Preoperative assessment of endometrial carcinoma by three-dimensional power Doppler angiography.

OBJECTIVE: Preoperative evaluation of the depth of myometrial invasion in endometrial carcinoma is challenging. The objective of this study was to evaluate the usefulness of three-dimensional power Doppler angiography (3D-PDA) in this setting. METHODS: Sonographic and histological data on 100 consecutive cases of endometrial carcinoma were analyzed. The endometrial and myometrial vascular indices VI (vascularization index), FI (flow index) and VFI (vascularization flow index) were calculated by 3D-PDA. The results were compared with a complete surgical staging. RESULTS: The mean ( ± SD) age of patients was 67.1 ± 8.8 (range, 33-87) years. Forty-six patients had deep (≥ 50%) myometrial invasion. Eight patients had metastases, seven of them with deep invasion. Three patients were found to have carcinomas of non-uterine origin on histology, and these were excluded from further statistical analysis. The median endometrial and myometrial vascular indices were higher in the group with deep invasion than in the group without. Following multivariable analysis of the indices only the endometrial FI was independently associated with deep invasion (OR, 1.061; 95% CI, 1.023-1.099; P = 0.001). However, a greater endometrial volume was also an independent predictor of deep invasion (OR, 1.109; 95% CI, 1.011-1.215; P = 0.028). CONCLUSION: Our study suggests that endometrial and, to a lesser degree, myometrial vascular indices and endometrial volume correlate with the depth of myometrial invasion in endometrial carcinoma.

Diamniotic omphalopagus conjoined twins in a diamniotic pregnancy.

OBJECTIVE: To present antepartal diagnostic findings including 2D/3D ultrasonography in a rare case of conjoined twins with diamniotic placentation. METHODS: In ultrasonographic examination, a communicating structure containing solid and cystic components together with cord vessels was found between the fetuses. The long axes of the fetuses were not parallel and they moved independently. Bladder configurations were absent. A fetal membrane from the chorioidal plate was imaged. RESULTS: Postmortem pathological examination revealed that the twins were conjoined by way of fused cloacal exstrophy and omphalocele, and the separate amniotic cavities communicated via a fused allantoic cavity. The placenta was monochorionic and diamniotic. DNA analysis of the twins and the placenta confirmed the monozygotic origin. CONCLUSION: Visualization of the amniotic membrane does not rule out conjoined twins in rare cases of monochorionic twin pregnancies.

Impaired cardiac adjustment to pregnancy in type I diabetes.

To assess the adaptation of the heart of diabetic subjects in the natural volume overload state of pregnancy, echocardiography was performed during each trimester and postpartum in 17 women with insulin-dependent diabetes mellitus (IDDM) and in 11 healthy women. The mean duration of diabetes was 14 yr and signs of microvascular complications were detected in 6 patients. The diabetic women had slightly smaller left ventricles than the control women already in the basal state (postpartum), and the pregnancy-induced increase in left ventricular size and stroke volume was less in the diabetic than in the control women. The heart rate rise also tended to be less in the diabetic women, resulting in a markedly smaller increase in cardiac output in this group (1.3 vs. 3.4 L/min, P less than .01). Left ventricular systolic function, wall thicknesses, or left atrial size did not differ between the groups at any point in the study. Minor collections of pericardial fluid were observed in 14 (76%) diabetic women and in 5 (45%) control women during the second and/or third trimester, but only 2 diabetic women had classic pericardial effusions. In conclusion, the normal hemodynamic adjustments to pregnancy seem to be impaired in women with IDDM. Preclinical diabetic cardiomyopathy and autonomic neuropathy may be involved in the observed alterations.

Effect of pregnancy on autonomic nervous function and heart rate in diabetic and nondiabetic women.

Supine and standing heart rate and heart rate responses to deep breathing and standing up (the 30-to-15 ratio), indices of autonomic nervous function, were measured during each trimester and postpartum in 25 women with insulin-dependent diabetes and 10 nondiabetic women. The groups did not differ with respect to autonomic function in the basal state (postpartum), and the heart rate response to deep breathing diminished progressively in both groups during pregnancy, although the change tended to be less pronounced in the diabetic women. The 30-to-15 ratio did not alter significantly during pregnancy. The diabetic women had a higher supine heart rate than the healthy women in the basal state, but the pregnancy-induced increase in heart rate was less in the diabetic women. Thus, the reversible diminution of heart rate response to deep breathing during pregnancy is a physiological finding and does not denote development of autonomic nervous dysfunction. Second, the increase in heart rate, a primary cardiovascular adjustment to pregnancy, seems to be blunted in diabetic women.

Effects of metoclopramide-induced hyperprolactinemia during early follicular development on human ovarian function.

Nine healthy women, aged 25 to 36 yr, were treated with metoclopramide (MC) (10 mg orally three times daily) from the first to the sixth day of their cycle (treatment A) for two successive cycles (n = 18) and six of these women later received MC from -3 to the fifth day of the menstrual cycle (treatment B) during one or two cycles (n = 10), to investigate the effects of hyperprolactinemia during the early phase of ovarian follicular growth. Comparisons were performed with control cycles in the same women. The treatment cycles were characterized by low serum concentrations of LH during the early follicular phase and at midcycle, low early follicular phase serum testosterone (T) levels and high luteal phase T and free T index values, with no significant differences between A and B treatment modalities. We classified the treatment cycles into two categories, seriously disturbed and normal or only slightly disturbed, on the basis of ultrasonographic findings and midcycle estradiol (E2) and luteal phase progesterone (P) concentrations. Folliculogenesis was seriously disturbed in 11 of the 28 treatment cycles (39%). During these cycles, midcycle serum LH and the LH to FSH ratio were lowered, luteal phase LH and FSH increased, midcycle E2 and luteal phase P and the P to E2 ratio decreased, luteal phase T and the free T index and androstenedione increased, and luteal phase 5 alpha-dihydrotestosterone decreased. During the early follicular phase and at midcycle the ratios of T to E2 and androstenedione to E2 were increased, and at midcycle and during the luteal phase of the cycle the ratio of T to 5 alpha-dihydrotestosterone was increased. These changes in steroid hormones were probably of ovarian origin since the serum concentrations of dehydroepiandrosterone sulfate and sex hormone-binding globulin were similar in seriously disturbed and control cycles. Four of the nine study subjects were hyperprolactinemia sensitive (disturbed folliculogenesis) and five hyperprolactinemia resistant (no disturbance in folliculogenesis). During the control cycles the hyperprolactinemia-sensitive women had significantly higher serum concentrations of T than the other women. The present observations indicate that hyperprolactinemia may impair the development of the ovarian follicles during their recruitment period, especially in women with relatively high serum T levels.

Physical exercise-induced changes and season-associated differences in the pituitary-ovarian function of runners and joggers.

The hormonal responses to energetic chronic exercise and to seasonal shift from autumn to spring were evaluated by measuring concentrations of serum FSH, LH, PRL, estradiol (E2), progesterone (P), testosterone (T), and sex hormone-binding globuline (SHBG) during 1 menstrual cycle in the autumn (light training season) and 1 in the spring (hard training season) in 18 endurance runners and 12 age-matched nonrunning women, and in 13 joggers and 11 age-matched nonjogging women. The appearance, growth, and maximal size of the ovarian follicles were monitored by ultrasonography. The high intensity training of the runners was associated with decreased concentrations of FSH on cycle days 7-8 in the autumn, E2 on cycle days 12-13 in the spring and days 22-23 in both seasons, P on cycle days 20-21 in both seasons and days 22-23 in the autumn, and T on cycle days 12-13, 14-15, and 22-23 in the spring. Jogging, however, did not alter the concentrations of these hormones. Using as criteria the presence of 2 or 3 abnormal values of the 3 indicators used for evaluation of folliculogenesis (midfollicular E2 lower than 0.09 nmol/liter, luteal phase P lower than 7 nmol/liter, and peak diameter of the largest ovarian follicle less than 15 mm), seriously disturbed folliculogenesis was found in 50% of the 32 study cycles of the runners and 9% of the 23 cycles of their controls (P less than 0.01). In all four study groups, there was a significant seasonal difference in the concentrations of ovarian hormones, with lowered E2, P, and T levels in the autumn. There were no differences in the serum concentrations of SHBG between the study groups or between the autumn and the spring. High training activity and a dark photoperiod appeared to independently suppress ovarian activity and were not associated with chronic changes in anterior pituitary hormone or SHBG concentrations.

Isolated prolactin deficiency in a woman with puerperal alactogenesis.

Idiopathic PRL deficiency was detected in a parturient woman with otherwise normal pituitary function. This PRL disorder first became manifest postpartum when she had no milk production, and oral metoclopramide failed to raise her serum PRL levels. Her second pregnancy occurred spontaneously after 3 yr of attempts to conceive. During the pregnancy, her serum PRL concentration was very low, varying from 4.5-7.8 ng/ml, and the puerperium was again characterized by alactogenesis. During normal menstrual cycles and after iv GnRH, TRH, metoclopramide, and insulin tolerance tests, serum PRL was only rarely detectable by RIA, at very low concentrations. Bioassay results confirmed the PRL deficiency. The results confirm that PRL is necessary for puerperal lactation and suggest that it is needed for normal ovarian function. The present data also suggest that the maternal pituitary is the main source of serum PRL during pregnancy, and the decidua has only a minor contribution in this respect.

Intravascular ultrasound contrast agent: an aid in imaging intervillous blood flow?

The aim of this study was to evaluate the applicability of an intravascular ultrasound contrast agent in examination of the uteroplacental circulation. Uteroplacental circulation in 25 singleton third trimester pregnancies was examined by power Doppler, first without and then with contrast agent enhancement (Levovist, Schering AG, Germany). Eight subjects had fetal growth retardation and 17 had normal-sized fetuses. The effect of the contrast agent was evaluated using computerized power Doppler signal intensity measurements. The Doppler signal intensity in the uteroplacental vessels increased within 25 sec of brachial venous injection of the contrast agent, yielding an effect which was recognizable up to 5-8 min later. There was clear enhancement of uteroplacental flow imaging after addition of the contrast agent in all of the examined pregnancies. The mean percentual intensity changes after administration of the contrast agent were 33 per cent (P<0.001) in the sub-placental myometrial area and 8 per cent (P<0.001) in the intraplacental area. No association was found between fetal growth retardation and intensity changes or absolute intensity parameters. In conclusion, intravascular ultrasound contrast agent facilitates imaging of the uteroplacental circulation. It may have a valuable role in determination of intervillous blood flow and in imaging blood perfusion in different regions of the placenta.

Intrahepatic cholestasis of pregnancy impairs the activities of human placental xenobiotic and steroid metabolizing enzymes in vitro.

Human placental xenobiotic metabolizing and aromatase activities were measured in placentae at term obtained from pregnancies diagnosed as intrahepatic cholestasis (IC). Compared with controls, several cytochrome P450-dependent (CYP) mono-oxygenases were significantly decreased in IC placentae: 7-ethoxycoumarin O-deethylase by 75 per cent, 7-ethoxyresorufin O-deethylase by 95 per cent, aromatase activity by 37 per cent and androstenedione formation, using testosterone as a substrate, by 20 per cent. These results demonstrate that maternal intrahepatic cholestasis effectively decreases CYP dependent metabolism in human placenta in vitro which may pose a potential risk to the wellbeing of the fetus. Because aromatase activity in IC placentae is significantly lower as compared with healthy controls, safety of the drug therapies which further inhibit aromatase activity are questioned.

Antepartum glucocorticoid therapy suppresses human placental xenobiotic and steroid metabolizing enzymes.

We investigated the effects of maternal gestational corticosteroid therapy on placental xenobiotic and steroid metabolizing enzymes at term in 20 glucocorticoid/betamethasone treated (with various doses) and control (n=10) women. A single dose of betamethasone (12 mg i.m. twice at a 24-h interval) was given to 15 mothers at risk of preterm delivery to prevent respiratory syndrome in their premature newborns. Five mothers were treated more than once. The gestation time in mothers receiving the glucocorticoid therapy varied from 22-38 gestational weeks. Compared with controls, a significant decrease in placental aromatase activity (53.6+/-18.0 pmol/mg/min versus 119+/-30 pmol/mg/min, P=0.0007) and placental CYP19 mRNA content (by 50 per cent ) was observed in mothers treated with glucocorticoids. Also the formation of androstenedione (13.2+/-8.1 pmol/mg/min, steroids versus 30.03+/-5.2 pmol/mg/min, controls, P< 0.001), using testosterone as the substrate, and 7-ethoxycoumarin O-deethylase (P< 0.05) and 7-ethoxyresorufin O-deethylase (P< 0.09) were slightly decreased in the glucocorticoid treated compared to control patients' values. The changes were not dependent on the number of treatments or the time between treatment and delivery. Our results demonstrate that even a single dose of glucocorticoid given to expectant mothers is associated with diminished placental steroid hormone and xenobiotic metabolizing enzymes at term. Further studies are needed to assess whether these changes affect the well-being of the fetus and its later development.

Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro.

We evaluated the impact of maternal drug abuse at term on human placental cytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoumarin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hydroxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreductase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between control and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activities (p < 0. 001), but not between ECOD and aromatase or P1OH and EROD activities; we also found significant correlations between blood cotinine and UGT activities (p < 0.01). In contrast, in controls (mothers who did not abuse drugs but did smoke cigarettes), the P1OH activity correlated with ECOD, EROD (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Our results (wider variation in ECOD activity among tissue from drug-abusing mothers and the significant correlation between P1OH and ECOD activities, but not with aromatase or EROD activities) indicate that maternal drug abuse results in an additive effect in enhancing placental xenobiotic metabolizing enzymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal homeostasis during pregnancy.

Fragile-X syndrome in east Finland: molecular approach to genetic and prenatal diagnosis.

Fragile X is the most common inherited form of mental retardation, having an incidence of one in 1,250 males. The fragile X syndrome results from amplification of the CGG repeat found in the fragile X mental retardation-1-gene (FMR-1). This CGG repeat shows length variation in normal individuals and is increased significantly in both carriers and patients. Non-retarded carriers of both sexes can be detected reliably only by direct DNA analysis of the fra(X) mutation. Here we investigate fragile X families using the intragenic probes St.B 12.3 and St.B 12.3 XX (J-L Mandel). Fragile X syndrome could be verified in 51 families of the population of 900,000 in East-Finland during 1989-92. The index cases of the syndrome were found by the help of health care personnel, 463 relatives of these families consented to be tested for the mutation of the FMR-1 gene. Ninety-three relatives with the full mutation and 127 healthy carriers with the premutation of the fragile X syndrome were diagnosed. In addition, 28 decreased males were obligate carriers. During the year 1992 prenatal diagnosis for fragile X was carried out in nine pregnancies. For understanding of the occurrence of fragile X syndrome and for better prevention of this syndrome in next generations, systematic genetic counseling and carrier screening in these families is essential.

A lethal autosomal recessive syndrome of multiple congenital contractures.

We describe 16 cases of a lethal syndrome with multiple congenital contractures from ten families. The main clinical findings included intrauterine growth retardation with marked fetal hydrops, multiple contractures, and facial abnormalities, especially micrognathia. At autopsy, pulmonary hypoplasia and muscular atrophy were present. There was a paucity of anterior horn motor neurons in the four studied cases. We think that the cases represent the same clinical entity, probably caused by homozygosity of an autosomal recessive gene. The syndrome resembles the Pena-Shokeir I syndrome, but seems to differ in some respects, including length of survival and presence of hydrops. Prenatal diagnosis of this syndrome is possible after the 16th week of pregnancy with ultrasound.

Intrauterine inflammation at term: a histopathologic study.

This study was undertaken to examine the presence of inflammation of the uterine and gestational tissues as defined by histopathology in clinically noninfected women with term gestation and intact fetal membranes and to evaluate its correlation with measured clinical variables and neonatal and maternal clinical outcome. Two hundred sixteen clinically noninfected term parturients who underwent cesarean section with intact membranes were analyzed for the presence of inflammatory lesions of the gestational tissues and uterus. Nine hundred eighty-one histologic samples were studied, including 212 samples from both chorion membranes and umbilical cords, and 209 placental, 192 myometrial, and 156 decidual samples. In 208 (96%) cases, either amniotic fluid (AF) or endometrial swab samples were cultivated for bacteria. In 148 (69%) cases, the AF leukocyte count was analyzed by the Gram stain method, and in 77 (36%), AF leukocyte esterase activity (LEA) was evaluated. Leukocytic infiltrations were present in samples from 41 (19%) women, varying from 2% to 10% in the different anatomic sites examined. However, after onset of labor, low-grade decidual inflammation was observed in 29% of cases. Cervical dilation (odds ratio, 4.7; 95% confidence interval, 2.4 to 9.3; P < .00003) and meconium-stained AF at the operation (odds ratio, 5.3; 95% confidence interval, 2.2 to 12.5; P < .00015) were associated with the histologic inflammatory lesions observed in decidual samples, independently of AF or endometrial microbial detection, AF leukocytes, or LEA.

Apolipoprotein E alleles in women with pre-eclampsia.

AIMS: To investigate the frequency of three apolipoprotein E (apoE) alleles among women with pre-eclampsia. METHODS: The presence of the three most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism in two groups of women: healthy pregnant women (n = 91) and pregnant women with a diagnosis of pre-eclampsia (n = 133). In addition, the frequencies of the alleles in the general population in this area are presented for comparison. RESULTS: The frequency of the apo epsilon 4 allele was 18.4% among women with pre-eclampsia and 18.7% among healthy pregnant women (Fisher's exact test; p = 0.941), which is close to the rate in the general population in this area (19%). None of the apolipoprotein E genotypes was significantly over-represented, and homozygous genotype epsilon 4 was not associated with more severe clinical disease than were the other genotypes. CONCLUSION: The observed profiles of allele and genotype frequencies confirm an equilibrium state between apoE polymorphism and pre-eclampsia and suggest that apoE does not play a major role in the development of pre-eclampsia.

Blood velocity waveforms of the fetal aorta in normal and hypertensive pregnancies.

Blood velocity waveforms were studied using a combination of real-time and Doppler ultrasonic equipment, a spectral analyzer, and on-line computer in the thoracic descending aorta of the human fetus. In 43 normal pregnancies (weeks 30 to 42) the median of mean velocity was 26.5 (24.1 to 27.9) cm/sec, that of the end-diastolic velocity 10.9 (7.9 to 13.4) cm/sec, the velocity acceleration 718.9 (620.3 to 844.1) cm/sec2, the resistance index 0.84 (0.80 to 0.89), and the pulsatility index was 2.49 (1.94 to 3.10). No differences in these values were observed in the fetuses of noncomplicated hypertensive pregnancies (N = 32), whereas the resistance index increased and the mean velocity and end-diastolic velocity decreased if fetal growth retardation was associated with maternal hypertension (N = 14). In the subgroup of fetal distress (N = 6), all of these parameters except velocity acceleration differed from the normal values, reflecting increased peripheral vascular resistance. This method may be of value in the follow-up of fetal well-being in risk pregnancies by giving an early sign of hemodynamic changes in developing hypoxia.

Intrauterine membranous cyst: a report of antenatal diagnosis and obstetric aspects in two cases.

A large, intrauterine membranous cyst originating from the subchorionic layer of the placenta was diagnosed by ultrasound in two pregnancies. The cyst was attached in both cases near the cord insertion. In one pregnancy this condition resulted in fetal growth retardation and diminution of umbilical circulation, but both of the deliveries were uncomplicated. This abnormality indicates careful monitoring of pregnancy and labor.

Pregnancy outcome with intrahepatic cholestasis.

OBJECTIVE: To determine the risk of adverse pregnancy outcomes resulting from intrahepatic cholestasis. METHODS: We analyzed 91 women with singleton pregnancies complicated by cholestasis who gave birth at Kuopio University Hospital from January 1990 to December 1996. Logistic regression analysis was used to compare pregnancy outcomes of this group with those of the general obstetric population (n = 16,818). RESULTS: Women of relatively advanced age (over 35 years) were at increased risk of developing intrahepatic cholestasis. Affected pregnant women delivered by cesarean significantly more often (25.3%) than the general obstetric population (15.8%). Intrahepatic cholestasis increased the low basic risk of preterm delivery and the need for neonatal care in the general population (odds ratio [OR] 2.73; 95% confidence interval [CI] 1.50, 4.95 and OR 2.15; 95% CI 1.21, 3.83, respectively). Otherwise, the courses of pregnancy were comparable in both groups. CONCLUSION: Intrahepatic cholestasis has an adverse effect on fetal development, and affected pregnancies merit closer surveillance. Delivery of infants when maturity is reached may minimize the risk of adverse outcomes.

Biometric and dynamic ultrasound assessment of small-for-dates infants: report of 260 cases.

The accuracy of 4 ultrasonic parameters and their combined use of detecting fetal growth retardation in a group of 260 small-for-dates infants are analyzed. Abdominal circumference measurement was the most accurate single ultrasonic technique. By combining this measurement with fetal cephalometry, it was possible to diagnose antenatally 96.8% of the small-for-dates infants. Fetal urinary production was below the normal mean in 94.3% of these infants. All except 1 asymmetric growth-retarded fetus had a fetal breathing movement rate lower than that of a normal fetus. The perinatal mortality was significantly decreased in a group of ultrasonically detected growth-retarded fetuses, as compared with the group of unrecognized small-for-dates fetuses.

Perinatal diagnostic evaluation of velamentous umbilical cord insertion: clinical, Doppler, and ultrasonic findings.

OBJECTIVE: To evaluate the association between velamentous cord insertion and adverse pregnancy outcome in singleton pregnancies, and to assess the diagnostic usefulness of nonstress testing (NST) and Doppler ultrasound in this condition. METHODS: We retrospectively reviewed 12,750 consecutive singleton, chromosomally normal pregnancies from July 1989 through December 1993 at the University Hospital of Kuopio, Finland. Of these, 216 were complicated by velamentous umbilical cord insertion, whereas the remaining 12,534 were normal controls. Using multiple regression analysis, we evaluated the risks by noting adverse infant outcomes: low birth weight (LBW), small for gestational age (SGA), preterm delivery, fetal death, admission to a specific infant care unit, low Apgar scores, neonatal acidemia, and abnormal intrapartum fetal heart rate (FHR) patterns. At prenatal visits, NST and Doppler ultrasound examinations were carried out as a routine part of obstetric care. RESULTS: Even after we controlled for confounding factors, velamentous umbilical cord insertion was associated with higher risk of LBW (odds ratio [OR] 2.32), SGA (OR 1.54), preterm delivery (OR 2.12), low Apgar scores at 1 and 5 minutes (ORs 1.76 and 2.47, respectively), and abnormal intrapartum FHR pattern (OR 1.59). Only 5% of the patients with abnormal insertion showed pathologic NST results at prenatal visits. Ultrasonographic examination was carried out on 80 patients with velamentous umbilical cord insertion as a routine part of obstetric care, and in only one case was direct visualization of the abnormal insertion successful. After we excluded pregnancies with preeclampsia, abnormal umbilical artery Doppler velocimetry was found in none of the cases examined (n = 48). CONCLUSION: There were substantial differences in pregnancy outcome measures between the subjects with velamentous umbilical cord insertion and controls. Current antepartum methods of tracing uteroplacental problems are not effective in the prenatal detection of abnormal insertion. Therefore, in future studies, the use of other diagnostic tools, such as color Doppler imaging of cord insertion, should be evaluated in high-risk pregnancies followed-up because of fetal growth restriction.