Perinatal complications following gestational diabetes mellitus how 'sweet' is ill?

OBJECTIVE: We tested the effect of patient compliance, fasting plasma glucose on oral glucose tolerance test, maternal body constitution, and the method of treatment (diet versus insulin) on the perinatal outcome of patients with gestational diabetes mellitus. STUDY DESIGN: A prospective population-based study compared the perinatal outcome of patients with gestational diabetes mellitus (n = 470) (diabetic with regard to the parameters specified above) and a contemporaneous control group (nondiabetic, n = 250). RESULTS: The diabetic and control groups were matched in demographic characteristics. Patient compliance reduced the rate of macrosomia (14.4%) and neonatal hypoglycemia (3.4%) but not to the levels of the control group (5.2% and 1.2% respectively, p < 0.05). The level of fasting plasma glucose on the oral glucose tolerance test had no effect on perinatal outcome. Intensified (insulin) treatment reduced the rate of macrosomia and large-for-gestational age infants in the subgroups with intermediate and high levels of fasting plasma glucose on the oral glucose tolerance test (9.5%/14.2% and 12.2%/24.2% respectively), again not to levels of the control group (5.2%/10.8%). Obese patients were found to have more perinatal complications than lean patients. Intensified (insulin) treatment has proved to be beneficial in terms of reducing the rate of perinatal complications in the obese patients, but not to the corresponding levels of the control group. Such treatment had no effect on the lean patients. CONCLUSIONS: Strict control of maternal hyperglycemia and high patient compliance are imperative for an effective reduction of perinatal complication in patients with gestational diabetes mellitus. The desired plasma glucose level in the glycemic control of these patients should be further reduced, thus bringing the rate of perinatal complications to that of the normal population.     

Teratogenicity of 3-deoxyglucosone and diabetic embryopathy

The increased rate of embryonic dysmorphogenesis in diabetic pregnancy is correlated with the severity and duration of the concurrent hyperglycemia during early gestation. Whole embryo culture was used to investigate a possible association of hyperglycemia-induced disturbances of embryo development with tissue levels of the three alpha-oxoaldehydes: glyoxal, methylglyoxal, and 3-deoxyglucosone (3-DG). Rat embryos exposed to high glucose levels in vitro showed severe dysmorphogenesis and a 17-fold increased concentration of 3-DG compared with control embryos cultured in a low glucose concentration. Exogenous 3-DG (100 micromol/l) added to the medium of control cultures yielded an increased embryonic malformation rate and a 3-DG concentration similar to that of embryos cultured in high glucose. Addition of superoxide dismutase (SOD) to the culture medium decreased the malformation rates of embryos exposed to either high glucose or high 3-DG levels, but it did not decrease the high embryonic 3-DG concentrations caused by either agent. Our results implicate the potent glycating agent 3-DG as a teratogenic factor in diabetic embryopathy. In addition, the anti-teratogenic effect of SOD administration appears to occur downstream of 3-DG formation, suggesting that 3-DG accumulation leads to superoxide-mediated embryopathy.     

Experimentally contaminated reabsorbable meshes: their evolution in abdominal wall defects

The effect of maternal hyperglycemia on fetal regional circulation in appropriate for gestational age and small for gestational age fetuses was evaluated. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on 15 appropriate for gestational age and 19 small for gestational age fetuses, ranging from 33 to 40 weeks' gestation before, 60 minutes, and 120 minutes after a maternal 75 g glucose load. The pulsatility index (PI) was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery, and umbilical artery. Simultaneously, maternal plasma glucose concentration was measured. Baseline PI value (1.50 +/- 0.31) for middle cerebral artery in small for gestational age fetuses was significantly lower than that (1.89 +/- 0.37) in appropriate for gestational age fetuses (p < 0.05); however, there were no significant differences in baseline PI values for other arteries in both groups. In appropriate for gestational age fetuses, the mean PI decreased from 1.89 +/- 0.37 to 1.47 +/- 0.33 at 60 minutes, and to 1.55 +/- 0.32 at 120 minutes (p < 0.05), but no changes were found in the other arteries. In small for gestational age fetuses, there was no significant change in PI value for each artery before and after maternal glucose load. Maternal hyperglycemia induces a significant decrease in cerebrovascular resistance in appropriate for gestational age fetuses but not in small for gestational age fetuses. These results provide a foundation for evaluating the effect of maternal hyperglycemia on fetal regional circulation.     

Abnormal functional connectivity in Alzheimer''s disease: intrahemispheric EEG coherence during rest and photic stimulation

Tolbutamide is a sulfonylurea oral hypoglycaemic agent with suspected teratogenicity in humans and demonstrated teratogenicity in laboratory animals, but the underlying mechanism is unknown. This study examined maternal-to-conceptus tolbutamide transfer on gestational days 9.5 and 10.5 and drug concentration in embryonic head, heart, and trunk regions on gestational day 10.5 after maternal dosing in mouse. Embryos exposed to tolbutamide in vitro on gestational day 8.5 were assayed for glucose uptake, glycolysis, and protein content after 6, 12, and 24 hr. Dose-dependent tolbutamide transfer from maternal serum to extraembryonic fluid occurred on gestational day 9.5 and 10.5, with highest tolbutamide levels in embryonic heart on gestational day 10.5. In vitro tolbutamide exposure on gestational day 8.5 decreased glycolysis at 6 hr, increased glycolysis at 24 hr, and had no effect on glucose uptake at 6, 12, or 24 hr. Embryonic protein content reflected growth retardation after 24 hr tolbutamide exposure. Thus, mouse embryos are directly exposed to tolbutamide after maternal dosing on gestational day 9.5 and 10.5, with concentration of drug within embryonic heart. Tolbutamide-induced changes in glucose metabolism are less apparent in whole embryos than reported in adult tissues.     

Fine-needle aspiration cytology of suture granulomas of the breast: a potential pitfall in the cytologic diagnosis of recurrent breast cancer

OBJECTIVE: To determine the relationship of serum theophylline concentration with electrolyte and glucose abnormalities across a broad range of theophylline concentrations. DESIGN: Retrospective review of a computerized laboratory database between June 1, 1984 and June 1, 1986. SETTING: A midwestern university medical center. PATIENTS: Eight hundred sixty-nine patients with serum theophylline concentrations of > 5.5 mumol/L and a random unmatched sample (control group) of 350 in- and outpatient adults and children with no history of reactive airways disease or theophylline exposure. RESULTS: Patients with measurable theophylline had a higher risk of hypokalemia, hyponatremia, hyperglycemia, hypophosphatemia, and hypomagnesemia compared with the unexposed control group. Unadjusted odds ratios (OR) were: (1) hypokalemia OR = 4.2 (95 percent CI 2.2 to 7.9); (2) hyponatremia OR = 5.4 (95 percent CI 2.0 to 12.9); (3) hypomagnesemia OR = 1.6 (95 percent CI 1.0 to 2.5); (4) hyperglycemia OR = 2.3 (95 percent CI 1.7 to 3.0); and (5) hypophosphatemia OR = 2.7 (95 percent CI 1.2 to 5.3). A linear concentration-response relationship was documented between serum theophylline concentration and all metabolic disturbances. CONCLUSIONS: Measurable theophylline was associated with increased risk for glucose and electrolyte abnormalities in a concentration-related fashion across a broad range of theophylline concentrations from 5.5 to > or = 110 mumol/L.     

Insulin-independent acute restoration of euglycemia normalizes the impaired glucose clearance during exercise in diabetic dogs

At rest and during exercise, chronic hyperglycemia, high free fatty acid (FFA) oxidation, and insulin deficiency in diabetes are well known to impair glucose clearance (metabolic clearance rate [MCR]). The effect of acute restoration of glycemia per se on MCR has been less well characterized. We therefore studied normal and alloxan-diabetic dogs both at rest and during exercise, as diabetic hyperglycemic or after acutely induced euglycemia (<160 min) generated by infusion of either insulin or phlorizin. Glucose uptake was similar under hyperglycemic and normoglycemic conditions both at rest and during exercise, indicating a precise balance between the mass effect of glucose and decreased MCR. Rest and exercise MCR was fourfold lower under conditions of hyperglycemia, but insulin-independent restoration of euglycemia improved basal MCR threefold and normalized MCR during exercise. High FFA turnover did not affect glucose uptake but was correlated with plasma lactate concentrations (r = 0.72, P < 0.001), suggesting that muscle fuel requirements are controlled by glucose oxidation and not uptake. We conclude that in alloxan-diabetic dogs, the impaired MCR may be an adaptive phenomenon because correction of hyperglycemia corrects MCR despite partial insulin deficiency and high FFA turnover. We speculate that constant glucose uptake despite hyperglycemia in diabetes may protect the muscle from excessive exposure to glucose.     

Age-dependent decrease in embryo implantation rate after in vitro fertilization

OBJECTIVE: To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN: Retrospective study using linear and biphasic models in a multivariate analysis. SETTING: Academic tertiary care institution. INTERVENTION(S): In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S): Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S): Woman's age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S): The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.     

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development

OBJECTIVE: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women. RESULTS: Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS: The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.     

Neuropsychological consequences of very low birth weight and asphyxia at term: follow-up until school-age

This prospective, longitudinal study examined neuropsychological consequences of different conditions associated with risks of perinatal asphyxia. Four groups of children, 5 to 9 years of age, were studied: (1) very low birth weight (VLBW) children born small for gestational age (SGA) (n = 34); (2) VLBW children born appropriate for gestational age (AGA) (n = 43); (3) children with signs of birth asphyxia at term (birth asphyxia) (n = 36), and (4) control children (n = 45). Moderately and severely disabled children were excluded. The WISC-R and the NEPSY, a new neuropsychological assessment consisting of attention, language, motor, sensory, visuospatial, and memory subtests, were administered. The VLBW-SGA group had the poorest test results. The VLBW-AGA group was somewhat less impaired, whereas the birth asphyxia group performed at the control group level. Impairment, when present, tended to be diffuse in all groups, affecting psychometric intelligence, naming, visuo-motor performance, tactile finger discrimination, attention, and phonological analysis.     

Psychiatric illness in patients with end-stage renal disease

The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.     

Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta-cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent oral and intravenous glucose tolerance tests (OGTT; IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks' gestation and returned between 1 and 6 months postpartum for a 75-g OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. At postpartum testing, 40% of the cohort had normal glucose tolerance, 50% had IGT, and 10% had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were the 30-min incremental insulin:glucose ratio during a 75-g OGTT (P = 0.0002) and the total area under the diagnostic 100-g glucose tolerance curve (P = 0.003). Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response (P = 0.0001), a diagnosis of GDM before 22 weeks' gestation (P = 0.003), and weight gain between prepregnancy and the postpartum examination (P = 0.03). All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the 3rd trimester were associated with the risk of IGT or diabetes within 6 months' postpartum. These results highlight the importance of pancreatic beta-cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the 3rd trimester in women with such a beta-cell defect.     

Aspects of fetal physiology from 18 to 37 weeks' gestation as assessed by blood sampling

OBJECTIVE: To construct reference ranges for fetal pH, oxygen pressure (PO2), and hematologic and biochemical blood constituents, which can be used to analyze changes with gestation and differences with maternal values, thus elucidating some aspects of fetal biology and the effects of the maternal and placental environments. METHODS: We assayed venous pH, PO2, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatine kinase, triglycerides, and cholesterol concentrations in 157 fetuses and 134 mothers who underwent fetal blood sampling from 18 to 37 weeks' gestation. None of the fetuses was infected or had chromosomal, hematologic, or hormonal abnormalities. RESULTS: All the variables analyzed were similar in fetuses sampled at the placental cord insertion (n = 125) or at the intrahepatic vein (n = 32). Maternal and fetal concentrations of glucose (r = 0.79, P < .001), urea (r = 0.96, P < .001), creatinine (r = 0.83, P < .001), and uric acid (r = 0.94, P < .001) correlated significantly, and their differences exhibited significant changes: the maternal-fetal differences of glucose and urea increased, whereas those of uric acid and creatinine decreased with advancing gestation. Fetal pH and PO2 decreased with gestational age, whereas hematocrit increased, similar to what has been described previously. All of the other variables, with the exception of amylase and cholesterol, changed significantly during the investigated period of pregnancy. Gestational age explained at least 40% of the variance in values of fetal total protein, pseudocholinesterase, alanine aminotransferase, creatine kinase, and triglycerides, but only 3-25% of the variation in the remainder. Most enzymes were higher in the fetus than in the maternal circulation, and all except alkaline phosphatase increased with gestational age. The maternal-fetal glucose difference correlated significantly with hematocrit, pH, and PO2, independent of gestational age and independent of each other. CONCLUSION: With the exception of aspartate aminotransferase, all of the analyzed fetal variables were different from the maternal values, and most changed with gestational age. The mechanisms leading to these fetal specificities remain mostly uncertain, but the provision of reference ranges for several blood constituents may be useful in the differential diagnosis of fetal disease.     

Successful medical management of isolated renal zygomycosis: case report and review

OBJECTIVE: Determination of gestational age-related fluctuations in heart rate in the umbilical artery of the early human fetus. METHODS: Doppler velocity recordings from human umbilical artery were obtained, in a cross-sectional study design in 137 singleton pregnancies at 10-20 weeks of gestation. After exclusion criteria were applied, data on 117 normal pregnancies were available and subdivided into group I: 10-12 weeks (n = 49); group II: 13-16 weeks (n = 43); and group III: 17-20 weeks (n = 25). Blood flow velocity waveforms were reconstructed from Doppler audio signals. Variability in heart rate was calculated using Fast Fourier Transforms (FFT). Individual heart rate variability power spectra were subdivided into frequency bands. RESULTS: Fetal heart rate variability decreases at 10-20 weeks and demonstrates a shift to lower frequencies at 17-20 weeks. CONCLUSIONS: Fetal heart rate variability is related to gestational age and shows a shift to lower frequencies which may reflect autonomic functional development.     

In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study

To assess whether erythropoietin (EPO) treatment is safe and reduces the need for transfusion, we randomized 44 preterm infants to an EPO group and a comparable control (CON) group. EPO 150 U/kg was given s.c. twice weekly for 6 wk from the 1st wk of life. Hematologic parameters, transfusion requirements, and growth were followed during therapy and for 6 mo thereafter. To better assess in which neonates EPO treatment was effective, we classified retrospectively the EPO and CON groups into uncomplicated neonates (EPO A: n = 9, birth weight = 1247 +/- 126 g, gestational age = 29.8 +/- 1.5 wk; CON A: n = 7, birth weight = 1217 +/- 145 g, gestational age = 29.9 +/- 1.5 wk) and neonates requiring artificial ventilation (EPO B: n = 16, birth weight = 1169 +/- 249 g, gestational age = 28.1 +/- 2 wk; CON B: n = 12, birth weight = 1173 +/- 215 g, gestational age = 28.3 +/- 2 wk). There were significant differences in reticulocytes between both uncomplicated and ventilated neonates in the EPO group compared with respective control groups. However, the need for transfusion was significantly less in the uncomplicated EPO group (EPO A: 0.44 +/- 0.73 versus CON A: 1.28 +/- 0.75, p < 0.05) but not in the neonates on ventilation (EPO B: 8.25 +/- 5 versus CON B: 7.75 +/- 3.7). In conclusion, early EPO administration reduces the need for transfusion in uncomplicated premature neonates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of donor-specific tolerance to cardiac xenografts in utero

BACKGROUND: Problems associated with heart transplantation, such as shortage of suitable organs and the side effects of immunosuppressive therapy, are especially serious for patients in the pediatric age group. Induction of donor-specific immunologic tolerance without immunosuppressive drugs would be ideal for clinical organ transplantation. In this study, we used a vascularized cardiac xenograft model to achieve donor-specific unresponsiveness without immunosuppression by manipulating the intrauterine immune response. METHODS: Lewis rats and Golden Syrian hamsters were used as the recipients and donors, respectively. Donor bone marrow cells (15 x 10(6) in 0.05 mL) were injected into each fetus of pregnant Lewis rats on days 9 (n = 2) and 16 (n = 2) of gestation. Donor hearts were heterotopically transplanted into each surviving (n = 8, n = 5) fetus of the Lewis rats at 8 weeks of age. Donor hearts were also transplanted into untreated rats as controls (n = 8). RESULTS: The mean cardiac xenograft survival time was 2.5 +/- 0.5, 7.4 +/- 4.1, and 2.8 +/- 0.8 days in the control group, gestational day 9 group, and gestational day 16 group, respectively. Chromosomal analysis of the day 9 group showed Golden Syrian hamster chromosomes as well as Lewis rat chromosomes. CONCLUSIONS: Cardiac xenograft survival was significantly prolonged by intrauterine exposure to xenograft bone marrow cells on day 9 but not on day 16 of gestation. Cardiac xenograft survival and chromosomal analysis of the recipient bone marrow suggested that chimerism was achieved between Golden Syrian hamsters and Lewis rats. Cardiac xenotransplantation may be possible by induction of donor-specific tolerance in utero.     

Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation.     

Effect of platelet activating factor on embryonic development and implantation in the mouse

Platelet activating factor (PAF) was administered to female mice in order to investigate its effect on ovulation rate and on oocyte quality including their in-vitro embryonic development, implantation and uterine receptivity. In experiment 1, 4-week-old female mice were assigned to receive PAF or phosphate buffered saline for 4 consecutive days. On the second day of this treatment, pregnant mares' serum gonadotrophin was administered and human chorionic gonadotrophin (HCG) 48 h later, after which copulation occurred. Oocytes were collected on the following day and evaluated. The mean number of oocytes and zygotes (two pronuclear stage embryos) recovered from the PAF-treated group was not different from the control group (31 versus 27), but the proportion of zygotes was higher in PAF-treated group than in controls (83 versus 68%, P < 0.05, PAF versus controls). Although the rate of in-vitro first cleavage was not different in the two groups (82 versus 69% respectively), hatching was higher in the PAF-treated group than control mice (99 versus 83%, P < 0.01). In experiment 2, the in-vitro developed blastocysts from experiment 1 were transferred into the uterus of day 3 pseudopregnant PAF-treated or control recipients. Three different combinations of intrauterine transfer were performed; PAF embryo to control recipient (PAF-->C: n = 19), control embryo to PAF recipient (C-->PAF: n = 19), and control embryo to control recipient (C-->C: n = 22). Implantation and abortion were assessed on day 19 posttransfer. The implantation rate of C-->PAF (23.7%) was lower than C-->C (31.1%, P < 0.05), but was not different from PAF-->C (31.2%). Further, C-->PAF showed a higher abortion rate per embryo (29.6%) than PAF-->C (12.7%, P < 0.05), but was not different from C-->C (24.4%). In the present study, PAF administration enables females to produce oocytes with a higher potential for fertilization, in-vitro development and implantation, but has a detrimental effect on uterine receptivity to embryos.     

Impact of Converging Chute Walls for Roller Compacted Concrete Stepped Spillways

A study utilizing a three-dimensional, 1:22 scale, physical model was conducted to evaluate the flow characteristics in the spillway with varying training wall convergence angles. The wall height required to contain the flow for conditions tested varied from critical depth at a 15° convergence angle to three times the critical depth at a 52° convergence angle. The results of the study may be used to estimate minimum training wall height for conditions where bulking due to air entrainment may reasonably be neglected.     

Assisted hatching in the treatment of poor prognosis in vitro fertilization candidates

OBJECTIVE: To access the effect of augmenting IVF with assisted hatching in the treatment of poor-prognosis patients. DESIGN: Thirty-three poor-prognosis IVF patients were treated with assisted hatching and were compared with 43 control subjects without assisted hatching. SETTING: Center for Reproductive Medicine, Swedish Medical Center, Englewood, Colorado. PARTICIPANTS: Seventy-six women undergoing IVF with a poor prognosis for pregnancy. Poor prognosis was defined as Elevated day 3 FSH level; age > or = 39 years; and multiple prior IVF failures. MAIN OUTCOME MEASURES: Pregnancy and implantation rates per embryo. RESULTS: The incidence of ongoing pregnancy in the assisted hatching group was 64% compared with 19% in the control group. Implantation rate per embryo transferred was 33% in the assisted hatching group versus 6.5% in the control group. CONCLUSIONS: These results demonstrate that assisted hatching, when applied to poor-prognosis patients, improves embryonic implantation and pregnancy rates.