Vaginal and abdominal delivery increases maternal urinary 6-keto-prostaglandin F1α excretion

Summary. To study the role of the antiaggregatory and vasodilatory prostacyclin (PGI₂) during human delivery, serial urine samples collected from 13 women delivered vaginally and from eight delivered abdominally were assayed for 6-keto-prostaglandin F_1α (6-keto-PGF_1α a breakdown product of PGI₂) by high-performance-liquid-chromatography and radioimmunoassay. In women delivered vaginally the mean urinary 6-keto-PGF_1α concentration was 41.9 (SE 8.3) ng/mmol creatinine, before the onset of labour and increased progressively to a maximum of 186.5 (SE 47.6) ng/mmol creatinine 2 h after delivery irrespective of the use of oxytocin and epidural analgesia. In women delivered by caesarean section under epidural anaesthesia, the urinary 6-keto-PGF_1α rose from 33.4 (SE 4.2) ng/mmol creatinine to 2153 (SE 314) ng/mmol creatinine 2 h after section. In both groups the increased levels had fallen by 24 h postpartum to levels below those found before delivery. In neonatal urine 6-keto-PGF_1α concentrations were some 12–30 times higher than those in postpartum urine. Thus, vaginal and abdominal delivery is accompanied by significant increases in maternal PGI₂ release, perhaps in the myometrium and/or intrauterine tissues. This may be of significance in the regulation of fetoplacental blood flow and in the prevention of intra- and postpartum thrombosis.     

Thromboxane A2 and prostacyclin levels in molar pregnancy

Summary. Plasma levels of thromboxane (TX) A₂ and prostacyclin (PGI₂), as measured by radioimmunoassay of their respective stable metabolites TXB₂ and 6–keto PGF_1α, were studied in six molar pregnancies immediately before, immediately following and 24 h after evacuation of the uterus. The mean (SD) levels for TXB₂ were 150 (41), 137 (32) and 125 (25) pg/ml respectively, and for 6–keto PGF_1α the respective values were 225 (52), 226 (127) and 213 (49) pg/ml. There was no significant difference in the levels of prostanoids between the samples taken at the various time intervals. The concentration of these prostanoids in molar intravesicular fluid was also determined. Their respective mean (SD) pg/ml values were 3682 (760) for TXB₂ and 2969 (744) for 6–keto PGF_1α. In 15 normal pregnancies of equivalent gestation, the mean amniotic fluid levels of TXB₂ and 6–keto PGF_lα were 34 (17) and 146 (86) pg/ml respectively. The ability of molar trophoblast to generate the prostanoids from [¹⁴C]arachidonic acid in vitro was also demonstrated. Mean (SD) values for TXB₂ and 6-keto PGF_1α were 12.2 (2.6) and 13.2 (1.8) pg/mg protein/min, respectively. It is likely that the high concentrations of prostanoids in vesicular fluid reflect the synthesizing ability of the villus vesicles. The mole contributes little to the circulatory prostanoids possibly because its villi are deficient in blood circulation.     

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2α

Summary. Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F_2α (PGF_2α), E₂ (PGE₂) and 6-oxo-prostaglandin F_1α (6-oxo-PGF_lα) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF_2α and PGE₂ were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF_2α was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF_1α (the stable metabolite of PGI₂) were low in both groups. These results confirm suggestions that PGF_2α is important in the aetiology of dysmenorrhoea and also indicate that PGE₂ may be involved.     

Maternal plasma prostaglandin E2 metabolite levels during human pregnancy and parturition

Summary. Because of methodological problems associated with the measurement in biological fluids of both prostaglandin E₂ (PGE₂) and its unstable principal circulating metabolite 13,14-dihydro-15-keto-PGE₂ (PGEM), there is little reliable information on these prostaglandins in human pregnancy and parturition. The recent discovery of a stable PGEM degradation product 11-deoxy-13,14-dihydro-15-keto-11β, 16-cyclo-PGE₂ (bicyclo-PGEM) has provided a means of studying endogenous plasma levels of PGEM which circumvents the problems encountered with direct measurements of PGE₂ and PGEM. Using a radioimmunoassay for bicyclo-PGEM we have therefore determined maternal peripheral plasma PGE₂ metabolite levels during human gestation. PGE₂ metabolite levels did not alter significantly during the second or third trimesters nor during labour. This contrasts with maternal peripheral plasma levels of the principal circulating metabolite of PGF_2α 13,14-dihydro-15-keto-PGF_2α (PGFM) which increases several fold during labour. Compared t o PGE₂ therefore. PGF_2α may be quantitatively the more significant prostaglandin associated with human parturition.     

Effect of cervical application of prostaglandin (PG) E2 on plasma 13,14-dihydro-15-keto-PGF2α and oxytocin in pregnant women at term

Summary. The concentrations of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) and oxytocin were measured by radioimmunoassay in the peripheral plasma of 21 women with low Bishop scores in whom cervical ripening and labour were induced with a cervical cap containing 1.5 mg of prostaglandin (PG) E₂, left in place for 6 h. Blood samples were taken before and at 3, 6, 9 and 24 h after the cap was applied. Four women (control group) had a cap without PGE₂. Labour began in 13 women receiving PGE₂, 12 of whom were delivered within 24 h. In these women plasma PGFM rose progressively to levels seen during spontaneous labour, paralleling the changes in cervical dilatation. The increase became significant at 6 h, when cervical dilatation was 4.5 cm (SEM 0.5). Plasma oxytocin also increased significantly while the cap was in place and then decreased. Plasma PGFM and oxytocin did not change in the control subjects, and in the eight women needing further induction of labour the initial rises were transient and not statistically significant.     

Immunohistological localization of pregnancyassociated endometrial α2-globulin (α2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate

Summary. Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial α₂-globulin (α₂-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. α₂-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for α₂-PEG before treatment although after MPA therapy all specimens obtained exhibited marked α₂-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize α₂-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of α₂-PEG production after stimulation with an oral progestogen.     

Vaginal Prostaglandin F2α Gel Before First Trimester Termination of Pregnancy

Summary: Tylose gel containing either 10 mg prostaglandin F_2α or sterile water was inserted into the posterior vaginal fornix of 130 patients either 12 hours or 4 hours before suction curettage. No benefit in terms of cervical softening or blood loss was noted in patients who received the prostaglandin gel.     

Termination of Pregnancy by Intra-uterine Prostaglandin F2α

Summary: Fourteen pregnancies between the 12th and 19th weeks of gestation were terminated by intra-uterine administration of prostaglandin F_2α. In 7 patients the method of administration was transcervically into the extra-ovular space; in the other 7, administration was directly into the amniotic sac. The methods of administration, the doses used, the side effects and results are discussed. The findings indicate that intra-amniotic administration is the procedure of choice: firstly, because of the incidence of genital tract infection after transcervical administration; secondly, because 3 patients in the transcervical group had incomplete abortions and required anaesthesia for curettage; and finally, the induction-abortion interval was significantly less when the drug was administered into the uterine cavity.     

Production of prostacyclin, 6-keto-PGFlα and thromboxane B2 by human umbilical vessels increases from the placenta towards the fetus

Summary. The aim of this study was to investigate the production of prostacyclin (PGI₂) and thromboxane B₂ (TXB₂) by incubated samples of umbilical arteries and veins taken at different distances (2, 10,20,30 cm) from the placenta to provide additional information relevant to the haemodynamics of umbilical blood flow. The production of PGI₂, and 6-keto-PGF_1α (the stable metabolite of PGI₂), was higher in both veins and arteries as the distance from the placenta at which the vessels were sampled was increased. A similar correlation between production by venous rings and distance from the placenta was observed for TXB₂, but there was no apparent gradient of TXB₂ production by the samples of arterial rings. No statistically significant variations were discernible in the ratio of 6-keto-PGF_1α:TXB₂ (∼50 in the veins and ∼20 in the arteries) in relation to the sampling distance. The significance of these high ratios is discussed in relation to umbilical blood flow and fetal well-being and development.     

Complex formation of pregnancy-specific α2–glycoprotein (SP1α) and heparin

Summary. The Schwangerschaftsprotein 1 (SP₁,)α values in blood measured by rocket immunoelectrophoresis are affected by the addition of anticoagulants. When compared with values in serum, those in heparin plasma were much higher, while those in sequestrene ethylenediaminetetra acetic acid), sodium citrate and fluoride oxalate were lower. On the other hand, SP₁ and SP₁β concentrations were not significantly affected in heparin or sequestrene and were only slightly depressed in sodium citrate and flouride oxalate. The effect of heparin on SP₁α in serum was dosedependent. We surmise that SP₁α forms a complex with heparin and that it may be involved in the coagulation system in pregnancy.     

Quantitative production of prostaglandin E2 and its metabolites by human fetal membranes

Summary. Cultured amnion, choriodecidua and intact fetal membrane produced similar quantities of prostaglandin E₂ (PGE₂) (1–5 ng/ml). Choriodecidua and intact fetal membrane also produced very high levels of PGE₂ metabolites (100–1000 ng/ml). The total production of PGE (PGE₂ metabolites) was similar in intact fetal membrane and in choriodecidua, suggesting that the amnion, although a source of PGE₂ contributes little to the overall PGE production by fetal membranes.     

Comparison of CO2 laser surgery and loop electrosurgical excision/fulguration procedure (LEEP) for the treatment of vulvar intraepithelial neoplasia (VIN)

The aim of this open clinical trial was to evaluate the therapeutic effectiveness of CO₂ laser vs. loop electrosurgical excision/fulguration procedure (LEEP) in 28 patients with vulvar intraepithelial neoplasia (VIN) (mean linear extent = 6 cm²). To avoid selection bias, in each patient half of the lesional area was treated with CO₂ laser excision/vaporization and the other half was electro-excised/fulgurated. All but three patients (89%) were followed for a minimum of 9 months, maximum 26 months, mean 12 months after last therapy. Complete response was obtained in 12 of 25 patients (48%) after a single laser/LEEP most of whom had 6 cm² or less lesional area. Repeated treatments(mean 3) yielded 19 of 25 (76%) disease-free patients at 9 months or longer. There was no significant (χ²) difference between the CO₂ laser- or LEEP-treated areas with respect to recurrence of disease, healing time (mean 18 days), postoperative discomfort (61%) and complications (11%)). The overall operating time when controlled for lesional size was twice as fast with the CO₂ laser (mean 8 min) than LEEP (mean 20 min). Laser and LEEP were more suitable for ablational and excisional procedures, respectively. LEEP may be an alternative to CO₂ laser for treating VIN, particularly those with a linear extent less than 6 cm².     

Amniotic fluid concentrations of secreted pregnancy-associated endometrial α1 and α2-globulins (α1- and α2-PEG)

Summary. The levels of pregnancy-associated endometrial α₁- and α₂-globulins (α₁- and α₂-PEG), the two major proteins synthesized and secreted by the endometrium in vitro have been assayed in 210 amniotic fluid specimens obtained at termination of pregnancy or by amniocentesis, or at delivery. α₁-PEG was undetectable until week 10 and thereafter rose to peak levels between weeks 20 and 24. Levels fell 15-fold by week 35 but substantial amounts were still present at parturition. α₂-PEG was present at highest levels during early pregnancy, at weeks 6–15, but thereafter levels rapidly fell until during weeks 31–42 α₂-PEG was detectable in only 3 of 25 specimens. During weeks 15–20, when α₂-PEG levels fell and α₁-PEG levels rose, a high correlation was observed between the week of gestation and the log of the ratios of the concentration of these proteins. These observations provide the opportunity to assess the role of endometrial and decidual dysfunction in the aetiology of pregnancy disorders.     

The Use of Prostaglandin F2α for the Induction of Mid-Trimester Abortion

Summary: Ninety-eight patients were given prostaglandin F_2α for the induction of mid-trimester abortion. In 42 the PGF_2α was administered by the extra-amniotic route and 37 aborted. A further 56 received the PGF_2α intra-amniotically and 55 aborted. Dose regimens are compared.     

A Double Blind Dose Trial of Intravaginal Prostaglandin F2α for Cervical Ripening and the Induction of Labour

Summary: A randomised double-blind trial involving 90 patients was set up to compare the efficacy of 25 mg PG F_2α, 50 mg PG F_2α and a placebo on cervical ripening when given in a vaginal tylose gel on the evening before surgical induction of labour. Preliminary stretching of the cervix and sweeping of the fetal membranes was not undertaken. In the 30 control patients, labour was not initiated and the mean improvement in the cervical score before surgical induction the next morning was 0.86. In the group of 30 patients receiving 25 mg PG F_2α, labour commenced during the night in 9 patients and the mean improvement in the cervical score was 3.76 (P < 0.0005); the corresponding figures for the 30 patients receiving 50 mg of PG F_2α were 10 patients coming into labour and cervical score improvement of 4.63 (P < 0.0005). he difference in the mean improvement of the cervical score between the 2 prostaglandin groups was not significant. Significantly fewer prostaglandin-treated patients needed augmentation during labour with intravenous oxytocin (P < 0.025) and there was a significant increase in the spontaneous delivery rate in the combined prostaglandin-treated group (P < 0.025). There was no statistical difference in the outcome of labour between the 2 prostaglandin groups. It was not possible to predict the patients whose cervices would not respond to PG F_2α pretreatment (15%) or those in whom labour would be initiated (30%). No side effects were experienced.     

Prostaglandin D2 release by endometrium and myometrium

Summary. Prostaglandin D₂ (PGD₂) release was studied using a super-fusion technique in endometrium and myometrium obtained at hysterectomy from 36 women with measured menstrual blood loss (range 4–840 ml). PGD₂ was produced by both tissues with greater rates from endometrium. Cyclical changes in release were found only in the endometrium with increased rates during menstruation and the midluteal phase. In the myometrium the highest release rates were present during menstruation at the start of the superfusion. No significant correlation was found between menstrual blood loss and endometrial or myometrial PGD₂ release.     

Cervical dilatation with 16,16-dimethyl-trans-Δ2 PGEl methyl ester vaginal pessaries before surgical termination of first trimester pregnancies

Summary. The effect of a vaginal pessary containing 1 mg of 16,16-dimethyl- trans -Δ² PGE₁ methyl ester inserted 3 h before surgical termination of first trimester pregnancies is described. All patients were primigravidae and had had no previous cervical operations. The treated group had a significant degree of cervical dilatation before operation and the force required to insert the largest dilator necessary was considerably reduced.     

Follicular fluid α1-antitrypsin—correlation with fertilizing capacity of oocytes

Summary. Follicular fluid and serum concentrations of α-antitrypsin (α₁-AT) were determined by radial immunodiffusion in 72 samples obtained from 33 infertile women undergoing in-vitro fertilization and embryo transfer. A statistically significantly lower concentration of α₁-AT was found in follicular fluids from which mature oocytes were recovered (mean 1.52, SE 0.06 g/l) than in those yielding immature oocytes (mean 2·96, SE 0·22 g/l). There was also a significantly higher rate of fertilization (85%) for oocytes from follicular fluids with α₁-AT concentrations of ≤2·0 g/l than for those obtained when the α₁-AT concentration was >2·0 g/l (only 25%). The mean follicular fluid α₁-AT concentration (1 ·52, SE 0·06 g/l) of follicles yielding mature oocytes was significantly lower than the relevant mean serum concentration (3·17, SE 0·10 g/l). There was, however, no significant difference between follicular and serum concentration of α₁-AT in the group yielding immature oocytes or in the serum concentrations between the different oocyte maturity groups. The measurement of follicular α₁-AT may be a useful adjunct in predicting which oocytes are mature and likely to be fertilized.     

Concentration of 13,14-dihydro-15-keto-prostaglandin E2 in the maternal peripheral plasma during labour of spontaneous onset

Summary. The concentration of 13, 14-dihydro-15-keto-PGE₂ (PGEM) was measured by radioimmunoassay in pregnant women in the third trimester, in women at term but not in labour and during labour of spontaneous onset. The plasma concentration of PGEM in pregnant women was elevated above that in a non-pregnant control group. Before the onset of labour no increase of PGEM concentration could be identified. Women in labour had higher PGEM plasma concentrations than before the onset of labour, although there was no progressive increase. Immediately after delivery PGEM levels reached a maximum, which decreased significantly to pre-labour values within 30 min. Artificial rupture of the membranes had no influence on plasma PGEM levels. It is concluded that labour is associated with an increased synthesis of PGE₂ and that PGE₂ may be inved in the mechanism of placental separation. The rapid disaearance of high PGEM levels after labour confirms that PGE₂ is probably synthesized mainly in the fetal compartment.     

Comparison of pregnancy-specific β1-glycoprotein (SP1) and ultrasound in predicting the date of delivery

Summary. The accuracy of ultrasound measurements (crown-rump length and gestational sac diameter) and the serum concentration of pregnancy-specific β₁-glycoprotein (SP₁) in the prediction of the date of birth was analysed in a study population of 94 patients. When measured before 8 weeks after the last menstrual period (LMP) the serum concentration of SP₁, was found to be a good predictor of the expected date of delivery and a good alternative to ultrasound, but it was of limited use when determined at a later gestation.