Spontaneous heterotopic pregnancy, simultaneous ovarian, and intrauterine: a case report.

Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extrauterine pregnancies occur at the same time. The occurrence of an ovarian heterotopic pregnancy is a singular event as it comprises only 2.3% of all heterotopic pregnancies, extremely rare among women who conceive naturally. A case of a 28-year old patient was treated for spontaneously conceived heterotopic pregnancy. The patient was admitted to our center with lower abdominal pain and amenorrhoea. A transvaginal ultrasound scan showed an ovarian and an intrauterine heterotopic pregnancy. This was managed laparoscopically. Considering spontaneous pregnancies, every physician treating women of reproductive age should be aware of the possibility of heterotopic pregnancy. It can occur in the absence of any predisposing risk factors; only with an early diagnosis and treatment the intrauterine pregnancies will reach viability with a great chance of a favorable obstetric outcome.

Cardiovascular risk factors in healthy women with previous small for gestational age infants.

AIM: To investigate whether healthy women with a previous pregnancy complicated by a small for gestational age (SGA) infant have normal endothelial function, carbohydrate and lipid metabolism, and normal inflammation parameters. MATERIAL AND METHODS: Brachial artery flow-mediated dilatation (FMD, endothelium-dependent) was measured in 16 subjects with previous SGA, and in 15 controls (CTR) with previous normal pregnancies. Lipid panel, glucose, insulin, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (s-ICAM), soluble vascular (s-VCAM-1) adhesion molecule-1 (s-VCAM-1), and androgens were also measured. RESULTS: FMD was reduced in women with previous SGA compared to controls (P < 0.0001). SGA women showed increased insulin resistance (P < 0.0001), s-ICAM-1 (P = 0.008), TNF-alpha (P = 0.02), testosterone (P = 0.03), and diastolic blood pressure (P = 0.01) than CTR. CONCLUSION: Endothelial dysfunction, reduced insulin sensitivity and subclinical inflammation are present in otherwise healthy women with previous SGA. These abnormalities show that the presence of a SGA infant in the obstetric history should be considered as a risk factor for cardiovascular disease later in life.

Longitudinal changes of adiponectin, carbohydrate and lipid metabolism in pregnant women at high risk for gestational diabetes.

To evaluate, in pregnant women at high risk for gestational diabetes (GDM), the longitudinal changes of adiponectin, carbohydrate and lipid metabolism, and to assess their independent value as risk factors for the development of GDM. Fifty women at beginning of pregnancy were studied. Adiponectin, insulin sensitivity (homeostasis model assessment, HOMA) and lipid panel were measured at 1st, 2nd and 3rd trimesters of pregnancy. Twelve patients developed GDM. In both groups, GDM and normal glucose tolerance (NGT), adiponectin decreased from 1st to 2nd and 3rd trimesters by about 5 and 20% (GDM, p < 0.05), and of about 17 and 25% in NGT (p < 0.05), respectively. Values observed in NGT were similar to those of GDM (F = 9.401; p = 0.238). The Cox regression model identified as the strongest independent risk factor for GDM HOMA over 1.24 (RR = 14.12) at 1st trimester, fasting glycaemia over 87 mg/dl (RR = 42.68) triglycerides over 158 mg/dl (RR = 5.87) and body mass index (BMI) over 27 kg/m(2) (RR = 4.38) at 2nd trimester. Adiponectin in high-risk women is characterised by a constant reduction throughout gestation, irrespective of the development of GDM. HOMA, fasting glycaemia, triglycerides and BMI, but not adiponectin are independent predictors of GDM.

Vaginal microbial flora and outcome of pregnancy.

BACKGROUND: The vaginal microflora of a healthy asymptomatic woman consists of a wide variety of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. The activity of Lactobacillus is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal flora. Increasing evidence associates abnormalities in vaginal flora during pregnancy with preterm labor and delivery with potential neonatal sequelae due to prematurity and poor perinatal outcome. Although this phenomenon is relatively common, even in populations of women at low risk for adverse events, the pathogenetic mechanism that leads to complications in pregnancy is still poorly understood. OBJECTIVE: This review summarizes the current knowledge and uncertainties in defining alterations of vaginal flora in non-pregnant adult women and during pregnancy, and, in particular, investigates the issue of bacterial vaginosis and aerobic vaginitis. This could help specialists to identify women amenable to treatment during pregnancy leading to the possibility to reduce the preterm birth rate, preterm premature rupture of membranes, chorioamnionitis, neonatal, puerperal and maternal-fetal infectious diseases. CONCLUSIONS: Vaginal ecosystem study with the detection of pathogens is a key instrument in the prevention of preterm delivery, pPROM, chorioamnionitis, neonatal, puerperal and maternal-fetal infections.

Cardiovascular risk factors in healthy women with previous gestational hypertension.

CONTEXT: Epidemiological studies indicate that gestational hypertension (Gh) during pregnancy is associated with increased risk of cardiovascular disease in later life. However, it is unclear whether particular metabolic and hemodynamic characteristics are related to this risk. OBJECTIVE: The objective of this study was to investigate endothelial function and carbohydrate and lipid metabolism in healthy, normotensive women with previous pregnancy complicated by Gh. DESIGN, SETTING, AND PARTICIPANTS: Brachial artery flow-mediated dilatation (FMD; endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured in 15 subjects with previous Gh and in 15 controls with previous normal pregnancies. Lipid panel, glucose, insulin, homocysteine, and androgens were also measured. RESULTS: FMD was significantly reduced in women with previous Gh compared with controls (P < 0.0001), whereas nitroglycerin-induced dilatation was comparable in both groups. Gh women showed increased fasting insulin (P = 0.011), insulin resistance measured by homeostasis model assessment (P = 0.018), free fatty acids (P = 0.0018), and testosterone (P = 0.0012) and decreased high-density lipoprotein cholesterol (P = 0.0017) compared with controls. Across all subjects, FMD showed a strong independent negative correlation with testosterone and homeostasis model assessment and a positive correlation with high-density lipoprotein cholesterol (r = -0.60, P = 0.0003; r = -0.43, P = 0.016; and r = 0.58, P = 0.0005, respectively). CONCLUSIONS: Endothelial dysfunction and early alteration of carbohydrate and lipid metabolism are present in otherwise healthy women with previous Gh. These abnormalities along with a relative hyperandrogenism could explain, at least in part, the increased risk for cardiovascular disease in later life in these women.

Maternal mortality in Italy, 1980-1996.

OBJECTIVE: To establish the extent of maternal mortality in Italy in between 1980 and 1996 in order to compare it with the international data. STUDY DESIGN: We conducted a retrospective study on maternal deaths in Italy from 1980 to 1996. Data have been collected by Italian Statistic Institute (ISTAT). We calculated both the maternal mortality rates and the percentages of causes of death in the whole period, according to WHO definitions. RESULTS: The data confirmed the trends of the previous decade: maternal mortality rates have decreased from 13.25 (1980) to 3.78 (1996) for 100000 live births. Haemorrhage and hypertension have been the main causes of maternal death, while pulmonary embolism has had a minor affect on maternal mortality rates compared to other countries, particularly in Europe. CONCLUSION: Italian data appear reassuring and encourage further investigations on detailed welfare problems.

Endothelial function in post-menopausal women: effect of folic acid supplementation.

BACKGROUND: Higher than normal homocysteine levels are associated with an increased incidence of adverse cardiovascular events in post-menopausal women, perhaps via hyperhomocysteinaemia-induced vascular endothelial damage. Because folic acid supplementation reduces homocysteine levels, we attempted to evaluate whether folic acid supplementation may affect endothelial function in post-menopausal women. METHODS: Brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerin-induced dilatation (endothelium-independent) before and after a methionine load were analysed in 15 healthy post-menopausal women. Plasma levels of folate, homocysteine, glucose, insulin and lipids were measured, as was blood pressure. All studies were repeated after 1 month supplementation with 7.5 mg/day of folic acid. RESULTS: After folate, endothelial function rose 37% over pre-folic acid supplementation value (P < 0.001), and flow-mediated dilation before folic acid was reduced by 62% subsequent to methionine loading (P < 0.0001); this reduction was still present after folic acid, but was only 19% (P < 0.001). Nitroglycerin-induced dilatation did not change in response to methionine loading before or after folic acid supplementation. Among the other cardiovascular risk factors studied, only high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol showed significant changes after folic acid supplementation, with a 6% increase (P < 0.03) and a 9% decrease (P < 0.03) respectively. CONCLUSIONS: Although preliminary, these results indicate that folic acid supplementation may improve endothelial function and lipid profile in post-menopausal women, thus contributing to reduce their cardiovascular risk.

Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome.

Obese women with polycystic ovary syndrome (PCOS) exhibit impaired endothelial function, which is strongly and directly correlated with both testosterone levels and insulin resistance. Endothelial dysfunction is considered a potent risk factor for macrovascular disease. Because troglitazone (Tgz) improves both hormonal profiles and insulin sensitivity, we tested whether Tgz treatment ameliorates endothelial function in these patients. We studied leg blood flow (LBF) responses to graded intrafemoral artery infusion of the endothelium-dependent vasodilator methacholine chloride (MCh) and to a 4-h hyperinsulinemic euglycemic clamp (120 mU/m(2) x min) in 10 PCOS, before and after 3 months treatment with Tgz (600 mg/d). A group of 13 obese women (OBW) matched for age, weight, body fat (>40% in both groups), blood pressure, and total cholesterol served as controls. PCOS patients exhibited elevated free testosterone (fT) and triglycerides (TG) and lower high density lipoprotein cholesterol levels compared with OBW [14.0 +/- 1.0 vs. 3.7 +/- 0.6 pmol/liter (P < 0.0001), 1.60 +/- 0.28 vs. 0.94 +/- 0.09 mmol/liter (P < 0.02), and 0.91 +/- 0.04 vs. 1.1 +/- 0.04 mmol/liter (P < 0.005), respectively]. Tgz treatment reduced fT levels, but did not improve the TG and high density lipoprotein profile [to 9.7 +/- 2.8 pmol/liter (P < 0.007), 1.49 +/- 0.34 mmol/liter (P = NS), and 0.93 +/- 0.07 mmol/liter (P = NS), respectively]. Basal LBF was unchanged after Tgz. In PCOS compared with OBW, insulin stimulated glucose disposal (52.7 +/- 6.6 vs. 85.5 +/- 4.4 micromol/kg fat-free mass x min; P < 0.0005) and vasodilation (increase in LBF, 22 +/- 14% vs. 59 +/- 15%; P < 0.05) were significantly improved after Tgz treatment to 68.8 +/- 7.2 micromol/kg fat-free mass x min (P < 0.0001) and 101 +/- 48% (P < 0.03), respectively. The increase in LBF in response to MCh in PCOS was markedly more pronounced after treatment (P < 0.01, by ANOVA) and was similar to that observed in OBW. Before Tgz treatment, maximal LBF increments in response to MCh were 130 +/- 25% and 233 +/- 29% in PCOS and OBW, respectively (P < 0.01). After Tgz treatment, PCOS values improved, achieving increments similar to those in OBW (245 +/- 45%; P < 0.04). Tgz treatment in PCOS improves both hormonal and metabolic features. These modifications are associated with improvement of endothelial function, suggesting that Tgz could be a useful tool to reduce the risk of macrovascular disease in women with PCOS and perhaps in other insulin-resistant syndromes.

Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity.

BACKGROUND: Amylin is a peptide co-secreted with insulin by pancreatic beta-cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2) has been suggested by in vitro and in vivo studies indicating an effect of amylin to cause insulin resistance and/or inhibit insulin secretion. METHODS: We have determined the effect of endogenous amylin on insulin secretion and insulin action in humans by performing 4-h hyperglycemic clamps during infusion of placebo or a specific amylin receptor antagonist (ARA) in paired, double-blinded, crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and ten obesity-matched DM2 subjects. RESULTS: Infusion of ARA alone had no effect on basal insulin, glucose or glucose turnover in any group. Under combined hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in insulin levels [AUC 33,565+/-3556 (placebo) to 44,562+/-1379 (ARA) pmol/l/min, p<0.01]. The concomitant increase in glucose disposal rate (GDR) was proportionate, indicating no change in insulin sensitivity (ISI 27.7+/-2.7 vs 27.3+/-2.1, p=NS). In obese subjects, basal insulin and the rise in insulin during the clamp were greater (AUC I 44% increase from 82,054+/-15 407 to 117,922+/-27,085, p<0.01), and also accompanied by a proportionate rise in GDR reflecting an unchanged insulin sensitivity (ISI 12.1+/-2.9 vs 10.8+/-3.0, p=NS). In lean and obese subjects, the C-peptide response to hyperglycemia was also augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was observed in diabetic subjects. CONCLUSIONS: The present data are consistent with an effect of endogenous amylin on the beta-cell to modulate and/or restrain insulin secretion, and indicate that endogenous amylin does not affect insulin action. These observations provide the first human evidence that amylin plays a role in the modulation of insulin secretion.

Abnormal carbohydrate metabolism during pregnancy : association with endothelial dysfunction.

OBJECTIVE: To evaluate whether abnormal endothelial function, a common finding in premenopausal women with type 2 diabetes, is present in early states of diabetes during pregnancy, such as impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Brachial artery flow-mediated dilatation (FMD) (endothelium-dependent) and nitrate-induced dilatation (NID) (endothelium-independent) were measured in 23 pregnant subjects with carbohydrate abnormalities (10 IGT, 13 GDM) and in 15 pregnant control subjects during the third trimester of gestation. High-resolution vascular ultrasonography was used to perform these investigations. A fasting lipid panel was obtained, and glucose and insulin values in response to a 100-g oral glucose load were also measured. RESULTS: FMD was significantly reduced in both groups of women with abnormal carbohydrate metabolism compared with control subjects (7.6 +/- 1.1% in the IGT group and 4.1 +/- 0.9% in the GDM group vs. 10.9 +/- 1.1% in control subjects, P < 0.04 and P < 0.0001, respectively). Significant difference in FMD was also observed between IGT and GDM groups (P < 0.04). NID was comparable in the three groups. Among all subjects, FMD showed a strong independent negative correlation with glycemic area (r=-0.60, P < 0.0001). CONCLUSIONS: Endothelial dysfunction, an early marker of macrovascular disease, is present in pregnancies complicated by IGT and GDM. This alteration, which seems to be directly related to glycemic levels, could explain, at least in part, the increased risk for concurrent hypertensive disorders during pregnancy in these women.