M. J. N. C. Keirse

SIGNIFICANT FALL IN PROGESTERONE AND RISE IN ŒSTRADIOL LEVELS IN HUMAN PERIPHERAL PLASMA BEFORE ONSET OF LABOUR

Abstract Plasma progesterone and œstradiol17β levels have been measured serially in thirty-three obstetrically normal young primigravidae from the 20th week of pregnancy up to and during spontaneous labour. Hormones were measured by radioimmunoassay using specific antisera. A significant fall in progesterone and rise in œstradiol occurred during the 5 weeks preceding labour. The plasma progesterone and œstradiol concentrations during labour were no different from those found in the week before labour. These changes are consistent with those found in other species and suggest that the onset of labour in human pregnancy occurs after the withdrawal of an inhibitory effect of progesterone on the myometrium and at a time of relative oestrogen dominance.

The fetal membranes as a possible source of amniotic fluid prostaglandins.

Biosynthesis and metabolism of prostaglandins was studied in human amniotic and chorionic membranes obtained at term. Using specific in vitro methods it was demonstrated that the fetal membranes contain an organization of enzymes regulating both synthesis and degradation of prostaglandins. Differentiation between amnion and chorion showed that virtually all of the biosynthesis and metabolism occurred in the chorion, whereas enzymatic activities in the amnion were negligible or low. The results suggest a high turnover of prostaglandins in the chorion, and its importance as a source of prostaglandins found in amniotic fluid is discussed.

METABOLISM OF PROSTAGLANDINS WITHIN THE PREGNANT UTERUS

The metabolism of E and F prostaglandins has been studied in both fetal and maternal tissues obtained from the pregnant human uterus. Both 15‐hydroxy‐prostaglandin dehydrogenase and 13,14‐prostaglandin reductase are shown to be widely distributed in these tissues. Comparison of the levels of enzyme activity in different tissues demonstrates that the greatest metabolism of prostaglandins takes place in the membranes and placenta and that there is much less in the myometrium and the decidua. The lowest enzyme activity was found in the umbilical cord, and no metabolism could be demonstrated in amniotic fluid or in umbilical venous blood. The significance of these findings is discussed.

Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion.

Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks gestation had an increased risk of spontaneous pre‐term labour and delivery in future pregnancies. This increased risk related mainly to previous second trimester abortions and not to previous first trimester abortions. Patients with one previous spontaneous pre‐term labour and delivery had a 37 per cent risk, and those with two or more pre‐term deliveries a 70 per cent risk of again delivering pre‐term. There appeared to be no beneficial effect of cervical suture on the incidence of pre‐term delivery in these patients.

EVIDENCE FOR A LOCAL CONTROL OF PROSTAGLANDINS WITHIN THE PREGNANT HUMAN UTERUS

Prostaglandin F (PGF) and 13,14‐dihydro‐15‐keto‐PGF (PGFM) have been measured in amniotic fluid in late human pregnancy. The method used to obtain amniotic fluid greatly influenced the levels of prostaglandins: fluid obtained by vaginal amniotomy contained significantly higher levels of both PGF and PGFM than samples taken at amniocentesis, reflecting an increase in synthesis and/or release of prostaglandin rather than a decrease in the rate of metabolism. After 36 weeks gestation there was no increase in levels of either PGF or PGFM if samples obtained by amniotomy and amniocentesis were considered separately, although if such samples were considered together a significant increase could be obtained. The apparently rapid change in prostaglandin concentrations in amniotic fluid in response to amniotomy strongly supports a local control of these compounds within the pregnant uterus.

CONCENTRATIONS OF THE PROSTACYCLIN METABOLITE, 6–KETO–PROSTAGLANDIN F1α, IN AMNIOTIC FLUID DURING LATE PREGNANCY AND LABOUR.

Concentrations of 6–keto–prostaglandin F1α (6–keto–PGF1α, the stable metabolite of prostacyclin, PGI2) have been measured in amniotic fluid obtained during late pregnancy and labour. Samples taken at amniotomy during spontaneous labour contained a significantly greater concentration of 6–keto–PGF1α than samples taken at amniotomy before the onset of labour (p <0.01). There was no correlation between the level of 6–keto–PGF1α, in amniotic fluid before labour and gestational age (p > 0 1). It is suggested that prostacyclin may have a functional role in the mechanism of parturition in man.

PROSTAGLANDIN DEHYDROGENASE IN THE PLACENTA BEFORE AND AFTER THE ONSET OF LABOUR

Inactivation of prostaglandins in the placenta was studied using an assay for 15‐hydroxy‐prostaglandin dehydrogenase (PGDH). Forty‐four patients with normal single pregnancies between 38 and 42 weeks gestation were studied. Placentae were obtained before the onset of labour in 9, after spontaneous labour in 18, and after oxytocin‐induced labour in 17 cases, PGDH‐activity ranged from 54 to 495 nanomoles PGF2α/g placenta/minute, with a mean±SEM of 207 ±18 nanomoles/g/minute. The results indicate that the PGDH content of the human placenta does not change markedly with the onset or during the process of labour. The length of either spontaneous or oxytocin‐induced labour was not influenced by the PGDH content of the placenta.

Thromboxane B2 in amniotic fluid before and during labour

Concentrations of thromboxane B2 (TXB2) have been measured in amniotic fluid obtained during late pregnancy and labour. Samples taken at amniocentesis contained significantly lower levels of TXB2 than samples taken by amniotomy for the induction of labour which in turn contained significantly less than when the same procedure was performed during labour. In the latter group there was no correlation between the degree of cervical dilatation and the concentration of TXB2. There was no correlation between gestational age and the concentration of TXB2 in amniotic fluid obtained at amniocentesis whereas there was a significant correlation (P<0·025) between these parameters when fluid was taken by amniotomy before labour. It is suggested that the relative activities of the enzymes responsible for the conversion of prostaglandin endoperoxides to prostaglandins, thromboxane A, and prostacyclin may be of great importance during parturition.

Prostaglandin metabolism in placenta and chorion before and after the onset of labor

Abstract Prostaglandin metabolism was studied in placenta and chorion obtained at term before the onset of labor, after spontaneous labor and after oxytocin-induced labor. Incubated with 500 ng PGF 2α per gram tissue and without added co-factors, placenta metabolized 269 ± 19 ng PGF 2α (mean ± SE, n = 18) and chorion 215 ± 21 ng PGF 2α (mean ± SE, n = 18) within 60 min. Inter-patient variations in the amount of PGF 2α metabolized and in the percentage of PGF 2α recovered under the form of its 15-keto- or its 13,14-dihydro-15-keto-metabolite, related neither to the onset nor to the cause of labor. The observations suggest that prostaglandin metabolism in placenta and chorion does not markedly decrease with the onset and during the process of labor.