Value of Schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein-A (PAPP-A) in the clinical management of threatened abortion

Summary. Pregnancy-associated plasma protein-A (PAPP-A) and Schwangerschaftsprotein 1 (SP₁) levels were measured in single serum samples from 60 patients admitted with vaginal bleeding in the first 14 weeks of pregnancy. When based on ultrasound diagnoses the prediction of non-viability (the predictive value) was 97% for SP₁ and 84% for PAPP-A. Whereas the prediction of viability (above –2SD of the normal range) with SP₁ was 88% the value with PAPP-A was only 57%; the poorer result obtained with PAPP-A probably reflects its longer half-life. Pregnancy outcome is not related to the duration of bleeding.     

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.     

Circulating placental proteins (hCG, SP1 and PP5) in trophoblastic disease

Summary. Scrum human chorionic gonadotrophin (hCG), pregnancyspecific β₁-glycoprotein (SP₁) and placental protein 5 (PP5) levels have been measured by radioimmunoassay in 20 patients (116 samples) with hydatidiform mole, one patient (nine samples) with invasive mole and 10 patients (103 samples) with choriocarcinoma. Measurement of both serum SP₁ and hCG are useful in the monitoring of these diseases. The presence of PP5 in hydatidiform mole and its absence in choriocarcinoma support the hypothesis that PP5 is closely associated with the invasive activity of malignant trophoblast.     

Human placental lactogen and pregnancy-specific β1-glycoprotein in pregnant diabetic women

Summary. Serum placental lactogen (hPL) and pregnancy-specific β₁ glycoprotein (SP₁) concentrations were measured in 16 insulin-dependent pregnant diabetic women and in 16 non-diabetic control subjects matched for placental weight. hPL concentrations were found to be significantly higher in diabetics with placental weight >90th centile compared with those in (i) non-diabetic controls with placental weight >90th centile and (ii) diabetics with placental weights <90th centile. SP_l concentrations were higher in both diabetic groups compared with those in their respective nondiabetic controls, but no difference existed between the two diabetic groups. In the control subjects infant birthweights were lower in the women with small placentae, but no such difference was observed between the two diabetic groups.     

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.     

Effect of vacuum curettage on the concentrations of plasma 6-keto-prostaglandin Flα and serum thromboxane B2

Summary. Serial plasma samples collected before and after vacuum curettage followed by methylergometrine injection in 10 women were assayed for 6-keto-prostaglandin F_lα (6-keto-PGF^1α). The mean 6-keto-PGF_lα concentration was 97.2 (SE 8.8) pg/ml before cervical dilatation. The concentration rose to 128.2 (SE 13.5) pg/ml (P < 0.10) immediately and to 133.3 (SE 17.8) pg/ml (P < 0.05) 1 h after curettage and returned to the initial value within 5 h. Neither methylergometrine nor anaesthesia, nor non-gynaecological surgery, caused changes in the level of plasma 6-keto-PGF_lα. The capacity of the platelets to produce thromboxane A² during spontaneous clotting of blood did not change during vacuum curettage, anaesthesia and non-gynaecological surgery, nor after methylergometrine. The evidence suggests that the pregnant myometrium and/or intrauterine tissues capable of generating prostacyclin (PGI₂) in vitro may release PG1₂ also in vivo .     

Prognostic significance of the new placental proteins in trophoblastic disease

Summary. Circulating levels of four specific placental proteins, human chorionic gonadotrophin (hCG), Schwangerschafts protein 1 (SP₁), placental protein 5 (PP5) and pregnancy-associated plasma protein A (PAPP-A), were measured in 31 patients with hydatidiform mole before treatment. Seven patients subsequently developed clinical chorio-carcinoma and three of them had pulmonary metastases. The estimations of hCG, PP5 and PAPP-A levels were found to be of no value in the prediction of malignant sequelae. Levels of SP₁≥ 16.5 i.u./l were associated with a higher incidence of subsequent malignant disease ( P < 0.05), the risk being at least nine times greater in these patients. The predictive value of high levels of SP₁ was 35%, the specificity 45.8% and sensitivity 100%.     

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.     

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.     

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.     

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.     

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.     

Oral Prostaglandins E2 and F2a in the Induction of Labour

Summary: Oral prostaglandins E₂ and F_2a were used to augment amniotomy in the induction of labour in 173 patients. The success rate was significantly higher with prostaglandin E₂ than with prostaglandin F_2a (89% and 75%, respectively). This was achieved despite a significantly lower incidence of gastrointestinal side effects. No serious maternal or fetal complications occurred with either drug. It is concluded that oral prostaglandin E₂ is more efficient than oral prostaglandin F_2a in the induction of labour.     

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.     

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.     

Prostaglandin E2, Fetal Maturation and Ovine Parturition

Summary: The major source of PGE₂ in ovine pregnancy is the placenta, with secretion occurring bidirectionally into fetal and maternal circulations. The placental output of PGE₂ appears to increase when demand on placental function is increased, suggesting that the normally observed increase in its concentration towards term is driven by the growing demands of the fetus. The fetal pituitary is also involved in the control of PGE₂ synthesis. PGE₂ has potent stimulatory actions on the fetal pituitary to increase both the absolute concentration and the bioactive fraction of ACTH-containing peptides in the fetal circulation. It also directly stimulates glucocorticoid secretion from the fetal adrenal gland.
We propose that PGE₂ provides a tonic stimulation of the fetal HPA axis in late gestation, contributing to phenomena such as the apparent insensitivity of the pituitary to Cortisol feedback and the increasing sensitivity of the fetal adrenal. Because of its apparent responsiveness to placental workload, it may transduce stimuli from the placenta and transmit them to the fetal HPA axis, giving a possible biochemical basis to the empirically observed correlation between fetal metabolic demand and gestation length.     

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.     

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.     

The serum pregnancy-specific β1-glycoprotein to betahuman chorionic gonadotrophin ratio as an index of prognosis in patients with choriocarcinoma

Summary. The ratio of serum pregnancy-specific β₁-glycoprotein (SP1) to the β-subunit of human chorionic gonadotrophin (β-hCG) before and after chemotherapy was measured in 12 patients with metastatic choriocarcinoma. The ratios before chemotherapy ranged between 0^.03 and 0^.75, with a mean value of 0^.34 (SD 0^.21). The ratio increased to over 1^.0 (1^.05–53^.3) after one or two courses of chemotherapy in seven of the 12 patients. These women achieved complete remission. In the other five patients who died of the disease due to drug resistance of the tumour, the ratio after chemotherapy was low (0^.04–0^.74) and tended to decline. These data suggest that the serum SPl/β-hCG ratio can be used to predict the prognosis of patients with choriocarcinoma.     

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.