Adhesive bowel obstruction: Incidence, recurrence and 30-day mortality in Danish women 1984-2013 - A national cohort study.

BACKGROUND: Adhesive bowel obstruction is a serious complication to abdominal surgery. It is unknown whether incidence and mortality rates have changed as new surgical procedures were introduced. METHODS: In a nationwide cohort of Danish women from 1984 to 2013, incidence of adhesive bowel obstruction and 30 days mortality were presented as standardized rates. Impact of treatment was analyzed by Cox regression and recurrent disease characterized by Kaplan Meyer estimates. RESULTS: Incidence of adhesive bowel obstruction increased 50% among women with no prior abdominal surgery. These women had 3-5 times lower incidence than those with a surgical record. 30-day mortality rate was 13%, highest in patients treated non-operatively. The mortality declined in recent years. Recurrent disease had lower mortality rates compared to the first episode. CONCLUSIONS: The incidence of adhesive bowel obstruction increased during the last 30 years, mortality after the first episode is high, while recurrent disease shows declining mortality rates.

Determinants of low risk of asthma exacerbation during pregnancy.

BACKGROUND: Assessment of asthma control every 4-6 weeks during pregnancy is recommended to reduce risk of exacerbation, and by that improve outcome. OBJECTIVE: To identify determinants of pregnancies with low risk of asthma exacerbation. METHODS: All pregnant women enrolled into the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital since 2007. Assessment of asthma control, adjustment of treatment, spirometry and measurement of exhaled nitric oxide (FE NO) were performed, and baseline characteristics and exacerbation history were collected at enrolment. Determinants of low-exacerbation risk pregnancies were identified by logistic regression analysis (stepwise backward elimination). RESULTS: In 1283 pregnancies, 107 exacerbations were observed. Multiple regression analysis revealed that no history of pre-pregnancy exacerbations (P < .001), no prescribed controller medication (P < .001), and clinically stable asthma at enrolment (P = .002) were significantly associated with low risk of exacerbation during pregnancy; with these combined characteristics, only two of 385 pregnancies were complicated by an exacerbation (OR 0.04, 95% CI 0.01-0.18, P < .001). CONCLUSION AND CLINICAL RELEVANCE: Clinically stable asthma at enrolment, together with no history of previous exacerbations and no prescribed controller medication, is a determinant of low risk of an asthma exacerbation during pregnancy, which may guide clinicians in individualizing surveillance of asthma during pregnancy.

Impact of lifestyle intervention for obese women during pregnancy on maternal metabolic and inflammatory markers.

BACKGROUND: Offspring of obese mothers have increased risk of developing obesity and related short- and long-term disease. The cause is multifactorial and may partly be explained by the unfavorable intrauterine environment. Intervention during pregnancy leading to a healthier lifestyle among obese may alter this. OBJECTIVE: To assess the effect of lifestyle intervention on markers of maternal metabolism and inflammation in 'the TOP (Treatment of Obese Pregnant Women) study', a randomized controlled trial. METHODS: In the TOP-study 425 participants with body mass index ⩾30 kg/m2 were randomized to intervention with dietary advices and physical activity assessed by pedometer (PA+D), physical activity assessed by pedometer (PA) or control (C). Of 389 participants completing the study 376 had available blood samples. Serum was analyzed for insulin, c-peptide, lipid profile, leptin, high-sensitivity CRP (hsCRP) and Soluble urokinase Plasminogen Activator Receptor (suPAR), in week 18-20 and 28-30, and simultaneously a 2-h oral glucose-tolerance-test was performed. Diet was assessed in gestational week 11-14 and 36-37 using a validated 360-item Food Frequency Questionnaire. RESULTS: Median levels of hsCRP in gestational week 28-30 were lower in each of the intervention groups (8.3 mg/l in PA+D group, P=0.03; and 8.8 mg/l in PA group, P=0.02) versus the control group (11.5 mg/l). Obtaining 11 000 steps per day as aimed for resulted in a 21% lower hsCRP compared to non-compliant women. Women reporting high carbohydrate intake had around 30% higher hsCRP concentrations in late gestation than women reporting the lowest intake. There were no differences in lipid profile or any of the metabolic markers in gestational week 28-30 when comparing the intervention and control groups. CONCLUSIONS: Lifestyle intervention in obese women can reduce hsCRP representing a marker of inflammation during pregnancy. The effect may partly be mediated by more physical activity and partly by changes in intake of carbohydrates and the glycaemic load.

Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols.

STUDY QUESTION: Are cumulative live birth rates (CLBRs) similar in GnRH-antagonist and GnRH-agonist protocols for the first ART cycle including all subsequent frozen-thaw cycles from the same oocyte retrieval? SUMMARY ANSWER: The chances of at least one live birth following utilization of all fresh and frozen embryos after the first ART cycle are similar in GnRH-antagonist and GnRH-agonist protocols. WHAT IS KNOWN ALREADY: Reproductive outcomes of ART treatment are traditionally reported as pregnancies per cycle or per embryo transfer. However, the primary concern is the overall chance of a live birth. After the first ART cycle with fresh embryo transfer, we found live birth rates (LBRs) of 22.8% and 23.8% (P = 0.70) for the GnRH-antagonist and GnRH-agonist protocols, respectively. But with CLBRs including both fresh and frozen embryos from the first oocyte retrieval, chances of at least one live birth increases. There are no previous randomized controlled trials (RCTs) comparing CLBRs in GnRH-antagonist versus GnRH-agonist protocols. Previous studies on CLBR are either retrospective cohort studies including multiple fresh cycles or RCTs comparing single embryo transfer (SET) with double embryo transfer (DET). STUDY DESIGN, SIZE, DURATION: CLBR was a secondary outcome in a Phase IV, dual-center, open-label, RCT including 1050 women allocated to a short GnRH-antagonist or a long GnRH-agonist protocol in a 1:1 ratio over a 5-year period using a web-based concealed randomization code. The minimum follow-up time from the first IVF cycle was 2 years. The aim was to compare CLBR between the two groups following utilization of all fresh and frozen embryos from the first ART cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women referred for their first ART cycle at two public fertility clinics, <40 years of age were approached. A total of 1050 subjects were allocated to treatment and 1023 women started standardized ART protocols with recombinant human follitropin-ß (rFSH) stimulation. Day-2 SET was planned and additional embryos were frozen and used in subsequent frozen-thawed cycles. All pregnancies generated from oocyte retrieval during the first IVF cycle including fresh and frozen-thaw cycles were registered. Ongoing pregnancy was determined by ultrasonography at gestational week 7-9 and live birth was irrespective of the duration of gestation. CLBR was defined as at least one live birth per allocated woman after fresh and frozen cycles. Subjects were censored out after the first live birth. Cox proportional hazard model was used to evaluate the relative prognostic significance of female age, BMI, the number of retrieved oocytes and the diagnosis of infertility in relation to the CLBR. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar and equal proportions of patients continued with frozen-thaw (frozen embryo transfer, FET) cycles after their fresh ART cycle in the GnRH-antagonist and GnRH-agonist arms. When combining all fresh and frozen-thaw embryo transfers from first oocyte retrieval with a minimum of 2-year follow-up, the CLBR was 34.1% (182/534) in the GnRH-antagonist group versus 31.2% (161/516) in the GnRH-agonist group (odds ratio (OR):1.14; 95% CI: 0.88-1.48, P = 0.32). Mean time to the first live birth was 11.0 months in the GnRH-antagonist group compared to 11.5 months in the GnRH-agonist group (P < 0.01). The total number of deliveries from all FET cycles where embryos were thawed were higher in the antagonist group 64/330 (19.4%) compared to the agonist group 43/355 (12.1%) ((OR): 1.74; 95% CI: 1.14-2.66, P = 0.01). The evaluation of prognostic factors showed that more retrieved oocytes were associated with a significantly higher CLBR in both treatment groups. For the subgroup of obese women (BMI >30 kg/m2), the CLBR was significantly higher in the GnRH-antagonist group (P = 0.02). LIMITATIONS, REASONS FOR CAUTION: The duration of the trial is a possible limitation with introduction of new methods as 'Freeze all' and 'GnRH-agonist triggering', but as these treatments were used in only few women, a systematic bias is not likely. Blastocyst culture of surplus embryos for freezing was introduced to both groups simultaneously, thereby minimizing the risk of bias. Furthermore, with a minimum of 2-year follow-up, a minority (<1%) still had cryopreserved embryos and no live birth at the end of the trial. The post hoc prognostic covariate analyses with multiple strata should be interpreted with caution. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS: With the improvement of embryo culture, freezing and thawing methods as well as a strategy of elective SET, CLBR until first live birth provides an all-inclusive success rate for ART. When comparing GnRH-antagonist and GnRH-agonist protocols, we find similar CLBRs, despite more oocytes being retrieved in the GnRH-agonist protocol. STUDY FUNDING/COMPETING INTERESTS: An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. TRIAL REGISTRATION DATE: 18 September 2008. DATE OF FIRST PATIENT'S ENROLLMENT: 14 January 2009.

Are Danish doctors comfortable teaching in English?

BACKGROUND: From 2012-2015, the Departments of Obstetrics and Gynecology and of Pediatrics at the University of Copenhagen conducted a project, "Internationalization at Home ", offering clinical teaching in English. The project allowed international students to work with Danish speaking students in a clinical setting. Using semi-quantitative questionnaires to 89 clinicians about use of English and need for training, this paper considers if Danish clinical doctors are prepared to teach in English. RESULTS: The majority self-assessed their English proficiency between seven and eight on a 10 unit visual analogue scale, with 10 equivalent to working in Danish, while 15 % rated five or less. However, one-fourth found teaching and writing in English to be twice as difficult than in Danish, and 12 % rated all teaching tasks in English at four or less compared to Danish. The self-assessed need for additional English skills was perceived low. CONCLUSION: Teaching in English was rated as 30 % more difficult than in Danish, and a significant subgroup of doctors had difficulties in all forms of communication in English, resulting in challenges when introducing international students in non-native English speaking medical departments.

Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles.

STUDY QUESTION: Is the risk of severe ovarian hyperstimulation syndrome (OHSS) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age?. SUMMARY ANSWER: There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH antagonist protocol. WHAT IS KNOWN ALREADY?: In the most recent Cochrane review, the GnRH antagonist protocol was associated with a similar live birth rate (LBR), a similar on-going pregnancy rate (OPR), and a lower incidence of OHSS (odds ratio (OR) = 0.43 95% confidence interval (CI): 0.33-0.57) compared with the traditional GnRH agonist protocol. Previous trials comparing the two protocols mainly included selected patient populations, a limited number of patients and the applied OHSS criteria differed, making direct comparisons difficult. In two recent large meta-analyses, no significant differences in LBR (OR = 0.86; 95% CI: 0.72-1.02) or in the incidence of severe OHSS were reported, while others found a lower LBR (OR = 0.82; 95% CI: 0.68-0.97) and a reduced risk of severe OHSS using the GnRH antagonist protocol (OR = 0.60; 95% CI: 0.40-0.88). STUDY DESIGN, SIZE, DURATION: Phase IV, dual-centre, open-label, RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed randomization code. This is a superiority study designed to detect a difference in severe OHSS, the primary outcome, between the two groups with a power of 80% and stratified for age, assisted reproductive technology (ART) clinic and planned fertilization procedure (IVF/ICSI). The secondary aims were to compare rates of mild and moderate OHSS, positive plasma (p)-hCG, on-going pregnancy and live birth between the two arms. None of the women had undergone previous ART treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: All infertile women referred for their first IVF/ICSI at two public fertility clinics, less than 40 years of age and with no uterine malformations were asked to participate. A total of 1099 subjects were randomized, including women with poor ovarian reserve, polycystic ovary syndrome and irregular cycles. A total of 49 women withdrew their consent, thus 1050 subjects were allocated to the GnRH antagonist (n = 534) and agonist protocol (n = 516), respectively. In total 1023 women started recombinant human follitropin-ß (rFSH) stimulation, 528 in the GnRH antagonist group and 495 in the GnRH agonist group. All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or >36 years, with the option to adjust dose at stimulation day 6. Clinical OHSS parameters were collected at oocyte retrieval, and Days 3 and 14 post-transfer. On-going pregnancy was determined by transvaginal ultrasonography at gestational weeks 7-9. In the intention-to-treat (ITT) analysis for reproductive outcomes, 1050 subjects were included. For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of severe OHSS [5.1% (27/528) versus 8.9% (44/495) (difference in proportion percentage point (Δpp) = -3.8pp; 95% CI: -7.1 to -0.4; P = 0.02)] and moderate OHSS [10.2% (54/528) versus 15.6% (77/495) (Δpp = -5.3pp; 95% CI: -9.6 to -1.0; P = 0.01) ] was significantly lower in the GnRH antagonist group compared with the agonist group, respectively. In the GnRH antagonist and agonist group, respectively, 4.7% (25/528) versus 8.5% (42/495) women were seen by a physician due to OHSS (P = 0.01), and 1.7% (9/528) versus 3.6% (18/495) were admitted to hospital due to OHSS (P = 0.06). No women had ascites-puncture in the GnRH antagonist group versus 2.0% (10/495) in the GnRH agonist group (P < 0.01). LBRs were 22.8% (122/534) versus 23.8% (123/516) (Δpp = -1.0pp; 95% CI: -6.3 to 4.3; P = 0.70) and OPRs were 24.9% (133/528) versus 26.2% (135/516) (Δpp = -1.3pp; 95% CI: -6.7 to 4.2; P = 0.64) per randomized subject in the GnRH antagonist versus agonist group, with a mean number of 1.1 versus 1.2 embryos transferred in the two groups. Pregnancy rates (PR) per randomized subject, per started gonadotrophin stimulation and per embryo transfer were all similar in the two groups. LIMITATIONS, REASONS FOR CAUTION: A possible limitation is the duration of the trial, with new methods, such as 'freeze all' and 'GnRH agonist triggering', being developed during the trial, the new methods were sought avoided, however a total number of 32 women had 'freeze all' and 'GnRH agonist triggering' was performed in three cases. Ultrasonic measurements were performed by different physicians and inter-observer bias may be present. Measures of anti-Mullerian hormone and antral follicle count, to estimate ovarian reserve and thus predict risk of OHSS, were not performed. Finally, the physicians were not blinded to GnRH treatment group after randomization. WIDER IMPLICATIONS OF THE FINDINGS: The short GnRH antagonist protocol should be the protocol of choice for patients undergoing their first ART cycle in females <40 years of age including both low and high responders when an age-dependent initially fixed gonadotrophin dose is used, as an increased risk of severe OHSS and the associated complications is seen in the long GnRH agonist group and as PRs and LBRs are similar in the two groups. Patients at risk of OHSS particularly benefit from the short GnRH antagonist treatment as GnRH agonist triggering can be used. STUDY FUNDING/COMPETING INTERESTS: An unrestricted research grant is funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER: EudraCT #: 2008-005452-24. ClinicalTrial.gov: NCT00756028. Trial registration date: 18 September 2008. Date of first patient's enrolment: 14 January 2009.

Reproducibility of 3-Dimensional Ultrasound Measurements of Placental Volume at Gestational Ages 11 - 14 Weeks.

OBJECTIVE: To evaluate the reproducibility of placental volume using three-dimensional ultrasound. METHODS: The VOCAL (Virtual Organ Computer-aided AnaLysis) technique involves rotating an image of an object along an established axis using predefined angles. This provides a number of sections to measure manually, resulting in the object being displayed with an estimated placental volume. Four predefined angles 30°, 15°, 9°, and 6°, creating 6, 12, 20 and 30 sections, respectively. Measurements of placenta volumes in 21 women with singleton pregnancies were performed at gestational age 11-14 weeks by a single consultant in Foetal Medicine and later processed by two observers. The intraobserver reproducibility between all four angles was calculated as the mean Coefficient of Variation. Interobserver reproducibility was assessed by Interclass Correlation Coefficient (ICC), Limits of Agreement (LOA) and illustrated in Bland-Altman plots. RESULTS: There was no significant difference in intraobserver variability between the four angles, p = 0.19, but a trend towards a lower coefficient of variation with the smallest angle was observed. A high intraobserver reproducibility was found using the 6° angle (ICC = 0.918 (0.812 - 0.966) and 0.983 (0.960- 0.993), LOA = [-22.9- 22.5] and [-14.3 - 12.1]), but interobserver reproducibility showed a wide range of agreement (LOA = [-50.5- 34.8]), particularly in cases with u-shaped placentas. CONCLUSION: The low interobserver reproducibility of VOCAL measurements of placentae requires significant differences between normal and abnormal cases if the technique should be implemented for clinical use.

Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score.

AIM: This study investigated whether newborn body composition is influenced by prepregnancy obesity and gestational weight gain (GWG) and explored any associations between body composition and birthweight standard score (z-score), categorised by size for gestational age. METHODS: We recruited 231 obese and 80 normal weight mothers and their newborn infants and assessed the babies' body composition using dual-energy X-ray absorptiometry. RESULTS: The total and abdominal fat masses of infants born to mother who were obese before pregnancy were 135 g (p < 0.001) and 18 g (p < 0.001) higher than the offspring of normal weight mothers. The infants' fat mass increased by 11 g (p < 0.001) for every kilogram of GWG. There were no associations between prepregnancy obesity and fat-free mass. The fat percentage was significantly higher in infants who were large for gestational age (15.3%) than small for gestational age (5.2%) and appropriate for gestational age (9.8%) (p < 0.001). Lower birthweight z-score was associated with a higher proportion of abdominal fat mass (p = 0.009). CONCLUSION: Infants born to obese mothers had higher fat mass at birth, with abdominal fat accumulation. Low birthweight was associated with a lower crude abdominal fat mass, but a higher proportion of total fat mass placed abdominally.

Increased risk of preterm delivery and pre-eclampsia in women with polycystic ovary syndrome and hyperandrogenaemia.

OBJECTIVE: To study the risk of adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), and to examine the role of hyperandrogenaemia. DESIGN: Cohort study. SETTING: Singleton pregnancies in women with PCOS identified at a private fertility clinic during 1997-2010 and a background population including all singleton deliveries at Hvidovre Hospital, Denmark, in 2005. POPULATION: A cohort of 459 women with PCOS and a background population of 5409 women. METHODS: Obstetric outcomes were extracted from national Danish registries and odds ratios (ORs) were calculated by multiple logistic regression analysis, adjusting for age, parity, and body mass index. MAIN OUTCOME MEASURES: Risk of pre-eclampsia, preterm delivery, and small for gestational age offspring in the entire PCOS population and in a subsample with hyperandrogenaemia. RESULTS: Women with PCOS had an increased risk of preterm delivery <37 weeks of gestation (OR 2.28; 95% confidence interval, 95% CI, 1.51-3.45; P < 0.0001). The elevated risk was confined to hyperandrogenic women with PCOS: preterm delivery before 37 weeks of gestation (OR 2.78; 95% CI 1.62-4.77; P < 0.0001), and was not seen in normoandrogenic women with PCOS (OR 1.35; 95% CI 0.54-3.39; P = 0.52). The overall risk of pre-eclampsia was not elevated (OR 1.69; 95% CI 0.99-2.88; P = 0.05) compared with the background population, but was significantly increased in the hyperandrogenic subsample (OR 2.41; 95% CI 1.26-4.58; P < 0.001). The risk of small for gestational age offspring was similar in all groups. CONCLUSION: Women with PCOS had an increased risk of preterm delivery compared with the background population. The increased risk was confined to hyperandrogenic women with PCOS who had a two-fold increased risk of preterm delivery and pre-eclampsia.

Physical activity during pregnancy in normal-weight and obese women: compliance using pedometer assessment.

The objectives of this prospective study were to compare physical activity in 70 normal-weight women with a body mass index (BMI) 20-25 kg/m(2), and 70 obese with a BMI ≥ 30 kg/m(2), before and during pregnancy, and to compare compliance using the pedometer. Physical activity before pregnancy was assessed by questionnaires and during pregnancy by a pedometer worn on 7 consecutive days every 4th week. Obese women were less physically active than normal-weight women both before (p <0.05) and during pregnancy (p <0.0012). Both the compliance and the physical activity gradually declined during gestation. The change in physical activity could be described by a significant interaction between BMI group, gestational age (p <0.007) and the day of the week (p <0.001) when using ANOVA and interaction analysis. Maternal weight gain was larger in the normal-weight than in the obese women, but lower in the non-compliant obese women compared with the compliant (p <0.05).

Polycystic ovary syndrome: infertility, cardiovascular, metabolic and obstetrical risks, laboratory and clinical outcomes -- the PICOLO Study.

OBJECTIVES: The primary objective of this multicenter study is to evaluate the relative impact of insulin resistance (IR) and body mass index (BMI) in women with polycystic ovary syndrome (PCOS) on (1) Key hemodynamic/thrombogenic variables, (2) Oocyte quality and early embryo development, (3) Fetal growth, placental function and adverse obstetric outcome. SECONDARY OBJECTIVE: To establish a PCOS database and biobank facilitating future basic and interventional research related to PCOS. DESIGN: A cross-sectional and longitudinal cohort study at four University Hospitals in Denmark. POPULATION INCLUSION: About 200 women fulfilling the Rotterdam Criteria and 100 women without PCOS recruited from 2010 to 2012. METHODS: The impact of PCOS, as well as the impact of IR and BMI on the hormonal, metabolic and hemostatic key variables will be analyzed combining conventional, molecular techniques and selected gene analysis. Oocytes will be characterized by gene expression of granulosa and cumulus cells and the early embryo development will be followed by time lapse microscopy. Fetal growth will be assessed by repeated ultrasound measurements, and the pregnancy outcome compared to maternal and fetal biochemical markers of growth and inflammation and clinical pregnancy complications. MAIN OUTCOME MEASURES: Metabolic and hemostatic risk-biomarkers, oocyte and embryo quality, adverse pregnancy outcome, fetal growth and placental function in women with PCOS.

Parity and risk of diabetes in a Danish nationwide birth cohort.

AIMS: The purpose was to elucidate the association between parity and the incidence of diabetes using national register data. METHODS: The study population consisted of all Danish women with a singleton delivery in 1982/1983 (n = 100,669), who subsequently had 74,966 deliveries. The included women were followed up via registries until the end of 2006 for subsequent deliveries, diagnosis of diabetes and death/emigration. RESULTS: A total of 2021 cases (2.0%) were diagnosed with diabetes in connection with hospitalization or outpatient treatment during follow-up. Analyses were adjusted for fetal weight and duration of gestation, both at index pregnancy. Cox regression analysis with parity as a time-varying exposure, stratified in two age groups, showed an association between parity and risk of a diagnosis of diabetes. In women <33 years of age, parity 2, 3 and 4 + were associated with an increased risk of being diagnosed with diabetes compared with parity 1 [relative risks: 1.6 (95% confidence interval 1.1-2.3), 2.8 (1.8-4.3) and 2.5 (1.3-4.8), respectively]. Among women >33 years of age, parity 2 was associated with a significantly lower risk of diabetes diagnosis compared with parity 1, whereas parity 4 + was associated with a significantly higher risk of diabetes diagnosis compared with parity 1. CONCLUSIONS: The study shows that the risk of diabetes diagnosis increases with parity in young Danish women. This may support a causal association between diabetes and parity.

Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome.

OBJECTIVE: To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. DESIGN: Cross-sectional study. SUBJECTS: A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. RESULTS: Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH. CONCLUSION: Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.

The effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on cardiovascular metabolic risk factors.

OBJECTIVES: Hormone treatment (HT) after the menopause affects lipid and carbohydrate metabolism and inflammation and may modify risk factors relevant for the clinical expression of the metabolic syndrome and cardiovascular disease. Tibolone has pharmacodynamic properties different from other hormone preparations. Here, we compare the effect of combined HT and tibolone on metabolic risk markers for the development of cardiovascular disease. METHODS: Postmenopausal women were randomly assigned to 1.25 or 2.5 mg/day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Cardiovascular risk factors were determined at baseline and after 12 months of treatment. RESULTS: Body mass index and blood pressure were unaffected by the HT. HOMA-IR decreased in the CEE/MPA group (3.69 vs. 3.38; p = 0.02). Treatment with tibolone increased tissue-type plasminogen activator activity (0.87 IU/ml vs. 1.21 IU/ml; p = 0.005) and C-reactive protein (0.83 mg/l vs. 1.88 mg/l; p < 0.001), and decreased plasminogen activator inhibitor activity (6.9 IU/ml vs. 2.0 IU/ml; p < 0.001) and triglycerides (0.99 vs. 0.87 mmol/l; p = 0.004). Both treatments decreased total cholesterol significantly. CONCLUSIONS: CEE/MPA and tibolone have comparable effects on most metabolic risk factors investigated. The effect of tibolone on fibrinolysis and triglycerides suggests that tibolone has a favorable pharmacological profile on these risk factors when compared to CEE/MPA.

Medical management of first trimester miscarriage according to ultrasonographic findings.

BACKGROUND: The efficacy of medical treatment of first trimester miscarriages may depend on the regimen used, the definition of success, clinical symptoms, and, possibly, on the ultrasonographic findings. Our primary aim was to assess if a single dose of misoprostol could reduce the number of surgical interventions in early pregnancy failure, and to compare efficacy in different ultrasonographically-defined subgroups. METHODS: A retrospective review of 355 consecutive patients treated for a first trimester miscarriage with a single dose of vaginal misoprostol (400 microg), followed by vaginal ultrasonography after either 1, 2 or 3 days. Treatment was successful if a complete abortion was diagnosed at follow-up. The women were divided into 4 ultrasonographically-defined groups: missed abortion with a crown rump length (CRL)>or=6 mm (Group A1) or CRL<6 mm (Group A2), anembryonic gestation with gestational sac>or=18 mm (Group B1) or <18 mm (Group B2). RESULTS: The overall success rate was 39.2% (139/355). The regimen was more efficacious in Group A2 (50%) and less efficacious in Group B1 (26.6%) than in the other groups. The success rates were lower 1 day after treatment (30.2%) compared to days 2 and 3 (43.6%; p<0.05), and the difference was largest in Group B1 (12.9 versus 35.4%; p<0.05). CONCLUSIONS: Single dose misoprostol reduced the number of surgical interventions. The success rates of medically-treated first trimester miscarriages varied according to the ultrasonographic definitions of pregnancy failure, time of assessment, and the criteria for success.

Different cerebrovascular effects of medroxyprogesterone acetate and norethisterone acetate in the New Zealand White rabbit.

OBJECTIVE: The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model. METHODS: Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and endothelin-1 were established. RESULTS: Treatment with MPA caused a significant increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p < 0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2. CONCLUSIONS: In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.

Prediction of late failure after medical abortion from serial beta-hCG measurements and ultrasonography.

BACKGROUND: Surgical treatment of failed medical abortion may be performed several weeks after initiation of the abortion. There are no recognized methods for early identification of these late failures. We assessed the prognostic values of beta-hCG and ultrasonography in predicting late failure after medical abortion. METHODS: A total of 694 consecutive women with gestational age (GA) <63 days were followed up with beta-hCG measurements initially on the day of treatment and on day 8 and day 15, after the medically induced abortion with mifepristone and gemeprost. Measurement of the endometrial thickness by ultrasonography was performed on day 15 after induction of medical abortion. Failures diagnosed after day 15 and within 15 weeks were identified and classified as late failures. All interventions in this group were due to bleeding problems. The predictive values of different absolute and relative beta-hCG levels and different endometrial thickness were analysed. RESULTS: Of all failures in the study period, 65% (32) were diagnosed after the 2 week follow-up, and categorized as late failures. The absolute and the relative beta-hCG values on days 8 and 15 as well as the endometrial thickness on day 15 were greater among late failures than successes. Used as a predictive test, the positive predictive values of these variables were low. CONCLUSION: Neither beta-hCG nor endometrial thickness can be used clinically as diagnostic tests in predicting late failure after medical abortion.

Acute effects of tibolone on cerebral vascular reactivity in vitro.

OBJECTIVE: To evaluate the acute effects of tibolone and its metabolites on cerebral vascular reactivity in vitro. METHODS: Ring segments of the posterior cerebral artery from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves with tibolone, 3alpha-OH-tibolone, 3beta-OH-tibolone, Delta(4) isomer and 17beta-estradiol were obtained before and after addition of the NO blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or the potassium-channel blocker tetraethylammonium chloride (TEA, 10(-2) mol/l). Additionally, the effects of the hormones on the concentration-response curves with calcium were examined. RESULTS: Tibolone and its metabolites induced a concentration-dependent relaxation comparable to that of 17beta-estradiol (area under the curve (AUC); tibolone vs. 17beta-estradiol: 242 vs. 251; p < 0.05, analysis of variance). L-NAME increased the AUC for all substances compared with controls (p < 0.05, Student's t test), except for 17beta-estradiol. Preincubation with TEA induced no changes. The concentration-dependent contraction curves with calcium were shifted rightward by all hormones. CONCLUSIONS: The study demonstrates that the acute relaxation induced by tibolone and its metabolites in cerebral arteries in vitro is comparable to that with 17beta-estradiol, and seems to be mediated by inhibition of voltage-gated calcium channels and possibly partly by a nitric oxide-dependent mechanism.

Emergency contraception: knowledge and use among Danish women requesting termination of pregnancy.

The aim of this study was to describe knowledge about and use of emergency contraception (EC) among Danish women requesting termination of pregnancy. The study included 1514 women (response rate 83.7%) referred during the period August 2000 to May 2001. Sufficient knowledge of EC was defined as knowledge about both the correct time limit and where to acquire the EC. We found adequate knowledge in 44.7%. These women were typically younger, better educated and more often singles, nulliparae, and users of contraception. No relation was found to the type of contraception used or to previous terminations of pregnancies. EC was used in the actual pregnancy by 6.6% and 24.1% had used it previously. Actual or formers users were characterized in the same way. The general knowledge about EC has not improved significantly during the last few years and there is still need for information about the correct use of EC.