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The study was designed to investigate the source of progesterone secretion during pituitary suppression and ovarian stimulation. It involved 416 women undergoing in-vitro fertilization (IVF) who were treated with gonadotropin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group 1), 139 women undergoing ovulation induction with HMG only (group II) and nine women who were diagnosed previously as late-onset adrenal hyperplasia and treated continuously with dexamethasone, in addition to ovulation induction (group III). During HMG treatment, serum oestradiol and progesterone were measured every 1-2 days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before human chorionic gonadotrophin (HCG) administration, the patients were prospectively randomized to treatment with dexamethasone or not and the hormones concentrations were measured again 12 h later. Mean age and pretreatment serum concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not significantly different in the patients with and without progesterone elevation. Pituitary down-regulation did not reduce the incidence of progesterone elevation (13.9 and 12.2% in groups I and II respectively), while in group III, progesterone concentrations did not increase. After dexamethasone administration a significant decrease in serum progesterone concentration was demonstrated (mean ± SD, -2.1 ± 1.4 and -1.6 ± 1.2 in groups I and II respectively, while in the untreated patients it increased (+1.9 ± 1.9 and +4.2 ± 4.8). The increase in serum progesterone concentrations was not accompanied by an increase in cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone administration the concentrations of cortisol, 11-deoxycortisol and LH significantly decreased. Progesterone concentration was positively correlated with both oestradiol concentration (r=0.290; P <0.05) and the number of oocytes retrieved (r=0.207; P <0.05). We conclude that at least a part of serum follicular-phase progesterone appears to be of adrenal origin. High oestrogen concentrations (or other ovarian factors) may cause changes in the hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of the complex 'cross-talk' between the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes. [ABSTRACT FROM PUBLISHER]

Objective: To determine whether the mode of delivery has a protective value on the immediate adverse neonatal neurological outcome of infants born from pregnancies complicated by preterm chorioamnionitis., Methods: A comparison of the immediate and long-term neurological outcome of preterm neonates (24-34 weeks' gestation) of pregnancies complicated by chorioamnionitis, was made between those born by Cesarean section and by vaginal delivery., Results: Of the 73 newborns, 54 (74%) survived the neonatal period; two (2.7%) had incomplete records, leaving 71 for analysis. Thirty (42.2%) were delivered by Cesarean section and 41 (57.7%) vaginally. The obstetric and neonatal characteristics were comparable. Twenty-four (80%) survived in the Cesarean group and 30 (73.2%) in the vaginal delivery group (NS). There was no significant difference in the immediate adverse neonatal neurological outcome between Cesarean and vaginal deliveries., Conclusions: The mode of delivery did not significantly affect the immediate neurological status of preterm infants exposed to antenatal intrauterine infection.

Leptin is secreted during pregnancy by the placenta and by the maternal and fetal adipose tissues. The leptin levels mainly reflect the amount of fat stored and thus are indicative of the energy balance, i.e., small-for-gestational-age (SGA) neonates represent the negative metabolic balance of in utero starved babies. We chose to compare maternal and umbilical cord leptin levels in pregnancies complicated by asymmetrical SGA versus those with appropriate-for-gestational-age (AGA) neonates as well as a model of multifetal growth concordant gestations in order to establish through the 'leptin link' the relative contributions of mother, fetus, and placenta to fetal weight. We found that the maternal leptin levels at delivery correlated poorly with the maternal weight gain/body mass index and with neonatal birth weight. Furthermore, the umbilical cord leptin levels correlated well with neonatal and placental weights in the AGA group but not in the SGA group. As in AGA singleton pregnancies, in multifetal uncomplicated pregnancies, the umbilical cord leptin levels correlated well with the birth weight of individuals, regardless of the status of the twin or triplet in the set. Thus, we speculated that in SGA neonates the birth weight represents the lean body weight and the low adipose tissue content (as opposed to the AGA neonates who have a substantial adipose tissue content) and, therefore, reflects mainly the basic placental contribution., (Copyright 2003 S. Karger AG, Basel)

Background: In a previous study we have found that in normal ovulatory women, serum inhibin B levels on days 4-6 of FSH administration correlated with the number of oocytes retrieved. In the current study we examined the significance of earlier inhibin B measurements in predicting the oocyte number, in both normal and low responders., Methods: Study A consisted of 19 patients undergoing their first IVF cycle (n = 10) or had a normal response ( vertical line 6 oocytes retrieved, n = 9), while study B consisted of 15 patients with a previous low ovarian response (16. Study B: oocyte number correlated significantly with inhibin B and inhibin A on all days of FSH treatment, even on day 2 (r = 0.90, P < 0.001 and r = 0.65, P < 0.05 for inhibin B and A respectively). No significant correlation was found with E(2) levels. In both studies, all patients with inhibin B >100 pg/ml on treatment day 2 had >6 oocytes., Conclusions: Our data suggest that serum inhibin B measured early during FSH stimulation may indicate whether sufficient oocytes will be retrieved, in both normal and low responders. Serum inhibin B measured during early FSH treatment may be of predictive value in monitoring ovarian stimulation treatment for IVF.

Background: The role of intravenous (IV) albumin administration in the prevention of ovarian hyperstimulation syndrome (OHSS) and in the improvement of IVF conception outcomes was evaluated in a prospective, randomized, placebo-controlled double blind study., Methods: Ninety-eight women were enrolled in the study and were consecutively assigned to either a treatment group or a control group. Eleven patients were lost to follow-up after assignment. Of the remaining 87 women, 46 received albumin on the day of oocyte retrieval, and 41 received 0.9% sodium chloride solution as a placebo control. Outcome measures included OHSS incidence rates and pregnancy rates in the two trial groups., Results: Four of the 46 patients in the study group developed severe OHSS and six developed moderate OHSS. In the control group, one of the 41 developed severe OHSS and five developed moderate OHSS. The difference in OHSS incidence rates between the two groups was not statistically significant [relative risk (RR) = 1.49, 95% CI = 0.59-3.73]. Fourteen patients (30%) in the intervention group conceived, compared with 16 patients (39%) in the control group. The difference in conception rates between the two groups was not statistically significant (RR = 0.78, 95% CI = 0.44-1.39)., Conclusions: Albumin appears to have no positive effect on OHSS or conception rates, while its use carries the risk of undesirable side effects, including exacerbation of ascites in OHSS, nausea, vomiting, febrile reaction, allergic reaction, anaphylactic shock and risk of virus and prion transmission. We suggest that this form of treatment should not be included in the prevention of OHSS.

Quality of life of 5% of the female population is impaired by urinary stress incontinence. Its cause is pelvic floor relaxation and the cure is surgical. The most widely performed operations are retropubic colposuspensions and sling operations, which have relatively high, well-proven cure rates. Yet because of the long rehabilitation required, gyneco-urologists seek minimally invasive ways to solve the problem. Vaginal colporrhaphy and laparoscopic operations are not common, but the recently reported TVT might become popular if proven effective.

Unlabelled: The aim of the present work was to review the published evidence on the association of Bell palsy (BP), an acute idiopathic peripheral facial paralysis of unknown etiology, with pregnancy. Reports have shown that women of reproductive age are affected two to four times more often than men of the same age, and pregnant women 3.3 times more often than nonpregnant women. The apparent predisposition of pregnant women to Bell palsy has been attributed to the high extracellular fluid content, viral inflammation, and immunosuppression characteristic of pregnancy, but findings are controversial. Most cases of Bell palsy occur in the third trimester or the puerperium. Onset is acute and painful. Some authors suggest that Bell palsy increases the risk of hypertension and toxemia of pregnancy, whereas the pregnant state, in turn, may affect the course and severity of disease. Recovery is usually good; poor prognostic markers are recurrence in subsequent pregnancy and bilateral disease, both of which are rare. Neonatal outcome is apparently unaffected, although this has been studied rarely. The preferred mode of management remains undecided; it is usually confined to supportive care. Corticosteroids in pregnancy are controversial. We think clinicians should be aware of these findings to avoid unnecessary testing and treatment and to help the patient cope with this acute, painful disease., Target Audience: Obstetricians & Gynecologists, Family Physicians, Learning Objectives: After completion of this article, the reader will be able to identify the potential etiologies of Bell palsy associated with pregnancy and to describe the clinical presentation of this condition in pregnancy and its likelihood for recovery.

Objective: To investigate the clinical efficacy of mild inhibition of ovarian steroidogenesis by very low-dose ketoconazole during induction of ovulation in patients with polycystic ovary syndrome (PCOS)., Design: Prospective, randomized, cross-controlled study in consecutive cycles., Setting: Large tertiary care center., Patient(s): Eighteen patients with PCOS undergoing hMG superovulation with or without ketoconazole., Intervention(s): A fixed hMG dosage was initiated on cycle days 5-9 in both of the study cycles. Further hMG adjustment was done according to serum E2 levels and follicular measurements. Ketoconazole was administered in one of the cycles by two protocols., Main Outcome Measure(s): Serum E2 and P levels, lead follicles, pregnancy rate, and development of ovarian hyperstimulation syndrome., Result(s): Although higher daily hMG doses were needed in cycles with ketoconazole compared with cycles without the drug, the peak E2 levels were substantially lower in the ketoconazole cycles. Although the number of lead follicles did not differ between treatments, the addition of ketoconazole significantly reduced the number of hyperstimulated cycles. Consequently, the cancellation rate dropped dramatically, thus yielding a higher pregnancy rate per patient in the ketoconazole protocols., Conclusion(s): Use of a very low dose of ketoconazole during ovulation induction effectively attenuates ovarian steroidogenesis in patients with PCOS. This effect may serve as an adjunct to better control the ovarian response in women who are prone to hyperstimulated cycles.

Umbilical artery velocity waves were obtained by Doppler ultrasonography before, during, and after 20 episodes of fetal heart rate (FHR) variable decelerations (VD) during the active stage of labor in 8 women. During 50% of the VD periods, the umbilical artery resistance flow parameters increased significantly (p < 0.01). The increase in resistance preceded the decrease in FHR in six episodes (30%) of VD (AR-VD group; arterial resistance VD) and did not precede the change in FHR in another ten episodes (50%) of VD (VR-VD group; venous resistance VD). In the AR-VD group the FHR accelerations occurred before the decelerations in only 1 case (17%), while in the VR-VD group FHR accelerations preceded the decelerations in 8 out of the 10 episodes (80%). Using these Doppler studies, it may be possible to differentiate between two groups of VD: AR-VD - which are caused by umbilical artery occlusion and thus preceded by a measurable increase in umbilical artery resistance - and VR-VD - which are not preceded by a measurable increase in umbilical artery resistance and may be caused by fetal hypoxia.

Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity.

Objective: Erythromycin is a stimulant of motor activity in the stomach, but its effects on the uterus have not been studied and only its antibiotic properties have been considered in the treatment of idiopathic preterm labor. The objective of this study was to characterize in vitro the effect of erythromycin on the contractility of the pregnant rat uterus., Study Design: Myometrial strips from pregnant rats were suspended in tissue baths Isometric contractions were monitored by force transducers in response to various agents that were added to the bath solution., Results: Erythromycin exposure caused a sustained decrease in phasic contractions induced by oxytocin or carbachol. This effect started at 0.01 mmol/L. At 1 mmol/L erythromycin reduced the contractions amplitude to 22% of the control and the frequency was reduced to 38% of control., Conclusion: We conclude that erythromycin produces a decrease in the pregnant rat myometrial activity in vitro, independent of the stimulant.

Objective: To assess the prevalence and incidence of postnatal depression and its relation to certain psychosocial factors., Method: A questionnaire was administered to 327 randomly selected pregnant women on the first or second postpartum day A and again 6 to 12 weeks later B. The questionnaire comprised a psychosocial and demographic self-report, and the 10-item Edinburgh Postnatal Depression Scale (EPDS)., Results: At time A the prevalence of postnatal depression was 9.9-22.3%, and at time B it was 5.2-12.4% (p < 0.0001). Four of the psychosocial determinants examined correlated significantly with depression at times A and B. These factors were: a positive psychiatric history, Oriental ethnic origin, being foreign born, inconvenient timing of pregnancy., Conclusion: Postnatal depression was less common than in most reported series. It was related to marital and social support, the circumstances of the pregnancy, and the degree of religious observance. Postnatal depression is a specific disorder, not equivalent to depression in the prenatal period.

Objective: To test the hypothesis that insulin acts though ovarian IGF-I receptors to produce excessive amounts of androgens in polycystic ovarian syndrome (PCOS), by measuring the binding capacity of IGF-I receptors on erythrocytes and relating the findings to the degree of hyperandrogenism and hyperinsulinaemia., Design: A case-control study of IGF-I receptors on erythrocytes of women with PCOS and age- and weight-matched controls., Patients and Methods: IGF-I receptors on erythrocytes, serum levels of androgens, IGF-I, GH, basal insulin and insulin response during oral glucose tolerance test (oGTT) were measured after induced or spontaneous withdrawal bleeding in 10 women with PCOS and eight normo-ovulatory women., Results: An increased number of IGF-I receptors was found on erythrocytes of patients with PCOS compared with the controls (P < 0.01), irrespective of their body mass index. Serum IGF-I levels were similar in both groups. The degree of hyperinsulinaemia, provoked by oGTT, correlated positively with basal insulin (r = 0.69; P = 0.003), but not with the number of IGF-I receptors. However, the number of IGF-I receptors correlated positively with androstenedione (r = 0.54, P = 0.0018)., Conclusions: The findings in the present study that the number of IGF-I receptors and not the insulin levels correlate with serum androstenedione support the theory that the hyperandrogenism in PCOS is not a direct effect of the hyperinsulinaemia, but IGF-I mediated.

Objective: To investigate whether elevated serum P levels after pituitary down-regulation signify adrenal enzyme defects or hyperandrogenism., Design: Prospective study., Setting: Assisted reproduction unit in a university medical center., Patient(s): Two hundred twenty-seven IVF patients treated by the long down-regulation protocol., Intervention(s): Oral dexamethasone (DEX) administration if P level exceeded 0.8 ng/mL (conversion factor to SI unit, 3.180) after pituitary suppression., Main Outcome Measure(s): Serum concentrations of P, E2, LH, DHEAS, and 17 alpha-hydroxyprogesterone and ACTH stimulation tests., Result(s): In eight patients (3.5%), serum P levels exceeded 0.8 ng/mL and E2 and LH levels confirmed pituitary down-regulation. Mean DHEAS levels in the patients in this group were significantly higher than in the other patients. All eight patients demonstrated a significant decrease in serum P level after DEX administration. In five patients the ACTH stimulation test suggested an adrenal defect. Five pregnancies were achieved after the addition of DEX to the treatment protocol., Conclusion(s): High serum P levels after pituitary down-regulation appear to be of adrenal origin and may be the first indication of an adrenal enzyme defect. Further investigation such as an ACTH stimulation test is recommended, followed by treatment with DEX if indicated.

The association of retropubic colposuspension for the treatment of urinary stress incontinence with genital prolapse has been reported previously. Described here is a case of an 83-year-old patient who had a colponeedle suspension and was readmitted because of genital prolapse 3 weeks after surgery. This case emphasizes the need for proper evaluation of the whole pelvic floor prior to any surgical treatment for urinary incontinence, and addition of appropriate surgical measures aimed to avoid later genital prolapse, if necessary.

Women undergoing ultrasound scanning for the detection of ovarian cancer benefit psychologically from the examination, which has been shown to reduce levels of anxiety, depression, hostility and complaints about somatic symptoms. However, it is not completely clear what aspects of the ultrasound examination are responsible for these effects, and how these beneficial psychological effects vary under different circumstances. This study examined, in particular, the effect of various levels of feedback on patients' anxiety levels before and after ultrasound examination. Two hundred and seven women were randomly assigned to two different experimental conditions: high feedback and low feedback. The subjects' levels of anxiety (both trait and state anxiety) were measured immediately before and after the ultrasound examination. The women's individual risk factors for ovarian cancer were also recorded. This study showed a significant decrease in the level of trait anxiety following ultrasound scanning. The decrease in anxiety did not relate to the level of feedback provided to the patients, nor to the woman's degree of risk for ovarian cancer. The results are discussed in terms of possible implications for clinical care and the allocation of resources in the medical system.

Objective: We report our experience on the gynecologic and obstetric features of 53 female patients with Gaucher's disease., Study Design: Each patient was interviewed for a detailed medical history, and all underwent a complete physical examination and laboratory work-up., Results: Delay of puberty onset was encountered in two thirds of the patients without subsequent infertility. Heavy menstrual bleeding was a major problem and was best treated with low-dose oral contraceptives. Of the 102 spontaneous pregnancies' 25 (24.5%) ended in spontaneous first-trimesters abortions; 72 continued beyond the twenty-second week. Nine patients (27.7%) were diagnosed as having Gaucher's disease during their first pregnancies. Aggravation of thrombocytopenia and anemia were prominent features, but antepartum blood transfusion was not required. Early postpartum hemorrhage and fever were increased after both cesarean and vaginal deliveries. Development of bone crisis in seven women during the third trimester and early postpartum periods recurred in subsequent pregnancies. Genotypes had not influenced the gynecologic or obstetric manifestations., Conclusions: Gynecologic and obstetric complications play a significant role in this patient population, representing an additional burden to female patients with Gaucher's disease.

Primary lymphoma of the ovary is an extremely rare cause of ovarian mass. Few cases have been recorded in English literature, and controversy still exists as to the existence of such an entity. We present a case whose diagnosis can be supported by rigorous diagnostic criteria--a long follow-up after surgery with only one course of adjunctive polychemotherapy. This case, together with a review of the literature, will enrich our knowledge on the issue and on the treatment of these patients.

Indomethacin is a non steroidal anti-inflammatory agent widely employed in the treatment of premature contractions. Indomethycin induced oligohydramnios is a well described side-effect, and is considered an indication for treatment discontinuation. We present a case of prolonged anhydramnios, secondary to indomethacin therapy with no apparent ill-effect on the fetus or neonate.

In a group of women in the first and early second trimesters of pregnancy, local thickening of a limited region of the myometrium was observed ultrasonically. This prospective study aimed to evaluate the incidence and nature of this phenomenon. Local myometrial thickening was observed in 72 women out of 5521 examined (1.3%). Twenty-two were given ritodrine hydrochloride 10 mg by mouth, and 46 were monitored for up to 60 min without treatment. The local myometrial thickening in the ritodrine hydrochloride-treated group disappeared in 21 out of 22 women (95.5%) compared with the observed group, where the phenomenon disappeared in only 37 women (80.4%). Local myometrial thickenings probably represent transient uterine contractions; they tend to appear early in pregnancy, are prolonged, and may respond to ritodrine hydrochloride.

Ultrasound examination at 9 weeks of gestation in a 34-year-old primigravida showed a twin pregnancy, with discrepancy in the sizes of the two gestational sacs, whereas the crown-rump lengths and fetal heart rates were virtually identical-the result being an abnormal sac size/crown-rump length ratio (early oligohydramnios). By 14 weeks discordant heart rates and umbilical artery flow velocities were detected, the discordance between the twins increasing as pregnancy progressed. Biparietal diameters, femoral lengths, and abdominal circumferences were also progressively discordant, and at 28 weeks the smaller twin had no heart beat. At 30 weeks the patient was delivered of a live 1,350-gram infant and a 400-gram dead fetus. This case suggests, in contradistinction to several previous reports, that fetal discordance in twin pregnancies (and perhaps intrauterine growth retardation in general) may be present as early as the first trimester.

Objectives: To determine at which gestational age the ultrasound finding of a breech presentation should compel us to follow the pregnancy more closely with repeat ultrasound examinations., Methods: A retrospective longitudinal investigation of ultrasound examinations in the second and third trimesters is reported. The study group consisted of 157 breech deliveries and a control group of 1325 vertex deliveries., Results: In the study population (breech delivery) 63.2% were presenting as breech during the 15th-19th weeks of pregnancy--almost the same percentage as in the vertex-born group (of which 55.2% were breech presentation). In the interval between 20 and 24 weeks the same relationship was observed (50.8% and 42.9%, respectively). From 25 weeks until delivery a statistically significant difference appeared between the breech-delivered group and the vertex-delivered group: during weeks 25-29 in the breech-delivered group, 70.6% were breech presentation compared with 28.9% in the vertex-born group (P < 0.0001). That difference increased as the pregnancy progressed., Conclusions: Patients found sonographically to be a breech presentation at 25 weeks' gestation or later are at high risk for malpresentation at delivery.

First-trimester spontaneous abortions have been predicted from alterations in the gestational sac size and embryonic heart rate. To evaluate which parameter or combination of parameters has the greatest predictive value, a prospective study was carried out during the first trimester of pregnancy. Pregnancy sac size, crown-rump length and heart rate were measured in 603 embryos, of which 580 continued beyond 13 weeks' gestation and 23 ended in first-trimester spontaneous abortions. Based on the continuing pregnancies, we constructed nomograms relating the ratio of mean sac diameter to crown-rump length (S/CR) to gestational age (last menstrual period [LMP]), to crown-rump length (CRL) and to embryonic heart rate (EHR). The S/CR ratios of the 23 embryos that spontaneously aborted in the first trimester were plotted on these nomograms to determine the significance of values falling outside the 95% confidence limits. Plotting the S/CR ratios of the aborted fetuses on the S/CR versus LMP nomogram gave a sensitivity of 78.3%, a specificity of 97.8% and a false-positive rate of 2.2%. The same population was evaluated for abortion risk using EHR nomograms, giving a sensitivity of 65.2%, specificity of 98.2% and false-positive rate of 1.8%. Our findings suggest that S/CR measurement in early pregnancy may be a simple and reliable method of predicting first-trimester abortions.

In view of increasing incidence of adenomyosis and endometriosis reported in recent years, we evaluated the incidence of these disorders in a unique ultra-orthodox Jewish population over the past 20 years by reviewing 1,434 hysterectomy specimens. The incidence of adenomyosis among the hysterectomy specimens decreased from 15.14% in the first 10 years of the period studied, to 9.24% in the second decade (p < 0.05). The incidence of endometriosis remained unchanged, and was very low (1.12%) compared to published data. Our findings highlight the possible effects of heredity, religious and social behavior on the etiology of endometriosis.

Umbilical artery flow curves were obtained by Doppler ultrasonography before, during, and after episodes of fetal bradycardia in the active stage of labor in 6 women. Between 126 and 1,607 Doppler wave forms were analyzed for each patient. During the periods of bradycardia all the umbilical artery resistance flow parameters increased (p < 0.00001). The increase in resistance did not precede the change in heart rate. This study presents an accurate and reproducible method for continuous evaluation of the changes in the impedance of fetal blood flow during fetal heart rate changes, thereby enabling detailed assessment of circulatory disturbances occurring during labor and delivery.

A previous survey of the seroprevalence of the herpes virus type 2 (HSV-2) infection in Israel provided us with an opportunity to study a) the prevalence of human papillomavirus (HPV) 16/18 in selected groups of women; b) the correlation between the infection with HSV-2, HPV-16/18 and Papanicolaou (PAP) pathology; and c) to identify groups of women who might benefit from routine PAP screening. Four different population groups of women aged 17-60 years were studied: groups 1 and 2 comprised healthy women government employees and kibbutz and moshav residents, respectively, and groups 3 and 4 comprised Jewish and non-Jewish women with gynecological complaints. In women without gynecological problems the prevalence of HPV-16/18 was 1.8% in group 1 and 0% in group 2. The prevalence was several-fold higher in the Jewish and non-Jewish gynecological clinic groups, 9% and 12%, respectively. There was no correlation between the prevalence of HSV-2 antibodies and HPV-16/18 infection in women without gynecological problems. One of the 692 women studied had markers of both infections. The very few cases of cervical intraepithelial neoplasia (CIN) II and CIN III occurred in women who were negative for HSV-2 and HPV-16/18 infection. Thus from our limited study, it is not possible to define any group of healthy women who might benefit from continuous PAP smear screening for cervical cancer.

Objective: To investigate the effects of a low-dose ketoconazole on ovarian steroidogenesis and on serum androgen levels in polycystic ovary syndrome (PCOS)., Design: In vitro, human granulosa-luteal cells were incubated with ketoconazole and radiolabeled steroid substrates, to follow their metabolic fate by thin-layer chromatography analysis. In vivo, normally cycling women (n = 7) in their luteal phase were administered one tablet of 200 mg ketoconazole at 8 A.M. Serum steroid levels, sampled basally and at 12 P.M., 4 P.M., and 8 A.M. the next morning, were compared with untreated control group (n = 7) values. Polycystic ovary syndrome women (n = 11) were similarly administered ketoconazole 6 to 10 days after occurrence of spontaneous menses. Adrenal origin of hyperandrogenemia was excluded by stimulation with ACTH and a normal basal DHEAS. The steroid diurnal variation was determined in the same patients a day before treatment., Results: In vitro, ketoconazole selectively inhibited the key steroidogenic cytochromes, namely P450scc, P45017 alpha, and P450arom (IC50 = 0.5 to 1.0 microgram/mL). In vivo, in the luteal phase, ketoconazole transiently decreased serum values (mean +/- SE) of E2 (19.2% +/- 2.1%) and P (38.3% +/- 8.5%) within 4 to 8 hours. The same low-dose ketoconazole, administered to PCOS women, decreased serum values of androstenedione (17.6% +/- 4.7%), T (24.6% +/- 7.6%), and free T (30.7% +/- 7.7%). In contrast, 17 alpha-hydroxyprogesterone increased concomitantly (78.5% +/- 10.8%), suggesting a greater suppressibility of the P45017 alpha lyase activity. The E2 levels in PCOS patients were slightly elevated (29.1% +/- 5.6%), resulting in a 1.7- to 2.3-fold increase of the E2:T ratio., Conclusions: These findings suggest that a low-dose ketoconazole may facilitate a decreased intraovarian T:E2 ratio, which may prove favorable for follicular maturation in PCOS.

Placenta percreta accompanied by intraabdominal hemorrhage and acute abdomen in the second trimester is described. Suturing the myometrial defect created by the protruding placenta prolonged the pregnancy and achieved a viable fetus. Successful achievement of hemostasis, prolongation of the pregnancy, and survival of mother and fetus should encourage "conservative" surgery.

Objective: Ovarian hyperstimulation is associated with a significant increase in ovarian steroid hormone production. Since such high levels of sex steroids may influence the activity of other endocrine glands, as well as affecting lipid metabolism, we studied the effect of ovarian hyperstimulation on the hormonal and lipid profile., Study Design: In ten patients who were treated with human menopausal gonadotropins (hMG) for in vitro fertilization (IVF), the serum levels of dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone, insulin, cortisol, growth hormone, thyroid-stimulating hormone, and prolactin, as well as total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triglycerides, and free fatty acids were monitored. These were correlated with estradiol and free and total testosterone levels., Results: Increased estradiol and free testosterone levels were associated with an increase in DHEA concentration. A correlation was found between increased estrogen level and decreased total cholesterol, triglyceride, and LDL-C levels; HDL-C levels remained unchanged. There was a positive correlation between the estradiol levels and free fatty acid elevation., Conclusion: Ovarian hyperstimulation induced changes in lipoprotein lipid content. However, the treated women faced no increase in cardiovascular risk, since their lipoprotein lipid levels were not affected.

A prospective trial to investigate feasibility of vaginal delivery after more than one cesarean section, and the safety of vaginal delivery for mother and neonate. Twenty-six pregnant women with a history of two or more cesarean sections were admitted to the delivery room and accepted trial of labor under internal fetal and uterine monitoring. Epidural anesthesia and oxytocin were applied when needed. A similar group of patients (controls) preferred repeated cesarean section. Nineteen women (73%) were successfully delivered by the vaginal route. There were no cases of uterine rupture or perinatal loss. The maternal complication rate was lower than that of the control group. Trial of labor in selected cases of two or more low-segment cesarean sections may be considered safe for mother and fetus.

Triiodothyronine (T3) treatment of pregnant rats for 6 days, 10 micrograms/100 g, resulted in a pronounced induction of enzymes related to gluconeogenesis and lipogenesis and of mitochondrial FAD-glycerophosphate dehydrogenase in the maternal liver, as previously observed in male rats. There was virtually no change in the activity of these enzymes in the placenta. However, there was a distinct induction of these enzymes in the fetal liver, even if increments in fetal serum and liver T3 were much smaller than on the maternal side. This indicates that changes in hepatic enzyme activities are a more sensitive index of fetal hyperthyroidism than T3 levels. The increased lipogenic capacity was expressed by greater incorporation of a tritium tracer into fatty acids. Administration of triamcinolone, 2 mg/100 g, for the last 5 days of gestation resulted in marked induction of maternal hepatic enzymes of lipogenesis, gluconeogenesis and of aspartate aminotransferase (ASAT), known to occur in male rats, as well as in a metabolic pattern of insulin resistance. The response of placental enzymes was limited to a small elevation in ASAT and phosphoenolpyruvate carboxykinase (PEPCK) activity. In the fetal liver there was no stimulation of lipogenic enzymes, but a marked induction of PEPCK and ASAT. The changes in the lipogenic capacity were confirmed by tritium incorporation into serum and liver fatty acids. These results demonstrate the marked sensitivity of specific fetal enzyme systems to the maternal iatrogenic hyperthyroidism or hypercorticism. The limited alterations in placental enzyme activities are in accord with the concept that placental metabolic stability fulfils a protective function toward the fetus.

Tubal pregnancy remains a clinical challenge in spite of improvements in diagnostic tests and procedures. In a prospective study we evaluated the role of the serum creatine kinase as a possible marker for tubal pregnancy. Three groups of 17 patients each were included in the study: group A, documented tubal pregnancy; group B, spontaneous abortion; and group C, normal pregnancy. Serum was tested for creatine kinase in all of the patients. Creatine kinase level was > 45 IU/L in all patients with tubal pregnancy, significantly higher than the level in patients in either of the two other groups (p < 0.0001). We conclude that a high serum creatine kinase level can be an important diagnostic test in the evaluation of a suspected tubal pregnancy.

FH-UFS is a rare syndrome characterized by bilateral femoral hypoplasia, together with facial dysmorphism. To the best of our knowledge, this is the first report describing prenatal ultrasonographic findings and in utero growth pattern of an infant with FH-UFS. Via analysis of our data it appears that the growth of the femur in our case was normal until the 24th week of pregnancy, at which time some in-utero insult occurred, resulting in temporarily arrested femoral growth. From the 34th week of pregnancy onward femoral growth rates returned to normal. We assume, therefore, that the etiology of FH-UFS is multifactorial. Only a combination of some hereditary proclivity, together with an intrauterine insult (possibly viral) could explain the appearance in the same fetus of cleft palate, developing at the 7th week of gestation, and a time-specific (25-32 weeks) disturbance of femoral growth.

A serological test for chlamydial infection was administered to 281 Jerusalem women in order to determine the rate and influence of Chlamydia on pregnancy outcome. Serological indication of active infection was present in 7.8% of the tested women, while 15.3% were shown to be positive for Chlamydia. Among the ultraorthodox subpopulation of Mea Shearim, serological indication of active infection was present among 5.9% of the women, and 12.3% of this population tested positive. In comparison, women from the secular subpopulation had 12.7% serological indication of active infection and 22.95% tested positive (P < 0.01). There were no statistically significant differences between pregnancy duration, birthweight, incidence of premature uterine contractions, premature rupture of membranes, and postpartum febrile morbidity in the infected and noninfected groups. Women with a previous history of induced abortions showed a significantly higher evidence of past Chlamydia infection (9.3%) when compared with the women who did not have an infection (1.4%) (P < 0.006). Among the ultraorthodox women with positive or active infection, 41% had suffered at least one spontaneous abortion, as compared with 25% of the religious women who had no serological evidence of infection.

Objective: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT)., Method: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests., Results: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05)., Conclusion: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.

Hormonal Replacement Therapy (HRT) is known to be accompanied by changes in blood lipid profile. The present prospective cohort study compared the blood lipid profile of healthy postmenopausal women treated with either (a) a preparation containing a fixed regimen of estradiol, estriol and norethisterone acetate (EENA, marketed under the trade name Trisequens); (b) a fixed protocol of conjugated equine estrogen and medroxyprogesterone acetate (CEEMPA, marketed under the trade name Premaril Plus); or with (c) a concurrent group which underwent no treatment. Blood lipid profiles (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG)) were performed at the beginning of the study and at 3-month intervals, for 9 months. The EENA-treated women showed a significant and profound decrease in TC and LDL-C when compared with their initial values, with the control group, and with the CEEMPA group. The CEEMPA group showed an increase in HDL-C values and a decrease in LDL-C values when compared with their initial values and with the control group, but no increase was shown when compared with an EENA group. There was a favorable decrease in the TC/HDL-C and LDL-C/HDL-C ratios in both treatment protocols. As the primary goal of prevention of coronary artery disease is total cholesterol reduction, the EENA protocol seems to be preferred.

Maternal metabolic aberrations during pregnancy complicated by diabetes are responsible for profound changes in all aspects of fetal intrauterine development and, later, short-, and long-range implications on the neonate and the child. In this article we review the evidence that has been accumulated in the literature linking the aberrant fuel mixture and fetal hyperinsulinemia to the long-range neonatal and childhood complications of the offspring of the diabetic mother.

The combination of amenorrhea, galactorrhea, and hyperprolactinemia in a young woman usually suggests a prolactin-secreting adenoma of the anterior pituitary gland. Primary thyroid failure may also be associated with hyperprolactinemia, galactorrhea and suprasellar enlargement of the pituitary. 2 women, aged 23 and 28, respectively, presented with the latter syndrome. 1 was even a candidate for neurosurgery. However, because serum TSH and prolactin levels were elevated, thyroxin replacement therapy was started. It induced normal menses, galactorrhea stopped, and in follow-up CT scans the pituitary become normal in size. Hyperprolactinemia with secondary hypothyroidism, caused by a pituitary adenoma, must be distinguished from primary hypothyroidism, also a cause of hyperprolactinemia.

Diabetes in pregnancy is associated with profound abnormalities in the hormonal and metabolic milieu and the maternal and fetal blood supply. These changes are likely to initiate structural and biochemical alterations in placental tissue, which may in turn be related to disturbances in placental function and metabolic performances. This review presents an update of information on the structural, biochemical and immunological characteristics of placental tissue and their correlation with placental function.

Ketoconazole (KCZ), a widely used antifungal drug, has been reported in humans to inhibit adrenal and testicular steroidogenesis by interfering with the cytochrome P-450-dependent enzymes. The purpose of this study was to investigate the drug effect on steroidogenic human granulosa-luteal cells, obtained by follicular aspiration from mature follicles of gonadotropin-treated women. Cells were cultured in long-term monolayers, and the steroid production was assayed by radioimmunoassay. A profound inhibition of ovarian cell secretion of progesterone (P), testosterone (T) and estradiol was found. At a low concentration (5 micrograms/ml), KCZ failed to inhibit the conversion of pregnenolone to P, mediated by the non-cytochrome 3 beta-hydroxysteroid dehydrogenase-isomerase enzyme (3 beta-HSDH). At a similar concentration, P secretion by human chorionic gonadotropin (hCG; 100 mIU/ml) -treated cells was decreased by 68% (P less than 0.001) and therefore, an inhibitory effect of KCZ on the cholesterol side-chain cleavage enzyme (P-450SCC) was assumed. A similar marked inhibitory effect (81%) (P less than 0.001) on T secretion was observed for hCG-stimulated cells given pregnenolone as substrate. The P-450 aromatase was profoundly inhibited (86%) (P less than 0.001) in a reversible manner, by a similar concentration (5 micrograms/ml) of KCZ. These findings suggest that KCZ has the capability to suppress human ovarian steroidogenesis similarly as in testis and adrenal.

A term amelic female infant was born to an apparently nonconsanguineous Arab Moslem couple. This was followed by the birth of 4 normal children. Afterwards, in 2 subsequent pregnancies, 2 amelic fetuses were diagnosed by transabdominal ultrasonography in the 18th and 12th week of gestation. Pregnancies were terminated and on autopsy both amelic fetuses had severe lung hypoplasia and aplasia of the peripheral pulmonary vessels. The first fetus also had apparently low-set ears and micrognathia, whereas the last had hydrocephaly and left cleft lip beside the lung hypoplasia and aberrant pulmonary artery. This appears to be a new autosomal recessive malformation syndrome.

Cocaine was previously regarded as a soft drug causing only mild damage. Its use during pregnancy, however, creates a variety of grave medical problems which necessitate immediate attention not only on the part of internists and psychiatrists but also, and more particularly, by obstetricians and pediatricians. The pregnancy of a cocaine-using woman must be carefully managed and regarded as a high-risk one. This in view of the numerous obstetric risks caused by the drug, notably premature separation of the placenta, increased incidence of stillbirths, congenital malformations, premature births, and intrauterine growth retardation. The neonatal monitoring must be focused on prevention of complications resulting from the withdrawal syndrome and associated conditions such as pneumonia, severe weight loss, and contagion from the mother. Moreover, efforts must be made to ensure a strict observation of the infant outside the hospital in view of the far greater incidence of idiopathic infant death in such cases. Owing to the sharp rise of the regular and occasional use of the drug and since pregnant women tend on anamnesis to deny any drug taking, we recommend a test of maternal urine for cocaine and other drugs whenever a suspicion to this effect arises. It is also advisable to test for the presence of such drugs in the urine of the neonate in cases of reasonable suspicion of maternal use during pregnancy, though a negative outcome of the urine test naturally does not rule out a possible use. Strict monitoring of positive cases, accompanied by preventive treatment, may contribute a great deal toward a reduction of perinatal morbidity and mortality associated with cocaine use use.

To evaluate the effect of disopyramide on uterine contractions during pregnancy, the drug was given for 48 hours to 10 women with indications for labor induction. Placebo was given to 10 other women with the same indications for induction. During the study period, regular uterine contractions occurred in 10 women in the study group, as compared with none in the control group (p less than 0.0001). Eight women in the study group were delivered of infants within 48 hours, as compared with none in the control group (p less than 0.0001). The mean time until the appearance of regular uterine contractions in the study group (4.15 +/- 1.76 hours) was significantly shorter (p less than 0.001) than that in the control group (56.13 +/- 5.28 hours). Patients who were not delivered of infants within 48 hours received other medications (prostaglandin E2, oxytocin). The mean maternal blood level of disopyramide at the time of appearance of uterine contractions was 1.52 +/- 0.9 mg/ml. The mean maternal level at delivery was 0.93 +/- 0.43 mg/ml and the cord blood level at the time of delivery was 0.33 mg/ml (cord blood/maternal level ratio = 0.36, r = 0.73, p less than 0.05). These results indicate that disopyramide should not be used in pregnancy for antiarrhythmic purposes because it may induce uterine contractions and delivery.

Leukocyte alkaline phosphatase (LAP) activity was studied in 50 women at delivery and in the newborn after delivery. The following findings were observed: (1) the LAP activity of newborns is lower than that of the mothers; (2) significant decrease in the LAP activity has been observed in newborns on the 4th day after delivery; (3) there are no significant differences between newborns from normal and prolonged labor; (4) immediately after delivery the LAP scores of male newborns are lower than those of females, but 4 days later these scores were reversed, and (5) 4 days after delivery, the LAP scores do correlate to the weight of the newborn.

The activity of several enzymes of regulatory importance for the pathways of glycolysis, gluconeogenesis and lipogenesis was investigated in the placenta and liver of pregnant rats and in the liver of non-pregnant female rats. The rats received daily hormonal treatments on Days 15 to 17 of pregnancy and enzyme activities were measured on Day 18. Chorionic gonadotropin induced minor changes in enzyme activity, apart from a decrease in the activity of hepatic enzymes of lipogenesis in non-pregnant rats. Triamcinolone induced a marked increase in enzymes of gluconeogenesis and a decrease in the activity of pyruvate kinase in the liver of pregnant and non-pregnant rats; in contrast, inverse changes in activity, these enzymes were observed in the placenta. This response in the placenta was considered to arise not from direct hormone effect, but from the accompanying hyperglycemia and hyperinsulinemia. Triamcinolone also increased the activity of hepatic acetyl-CoA carboxylase in pregnant and non-pregnant rats, whereas it reduced the activity of this enzyme in the placenta. Estrogen produced changes similar to those of triamcinolone in the liver and placenta, except that it depressed the activity of acetyl-CoA carboxylase in both tissues. Progesterone had little effect on placental and hepatic enzymes. In general, the changes induced by these hormones in the placenta affected fewer enzymes than in the liver, were less extensive in magnitude and not necessarily in the same direction as in the liver. This indicates that the regulatory placental enzymes are subject to specific control mechanisms not necessarily influenced by direct hormone action.