Clinical, hormonal and sonographic predictors of successful RU-486-induced abortions.

To evaluate which method, clinical, hormonal or sonographic, can be used as the best predictor of successful RU-486-induced abortions, 20 healthy women with fetal cardiac activity, between 6 and 9 weeks from the last menstrual period and desiring abortion, were studied. Fourteen women (70%) successfully aborted, and 6 (30%) failed to abort within 7 days following therapy. A small hematoma, seen as a localized detachment of the gestational sac, was observed in the decidua capsularis in women who aborted successfully. A significant decrease in plasma levels of estradiol and progesterone (p < 0.04) and significantly increased cortisol levels (p < 0.001) in the plasma of the 14 patients who aborted were noted by the 7th day following treatment. No significant changes were observed in the 6 nonaborting patients. In conclusion, the differences in the early sonographic findings may be helpful in the early prediction of successful RU-486 administration.

Acceptability and skin reactions to transdermal estrogen replacement therapy in relation to climate.

The acceptability and skin reaction of Estraderm Transdermal Therapeutic Systems as a function of climatic variability were examined in various zones which alter considerably in their temperature and humidity. An open, noncomparative prospective study was carried out in four institutional out-patient menopausal clinics in varying climatic areas. Eighty symptomatic postmenopausal patients without previous estrogen replacement were examined. Estraderm T.T.S. 50 was applied twice weekly in four weekly cycles. Norethisterone-acetate tablets (1 mg), were taken orally for 12 consecutive days. Using a questionnaire, the subjects were asked about the efficacy of the treatment on postmenopausal symptoms, the adhesiveness and tolerability. The results were matched with the meteorological conditions. The duration of the study was 6 months. Acceptability of Estraderm T.T.S. is high (78.7%). Discontinuation of treatment was found in 21.3% of the study group. The main reason for discontinuation is due to skin reactions which occurred in 14 of the 80 patients (17.5%). Meteorological conditions in this study did not influence the rate of skin reactions. No difference in acceptability of the treatment was found in relation to the mean temperature and mean humidity as registered in the dry desert and the humid coastal areas.

Neurologic involvement in hypertensive disease of pregnancy.

Neurologic manifestations of pregnancy-induced hypertension (PIH) vary from diffuse symptoms such as headache and confusion to focal signs such as paralysis and visual loss. Recognition of the neurologic symptoms associated with PIH is essential for early diagnosis of severe preeclampsia and eclampsia. The recent advances in neuroradiologic imaging, including the use of computed tomography (CT) scans and magnetic resonance imaging (MRI), have greatly enhanced our understanding of the correlation between neurologic complaints and neuroanatomic pathological changes characteristic of preeclampsia and eclampsia. The aim of this review is to summarize the current knowledge on the pathophysiologic changes in the central nervous system (CNS) caused by PIH. The diagnostic possibilities offered by new imaging techniques are emphasized.

Renal and ocular manifestations of hypertensive diseases of pregnancy.

Hypertensive diseases of pregnancy are commonly manifested in renal and ocular changes. Proper evaluation of findings provided by urine analysis, renal biopsy and examination of the optic fundi, visual acuity, and visual fields may help in assessing the severity of the disease and the need for obstetric intervention. Furthermore, renal and ocular changes are important guides in the differential diagnosis of hypertensive disorders of pregnancy. Renal and ocular lesions have also been found to have important prognostic implications. Review of the current knowledge on renal and ocular pathophysiologic changes induced by hypertension in pregnancy, may in addition shade light on the obscure etiology of this common entity.

A simple scoring system for the treatment of cervical incompetence diagnosed during the second trimester.

Twenty-four women with second-trimester cervical incompetence underwent emergency cerclage. The appropriateness of cervical cerclage was analyzed according to a scoring system (Cervical Incompetence Scale; CIS) which measures the degree of cervical effacement, cervical dilatation and protrusion of fetal membranes into the cervical canal. Patients with low CIS (0-3 points) were found to have a more favorable pregnancy outcome than patients with high-score cervical incompetence (5-8 points), i.e. fewer complications following the procedure, 33.3 and 87.5%, respectively, fewer pregnancy losses (22.2 and 75%, respectively) and a significantly prolonged postoperative pregnancy course (mean gestation 33.2 and 24.4 weeks at delivery, respectively). The chances of a successful pregnancy outcome were evaluated at 87.5%; the outcome was successful in patients with low CIS presenting with effacement of the uterine cervix of less than 50%, cervical dilatation of less than 1.5 cm and with fetal membranes remaining in the cervical canal. On the basis of these results, we conclude that the emergency cerclage operation in carefully selected patients with midtrimester cervical incompetence may improve the outcome of pregnancy. This selection is facilitated by the use of a new cervical incompetence scoring system described herein.

Meteorological factors in hypertensive disorders, vaginal bleeding and premature rupture of membranes during pregnancy.

In order to determine whether there is a correlation between meteorological factors and the occurrence of hypertensive disorders, vaginal bleeding during pregnancy and premature rupture of the fetal membranes, we stratified all the patients hospitalized with such complications between the years 1984 and 1988 by the months of occurrence, weather, humidity and heat. During this period, there were 276 women hospitalized with exacerbation of hypertension and toxemia, 349 because of vaginal bleeding during pregnancy and 35 women following premature rupture of the fetal membrane between 30 and 33 weeks of gestation. The occurrence of pre-eclampsia and exacerbation of pregnancy-induced hypertension was significantly increased in the winter months (p less than 0.001).

Fetal habituation to sound stimulus in various behavioral states.

The correlation between arousal state and fetal habituation was tested. Four behavioral states were determined according to fetal heart activity and movement pattern in 52 fetuses. Repeated wide low-frequency sound was used as external stimulus. Ceasing of response to 5 consecutive stimuli indicated habituation. The time from response to habituation was defined as habituation time. Although fetuses in a lower arousal state habituate more rapidly, the difference is not statistically significant.

Breast stimulation in late pregnancy. Effect on prostaglandin secretion.

The effect of breast stimulation on the prostaglandin secretion was tested in 13 patients at 38-40 weeks of gestation. Uterine contractions following breast stimulation were documented in all cases. There was an increase in prostaglandin metabolite levels 10 min after breast stimulation.

Immunization by paternal leukocytes for prevention of primary habitual abortion: results of a matched controlled trial.

Habitual abortion is a difficult clinical problem, as no cause can be found for abortion in over 50% of patients. At the habitual abortion clinic of the Sheba Medical Center, immunological activity is tested and patients who are considered suitable are offered immunopotentiation with paternal leukocytes. Patients are only treated if they have no other cause for habitual abortion, no lupus anticoagulant and no antipaternal complement-dependent antibodies (APCA). Immunization is thought to potentiate the maternal immune response to paternal antigens encountered on the trophoblast. The production of APCA antibody indicates that an immune response has occurred. Of the 156 patients so far immunized, 109 have developed these antibodies. To date, 79 of these 156 patients have become pregnant. Sixty-seven patients (with 3-12 miscarriages each) belong to the antibody-positive group. Sixty-four of the 89 subsequent pregnancies have been carried past their previous dates of abortion. Forty-seven live births have occurred. By contrast, 12 patients have been pregnant in the antibody-negative group, of the 16 subsequent pregnancies only 6 were successful. A control group is available for comparison. This consists of patients suitable for immunization, but not immunized. Of these patients, only 11 of 30 pregnancies have been carried to term.

Human fetal behavioral state at term.

The present study was designed to test the existence of behavioral states in the fetus at term using simplified techniques. For this purpose simultaneous recording of the fetal heart activity by means of phonocardiotocography and of fetal body movements by means of real-time ultrasound was performed by using a multichannel recorded. The fetal heart activity was analyzed for two parameters: (1) long-term variability and (2) baseline accelerations. The fetal body movements were classified into three types. 880 min of recording time from 50 fetuses at 37-41 weeks of gestation were analyzed. Each segment of 1 and 3 min was classified into four distinct states, according to the combination of the above parameters. The segments that failed to fit into one of these states were labeled as 'no state'. The frequency of each parameter was also independently calculated. The results were statistically analyzed by using a computer. The significance of the difference between the observed frequencies of the various states and their expected frequencies (obtained by the frequencies of the individual parameters) was calculated by the chi 2 test. Behavioral states of a duration of 3 min were observed in 45.6% of the total periods recorded which is significantly higher (p less than 0.001) than the 4.1% expected.

Successful outcome of pregnancy following complete removal of uterine septum during cesarean section.

Two cases are described where a malformed uterus was the reason for either repeated abortions or premature deliveries resulting in fetal loss. In both cases the removal of the septum during cesarean section resulted in uneventful postoperative courses, and subsequently in successful pregnancies and births of healthy infants to both women.

In vitro fertilization in Kock's ileostomy patients. Prior evaluation by pelvic ultrasonography.

The study describes Kock's continent ileostomy in 2 females, both of whom were suffering from tubal infertility. Appropriate placement of the abdominal pouch, permitting in vitro fertilization embryo transfer treatment, was present in 1 patient. In the other patient, an ultrasonographic examination demonstrated the pouch covering the entire surface area of both ovaries. Oocyte aspiration was thus precluded for fear of penetrating the pouch. Ovum pickup in the presence of a Kock continent ileostomy can be conducted safely and without risk, if the pouch is correctly positioned above the small pelvis. Ultrasonography facilitated the ability to locate the patients' ovaries and precise position of the pouch.

Selection of patients with habitual abortion for paternal leucocyte immunization.

After potentiation of the immune response in habitual aborters 75-85% of subsequent pregnancies are claimed to result in healthy term infants. However, all publications to date have either been based on the authors concept of the immune processes involved or an attempt to demonstrate the efficacy of treatment either empirically or by matched trials. As immunization is coming into wider clinical use, it is necessary to determine which patients will benefit from this form of treatment. This paper presents our experience with paternal leucocyte immunization over the period 1985-1988. 207 patients were classified on a clinical basis and by immunological testing. 143 patients have been immunised, 129 pregnancies have occurred in 108 patients. The vast majority of our patients have recurrent missed abortions. Only six women habitually aborted live fetuses. Two had subsequent live births. Secondary aborters seem to do well in subsequent pregnancies, whether immunized or not. The patient most likely to benefit from immunization is the Primary missed aborter who does not possess antipaternal antibody (APCA), but is induced to produce APCA by immunization. Using these criteria, 75% success rates are observed in the subsequent pregnancy. This success rate is irrespective of HLA antigen sharing or in-vitro mixed lymphocyte reactivity.

Beta-endorphin levels in the follicular fluid of human oocytes fertilized in vitro.

This study was carried out in order to investigate the relationship between beta-endorphin (beta-ep) levels in plasma and follicular fluid and fertilization rates of oocytes from women undergoing treatment in our in vitro fertilization and embryo transfer program. Nine women suffering from severe tubal damage, with regular menstrual cycles, were studied. Follicular growth was induced with clomiphene citrate, combined with human menopausal gonadotropins. Analysis of follicular fluids and plasma showed no significant difference in beta-ep levels. The larger follicles (greater than 2 ml volume) had significantly higher beta-ep levels than smaller follicles (less than 2 ml volume; p less than 0.001); however, there was no significant difference in the fertilization rates of their oocytes.

Failure to improve ovarian response by combined gonadotropin-releasing hormone agonist and gonadotropin therapy.

Nineteen women were treated with the gonadotropin-releasing hormone (GnRH) agonist buserelin in order to suppress the pituitary prior to gonadotropin treatment. Eight women were oligomenorrheic, 6 had polycystic ovarian disease (PCOD) and 5 women had normal cycles. Buserelin was administered for 3 weeks before ovarian stimulation, and the pituitary down-regulation was proven by provocative tests. Ovarian stimulation was then achieved by human menopausal gonadotropin (hMG) 2 ampules a day. Several abnormal responses to the combined buserelin/hMG treatment were noted in some patients. This included a sudden decrease in E2 level without LH surge (2 patients), induced follicular growth with buserelin instead of ovarian suppression (2 patients) and ovarian hyperstimulation syndrome in 3 patients with PCOD. From this we conclude that although pituitary suppression can easily be achieved by GnRH analog administration, this does not ensure the prevention of unwanted responses. It is possible that the common denominator for these abnormal responses is that they are ovarian in origin, hence they occur in spite of pituitary down-regulation. Close monitoring of the suppression and stimulation stages will detect most cases of such failures. Furthermore it is possible that not all patients are suitable for the combined treatment of gonadotropin and GnRH agonist.

The association of pregnancy-induced hypertension and uterine malformations.

To evaluate the incidence of pregnancy-induced hypertension (PIH) in women with congenital uterine malformations, we examined the pregnancy complications of 67 women with uterine anomalies demonstrated by hysterosalpingography (HSG). The study group was compared with a control group of 130 women with normal-shaped uterus proven by HSG-matched for age, parity and presenting complaint. A significantly increased (p less than 0.04) rate of PIH was found for women with uterine malformation as well as a 2-fold higher frequency of preeclampsia. The etiology for this association is unknown, however; it is suggested that uterine malformation is a predisposing condition to PIH.

The improving outcome of triplet pregnancies.

During the period 1975 to 1988, 78 triplet pregnancies that reached a gestational age greater than or equal to 20 weeks were treated in our department--a prevalence of 1/849 deliveries. A total of 69 (88%) of the pregnancies occurred after treatment with ovulation-induction agents. The most common complication of pregnancy was premature contractions. Elective cervical cerclage neither prolonged gestation nor decreased fetal loss. The mean gestational age at delivery was 33.2 weeks + 3.8 weeks and 86% of the patients were delivered of premature infants. The perinatal and neonatal mortality rates were 93/1000 and 51/1000, respectively. Our results show a higher proportion of low Apgar scores and respiratory disorders in the third vaginally delivered infants. Follow-up of very low birth weight infants revealed four infants (10.5%) with severe neurologic handicaps. Results of this study suggest that cesarean section is the preferred mode of delivery in triplet pregnancies. Maternal, fetal, and neonatal risks of triplet gestations are relatively low and compare favorably with recent reports on twin pregnancies.

Hot flushes during Gn-RH analogue administration despite normal serum oestradiol levels.

Five out of 6 normally-menstruating women who were treated with a potent gonadotropin-releasing hormone (Gn-RH) agonist in order to achieve medical hypophysectomy developed hot flushes despite having normal oestradiol (E2) levels. The Gn-RH agonist was administered subcutaneously for 6 days and then intranasally for a further 14 days. A dose of 2 mg of E2 benzoate was injected intramuscularly once a week for 2 consecutive weeks. This combined treatment resulted in low peripheral gonadotropin levels but normal serum E2 concentrations. Four (4) women developed mild to moderate hot flushes and there was 1 case of flushes severe enough to necessitate cessation of treatment. The flushes occurred in the second week of Gn-RH analogue treatment when the level of serum luteinizing hormone (LH) was low and the pituitary was unresponsive to provocative tests, despite the fact that the patients' E2 levels were normal (mean 250 +/- 25 pg/ml). It is suggested that neither LH pulsatility nor low peripheral E2 levels are mainly responsible for the development of hot flushes. It is possible that Gn-RH, a hypothalamic decapeptide, may play a major role or act as a mediator in the aetiology of hot flushes.

The role of gonadotropins in the etiology of ectopic pregnancy.

Our study indicates that the high rate of EP in MAP(+) patients, treated with hMG/hCG, is due to the fact that it is a selected group of infertile patients with probable additional underlying tubal disease. Absence of EP in MAP(-) patients indirectly support the theory that a mechanical factor is at work. It is, therefore, our opinion, that the cause of ectopic pregnancy lies in the patient and not in the drug (hMG/hCG).