Induction of abortion in early pregnancy with mifepristone in conjunction with gemeprost.

This study was performed to investigate the efficacy of oral mifepristone and vaginal gemeprost for termination of early pregnancy. Eighty women requesting first trimester abortion and with amenorrhea of less than 56 days were included. Gestational age was confirmed with ultrasonography. Mifepristone was administered as a single 600 mg dose followed after 48 hours by a vaginal pessary containing 1 mg gemeprost. One woman did not return for gemeprost and later had a vacuum aspiration performed. There was complete abortion in all remaining women. No serious side effects were registered and the number of women requiring opioid analgesia was low (8%). The conclusion is that this treatment is a genuine alternative to vacuum aspiration but medical supervision is necessary for some time after gemeprost administration.

PIP: Physicians at Huddinge University Hospital in Stockholm, Sweden, administered a 600 mg dose of mifepristone (RU-486) then a vaginal pessary of 1 mg gemeprost ( a prostaglandin analogue) 48 hours later to 80 healthy 18-46 year old women requesting 1st trimester abortion (gestational age = 56 days). The physicians wanted to determine the side effects and efficacy of the RU-486/gemeprost regimen to induce abortion. 1 woman did not return for the vaginal pessary and later underwent vacuum aspiration. Just 1 woman experienced a complete abortion before gemeprost treatment. The remaining 78 women experienced complete abortion after gemeprost treatment. Uterine bleeding began immediately for 26 women and on days 1 an 2 for the remaining 52 women. It lasted from 3 to 17 days. Even though most women suffered some pain after gemeprost treatment, just 6 women (8%) needed to take an opioid analgesic. The mean hemoglobin level fell significantly on day 7 (from 127 to 123 g/l; p .01), but essentially returned to preabortion levels by day 14. None of the women needed a blood transfusion. Blood loss was comparable to that of vacuum aspiration. None of the women experienced severe side effects. These findings indicated that termination of early pregnancy with RU-486 and gemeprost is an acceptable option to vacuum aspiration. This regimen should be administered under close medical supervision just in case women need analgesia and to detect the few treatment failures.

Induction of abortion in early pregnancy with mifepristone.

Seventy women requesting first trimester abortion and with amenorrhea of less than 42 days were treated with a single 600-mg dose of mifepristone. Mifepristone is a synthetic 19-norsteroid with strong progesterone receptor antagonist properties. Complete abortion was achieved in 56 women (80%), 2 women (3%) had an incomplete abortion and 12 women (17%) had a continuing pregnancy. No relationship between rate of success and gestational age could be demonstrated. There was no serious side effects and the treatment was favorably received by the women concerned. It is concluded that this treatment is a safe and very acceptable alternative to vacuum aspiration for termination of early pregnancy.

Reproductive hormones during termination of early pregnancy with mifepristone.

Thirteen women received a single oral dose of 600 mg mifepristone (RU486; Roussel-Uclaf, Paris, France) on day 0 to induce first-trimester abortion. Eleven women had a complete abortion, and 2 had a continuing pregnancy and were considered as failures. Plasma levels of human chorionic gonadotropin (hCG) increased from day 0 in all women, but dropped sharply after day 3 in women with successfully induced abortion. In these women, the levels of progesterone, 17 alpha-hydroxyprogesterone and estradiol-17 beta increased from day 0 to day 1 and then dropped. In the 2 failed inductions, the steroid levels remained virtually unchanged. In the complete abortions, the main prostaglandin F2 alpha metabolite, 15-keto-13,14-dihydro-PGF2 alpha, increased to a significant peak at day 6 followed by a significant fall to day 14. These findings supports a direct effect of mifepristone on the decidua, initiating prostaglandin synthesis. It is also suggested that there is a luteolytic effect of prostaglandin F2 alpha, as the levels of corpus luteum steroids started to fall before the drop in hCG.

Termination of early human pregnancy with epostane.

Fifty-six healthy women, with a gestational length of less than 49 days from the last menstrual period, who requested termination of pregnancy were treated with Epostane, a progesterone synthesis inhibitor. Epostane, which competitively inhibits the 3 beta-hydroxy steroid dehydrogenase enzyme system, was given in the dose 200 mg X 4 for seven days. Physical examination, routine laboratory screening and determination of hCG, progesterone, estradiol and cortisol was performed on days 0, 7 and 14. The treatment resulted in 84% complete abortions (90% among women completing therapy). Two women experienced vaginal bleeding only, while 7 were non-responders. Among subjective side effects nausea dominated totally and was also the reason for discontinuation in 4 cases. The average length of bleeding among women with complete abortions was 10.7 days and the decrease in hemoglobin and hematocrit was very slight. Routine laboratory values remained within the normal range. Cortisol levels were elevated on day 7 compared to days 0 and 14, but all single values were within the normal limits.

PIP: 56 healthy women, with a gestational length of 49 days from the last menstrual period, who requested termination of pregnancy were treated with Epostane, a progesterone synthesis inhibitor. Epostane, which competitively inhibits the 3 beta-hydroxy steroid dehydrogenase enzyme system, was given in the dose 200 mg x 4 for 7 days. Physical examination, routine laboratory screening, and determination of hCG, progesterone, estriadol, and cortisol were performed on days 0, 7, and 14. The treatment resulted in 84% complete abortions (90% among women completing therapy). 2 women experienced vaginal bleeding only, while 7 were non-responders. Among subjective side effects nausea dominated totally and was also the reason for discontinuation in 4 cases. The average length of bleeding among women with complete abortions was 10.7 days and the decrease in hemoglobin and hematocrit was very slight. Routine laboratory values remained within the normal range. Cortisol levels were elevated on day 7 compared to days 0 and 14, but all single values were within the normal limits.

Induction of labor and cervical ripening with oral PGE2 in risk pregnancies. A placebo-controlled study.

A double-blind, placebo-controlled study was undertaken to evaluate the priming effect on the cervix and also the effect on the subsequent induction of labor. 0.5 mg oral PGE2 or placebo was given hourly for two 12-h periods. A total of 191 women with risk pregnancies and Bishop score less than or equal to 5 were studied. The induction of labor was carried out with oxytocin or oral PGE2 in a randomized manner. Labor was induced in 39% of the women during the PGE2 priming. The best result, 71% vaginal deliveries, was achieved with the combination of PGE2 priming and induction of labor with oxytocin.

Cervical dilatation with meteneprost vaginal suppositories in first trimester abortion.

Forty nulliparous women were treated with vaginal suppositories containing Meteneprost (9-deoxo-16, 16-dimethyl-9-methylene PGE2) (Upjohn Co.) 10 mg or placebo prior to termination of first trimester pregnancy in a double-blind study. The suppository was inserted three hours before vacuum aspiration. The cervical diameter as measured by the size of the largest Hegar dilatator inserted without resistance was significantly larger in women treated with Meteneprost. The operative blood loss was also reduced in the Meteneprost group.

A Gemeprost vaginal suppository for cervical priming prior to termination of first trimester pregnancy.

A randomized, double-blind, placebo-controlled, multicentre study was conducted to assess the efficacy and tolerance of a single 1.0 mg Gemeprost (16, 16-dimethyl-trans-delta 2PGE1 methyl ester) vaginal suppository for dilatation of the cervix uteri prior to vacuum aspiration termination of first trimester pregnancy in nulliparous women. The suppository was inserted three hours before vacuum aspiration. In the six centres involved, the preoperative cervical diameter was significantly greater in women treated with Gemeprost. Further mechanical dilatation was either unnecessary or significantly easier than in placebo-treated women. A significant reduction in operative blood loss was noted in the Gemeprost group.

PIP: A randomized, double-blind, placebo-controlled, multicenter study was conducted to assess the efficacy and tolerance of a single 1.0 mg Gemeprost (16, 16-dimethyl-trans-delta 2PGE1 methyl ester) vaginal suppository for dilatation of the cervix uteri prior to vacuum aspiration termination of 1st trimester pregnancy in nulliparous women. The suppository was inserted 3 hours prior to vacuum aspiration. In the 6 centers involved, the preoperative cervical diameter was significantly greater in women treated with Gemeprost. Further mechanical dilatation was either unnecessary or significantly easier that in placebo-treated women. A significant reduction in operative blood loss was noted in the Gemeprost group.

Dilatation of the cervix by oral PGE2 before first-trimester termination of pregnancy.

Twenty-four patients--all primigravidae with an especially narrow, rigid cervix--were given PGE2 tablets or placebo tablets in order to prime the cervix before first trimester termination of pregnancy. 1.5 mg PGE2 or placebo tablets were administered hourly for 12 hours on the day before vacuum aspiration. The diameter of the cervix was measured by means of a Hegar dilator prior to administering the tablets and also before the vacuum aspiration the following day. The plasma level of 15-keto-13,14-dihydro-PGF2 alpha was determined before the treatment and again before the vacuum aspiration. All the 12 patients treated with PGE2 tablets had an average change in cervix diameter of 2 mm, whereas in the placebo group the average change was 0.58 mm.

PIP: The effect of orally given prostaglandin E2 (PGE2) on cervical dilatation was assessed by administering PGE2 tablets or placebo tablets to 24 patients prior to 1st trimester pregnancy termination in a double blind study conducted in Sweden. Various PG treatment regimes were used by previous investigators to induce dilatation of the cervix for the purpose of reducing the risk of cervical laceration or perforation during termination. In the present study 1.5 mg of oral PGE2 was administered hourly for 12 hours on the day preceding termination to 12 patients and placebos were administered in the same manner to the other 12 patients. All of the patients were primigravidae and had narrow and rigid cervices. Cervical dilatation was measured, using a Hegar dilator, just prior to PGE2 or placebo administration and, again, approximately 24 hours later, or just prior to termination by vacuum aspiration. For 10 of the patients in each treatment group, blood samples were drawn before PGE2 or placebo administration and again just prior to termination to assess any changes in the plasma level of 15-keto-13,14-dihydro-PGF2 alpha. For the remaining 2 patients in each treatment group, intrauterine pressure was assessed prior to and during PGE2 and placebo administration. For the PGE2 treatment group there was a significant increase in the mean internal diameter of the cervix from 3.42 mm +or- 0.99 mm prior to PGE2 administration to 5.42 mm +or- 0.99 mm prior to termination (p0.001). In contrast, the placebo group had a mean increase in the diameter of the cervix of only .58 mm, and this increase was not significant. There was a significant increase in the plasma level of 15-keto-13,14-dihydro-PGF2 alpha among the PGE2 treated group (p0.05). Prior to treatment the mean level for both groups was 39 pg/ml, and prior to termination it was 65 pg/ml for the PGE2 group and 40 pg/ml for the placebo group. The slight increase in the placebo group was not significant. Patients with the greatest increase in cervix dilatation appeared to have the highest 15 keto-13,14-dihydro-PGF2 levels. Possible explanations for the rise in the PGE2 treatment group were discussed. For the PGE2 treatment group, contractions with an amplitude of 10-20 mm hemoglobin, and at intervals of 1-2 minutes, were registered 3 hours after treatment. The contractions did not increase after the first 3 hours and did not cause patient discomfort. 58% of the patients had gastrointestinal side effects. These effects are common when PGE2 is administered orally or intravenously.

Priming and induction of labor with oral PGE2 in patients with low Bishop score.

Oral prostaglandin in hourly doses of 0.5 mg PGE2 was given to 58 patients with an initial Bishop score of five or less, for two 12-hour periods in order to prime the cervix. After priming, the patients were induced with oral PGE2; 90% of these patients were delivered. In a control group comprising 59 patients induced with oxytocin, the delivery rate was only 51%.

Diagnosis in utero of congenital hydrocephalus by sonography and computerized tomography.

Four patients with suspected fetal hydrocephalus in utero were examined by means of sonography and computerized tomography (CT). The diagnosis was confirmed in 3 cases, while the fourth was found to be normal. The mean radiation dose absorbed by the maternal ovaries was estimated by phantom measurements.

Rhythmic changes in estriol excretion during pregnancy.

Different biologic rhythms with effect on one and the same parameter may cause a complicated signal pattern in which no regularity can be visually identified. In this study an autocorrelation function approach, well established in the interpretation of electroencephalograms, was shown to be applicable also in the interpretation of processes with few points of observation. This technique, used on the excretion of estriol in urine, reveals several rhythms with wavelengths between 6 and 72 hours. Interference between these signals may explain the irregular visual appearance of plots of subsequent estriol determinations and the considerable rise and fall of urinary estriol excretion during pregnancy. The presence of two independent sources of the rhythms is suggested. It is concluded that the complicated and individual rhythmic changes in urinary excretion of estriol results in a low diagnostic specificity for fetoplacental malfunction of this component.

Catecholamine metabolites in amniotic fluid as indicators of intrauterine stress.

The catecholamine metabolites HMPG and VMA have been determined in samples of amniotic fluid in 38 uncomplicated pregnancies, seven cases of IUGR, and six cases of diabetes. A successive increase of HMPG and VMA was found toward the end of the pregnancy. HMPG and particularly the HMPG/VMA ratio were significantly higher in the amniotic fluid of the growth-retarded fetuses than in the uncomplicated cases. No significant difference was found between the diabetic and uncomplicated cases.

Total cortisol and L/S-ratio in amniotic fluid in late pregnancies complicated by diabetes mellitus.

68 samples of amniotic fluid from 47 women with varying severity of diabetes mellitus and 48 samples from 43 normal women were obtained in the 31st to 40th week of pregnancy before onset of labour. The concentration of total cortisol and the L/S-ratio in amniotic flud were determined and related to gestational age. There was a continous rise of total cortisol with advancing gestational age in the diabetic pregnancies similar to that found in normal pregnancy. Diabetic pregnancies were associated with slightly lower amniotic fluid cortisol levels without significant difference to values found in normal pregnancy. The severity of the disease did not affect the cortisol levels in amniotic fluid. There was no correlation between total cortisol levels and L/S-ratios in amniotic fluid. Determination of total cortisol in amniotic fluid can thus not replace measurements of L/S-ratios to predict fetal lung maturation.