Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study.

STUDY QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? SUMMARY ANSWER: PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). WHAT IS KNOWN ALREADY: Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. STUDY DESIGN, SIZE, DURATION: This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12 631 FET cycles in 10 060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. MAIN RESULTS AND THE ROLE OF CHANCE: In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age <35 years, 1.45 (95% CI: 1.21, 1.75) for ages 35-37 years, 1.89 (95% CI: 1.56, 2.29) for ages 38-40, 2.62 (95% CI: 1.94-3.53) for ages 41-42, and 3.80 (95% CI: 2.52, 5.72) for ages >42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age <35 years, 1.37 (95% CI: 1.14, 1.64) for ages 35-37 years, 1.68 (95% CI: 1.40, 2.03) for ages 38-40 years, 2.19 (95% CI: 1.65, 2.90) for ages 41-42, and 2.31 (95% CI: 1.60, 3.32) for ages >42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age <35 years, 0.85 (95% CI: 0.65, 1.11) for ages 35-37 years, 0.81 (95% CI: 0.60, 1.08) for ages 38-40, 0.86 (95% CI: 0.58, 1.27) for ages 41-42, and 0.58 (95% CI: 0.32, 1.07) for ages >42 years. LIMITATIONS, REASONS FOR CAUTION: The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. STUDY FUNDING/COMPETING INTEREST(S): There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey.

BACKGROUND: Coronary heart disease (CHD) mortality continued to decline from 1985 to 1997. METHODS AND RESULTS: We tabulated CHD deaths (ICD-9 codes 410 through 414) in the Minneapolis/St Paul, Minnesota, area. For 1985, 1990, and 1995, trained nurses abstracted the hospital records of patients 30 to 74 years old with a discharge diagnosis of acute CHD (ICD-9 codes 410 or 411). Acute myocardial infarction (AMI) events were validated and followed for 3-year all-cause mortality. Between 1985 and 1997, age-adjusted CHD mortality rates in Minneapolis/St Paul fell 47% and 51% in men and women, respectively; the comparable declines in US whites were 34% and 29%. In-hospital mortality declined faster than out-of-hospital mortality. The rate of AMI (ICD-9 code 410) hospital discharges declined almost 20% between 1985 and 1995, whereas the discharge rate for unstable angina (ICD-9 code 411) increased substantially. The incidence of hospitalized definite AMI declined approximately 10%, whereas recurrence rates fell 20% to 30%. Three-year case fatality rates after hospitalized AMI decreased consistently by 31% and 41% in men and women, respectively. In-hospital administration of thrombolytic therapy, emergency angioplasty, ACE inhibitors, beta-blockers, heparin, and aspirin increased greatly. CONCLUSIONS: Declining out-of-hospital death rates, declining incidence and recurrence of AMI in the population, and marked improvements in the survival of AMI patients all contributed to the 1985 to 1997 decline of CHD mortality in the Minneapolis/St Paul metropolitan area. The effects of early and late medical care seem to have had the greatest contribution to rates during this time period.

Secular trends in dietary macronutrient intake in Minneapolis-St, Paul, Minnesota, 1980-1992.

Trends in dietary macronutrient intake were evaluated in population-based surveys conducted in adults aged 25-74 years in 1980-1982, 1985-1987, and 1990-1992 in the seven-county Minneapolis-St. Paul metropolitan area. A 24-hour dietary recall (n = 6,499) was completed by a random 50% sample. The authors obtained energy intake for each macronutrient (protein, carbohydrate, fat, saturated fat, monounsaturated fat, polyunsaturated fat, and alcohol). Tine trends for percentage of total energy were analyzed using a generalized linear mixed model. While energy intake remained stable over time, macronutrient composition changed substantially. In 1980-1982, the caloric distribution for men comprised 15.8% protein, 39.4% fat, 40.9% carbohydrate, and 3.9% alcohol; similar findings were observed in women (15.7% protein, 38.9% fat, 43% carbohydrate, and 2.4% alcohol). From 1980 to 1992, total fat intake decreased 4.7% in men and 4.9% in women (p < 0.001). The decline was greatest for monounsaturated fat, although saturated and polyunsaturated fat intake also fell. During this same period, carbohydrate intake increased 5.7% and 5.8% in men and women, respectively (p < 0.001). Alcohol intake decreased in men and women (p < 0.01), while protein intake remained stable. In summary, the Minneapolis-St. Paul metropolitan area diet shifted substantially during the 1980s toward more carbohydrate and lower fat and alcohol intake.

Differences and trends in antioxidant dietary intake in smokers and non-smokers, 1980-1992: the Minnesota Heart Survey.

PURPOSE: Differences and secular trends in dietary antioxidant vitamin intake (vitamins E, C, and beta-carotene) in current non-smokers, light smokers, and heavy smokers were examined as part of the Minnesota Heart Survey. METHODS: Three cross-sectional surveys were conducted in adults ages 25-74 years in 1980-82 (N = 1682), 1985-87 (N = 2326), and 1990-92 (N = 2487). Dietary information was obtained from a 24-hour dietary recall. Smoking was assessed through self-report. Intakes were adjusted for age, energy intake, body mass index, education level, and exercise level (vitamins E, C and beta-carotene). RESULTS: Antioxidant vitamin intakes were significantly higher in non-smokers than in light (1-20 cig/day) and heavy smokers (>20 cig/day) when all three survey periods were combined. In men, mean vitamin E intake was 9.2 mg, 8.6 mg, and 7.8 mg for non-smokers, light smokers, and heavy smokers, respectively. Results were similar in men for beta-carotene (non-smokers 1408 microg, light smokers 1287 microg, and heavy smokers 1064 microg), and vitamin C (non-smokers 81 mg, light smokers 67 mg, and heavy smokers 56 mg). Women had results of similar magnitude and direction. From 1980-92, secular trends in men showed non-significant increases from 1980-82 to 1990-92 in beta-carotene (+6.1%), while decreases were observed in vitamins E (-1.1%) and C (-2.6%). In contrast, women had large decreases in all antioxidant vitamin intakes: vitamin E (-13%), vitamin C (-18.6%), and beta-carotene (-16.2%). CONCLUSIONS: Light and heavy smokers had a significantly lower overall mean dietary antioxidant vitamin intake than non-smokers. Over the decade, antioxidant dietary intake remained relatively stable in men and decreased in women in Minneapolis-St. Paul, despite improvements in access to antioxidant rich fruits and vegetables.

Components of variance in a group-randomized trial analysed via a random-coefficients model: the Rapid Early Action for Coronary Treatment (REACT) trial.

Rapid Early Action for Coronary Treatment (REACT) was a multisite trial testing a community intervention to reduce the delay between onset of symptoms of acute myocardial infarction (MI) and patients' arrival at a hospital emergency department. The study employed a group-randomized trial design, with ten communities randomized from within matched pairs to each of two conditions. REACT also employed continuous data collection, based on surveillance of heart attack patients in community emergency departments. They analysed their data by comparing the mean slope for delay time in the ten intervention communities to the mean slope estimated in the ten control communities. Because no estimates of slope variation were available a priori, REACT was sized using approximations based on more traditional designs. In this paper, we present the slope and residual error variances as estimated from the REACT data and examine their influence on the power of the trial post hoc. We also examine the power of the trial as it would have been given a more traditional pretest-post-test design with analysis via a comparison of the net difference in condition means pretest vs post-test.

Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease. OBJECTIVE: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease. MEASUREMENTS: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995. RESULTS: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat. CONCLUSIONS: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.

Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease: The Rapid Early Action for Coronary Treatment (REACT) Trial.

CONTEXT: Delayed access to medical care in patients with acute myocardial infarction (AMI) is common and increases myocardial damage and mortality. OBJECTIVE: To evaluate a community intervention to reduce patient delay from symptom onset to hospital presentation and increase emergency medical service (EMS) use. DESIGN AND SETTING: The Rapid Early Action for Coronary Treatment Trial, a randomized trial conducted from 1995 to 1997 in 20 US cities (10 matched pairs; population range, 55,777-238,912) in 10 states. PARTICIPANTS: A total of 59,944 adults aged 30 years or older presenting to hospital emergency departments (EDs) with chest pain, of whom 20,364 met the primary population criteria of suspected acute coronary heart disease on admission and were discharged with a coronary heart disease-related diagnosis. INTERVENTION: One city in each pair was randomly assigned to an 18-month intervention that targeted mass media, community organizations, and professional, public, and patient education to increase appropriate patient actions for AMI symptoms (primary population, n=10,563). The other city in each pair was randomly assigned to reference status (primary population, n=9801). MAIN OUTCOME MEASURES: Time from symptom onset to ED arrival and EMS use, compared between intervention and reference city pairs. RESULTS: General population surveys provided evidence of increased public awareness and knowledge of program messages. Patient delay from symptom onset to hospital arrival at baseline (median, 140 minutes) was identical in the intervention and reference communities. Delay time decreased in intervention communities by -4.7% per year (95% confidence interval [CI], -8.6% to -0.6%), but the change did not differ significantly from that observed in reference communities (-6. 8% per year; 95% CI, -14.5% to 1.6%; P=.54). EMS use by the primary study population increased significantly in intervention communities compared with reference communities, with a net effect of 20% (95% CI, 7%-34%; P<.005). Total numbers of ED presentations for chest pain and patients with chest pain discharged from the ED, as well as EMS use among patients with chest pain released from the ED, did not change significantly. CONCLUSIONS: In this study, despite an 18-month intervention, time from symptom onset to hospital arrival for patients with chest pain did not change differentially between groups, although increased appropriate EMS use occurred in intervention communities. New strategies are needed if delay time from symptom onset to hospital presentation is to be decreased further in patients with suspected AMI. JAMA. 2000;284:60-67

Mortality, hospital discharges, and case fatality for pulmonary embolism in the Twin Cities: 1980-1995.

Pulmonary embolism (PE) causes substantial morbidity and mortality, but little information is available regarding recent secular trends for PE. This study determined trends for PE in adults ages 30 to 84 years in the Minneapolis-St. Paul metropolitan area from 1980 to 1995. The age-adjusted mortality rate for PE decreased approximately 50% during the study period; the rate ratio (RR) for 1992-95 compared to 1980-83 was 0.41 in men [95% confidence interval (CI) 0.31-0.55] and was 0.60 in women (95% CI 0.46-0.79). The hospital discharge rate for PE also decreased from 1980-83 to 1988-91 (RR 0.69, 95% CI 0.63-0.76 in men; RR 0.72, 95% CI 0.66-0.78 in women), but increased slightly between 1988-91 and 1992-95. The case fatality rate for PE decreased approximately 60% during the period (RR 0.38, 95% CI 0.28-0.51 in men; RR 0.37, 95% CI 0.28-0.50 in women). The PE trends were paralleled by declining hospital discharge rates for phlebitis and thrombophlebitis. These data support a changing natural history or possible improvements in the prevention, diagnosis, and treatment of PE between 1980 and 1995.

Effectiveness of monetary incentives for recruiting adolescents to an intervention trial to reduce smoking.

BACKGROUND: The study objective is to evaluate the effect of monetary incentives on response rates of adolescents to a smoking-related survey as the first step toward participation in an intervention trial. METHODS: A sample of 4,200 adolescent members of a managed care organization were randomized to one of four incentive groups: a $2 cash group, a $15 cash group, a $200 prize drawing group, or a no-incentive group. We compared group-specific response rates and willingness to be contacted about future study activities, as well as costs. RESULTS: Incentives increased survey response rates (55% response without incentive vs. a 69% response with incentive), with response of 74% in the $15 cash group, 69% in the token group, and 63% with a prize incentive. Incentives did not adversely affect willingness of adolescents to be contacted about a smoking intervention, (65% willing with incentives vs. 60% without, P = 0.03). In terms of cost per additional survey completed, token and prize groups were marginally more expensive than the no-incentive group ($0.40 and $1.42, respectively) while the large cash incentive was substantially more costly ($11.37). CONCLUSIONS: Monetary incentives improve response rates to a mailed survey, without adverse impact on willingness to further participate in intervention activities. However, a variety of issues must be considered when using incentives for recruitment to intervention studies.