Yoon Frederiksen

Stress, distress and outcome of assisted reproductive technology (ART): a meta-analysis

BACKGROUND A number of studies have investigated the relationship between psychological factors such as stress and distress (measured as anxiety and depression) and outcomes of assisted reproductive technology (ART). The results, however, are inconsistent, and the strength of any associations remains to be clarified. We conducted a systematic review and meta-analysis of the results of studies reporting on the associations between stress, anxiety, and depression and ART outcomes. METHODS Prospective studies reporting data on associations between stress or distress in female patients and ART outcome were identified and evaluated by two independent researchers according to an a priori developed codebook. Authors were contacted in cases of insufficient data reporting. Stress was defined as perceived stress, work-related stress, minor life events or major life events, and distress was defined as anxiety or depression. RESULTS A total of 31 prospective studies were included. Small, statistically significant, pooled effect sizes were found for stress [ESr, effect size correlation) = -0.08; P = 0.02, 95% confidence interval (CI): -0.15, -0.01], trait anxiety (ESr = -0.14; P = 0.02, 95% CI: -0.25, -0.03) and state anxiety (ESr = -0.10, P = 0.03, 95% CI: -0.19, -0.01), indicating negative associations with clinical pregnancy rates. A non-significant trend (Esr = -0.11, P = 0.06) was found for an association between depression and clinical pregnancy. For serum pregnancy tests and live birth rates, associations between trait anxiety or state anxiety were not significant. The fail safe number did not exceed the suggested criterion in any analyses, between-study heterogeneity was considerable and the mean age, mean duration of infertility and percentage of first time ART attenders in the study samples were found to moderate several of the associations. CONCLUSIONS Small but significant associations were found between stress and distress and reduced pregnancy chances with ART. However, there were a limited number of studies and considerable between-study heterogeneity. Taken together, the influence of stress and distress on ART outcome may appear somewhat limited.

Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis

Objective To evaluate the evidence on the efficacy of psychosocial interventions for improving pregnancy rates and reducing distress for couples in treatment with assisted reproductive technology (ART). Design Systematic review and meta-analysis. Data sources PsycINFO, PubMed, EMBASE, CINAHL, Web of Science and The Cochrane Library between 1978 and April 2014. Study selection Studies were considered eligible if they evaluated the effect of any psychosocial intervention on clinical pregnancy and/or distress in infertile participants, used a quantitative approach and were published in English. Data extraction Study characteristics and results were extracted and the methodological quality was assessed. Effect sizes (ES; Hedges g) were pooled using a random effects model. Heterogeneity was assessed using the Q statistic and I2, and publication bias was evaluated using Egger’s method. Possible moderators and mediators were explored with meta-analyses of variances (ANOVAs) and meta-regression. Results We identified 39 eligible studies (total N=2746 men and women) assessing the effects of psychological treatment on pregnancy rates and/or adverse psychological outcomes, including depressive symptoms, anxiety, infertility stress and marital function. Statistically significant and robust overall effects of psychosocial intervention were found for both clinical pregnancy (risk ratio=2.01; CI 1.48 to 2.73; p<0.001) and combined psychological outcomes (Hedges g=0.59; CI 0.38 to 0.80; p=0.001). The pooled ES for psychological outcomes were generally larger for women (g: 0.51 to 0.73) than men (0.13 to 0.34), but the difference only reached statistical significance for depressive symptoms (p=0.004). Meta-regression indicated that larger reductions in anxiety were associated with greater improvement in pregnancy rates (Slope 0.19; p=0.004). No clear-cut differences were found between effects of cognitive–behavioural therapy (CBT; g=0.84), mind–body interventions (0.61) and other intervention types (0.50). Conclusions The present meta-analysis suggests that psychosocial interventions for couples in treatment for infertility, in particular CBT, could be efficacious, both in reducing psychological distress and in improving clinical pregnancy rates.

Evaluation of the noradrenergic system in Parkinson’s disease: an 11C-MeNER PET and neuromelanin MRI study

Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinsons disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behaviour disorder (RBD) accompanies Parkinsons disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while 11C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinsons disease with loss of noradrenergic function. Thirty non-demented Parkinsons disease patients [16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn and Yahr, 2.3 ± 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with 11C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinsons disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (P < 0.001) and widespread reduced binding of 11C-MeNER (P < 0.001), which correlated with amount of REM sleep without atonia. Parkinsons disease with RBD was also associated with a higher incidence of cognitive impairment, slowed EEG activity, and orthostatic hypotension. Reduced 11C-MeNER binding correlated with EEG slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinsons disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinsons disease, and may be of relevance when treating these conditions in Parkinsons disease.

Psychosocial predictors of posttreatment pain after nonmetastatic breast cancer treatment: a systematic review and meta-analysis of prospective studies

Background The search for risk factors of pain after breast cancer, which affects a considerable proportion of the women, has primarily focused on clinical factors. The aim of this meta-analysis was to explore the less well-studied psychosocial predictors of pain after breast cancer treatment. Methods Two independent searches were conducted in PubMed, PsycINFO, Web of Science, and CINAHL. Eligible studies were prospective, observational studies of women aged ≥18 years, diagnosed and treated for nonmetastatic breast cancer ≥3 months previously. Additional inclusion criteria were that studies had assessed at least one pain outcome and at least one psychosocial predictor. The psychosocial predictors investigated included: 1) psychological–behavioral states, 2) psychological traits, and 3) social support. Effect size correlations (ESr) were chosen as the effect size and pooled using a random effects model. We also explored a number of study characteristics as possible moderators of the effect with meta-regression. Results Of the total of 13 eligible studies identified, most studies measured psychosocial predictors at presurgery. Neither psychological–behavioral states (ESr: 0.05; p=0.13; K=11) nor psychological traits (ESr: 0.02; p=0.48; K=6) emerged as statistically significant predictors of pain. In contrast, higher levels of social support were statistically significantly associated with less pain (ESr: −0.24; p<0.001; K=4). In studies of psychological–behavioral states, longer follow-up was associated with smaller effect sizes (p=0.023). Furthermore, older mean sample age was associated with larger effect sizes for both psychological–behavioral states (p=0.0004) and psychological traits (p=0.035). Conclusion The results of this meta-analysis suggest that psychosocial factors measured at presurgery may only be of modest predictive value in identifying women at risk of developing pain after breast cancer treatment. While speculative, psychosocial factors may play a larger role in the postsurgery trajectory, which could be valuable to investigate in future studies.

Comparison of three infertility-specific measures in men and women going through assisted reproductive technology treatment:

We compared the psychometric properties of COMPI Fertility Problem Stress Scales, Fertility Problem Inventory, and Fertility Quality of Life Tool in 293 patients enrolled for assisted reproductive technology. COMPI Fertility Problem Stress Scales and Fertility Problem Inventory subscales presented higher internal consistency. COMPI Fertility Problem Stress Scales differentiated best between its domains. Fertility Problem Inventory revealed better concurrent validity. Fertility Quality of Life Tool presented better fit. While discrimination for depression was similar between measures, Fertility Quality of Life Tool was better at discriminating anxiety. Results suggest that while all compared measures are reliable and valid in assessing the psychosocial adjustment to infertility, the choice of measure should be based according to the assessment goals.

Decreased noradrenaline transporter density in the motor cortex of Parkinson's disease patients: Cortical Noradrenaline Transporter

Reduced noradrenaline levels have been reported to occur in the motor cortices of PD patients postmortem. Imaging techniques have recently become available to specifically study noradrenergic terminal function in vivo using PET. The objective of this study was to evaluate cortical 11C‐MeNER binding in PD patients. Thirty PD patients and 12 healthy control subjects comparable in age, sex, and cognitive performance underwent PET imaging with 11C‐MeNER, a specific ligand of the noradrenaline transporter. Cortical noradrenaline transporter binding was compared at a voxel level using Statistical Parametric Mapping, whereas cortical thickness was assessed using FreeSurfer software with MRI. PD patients showed reduced 11C‐MeNER binding in the primary motor cortex unrelated to cortical thickness; other cortical regions did not differ between groups. In a subgroup analysis, patients with higher Hoehn & Yahr stage exhibited more pronounced 11C‐MeNER binding reductions. Loss of cortical noradrenergic projections to the primary motor cortex occurs in PD associated with disease stage.

Predictors of pain during oocyte retrieval.

Abstract Introduction: Pain during oocyte retrieval remains prevalent despite detailed and specific pain management protocols. Exploring the role of psychosocial risk factors of pain during the oocyte retrieval could identify possible targets for prevention. The present study assessed pain prevalence and possible risk factors for experiencing extreme pain levels in a large cohort of women receiving assisted reproductive technologies (ART) treatment. Methods: Participants were 810 first attendees about to begin treatment with ART. The participants completed questionnaires at three time points: at their 21st day of the cycle, during the waiting time before the oocyte retrieval surgery and after the oocyte retrieval. Results: Fifty-one (6.9%) of the women reported the oocyte retrieval to be very or extremely painful. The results of a multiple logistic regression indicated that the significant predictors of high pain intensity, measured before the oocyte retrieval, were negative gynecological experiences and side effects of hormonal treatment. Variables measured after the oocyte retrieval associated with pain intensity were higher levels of anxiety during the oocyte retrieval, lower levels of perceived control and longer duration of the procedure. Discussion: The findings of the present study may help to identify those women who are at increased risk of experiencing unacceptable pain levels during oocyte retrieval procedures and the medical staff is advised to take psychological factors into account.

P365 Automated chin EMG analysis for quantification of REM sleep without atonia

Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by dream enactment due to a failure of normal muscle atonia. Visual assessment of this muscle activity is time consuming and rater-dependent. A computer program with an automated scoring algorithm would thus be a valuable asset for sleep professionals scoring RBD. Methods An electromyogram (EMG) computer algorithm for scoring ‘tonic’ (2× root mean square (RMS) of baseline EMG activity for > 15 s per 30 s epoch), ‘phasic’ (max amplitude > 4×RMS baseline (or 2× during concomitant ‘tonic’ activity), 3 s epochs) and ‘any’ (‘tonic’ and/or ‘phasic’) submental muscle activity during REM sleep was created using the criteria’s of McCarter et al. [1]. For validation of the computer algorithm, visual scoring of EMG activity done by two blinded board-certified sleep professionals was compared to scoring of the computer algorithm in the first consecutive 10 Parkinson’s disease (PD) patients with RBD (PDRBD+) and 10 PD patients without RBD (PDRBD−) using regression analysis and Kappa statistics. Subsequently, 29 non-RBD subjects (14 PDRBD− and 15 healthy controls) and 23 RBD subjects (16 PDRBD+ and 7 idiopathic RBD subjects) were analyzed with the computer algorithm to test for discrimination power between RBD and non-RBD subjects. Results The computer algorithm showed high congruency with human ratings on single epoch level (using Kappa statistics: ‘tonic’ activity κ  = 0.74 & κ  = 0.78, ‘phasic’ activity κ  = 0.80 & κ  = 0.76, ‘any’ activity κ  = 0.83 & κ  = 0.82), which was similar to the κ values between the two human raters (‘tonic’ activity κ  = 0.64, ‘phasic’ activity κ  = 0.79, ‘any’ activity κ  = 0.82). In the discrimination analysis, all RBD subjects were correctly identified by excess of submental muscle activity, when artifacts were removed before analysis. At an individual patient level, cut-off values with full differentiation between non-RBD and RBD subjects were obtained for ‘phasic’ and ‘any’ activity (cut off values at > 10% of REM sleep; range of non-RBD subjects, 1.3–8.2% for ‘phasic’ and ‘any’; range of RBD subjects, 13.2–64.5% for ‘phasic’ and 13.3–77.4% for ‘any’, respectively). Conclusion Our proposed automated computer algorithm allows a fast quantitation of ‘tonic’, ‘phasic’, and ‘any’ EMG activity with good agreement to visual ratings and was able to detect and rate REM sleep without atonia. The computer algorithm seems a promising tool to be used in the clinical setting for supporting a diagnosis of RBD.