Beneficial aspect of oral estriol as hormone replacement therapy: consideration on bone and lipid metabolism.

To improve the quality of life of elderly people in Japanese society where women have the longest life expectancy in the world, osteoporosis, and hyperlipidemia are among the major targets of medical treatment. To differentiate two types of regimens for hormone replacement therapy (HRT), we tried to evaluate the efficacy on lipid and bone metabolism. With informed consent, 34 postmenopausal women of more than 2 years were assigned to receive 1 of 2 types of HRT (the HRT group) for 12 months observation: one with a combination of conjugated equine estrogen (CEE) 0.625 mg/day and medroxyprogesterone acetate (MPA) 2.5 mg/day (the CEE group), and the other with oral estriol (E3) 2 mg/day (the E3 group). Parameters of serum lipid were measured, as well as those of bone metabolism with bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) using QDR-2000. In HRT groups, lipid and bone metabolism were confirmed to be improved. Whereas, an increase of triglycerides (TG) observed in the CEE group was not observed in the E3 group. Thus, in the clinical management of postmenopausal women, oral E3 preparation as an alternative regimen for HRT for CEE might be efficacious.

Decreased factor XII activity is associated with recurrent IVF-ET failure.

PROBLEM: A decrease in factor XII (FXII) activity has been observed in women with unexplained recurrent miscarriages. Because of the many similarities between recurrent in vitro fertilization-embryo transfer (IVF-ET) failure and early pregnancy loss patients, we investigated whether women with recurrent IVF-ET failure had low FXII activity. METHOD OF STUDY: Blood from 110 patients with three or more IVF-ET failures was tested for FXII activity, autoantibodies and other coagulation parameters. These patients were compared with 191 recurrent miscarriage patients, 87 controls. FXII activity was measured by an activated partial thromboplastin time (APTT) assay. RESULTS: Factor XII activity of the IVF-ET failure group (median 79.5, range 37-150) was significantly lower than that of control group (median 109, range 35-225, P < 0.001 by Mann-Whitney test) or that of recurrent pregnancy loss (RPL) group (median 92, range 20-205). The FXII activity of IVF-ET failure patients was positively correlated with age, but not associated with the number of IVF-ET failures, infertile duration, autoantibodies, or other coagulation parameters. CONCLUSION: Decreased FXII activity may causally relate to reproductive failure.

Non-invasive assessment of arterial stiffness in appropriate-for-gestational age newborn infants.

BACKGROUND: Quantitative information about the elastic properties of the large arteries can be obtained by determination of the pressure and the pulsatile changes of arterial diameter. OBJECTIVE: To study the stiffness of major branches (common carotid artery; CCA, abdominal aorta; AA and femoral artery; FA) in newborn infants. STUDY DESIGN: The arterial stiffness index (SI) values were measured with a phase locked loop ultrasound technique to estimate the arterial systolic and diastolic diameters and their correlation with blood pressure. SUBJECTS: We studied 62 appropriate-for-gestational age infants (between 30 and 41 weeks of gestation at birth) including 33 preterm infants. RESULTS: The systolic and diastolic diameters of the CCA, AA and FA, as well as the SI, increased with the gestational age at birth. In the SI of the FA, there was considerable variation in the individual values for a given gestational age at birth. The gestational age associated increase in stiffness was statistically significant only in the CCA and the AA. Although the mechanical properties of the FA were significantly influenced by physical activities during the active waking and quiet sleeping states, the calculated SI values were less vulnerable to these activities in the central arteries. CONCLUSION: These results indicate that the SI of the FA (peripheral muscular artery) is modified appreciably by vasoactive stimuli. The mechanical properties of the deeper elastic arteries in newborn infants provide sufficiently reliable information about changes caused by development.

Evaluation of cardiac function of the fetus by inferior vena cava diameter pulse waveform.

BACKGROUND: The diameter pulse waveforms (DPWs) are known to reflect the pressure waveforms at the target vessel. Our purpose was to clarify the usefulness of DPWs recorded noninvasively from the fetal inferior vena cava (IVC) for detecting cardiac function. METHODS: A paired ultrasonic phase-locked echo tracking system was used to follow the movement of diametrically opposite points of the IVC. RESULTS: We studied 90 healthy fetuses (20-40 weeks, normal group) and 21 fetuses with cardiac abnormalities. The 4 component (A, X, V, and Y) waves of the DPW were identified. In the normal group, there was an increase in the depth of X and Y descents with advancing gestation. The 21 fetuses with suspected cardiac dysfunction were divided into normal and cardiac dysfunction subgroups, according to the values of fractional shortening and preload index. Of these, 11 fetuses with cardiac dysfunction had significantly higher incidence of shallow X nadir (P < .001) than the remaining 10 fetuses with normal cardiac function. CONCLUSION: The DPW analysis in the fetal IVC proved useful for detecting fetal cardiac dysfunction in utero.

Uteroplacental circulation, preeclampsia, and maternal abdominal aortic stiffness in normal and compromised pregnancies.

A study of 82 normal and 60 compromised pregnant women who were identified by uterine artery Doppler flow waveform systolic/diastolic ratio >95th percentile (increased peripheral resistance) was carried out to examine the elastic properties of the maternal abdominal aorta (AA). An aortic stiffness index (SI) was measured between 18 and 40 weeks at four-weekly intervals with a phase-locked loop ultrasound technique to estimate the aortic systolic and diastolic diameters and their correlation with blood pressure. In the normal group, the aortic systolic and diastolic diameters, as well as the SI, increased with the maternal age. In the compromised group, aortic diameter and blood pressure were normal, but the SI during the early second trimester was increased. Twenty-two women from the compromised group with an SI above the 95th percentile for their age had a significantly higher prevalence of preeclampsia in comparison with women with a normal SI (P<0.001). The aortic SI was significantly higher in severe than in mild preeclampsia. This study demonstrates that stiffness of the AA is increased in pregnant women with preeclampsia and that a progressive increase of the SI in serial studies is associated with severity of the disease. Aberrant hemodynamic adaptation in preeclampsia seems to include increased stiffness of the larger artery besides high resistance in small peripheral arteries.

Normal and abnormal diameter pulse waveforms in the fetal inferior vena cava.

OBJECTIVES: To study the diameter pulse waveforms (DPWs) recorded noninvasively from the fetal inferior vena cava (IVC) in human fetuses. METHODS: We studied 90 normal fetuses (20 to 40 weeks), ten fetuses with abnormalities of cardiac structure, and seven fetuses with arrhythmia. A paired ultrasonic phase-locked echo tracking system was used to follow the movement of diametrically opposite points of the IVC. RESULTS: The four component (A, X, V, Y) waves of the DPW were identified. In the normal group, there was an increase in the depth of X and Y nadirs. The abnormal group was divided into two subgroups. In 12 fetuses (five pulmonary stenosis, seven arrhythmia) there was a high pulsatile pattern with deep nadir from the A peak to X trough so that the pulsatility of the waveform appeared increased. The cause of the high pulsatility was due to a marked change of intraatrial pressure. In five fetuses with tricuspid regurgitation, this change was shallow and the pulsatility appeared reduced. Clinical outcome was significantly worse in the low pulsatile subgroup. CONCLUSION: The low pulsatility waveform may indicate depressed myocardial function. Measuring the DPW provides a simple method for obtaining important information about fetal cardiac performance.

Characteristic diameter pulse waveform patterns of the inferior vena cava in fetuses with abnormalities of cardiac structure.

BACKGROUND: Changes in the vessel lumen diameter pulse waveform closely follow changes in the transmural pressure pulse waveform. AIM: To study diameter pulse waveform recorded noninvasively from the fetal inferior vena cava (IVC) in fetuses with cardiac abnormality. STUDY DESIGN: A paired ultrasonic phase-locked echo tracking system with a high sampling frequency (3000 Hz) was used to follow the movement of diametrically opposite points of the IVC. The lumen was measured as the interval between these points. SUBJECTS: We studied 80 normal fetuses (20 to 40 weeks) and 11 fetuses with cardiac abnormality. RESULTS: The four component waves of the IVC diameter pulse waveform (A, X, V, Y) were identified and measured in the fetal recording. In the normal group, the A and V values increased linearly with advancing gestation. There was an increase in the depth of X and Y descents. Each cardiac abnormality produced characteristic changes in the A, X, V and Y waves of the IVC diameter pulse waveform. The most impressive IVC diameter pulse waveform pattern in fetal cardiac abnormality was the depth of the X descent from the A crest to X trough. In the circumstance of pulmonary stenosis, the A wave was large and prominent (deeper X descent, high pulsatility waveform). In the presence of a dilated right ventricle, or an incompetent tricuspid valve, the X descent was shallow (low pulsatility waveform). CONCLUSION: The fetal IVC diameter pulse waveform can be simply recorded. The high pulsatility waveform may result from increased end-diastolic pressure with a consequent increased resistance to flow into the ventricle from the atrium. The low pulsatility waveform may indicate depressed myocardial function.

Inferior vena cava diameter pulse waveforms in the human fetus: relationship with flow velocity waveform.

Our purpose was to evaluate the hemodynamic significance of fetal inferior vena cava (IVC) flow velocity waveform indices during fetal development in relation to the diameter pulse waveform. Doppler ultrasound and a phase locked loop echo tracking system were used to measure flow velocity waveform and diameter pulse waveform, respectively. Twenty-seven normal singleton pregnancies were examined from 20 weeks until term at 4-week intervals. The diameter pulse waveform consisted of four waves (A, X, V, and Y waves). The A value (end-diastolic diameter) was associated with the end-diastolic pressure, which causes reverse flow during right atrial contraction. In normal fetuses, a weight-related lower end-diastolic diameter suggested that the end-diastolic pressure was decreased. Except for a positive correlation between the percent reverse flow during atrial contraction and the A value per unit fetal weight, no correlations were found between diameter waveform indices and blood flow velocity waveform indices. The peak velocity index of the velocity waveform significantly correlated with the umbilical artery flow velocity waveform systolic/diastolic ratio. The fetal IVC velocity waveform indices did not yield unequivocal information as to changes in central venous pressure, for which purpose the diameter pulse waveform analysis would seem to be the only available method.

Stiffness of systemic arteries in appropriate- and small-for-gestational-age newborn infants.

OBJECTIVE: The purpose of this work was to study the stiffness of systemic arteries in appropriate and small for gestational age newborn infants. The distance between diametrically opposite points of the arterial lumen was measured with a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager. PATIENTS AND METHODS: A cross-sectional study of 51 appropriate for gestation age infants including 22 preterm infants was done to obtain normal data. We also studied 47 small for gestational age infants, who were identified antenatally by an umbilical artery Doppler flow waveform pulsatility index > 95th percentile. The stiffness index of the common carotid artery and abdominal aorta was calculated from the relationship between systemic blood pressure and arterial diameter during the cardiac cycle. RESULTS: In the appropriate for gestation age group, the systolic and diastolic diameters of the common carotid artery and abdominal aorta, as well as the stiffness index, increased with the gestational age at birth. In the small for gestational age group, the arterial diameters and blood pressure were also within the reference range. Using the arterial stiffness index values from the appropriate for gestation age group, the small for gestational age group was divided into 3 subgroups: 18 infants with normal stiffness index values for both arteries, 19 infants with a high stiffness index of the abdominal aorta, and 10 infants with a high stiffness index for both arteries. The clinical outcome was significantly worse in the latter 2 subgroups compared with the normal infants and was also worse in the infants with a high stiffness index for both arteries compared with the high abdominal aorta subgroup. CONCLUSION: The antenatal increase of afterload caused by a high placental vascular resistance was associated with a decrease of aortic distensibility in the compromised small for gestational age infants, suggesting that the structure of the aortic wall was altered. In the most profoundly compromised small for gestational age infants, the high stiffness index of both the common carotid artery and abdominal aorta may indicate more extensive arterial damage.

Abnormal placental cord insertion may induce intrauterine growth restriction in IVF-twin pregnancies.

BACKGROUND: This study determined whether twins conceived through assisted reproduction technology (ART) have an increased risk of perinatal complications compared with natural twin pregnancies and investigated potential associated major risk factors. METHODS: This retrospective study consisted of 199 twins born between 1994 and 2003. There were four groups according to conception modalities: 97 twins after spontaneous pregnancy, 24 after induced ovulation, 28 after intrauterine insemination (IUI) and 50 after IVF with embryo transfer. Analysis included preterm birth, Caesarean delivery, weight discordance, intrauterine growth restriction (IUGR), low-birth-weight, Apgar score, chorionicity, gross placental pathology and placental umbilical cord insertion (UCI) site. RESULTS: A significant difference was found in IUGR between the IVF group (7.0%) and spontaneous pregnancy group (14.9%). When maternal age was >30 years there was a 2.86-fold increase in the risk of IUGR. There was a 3.69-fold increased risk of IUGR in the presence of abnormal UCI (odds ratio 3.69, 95% CI 1.62-8.42) and a 2.18-fold increased risk of abnormal UCI in monochorionic twins when compared with dichorionic twins (odds ratio 2.18, 95% CI 1.30-3.66). CONCLUSION: Twins conceived through ART are not at an increased risk of perinatal complications. A relationship has been found between abnormal UCI and IUGR.

Evaluation of 25 years of Uterine Cervical Cancer Screening at Tokai University Hospital Health Evaluation and Promotion Center.

The total number of persons who underwent uterine cervical cancer screening at the Tokai University Hospital Health Evaluation and Promotion Center during the 25-year period from January 1976 to March 2001 was 30,173 (gross number: 111,181). Since 1995, more than 6,500 females have visited the center annually, and more than 70% were 40-59 years of age. Among these females, 849 exhibited atypical changes higher than class IIIa in the cytological examination (class IIIa: 779, IIIb: 43. IV: 14 and V: 13), and the detection rate was 0.76%. In examining the relationship between the age and number of visits to the center and the detection rate of atypical changes observed in the cytological examination, patients in their 40s exhibited the highest detection rate (1.31%), and the rate at the first screening was 1.19%. Analysis of the age distribution for the detection rate of atypical changes in the cytological examination before 1989 and after 1990 showed that persons in their 40s and 50s had high rates (1.62% and 1.69%, respectively) before 1989, but since 1990 persons in their 20s, 30s and 40s exhibited high rates (2.86%, 2.16% and 2.61%, respectively) (p ＜ 0.001). This suggests a lowering of the age at which atypical changes are observed in the cytological examination.

Preservation of tubal function following methotrexate treatment for ectopic pregnancy.

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.