Simulator training and non-technical factors improve laparoscopic performance among OBGYN trainees.

OBJECTIVE: To investigate how simulator training and non-technical factors affect laparoscopic performance among residents in obstetrics and gynecology. DESIGN: In this prospective study, trainees were randomized into three groups. The first group was allocated to proficiency-based training in the LapSimGyn(®) virtual reality simulator. The second group received additional structured mentorship during subsequent laparoscopies. The third group served as control group. At baseline an operation was performed and visuospatial ability, flow and self-efficacy were assessed. All groups subsequently performed three tubal occlusions. Self-efficacy and flow were assessed before and/or after each operation. SETTING: Simulator training was conducted at the Center for Advanced Medical Simulation and Training, Karolinska University Hospital. Sterilizations were performed at each trainee's home clinic. POPULATION: Twenty-eight trainees/residents from 21 hospitals in Sweden were included. METHODS/MAIN OUTCOME MEASURES: Visuospatial ability was tested by the Mental Rotation Test-A. Flow and self-efficacy were assessed by validated scales and questionnaires. Laparoscopic performance was measured as the duration of surgery. Visuospatial ability, self-efficacy and flow were correlated to the laparoscopic performance using Spearman's correlations. Differences between groups were analyzed by the Mann-Whitney U-test. RESULTS: No differences across groups were detected at baseline. Self-efficacy scores before and flow scores after the third operation were significantly higher in the trained groups. Duration of surgery was significantly shorter in the trained groups. Flow and self-efficacy correlate positively with laparoscopic performance. CONCLUSIONS: Simulator training and non-technical factors appear to improve the laparoscopic performance among trainees/residents in obstetrics and gynecology.

Diverse mechanisms of endothelium-derived hyperpolarizing factor-mediated dilatation in small myometrial arteries in normal human pregnancy and preeclampsia.

This ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 µm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H(2)O(2) and cytochrome P450 2C9 (CYP2C9). Transmission electron microscopy was used to visualize morphological prerequisites for MEGJs. In normal pregnancy, EDHF through MEGJs appeared to be a predominant mediator conferring endothelium-dependent relaxation in small myometrial arteries. In preeclampsia, bradykinin-induced relaxation was reduced via compromised EDHF-type responses, in which the contribution of MEGJs became negligible. The attenuated role of MEGJs to endothelium-dependent relaxation was partly compensated through the contribution of H(2)O(2) or other endothelium-derived relaxing factors. CYP2C9 products of arachidonic acid had no effect on EDHF-type relaxation in arteries of women with normal pregnancy or with preeclampsia. We suggest that EDHF-type responses via MEGJs are primarily targeted in small myometrial arteries in women with preeclampsia. This could significantly contribute to the impaired uteroplacental blood flow in this disorder.

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.

Endothelin converting enzyme (ECE) activity in normal pregnancy and preeclampsia.

OBJECTIVE: Enhanced production of endothelin-1, due to endothelial cell dysfunction has been considered to be the cause of increased plasma levels of endothelin-1 in preeclampsia. The present study was aimed at analyzing endothelin-converting-enzyme activity, (which reflect the production rate of endothelin-1 (ET-1) from big endothelin-1 (big ET-1)), big endothelin-1, and endothelin-1 concentrations from women with preeclampsia compared to normal pregnant women. Moreover, we analyzed plasma levels of these substances longitudinally throughout normal pregnancy. STUDY DESIGN: Twenty-nine pregnant healthy women were recruited to the study. Blood samples were obtained at 18, 28, and 38 weeks gestation and six weeks postpartum. Twenty-seven women with preeclampsia were included. Blood samples were taken at diagnosis (average 35 weeks gestation; range 27-39 weeks) and six weeks postpartum. Endothelin-1 was analyzed by enzyme linked immunoassay (ELISA) and big-ET-1 by radioimmunoassay (RIA). Endothelin-converting-enzyme activity was measured using big endothelin-1 as a substrate and thiorphan as an inhibitor of serum neutral endopeptidase. The amount of endothelin-1 generated during one hour was measured by RIA. Mean +/- SEM is given. RESULTS: In normal pregnancy endothelin-1 concentrations at 38 weeks and postpartum were increased by 30% (p < 0.01) and 50% (p < 0.001), respectively compared with the second trimester values. Endothelin-converting-enzyme activity did not change. At diagnosis endothelin-1 was higher in women with preeclampsia than in the controls at 38 weeks (0.96 +/- 0.07 vs. 0.64 +/- 0.06 pmol/L; p < 0.001). Likewise, endothelin-converting-enzyme activity was higher in the preeclampsia group (222 +/- 15 vs. 172 +/- 8 pmol ET/ml/h; p < 0.01). This difference remained at six weeks postpartum. CONCLUSION: Our findings imply enhanced ET-1 production in preeclampsia. The elevated endothelin-converting-enzyme activity postpartum may indicate an inherent endothelial dysfunction predisposing to preeclampsia or that preeclampsia may cause irreversible changes in endothelial function.

Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites.

We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries ( approximately 200 mum) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE (n = 13) and NP (n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced (P < 0.05). All women within the PE group were divided into two subgroups: with more (group 1) or less (group 2) than 50% reduction of EDHF-typed responses after 18-alpha-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H(2)O(2) and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H(2)O(2) or cytochrome P-450 epoxygenase metabolites of AA.

Urine albumin/creatinine ratio for the assessment of albuminuria in pregnancy hypertension.

BACKGROUND: An accurate method to assess albuminuria in pregnancy is mandatory to diagnose pre-eclampsia. Twenty-four-hour urine collection is still the only universally accepted method. This is, however, a cumbersome and inconvenient method. Therefore, the present study aimed at assessing the accuracy of a spot urine albumin/creatinine ratio in pregnant women with hypertension. MATERIAL AND METHODS: In 54 pregnant women with blood pressure >or=140/90 mmHg, 24-h albumin excretion and subsequent albumin/creatinine ratio on morning spot urine were analyzed in the individual patients. Altogether 75 paired samples were included. Receiver operating characteristic curves, relating different albumin/creatinine ratio cut-off values to 24-h albumin excretion >300 mg were constructed. Correlations were assessed by Spearman rank correlation tests. RESULTS: The area under the receiver operating characteristic curve was 0.985. At the optimal cut-off albumin/creatinine ratio value of 27 mg/mmol the sensitivity, specificity, positive and negative predictive value for detecting albuminuria >300 mg/24 h were: 95, 100, 100 and 86% respectively. There was a close correlation between albumin/creatinine ratio and 24-h albumin excretion values (r=0.95; p<0.001). CONCLUSIONS: It is suggested that in most cases the more cumbersome 24-h urine collection can be replaced by the more convenient albumin/creatinine ratio on spot urine.

Is fetal growth impaired after in vitro fertilization?

BACKGROUND: The objective was to study fetal growth parameters in in vitro fertilization (IVF) pregnancies and to investigate the relationship between fetal growth and maternal blood pressure. METHODS: We examined 64 women, pregnant after in vitro fertilization, with repeated ultrasound examinations measuring biparietal diameter, femur length, abdominal diameter and fetal weight at 24, 30, and 36 weeks of gestation. We calculated deviations in percent from expected values in regards to biparietal diameter, femur length, abdominal diameter, and fetal weight. Blood pressure was measured every second week. RESULTS: Biparietal diameter in the study group was significantly smaller at 24 (-3.3%, 95%CI -4.4 to -2.2) and 30 (-1.4%; 95%CI -2.5% to -0.3) weeks. Femur length differed significantly on all three occasions, at 24 (-6.3%; 95%CI -7.7 to -5.1), 30 (-6.6%; 95%CI -8.0 to -5.3), and 36 (-3.9%; 95%CI; -5.0 to -2.8) weeks. Abdominal diameter demonstrated a significant deviation at 24 weeks (-1.6%; 95%CI -2.8 to -0.4). Fetal weight did not reach significant deviations at any gestational age. There was no correlation between deviation of the individual growth parameters or estimated fetal weight and elevated blood pressure. CONCLUSION: The growth pattern of in vitro fertilization pregnancies does not seem to differ from spontaneously conceived pregnancies to any appreciable extent. In the present material, no relationship between fetal growth and maternal blood pressure could be observed. We could not show that an impaired fetal growth predates the development of hypertension.

Effects of blockade of the endothelin receptor A and inhibition of nitric oxide synthesis on uteroplacental and renal blood flow in awake pregnant rats.

OBJECTIVE: The aim of this study was to evaluate the role of the ETA receptor and nitric oxide (NO) in the regulation of uteroplacental and renal blood flow in pregnant rats. STUDY DESIGN: Regional blood flows were measured by the microsphere technique in pregnant Sprague-Dawley rats (term 23 days). Blood flow was measured before and after ETA receptor blockade (BQ-123, 1 mg/kg) at gestational day (GD) 19 or 21 (n=8 and n=9, respectively). In 2 additional groups blood flow was measured before and after NO synthase inhibition (L-NAME 2 microg/min) at GD 19 or 21 (n=10 in each group). RESULTS: BQ-123 significantly increased placental and myometrial blood flows by almost 80% and 35%, respectively, at both gestational ages. BQ-123 did not alter renal blood flow. No effect on placental or myometrial blood flow was observed after L-NAME infusion, neither at GD 19 nor GD 21. Renal blood flow decreased by nearly 35% in both groups after L-NAME. CONCLUSION: There is an important role for endogenous ET in the regulation of uteroplacental blood flow in the rat. NO contributes to a significant vasodilatation in the renal vasculature; however, NO appears not to be involved in the maintenance of uteroplacental blood flow in the awake pregnant rat.

The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women.

We studied the importance of endothelium-derived hyperpolarizing factor (EDHF) vs. nitric oxide (NO) and prostacyclin (PGI(2)) in bradykinin (BK)-induced relaxation in isolated small subcutaneous arteries from normal pregnant women. We also explored the contribution of cytochrome P-450 (CYP450) product of arachidonic acid (AA) metabolism, hydrogen peroxide (H(2)O(2)), and gap junctions that have been suggested to be involved in EDHF-mediated responses. Isolated arteries obtained from subcutaneous fat biopsies of normal pregnant women (n = 30) undergoing planned cesarean section were mounted in a wire-myography system. In norepinephrine-constricted vessels, incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in relaxation to BK. Simultaneous incubation with L-NAME and indomethacin failed to modify this response further. BK-mediated dilatation in the presence of K(+)-modified solution was decreased to similar level as obtained after incubation with L-NAME. Incubation with L-NAME abolished BK-induced responses in K(+)-modified solution. Sulfaphenazole, a specific inhibitor of CYP450 epoxygenase, and catalase (an enzyme that decomposes H(2)O(2)) did not affect the EDHF-mediated relaxation because concentration-response curves to BK were similar in arteries after incubation with L-NAME vs. L-NAME + sulfaphenazole and L-NAME + catalase. The inhibitor of gap junctions, 18 alpha-glycyrrhetinic acid, significantly reduced BK-mediated relaxation both without and with incubation with L-NAME. We found that both NO and EDHF, but not PGI(2), are involved in the endothelium-dependent dilatation to BK. BK-induced relaxation is almost equally mediated by NO and EDHF. CYP450 epoxygenase metabolites of AA or H(2)O(2) do not account for EDHF-mediated response; however, gap junctions are involved in the EDHF-mediated responses to BK in subcutaneous small arteries in normal pregnancy.

Male gender predisposes to prolongation of pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the association between fetal gender and prolonged pregnancy. STUDY DESIGN: All deliveries in Sweden between 1987 and 1996 were evaluated for participation in this study. Inclusion criteria included (1) singleton pregnancy, (2) the absence of apparent congenital or chromosomal anomalies, (3) accurate dating established by early second trimester ultrasound examination, and (4) gestational age at delivery of > or =37 weeks (ie, > or =259 days). Initially, we calculated the mean gestational age at delivery and the percentage of prolonged pregnancies by fetal gender. Subsequently, the Mantel-Haenszel chi-square analysis was used to calculate the weekly odds ratios and their corresponding 95% confidence intervals for the delivery of a male fetus beyond 37 weeks of gestation. RESULTS: The study population comprised 656,423 deliveries; 333,192 were male deliveries, and 323,231 were female deliveries (male/female ratio, 1.03). The mean gestational age at delivery was significantly higher in male fetuses (280.6 +/- 8.9 days vs 279.8 +/- 8.6 days, respectively; P <.0001). The percentage of pregnancies that delivered beyond term was significantly higher for male relative to female fetuses (26.5% vs 22.5% [P <.000001] at > or =41 weeks of gestation and 7.6% vs 5.5% [P <.000001] at > or =42 weeks of gestation, respectively). The weekly odds ratios for a delivery of a male fetus beyond term were 1.14, 1.39, and 1.50 at 41, 42, and 43 weeks, respectively. CONCLUSION: Male gender significantly predisposes to the prolongation of pregnancy to the extent that, by 43 weeks of gestation, there are 3 male deliveries for every 2 female deliveries.

Endothelial dysfunction in uterine circulation in preeclampsia: can estrogens improve it?

OBJECTIVE: The purpose of this study was to evaluate whether a 3-hour incubation with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation and alter pressure-induced basal tone in myometrial resistance arteries from women with preeclampsia and to evaluate the role of nitric oxide in the responses that were observed. STUDY DESIGN: Blood flow- and bradykinin-mediated dilatation and responses to intraluminal pressure of 60 and 80 mm Hg were compared before and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated myometrial arteries with the pressure myography technique. In separate experiments, the role of nitric oxide on 17beta-estradiol-induced responses was evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L). Endothelial morphologic condition was evaluated by scanning electron microscopy. RESULTS: Incubation with 17beta-estradiol significantly improved blood flow-mediated dilatation compared with initial blood flow-mediated response in arteries from women with preeclampsia. This effect was nitric oxide mediated, because the nitric oxide synthase inhibitor abolished the response. Arteries from women with preeclampsia demonstrated impaired bradykinin-mediated dilatation compared with that obtained in arteries from normal pregnant women. The 17beta-estradiol had no effect on bradykinin-mediated dilatation in arteries from women with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with the tone that developed at 60 mm Hg in arteries from women with preeclampsia was reduced after incubation with 17beta-estradiol. This reduction was also nitric oxide mediated. Morphologic signs of endothelial dysfunction were evident in arteries from women with preeclampsia. CONCLUSION: The 17beta-estradiol improved impaired blood flow-mediated dilatation and reduced basal tone through a nitric oxide-mediated pathway in isolated myometrial arteries from women with preeclampsia.

Cerebral perfusion pressure, and not cerebral blood flow, may be the critical determinant of intracranial injury in preeclampsia: a new hypothesis.

OBJECTIVE: The relationship between cerebral perfusion pressure (CPP) and cerebral blood flow is unclear in preeclampsia. Our objective was to clarify this issue by comparing normal pregnant women to those with mild and severe preeclampsia. STUDY DESIGN: Patients with mild (n = 72) and severe (n = 120) preeclampsia underwent transcranial Doppler (TCD) imaging of the maternal middle cerebral artery (MCA). At the same time, blood pressure was taken with a Dinamap monitor (Dinamap; Criticon Inc, Tampa, Fla). CPP, resistance area product (RAP), and the cerebral flow index (CFI) were calculated by standard formulas. Data were plotted on normative curves for pregnancy (5% and 95%) and compared by chi(2) and Mann-Whitney U tests. RESULTS: CFI is usually normal in both severe (75%) and mild (72%) cases. If CFI is abnormal in severe cases, it may be either increased (14%) or decreased (10%), although in mild cases almost all abnormal CFI (25%) is lower than normal. In those cases with low or normal CFI, severe cases are associated with a significantly higher CPP, RAP, and MAP than mild cases (P <.05), although the CFI is not significantly different. A significant proportion of severe cases have high CPP (52%), whereas in mild cases the CPP is almost always normal (87%). Overall, in severe cases the RAP is abnormally high, although it is within the normal range in mild cases. CONCLUSIONS: One of the fundamental differences between mild and severe cases relates to the degree of cerebral perfusion pressure that the MCAs are subjected to. Because most preeclamptic women, regardless of degree of severity, have a normal CFI, it appears that autoregulation is generally intact. Because women with severe cases are more prone to cerebral catastrophe than those with mild preeclampsia, uncontrolled CPP may cause barotrauma and vessel damage, leading to hypertensive encephalopathy and overperfusion injury. Therapeutic strategies that ensure reduction of the CPP with maintenance of the CFI seem most likely to prevent the cerebral injuries (overperfusion or underperfusion) that cause seizures or death in women with preeclampsia.

Vascular endothelial growth factor induced functional and morphologic signs of endothelial dysfunction in isolated arteries from normal pregnant women.

OBJECTIVE: The purpose of this study was to determine the effects of vascular endothelial growth factor on basal tone, endothelium-dependent dilatation, permeability, and morphologic features of endothelium in isolated arteries from normal pregnant women. We hypothesized that vascular endothelial growth factor might induce signs of endothelial dysfunction. STUDY DESIGN: Arteries (approximately 200 microm) were dissected from subcutaneous fat biopsy specimens that were obtained at cesarean delivery and mounted on a pressure arteriograph. Changes in basal tone, dilatation to bradykinin (1 nmol/L to 3 micromol/L) before, during, and after 3 hours of incubation with vascular endothelial growth factor (0.5 or 1 nmol/L), vascular endothelial growth factor (0.5 nmol/L) plus bosentan (a nonselective endothelin receptor A and B antagonist, 1 micromol/L), or vehicle were compared. Scanning electron microscopy was applied for endothelial morphologic features. Permeability to Evans blue dye was evaluated in arteries after incubation with vascular endothelial growth factor, vascular endothelial growth factor plus angiopoietin-1, or vehicle, and in arteries that were obtained from women with preeclampsia. RESULTS: Basal tone was higher after 60 minutes of incubation with vascular endothelial growth factor (0.5 nmol/L) compared with vehicle (29% +/- 5% [n = 10] vs 10% +/- 4% [n = 7], P =.006). Combination of vascular endothelial growth factor with bosentan failed to increase the tone (n = 4). Bradykinin-mediated dilatation was impaired in arteries that were incubated with vascular endothelial growth factor 0.5 nmol/L (max dilatation: 287% +/- 16% vs 160% +/- 23% [n = 10], P =.0001) or vascular endothelial growth factor 1 nmol/L (max dilatation: 207% +/- 21% vs 88% +/- 4% [n = 3], P =.003). Bradykinin-mediated dilatation was similar after incubation with vehicle (n = 7) or the combination of vascular endothelial growth factor plus bosentan (n = 4). Evans blue dye staining was higher after incubation with vascular endothelial growth factor but was reversed by the addition of angiopoietin-1. Scanning electron microscopy demonstrated the development of intercellular gaps. CONCLUSION: Vascular endothelial growth factor impaired bradykinin-mediated dilatation and enhanced basal tone and permeability. This might indicate a potential role for vascular endothelial growth factor in the development of endothelial dysfunction in pregnancy. Angiopoietin-1 inhibited the vascular endothelial growth factor-induced vascular leakage, which may have therapeutic implications in preeclampsia.