成熟有效49例(96.08%),对照组有效16例(32.65%),COOK组促宫颈成熟有效率显著高于对照组,差异有统计学意义(P0.05)。COOK组诱发临产时间明显少于对照组,两组差异有统计学意义(P0.05)。COOK组阴道分娩41例(80.39%),剖宫产10例(19.61%);对照组阴道分娩20例(40.82%),剖宫产29例(59.18%),COOK组阴道分娩率明显高于对照组,剖宫产率明显低于对照组,两组差异均有统计学意义(P0.05)。两组之间的总产程、羊水污染率、新生儿窒息率、产后出血率等围产结局无显著差异(P0.05);COOK组引产过程中出现不良反应6例(11.76%),对照组5例(10.20%),两组无显著差异(P0.05)。结论:COOK双球囊导管促宫颈成熟及引产效果明显优于缩宫素,且不增加不良反应的发生,由于操作简单,有效性和安全性高,值得国内临床推广。     

The concurrent in vitro and in vivo release of PGE2 from controlled-release hydrogel polymer pessary for cervical ripening

Twenty five patients booked for induction of labour, at 38 weeks or more gestation, were administered a controlled release vaginal polymer pressary containing 10mg prostaglandin E₂(PGE₂), designed to release 0.6mg per hour in vivo. The release profile from the polymer was linear throughout the eight hour observation period with a correlation coefficient of 0.81, and regression slope of 0.93 mg/hr. with 95% confidence intervals of 0.63mg/hr. to 1.23 mg/hr. This compared with a concomitatnt release profile in vitro which was uniform with time for the first five hours, but then continued at a decreasing rate with a correlation coefficient of 0.98. The relationship between PGE₂ release and cervical score change was linear, with a correlation coefficient of 0.65. The results show that PGE₂ release from the pessary in vivo is predictable, and suggest that the controlled release pessary offers the advantages of greater control of cervical ripening than alternative vehicles currently available.     

Prostaglandin metabolite levels during cervical ripening with a controlled-release hydrogel polymer prostaglandin E2 pessary

Prostaglandin E and F metabolite (PGEM and PGFM) concentrations in peripheral plasma were assayed following the vaginal administration of a controlled release hydrogel polymer pessary designed to release 0.6 mg PGE2 per hour in vivo. A linear relationship between calculated PGE2 release from the pessary and PGEM levels was observed with a correlation coefficient of 0.78. A significant rise in PGEM levels occurred two hours following pessary administration, with significantly higher PGEM levels in patients delivering within the eight hour observation period compared with those delivering later. PGFM levels increased more slowly. The results suggest that PGE2 released by the pessary crosses the vaginal epithelium and may stimulate endogenous prostaglandin production. The controlled rise of metabolites in association with the polymer pessary suggest that it should provide greater control in labour induction than other vehicles we have studied, but this should be confirmed by clinical trials.     

Prolonged pregnancy: the management debate.

A prospective trial was conducted to compare the effects of conservative management of prolonged pregnancy (conservative group) with routine induction of labour at 42 weeks'' gestation (active group) in otherwise uncomplicated pregnancies. Of the 402 pregnancies studied, 207 (51%) were allocated to conservative management and 195 (49%) were allocated to have labour induced. The groups were well matched for age, parity, and smoking habits. One hundred and sixty six (80%) of the patients in the conservative group went into spontaneous labour. Of the remainder, two underwent elective caesarean section, 19 had labour induced because of clinical concern, and the remaining 20 had labour induced at the patient''s own request. One hundred and twenty five (64%) of the patients in the planned active group underwent induction of labour. Of the remaining 70, 49 went into spontaneous labour and 21 (11%) asked that they should not have labour induced. Comparison of the two groups showed no difference in the length of the first stage of labour but a trend towards an increased need for intervention for fetal distress (p less than 0.06) in the active group. There were no differences in the length of the second stage, the need for intervention, or the mode of delivery. In terms of Apgar scores the neonatal outcome was not significantly different between the two groups, but a greater proportion of the babies (15% v 8%) in the active group required intubation. Umbilical cord venous pH estimated in the last 183 consecutive deliveries in the study showed a significantly lower mean value in the active group (p less than 0.05). There was no difference in birth weight between the two groups. Two deaths occurred in the study. There was a stillbirth in the conservative group at 292 days after massive abruption, and one neonatal death in the active group owing to multiple congenital abnormalities. The outcome for mother and baby in patients from both groups who went into spontaneous labour was generally good. The outcome for patients for whom conservative management was planned but induction became necessary was no different from that of patients who underwent planned induction at term. Thus from our results we can find no evidence to support the view that women with normal prolonged pregnancy should undergo routine induction of labour at 42 weeks'' gestation.     

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis

BackgroundPreterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.Methods and findingsWe conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.ConclusionsThese results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.Trial registrationISRCTN Registry ISRCTN 02235181.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02235181","term_id":"NCT02235181"}}NCT02235181.

Jane Norman and co-workers report an evaluation of a cervical pessary for prevention of preterm birth in women with a short cervix bearing twins.     

The systemic absorption from the vagina of prostaglandin E2 administered for the induction of labour

The absorption rates of PGE2 released from tablets, gel and pessary bases inserted into the vagina for the induction of labour in a total of 27 patients have been measured by means of serial plasma 15-keto-PGE2 levels. The results are discussed with a view to obtaining both the optimum dose of PGE2 and vehicle of release.     

Differences in intrapartum obstetric care provided to women at low risk by family physicians and obstetricians.

To determine differences in practice style and to examine maternal and neonatal outcomes, we reviewed the hospital charts of 1115 women admitted by family physicians and 1250 women admitted by obstetricians who gave birth at one of three teaching hospitals in Toronto between April 1985 and March 1986. All the women in the two groups were categorized retrospectively as being at low risk at the onset of labour on the basis of their prenatal records and their admission histories and physical examination results. There were higher proportions of younger women and women of lower socioeconomic status in the family physician group than in the obstetrician group (p less than 0.001). The rates of interventions, including artificial rupture of the membranes, induction, augmentation, low forceps plus vacuum extraction, episiotomy and epidural anesthesia, were all higher in the obstetrician group. The mean birth weight and the cesarean section rate were the same in the two groups. Differences in labour and delivery outcomes between the two groups, including a higher rate of spontaneous vaginal delivery for the family physicians, reflected a more "expectant" practice style by family doctors. However, there were no significant differences in the rates of maternal or neonatal complications. A practice style characterized by a higher rate of interventions was not associated with improved maternal or newborn outcome in this low-risk setting.     

Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol

The effects of alfaxalone and propofol on neonatal vitality were studied in 22 bitches and 81 puppies after their use as anesthetic induction agents for emergency cesarean section. After assessment that surgery was indicated, bitches were randomly allocated to receive alfaxalone 1 to 2 mg/kg body weight or propofol 2 to 6 mg/kg body weight for anesthetic induction. Both drugs were administered intravenously to effect to allow endotracheal intubation, and anesthesia was maintained with isoflurane in oxygen. Neonatal vitality was assessed using a modified Apgar score that took into account heart rate, respiratory effort, reflex irritability, motility, and mucous membrane color (maximum score = 10); scores were assigned at 5, 15, and 60 minutes after delivery. Neither the number of puppies delivered nor the proportion of surviving puppies up to 3 months after delivery differed between groups. Anesthetic induction drug and time of scoring were associated with the Apgar score, but delivery time was not. Apgar scores in the alfaxalone group were greater than those in the propofol group at 5, 15, and 60 minutes after delivery; the overall estimated score difference between the groups was 3.3 (confidence interval 95%: 1.6–4.9; P < 0.001). In conclusion, both alfaxalone and propofol can be safely used for induction of anesthesia in bitches undergoing emergency cesarean section. Although puppy survival was similar after the use of these drugs, alfaxalone was associated with better neonatal vitality during the first 60 minutes after delivery.     

The systemic absorption from the vagina of prostaglandin E2 administered for the induction of labour

The absorption rates of PGE₂ released from tablets, gel and pessary bases inserted into the vagina for the induction of labour in a total of 27 patients have been measured by means of serial plasma 15-keto-PGE₂ levels. The results are discussed with a view to obtaining both the optimum dose of PGE₂ and vehicle of release.     

苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清HIF-1α、LXA4、ET-1表达的影响

目的:探讨苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清缺氧诱导因子-1α(HIF-1α)、血脂氧素A4(LXA4)、内皮素-1(ET-1)表达的影响。方法:选择2013年1月至2018年3月我院接诊的88例缺氧缺血性脑病新生儿作为本研究对象,将其按照随机数表法分为试验组45例和对照组43例。对照组在常规治疗基础上给予脑苷肌肽注射液2 mL加入0.9%氯化钠溶液50 mL中静脉滴注,1次/d;试验组在对照组基础上给予苯巴比妥钠注射液肌肉注射,首次剂量10 mg/kg/次,24 h内可重复给药2~3次,24 h总剂量最高不超过30 mg/kg,之后以5 mg/kg/d的维持剂量,分2次使用,均连续治疗14 d。比较2组的临床疗效、临床症状恢复时间、治疗前后血清HIF-1α、LXA4、ET-1水平、神经行为评分(NBNA)、心理运动发育指数(PDI)、智力发育指数(MDI)的变化及不良反应的发生情况。结果:治疗后,试验组临床疗效总有效率为93.33%,显著高于对照组(76.74%,P<0.05),原始反射、肌肉张力、意识障碍恢复时间均明显短于对照组(P<0.05),血清HIF-1α、ET-1水平均明显低于对照组,而血清LXA4水平、NBNA评分、PDI评分、MDI评分明显高于对照组(P<0.05)。两组治疗期间均未有发热、皮疹、肝肾功能障碍等不良反应发生。结论:苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病疗效明显优于脑苷肌肽治疗,其可有效调节血清HIF-1α、LXA4、ET-1水平,促进神经功能恢复,且安全性高。     

Comparison of natural and synthetic prostaglandin E2 tablets in labour induction.

A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects.     

Effect of stress-like concentrations of cortisol on follicular development and the preovulatory surge of LH in sheep

Stress-like concentrations of cortisol increase the negative feedback potency of oestradiol in castrated male sheep. A similar cortisol-dependent response in female sheep might be expected to suppress gonadotrophin secretion and impair follicular development and ovulation. The oestrous activity of 21 female sheep was synchronized using progestogen-treated vaginal pessaries to test this hypothesis. Stress-like concentrations of cortisol (60-70 ng ml-1) were established by continuous infusion of cortisol (80 micrograms kg-1 h-1; n = 13) beginning 5 days before, and continuing for 5 days after, pessary removal. Control animals (n = 8) received a comparable volume of vehicle (50% ethanol-saline) over the 10 day infusion period. Serum concentrations of oestradiol increased progressively in control sheep during the 48 h immediately after pessary removal. This increase in serum oestradiol was blocked or significantly attenuated in sheep receiving stress-like concentrations of cortisol. Preovulatory surge-like secretion of LH was apparent in control animals 58.5 +/- 2.1 h after pessary removal. In contrast, surge-like secretion of LH was not observed during the 5 days after pessary removal in 54% (7 of 13) of sheep receiving cortisol. Moreover, the onset of the surge was significantly delayed in the cortisol-treated ewes that showed surge-like secretion of LH during the infusion period. The ability of episodic pulses of exogenous GnRH to override the anti-gonadal effect of cortisol was examined in a second study. Oestrous activity of 12 ewes was synchronized using progestogen-containing pessaries as described above. Ewes were randomly assigned to one of three treatment groups (n = 4 ewes per group). Animals received cortisol (100 micrograms kg-1 h-1; groups 1 and 2) or a comparable volume of vehicle (group 3) beginning 5 days before, and continuing for 2 days after, pessary removal. Pulses of GnRH (4 ng kg-1 h-1, i.v.; group 1) or saline (groups 2 and 3) at 1 h intervals were initiated at pessary removal and continued for 48 h. Serum concentrations of oestradiol were not significantly increased after pessary removal in sheep receiving cortisol alone. Conversely, serum concentrations of oestradiol increased progressively during the 48 h after pessary removal in control ewes and in ewes receiving cortisol and GnRH. At the end of infusion, serum concentrations of oestradiol did not differ (P > 0.05) between control (7.7 +/- 0.8 pg ml-1) ewes and ewes receiving cortisol and episodic GnRH (6.4 +/- 1.3 pg ml-1). Moreover, these values were significantly greater (P < 0.05) than the serum concentrations of oestradiol in animals receiving cortisol (1.0 +/- 0.4 pg ml-1) alone. Collectively, these data indicate stress-like concentrations of cortisol block or delay follicular development and the preovulatory surge of LH in sheep. In addition, episodic GnRH overrides cortisol-induced delay in follicular maturation.     

Induction of labour by low amniotomy and oral administration of a solution compared to a tablet of prostaglandin E2

Labour was induced in 35 women by low amniotomy and the simultaneous oral administration of prostaglandin E₂ tablets (0.5 mg) hourly. The results of this group are compared to those of a similar number of patients who had labour induced by low amniotomy and the simultaneous administration of oral prostaglandin E₂ solution. There were no clinically significant differences between the two groups. Both methods are effective adjuncts to low amniotomy for the induction of labour, with an acceptable incidence of side effects.     

Insemination time and dilution rate of cooled and chilled ram semen affects fertility

Adult Merino ewes (n=448) were apportioned into two groups and inseminated with: extended at 30 degrees C with skim milk and stored for 6h at 15 degrees C (cooled semen) or extended with skim milk-citrate trisodium with egg yolk and stored for 24h at 5 degrees C (chilled semen). Each group was further subdivided according to the time of cervical insemination at 42, 46 and 50h after pessary (MAP-60 mg) removal and according to the dilution of the semen (120 x 10(6) spermatozoa in 0.05, 0.1 and 0.2 ml). The pregnancy rate after insemination with cooled semen was 50% better than that after chilled semen (56.7 vs. 37.5%; P<0.001). Pregnancy rate was not affected by the volume of insemination; however, there was a tendency of increased lambing rate with an insemination dose of 0.1 cc (1:2, dilution), especially when the ewes were inseminated with cooled semen. The effect of time on insemination was significant only in ewes inseminated with chilled semen at 5 degrees C (P<0.01). Insemination carried out 46 h after pessary removal resulted in higher pregnancy and lambing rate (36.5, 31.1; 52.0, 45.3; and 24.0, 20.0 at 42, 46 and 50h, respectively). Pregnancy of ewes inseminated with chilled semen at 46 h after pessary removal was similar to that obtained using cooled semen (52.0 vs. 56.7%). From this study, it is concluded that advancing the time of insemination with chilled semen at 5 degrees C improves pregnancy and that the lambing obtained under these conditions is similar to the one obtained with cooled semen.     

天麻素对全麻宫颈癌根治术患者术后认知功能及S-100beta影响

目的：探讨天麻素对全身麻醉下宫颈癌根治术患者术后认知功能及S-100beta的影响。方法：选取我院妇科收治的宫颈癌患者 86 例，随机数字表法分为两组，两组患者均在全身麻醉下行全子宫双附件切除联合盆腔淋巴结清扫术。对照组术后予以抗感染、 肠外营养支持等常规术后治疗，实验组术后常规治疗的基础上加用天麻素注射液。两组患者分别于麻醉前、手术后6 h、1 d、3 d及 7 d 测定MMSE 评分及血中S-100beta水平。结果：两组患者全麻宫颈癌根治术后均出现中度认知障碍，MMSE 评分较麻醉前下降， 与对照组同期比较，实验组术后3 天、7 天MMES 评分较高，差异具有统计学意义（P＜0.05）；两组患者宫颈癌根治术后血中 S-100beta蛋白水平升高，与对照组同期比较，实验组术后1 d、3 d与7d S-100beta水平较低，差异具有统计学意义（P＜0.05）。结论：天 麻素能够明显改善全麻宫颈癌根治术患者术后认知功能障碍，降低S-100beta蛋白水，提高术后恢复效果，对临床具有指导意义。