A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer.

STUDY QUESTION: Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER: The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY: Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION: A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE: In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION: During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS: The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registration number NCT03445923. TRIAL REGISTRATION DATE: 26 February 2018. DATE OF FIRST PATIENT'S ENROLMENT: 11 June 2018.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

OBJECTIVE: To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media. DESIGN: Randomized, double-blinded sibling trial. SETTING: Independent in vitro fertilization (IVF) clinics. PATIENT(S): One hundred twenty-eight patients, with 1,356 zygotes randomized into two study arms. INTERVENTION(S): Embryos randomly allocated into two study arms to compare embryo development on a time-lapse system using a single-step medium or sequential media. MAIN OUTCOME MEASURE(S): Percentage of good-quality blastocysts on day 5. RESULT(S): Percentage of day 5 good-quality blastocysts was 21.1% (standard deviation [SD] ± 21.6%) and 22.2% (SD ± 22.1%) in the single-step time-lapse medium (G-TL) and the sequential media (G-1/G-2) groups, respectively. The mean difference (-1.2; 95% CI, -6.0; 3.6) between the two media systems for the primary end point was less than the noninferiority margin of -8%. There was a statistically significantly lower number of good-quality embryos on day 3 in the G-TL group [50.7% (SD ± 30.6%) vs. 60.8% (SD ± 30.7%)]. Four out of the 11 measured morphokinetic parameters were statistically significantly different for the two media used. The mean levels of ammonium concentration in the media at the end of the culture period was statistically significantly lower in the G-TL group as compared with the G-2 group. CONCLUSION(S): We have shown that a single-step culture medium supports blastocyst development equivalently to established sequential media. The ammonium concentrations were lower in the single-step media, and the measured morphokinetic parameters were modified somewhat. CLINICAL TRIAL REGISTRATION NUMBER: NCT01939626.

Role of Headmasters, Teachers, and Supervisors in Knowledge Transfer about Occupational Health and Safety to Pupils in Vocational Education.

BACKGROUND: Young people are at an increased risk for illness in working life. The authorities stipulate certain goals for training in occupational health and safety (OHS) in vocational schools. A previous study concluded that pupils in vocational education had limited knowledge in the prevention of health risks at work. The aim of the current study, therefore, was to study how OHS training is organized in school and in workplace-based learning (WPL). METHODS: The study design featured a qualitative approach, which included interviews with 12 headmasters, 20 teachers, and 20 supervisors at companies in which the pupils had their WPL. The study was conducted at 10 upper secondary schools, located in Central Sweden, that were graduating pupils in four vocational programs. RESULTS: The interviews with headmasters, teachers, and supervisors indicate a staggered picture of how pupils are prepared for safe work. The headmasters generally give teachers the responsibility for how goals should be reached. Teaching is very much based on risk factors that are present in the workshops and on teachers' own experiences and knowledge. The teaching during WPL also lacks the systematic training in OHS as well as in the traditional classroom environment. CONCLUSION: Teachers and supervisors did not plan the training in OHS in accordance with the provisions of systematic work environment management. Instead, the teachers based the training on their own experiences. Most of the supervisors did not receive information from the schools as to what should be included when introducing OHS issues in WPL.

Knowledge and Experiences of Risks among Pupils in Vocational Education.

BACKGROUND: Young male and female workers are over-represented in statistics concerning negative outcomes of poor work environment and risky work. Young workers often have low awareness of risk, a lack of safety training, and inadequate introduction to the work. The aim of this study was to identify the knowledge and experiences of pupils of vocational schools concerning potential work environment risks in their future work. METHODS: The study design was a dual one, and included a questionnaire and focus group interviews. The study group consisted of 239 pupils from 10 upper secondary schools, who were graduating pupils in four vocational programs: the Industrial Technology Programme, the Restaurant Management and Food Programme, the Transport Programme, and the Handicraft Programme (in which students specialize in wood products). The upper secondary schools were located in the central region of Sweden. RESULTS: The pupils had limited knowledge that employers must, by law, conduct risk analyses and prevent risks. Many felt that they themselves are mainly responsible for performing their tasks safely. Pupils in all programs mentioned acute risk as the greatest risk at work. The theoretical education about safety at work was provided in the 1(st) year of the 3-year vocational programs. CONCLUSION: A systematic approach to pupils' training in work environment, which is a basis for a safe and healthy workplace, is lacking. The study findings indicate that pupils are offered knowledge far from that intended by laws and by state-of-the-art occupational health risk research.

Swedish entrepreneurs' use of occupational health services.

Small-scale enterprises are less often covered by occupational health services and have insufficient awareness about health and risks in the work environment. This study investigated how Swedish entrepreneurs in small-scale enterprises use occupational health services. The study used a questionnaire sent in two waves, 5 years apart. At baseline, 496 entrepreneurs responded, and 251 participated 5 years later. The questionnaire included items about affiliation with and use of occupational health services, physical and psychosocial work environments, work environment management, sources of work environment information, and membership in professional networks. Only 3% of entrepreneurs without employees and 19% of entrepreneurs with employees were affiliated with an occupational health service. Entrepreneurs affiliated with occupational health services were more active in work environment management and gathering information about the work environment. The occupational health services most used were health examinations, health care, and ergonomic risk assessments. Affiliation with occupational health services was 6% at both measurements, 4% at baseline, and 10% 5 years later.

Entrepreneurs' self-reported health, social life, and strategies for maintaining good health.

OBJECTIVES: This study investigated the association between self-reported good health and self-valued good social life. An additional aim was to examine entrepreneur's strategies for maintaining good health. METHODS: The study design included a two-wave questionnaire, with five years between the surveys (2001 and 2006), and qualitative interviews. The study group consisted of 246 entrepreneurs from the central region of Sweden and represented ten different trades. Entrepreneurs reporting good health in both 2001 and 2006 were compared with entrepreneurs reporting poor health on both occasions or with inconsistent answers. Six of the entrepreneurs were strategically chosen for the interview study. RESULTS: Consistent good health was reported by 56% of the entrepreneurs. Good social life in 2001 was associated with an increased odds ratio (OR) for consistent good health when the analyses were adjusted for physical work conditions and job satisfaction (OR 2.12, 95% CI 1.07-4.17). Findings for good leisure time, weekly moderate physical exercise, and a rating of work being less or equally important as other life areas, were similar but not statistically significant when job satisfaction was considered in the analyses. Strategies for maintaining good health included good planning and control over work, flexibility at work, good social contact with family, friends and other entrepreneurs, and regular physical exercise. CONCLUSION: This study demonstrated an association between self-reported good health and good social life for entrepreneurs in small-scale enterprises. In addition, the entrepreneurs emphasised strategies such as planning and control over work and physical exercise are important for maintaining good health.

Systematic Work Environment Management: experiences from implementation in Swedish small-scale enterprises.

Small-scale enterprises face difficulties in fulfilling the regulations for organising Systematic Work Environment Management. This study compared three groups of small-scale manufacturing enterprises with and without support for implementing the provision. Two implementation methods, supervised and network method, were used. The third group worked according to their own ideas. Twenty-three enterprises participated. The effects of the implementation were evaluated after one year by semi-structured dialogue with the manager and safety representative. Each enterprise was classified on compliance with ten demands concerning the provision. The work environment was estimated by the WEST-method. Impact of the implementation on daily work was also studied. At the follow-up, the enterprises in the supervised method reported slightly more improvements in the fulfilment of the demands in the provision than the enterprises in the network method and the enterprises working on their own did. The effect of the project reached the employees faster in the enterprises with the supervised method. In general, the work environment improved to some extent in all enterprises. Extensive support to small-scale enterprises in terms of advise and networking aimed to fulfil the regulations of Systematic Work Environment Management had limited effect - especially considering the cost of applying these methods.

Physiological and psychological stress reactions in relation to classroom noise.

OBJECTIVES: This study tested the hypothesis that classroom noise is related to stress reactions among primary school children. Stress was monitored via symptoms of fatigue and headache, systolic blood pressure, reduced diurnal cortisol variation, and indicators of emotional distress. METHODS: In three classrooms of pupils in the fourth grade (10 years of age), daily measurements of equivalent sound levels (Leq) were made during 4 weeks, evenly distributed from September to December. One day each week of the study, the pupils answered a questionnaire about disturbance and symptoms, and blood pressure and salivary cortisol were measured. In the first and fourth week, the children also performed a standardized drawing test concerning emotional indicators. RESULTS: Daily measurements of equivalent sound levels in the classes (Leq during schoolday) ranged from 59 to 87 dB(A). Equivalent sound-levels were significantly related to an increased prevalence of symptoms of fatigue and headache and a reduced diurnal cortisol variability. Blood pressure and emotional indicators were not significantly related to sound levels. CONCLUSIONS: Current sound levels in Swedish classrooms may have a negative health impact, being directly or indirectly related to stress reactions among children. This finding indicates that noise should be focused on as a risk factor in the school environment.

Self rated health and working conditions of small-scale enterprisers in Sweden.

This study was an investigation of prevalence and associations between self-rated health and working conditions for small-scale enterprisers in a county in Sweden. A postal questionnaire was answered by 340 male and 153 female small-scale enterprisers in different sectors, with a response rate of 66%. For comparative purposes, data from a population study of 1,699 employees in private companies was included in the analyses. Differences were tested by Chi(2)-test and associations were presented as odds ratios (OR) with a 95% confidence interval (95% CI). The frequency of health problems in male enterprisers was higher than in employees in the private sector, while the frequency of health problems in female enterprisers was equal to that of the control employees. The main findings highlighted that male enterprisers reported higher rate of health problems and female enterprisers equal rate compared with employees in the private sector. Enterprisers stated musculoskeletal pain (women 59%, men 56%) and mental health problems (women 47%, men 45%) as the most frequent health problems. Poor job satisfaction, reported by 17% of the females and 20% of the male enterprisers, revealed an OR of 10.42 (95% CI 5.78-18.77) for poor general health. For the enterprisers, the most frequent complaints, musculoskeletal pain and mental health problems, were associated with poor job satisfaction and poor physical work environment. An association between poor general health and working as an enterpriser remained after adjusting for working conditions, sex and age.