Early pregnancy termination with mifepristone and misoprostol in the United States

BACKGROUND: Mifepristone and a prostaglandin have been used successfully to terminate pregnancy in Europe and China. We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks' duration. METHODS: We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers. The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment. RESULTS: Two thousand fifteen women completed the final assessment. Among them, pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92 percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395 of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent. Failures, defined as cases requiring surgical intervention for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increased with increasing duration of pregnancy. The largest increase was in failures representing ongoing pregnancy, which increased from 1 percent in the < or =49-days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain, nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing gestational age. Two percent of the women in the < or =49-days group, as compared with 4 percent in each of the other two groups, were hospitalized, underwent surgical interventions, and received intravenous fluids (P=0.008). CONCLUSIONS: This mifepristone-misoprostol regimen is effective in terminating pregnancies, especially in women with pregnancies of 49 days' duration or less.     

Transvaginal sonographic diagnosis of short-rib polydactyly dysplasia at 13 weeks' gestation

Short-rib polydactyly dysplasia (SRP) is an autosomal recessive, lethal skeletal dysplasia. Sonographic assessment of subsequent pregnancies is, therefore, recommended. This case indicates that this diagnosis can be made in the latter part of the first trimester. A 30-year-old multigravid woman presented at 13 weeks' gestation for an ultrasound examination. She had had a termination of pregnancy for a fetus with pathologically confirmed short-rib polydactyly dysplasia, type I (Saldino-Noonan). On transvaginal sonography, a narrow chest, symmetrical micromelia, polydactyly and anasarca were present. An autopsy confirmed recurrent SRP. Short-rib polydactyly dysplasia may be diagnosed with transvaginal sonography in the first trimester.     

Methotrexate and misoprostol to terminate early pregnancy

BACKGROUND: Although medical termination of pregnancy is available in Europe and China as an alternative to surgical termination, political and social factors have blocked medical approaches to pregnancy termination in the United States. Methotrexate, which is toxic to trophoblastic tissue, has been used safely to treat unruptured ectopic pregnancies. This report describes the use of a single low dose of methotrexate followed by intravaginal misoprostol for the medical termination of early pregnancy. METHODS: Women seeking termination of pregnancy were selected for this study on the basis of their good general health, emotional stability, and a pregnancy of 63 days or less in duration. Each woman received an intramuscular dose of methotrexate (50 mg per square meter of body-surface area). Five to seven days later, 800 micrograms of misoprostol was administered intravaginally. If abortion did not occur after seven days, the women was offered a second dose of misoprostol or vacuum aspiration. Successful abortion was defined as a complete termination of pregnancy within seven days after the first or second administration of misoprostol. RESULTS: A total of 171 of the 178 women enrolled in the study (96 percent) had successful medical abortions. Twenty-five women (14 percent) did not have an abortion after the first dose of misoprostol and received a second dose. Eighteen subsequently had complete abortions, but seven required suction curettage. In all seven women who required suction curettage, there was histologic evidence of disruption in the conceptus. No important side effects or complications were noted. CONCLUSIONS: The combination of methotrexate and misoprostol represents a safe and effective alternative to invasive methods for the termination of early pregnancy.     

Termination of pregnancy on embryopathic grounds--means to medical decision-making

Now that german legislators have dispensed with explicit formulation of an embryopathic indication, such cases are covered by the unlimited medical indication as defined under Sec. 218a para, 2 of the German Criminal Code. Determining such an indication "in accordance with medical findings" presents the physician with an extremely difficult diagnostic task. Since basic social consensus does not exist with regard to the content of decisions based on embryopathic grounds, quality assurance measures can only target the decision-making process. The central means that the physician has of determining the extent of the related conflict consists of discussion with the patient of her assessment of the situation. Seen in this context, abolition of the patient's obligation to seek counselling in such cases, as arising in connection with relinquishment of explicit formulation of the embryopathic indication, constitutes an incorrect legislational decision that contradicts the entire concept of the law. On the physician's part, this can be countered by guaranteeing that the patient is provided with comprehensive medical information and encouraging her to partake of in social counselling.     

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from S?o Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.     

A study on the optimal regimen of mifepristone with prostaglandin for termination of early pregnancy

One thousand and thirty-five women in early pregnancy (< or = 49 days), who requested medical abortion were randomly allocated into 8 groups. Mifepristone and 15-methyt-PGF2 alpha vaginal suppository (PG05) and misoprostol oral (tablets) were given as the following 8 regimens: group 1 (n = 195): a single dose of mifepristone 200 mg + PG05 1 mg on the 3rd or 4th day; group 2 (n = 249): mifepristone 25 mg b.i.d. (total amount of 150mg) + PG05 1mg on the 3rd or 4th day; group 3 (n = 67): mifepristone 25 mg b.i.d. (total amount of 125mg) + PG05 1mg in the morning of the 3rd day; group 4 (n = 108): a single dose of mifepristone 200mg + misoprostol 600 micrograms on the 3rd day; group 5 (n = 199): a single dose of mifepristone 150mg + misoprostol 600 micrograms on the 3rd day; group 6 (n = 60): mifepristone 50 mg was given immediately, then 25 mg b.i.d. (total amount of 150mg + misoprostol 600 micrograms; group 7 (n = 123): mifepristone 50 mg in the morning and 25mg in the evening for two days (total amount of 150 mg) + misoprostol 600 micrograms; group 8 (n = 34): mifepristone 25 mg b.i.d. (total amount of 125mg) + misoprostol 400 micrograms. As a result, the complete abortion rate of each group was 92.8%, 95.2%, 92.5%, 93.5%, 87.4%, 98.4%, 92.7% and 94.1% successively. The rate of group 5 was significantly lower than that of group 2 and 6 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

辞退福利的中外比较及思考

阐述辞退福利概念,并从确认、计量和披露三个角度对我国企业会计准则和国际会计准则在辞退福利方面的规定进行比较,分析表明我国企业会计准则还需完善,为此应明确规定恰当的折现率,提高辞退福利披露的信息质量等.     

The place of oral contraceptives and pregnancy in the aetiology of amenorrhoea, a study of 188 cases of secondary amenorrhoea lasting more than one year (author''s transl)

Platelet function was assessed before and one week after acute alcohol withdrawal in eighteen male alcoholics. Compared to normal male controls, the platelets of the alcoholics were slightly hypoaggregable on admission but became hyperaggregable one week after commencement of alcohol withdrawal therapy. The changes were most noticeable in those patients who were alcoholaemic on admission and when using ADP or adrenaline as aggregating agents. There was no consistent change in platelet counts or in platelet adenine nucleotide levels, both of which were normal.     

Vaginal misoprostol compared with vaginal gemeprost in termination of second trimester pregnancy. A randomized trial

This case report details a single patient with pure red cell aplasia (PRCA) associated with clonal CD3+, TCRalphabeta+, TCR-Vbeta8+, CD8+, CD57+ large granular lymphocytosis whose anaemia did not respond to conventional immunosuppressive therapy but did respond to cyclosporin A (CsA). The patient has become dependent on CsA for 7 years in order to control anaemia due to associated PRCA.     

Histological study of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins

OBJECTIVE: To study the histological changes of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins (PG). METHODS: A total of 24 women who requested medical abortion was recruited. For each woman, 3 cervical biopsies were taken: before mifepristone treatment; 48 hours after mifepristone 150 mg single dose treatment (i.e. immediately before PG administration); and 1 hour after gestational sac expulsion. Specimens were studied by optical and electron microscopy. RESULTS: Significant collagenolysis as demonstrated by marked reduction and irregularity of collagen fibers, abundant accumulation of an amorphorous material of ground substance, and infiltration of neutrophilic polymorphonuclear leukocytes were shown in stroma as well as in the deep portion of cervix after mifepristone as compared to the samples of early pregnant cervix before treatment. These changes presented to a further extent after the expulsion of gestational sac. CONCLUSION: The changes observed were similar to previous reports during cervical dilatation in term delivery. The present study confirmed the histological cervical ripening effect by mifepristone and suggested it may be used as cervical ripening agent before induction of labor as well.     

Chronic oxygen dependency in infants born at 24-32 weeks' gestation: the role of antenatal and neonatal factors

OBJECTIVES: To study the incidence of chronic oxygen dependency (COD) among ventilated survivors born at 24-32 weeks gestation from 1986 to 1994 and to identify antenatal and neonatal factors that may have changed with time; and to identify antenatal and neonatal factors that could contribute to the development of COD in infants born at 24-32 weeks gestation using a case control model. METHODOLOGY: Infants born at 24-32 weeks gestation in one tertiary referral centre between 1986 and 1994 and admitted to the neonatal intensive care unit for respiratory support were studied. Data accumulated prospectively since 1986 in survivors of ventilation were analyzed to identify antenatal and neonatal factors that could have changed with time. The cohort of infants who developed COD were matched for gestation and time of birth with a control group of infants who did not have COD. Significant factors that could have contributed to the development of COD were identified using forward logistic regression analysis. RESULTS: The number of mothers admitted for threatened premature labour (TPL), and pregnancy induced hypertension decreased with time while the use of antenatal steroids and maternal antibiotics increased. More infants were delivered by Caesarean section during the later years. There was an increase in neonatal septicaemia with time while there were decreases in hyaline membrane disease, pneumothorax, pulmonary interstitial emphysema, use of high peak inspiratory pressure (PIP) and high inspired oxygen. The incidence of COD decreased. The case controlled study revealed a significant positive association between COD and male gender, birthweight less than the 10th percentile for gestation, PIP over 30 cm H2O, septicaemia and significant patent ductus arteriosus (PDA) requiring indomethacin. There was a negative association with TPL. CONCLUSIONS: Further decrease in COD can be achieved only if septicaemia, PDA and the use of high PIP can be avoided. The most effective way of reducing the incidence of COD is by reducing the incidence of prematurity.     

An analysis of neonatal morbidity and mortality in maternal (in utero) and neonatal transports at 24-34 weeks' gestation

Sophisticated neonatal transport has improved the safety of transporting preterm infants, but may not substitute for the benefits of in utero transport. To describe gestational age trends and assess differences in complications between maternal (in utero) and neonatal transports, we analyzed maternal and neonatal transports, over 3 years, to the only tertiary center in the region. Those who delivered between 24 and 34 weeks' gestation were included in the analysis. Gestational age trends for each complication are described, showing, in general, decreasing morbidity with gestational age in both groups. These trends were usually parallel, but not equal. A significantly greater mean neonatal intensive care unit (p = 0.003) and total length of stay (p = 0.006) as well as longer ventilator time (p = 0.01) and oxygen therapy exposure (p = 0.018) were noted in those transported neonatally. The incidence of respiratory distress syndrome (p < 0.001), bronchopulmonary dysplasia (p = 0.027), intraventricular hemorrhage (p = 0.041), intraventricular hemorrhage grades III and IV (p = 0.008), patent ductus arteriosus (p = 0.032), and mortality (p = 0.001) were all significantly greater among the neonatal transports. The differences were not significant for retinopathy of prematurity, hyperbilirubinemia, necrotizing enterocolitis, periventricular leukomalacia, and culture proven sepsis. Specialized neonatal transport and advanced neonatology techniques have not removed the significant advantage of decreased morbidity, mortality, and length of hospital intervention resulting from maternal (in utero) transport.     

Efficacy of intravaginal misoprostol in second-trimester pregnancy termination: a randomized controlled trial

The third and final article of the series covers the mechanism a general dental practitioner should follow when alerting the authorities to a child at risk, and the subsequent investigations and actions that follow such a report.     

Termination of therapy: An effort at integration.

This article explores convergences and divergences among 3 different approaches to termination in therapy. Of particular concern are questions of what constitutes the "reality" of termination. Is refusal to taper off sessions or to keep the door open for potential resumption of the work a useful aid in helping the patient come to terms with the reality of termination's finality? Or is it a needless imposition on the patient of a particular view of the therapeutic process that happens to be held by the therapist? Also examined are the complexities of what it means for the process of termination to be pursued collaboratively and the implications for termination decisions of contemporary insights into the 2-person nature of the therapeutic process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A two-dimensional protein map of human amniotic fluid at 17 weeks' gestation

Using updated technical procedures (immobilized pH gradients for isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: IPG/SDS-PAGE) we provide a two-dimensional (2-D) map of amniotic fluid (AF) proteins. This map comprises over 800 silver-stained spots. Over 150 spots have been identified by matching on the net with human plasma and cerebrospinal fluid maps available from SWISS 2DPAGE database; several additional spots were assigned by immunoblotting and/or microanalytical techniques. This report details our investigation on AF proteins focusing on the 17th week of gestation, when AF is most commonly used for clinical evaluation of fetal disorders. As a whole, the map displays a number of potential markers for fetal development and for gestation abnormalities. The 2-D electrophoretic technique allows the monitoring of all these proteins at the same time along with additional spots that may prove of diagnostic significance.     

Identifying twin gestations at low risk for preterm birth with a transvaginal ultrasonographic cervical measurement at 24 to 26 weeks' gestation

OBJECTIVE: Because twins are a high-risk group for preterm birth, many clinicians routinely use prophylactic interventions such as home bed rest, hospital bed rest, oral tocolytics, or home uterine activity monitoring to prevent preterm delivery. We sought to identify twin gestations at low risk for spontaneous preterm birth with transvaginal ultrasonography of the cervix to avoid the unnecessary use of prophylactic interventions in these pregnancies. STUDY DESIGN: We measured cervical length at 24 to 26 weeks' gestation by transvaginal ultrasonography in women with twin gestations referred to our prematurity prevention clinic. Each delivery was classified as (1) spontaneous preterm birth < 34 weeks' gestation, (2) delivery at > or = 34 weeks' gestation with intervention, or (3) delivery at > or = 34 weeks' gestation without intervention. Intervention included strict bed rest at home or in the hospital, either parenteral or oral tocolysis, or both, or home uterine activity monitoring. Indicated preterm deliveries and patients with cerclage were excluded from this analysis. The ability of transvaginal cervical length to predict women who would deliver at > or = 34 weeks without intervention was evaluated. A cervical length of 35 mm was chosen by scatter diagram as the best cutoff to discriminate between the group delivered at term without intervention and the other two groups. RESULTS: Of 85 women with twin gestations who underwent ultrasonographic cervical length measurements at 24 to 26 weeks' gestation, 17 had spontaneous preterm birth at < 34 weeks, 23 were delivered at > or = 34 weeks but required intervention, and 45 were delivered at > or = 34 weeks without intervention. The mean cervical length for those delivered at > or = 34 weeks' gestation without intervention (36.4 +/- 5.8 mm) was significantly greater (p < 0.0001) than the mean for those delivered preterm (27.4 +/- 8.5) and those delivered at > or = 34 weeks' gestation who required intervention (27.7 +/- 10.5 mm). The sensitivity, specificity, and positive and negative predictive values of a cervical length > 35 mm for predicting delivery at > or = 34 weeks' gestation are 49%, 94%, 97%, and 31%, respectively. CONCLUSION: A transvaginal ultrasonographic measurement of the cervix of > 35 mm at 24 to 26 weeks in twin gestations can identify patients who are at low risk for delivery before 34 weeks' gestation.     

The limit of viability--neonatal outcome of infants born at 22 to 25 weeks' gestation

BACKGROUND: With improved survival of preterm infants, questions have been raised about the limit of viability. To provide better information and counseling for parents of infants about to be delivered after 22 to 25 weeks' gestation, we evaluated the mortality and neonatal morbidity of preterm infants born at these gestational ages. METHODS: We studied retrospectively all 142 infants born at 22 to 25 weeks' gestation (as judged by best obstetrical estimate) from May 1988 through September 1991 in a single hospital. Mortality in the first six months, including stillbirths, and neonatal morbidity (i.e., the presence of intracranial pathologic conditions, chronic lung disease, and retinopathy of prematurity) were analyzed. RESULTS: Fifty-six infants (39 percent) survived for six months. Survival improved with increasing gestational age; none of 29 infants born at 22 weeks' gestation survived, as compared with 6 of 40 (15 percent) born at 23 weeks, 19 of 34 (56 percent) born at 24 weeks, and 31 of 39 (79 percent) born at 25 weeks. There were seven stillbirths at 22 weeks' gestation and four stillbirths at 23 weeks. The more immature the infant, the higher the incidence of neonatal complications as determined by the number of days of mechanical ventilation, the length of the hospital stay, and the presence of retinopathy of prematurity, periventricular or intraventricular hemorrhage, or periventricular leukomalacia. Only 2 percent of infants born at 23 weeks' gestation survived without severe abnormalities on cranial ultrasonography, as compared with 21 percent of those born at 24 weeks and 69 percent of those born at 25 weeks. CONCLUSIONS: We believe that aggressive resuscitation of infants born at 25 weeks' gestation is indicated, but not of those born at 22 weeks. Whether the occasional child who is born at 23 or 24 weeks' gestation and does well justifies the considerable mortality and morbidity of the majority is a question that should be discussed by parents, health care providers, and society.