A comparative study of plasma 17beta-oestradiol, progesterone, placental lactogen and chorionic gonadotrophin in abortion induced with intra-amniotic prostaglandin F2alpha

Serial estimations were made in plasma of 17beta-oestradiol (E2), progesterone and human placental lactogen (HPL) in 43 patients and of human chorionic gonadotrophin (HCG) in 34 patients during mid-trimester abortions induced with intra-amniotic prostaglandin F2alpha (PGF2alpha. Mean plasma concentrations of all the hormones showed a progressive fall after PGF2alpha. There was no relationship between the fall in levels of progesterone, HPL and HCG and the induction-abortion interval, signs of fetal distress or of intrauterine fetal death. Both the control level and the rate of fall of E2 were related to the induction-abortion interval and a rapid decline preceded intrauterine fetal death. The relationships of the progesterone/E2 ratio and the amniotic fluid volume/progesterone ratio to the induction-abortion interval were examined. The variation in the time at which significant falls in the concentration of individual hormones occurred was probably related to their respective half-lives in plasma.     

Extra-amniotic saline infusion for induction of labour in antepartum fetal death: a cost effective method worthy of wider use

OBJECTIVE: To compare the effectiveness of extra-amniotic saline with intra-amniotic prostaglandin F2 alpha in inducing labour in pregnancies with intrauterine fetal death. DESIGN: A randomised controlled trial. PARTICIPANTS: One hundred and twenty-one women in the extra-amniotic saline group and 123 women in the intra-amniotic prostaglandin group, performed at Harare Maternity Hospital, Zimbabwe during the period October 1994 to February 1996. RESULTS: The two methods were equally effective in achieving delivery. The number of women not delivering within 48 hours of recruitment was 6% for the extra-amniotic saline group compared with 11% for the intra-amniotic prostaglandin group (relative risk [RR] 0.51, 95% CI 0.21-1.22). The extra-amniotic saline group required augmentation with Syntocinon more frequently than the intra-amniotic prostaglandin group: 22% compared with 7% (RR 3.1, 95% CI 1.5-6.2). There were more complications associated with the intra-amniotic prostaglandin group: five women developed hypertonic contractions compared with none in the extra-amniotic saline group. In addition 23% of women in the intra-amniotic prostaglandin group developed acute vasovagal-like symptoms lasting for about 10 to 15 minutes which were distressing for the women. There was no evidence of any increase in febrile morbidity from extra-amniotic saline (RR 0.8, 95% CI 0.75-1.1). CONCLUSION: Extra-amniotic saline infusion in successful in inducing labour in antepartum fetal deaths after 20 weeks of gestation. This method has been shown to be safe and well tolerated by the women and should be considered in areas with limited resources. This method should be evaluated further for inductions of labour with a live fetus.     

Prostaglandins and thromboxanes in amniotic fluid during rivanol-induced abortion and labour

Abortion or delivery were induced by extra-amniotic instillation of Rivanol during the second trimester in twelve patients and during the third trimester in two patients with fetal death and one patient with fetal acrania. Serial sampling of amniotic fluid was performed through a transabdominal catheter and the levels of free arachidonic acid (AA), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) were determined. The levels of AA, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and TXB2 in amniotic fluid increased significantly during induction with the exception of AA in fetal death which was high and remained constant during induction. Furthermore, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 were all significantly correlated to AA. These observations suggested that free AA is released during Rivanol-induction of abortion and labour giving an increased synthesis of PGF2 alpha, PGE2 prostacyclin and thromboxane A2 in the fetal membranes and the decidua but not in the fetus. This increase might be relevant for the initiation and progress of abortion and labour in these patients.     

Therapeutic midtrimester abortion by the intra-uterine administration of prostaglandins. Experience of Groote Schuur Hospital, 1974-1975

During the period from 1 January 1974 to 31 December 1975, 71 therapeutic midtrimester abortions were performed at Groote Schuur Hospital by the intra-uterine administration of prostaglandins. Both the extra- and intra-amniotic routes of administration proved to be uniformly successful but the latter route was associated with fewer side-effects. The intra-amniotic administration of 30 mg prostaglandin F2alpha in combination with 60 g urea is the recommended method for achieving midtrimester abortion. If the method described is strictly adhered to, it provides a single-dose regimen which is uniformly successful and which is associated with few complications.     

A comparison of oral prostaglandin E2 and intravenous oxytocin for induction of labor in normal and high-risk pregnancies

The efficacy of oral prostaglandin E2 (PGE2) for induction of labor has been compared to that of intravenous oxytocin. There were 49 patients in each series. The over-all success rate with PGE2 is 82 per cent; with oxytocin, 65 per cent. PGE2 is at least as effective as oxytocin regardless of Bishop score or gravidity. There was no difference in the duration of labor in successful inductions with PGE2 or oxytocin. Nausea and diarrhea are more common with PGE2 but in only one case was this severe enough to warrent discontinuing the medication. One case of uterine hypertonus occurred in each series. No serious harmful effects on mother or fetus were noted with PGE2. These data support the concept that oral PGE2 administration is a safe and effective alternative to intravenous oxytocin for induction of labor in normal and high-risk pregnancies.     

Experimental amniocentesis and teratogenesis. 1. Evaluation of the intra-amniotic route of treatment in teratological studies

Experiments were designed to evaluate the usefulness of the intra-amniotic route of administration of test-substances in teratological studies. Particular attention was given to the differences in fetal parameters of growth and development and the incidence of fetal mortality between treated and untreated offspring which might be induced as a result of the treatment. Amniocentesis on gestational days 14, 15 or 16 produced a high incidence of fetal mortality and a significant reduction in the weights and crown-rump lengths of treated offspring. With increasing gestational age at the time of treatment and by reducing the volume of solvent injected, fetal mortality was decreased.     

Undetectable maternal serum unconjugated estriol levels in the second trimester: risk of perinatal complications associated with placental sulfatase deficiency

OBJECTIVE: Our purpose was to determine the prevalence of undetectably low second-trimester maternal serum unconjugated estriol levels and the association with increased perinatal morbidity or mortality in pregnancies at risk for placental sulfatase deficiency. STUDY DESIGN: Nine centers in New England identified singleton pregnancies with undetectably low unconjugated estriol levels. Each unexplained case was matched with four controls; pregnancy outcome information was sought. RESULTS: Among 130,295 pregnancies surveyed, undetectably low unconjugated estriol levels were identified in 167 (13/10,000). Explanations included fetal death (53), overestimated gestational age (50), nonpregnancy (12), and chromosome abnormalities (5). The 41 unexplained cases were compared with 163 matched controls. Male offspring were more frequent (85%) among cases than among controls (55%). Although rates of perinatal complications were not significantly different, primary cesarean sections occurred about twice as often among cases. No perinatal deaths occurred. CONCLUSIONS: Neither severity of symptoms nor perinatal morbidity or mortality currently warrant routine interpretation of unexplained undetectably low unconjugated estriol levels as a marker for placental sulfatase deficiency.     

Protein kinase A activators inhibit agonist induced prostaglandin production in human amnion

Prostaglandin (PG) production by human amnion has been postulated to have a role in the onset of labor. Previous work by ourselves and others has demonstrated that oxytocin, phorbol esters and epidermal growth factor (EGF) increase PGE2 production in human amnion cells by activation of the Phospholipase C/Protein Kinase C (PKC) cascade system. The present study was undertaken to determine the effect of prior activation of the Adenylate Cyclase cascade system upon subsequent stimulation of PGE2 production by oxytocin, phorbol 12-myristate-13-acetate (PMA) or EGF in amnion cells and membrane discs. Isoproterenol, forskolin and dibutyryl cyclic adenosine monophosphate (dbcAMP) were utilized to activate the Adenylate Cyclase system at the receptor, enzyme and second messenger level. In control amnion cells, oxytocin, PMA and EGF each provoked dose dependent increases in PGE2 production. In cells preincubated with dbcAMP, forskolin or isoproterenol, agonist stimulated PGE2 production was markedly (50-90%) inhibited (p < 0.01). Inhibition was dose dependent upon preincubator concentrations. Maximal inhibition by adenylate cyclase activators occurred with 2-4 h of preincubation. In membrane discs, forskolin preincubation also inhibited oxytocin, PMA and EGF stimulation of PGE2 production. Activation of the Adenylate Cyclase system in human amnion cells or membrane discs inhibits the subsequent action of potent stimulators of PGE2 production in human amnion.     

Plasma concentrations of unconjugated estrone, estradiol-17beta and estriol, and HCS throughout pregnancy in diabetics and gestational diabetics

Plasma unconjugated estrone (E1), estradiol-17beta (E2) and estriol (E3), and HCS were measured in the same plasma samples collected throughout pregnancy in 19 gestational diabetics (GD) and 21 diabetics (D). When compared to the results obtained in 22 normal subjects, plasma levels of E1 and E2 were significantly elevated in D in the second half of gestation. The results were intermediate although closer to the normals, in GD. E3 values were not different from the normals in both D and GD. HCS values were lower than normal in early pregnancy in both D and GD. In late pregnancy HCS levels were not different from normal in either D or GD, although some individual values were much above the upper limit in some diabetic patients. The hormonal ratios in D and GD parallel those in normals, although E3/E2 and HCS/E2 were lower in D. These results are discussed with respect to the different behaviour of E2 and E3, taking into account the difference in their respective biosynthetic pathways. Besides a possible quantitative modification of the placental function in D, the results could tentatively be explained by a qualitative change in the fetal estrogen precursors to placental aromatization, in favour of the 16 non-hydroxylated compound. However, maternal modifications in precursor production or in estrogen metabolism can be an alternative hypothesis. Finally, the present work does not support the hypothetical estrogen deficiency in diabetic pregnancy. Estrogen treatment appears to have no objective justification.     

Midtrimester pregnancy termination for fetal malformations. Use of intravaginal prostaglandin E2

OBJECTIVE: To compare outcome differences and responses to treatment in pregnancies complicated by either major fetal malformations or previous fetal death in the second trimester. STUDY DESIGN: Data were analyzed from a computerized perinatal database and individual hospital records for singleton gestations between 14 and 23 weeks undergoing labor induction with prostaglandin E2 (PGE2) suppositories (20 mg intravaginally every three to five hours). RESULTS: Between January 1993 and June 1995, 65 pregnancies underwent induction of labor for either a lethal fetal malformation (38) or death (27). As compared with the fetal death group, the malformation group required more suppositories (median 4, range 1-10, versus median 3, range 1-6; P < .05) and needed a greater total dosage (77.5 +/- 38.5 mg versus 61.8 +/- 37.8 mg, P < .05). The mean time from initiation of treatment until delivery was two hours longer in the malformation group. There were no significant differences between the two treatment groups in incidence of maternal side effects or of retained placentas requiring operative intervention. CONCLUSION: Patients who undergo second-trimester induction of labor for major fetal malformations using intravaginal PGE2 should be counseled that the dosage of the drug is greater and that labor may last longer than in pregnancies complicated by a previous fetal death.     

The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

Transcervical embryoscopic diagnosis of conjoined twins in a ten-week missed abortion

Embryoscopic diagnosis of conjoined twins presenting with a missed abortion has never been reported. The morphological and pathological examinations, and the exact time of death in the conceptus of a missed abortion are seldom clearly delineated. The newly developed field of embryoscopy has created a new frontier in early embryonic/fetal visualization and is able to confirm the sonographic diagnosis. In this report, we used a transcervical endoscope to verify conjoined twins (thoraco-omphalopagus) in a 10-week missed abortion. Based on the size and the external features of the dead embryo, which exhibited developmental arrest at nine weeks and three days of menstrual age, we estimated that the embryo had died four days before examination. The whole procedure proceeded smoothly without any immediate complications.     

Termination of abnormal intrauterine pregnancies with intramuscular administration of dihomo 15 methyl prostaglandin F 2alpha

A synthetic compound, 2a, 2b dihomo 15 (S) 15 methyl prostaglandin F 2 alpha methyl ester given 8-hourly by intramuscular injection was used to terminate pregnancies in 72 patients with a missed abortion, intrauterine fetal death, molar or anencephalic pregnancies. Treatment was successful in all cases. A 4 mg dose of loperamide given orally at 15 to 30 minutes before the injection of prostaglandin analogue prevented diarrhoea as a side effect.     

Effects of 16,16-Dimethyl-trans-delta 2-PGE1 methyl ester (ONO-802) on uterine, placental and ovarian circulation (author's transl)

Doses of the drugs which produce uterine contraction were given intravenously to various species of animals. Placental and ovarian circulations were measured by the thermocouple method and/or microangiography. Uterine arterial blood flow (UABF) was measured by the electromagnetic flowmeter. Both placental blood flow (PBF) and UABF decreased with the administration of ONO-802, PGE1 or PGF2 alpha to to rabbits and dogs. Oxytocin and noradrenaline also decreased PBF in rabbits. ONO-802 or PGE1 lowered arterial blood pressure (BP) in rats, rabbits and dogs. PGE2 alpha elevated BP in rats and dogs and lowered it in rabbits. Oxytocin produced no changes in PB while noradrenaline elevated BP in rabbits. Ovarian blood flow in pregnant rabbits was reduced by ONO-802, PGE1 or PGF2 alpha. Little influence was seen with oxytocin. Regarding the luteal microvasculature in pregnant rats, ONO-802, PGF2 alpha and noradrenaline exhibited vasoconstricting effects. PGF2 alpha induced abortion and decreased plasma progesterone levels. These results suggest that the inhibitory effects of ONO-802 on the uterine and placental circulation are strongly influenced by the uterine contractile effect and that the inhibitory effect on the ovarian circulation in rats is one of pharmacological effects not concerned with the abortifacient or luteolytic effect.     

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometrium. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.     

Head-to-cervix force: an important physiological variable in labour. 1. The temporal relation between head-to-cervix force and intrauterine pressure during labour

OBJECTIVE: To investigate the relation between the rise in intrauterine pressure and rise in fetal head to cervix force in normal, slow and induced labour. DESIGN: Prospective observational study. SETTING: The labour ward of a London teaching hospital. PARTICIPANTS: Forty patients were recruited from the antenatal clinic and labour ward of a West London Hospital. Five had normal onset and progression of labour, 14 had slow progression of labour and 21 had induced onset of labour. METHOD: Intrauterine pressure and head-to-cervix force was measured simultaneously using an intrauterine pressure catheter and a specially designed four sensor head-to-cervix force probe. RESULTS: For each contraction of each labour, scattergrams of force by pressure were plotted. Three patterns were observed. When the rise in pressure preceded the rise in force, a positive 'loop' was generated. When the rise in pressure and force occurred simultaneously a linear pattern was generated (a neutral 'loop'). When the rise in pressure lags the rise in force, a negative 'loop' was generated. In normally progressive labour the distribution of loops was 29.1%, 22.6% and 48.3%, respectively, in slow labour the distribution was 26.1%, 14.1% and 59.8% and in induced labour the distribution was 33.8%, 14.4% and 51.8%. These distributions were not statistically different. However, a higher proportion of negative loops was observed in labours augmented with oxytocin compared to those receiving no oxytocin (MW-U = 87, P = 0.036). No differences were observed comparing parity, use of PGE2, epidural analgesia, or mode of delivery. Contraction frequency (number/10 minutes) was inversely correlated to the percentage of negative loops (rs = -0.34, P = 0.033) and positively correlated with percentage of positive loops (rs = 0.36, P = 0.027). CONCLUSIONS: This is the first report of the temporal relation between intrauterine pressure and head-to-cervix force in labour. The most common pattern is that the rise in pressure lags the rise in force, suggesting that a seal has to be created between the fetal head and cervix before a rise in pressure can occur. When oxytocin is given in labour, a higher proportion of loops are negative indicating that there is poor application of the fetal head and cervix in a greater proportion of contractions.     

The use of oral prostaglandin E2 to induce labor at term

Prostaglandin E2 (PGE2) was given to 60 patients to induce labor at term. Two dosage schedules were used: 30 patients were given 0.5 mg hourly and 30 patients were given 1.0 mg hourly. Membranes were ruptured when active labor had occurred. The Bishop score was used for inducibility quotient. In general, the higher the Bishop score, the shorter the delivery time. The 1.0 mg dosage schedule decreased the induction time in both nulliparas and multiparas. There were 55 vaginal deliveries. Five patients were delivered by cesarean section for obstetrical indications; two were in active labor. The overall success rate was 91.6%. No fetal distress occurred that could be attributed to the PGE2. Maternal complications consisted of nausea and vomiting.     

Morphological change of lipids in the vaginal epithelium after intrauterine fetal death (lipid test)

The authors studied the lipid content of the vaginal epithelium of gravida in whom intrauterine fetal death had occurred. Fifteen gravida in the 6th to 10th month of gestation were examined and an unusual, inconsistent with the respective gestation term increase in the intra- and extra-cellular lipid content of the vaginal epithelium demonstrated. This is related to a decrease in the amount of estrogen hormones secreted by the placenta. A cytochemical 'lipid test' based on the above findings has been developed by the authors for the diagnosis of intrauterine fetal death during the second half of pregnancy.     

Induction of labor by intracervical prostaglandin gel and oxytocin infusion in primigravid women with unfavorable cervix

The rate of Cesarean Section for failed induction of labor and maternal and fetal compilations are high when labor is induced in a nulliparas women with an unripe cervix by amniotomy and oxytocin infusion. Prostaglandins (PG) in different forms have been used for ripening the cervix with an aim of reducing these problems. A prospective randomized trial was performed on one hundred primigravid women between 37 and 42 weeks of gestation with singleton pregnancy, cephalic presentation and unfavorable cervix (Modified Bishop Score < or = 5) in the department of Obstetrics & Gynaecology of Institute of Postgraduate Medicine & Research from 1st May 1996 to 30th April 1997. In this study the efficiency of prostaglandin E2 intracervical (PGE2 IC) gel in induction of labor in a group of primigravid women with unripe cervix was assessed and compared with another group with similar characteristics using oxytocin infusion and artificial rupture of membrane (ARM). The Modified Bishop Score (MBS), interval between IOL and onset of labor and the duration of labor after insertion of PGE2 gel was significantly different from those of oxytocin infusion group. But the Apgar Score at 1 & 5 min had shown no statistically significant difference. Any significant difference could also not be detected in the mode of delivery between the two induction group. The proportion of emergency Cesarean Section (CS) was high in the oxytocin infusion group than that of in the prostaglandin group. There was also no significant difference regarding the acceptability of both the induction methods.     

Maternal occupation in the leather industry and selected congenital malformations

OBJECTIVE: Our purpose was to measure intra-amniotic pressure before and after decompression amniocentesis in twin-twin transfusion syndrome. STUDY DESIGN: Intra-amniotic pressures were measured during decompression amniocentesis on 18 occasions in 5 pregnancies complicated by twin-twin transfusion syndrome. The intra-amniotic pressure was determined with a water manometer before and after removal of amniotic fluid. For comparison, intra-amniotic pressure was determined in 10 uncomplicated gestations. RESULTS: Initial intra-amniotic pressures in twin-twin transfusion gestations (mean, 17.2 +/- 5.2 cm H2O; range, 5.5 to 33.0 cm H2O) were higher than those of the uncomplicated gestations (mean, 8.4 +/- 3.3 cm H2O; range, 3.5 to 13.5 cm H2O; p < 0.002). Intra-amniotic pressures following therapeutic amniocentesis (mean, 10.9 +/- 5.1 cm H2O; range, 3.5 to 23.0 cm H2O) were not different from those of the uncomplicated gestations (p = 0.16). CONCLUSION: The intra-amniotic pressure in twin-twin transfusion gestations is higher than that of the uncomplicated gestation. Decompression amniocentesis reduces intra-amniotic pressure to that of the uncomplicated gestation.