Prostaglandin E2 induced abortion with vaginal suppositories in a contraceptive diaphragm

PGE2 (prostaglandin E2), 20 mgm vaginal suppositories were administered to 2 groups of women seeking termination of pregnancy. 1 group had the suppository inserted inside a contraceptive diaphragm. Statistical comparisons were carried out for instillation to abortion time, side effects, and intrauterine pressure parameters. The usage of the diaphragm significantly reduced side effects, and resulted in an instillation to abortion time of 12.8 + or - 2.3 hours with no failures. The quantitative analysis of the uterine pressure recordings revealed activity significantly different than that seen with intraamniotic or extraovular PGF2alpha. The development of uterine activity simulates that of normal labor in that elevation of resting pressure does not occur and maximum active pressure evolves slowly.     

Prostaglandin E2 induced abortion with vaginal suppositories in a contraceptive diaphragm

Prostaglandin E₂, 20 mgm vaginal suppositories were administered to two groups of women seeking termination of pregnancy. One group had the suppository inserted inside a contraceptive diaphragm. Statistical comparisons were carried out for instillation to abortion time, side effects, and intra-uterine pressure parameters. The usage of the diaphragm significantly reduced side effects, and resulted in an instillation to abortion time of 12.8 ± 2.3 hours with no failures. The quantitative analysis of the uterine pressure recordings revealed activity significantly different than that seen with intra-amniotic or extra-ovular PG F_2α. The development of uterine activity simulates that of normal labor in that elevation of resting pressure does not occur and maximum active pressure evolves slowly.     

Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm.

Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E2 suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE2 suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE2 suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2 degrees F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last adminstration of PGE2. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE2 suppositories is a very effective abortifacient technque during the midtrimester, however the use of PGE2 in conjunction with a diaphragm did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE2 suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.     

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.     

The cervical relaxant properties of prostaglandin E2 in non pregnant subjects

To determine the cervical relaxant properties and side effects of intravaginal administration of prostaglandin E2 (PGE2) in nonpregnant patients, 5 subjects in midluteal phase were given 20 mg of PGE2 by intravaginal suppository. In 4 patients, no change was found in the diameter of the internal cervical os 12 hours after treatment; the other patient showed an increase of 1 mm. 4 of 5 experienced prolonged nausea, 3 experienced severe vomiting, 2 had diarrhea, all 5 suffered chills, 3 had tachycardia, 4 had fevers, 4 had abdominal cramping, and 1 suffered hypotension. These side effects were severe and their potential seriousness makes this drug inappropriate for use in nonpregnant patients via this route of administration.     

Development of a vaginal gel containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 for cervical dilatation and pregnancy termination

A stable hydrophilic gel for vaginal administration containing 9-deoxo-16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2) was developed and its clinical usefulness for preoperative cervical dilatation and for termination of first and second trimester pregnancy evaluated in 521 pregnant patients admitted to the hospital for therapeutic abortion. Following vaginal administration of 3 mg of 9-methylene PGE2 gel a peak plasma level of between 3.5 and 10 ng/ml was found 3 to 6 hours following treatment. The "bioavailability" of the drug was in the order of 25-30%. 9-methylene PGE2 was found to be equally effective as 1 mg Cervagem for preoperative cervical dilatation. With a pretreatment period of 3 hours side effects were rare with both compounds. If the pretreatment period was extended to 12 hours the degree of cervical dilatation, but also the frequency of side effects increased significantly. Repeated administration of 9-methylene PGE2 was found to be effective (96% complete abortion) in terminating very early pregnancy provided the total dose was 10 mg or more. During second trimester the minimum effective dose was 4.5 mg of the compound repeated every fourth hour. The results of the present study have shown that with the new gel formulation the amount of 9-methylene PGE2 needed to terminate first and second trimester pregnancy was approximately ten times less in comparison with the previously used lipid base suppositories. The treatment was also associated with a low frequency of side effects.     

Endocervical prostaglandin E2 gel for preinduction cervical softening

A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.     

Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm

Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E₂ suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE₂ suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE₂ suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2° F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last administration of PGE₂. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE₂ suppositories is a very effective abortifacient technique during the midtrimester, however the use of PGE₂ in conjunction with a diaphrgam did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE₂ suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.     

Preinduction cervical priming in high risk pregnancy — experience with a new sustained release PGE2 vaginal film

Experience with a new sustained release PGE2 formulation is presented. 111 high risk primiparae with very poor cervical scores (<3) were studied. In 59 patients, labour was induced by forewater amniotomy and I.V. oxytocin. In the remaining 52 patients, film containing 850 ug of PGE₂ was inserted into the vagina to ripen the cervix 24 hours prior to induction of labour. Indications for elective delivery and maternal characteristics were similar in both groups. There were significant changes in the cervical state within 12 hours of vaginal insertion. By 24 hours, 19 patients receiving vaginal film (36.5%) had established labour of whom 13 proceeded to vaginal delivery. Significantly fewer patients in the priming group required Caesarean delivery. No untoward maternal or fetal side effects were observed.Safety, ease of administration and efficacy make this new PGE₂ formulation a useful agent for priming of the very poor primiparous cervix prior to induction of high risk labour.     

Effect of intravaginal instillation of some non-steroidal oral antifertility agents on pregnancy in rats

A study was conducted of the effect of intravaginal instillation of 3 nonsteroidal oran antifertility agents in pregnant rats. The 3 compounds used were 2-phenyl-3-rho-beta-pyrrolidinoethoxyphenyl-6-methox y benzofuran hydrochoride (DBF), 20 mg/kg; 2-phenyl-3-rho-beta-pyrrolidi noethoxyphenyl-naptha (2:1,b furan (NF), 10 mg/kg; and Centchroman, 1.25 mg/kg. These agents were administered on Day 1 postcoitum at the single-day oral contraceptive dose. Control animals were inserted with a pellet containing only carboxymethyl cellulose. Only Centchroman was 100% effective in preventing pregnancy. Even at half the normal dose, Centchroman was effective. Of the 3 compounds, only Centchroman has an antiprogestational property which may be contributing to Centchroman's high antifertility activity by the vaginal route and may prevent side effects.     

Synthesis and biological properties of 9-deoxo-16,16-dimethyl-9-methylene-PGE2.

The in vivo monkey uterine stimulating potency of 9-deoxy-16,16-dimethyl-9-methylene-PGE2 is similar to that of 16,16-dimethyl-PGE2 and approximately 15 times that of PGE2. Low doses of this compound stimulated uterine contractions when administered vaginally. Pregnancy was terminated prematurely following subcutaneous, intramuscular or vaginal suppository treatment. Estimates of potential for gastrointestinal side effects using the rat enteropooling assay and in vivo monkey effects indicate that diarrhea will be substantially reduced with retention of uterine stimulating potency.     

The mechanism of prostaglandin action on the early pregnant human uterus

To extend observations in 11 weeks pregnant patients the mechanism of prostaglandin (PG) action has been examined in 6 weeks pregnant women (LMP). In 10 gravidas menstrual induction was attempted with a single slow release vaginal suppository containing 3000 microgram (155)-methyl PGF2 alpha methyl ester (U-36,384). In 10 additional gravidas menstruation was provoked by the intramuscular injection of 500 microgram 16-phenoxy-omega-tetranor PGE2 methyl sulfonylamide (Sulproston) at 4 hour intervals, totalling 1250 +/- 154 microgram. The PGF2 alpha and PGE2-analogues provoked similar changes in hormone levels and uterine function, sequentially measured by radioimmunoassays and the recording of intrauterine pressure. However, the effects of the intramuscular regimen developed earlier. Both treatments successfully terminated early pregnancy with clinical symptoms of menstruation if they irreversible compromised the conceptus within 12 hours. However, while both formulations represent advances in postconceptional therapy, only further modifications may closely approximate the "ideal" method of non-surgical menstrual induction.     

Plasma concentration of 13,14-dihydro-15-keto-PGE2 (PGEM) after various ways of cervix ripening with PGE2

PGEM concentration was determined radioimmunologically in a non-pregnant woman, in whom PGE2 was infused intravenously at increasing rates and in women, in whom labor was induced by various methods for local application of PGE2. There was excellent correlation between the amount of PGE2 infused intravenously and the levels of PGEM determined in the peripheral plasma. The following methods of local application of PGE2 were included in the study: 0.4 mg PGE2 gel placed retroamnially by means of a balloon catheter, 0.4 and 0.5 mg PGE2 applied endocervically and 3 mg PGE2 placed intravaginally in form of a single vaginal tablet; also included was a control-group, where only vaginal examination was performed. Bloods were drawn before, 30 minutes, 1, 2 and 3 hours after PGE2 administration. Mean levels of PGEM in the maternal peripheral plasma did not change neither within nor between the various groups. It is concluded from the present study, that local application of doses currently used to soften the cervix and/or induce labor at term do not lead to the same PGEM-concentration in the maternal blood as after intravenous infusion of PGE2 in doses normally used to induce labor.     

Vaginally administered PGF2alpha for cervical dilatation in nulliparas prior to suction curettage

Because of the need for an atraumatic method to dilate the cervix when performing artificial abortion by suction curettage, cervical dilatation following vaginally administered PGF2alpha was studied. A 50 mg PGF2alpha vaginal suppository was administered to 40 (treated group) first trimester nulliparas 3 hours prior to progressive cervical dilatation from a 19 (circumference in mm) Pratt dilator to a 35 Pratt dialator. The smallest-sized dilator that met resistance was interpreted as being the amount of clinically significant cervical dilatation. The results were compared to 20 (control group) first trimester nulliparas who received no PGF2alpha studied in an identical manner. Independent of gestational age, treated patients were dilated significantly more than the control patients. When subjects of similar gestational age were compared, PGF2alpha treated subjects were more often dilated sufficiently to perform abortion (55%) by suction curettage than control group subjects (5%). Those PGF2alpha subjects needing further dilatation to accept an appropriate sized cannula for their gestational age needed less dilatation than did those subjects of similar gestational age in the control group. No serious complications of PGF2alpha per se were observed and the most frequent side effects, vomiting and diarrhea, did not appear severe enough to limit the clinical practicability of the method.     

Prostaglandin E2 in a diaphragm a further note

In a previous study we reported that the administration of Prostaglandin E₂ suppositories in a vaginal contraceptive diaphragm enhanced the effectiveness of the drug and reduced the incidence of side effects by 50%.1 Since that study there have been two reports which could not verify our experiences. 2, 3 Therefore we attempted to look at the problem again.     

Induction of second trimester abortion: Comparison between vaginal 15-methyl-PGF2α methyl ester and intra-amniotic PGF2α

The efficiency and acceptability of a single-dose, long-acting vaginal suppository containing 3.0 mg of 15-methyl PGF_2α methyl ester was compared with intra-amniotic administration of 50 mg of PGF_2α in 100 patients with a second trimester pregnancy termination. Within 24 hours, 78 per cent of the patients in the vaginal group and 92 per cent in the intra-amniotic group had aborted. The mean induction-abortion interval was 17.9 hours in the vaginal group and 15.8 hours in the intra-amniotic group.Gastrointestinal side-effects were more frequent, but the procedure was less painful, with vaginal 15-methyl PGF_2α methyl ester than with intra-amniotic PGF_2α.The vaginal route is technically simple for adaptation to large-scale use, but the high frequency of gastrointestinal side-effects still limits the acceptability of 15-methyl PGF_2α methyl ester in vaginal administration.     

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.     

Intra-amniotic prostaglandin F2α and urea for abortion

Prostaglandin F_2α (PGF_2α) 20 mg combined with urea 80 g was injected intra-amniotically in 20 patients to induce mid-trimester abortion. Abortion resulted in all subjects within 24 hours in a mean time of 12 hours 38 minutes (range 5 hours 50 minutes to 20 hours 45 minutes).Plasma sex steroids were evaluated before and hourly for 5 hours after the injection. A progressive decline in levels occurred with time. Decreases in plasma progesterone, estrone, estradiol and estriol were significant as soon as one hour after injection.Gastrointestinal side effects occurred with a greater frequency than when a comparable dose of PGF_2α is given alone and 2 patients had small cervical lacerations requiring suture. Further studies are indicated to establish whether a lower dose of PGF_2α will be associated with fewer side effects and be as effective.     

Cervical ripening with intravaginal prostaglandin E2 gel.

We describe a technique of administering prostaglandin E2 (PGE2) in a viscous cellulose gel into the vagina to ripen the unfavourable cervix in patients requiring induction of labour. A total of 168 primigravidae were studied, of whom 102 received 2 mg PGE2 in 2% gel and 66 received 5 mg PGE2 in 4% gel. In the latter group, the state of the cervix was significantly improved in 58 patients (87.9%), while 32 (48.5%) had started labour before planned induction. There were no maternal or fetal side effects or complications.     

调节阴道微环境在治疗妊娠期复发性念珠菌性阴道炎中的作用

目的初步探讨应用乳杆菌活菌胶囊在治疗妊娠期复发性念珠菌性阴道炎中的作用。方法将2009年12月。2011年12月共266例在我院产科门诊就诊的妊娠期复发性念珠菌性阴道炎患者随机分为试验组和对照组,试验组给予克霉唑联合中药及乳杆菌活菌胶囊治疗,对照组仅给予克霉唑联合中药治疗,观察采用乳杆菌活菌胶囊调节阴道内微环境后的临床疗效,远期自愈率及复发率。结果两组的近期治愈率相似,近期治疗效果分布无显著性差异（P〉0．05）,但给予乳酸杆菌活菌胶囊治疗远期自愈率28．57％明显高于对照组,远期复发率为11．03％,明显低于对照组的26．92％,分娩时复发率（10．29％）明显低于对照组（29．23％）,两者比较有显著地统计学意义（P〈0．05）。结论克霉唑联合中药及乳杆菌活菌胶囊治疗妊娠期复发性念珠菌性阴道炎临床效果好,远期自愈率高,复发率低,副反应小。