Intramuscular 16-phenoxy PGE2 ester for pregnancy termination.

A new PGE2 derivative (16-phenoxy PGE2 methyl sulfonylamide sulprostone) was administered by the i.m. route to 48 women pregnancy in any of the three trimesters. The indications for pregnancy interruption were either serious medical problems in intact pregnancies (21 cases) or due to fetal death in utero (27 cases). Single doses of 500 micrograms were repeated every 4 hours in the former group or every 6 hours in the latter category for a maximum period of 24 hours. The treatment was successful in 81% of intact pregnancies and in 92.6% of fetal death cases with an overall mean induction interval of 12.9 hours. More than half the subjects did not experience any side effects apart from mild or moderate uterine colics. An overall mean of 1.4 episodes of vomiting or diarrhoea per induction trial was quite acceptable from the clinical point of view. The absence of serious complications in the group of critically sick women speaks in favor of the relative safety of the drug.     

Clinical evaluation of endocervical prostaglandin E2-triacetin-gel for preinduction cervical softening in pregnant women at term

In an open randomized clinical trial 100 pregnant women with low Bishop Scores at term were treated either with intracervical Prostaglandin (PG) E₂ (0.5 mg in 2.5 ml triacetin-gel) 12 hours before labor induction with intravenous oxytocin or with oxytocin infusion alone. In 46 of the 50 pretreated patients (92 %) the Bishop Score progressed at least 3 points, in four cases only 2 points. The mean Bishop score in the untreated patients increased insignificantly. After PGE₂-gel administration 16 patients delivered during the 12 hour interval compared to 3 in the group without pretreatment. The first induction attempt was successful in 14 (64 %) of the 22 patients that were left to be induced after cervical softening and in 26 (57 %) of the 47 women without cervical priming. The Cesarean section rate was 10% (n=5) in the PGE₂-gel group and 12% (_n=6) in the control group. Dosage of oxytocin required for labor induction was significantly lower after cervical softening. No serious fetal or maternal side effects were observed after PGE₂ pretreatment.     

Hormone changes in relation to the time of fetal death after prostaglandin-induced abortion

The changes in unconjugated estradiol-17β and estriol, progesterone and chorionic somatomammotropin (HCS) in peripheral plasma have been studied in 18 women at 30-minute intervals following intra-uterine prostaglandin E₂ administration for therapeutic termination of second trimester pregnancy. The hormonal changes were related to the time of fetal death detected by the disappearance of fetal heart pulsations. Prostaglandin E₂ was given by the intra-amniotic route with urea (5 patients) or with intravenous oxytocin (5 patients), or by the extra-amniotic route with intravenous oxytocin (8 patients). Fetal death occurred rapidly with intra-amniotic PGE₂, but usually at a late stage with extra-amniotic PGE₂. Three fetuses in the extra-amniotic group died at or just before abortion. A variety of fetal heart changes were noted and the time of fetal death did not appear to influence the time of abortion within each treatment subgroup.Estradiol and estriol showed a slight but persistent fall over 24 hours prior to induction of abortion. A more rapid fall usually occurred after induction, with a consistent fall around the time of fetal death. Progesterone and HCS usually fell much less before and immediately after fetal death. A marked rise in estradiol sometimes occurred before fetal death, particularly in the intra-amniotic PGE₂ and urea subgroup. Estriol levels declined more rapidly before than after fetal death, whereas fetal death had less consistent effects on the other hormones. All hormones had usually fallen considerably at the time of abortion, and in some individuals marked fluctuations in hormone levels were seen.     

Controlled trial of induction of labor by vaginal suppositories containing prostaglandin E2

A group of 84 women at 39 – 43 weeks of pregnancy were randomly allocated to a blind trial of induction of labor with vaginal suppositories containing inert material or either 0.2 mg or 0.4 mg of prostaglandin E₂. The suppositories were self-administered every two hours during waking hours on two successive days until labor started or 15 had been used. Side-effects were absent. Labor was established within 48 hr of insertion of the first suppository in 9.3% of control patients, 65.4% of those treated with 0.2 mg PGE₂ and 85.7% of those treated with 0.4 mg PGE₂. The mean Apgar scores in the three groups were the same. The mean total dose of PGE₂ were 2.0 mg (0.2 mg group) and 2.3 mg (0.4 mg group). It is concluded that vaginal PGE₂ is an effective and acceptable method of inducing labor at term.     

Management of missed abortion and fetal death in utero

Termination of pregnancy in missed abortion and intra-uterine fetal death was accomplished using vaginal suppositories of 20 mg PGE₂ in 31 cases and the results were compared with oxytocin induction (with or without estrogen pre-treatment) in 17 cases at the doses routinely used in our hospital. The PG suppositories proved much more superior (96.7%) than oxytocin (47.7%), but induced a higher rate of side effects. The latter were not serious and were generally tolerated by the patients. There was a positive correlation between duration of fetal retention in utero and the induction expulsion time. The over all patient acceptance of the method was quite favourable and the approach appears to be a definite advance towards management of these cases.     

Essential fatty acid deficiency and platelet fatty acids of normotensive and genetically hypertensive rats

Termination of pregnancy in missed abortion and intra-uterine fetal death was accomplished using vaginal suppositories of 20 mg PGE₂ in 31 cases and the results were compared with oxytocin induction (with or without estrogen pre-treatment) in 17 cases at the doses routinely used in our hospital. The PG suppositories proved much more superior (96.7%) than oxytocin (47.7%), but induced a higher rate of side effects. The latter were not serious and were generally tolerated by the patients. There was a positive correlation between duration of fetal retention in utero and the induction expulsion time. The over all patient acceptance of the method was quite favourable and the approach appears to be a definite advance towards management of these cases.     

Induction of Abortion by Extra-amniotic Administration of Prostaglandins E2 and F2 α

The use of prostaglandins E₂ and F₂α, administered by extra-amniotic instillation, for the induction of abortion was studied in 94 patients in the first and second trimesters of pregnancy. Abortion was successfully induced in 87% of patients within 36 hours and in 94% within 48 hours. The mean abortion time was 22·4 hours. In 60% of patients abortion was complete.Though the differences were not statistically significant, on average multigravid patients aborted more quickly than primigravidae, while the mean abortion time in PGE₂-treated patients was less than in those receiving PGF₂α.No serious complications occurred. Some side effects were observed. Occasional vomiting was the commonest symptom but the incidence of side effects was lower than with alternative routes of administration. A leucocytosis was often noted but there were no significant instances of infection.The method has proved a safe and effective means of terminating pregnancies in the second trimester.     

Role of endogenous prostaglandins in pregnancy termination by 15-methyl PGF2α

Thirty pregnant women with foetal death in utero received 15-methyl PGF_2α to terminate their pregnancies. Two groups (15 cases each) matched for age, gravidity and age of pregnancy were studied. One group received indomethacin suppositories before and during the PG induction while the second group received the prostaglandin analogue therapy only. The group which received the prostaglandin biosynthesis inhibitor showed a longer induction-termination interval, more PG ampoules were used and the number of failed cases was higher. Thus, the Release of Endogenous prostaglandins seems to play a complementary role in the therapeutic termination of pregnancy.     

Prospective study of human parvovirus (B19) infection in pregnancy. Public Health Laboratory Service Working Party on Fifth Disease.

OBJECTIVE--To determine the fetal infection rate and outcome of pregnancy among women who acquire infection with human parvovirus (B19) in the antenatal period. DESIGN--Prospective study of infected pregnancies till time of delivery or abortion with virological investigation of fetuses, neonates, and 1 year old infants. SETTING--England and Wales during 1985-8. PATIENTS--190 Pregnant women with serologically confirmed B19 infection in pregnancy, their fetuses, neonates, and 1 year old infants. RESULTS--Of 186 mothers who elected to go to term, 156 (84%) delivered a normal baby. Follow up of 114 of these infants to the age of 1 year disclosed no appreciable abnormalities, although 27 had serological evidence of intrauterine infection. The overall fetal loss rate (30 cases; 16%) was similar to that in an uninfected antenatal sample (unmatched), but there was a pronounced excess of fetal loss in the second trimester in the B19 infected mothers (11.8%; 95% confidence interval 6.8% to 17.8%). Based on virological findings in the aborted fetuses the risk of fetal death due to B19 in an infected pregnancy was estimated to be 9%. The transplacental transmission rate was estimated to be 33%. CONCLUSIONS--Most women with B19 infection in pregnancy had a satisfactory outcome, but there was nevertheless a substantial risk of fetal loss in the second trimester. In view of the absence to date of any evidence of damage to babies who survive maternal infection therapeutic termination of pregnancy is not indicated.     

Midtrimester abortion induced by serial intravaginal administration of prostaglandin E2 suppositories in conjunction with a contraceptive diaphragm

Midtrimester abortion was successfully induced in 68 of 69 patients with serial intravaginal administration of prostaglandin E₂ suppositories behind a contraceptive diaphragm. The mean abortion time for the successful inductions was 13.07 hours; multiparous patients aborted somewhat faster, mean 12.72 hours, as compared to nulliparous patients, mean 14.22 hours. In 36 patients the PGE₂ suppositories were placed behind an intact diaphragm and the mean abortion time was 14.89 hours. In 33 patients the PGE₂ suppositories were placed behind a diaphragm modified by having an opening incised in the center, the mean time in these patients was 11.96 hours. Of the 68 successful abortions 59% of the patients aborted in 12 hours or less and 88% aborted within 24 hours. The most frequently encountered side effect was temperature elevation of 2° F or higher which occurred in 68% of the patients. Temperatures returned to normal levels within 4 to 6 hours after the last administration of PGE₂. Gastrointestinal side effects occurred in 45% of patients, but these side effects were well tolerated and did not require termination of drug administration in any of the patients. Intravaginal administration of PGE₂ suppositories is a very effective abortifacient technique during the midtrimester, however the use of PGE₂ in conjunction with a diaphrgam did not appreciabley improve the technique although the amount of drug administered and the incidence of side effects was somewhat lower than when the PGE₂ suppositories are used alone. If a diaphragm is to be used, a modified diaphragm is indicated since it simplifies the clinical management of the abortion, eases administration of the suppositories and permits a more accurate estimation of cervical changes, vaginal bleeding and abortion.     

Serum relaxin levels in prostaglandin E2 induced abortions

Relaxin, a peptide hormone produced only by the corpus luteum of pregnancy, can be used as a marker of luteal function in human pregnancy. Serum immunoreactive relaxin levels were measured serially in six women having second trimester abortions induced with intravaginal prostaglandin E2 (PGE₂) suppositories. All patients aborted within 17 hours of the first suppository. No significant changes were detectable in serum relaxin levels in any of the patients. It is concluded that PGE₂ does not interfere with the corpus luteum's ability to secrete relaxin in the second trimester of human pregnancy.     

High risk maternal factors related to fetal wastage in rural Bangladesh

An analysis of the relationship between fetal mortality (early fetal death and stillbirth), pregnancy order, maternal age, and previous fetal deaths in a rural Bangladesh population characterized by high fertility and mortality and the virtual absence of obstetric and other medical care indicates that early fetal wastage and stillbirth are higher among pregnancy orders 1 and 6, or higher than among orders 2 and 3, with the increased risk particularly apparent among those pregnancies following 2 or more previous fetal deaths. The data consist of the 21,144 pregnancies that occurred to the women in Matlab, Bangladesh, 1966-1969. By a multiple regression technique allowing for pregnancy order and previous fetal deaths, adjustments were made for age of the mother, and after allowances were made for previous fetal deaths, adjustments were made for pregnancy order. Results show the fewest fetal deaths in 2nd and 3rd pregnancies, and most at the highest parities. 10% of all pregnancy terminations 1966-1969 were registered as fetal deaths. Women in the higher pregnancy orders who have not experienced previous fetal deaths or only 1 fetal death have only a slight increase in the risk of fetal death compared to women in pregnancy orders 2 and 3. It is concluded that the virtual absence of medical care facilities is responsible for the large numbers of fetal deaths due to complications of gestation, delivery, and environmental influences. It also results in a higher maternal mortality of women with pregnancy complications related to fetal deaths. This absence of obstetric care and the high maternal mortality in this population may allow only women without reproductive impairments to reach the higher pregnancy orders.     

The possible mode of action of prostaglandins: VII - evidence of an antifertility effect of prostaglandin E1 in rats

Prostaglandin E₁ (PGE₁) of 5 mg/kg body weight was found to be ineffective to induce luteolysis in 100% of the test animals when injected either, on day 3, day 5 or day 7 of pregnancy. While, conversely the same dose schedule was absolutely potent in the induction of luteolysis and resorption of fetuses, placentae when tested on day 10 or day 13 of pregnancy. Progesterone alongwith PGE₁ consistently prevented the abortifacient efficacy of PGE₁. Moreover, it was observed that PGE₁ could also successfully terminate pseudopregnant state in the bilaterally hysterectomized rats between fortyeight and ninetysix hours after the injection. It was suggested that the luteolytic or abortifacient efficacy of PGE₁ is not the exclusive reflection of an augmented activity of uterine musculature.     

Perinatal outcome of pregnancies in women aged 40 and over

Perinatal outcome of pregnancies at forty and over was analyzed starting from the diagnosis of pregnancy to seven days following delivery. Retrospectively, pre-gestational health and reproduction status were dealt with, as well as the course of pregnancy, deliveries, and newborn children (study group). The control group was composed of pregnant women aged 20 to 29, who were identical to study group in terms of parity. Statistical data processing was done by means of chi2-test, and contingency 2 x 2 tables. The difference was significant if p < 0.05. Out of 2,099 diagnosed wanted pregnancies at forty and over, 415 (19.8%) had a miscarriage, in 33 (1.6%) an artificial abortion was performed after determining the fetus karyotype and 1,651 (78.2%) of pregnant women delivered. In 66.2% of pregnancies the fetus karyotype was determined and in 33 (2.5%) fetuses chromosomal abnormalities were found Incidence of deliveries at 40 and over is 1.38%, which is a 35.6-percent increase in the last ten years. Nullipara and pluripara had an increase, and multipara had a decrease. Pre-gestational health and reproduction status in study group is lower than in control group. Complications during pregnancy: threatened abortion, EPH gestosis, placenta praevia, gestational diabetes, late fetal death are more frequent than in control group (p < 0.05). In intrapartal terms, more frequent were induction of delivery, meconium-stained amniotic fluid, fetal distress, operative vaginal deliveries, and Cesarean section (p < 0.05). In neonatal outcome there are more premature infant, there are more VLBW, LBW, SGA, newborn with low Apgar index values, and the total perinatal death is greater than in the control group (p < 0.05). In perinatal terms, (from the diagnosis to the seventh day following delivery) 1,617 children survived (77.0%), meaning that perinatal loss was 482 (23.0%). Authors conclude that pregnancy at 40 and over is a high-risk pregnancy. There is a high risk of pre-gestational and gestational complications, and perinatal loss is high. Therefore, those pregnancies are not desirable from the medical point of view.     

Preinduction cervical priming in high risk pregnancy — experience with a new sustained release PGE2 vaginal film

Experience with a new sustained release PGE2 formulation is presented. 111 high risk primiparae with very poor cervical scores (<3) were studied. In 59 patients, labour was induced by forewater amniotomy and I.V. oxytocin. In the remaining 52 patients, film containing 850 ug of PGE₂ was inserted into the vagina to ripen the cervix 24 hours prior to induction of labour. Indications for elective delivery and maternal characteristics were similar in both groups. There were significant changes in the cervical state within 12 hours of vaginal insertion. By 24 hours, 19 patients receiving vaginal film (36.5%) had established labour of whom 13 proceeded to vaginal delivery. Significantly fewer patients in the priming group required Caesarean delivery. No untoward maternal or fetal side effects were observed.Safety, ease of administration and efficacy make this new PGE₂ formulation a useful agent for priming of the very poor primiparous cervix prior to induction of high risk labour.     

Indomethacin increases abortifacient effect of PGE2 in man

Results of this study indicate that pretreatment with indomethacin significantly increases the abortifacient effect of an intravenous infusion of PGE₂ in patients admitted for abortion as a result of fetal death in utero. Indomethacin pretreatment shortened the duration of PGE₂-induced abortion in primigravid and multigravid groups of patients by about 4 and 2 hours respectively. When primigravid and multigravid groups were combined, the dose of PGE₂ needed for complete delivery decreases in the indomethacin-treated group by 39.9%.     

Induction of labour with sulprostone after foetal death and in hydatidiform mole

Induction of uterine contractions was carried out with an intravenous infusion of sulprostone, a 16-phenoxy derivate of methylsulphonylamid prostaglandin E₂ in 21 patients after intrauterine foetal death and in seven patients having hydatidiform mole. The mean total dose of sulprostone was estimated as 1100–1300 μg in different groups. The mean induction-delivery time was 7–13 hours. Expellation of the foetus occurred in 20 out of 21 cases during 24 hours after commencement of sulprostone infusion. In all patients having molar pregnancy uterine contractions induced with sulprostone opened the uterine cervix for evacuation. The drug was clinically well tolerated without any serious side-effects.     

Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.     

Effect of estrogen and progesterone treatment on the depressor response to prostaglandin E2 in ovariectomized women

The effect of exogenous estrogen and progesterone on the response of the systemic arterial pressure to prostaglandin E₂ (PGE₂) was studied in 15 ovariectomized women. All experiments were performed on the 7th postoperative day. Arterial blood pressure was measured in all women in supine position at one minute intervals by an automatic recorder. PGE₂ infused intravenously in all subjects for 10 minutes. Ten of the women who were given intramuscular injections of either estradiol benzoate (10 mg) or inert vechicle 60–65 hours before the experiment, showed a significant decline in both systolic and diastolic blood pressure during the PGE₂ infusion. In contrast, the remaining of the women who were injected with progesterone intramuscularly also 60–65 hours before the experiment, did not present any significant alterations in blood pressure during or after the infusion of PGE₂. These results suggest that, in ovariectomized women, progesterone treatment prevents the depressor response to PGE₂. This may be due to increased inactivation of PGE₂ by various tissues.     

Immunohistochemical demonstration of RECK protein and interleukin-6 in fetal membranes from singleton pregnancies with late preterm delivery,intact membranes and histological chorioamnionitis

ABSTRACT

We investigated whether chorioamnionitis affects immunohistochemical demonstration of RECK protein and interleukin-6 (IL-6) expression in fetal placental membranes following late preterm delivery with intact membranes. Fetal membranes of 28 women with single pregnancy, preterm delivery and histologically documented chorioamnionitis at gestational age 34?36^6/7 weeks constituted the chorioamnionitis study group. The control group consisted of 28 fetal membranes from women with preterm deliveries at the same gestational age without histological chorioamnionitis. Immunohistochemistry was performed using monoclonal antibodies against RECK protein and IL-6. We found a statistically significant difference in RECK expression between the chorioamnionitis and control groups; however, we found no difference in IL-6 expression between the groups. We demonstrated that RECK expression is down-regulated in fetal membranes from pregnancies with spontaneous late preterm birth and intact membranes, which suggests its role in preterm parturition. Equal expression of IL-6 in fetal membranes of pregnancies with and without histological chorioamnionitis is an intriguing and unexpected observation that requires further investigation.