No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis.

STUDY QUESTION: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? SUMMARY ANSWER: The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. WHAT IS KNOWN ALREADY: Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. STUDY DESIGN, SIZE, DURATION: This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). LIMITATIONS AND REASONS FOR CAUTION: The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. WIDER IMPLICATIONS OF THE FINDINGS: There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.

Prediction of live birth in frozen-thawed single blastocyst transfer cycles by pre-freeze and post-thaw morphology.

STUDY QUESTION: What pre-freeze and post-thaw morphological parameters can be used to predict live birth outcomes after frozen-thawed blastocyst transfer cycles? SUMMARY ANSWER: Pre-freeze blastocoele expansion and trophectoderm (TE) grade and post-thaw degree of re-expansion are the most significant predictors of live birth in frozen-thawed blastocyst transfer cycles. WHAT IS KNOWN ALREADY: Currently, blastocoele re-expansion after thawing is used to indicate blastocyst cryosurvival and reproductive potential. The predictive roles of other pre-freeze and post-thaw morphological parameters are neglected. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of all the patients who received a frozen-thawed single blastocyst transfer (n = 1089) at our clinic between March 2008 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pre-freeze morphological parameters analyzed for all blastocysts included grade of blastocoele expansion, inner cell mass and TE. A group of blastocysts (n = 243) were also graded for post-thaw parameters: degree of blastocoele re-expansion, viability and cell contour. Univariate and multivariate generalized estimating equations (GEEs) models were used to identify the confounders that statistically significantly affected live birth outcomes and to investigate the independent effect of significant pre-freeze and post-thaw morphological parameters. Stepwise logistic regression analysis was used to select the best independent morphological predictors of live birth. Pearson correlations and linear regression analyses were performed to determine the relationship between morphological parameters and possible covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Multivariate GEE models estimated that the odds of live birth increased by ∼36% for each grade of expansion (P = 0.0061) and decreased by 29% for blastocysts with grade B TE compared with grade A TE (P = 0.0099). Furthermore, the odds of live birth increased by ∼39% (P = 0.0042) for each 10% increase in degree of re-expansion. Blastocoele expansion and TE grade were selected as the most significant pre-freeze morphological predictors of live birth and degree of re-expansion was selected as the best post-thaw parameter for prediction of live birth. LIMITATIONS, REASONS FOR CAUTION: Blastocysts with poorer grades of morphology were not cryopreserved or transferred, limiting the ability to generalize our findings for grades of morphology not included in this study. WIDER IMPLICATIONS OF THE FINDINGS: Blastocysts with higher pre-freeze grades of expansion and TE, irrespective of day of cryopreservation, should be given priority when thawing. Subsequently, re-expanding blastocysts, assessed within 2-4 h, with >60% viability should be transferred. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There was no competing interest. TRIAL REGISTRATION NUMBER: not applicable.

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial.

BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363.

Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer.

BACKGROUND: In order to select the best blastocyst for transfer, in humans, three morphological parameters have routinely been used, i.e. degree of blastocoele expansion and appearance of both the trophectoderm (TE) and the inner cell mass (ICM). Although it has been shown that blastocysts with highest scores for all three parameters achieve highest implantation rates, their independent ability to predict pregnancy outcome remains unclear. METHOD: This study is a retrospective analysis of 1117 fresh day 5 single blastocyst transfers and their live birth outcome related to each morphological parameter. RESULTS: All three parameters had a significant effect on live birth however, once adjusted for known significant confounders, it was shown that TE was the only statistically significant independent predictor of live birth outcome. CONCLUSIONS: This study has shown, for the first time, the predictive strength of TE grade over ICM for selecting the best blastocyst for embryo replacement. It may be that, even though ICM is important, a strong TE layer is essential at this stage of embryo development, allowing successful hatching and implantation.

Obstetric outcomes after transfer of vitrified blastocysts.

BACKGROUND: It has been claimed that the risks to the child resulting from vitrification as compared with the slow-freezing technique, may be higher owing to the high concentrations of potentially toxic cryoprotectants. We therefore retrospectively compared the obstetric and neonatal outcomes in a cohort of children born after transfer of vitrified blastocysts, fresh blastocysts and slow-frozen early cleavage stage embryos. METHODS: All children born after transfer of vitrified blastocysts (n = 106), fresh blastocysts (n = 207) and slow-frozen early cleavage stage embryos (n = 206) during the period January 2006 to May 2008 at Fertility Center Scandinavia were included. Data on obstetric and neonatal outcomes were obtained from medical records from the antenatal and delivery clinics. RESULTS: For singletons, there were no significant differences between the groups in gestational age, mortality or birth defects. After adjustment for parity and BMI, birthweight was significantly higher in singletons born after transfer of vitrified blastocysts as compared with after transfer of fresh blastocysts (median 3560 versus 3510 g, P = 0.0311). More singletons born after transfer of fresh blastocysts were small for gestational age compared with singletons born after transfer of vitrified blastocysts (12.1 versus 3.0%, P = 0.0085). A higher rate of major post-partum haemorrhage was observed in the vitrified blastocyst group as compared with the other two groups (25.0 versus 6.0 and 7.5%). CONCLUSIONS: No adverse neonatal outcomes were observed in children born after transfer of vitrified, as compared with fresh blastocysts or after transfer of slow-frozen early cleavage stage embryos.

Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.

BACKGROUND: In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo. METHODS: One hundred and seventy-three embryos diagnosed as chromosomally abnormal, 22 with no PGS result and four degenerated embryos originally diagnosed as normal were fixed and reanalysed by fluorescence in situ hybridization. RESULTS: In total, 199 embryos were fixed, of which 166 were successfully reanalysed. One hundred and sixty embryos were found to be chromosomally abnormal; 48 of the reanalysed embryos with an initial diagnosis (149) had at least one cell with exactly the same chromosomal constitution shown in the first PGS analysis (34.2%). The reanalysis confirmed the initial overall chromosomally abnormal status of the embryo in 95.9% of the cases. Of all chromosomally abnormal embryos, 4.1% were diagnosed as false positive. The risk for false negative rate was at least 4.1%. CONCLUSIONS: PGS seems to be a good method for selecting against chromosomally abnormal embryos but not for determining an embryo's exact chromosomal constitution.

Preimplantation genetic screening in women of advanced maternal age caused a decrease in clinical pregnancy rate: a randomized controlled trial.

BACKGROUND: Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate. METHODS: We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. RESULTS: The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039). CONCLUSIONS: Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. TRIAL REGISTRATION NUMBER: ISRCTN38014610.

Increasing glucose levels and BMI predict future heart failure experience from the Reykjavík Study.

BACKGROUND: Heart failure is common in diabetes and ischaemic heart disease is the most likely link. Still, it has been suggested that the relation extends beyond such disease. METHODS: 7060 subjects with two or more visits in the Reykjavík Study were followed--during 30 years from 1967. All underwent oral glucose tolerance tests. Disease status was defined according to the glycaemic level and presence of heart failure. The incidence and predictive factors for these diseases were determined. FINDINGS: Age and sex standardized incidence of heart failure was 5.3/1000/year, of diabetes 4.6/1000/year and abnormal glucose regulation 12.6/1000/year. Body mass index (BMI) and fasting glucose predicted the development of these conditions (p<0.001). Increasing fasting glucose by 1 mmol/l increased the risk for heart failure by 14% (p=0.04) after adjusting for IHD, BMI and other risk factors for CVD. There was a strong association between diabetes and heart failure, OR 3.0 (2.3-4.0), and abnormal glucose regulation and heart failure, OR 1.8 (1.5-2.3). Diabetes and heart failure were, however, not independent predictors of each other. INTERPRETATION: There was an independent relationship between increases in fasting glucose and development of heart failure. BMI was a strong predictor of heart failure. Although fasting glucose and BMI were significant risk factors for glucose disturbances and heart failure the conditions themselves did not independently predict each other.

Predictors of ongoing implantation in IVF in a good prognosis group of patients.

BACKGROUND: The aim of this study was to investigate whether, in a large randomized trial, it is possible to identify specific maternal and/or embryo variables that could independently correlate with ongoing implantation in IVF/ICSI. METHODS: In a Scandinavian study, 661 women were randomized to elective single embryo transfer or double embryo transfer. Women aged <36 years undergoing their first or second IVF cycle and with at least two good quality embryos were eligible. Only one cycle per subject was included. In the present study, cycles with 0 or 100% ongoing implantation (n = 520) were analysed regarding maternal and embryo variables. RESULTS: In this selected study group, the ongoing implantation rate was 195/734 (26.6%). In the univariate analysis, first IVF cycle, conventional IVF as fertilization method and 4-cell embryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI and non-4-cell embryos. In the multivariate analysis the same variables correlated independently to ongoing implantation. In addition, ovarian sensitivity correlated independently to ongoing implantation. CONCLUSION: This information should be used when selecting the number of embryos for transfer with the overall aim to reduce the rate of multiple births while maintaining a satisfactory birth rate.

Avoidance of multiple pregnancy by use of single embryo transfer.

The benefits of single embryo transfer (SET) for both mother and child are evident. Already twin pregnancies constitute a relatively serious problem exemplified by the incidence of cerebral palsy, which will increase significantly as well as a risk for premature birth. Selective embryo reduction in countries where this is allowed may be one way to acutely solve the situation. In the beginning the use of natural cycle in vitro fertilization (IVF) avoided the problem, but with the introduction of controlled ovarian hyperstimulation predominantly by use of gonadotrophins in the early 1980ies the temptation to replace more than 1 embryo at a time became too strong. SET with maintenance of acceptable pregnancy rates can only be achieved if tools (improved morphological criteria, biomarkers, preimplantation genetic screening) to select the most viable/normal embryos are at hand together with improved cryopreservation procedures. In reports from Finland and Belgium already 5 years ago, elective single embryo transfer (eSET) was shown to reach almost the same success rates as double embryo transfer (DET) in selective patient groups (age under 37, good quality embryos). The indications for eSET have increased during the last years. In Finland the initiative came from the IVF clinics while in Sweden a legislative process (in act from January 2003) resulted in the recommendation that eSET should be used in the vast majority of the IVF cycles. In both these Nordic countries around 60% of the transfers are today eSET and the multiple pregnancy rate below 10% with no triplets. From an economical point of view, it is of course evident that multiple pregnancies with the numerous potential complications should be avoided altogether. Countries where IVF is included in the government health insurance will thus most likely show the way towards an even more successful, safer and cheaper treatment of infertile couples in the future.

Internalization of cellular fragments in a human embryo: time-lapse recordings.

An observation is reported of internalization of a cellular fragment into a blastomere from a human embryo, as documented by time-lapse photography. The fragment, created during the first mitotic cleavage was reabsorbed into one of the mother blastomeres in less than 5 min. The time-lapse sequence, shown here as a series of still photographs, provides the first direct evidence that cellular fragments in human embryos can 'disappear' during the culture period, a phenomenon that is common in human IVF. The time-lapse sequence itself may be viewed on the internet at www.rbmonline.com/Article/633.

Early embryo cleavage is a strong indicator of embryo quality in human IVF.

BACKGROUND: In order to decrease multiple birth rates without decreasing birth rates overall, it is important to increase the capability of selecting the most optimal embryos for transfer. It has been shown that human embryos which cleave early, i.e. complete the first mitotic division within 25-27 h post insemination, provide higher pregnancy and implantation rates. METHODS AND RESULTS: In this prospective study, an evaluation of 10 798 scored embryos showed that early cleavage resulted in a significantly higher proportion of good quality embryos compared with late cleavage (62.5 versus 33.4%, P < 0.0001). When examining both day 2 and day 3 transfers together, early-cleaving embryos (306 transfers) gave rise to significantly higher rates of pregnancy/transfer (40.5 versus 31.3%, P = 0.0049), implantation (28.0 versus 19.5%, P = 0.0001) and birth/ongoing pregnancy (34.3 versus 24.0%, P = 0.0009) than did late-cleaving embryos (521 transfers). A stepwise logistic regression of all data showed that the total number of good quality embryos and female age were independent predictors of both pregnancies and birth. For intracytoplasmic sperm injection (ICSI) embryos, early cleavage was found to be an independent predictor of birth. CONCLUSIONS: Early embryo cleavage is a strong biological indicator of embryo potential, and may be used as an additional embryo selection factor for ICSI embryos.

The relationship between educational level and mortality. The Reykjavík Study.

OBJECTIVE: Epidemiological studies have indicated an association between socioeconomic factors and health. It has not been clearly established whether this association is wholly or partly independent of classical risk factors. Our objective was to estimate the relationship between educational level and coronary artery disease (CAD), mortality and all-cause mortality. The Reykjavík Study involving 18 912 participants followed-up 4-30 years provides an ideal opportunity to address this question. DESIGN AND SUBJECTS: The participants were aged 33-81 years and living in the Reykjavík area. They were divided into four groups according to education. The standard risk factors were assessed on entry and mortality, and cause of death registered during follow-up. Multiple Cox regression analysis was applied to assess the relationship between age at examination, year of examination, educational level and mortality. RESULTS: The all-cause mortality and CAD mortality was significantly related to education, even after adjustment for classical risk factors. For men, 14% (95% CI: 2-24) reduction was found in CAD mortality for those having high school education relative to elementary school. The figures for junior college and university education were 17% (95% CI: 1-31) and 38% (95% CI: 21-32), respectively. These figures were only slightly lower when major CAD risk factors were controlled for and still significant. Similar figures were found for all-cause mortality. For women 34% (95% CI: 18-48) reduction was found in CAD mortality for high school education and 55% (95% CI: 22-74) for junior college, but too few had university education for reliable results. The figures were lower for all-cause mortality, but significant. The figures were reduced when major CAD risk factors were controlled for, but still significant. CONCLUSION: Education is a strong protective factor both for all-cause and CAD mortality. Only a small part of this effect can be explained through conventional risk factors.

Preimplantation genetic diagnosis (PGD): the Gothenburg experience.

BACKGROUND: A program for preimplantation genetic diagnosis of pre-embryos from patients with hereditary disorders was set up in our unit at Sahlgrenska University Hospital in 1994. The majority of the patients were carriers of X-chromosome linked disorders; a few patients were translocation carriers. In this paper we describe our experiences of our first 36 cycles, 30 gender determinations and six analyses of embryos with possible translocations. METHODS: Conventional hormone replacement treatment with intracytoplasmic sperm injection to fertilize the eggs followed by blastomere biopsy and fluorescent in situ hybridization at the eight cell stage was used for sexing as well as detection of translocations. RESULTS: Out of the 30 cycles in 13 patients for gender determination, blastomere biopsies could be carried out in 25 cycles. Transfer of normal female embryos (XX) was performed in 18 cycles, resulting in five pregnancies (pregnancy rate 27.8%) and an implantation rate of 20% per transfer. Three girls have been born. Hence the take home baby rate was 16.7% per transfer and 10% per started cycle. Six cycles (three patients) for detection of translocations in embryos were performed. Diagnosis was possible in four cycles. Transfer of normal embryos was carried out in one cycle. No pregnancy was achieved. CONCLUSION: Successful PGD in its clinical application demands close collaboration between a large group of specialists. Even so, the success rate is considerably lower than after conventional IVF or ICSI procedures. Taking into account the stress caused to the parents facing late interruption of pregnancy following conventional prenatal diagnosis we are convinced that this technique is well worthwhile continuing and refining.

Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation.

Uneven blastomere cleavage in human embryos of 'good morphology', i.e. those normally used for transfer, is a phenomenon which has been poorly investigated. The main objective in this study was to probe deeper into the aetiology behind previous findings that embryos with uneven cell cleavage have a lower developmental capacity in comparison with evenly cleaved embryos. Our hypothesis was that uneven cleavage may result in embryos with a higher degree of aneuploidy and/or multinuclear rate, which in turn might help to explain their low implantation rate. In the first part of the study, 378 embryo transfers performed over a 3-year period were analysed retrospectively, where all the transferred embryos in each cycle were of identical morphology score and cleavage stage. In the second part of the study, multicolour fluorescence in-situ hybridization (FISH) analyses on good quality embryos, representing the uneven (n = 11) and even (n = 13) study groups were performed. When comparing day 2 transfers between 4-cell embryos, it was found that unevenly cleaved embryos had significantly lower implantation (23.9 and 36.4%) and pregnancy rates (37.6 and 52.9%) compared with evenly cleaved embryos. A significantly higher degree of aneuploidy (29.4 and 8.5%) and multinuclear rate (21.1 and 2.1%) in blastomeres from uneven embryos was also found. It is concluded that uneven blastomere cleavage has a negative effect on both pregnancy and implantation rates in human IVF, and that this can partly be explained by a higher degree of aneuploidy/multinuclear rate. In the light of the results obtained, a new approach in the current embryo scoring system, placing more emphasis on blastomere size, is recommended.

The position of the metaphase II spindle cannot be predicted by the location of the first polar body in the human oocyte.

When performing intracytoplasmic sperm injection (ICSI) on human oocytes, the injection is traditionally made at the 3 o'clock position, with the first polar body (PB) at the 12 or 6 o'clock position. This has been based on the assumption that the second meiotic metaphase II (MII) spindle lies in close proximity to the first PB. The objective of this study was to document the actual spatial relationship between the first PB and the MII spindle both in in-vivo matured (fresh) human MII oocytes and in oocytes matured in vitro. We found that the MII spindle was, on average, not located directly adjacent to the PB. The in-vivo group (n = 54) showed a mean deviation of the MII spindle from the position of the PB of 41. 7 degrees and the in-vitro group 26.6 degrees (n = 43). The difference between the angle of the two groups was statistically significant (P = 0.005), indicating that the lateral displacement of the first PB is only partly due to the denuding procedure during ICSI, because the in-vitro matured oocytes were denuded before extrusion of the first PB. The majority of the MII spindles in both groups were found in the same hemisphere as the first PB, suggesting that care should be taken to avoid damaging the MII spindle by inserting the ICSI needle in the other half of the oocyte.

[In search for explanatory factors in the relationship between educational level and mortality.].

OBJECTIVE: The connection between socioeconomic status and mortality is well known in Western countries. Educational level has frequently been used as a socioeconomic indicator. In a recent Icelandic prospective study, an inverse relationship between educational level and mortality was shown. The objective of the present study is to consider possible explanatory factors. MATERIAL AND METHODS: This study was a part of the Reykjavík Study. A stratified sample of 400 people was taken from one of six study groups. The sample was equally divided between the sexes and four educational levels. Mean age of the sample was 72.7 years. Participants completed a questionnaire concerning knowledge of risk factors for coronary heart disease, expected response to symptoms of cardiac infarction, social network and use of health care. Response rate was 78.5%. The relationship between answers and educational level was assessed with logistic regression. RESULTS: People with higher education were more likely to be in personal contact with nurses and doctors and receive advice concerning health and treatment from them. Participants were generally satisfied with the Icelandic health care system and seemed generally to have good access to it. A relationship with educational level was not shown. A larger proportion of those with lower education had regular communication with their general practician. CONCLUSIONS: Our results suggest that certain health care services are integrated into the social network of those with higher education. This may lower their morbidity and mortality. Other hypotheses concerning possible explanatory factors for differences in health were not supported.

[Validation of an Icelandic version of the Geriatric Depression Scale (GDS).].

OBJECTIVE: Health-related quality of life (HRQL) is increasingly used to estimate needs for medical treatment, to evaluate its outcome and quality of care. The aim of this study was to compare the HRQL of several diagnostic groups before and after treatment with the HL-test (HL = IQL, Icelandic Quality of Life test) and to study its validity for measuring changes in quality of life. MATERIAL AND METHODS: Patients on waiting lists for coronary catheterization, orthopedic or urologic operations, patients in psychiatric out-patient treatment and patients entering treatment for alcohol dependence were asked to fill in the HL-test, a total of 1195 patients. Three months after treatment they were retested. The results of tests were standarized with population norms available to make them directly comparable with those of the general population. RESULTS: The response rate was 75% in each round. The HRQL of all patients was reduced in all aspects compared to that of the general population, that of the heart and urology patients less so than that of the orthopedic and psychiatric patients. Each group had a specific profile, especially marked for the orthopedic and psychiatric patients. Following treatment the HRQL or some aspects of it improved in all groups, especially for those which it had been most impaired. CONCLUSIONS: Studies of HRQL provide information useful for planning and delivery of health services. The HL-test is an instrument with good validity and reliability which is easy to use for such studies.

[Survival and trends of ocurrence of left ventricular hypertrophy, gender differences during 1967-1992. The Reykjavík Study.].

OBJECTIVE: We estimated the prevalence and incidence of left ventricular hypertrophy (LVH) in this large prospective cohort study of almost 20,000 participants and identified risk factors in them. Predictive factors of its appearance were evaluated along with morbidity and mortality calculations. MATERIAL AND METHODS: LVH was defined as Minnesota Code 310 on ECG. Everyone with this code at first visit was defined as a prevalence case and those who developed it between subsequent visits were incidence cases. Risk factors at the time of the diagnosis of LVH were determined with logistic regression. Predictive factors for acquiring this ECG abnormality were determined by Poisson regression. The comparison cohort were all other participants in the Reykjavík Study stages I-V. RESULTS: Two hundred ninety-seven men and 49 women were found to have LVH or 3.2% and 0.5%, respectively. The incidence was 25/1000/year among men and 6/1000/ year among women. Prevalence in both genders increased with increasing age. Risk factors at the time of diagnosis were systolic blood pressure (odds ratio pr. mmHg (OR) 1.02; 95% confidence interval (CI): 1.01-1.03), age (OR pr. year: 1.04; 95% CI: 1.02-1.05), silent myocardial infarction (MI) (OR: 3.18; 95% CI: 1.39-7.27) and ST-T changes (OR: 3.06; 95% CI: 2.14-4.38) among men and systolic blood pressure and age for women with similar odds ratio. Predictive factors for acquiring LVH were systolic blood pressure (incidence ratio (IR): 1.01; 95% CI: 1.01-1.02) and angina with ECG changes (IR: 2.33; 95% CI: 1.08-5.02) among men and systolic blood pressure among women (IR: 1.03; 95% CI: 1.01-1.04). In men severe smoking seemed to have a protective effect against developing LVH (IR: 0.36; 95% CI: 0.18-0.71). The risk for coronary mortality was significantly increased among women with hypertrophy (hazard ratio (HR): 3.07; 95% CI: 1.5-6.31) and their total survival was poorer with increasing time from diagnosis of LVH (HR: 2.17; 95% CI: 1.36-3.48). CONCLUSIONS: We conclude that the presence of LVH and its appearance is associated with age and increased blood pressure among both genders. Women with LVH have poorer survival than other women and they are at threefold risk of dying of ischemic heart disease. This could indicate that criteria for detecting LVH on ECG detect both mild and severe hypertrophy among men but only the severe hypertrophy cases among women. More sensitive ECG methods may have to be used to detect mild, moderate and severe LVH among both genders in order to differentiate the severity of LVH based on the ECG diagnosis.

The prevalence and prognosis of third-degree atrioventricular conduction block: the Reykjavik study.

OBJECTIVES: The objectives of this study were to find the prevalence of third-degree atrioventricular block in representative population sample and to estimate its prognostic significance. Most earlier studies have been performed on hospital patients and some professional groups. SETTING AND SUBJECTS: In the Reykjavik Study, a prospective cardiovascular population study, 9139 men and 9773 women aged 33-79 years were examined in 1967-91. Electrocardiograms were taken and coded according to the Minnesota code. Third-degree atrioventricular block was found in 11 persons, seven male and four female, an overall prevalence of 0.04%. All of these individuals had signs of dysrhythmia on electrocardiograms taken later, and in addition some other heart disease. The heart block was temporary in seven individuals (64%); six (55%) needed a pacemaker. CONCLUSIONS: The prevalence of third-degree atrioventricular block in this general population was low. The block was temporary in the majority of subjects. All had some underlying heart disease, which may affect the prognosis more than the heart block. Fewer subjects than expected were found to need a pacemaker.