Rupture of the uterus following treatment with 16-16-dimethyl E 2 prostaglandin vagitories.

Rupture of the uterine body was found after induction of therapeutic abortion with vaginal suppositories containing 16, 16-dimethyl prostaglandin E 2 in a 20-year-old primigravida. A short discussion is given on the cervical complications that can occur after prostaglandin induction of abortion, stating that rupture of the uterine body also can be seen. So far, no prostaglandin compound seems to avoid such complications.     

Uterine rupture as a complication of second trimester abortion using intraamniotic prostaglandin E2 and augmentation with other oxytocic agents

Two cases of ruptured uterus are presented following attempted induction of midtrimester abortion using intra-amniotic prostaglandin E₂ and augmentation with other oxytocic agents. With continued uterine stimulation the diagnosis of rupture may not be obvious and the diagnostic features are discussed. Patients of high parity appear to be particularly susceptible to uterine rupture during induced midtrimester abortion.     

Prostaglandin-induced pregnancy termination: Further studies using gemeprost (16, 16 dimethyl-trans-Δ-PGE1 methyl ester vaginal pessaries in the early second trimester

The use of gemeprost (16, 16 dimethyl-trans-Δ²-PGE₁ methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 ± 0.1 1mg gemeprost pessaries. The mean induction — abortion interval was 881 ± 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occured in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.     

Prostaglandin-oxytocin Enhancement and Potentiation and their Clinical Applications

The pharmacological phenomena of enhancement and potentiation of uterine response occur respectively when combinations of some prostaglandins and oxytocin are given serially and simultaneously to a patient. Employing these phenomena allows small doses of the drugs to achieve the same effects as a large dose given alone. In a pilot study of the use of the combination of prostaglandin and oxytocin for the induction of mid-trimester abortion seven of nine women were aborted within 48 hours. Side effects attributable to prostaglandin were eliminated or reduced in severity.     

Decreased smooth muscle side effects with 16, 16-dimethyl-trans-delta2-PGE1 methyl ester in Japanese monkey (Macaca Fuscata Fuscata).

The smooth muscle stimulating activity of a new PGE1 analog, 16, 16-dimethyl- trans delta2 -PGE1 methyl ester (ONO-802) was evaluated by simultaneously recording the EMG of the uterus and intestines, along with urinary bladder pressure, and blood pressure in pregnant and non-pregnant Japanese monkeys (Macaca fuscata fuscata). Single intravenous injections of ONO-802 in increasing dosages (0.2-5 microgram/kg) were found to be 50-100 times or more effective in inducing uterine contraction than PGF2alpha and PGE1. A mild, transient gastrointestinal muscle stimulating activity was observed, but change in urinary bladder pressure and blood pressure was not evident. ONO-802 induced uterine contractions in the pregnant animals were 10 times greater than in the non-pregnant animals. These results suggest that ONO-802 may be a suitable clinical prostaglandin for use in therapeutic abortion.     

Uterine trauma associated with midtrimester abortion induced by intra-amniotic prostaglandin F2α with and without concomitant use of oxytocin

Five of 80 (6.2%) nulliparous women sustained uterine trauma in association with midtrimester abortion induced by intra-amniotic prostaglandin F_2α and intravenous oxytocin. All five women suffered cervical lacerations, one extending to the lower uterine segment of the corpus and another associated with myometrial necrosis caused by cornual sacculation and ischemia. No uterine trauma was observed among 95 parous women aborted in the same fashion during this study. The different mechanisms of cervical dilatation in the parous woman and the nullipara are offered as an explanation for this difference. Thirty-nine other cases of uterine injury associated with the use of intra-amniotic prostaglandin F_2α from the literature were reviewed, and found to indicate that midtrimester abortion induced by intra-amniotic prostaglandin F_2α is associated with a significant risk of uterine trauma in the nullipara. The risk seems to increase with the use of oxytocin and with increasing gestational age.     

The antagonism by anti-inflammatory analgesics of prostaglandin f 2 alpha-induced contractions of human and rabbit myometrium in vitro.

The anti-inflammatory analgesic drugs, aspirin, indomethacin, phenylbutazone, mefenamic acid ibuprofen and flurbiprofen are shown to inhibit in a dose-dependent manner the force of contraction of isolated human pregnant myometrial strips which have been stimulated to contract by adding prostaglandin (PG) F2alpha to the tissue bath. These drugs and also flufenamic acid and salicin show a similar antagonism of the action of PGF2alpha with isolated rabbit non-pregnant myometrium. The ratio of the inhibitory concentration in vitro to the maximum plasma level after a normal dose in vivo suggests that phenylbutazone and possibly ibuprofen may be capable of inhibiting human uterine contractions in vivo. Patients who were treated with aspirin during induction of abortion using PGF2alpha during the second trimester of pregnancy showed no significant change in the induction-abortion interval compared with patients not taking aspirin.     

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.     

Induction of abortion by intra- and extra-amniotic prostaglandin F2 administration

PGF2 alpha was administered intrauterine in 115 patients during the 11th to 20th week of pregnancy for abortion induction. An intra-amniotic method was used in 61 cases, an extra-amniotic one in 54 cases. Average total dose administered was 35.1 (range 5 to 65 mg) in the amniotic group and 6358 mcg (range 1500 to 14000 mcg) in the extra-amniotic group. The intra-amniotic group had an abortion rate of 92% and a 74% rate of side effects, mainly gastrointestinal irritation. Corresponding figures for the extra-amniotic group were 72% and 54% respectively. In the extra-amniotic group, doses of 4750 mcg or more increased the abortion rate up to 80% and side effects up to 64%. There were no serious complications. The intra-amniotic approach of prostaglandin induction is suitable for second trimester therapeutic abortions. The extra-amniotic approach is useful in cases of fetus mortuus and hydatiform mole.     

Blood Coagulation Changes during Mid-trimester Abortion Induced by Prostaglandin F2α

Serial studies on the coagulation system were made during second-trimester abortion induced by extra-amniotic, intra-amniotic, vaginal, and intravenous prostaglandin F₂α. No significant changes were found in the prothrombin time, partial thromboplastin time, or levels of fibrin-fibrinogen degradation products. An increase in the activity of factor X occurred with all routes of administration; the activity of factor VIII increased during extra-amniotic, vaginal, and intravenous administration; factor V activity increased during extra-amniotic and vaginal administration; and the activity of factor VII-X complex increased slightly at the time of abortion with all methods.The findings suggest that though prostaglandin induction of second-trimester abortion produces changes in the coagulation system the effects are much less than those which accompany induction of abortion by hypertonic saline or abdominal delivery in late pregnancy.     

Coagulation Changes during Termination of Pregnancy by Prostaglandins and by Vacuum Aspiration

Serial studies on coagulation factors were performed on 12 patients having termination of mid-trimester pregnancy by extra-amniotic prostaglandin F₂α and 11 patients terminated by vacuum aspiration during the first trimester. A significant change in the activity of factors V, VII and X, VIII, and X, and a decrease of the prothrombin time and platelet count were found with prostaglandin termination but no such changes occurred during vacuum aspiration. These findings suggest that the coagulation system is activated during induction of mid-trimester abortion with extra-amniotic prostaglandin F₂α. This is probably related to the physiological changes in the coagulation mechanism which occur by the second trimester of pregnancy. Termination of pregnancy in the mid-trimester may, however, be expected to give rise to defective blood coagulation and thromboembolic complications.     

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 receptor subtype EP-2 is not involved in the induction of non-pregnant guinea pig uterine contractions associated with terminal pregnancy

Prostaglandin E2 (PGE2) exerts its biological effects through 4 different receptor subtypes, EP-1, EP-2, EP-3, and EP-4. Recently we have demonstrated the importance of the prostaglandin E2 receptor subtype EP-2 in the healing of bone defects and fractures. This discovery led to the identification of CP-533,536, an EP-2 selective agonist, a promising therapeutic alternative for the enhancement of bone healing and the treatment of fractures (J Bone Miner Res 18 (2003) 2033). PGE2 has a myriad of effects throughout the body including the induction of uterine contractions, which results in termination of pregnancies. Our objective in this study was to determine the role of the EP-2 receptor and specifically that of CP-533,536, an EP-2 specific agonist, to induce uterine contractions and terminate pregnancy in guinea pigs, an animal model of human pregnancy. Preliminary experiments confirmed earlier reports that the guinea pig uterus was more sensitive than that of the rat. The guinea pig uterus contains the four PGE2 receptor subtypes, and ex vivo treatment of the uterus with PGE2 as expected causes profound uterine contractions. However, using receptor selective prostaglandin agonists including CP-533,536 we showed that the EP-1 and 3 receptors not the EP-2 receptor is responsible for the induction of uterine contractions of PGE2. Further, CP-533,536 did not antagonize the ability of PGE2 to induce uterine contractions in this model.     

Prostaglandin-induced pregnancy termination: further studies using gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries in the early second trimester

The use of gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 +/- 0.1 1 mg gemeprost pessaries. The mean induction-abortion interval was 881 +/- 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occurred in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.     

Prostaglandin-induced Abortion: Assessment of Operative Complications and Early Morbidity

A total of 626 patients undergoing a prostaglandin-induced abortion, the majority in the second trimester, have been analysed for complications occurring during inpatient treatment. Of the last 155 consecutive patients 143 were critically assessed six to eight weeks after abortion for morbidity occurring during their early recovery period.Blood loss of 250 ml or more occurred in 68 patients, pyrexia in 34, pelvic infection in three, and readmission in 14 of the 626 patients studied, and a transfusion was required in eight.Bleeding after abortion stopped within six weeks in all 143 of the 155 consecutive patients assessed but three required readmission for uterine curettage. Menstruation was re-established within six weeks of abortion in 106 patients.The incidence of operative morbidity was similar to that reported for first trimester abortion and better than that in most reported series of second trimester abortions.     

The use of oral prostaglandin E2 in the management of intrauterine fetal death

12 otherwise healthy patients with intrauterine fetal death 1 to 6 weeks earlier were treated with oral prostaglandin E2. 9 of the 12 patients delivered within 48 hours after treatment began. 2 others delivered with 48 hours after unsuccessful treatment ceased. In a third patient the cervix relaxed after treatment, and the uterine contents were removed by curettage. No serious complications, such as hemorrhage occurred. The uterus seemed surprisingly responsive to oral prostaglandin E2 in cases of intrauterine fetal death.     

The antagonism by anti-inflammatory analgesics of prostaglandin F2α-induced contractions of human and rabbit myometrium

The anti-inflammatory analgesic drugs, aspirin, indomethacin, phenylbutazone, mefenamic acid, ibuprofen and flurbiprofen are shown to inhibit in a dose-dependent manner the force of contraction of isolated human pregnant myometrial strips which have been stimulated to contract by adding prostaglandin (PG) F_2α to the tissue bath. These drugs and also flufenamic acid and salicin show a similar antagonism of the action of PGF_2α with isolated rabbit non-pregnant myometrium. The ratio of the inhibitory concentration to the maximum plasma level after a normal dose suggests that phenylbutazone and possibly ibuprofen may be capable of inhibiting human uterine contractions . Patients who were treated with aspirin during induction of abortion using PGF_2α during the second trimester of pregnancy showed no significant change in the induction-abortion interval compared with patients not taking aspirin.     

几丁糖和透明质酸钠对宫腔粘连的防治效果及并发症的影响

目的:探讨几丁糖和透明质酸钠对宫腔防粘连效果及并发症的影响。方法:回顾性分析本院2013年9月~2014年9月收治的150例人工流产患者的临床资料,均实施常规无痛人流手术,按照术前处理方式的不同分为空白对照组(50例)和几丁糖组(50例)、透明质酸钠组(50例)。术后随访6个月,观察两组的阴道流血持续时间和月经复潮时间,以及术后第14 d子宫内膜厚度和术后粘连发生情况、并发症发生情况,并进行比较。结果:术后几丁糖组和透明质酸钠组的阴道流血持续时间和月经复潮时间,以及术后第14 d天子宫内膜厚度和术后粘连发生情况、并发症发生率与空白对照组之间均存在统计学差异,各项指标均显著优于空白对照组,P0.05,但几丁糖组和透明质酸钠组二组间比较差异无统计学意义,P0.05。结论:对人工流产患者予以几丁糖和透明质酸钠处理均可以获得良好的临床效果,有效减少术后粘连以及各种并发症的出现。     

The induction of labour by the intravenous infusion of prostaglandin F2alpha

Labour was induced by the intravenous infusion of prostaglandin F2alpha in 106 patients at 36-44 weeks of pregnancy. The induction was successful in 80% of the women. The total dose needed ranged from 0.1 to 14.2 mg of PGF2alpha. The uterine activity and fetal heart rate were recorded by cardiotocography. The contraction pattern and induction-delivery time were the same as reported for induction with oxytocin. In one case uterine hyperactivity occurred after rupture of the membranes. No serious adverse effects were seen, but in a few cases local irritation was noted at the site of infusion. The condition of the infants was generally good. It might be concluded that PGF2alpha seems valuable for the induction of labour, but due to the risk for over-stimulation careful supervision is needed.     

Menstrual induction with PGF2 alpha and PGE2.

The "prostaglandin impact" (PGI), a massive intrauterine dose of PG, converts the refractory pregnant uterus into a reactive organ by provoking a regulatory imbalance. This regulatory conversion releases the endogenous mechanism of menstruation or abortion. During initial studies, PGI successfully provoked menstrual induction (MI) in 22 and subsequently in 65 volunteers. These results were confirmed and complemented by 2 independent trials in 14 and 36 gravidas respectively. The best clinical outcome was obtained in 20 volunteers, when a "PG-Pellet" (a mini-suppositorium) was inserted in utero, containing only 2.5 mg PGF2alpha. These 157 trials in sedated volunteers had the common features of over 90% efficiency, transient and medically acceptable side effects and infrequent complications. The present study of 542 volunteers focused upon the collection of clinical data regarding efficacy, side effects and complications of MI. All patients had committee approval for legal abortion, during the 2nd week of their missed menstrual period. They volunteered to participate because of their preference for pharmacological rather than surgical pregnancy termination. The clinical outcome of the 542 MI with 5 mg PGF2alpha (428 cases) and 1.5 mg PGE2 (114 cases) was identical. On the average, 95% of the gravidas had complete evacuation of the uterus with the clinical symptoms of delayed menstruation rather than abortion; they experienced spontaneous menstruation in 34 days after having received a single dose of PG.