Prostaglandin E and F2 alpha concentration in the cervical mucus and mechanism of cervical ripening.

OBJECTIVE: To study the mechanism of cervical ripening by determination of prostaglandin E (PGE) and F2 alpha (PGF2 alpha) concentrations in cervical mucus during the course of pregnancy. STUDY DESIGN: Cervical mucus was collected from 99 pregnant women attending the mother care unit of the department. Women with sexual intercourse within the last 24 hours before sampling and subjects with bacterial vaginosis were analysed separately. RESULTS: Eleven women had sexual intercourse within 24 hours before sampling. The concentration of PGE in their cervical mucus was high corresponding to 2000-4000 pg/mg w w lasting for a period of 10-12 hours postcoitally, whereas the levels of PGF 2 alpha only increased slightly. Bacterial vaginosis was accomplished by a slight but significant elevation of PGF2 alpha levels but only of a minor increment of the PGE values. The prostaglandin concentrations in the mucus from the remaining 68 women were for PGE 102.75 +/- 111.51 and for PGF2 alpha 97.54 +/- 82.48 pg/mg w w (mean +/- SD). Although the values were scattered the concentrations remained at approximately the same level throughout pregnancy and there was no tendency towards an increment during the last weeks of pregnancy when cervical maturation is apparent. CONCLUSION: Cervical softening seems not to be accomplished by a massive local release of prostaglandins but rather the result of a number of different mechanisms more or less influenced by minor alterations of prostaglandin synthesis and release. Involved in these mechanisms are probably neutrophil-derived collagenases.

Leukocyte subpopulations in the human uterine cervical stroma at early and term pregnancy.

Leukocyte subsets were detected by immunohistochemical methods in cervical tissue in either the first trimester or at term pregnancy. In tissue obtained during first trimester lower total numbers of leukocytes were observed in comparison with late pregnancy (2.7 cells/0.04 mm2 versus 5.5 cells/0.04 mm2). The major subgroup of leukocytes present in early pregnancy was T-lymphocytes. The majority of these cells were of the suppressor/cytotoxic subtype. Neutrophils were present at about 1/5th of the density of T-lymphocytes. Very few macrophages were observed at this stage. At term pregnancy, neutrophils were present in significantly higher numbers than during first trimester with no difference between tissue obtained before or during active labour. Macrophages were present at about 10-fold higher density than during early pregnancy. In conclusion, tissue-bound leukocytes are present in the human cervix at a higher density in late pregnancy compared to first trimester. The increased densities of neutrophils and macrophages at this stage indicate a role for these cells during cervical ripening.

Prostaglandin release from human cervical tissue in the first trimester of pregnancy after preoperative dilatation with hygroscopic tents.

Preoperative dilatation with hygroscopic tents before first trimester abortion by vacuum aspiration is widely accepted and reduces the risk of early and late complications. A softening effect and a reduced compliance to mechanical dilatation occurs in addition to pure mechanical dilatation of the cervix. If this softening is an effect of local prostaglandin release, however, is unknown. Prostaglandin (PG) release in vitro from cervical biopsies following dilatation in vivo by a synthetic hygroscopic tent (Dilapan) for periods of 4 h and 18 h was compared with that of biopsies from untreated women. No difference was observed between the release of PGE2, PGF2 alpha, or 6-keto-PGF1 alpha. No significant difference was found in the tissue water content between treated and untreated women (83.8% versus 83.2%). Prostaglandins were also extracted from an alternative cervical dilator, Lamicel (a polyvinyl sponge impregnated with magnesium sulfate), and compared with the corresponding values from women pretreated with the cyclooxygenase inhibitor indomethacin before application of the tent. Significantly higher concentrations of PGE2 and PGF2 alpha but not of 6-keto-PGF1 alpha were found in women who had not been indomethacin-treated compared with indomethacin-treated women. Slices of the cervix from non-pregnant women operated upon for benign conditions were divided into an outer stromal layer and an inner layer, including the mucosa, and the PG-release in vitro was measured. The inner layer of the cervix showed a significantly higher release of PGE2 and PGF2 alpha compared with the outer layer. Lamicel treatment before first trimester abortion results in a significant dilatation of the cervix and a reduced compliance to mechanical dilatation, and this study supports the hypothesis that this effect is mediated via a local PG-release from the cervix. It seems reasonable to believe that Dilapan treatment too has the capacity to induce PG-release from the cervix, but this could not be demonstrated in this study, probably because needle biopsies taken mainly from the outer cervical layers were analyzed.

Effects of mifepristone and progesterone on collagen synthesis in the human uterine cervix.

Antiprogestins are used to induce first trimester abortion and to dilate the cervix before vacuum aspiration. Cervical dilatation is associated with profound changes in the connective tissue. In what respect antiprogestins interfere with this process has hitherto been sparsely investigated. The aim of present study was to examine the influence of the antiprogestin mifepristone on cervical collagen synthesis in nonpregnant, early and late pregnant women. The effects were compared with those of progesterone. The content of collagen in cervical tissue was determined by measuring hydroxyproline. Collagen synthesis was studied in vitro either by incubation of cervical tissue specimens from women, pretreated with mifepristone in vivo, in the presence of 14C-proline or by incubation of cervical tissue of not pretreated women in the presence of the isotope and mifepristone or progesterone. Pretreatment with mifepristone, but not progesterone, induced a significant increase in cervical dilatation. The cervical concentration of collagen was not altered after mifepristone administration. Pretreatment with mifepristone did not quantitatively influence the time course of radiolabeling in vitro or the pattern of radiolabeling in different protein components as revealed by electrophoresis. In vitro mifepristone, like progesterone, reduced the incorporation of 14C-proline. From the present data we conclude that mifepristone pretreatment in connection with first trimester abortion is not associated with any major changes, qualitatively or quantitatively, of collagen synthesis. However, we cannot exclude that mifepristone still may affect the de novo formation of collagen since mifepristone, administered in vitro, did reduce collagen synthesis.

Dilapan tent-gemeprost regimen vs. combinations of extra-amniotic Rivanol-Laminaria/Lamicel and oxytocin for second trimester abortion.

OBJECTIVE: To compare a new regimen for second trimester abortion using Dilapan and vaginal gemeprost suppositories with extra-amniotic Rivanol instillation and oxytocin i.v. immediately or 16 h after instillation. METHODS: A prospective study was performed in 153 women to analyze the induction-abortion interval, the use of analgesics and the complication rate. Wilcoxon's rank sum test was used for statistical evaluation. RESULTS: The mean induction-abortion interval was significantly shorter in the Dilapan-gemeprost-treated women than in the immediate or 16-h Rivanol-oxytocin-treated women, 12.5 vs. 23.3 and 26.8 h, respectively. The 24-h cumulative abortion rate was 91% in the former group vs. 49% and 61%, respectively. The use of analgesics was less frequent among the Dilapan-gemeprost-treated women, whereas the complication rate did not differ. CONCLUSIONS: The Dilapan-gemeprost treatment was advantageous with respect to a shorter induction-abortion interval and ease of handling. However a minority of women do not respond to this treatment and it is therefore necessary to employ alternative methods to complete the abortion in these cases.

Cervical mucus concentration of prostaglandins E2 and F2 alpha after pretreatment with mifepristone in the first trimester of pregnancy.

Cervical dilatation and softening after pretreatment with mifepristone are well documented. As this effect is similar to that observed after local application of prostaglandin E2 (PGE2) it is tempting to speculate that the effect of mifepristone is mediated via an increase of the endogenous secretion of prostaglandins from the cervical mucosa. Eighteen healthy women in the first trimester of pregnancy were treated with oral mifepristone (200 mg) 48 and 24 hours before legal abortion by vacuum aspiration and 18 women in the same age of gestation without any pretreatment served as controls. Cervical mucus was collected for measurement of prostaglandins by radioimmunoassay before administration of the drug and in connection with vacuum aspiration. The cervical dilatation at the time of surgery was significantly increased in women given mifepristone as compared with untreated women (7.6 versus 5.8 mm). The wet weight of collected cervical mucus was significantly increased in mifepristone treated women. The amount of PGE2 and prostaglandin F2 alpha per sample was unchanged in mifepristone-treated women, whereas the concentration was lower as an effect of dilution due to an increased yield in cervical secretion observed after mifepristone treatment. The present observation does not give any support to the hypothesis that mifepristone-induced cervical maturation is mediated via an increase in cervical prostaglandin production.

Cervical smooth muscle contractile activity after treatment with mifepristone and progesterone.

Contractile activity of the uterine cervix in vitro was studied in women pretreated with mifepristone 200 m chi 2 or progesterone suppositories 100 mg before cervical dilatation and vacuum aspiration in the first trimester. Mifepristone increased the dilatation of the cervix as measured prior to operation whereas progesterone had no effect. Spontaneous muscle activity and contraction frequency were not affected by either drug. Neither the inhibitory response to PGE2 nor the excitatory response to noradrenaline were significantly different from that in placebo-treated women. It is concluded that the cervical smooth muscle has no major role in the dilatatory effect of mifepristone in the cervical canal.

Pregnancy and delivery in patients with urinary diversion through the continent ileal reservoir.

The social and psychologic sequelae after external urinary diversion are known to be fewer in patients with urinary diversion through the continent ileal reservoir (Kock pouch) compared with those with diversion through the incontinent ileal conduit. Therefore, in young female patients treated surgically with urinary diversion through the continent ileal reservoir, a number of pregnancies can be expected. We report herein the results of four pregnancies in three women with this type of reservoir. All deliveries were vaginal. One patient showed urinary obstruction at the end of the pregnancy and delivery was induced. This particular infant was treated with phototherapy because of hyperbilirubinemia; the other three infants were mature. No damage to renal function was noted and revisional surgical treatment of the reservoir was not necessary in any. Consequently, pregnancy is not contraindicated after urinary diversion through the continent ileal reservoir (Koch pouch).

No abortion-inducing effect of the ulcer-healing dose of the synthetic prostaglandin E2 analogue enprostil in first trimester.

Milligram-range doses of E2 prostaglandins have long been used to induce labor or abortion in the second and third trimesters of pregnancy. Enprostil, a synthetic dehydroprostaglandin E2 structural analogue, is administered in microgram doses for the treatment of acute duodenal ulcer and acute gastric ulcer. This study examined the effect of the ulcer-healing dose and twice the ulcer-healing dose upon women in the first trimester of pregnancy. Two hundred and seven women who had requested legal abortion in the first trimester participated in two randomized, double-blind, placebo-controlled, parallel studies. They received two doses of enprostil 35 micrograms (the recommended dose for the treatment of duodenal and gastric ulcer) (n = 51), 70 micrograms (twice the recommended dose) (n = 53), or placebo (n = 103) 12 h apart. No drug-induced abortions occurred in any of the first-trimester pregnancies. Vaginal bleeding occurred in 4% of volunteers receiving the lower dose and 4% receiving the higher dose of enprostil. Vaginal bleeding occurred in up to 2% of volunteers on placebo. Although not recommended for pregnant women, if enprostil is given inadvertently to pregnant women with ulcers, it is unlikely to endanger the pregnancy during the first trimester.

Preoperative dilatation of the cervix at legal abortion with a synthetic, fast-swelling hygroscopic tent.

Preoperative dilatation of the cervix at first trimester legal abortion has been shown to facilitate the vacuum aspiration procedure and to reduce per- and postoperative complications as well as late sequelae. The present study represents a clinical trial in which a new synthetic hygroscopic tent, Dilapan, has been evaluated. Dilapan tents of different diameters with different durations of cervical exposure were tested on a case material of 450 nulliparous women. It was found that treatment with 4 mm tents during 3-4 h or 3 mm tents during 16-20 h produced a cervical dilatation that allowed an easy evacuation of the uterus with a minimum of complications. The advantage of this particular tent is its property of rapid swelling.

Ectopic pregnancy: in vitro effects of prostaglandins on the oviduct and corpus luteum.

An in vitro model for evaluation of pharmacologic treatment of ectopic pregnancy (EP) was designed. In cases of EP, specimens from the tubal wall, the tubal artery, and the corpus luteum capsule were used for contractility studies. In addition, tissue slices from the corpus luteum of EP were incubated for determination of progesterone production. In vitro administration of prostaglandin F2 alpha (PGF 2 alpha) induced a marked increase in activity of the tubal muscle and pronounced constriction of the tubal artery. PGF2 alpha also reduced the human chorionic gonadotropin-induced increase in progesterone production from the corpus luteum. PGE2 conversely, inhibited the tubal muscle activity and had a moderate constrictive effect on the tubal artery. Furthermore PGE2 increased the progesterone formation from the corpus luteum. In theory, the demonstrated in vitro effects indicate that as opposed to PGE2 compounds, PGF2 alpha compounds may be useful for pharmacologic treatment of EP.

Transfer of terbutaline across the human placenta in late pregnancy.

Placental transfer of terbutaline was studied in 22 women in late pregnancy who were delivered by elective Caesarian section. A single i.v. dose of terbutaline (0.25 or 0.5 mg) was given at various times (13-295 min) before delivery. Immediately after delivery, one blood sample was drawn from the placental side of the umbilical vein and one from the mother's antecubital vein. By use of gas chromatography plus mass spectrometry terbutaline was assayed in maternal plasma and in plasma and whole blood from the umbilical vein. Plasma concentrations in the mothers (Cmv) were initially 7 micrograms/L, while the highest umbilical venous level ( Cuv ) recorded was 3.5 micrograms/L. The ratio Cuv /Cmv increased continuously during the time interval studied and approached unity after 2-3 h. The blood:plasma concentration ratio in venous umbilical blood was initially low. It reached unity after about 60 min, but increased steadily to about 1.5 during the time of study. Thus there was a continuous uptake of terbutaline from plasma into the erythrocytes. The slow in vivo equilibration of terbutaline between plasma and erythrocytes is probably due to the low lipophilicity of the drug. However, the latter characteristic did not seem to impede its diffusion across the placenta to any great degree.