Charlotte Ørsted Hougaard

Prospective longitudinal cohort study on cumulative 5-year delivery and adoption rates among 1338 couples initiating infertility treatment

BACKGROUNDnThe objective was to assess crude 5-year delivery rates after assisted reproductive technology (ART) treatment, intrauterine inseminations (IUI), spontaneous conceptions (SC) and adoptions in a large infertile cohort.nnnMETHODSnA prospective longitudinal survey comprised 1338 infertile couples starting public infertility programmes offering IUIs and three free ART cycles during 2000-2001. The cohort was cross-linked with the National Medical Birth Register to obtain delivery rates for all 1338 couples. More detailed data were available from 817 women responding to a 5-year follow-up questionnaire (response rate 74.7%). Fifty-seven percent (466/817) of the couples had received treatment prior to inclusion in the study with an average of 4.1+/-2.8 infertility treatments before referral.nnnRESULTSnOf the 1338 couples, 69.4% had at least one delivery within 5-years of follow-up. For women <35 years 74.9% had delivered compared with 52.2% of those aged > or =35 years. The mean number of children was 1.6, and 52.1% had more than one child. Of the 817 women who provided questionnaire data, 18.2% (149/817) delivered after SC, two-thirds of these after a previous ART delivery. Adoption of a child occurred for 5.9% (48/817) of the women. Positive prognostic factors for delivery were male infertility, female age <35 years, <3 years of infertility and less than three previous treatment cycles.nnnCONCLUSIONSnA crude delivery rate of 69.4% in the total population 5 years after referral to tertiary hospital centres with 6.6% deliveries after SC in the subpopulation responding to the questionnaire indicates a high efficacy of modern infertility treatments.

Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples

This study investigated the impact of womens body mass index (BMI) on the outcome after consecutive IVF/intracytoplasmic sperm injection cycles in 487 patients initiating treatment with 5-year follow-up. The total number of cycles was 1417. In total 103 (21.1%) were overweight (BMI 25-29.9 kg/m²) and 59 (12.1%) were obese (BMI ≥ 30 kg/m²). Number of initiated cycles/woman (P=0.01), number of cancelled cycles/woman (P < 0.01) and the total dose of gonadotrophin used/cycle (P < 0.01) rose with increasing BMI. A negative linear association between BMI and the number of retrieved oocytes (B=-0.243, P < 0.001) and an inverse U-shaped relationship between BMI and the number of developed embryos was seen, with less embryos available among underweight and obese women (P=0.03). The number with positive serum human chorionic gonadotrophin/cycle decreased significantly with increasing BMI (P < 0.01). The ongoing pregnancy rate/cycle among the obese women was lower (20.8% versus 28.3% in normal-weight women; P=0.04). Live-birth rate per cycle was 15.2% versus 21.5%. Multiple logistic regression analysis showed that the only independent predictors of live birth were womens age (P=0.037), womens BMI (P=0.034) and mens age (P=0.040).

Characterisation of a cell swelling‐activated K+‐selective conductance of Ehrlich mouse ascites tumour cells

1 The K+ and Cl− currents activated by hypotonic cell swelling were studied in Ehrlich ascites tumour cells using the whole‐cell recording mode of the patch‐clamp technique. 2 Currents were measured in the absence of added intracellular Ca2+ and with strong buffering of Ca2+. K+ current activated by cell swelling was measured as outward current at the Cl− equilibrium potential (ECl) under quasi‐physiological gradients. It could be abolished by replacing extracellular Na+ with K+, thereby cancelling the driving force. Replacement with other cations suggested a selectivity sequence of K+ > Rb+ > NH4≈ Na+≈ Li+; Cs+ appeared to be inhibitory. 3 The current‐voltage relationship of the volume‐sensitive K+ current was well fitted with the Goldman‐Hodgkin‐Katz current equation between ‐130 and +20 mV with a permeability coefficient of around 10−6 cm s−1 with both physiological and high‐K+ extracellular solutions. 4 The class III antiarrhythmic drug clofilium blocked the volume‐sensitive K+ current in a voltage‐independent manner with an IC50 of 32 μM. Clofilium was also found to be a strong inhibitor of the regulatory volume decrease response of Ehrlich cells. 5 Cell swelling‐activated K+ currents of Ehrlich cells are voltage and calcium insensitive and are resistant to a range of K+ channel inhibitors. These characteristics are similar to those of the so‐called background K+ channels. 6 Noise analysis of whole‐cell current was consistent with a unitary conductance of 5.5 pS for the single channels underlying the K+ current evoked by cell swelling, measured at 0 mV under a quasi‐physiological K+ gradient.

Addressing Social Inequality in Aging by the Danish Occupational Social Class Measurement

Objective: To present the Danish Occupational Social Class (DOSC) measurement as a measure of socioeconomic position (SEP) applicable in a late midlife population, and to analyze associations of this measure with three aging-related outcomes in midlife, adjusting for education. Method: Systematic coding procedures of the DOSC measurement were applied to 7,084 participants from the Copenhagen Aging and Midlife Biobank (CAMB) survey. We examined the association of this measure of SEP with chronic conditions, self-rated health, and mobility in logistic regression analyses, adjusting for school education in the final analysis. Results: The measure of SEP showed a strong social gradient along the social classes in terms of prevalence of chronic conditions, poor self-rated health, and mobility limitations. Adjusting for school education attenuated the association only to a minor degree. Discussion: The DOSC measure was associated with aging-related outcomes in a midlife Danish population, and is, thus, well suited for future epidemiological research on social inequalities in health and aging.

K+ currents activated by leukotriene D4 or osmotic swelling in Ehrlich ascites tumour cells

K+ and Cl– currents activated by hypoosmotic cell swelling (IK,vol and ICl,vol) or after addition of leukotriene D4 (LTD4) to cells in isotonic medium were studied in Ehrlich ascites tumour cells. IK,vol and ICl,vol were not affected by strong buffering of intracellular Ca2+ or by additional removal of extracellular Ca2+. In isotonic media, 5xa0nmol/l LTD4 activated large K+ but not Cl– currents. The LTD4-activated IK was, as has been shown previously for IK,vol, insensitive to charybdotoxin (ChTX) but was blocked by the antiarrhythmic drug clofilium. The current/voltage (I/V) relation for the LTD4-activated IK was, as recently demonstrated for IK,vol, well fitted by the Goldman-Hodgkin-Katz current equation between –130xa0mV and 30xa0mV in both physiological and K+-rich extracellular solutions. LTD4 had no additional effect on the magnitude of IK in Ehrlich cells already activated by the hypoosmotic stimulus. Nevertheless, the onset time for IK after hypoosmotic cell swelling was significantly less in the presence of LTD4. The similar I/V relation, pharmacological sensitivity and lack of additivity suggest that hypoosmotic swelling and addition of LTD4 activate the same K+ channels in Ehrlich cells. The influence of [Ca2+]i appears, however, to differ between IK,vol and the IK activated by LTD4 in that the latter was reduced significantly by strong buffering of [Ca2+]i. This might reflect the involvement of some additional factor in the hypoosmotic activation of K+ channels besides the stimulation mediated by LTD4.

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVEnTo examine the association between socioeconomic position and coping strategies in musculoskeletal pain.nnnDESIGN AND SUBJECTSnCross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain.nnnMETHODSnData was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class.nnnRESULTSnAmong women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II.nnnCONCLUSIONnIt is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.

Coping with unemployment: Does educational attainment make any difference?

Aims: The aim of this study was to examine the cross-sectional association between educational attainment and coping strategies with unemployment in a random sample of 37- to 56-year-old Danish men and women in long-term unemployment. Methods: Data were based on a survey among 575 men and 1,064 women who had been unemployed at least 70% of the time during a three-year period (October 1996 to October 1999). The outcome measures were two scales for coping with unemployment, one for problem-solving coping, and one for avoidant coping. Educational attainment was measured by years of vocational training. Results: A significant association was found between low educational attainment and low use of problem-solving coping among both men, OR=1.81 (95% CI 1.19—2.75), and women, OR=1.57 (1.13— 2.18). Adjustment for cohabitation status, self rated health, economic strain, and unemployment status did not change this association substantially. High use of avoidant coping was associated with low educational attainment among men, OR=1.57 (0.98—2.51). For women, medium educational attainment was significantly associated with low use of avoidant coping, OR=0.60 (0.42—0.85). This result was not affected by adjustment for the covariates. Conclusions: Coping strategies are considered a potential modifier of the impact of unemployment on health and well-being. In this study, differences in coping strategies with unemployment were associated with educational attainment.

Intracellular signalling involved in activation of the volume-sensitive K+ current in Ehrlich ascites tumour cells.

The cell swelling-activated K+ channel in Ehrlich ascites tumour cells has a conductance of 5 pS estimated from noise analysis of the volume-sensitive whole-cell K+ current (I(K,vol)). I(K,vol) exhibits Goldman-Hodgkin-Katz type behaviour and is insensitive to clotrimazole, apamin and charybdotoxin (ChTX), but inhibited by clofilium. Its small conductance, lack of intrinsic voltage-dependence and peculiar pharmacological profile are similar to properties described for the two-pore domain background K+ TASK channels. Neither Ca2+ nor ATP work as initiators in the activation of I(K,vol). In contrast, several investigations in Ehrlich cells suggest an important role for leukotriene D4 (LTD4) in the activation of I(K,vol). Under isotonic conditions, LTD4 activates Ca2+-dependent, ChTX-sensitive K+ channels as well as Ca2+-independent. ChTX-insensitive K+ channels. The LTD4-activated, ChTX-insensitive K+ current exhibits a current-voltage relation, pharmacological profile and single channel conductance similar to that of I(K,vol), indicating that LTD4 is the signalling molecule responsible for activation of the volume-sensitive K+ channels in Ehrlich cells. Hypotonic swelling of Ehrlich cells results in translocation of the 85-kDa cytosolic (c) PLA2alpha to the nucleus where it is activated. This activation leads to an increase in arachidonic acid release followed by an increased release of leukotrienes, and is essential in cell swelling-induced activation of I(K,vol) and of the organic osmolyte channels.

Incidence of depression and influence of depression on the number of treatment cycles and births in a national cohort of 42 880 women treated with ART

STUDY QUESTIONnDoes prior depression in women treated with assisted reproduction technology (ART) influence the number of treatment cycles and ART live births?nnnSUMMARY ANSWERnWomen with a depression diagnosis prior to ART treatment initiated statistically significantly fewer ART treatment cycles and had a lower mean number of ART live births compared with women with no history of depression.nnnWHAT IS KNOWN ALREADYnPrevious studies have shown an increased prevalence of depressive symptoms in fertility patients than in the comparison groups.nnnSTUDY DESIGN, SIZE, DURATIONnA register-based national cohort study, including all women (n = 42,915) treated with IVF, ICSI, frozen embryo transfer and oocyte recipient cycle in Denmark from 1 January 1994 to 30 September 2009 extracted from the IVF register (ART cohort). Data on births and depression diagnoses were obtained by linking to the Danish Medical Birth Register (1994-2010) and the Danish Psychiatric Central Research Register (1969-2010).nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnFor each woman in the ART cohort, we included five age-matched women from the female background population not having received ART treatment. This comparison group was cross-linked with identical register data as the ART cohort. Women with incomplete ART information or a depression diagnosis before 18 years of age were excluded; remaining n = 42,880. The ART cohort was grouped into (i) women with a depression diagnosis and (ii) women never diagnosed with depression. In the ART group with depression, analyses were specified on women with their first depression prior to ART treatment. In total, 2.6% of the women in the ART cohort had a depression diagnosis. For the incidence rate ratio (IRR) 39,194 women from the ART cohort (3686 women were excluded due to migration) were compared with 206,005 women from the age-matched comparison group who did not receive ART treatment.nnnMAIN RESULTS AND THE ROLE OF CHANCEnOf the women in the ART cohort with a depression diagnosis, 34.7% had their first depression diagnosis prior to ART treatment, 4.7% during ART treatment and 60.7% after ART treatment. The mean number of initiated ART cycles was significantly lower in the ART group of women having a depression diagnosis prior to ART treatment [2.55 (±1.78)] compared with the ART group of women without a depression diagnosis [3.22 (±2.31); P < 0.001; P < 0.001]. Women having a depression diagnosis prior to ART treatment had a lower mean number of ART live births [0.82 (±0.73)] compared with women without a depression diagnosis [1.03 (±0.81); P < 0.001]. The incidence rate of first and recurrent depression diagnoses in the ART cohort was significantly lower compared with the age-matched background population group; IRR = 0.80 (P < 0.001) and IRR = 0.77 (P < 0.001).nnnLIMITATIONS, REASONS FOR CAUTIONnOnly clinical depression diagnoses treated in a psychiatric hospital setting are included. The age-matched comparison group from the background population is heterogeneous as it consists of women differing in fertility status (both mothers and childless women).nnnWIDER IMPLICATIONS OF THE FINDINGSnFewer women in the ART cohort developed depression over time compared with the age-matched background population, which might reflect a healthy patient effect of the women seeking ART treatment. Women with a depression diagnosis before ART treatment receive fewer ART treatments and are less likely to achieve an ART live birth. These women might be more vulnerable and we recommend that they be offered more psychiatric attention before starting, as well as during and after ART treatment.nnnSTUDY FUNDING/COMPETING INTEREST(S)nResearch grants are funded by the Danish Health Insurance Foundation and Merck Sharp & Dohme. The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare.nnnTRIAL REGISTRATION NUMBERnN/A.

Economic consequences of incident disease: The effect on loss of annual income

Aims: To estimate the effect of incident disease on loss of annual income on an individual level, to analyse whether loss of job mediates the effect on loss of annual income, to analyse whether an association is modified by socioeconomic position, and to determine whether the effect on annual income is similar across three different diagnostic categories with different consequences in terms of functional limitations. Methods: This was a register-based study with a longitudinal design using a register of the Danish population covering 412,450 person years. Data on hospitalization are linked to information on income and employment. The setting was a 10% random sample of all individuals living in Denmark and aged 43—60 years in 1996—99. Results: Male cases of acute myocardial infarction (AMI), female cases of breast cancer and both male and female cases of intervertebral disease were associated with an increased and equally strong risk for experiencing a loss of annual income corresponding to one income decile (>25,000 DKK) in the year following disease (odds ratio (OR) from 1.37 (95% confidence interval (CI) 1.09—1.72) to 1.57 (95% CI 1.21—2.04)). No significant effect of female AMI was found. The effects of intervertebral disease and male AMI were mediated by loss of employment. This was not the case for breast cancer. No modifying effects of income level or occupational class were found. Conclusions: Despite different functional limitations, the three disorders have equally strong effects on annual income. This might be interpreted as a buffering effect of the welfare policies in relation to the more discriminating demands of the labour market.