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ObjectivesRegistries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART).DesignA registry-based cohort study.SettingAll coronary care units and cardiac rehabilitation (CR) centres in Sweden.ParticipantsPatients attending a CR visit at 1-year post-MI 2006–2019 were included (n=81 363, 18–74 years, 74.7% men).Outcome measuresOutcome measures at 1-year follow-up included blood pressure (BP) ResultsThe proportion of patients attaining the targets for BP90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, pConclusionsWhile little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006–2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

Background Sleep-related breathing disorders (SRBDs), particularly obstructive sleep apnoea, are associated with increased cardiovascular (CV) risk. However, it is not known whether individual questions used for SRBD screening are associated with major adverse CV events (MACE) and death specifically in patients with chronic coronary syndrome (CCS). Methods Symptoms associated with SRBD were assessed by a baseline questionnaire in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. The patients reported the frequency (never/rarely, sometimes, often and always) of: 1) loud snoring; 2) more than one awakening/night; 3) morning tiredness (MT); 4) excessive daytime sleepiness (EDS); or 5) gasping, choking or apnoea when asleep. In adjusted Cox regression models, associations between the frequency of SRBD symptoms and CV outcomes were assessed with never/rarely as reference. Results During a median follow-up time of 3.7 years, 1,588 MACE events (541 CV deaths, 749 nonfatal myocardial infarctions [MI] and 298 nonfatal strokes) occurred. EDS was associated (hazard ratio [HR], 95% confidence interval [CI]) with increased risk of MACE (sometimes 1.14 [1.01-1.29], often 1.19 [1.01-1.40] and always 1.43 [1.15-1.78]), MI (always 1.61 [1.17-2.20]) and all-cause death (often 1.26 [1.05-1.52] and always 1.71 [1.35-2.15]). MT was associated with higher risk of MACE (often 1.23 [1.04-1.45] and always 1.46 [1.18-1.81]), MI (always 1.61 [1.22-2.14]) and all-cause death (always 1.54 [1.20-1.98]). The other SRBD-related questions were not consistently associated with worse outcomes. Conclusions In patients with CCS, gradually higher levels of EDS and MT were independently associated with increased risk of MACE, including mortality.

Aim: Our aim was to investigate the characteristics, treatment and prognosis of patients with myocardial infarction (MI) treated outside a cardiology department (CD), compared with MI patients treated at a CD. Methods: A cohort of 1310 patients diagnosed with MI at eight Swedish hospitals in 2011 were included in this observational study. Patients were followed regarding all-cause mortality until 2018. Results: A total of 235 patients, exclusively treated outside CDs, were identified. These patients had more non-cardiac comorbidities, were older (mean age 83.7 vs. 73.1 years) and had less often type 1 MIs (33.2% vs. 74.2%), in comparison with the CD patients. Advanced age and an absence of chest pain were the strongest predictors of non-CD care. Only 3.8% of non-CD patients were investigated with coronary angiography and they were also prescribed secondary preventive pharmacological treatments to a lesser degree, with only 32.3% having statin therapy at discharge. The all-cause mortality was higher in non-CD patients, also after adjustment for baseline parameters, both at 30 days (hazard ratio (HR) 2.28, 95% confidence interval (CI) 1.62&ndash, 3.22), one year (HR 1.82, 95% CI 1.39&ndash, 2.36) and five years (HR 1.62, 95% CI 1.32&ndash, 1.98). Conclusions: MI treatment outside CDs is associated with an adverse short- and long-term prognosis. An improved use of percutaneous coronary intervention (PCI) and secondary preventive pharmacological treatment might improve the long-term prognosis in these patients.

Purpose Assisted reproductive technology (ART) treatments with donor sperm have been allowed for women in lesbian relationships (WLR) since 2005 in Sweden, but for single women (SW), these became approved only recently in 2016. This study was conducted to compare the outcomes of ART treatments in SW vs. WLR. Methods This is a prospective controlled cohort study of 251 women undergoing intrauterine insemination (D-IUI) or in vitro fertilization (D-IVF) using donor sperm between 2017 and 2019 at the department of Reproductive Medicine, Karolinska University Hospital. The cohort comprised 139 SW and 112 WLR. The main outcomes included differences in live birth rate (LBR) and cumulative live birth rate (cLBR) between the groups. The SW underwent 66 D-IUI and 193 D-IVF treatments and WLR underwent 255 D-IUI and 69 D-IVF treatments. Data on clinical characteristics, treatment protocols and clinical outcomes were extracted from the clinic’s electronic database. The outcomes of D-IUI and D-IVF were separately assessed. Results The cohort of SW was significantly older than WLR (37.6 vs. 32.4 years, P P P P = 0.019), respectively. There was no statistically significant difference in the main outcome LBR between the two groups, or between the two different types of treatment, when adjusted for age. Perinatal outcomes and cLBR were also similar among the groups. Conclusions SW were, on average, older than WLR undergoing treatment with donor sperm. No significant differences were seen in the LBR and cLBR when adjusted for age between the two groups and between the two types of treatment (D-IVF vs. D-IUI). Trial registration ClinicalTrials.gov NTC04602962.

Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is common. There are limited data on the mechanisms and prognosis for reinfarction in MINOCA patients. Methods: In this observational study of MINOCA patients hospitalized in Sweden and registered in the SWEDEHEART registry between July 2003 and June 2013 and followed until December 2013 we identified 9,092 unique patients with MINOCA out of 199,163 MI admissions in total. The 570 (6.3%) MINOCA patients who were hospitalized due to a recurrent MI constituted the study group. Results: The mean age was 69.1 years and 59.1% were women. The median time to readmission was 17 months. A total of 340 patients underwent a new coronary angiography and 180 (53%) had no obstructive coronary artery disease (CAD) and 160 (47%) had obstructive CAD; 123 had one-vessel, 26 had two-vessel, 9 had three-vessel disease and two had left main together with one-vessel disease. Male gender, diabetes, peripheral vascular disease, higher levels of creatinine and ST-elevation at presentation were more common in patients with MI with obstructive CAD than in patients with a recurrent MINOCA. Mortality during a median follow-up of 38 months was similar whether the reinfarction event was MINOCA or MI with obstructive CAD 13.9% vs. 11.9% (p=0.54). Conclusions: About half of patients with reinfarction after MINOCA who underwent coronary angiography had progression of coronary stenosis. Angiography should be strongly considered in patients with MI after MINOCA. Mortality associated with recurrent events was substantial, though there was no difference in mortality between those with or without significant CAD.

Background Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults. Method This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1–17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy. Discussion This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas. Trial registration The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017–004187-35) and published at ClinicalTrials.gov (NCT03781700, initial release 12/14/2018).

Importance: Suboptimal use of medications is a leading cause of health care–related harm. Medication reviews improve medication use, but evidence of the possible benefit of inpatient medication review for hard clinical outcomes after discharge is scarce. Objective: To study the effects of hospital-based comprehensive medication reviews (CMRs), including postdischarge follow-up of older patients’ use of health care resources, compared with only hospital-based reviews and usual care. Design, Setting, and Participants: The Medication Reviews Bridging Healthcare trial is a cluster randomized crossover trial that was conducted in 8 wards with multiprofessional teams at 4 hospitals in Sweden from February 6, 2017, to October 19, 2018, with 12 months of follow-up completed December 6, 2019. The study was prespecified in the trial protocol. Outcome assessors were blinded to treatment allocation. In total, 2644 patients aged 65 years or older who had been admitted to 1 of the study wards for at least 1 day were included. Data from the modified intention-to-treat population were analyzed from December 10, 2019, to September 9, 2020. Interventions: Each ward participated in the trial for 6 consecutive 8-week periods. The wards were randomized to provide 1 of 3 treatments during each period: CMR, CMR plus postdischarge follow-up, and usual care without a clinical pharmacist. Main Outcomes and Measures: The primary outcome measure was the incidence of unplanned hospital visits (admissions plus emergency department visits) within 12 months. Secondary outcomes included medication-related admissions, visits with primary care clinicians, time to first unplanned hospital visit, mortality, and costs of hospital-based care. Results: Of the 2644 participants, 7 withdrew after inclusion, leaving 2637 for analysis (1357 female [51.5%]; median age, 81 [interquartile range, 74-87] years; median number of medications, 9 [interquartile range, 5-13]). In the modified intention-to-treat analysis, 922 patients received CMR, 823 received CMR plus postdischarge follow-up, and 892 received usual care. The crude incidence rate of unplanned hospital visits was 1.77 per patient-year in the total study population. The primary outcome did not differ between the intervention groups and usual care (adjusted rate ratio, 1.04 [95% CI, 0.89-1.22] for CMR and 1.15 [95% CI, 0.98-1.34] for CMR plus postdischarge follow-up). However, CMR plus postdischarge follow-up was associated with an increased incidence of emergency department visits within 12 months (adjusted rate ratio, 1.29; 95% CI, 1.05-1.59) compared with usual care. There were no differences between treatment groups regarding other secondary outcomes. Conclusions and Relevance: In this study of older hospitalized patients, CMR plus postdischarge follow-up did not decrease the incidence of unplanned hospital visits. The findings do not support the performance of hospital-based CMRs as conducted in this trial. Alternative forms of medication reviews that aim to improve older patients’ health outcomes should be considered and subjected to randomized clinical trials. Title in dissertation list of papers: Effects of hospital-based comprehensive medication reviews including post-discharge follow-ups on older patients’ healthcare utilisation (MedBridge trial): a pragmatic cluster-randomised crossover trial

Introduction: While prevention strategies that target S tandard M odifiable cardiovasc u lar R isk F actors (SMuRFs: hypertension, diabetes mellitus, hypercholesterolemia, smoking) are critical to reduce coronary heart disease risk, myocardial infarction (MI) in the absence of SMuRFs is not infrequent. Methods: We examined the presenting features, treatment, short- and long-term outcomes of patients with ST-segment-elevation MI (STEMI) without SMuRFs compared to STEMI patients with >0 SMuRFs in the national Swedish MI registry SWEDEHEART between 2006-2018. Adjusted logistic regression models were used to determine outcome predictors of all cause 30-day mortality. Kaplan Meir survival analysis was performed. Results: 8,400 (14%) of 60,692 patients without a history of coronary artery disease had no SMuRFs. Patients with and without SMuRFs had the same rate of primary PCI but lower rate of multivessel disease (37% vs. 44%). SMuRF-less patients had higher rates of unadjusted all-cause mortality at 30 days (12% vs. 8%, P Conclusions: 14% of STEMI presentations occurred in the absence of SMuRFs. Higher rates of 30-day mortality in SMuRF-less STEMI patients, especially among women, highlight the need for improved risk stratification and evidence-based pharmacotherapy during the post MI period, irrespective of baseline risk factors and sex. Figure 1. Kaplan Meier survival curves for patients with and without SMuRFs. A) Women. B) Men. C) LVEF < 40%. D) LVEF > 40%.

Background Systematically monitoring results within cardiac rehabilitation (CR) has been highlighted as a possible way to improve CR outcomes. The nationwide SWEDEHEART registry has monitored quality of care post myocardial infarction (MI) in Sweden since the 1990s. Follow-up data describing treatment and outcomes within CR has been collected since 2006. Purpose To describe changes in risk factor control and use of secondary preventive medication for post MI patients after completion of CR in Sweden 2006–2017, and to compare with trends in the EUROASPIRE surveys. Methods All patients who suffered an MI and attended a one-year CR follow-up visit registered in SWEDEHEART 2006–2017 were included (n=66 666, 18–74 years, 75% men). Trends in risk factor control and secondary preventive medication were collected yearly and analyzed over the time period using Cochran-Armitage trend test. Comparisons were made to data from the EUROASPIRE III (2006–2007), IV (2012–2013) and V (2016–2017) surveys, where patients with coronary artery events or interventions were interviewed at approximately 1.2 years after the index event (n=25 225, 18–80 years, 74% men). Results Trends in blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) control, smoking, and central obesity are shown in the Figure. The proportion of patients achieving BP goal Conclusion Between 2006–2017, considerable improvements were achieved in risk factor control and use of secondary preventive medication for MI patients completing CR in Sweden, where all patients were monitored through the SWEDEHEART registry. The improvements were larger than observed in the EUROASPIRE surveys during the same time period. Continuous and nationwide auditing of CR outcomes, as well as local review of performance, could be possible explanations for some of the observed differences. Figure 1 Funding Acknowledgement Type of funding source: None

In this study, ovarian stimulation using highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) for IVF were compared in two large assisted reproduction technique centres in Sweden. A total of 5902 women underwent 9631 oocyte retrievals leading to 8818 embryo transfers (7720 on day 2): single embryo transfers (74.2%); birth rate per embryo transfer (27.7%); multiple birth rate (5.0%); incidence of severe ovarian hyperstimulation syndrome (0.71%). Compared with ovarian stimulation with rFSH, women who received HP-HMG were older, had higher dosages of gonadotrophins administered, fewer oocytes retrieved and more embryos transferred. After multivariate analysis controlling for age and generalized estimating equation model, no differences were found in delivery outcomes per embryo transfers between HP-HMG and rFSH, independent of gonadotrophin releasing hormone analogue (GnRH) used. Logit curves for live birth rate suggested differences for various subgroups, most prominently for women with high oocyte yield or when high total doses were used. Differences were not significant, perhaps owing to skewed distributions of the FSH compounds versus age and other covariates. These 'real-life patients' had no differences in live birth rate between HP-HMG and rFSH overall or in subgroups of age, embryo score, ovarian sensitivity or use of GnRH analogue regimen.

Background Recommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence. Objectives The authors analyzed the association between self-reported exercise and mortality in patients with stable CHD. Methods A total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated. Results A graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical–Coronary Heart Disease) risk score (p for interaction = 0.0007). Conclusions In patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, β-blockers, dual antiplatelet therapy, and long-term cardiovascular events. Methods: This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199 162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure. Results: At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68–0.87), 0.82 (0.73–0.93), and 0.86 (0.74–1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and β-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74–1.08). Conclusions: The results indicate long-term beneficial effects of treatment with statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on outcome in patients with MINOCA, a trend toward a positive effect of β-blocker treatment, and a neutral effect of dual antiplatelet therapy. Properly powered randomized clinical trials to confirm these results are warranted.

Purpose To investigate the impact of symptomatic and surgically confirmed endometriosis on ovarian sensitivity index (OSI) and cumulative live-birth rates (LBR) using predominantly single embryo transfer (SET). Methods Cross-sectional case-control study in a University-based ART program. Women with symptomatic and surgically confirmed endometriosis (N = 172), who underwent IVF/ICSI at Karolinska University Hospital were compared to controls without clinically suspected endometriosis (N = 2585). Two thousand seven hundred fifty-seven patients underwent 8236 treatment cycles (4598 fresh and 3638 frozen cycles). Primary outcome measures included Ovarian Sensitivity Index (OSI) estimated as collected oocytes/FSH dose and cumulative LBR/oocyte pickup (OPU). Generalized estimated equation (GEE) model accounting for dependencies between consecutive treatments were applied. Secondary outcomes included number of oocytes, pregnancy rate per OPU and per ET, LBR per ET, and miscarriage rate. Results Patients diagnosed with endometriosis had significantly fewer oocytes collected (8.47 vs. 9.54, p = 0.015) and lower OSI (p = 0.011) than controls. There were no differences in cycle cancelations (p = 0.59) or miscarriages (p = 0.95) between the two groups. Cumulative LBR/OPU did not differ between women with endometriosis and controls (35.6% vs. 34.7%, respectively, p = 0.83). In both groups, more than 60% of women had consecutive FETs after fresh ETs (p = 0.49) with SET in > 70% of cases. The results were similar whether ovarian endometrioma was present or not. Conclusions Our data support that a diagnosis of endometriosis, with or without present endometrioma, does not negatively affect ART cumulative results. The impact of endometriosis was discernible on OSI but not on clinical relevant outcomes including pregnancy and LBR.

Background Obesity, assessed as body mass index (BMI), is an established risk factor for development of coronary heart disease (CHD). However, in patients with heart failure and atrial fibrillation there is an “obesity paradox” with better prognosis among obese patients. The association between BMI and cardiovascular outcomes in patients with stable CHD is unclear. Methods The prospective STABILITY trial included 15,828 patients with stable CHD with a follow-up of 3–5 years (median 3.7) on optimal secondary preventive treatment. BMI and waist circumference were measured at baseline (n=15,785). All cardiovascular outcomes were centrally adjudicated. Associations between obesity indices and outcomes were evaluated by multivariable Cox regression analyses with adjustments for age, sex, study treatment, and clinical risk factors. Results Mean age was 64 years and 19% were females. In total, 3250 (20.9%) patients had BMI 25 and 30. Underweight (BMI Figure 1 Conclusion In patients with stable CHD on optimal secondary prevention BMI had a U-shaped association with the risk of MACE, death, and heart failure and a linear association with the risk of MI. The lowest risk for MACE was seen for BMI between 25 and 30, considered as overweight. The findings do not support current recommendations to achieve an ideal BMI of 20–25 for weight adjustments in patients with CHD. Acknowledgement/Funding The original STABILITY study was funded by GlaxoSmithKline

Objective The universal definition of myocardial infarction (MI) differentiates MI due to oxygen supply/demand mismatch (type 2) from MI due to plaque rupture (type 1) as well as from myocardial injuries of non-ischaemic or multifactorial nature. The purpose of this study was to investigate how often physicians agree in this classification and what factors lead to agreement or disagreement. Methods A total of 1328 patients diagnosed with MI at eight different Swedish hospitals 2011 were included. All patients were retrospectively reclassified into different MI or myocardial injury subtypes by two independent specially trained physicians, strictly adhering to the third universal definition of MI. Results Overall, there was a moderate interobserver agreement with a kappa coefficient (κ) of 0.55 in this classification. There was substantial agreement when distinguishing type 1 MI (κ: 0.61), compared with moderate agreement when distinguishing type 2 MI (κ: 0.54). In multivariate logistic regression analyses, ST elevation MI (P

Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)?A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos.Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO.This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles.The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments.The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P =0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P =0.001, respectively).Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results.To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO.None.Not applicable.

Background The major determinants and prognostic importance of self‐reported health in patients with stable coronary heart disease are uncertain. Methods and Results The STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial randomized 15 828 patients with stable coronary heart disease to treatment with darapladib or placebo. At baseline, 98% of participants completed a questionnaire that included the question, “Overall, how do you feel your general health is now?” Possible responses were excellent, very good, good, average , and poor . Adjudicated major adverse cardiac events, which included cardiovascular death, myocardial infarction, and stroke, were evaluated by Cox regression during 3.7 years of follow‐up for participants who reported excellent or very good health (n=2304), good health (n=6863), and average or poor health (n=6361), before and after adjusting for 38 covariates. Self‐reported health was most strongly associated with geographic region, depressive symptoms, and low physical activity ( P HR ]: 2.30 [95% confidence interval ( CI ), 1.92–2.76]; adjusted HR : 1.83 [95% CI , 1.51–2.22]), cardiovascular mortality ( HR : 4.36 [95% CI , 3.09–6.16]; adjusted HR : 2.15 [95% CI , 1.45–3.19]), and myocardial infarction ( HR : 1.87 [95% CI , 1.46–2.39]; adjusted HR : 1.68 [95% CI , 1.25–2.27]; P Conclusions Self‐reported health is strongly associated with geographical region, mood, and physical activity. In a global coronary heart disease population, self‐reported health was independently associated with major cardiovascular events and mortality beyond what is measurable by established risk indicators. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 00799903.

Previous studies have suggested that antimüllerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality.The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos.The study was a prospective cohort study between April 2008 and June 2011.The study was done at a university-affiliated private infertility center.The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles.AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome.Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured.AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH2.94 ng/mL (75th percentile), Ptrend.0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores.AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

We appreciate the valuable comments by Ciliberti et al in their letter to the editor on our article on medical therapy in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA).1 Ciliberti et al raise several important issues on which we are happy to further comment. Our study population consisted of 9136 consecutive patients with acute myocardial infarction (AMI) and without any significant obstruction (≥50%) on coronary angiography reported to the nationwide quality registry, SWEDEHEART, during a 10-year period. We agree that there is a heterogeneity in this real-life population in terms of the underlying mechanisms for MINOCA. There is certainly a significant group of patients given the clinical diagnosis of MINOCA …

Introduction: Physical activity (PA) reduces the risk of events in patients with stable coronary heart disease (CHD). Biomarkers reflecting myocardial dysfunction, renal function and inflammatory activity are associated with outcomes in stable CHD. It is poorly known to what extent the benefits of PA may be linked to biomarker levels. Hypothesis: The association between PA and outcomes may be mediated by processes indicated by changes in the levels of prognostic biomarkers. Methods: At baseline, 15,486 patients with stable CHD participating in the global STABILITY trial, completed a baseline lifestyle questionnaire including self-reporting on hours spent each week on mild, moderate and vigorous exercise, corresponding to approximately 2, 4 and 8 METS, respectively. Plasma levels of high-sensitivity (hs) C-reactive protein (hs-CRP), hs-troponin T (hs-TnT), N-terminal pro-B type natriuretic peptide (NT-proBNP), cystatin-C, growth differentiation factor-15 (GDF-15) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were assessed from plasma samples obtained at baseline. Associations between PA and biomarker levels were evaluated after multivariable adjustments (age, gender, traditional clinical cardiovascular risk factors and standard biomarkers including cholesterol levels) with sedentary patients as reference. Results: Associations between levels of PA and hs-CRP, hs-TnT, NT-proBNP, cystatin C, GDF-15 and activity of Lp-PLA2 are shown in the Table, after adjustments for co-variables. PA was independently and inversely associated with all biomarker levels, except for Lp-PLA2. Conclusions: Increasing PA, was independentlyand inversely associated with levels of most clinically important biomarkers, except for Lp-PLA2. The effects of PA on outcomes may partly be explained by disease processes reflected by changes in biomarker levels.

Study question Which embryo score variables are most powerful for predicting live birth after single embryo transfer (SET) at the early cleavage stage? Summary answer This large prospective study of visual embryo scoring variables shows that blastomere number (BL), the proportion of mononucleated blastomeres (NU) and the degree of fragmentation (FR) have independent prognostic power to predict live birth. What is known already Other studies suggest prognostic power, at least univariately and for implantation potential, for all five variables. A previous study from the same centre on double embryo transfers with implantation as the end-point resulted in the integrated morphology cleavage (IMC) score, which incorporates BL, NU and EQ. Study design, size and duration A prospective cohort study of IVF/ICSI SET on Day 2 (n = 6252) during a 6-year period (2006-2012). The five variables (BL NU, FR, EQ and symmetry of cleavage (SY)) were scored in 3- to 5-step scales and subsequently related to clinical pregnancy and LBR. Participants/materials, setting, methods A total of 4304 women undergoing IVF/ICSI in a university-affiliated private fertility clinic were included. Generalized estimating equation models evaluated live birth (yes/no) as primary outcome using the embryo variables as predictors. Odds ratios with 95% confidence intervals and P-values were presented for each predictor. The C statistic (i.e. area under receiver operating characteristic curve) was calculated for each model. Model calibration was assessed with the Hosmer-Lemeshow test. A shrinkage method was applied to remove bias in c statistics due to over-fitting. Main results and the role of chance LBR was 27.1% (1693/6252). BL, NU, FR and EQ were univariately highly significantly associated with LBR. In a multivariate model, BL, NU and FR were independently significant, with c statistic 0.579 (age-adjusted c statistic 0.637). EQ did not retain significance in the multivariate model. Prediction model calibration was good for both pregnancy and live birth. We present a ranking tree with combinations of values of the BL, NU and FR embryo variables for optimal selection of the embryo/s to transfer, providing a revised IMC score. The five embryo variables had similar effects over all age groups. Limitations, reasons for caution Limitations of the present study are those inherent for real-time visual scoring, including risks of inter-observer variation and the hazards of fixed time-point scoring procedures in a dynamic process. The study is restricted to Day-2 transfers. Wider implications of the findings To our knowledge this is the largest prospective, SET study performed with the explicit aim of constructing an evidence-based embryo score for the ranking and selection of early cleavage stage embryos. In line with previous research, our data suggest that the symmetry of cleavage variable may be omitted when scoring embryos in the early cleavage stage. We suggest that, following validation in other populations, the revised IMC score may be used when international standards for embryo scoring are discussed. Study funding/competing interest Carl von Linne Clinic, Uppsala and the Department of Women's and Children's Health and the Family Planning Fund in Uppsala, Uppsala University, Uppsala, Sweden financed this study. There are no competing interests to declare.

Self-Reported General Health And Outcomes In Patients With Stable Coronary Artery Disease : Experiences From The Global Stability Trial

To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC.Prospective observational study.University-affiliated private infertility center.2,092 women undergoing 4,308 IVF-ICSI cycles.AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age.Pregnancy rate, live-birth rate, and stimulation outcome parameters.The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved.Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

The objective of this study was to evaluate the associations of basal gonadotrophins with pregnancy and delivery rates at IVF/ICSI.A prospective observational study was conducted at a university-affiliated private infertility centre. Patients were 745 women, who underwent 1328 IVF/ICSI treatment cycles. Basal FSH, basal LH and combinations of FSH and LH versus treatment data and pregnancy and delivery rates were measured.Combinations of FSH and LH gave significantly better information than the LH:FSH ratio, or each gonadotrophin alone: highest mean pregnancy rate (39%) was achieved in women with low FSH (6.7 U/l) and with high LH levels (4.9 U/l), whereas pregnancy rate was lowest (22%) in women with high FSH and low LH levels. Pregnancy rates were intermediate (27-28%) if FSH and LH were either both low or both high (P for trend = 0.0004). Associations to delivery rates and measures of ovarian response and embryo quality followed the same pattern.Basal LH modifies and improves the information given by basal FSH alone. Low FSH level combined with high LH probably reflects a well-preserved ovarian reserve and is associated with the highest success rates at IVF/ICSI.

To investigate whether menstrual cycle length correlates with success rates at IVF/intracytoplasmic sperm injection (ICSI) and could be used as a marker of ovarian reserve.Prospective observational study.Private infertility centre.A total of 6271 IVF/ICSI treatment cycles.Self-reported mean number of menstrual days during the last year was recorded before initiation of IVF/ICSI treatment.Relations between menstrual cycle length and pregnancy and delivery rates.Increasing age was associated with a subtle shortening of mean menstrual cycle length. Menstrual cycle length correlated linearly with pregnancy and delivery rates, even after age adjustment. The chance of delivery after IVF/ICSI was almost doubled for women with a menstrual cycle length34 days compared with women with a menstrual cycle length26 days. Menstrual cycle length was also significantly associated with ovarian response to FSH/hMG stimulation and embryo quality.Mean menstrual cycle length is highly related to success rates in assisted reproduction, independently of age. A precise menstrual cycle history could be used as a simple marker of ovarian reserve.

Objective To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Design Retrospective cross-sectional study. Setting University-affiliated private center. Patient(s) The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist–recombinant FSH protocol). Intervention(s) None. Main Outcome Measure(s) The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. Result(s) OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. Conclusion(s) The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns.

Purpose: To investigate whether unrecognised myocardial infarctions (UMI) detected by late enhancement cardiac magnetic resonance (CMR) in patients with stable coronary artery disease is associated with stenotic lesions on coronary angiography. Methods: In this multicenter study we included patients (65±8 years-of-age) scheduled for coronary angiography with symptoms of angina, but without previously known myocardial infarction (MI) or coronary intervention. CMR was performed on a clinical 1.5T scanner and consisted of delayed-enhancement images using an inversion recovery gradient echo sequence covering the entire left ventricle in the short-axis and three long-axis views. At CMR, areas of delayed contrast enhancement that were visible in at least two imaging planes were noted and localised using the AHA 17-segment model. They were categorised in four groups where "subendocardial" and "transmural" in the following were labelled UMI, whereas "no late enhancement" and "other" were labelled no MI. CMR was followed by coronary angiography and the degree of narrowing of the diameter in each of the 19 coronary segments was categorized as 0-29% (normal), 30-49%, 50-69%, 70-99% or 100% (occlusion). If stenosis was 30% or above we determined visually, depending on the individual coronary anatomy, which of the myocardial segments in the AHA 17-segment model that downstream of the stenosis were affected by the lesion. Both CMR and coronary angiography were first evaluated separately by two independent radiologists and then in consensus, blinded for the result on the other examination. Results: 1. An analysis of the first 104 out of totally 267 included subjects showed that 26 out of the 104 had UMIs with a subendocardial component at CMR. 23 of those 26 subjects had at least one stenosis ≥70% at coronary angiography and 25 of 26 had at least one stenosis ≥30%. 2. An UMI was present in 53 out of 1768 (104*17) myocardial segments. 33 (62%) of those 53 segments were supplied by a coronary branch with ≥70% stenosis at coronary angiography. The prevalence of UMI was 1.6, 4.7 and 17.3% in the myocardial segments supplied by a coronary branch with a stenosis

Background A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient. Methods In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years. Results UMIs were found in 25 % of patients. There was a strong association between stenotic lesions (≥70 % stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis ≥ 70 % as compared to