| 1. |
- Ahlström, Aisling, 1976, et al.
(författare)
-
A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
-
Tidskriftsartikel (refereegranskat)abstract
- 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. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Ahlström, A., et al.
(författare)
-
No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
-
Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
-
Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
|
|
| 6. |
- Blixt, Maria, et al.
(författare)
-
MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
- 2022
-
Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 11:1, s. 34-
-
Tidskriftsartikel (refereegranskat)abstract
- Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
|
|
| 7. |
|
|
| 8. |
- Mishra, Sushmit, 1981-
(författare)
-
Exploring Cognitive Spare Capacity : Executive Processing of Degraded Speech
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cognitive resources, specifically working memory capacity are used for listening to speech, especially in noise. Cognitive resources are limited, and if listeners allocate a greater share of these resources to recovering the input signal in noise, fewer resources are available for interpreting and encoding its linguistic content. Although the importance of CSC for individual success in communicative situations has been acknowledged, this concept has not hitherto been explored experimentally. In this thesis, a CSC test (CSCT) was developed and administered to young adults with normal hearing and older adults with age-related hearing loss. CSCT required executive processing of speech at different memory loads with and without visual cues in different noise conditions. A free recall task using the same material was administered for comparison purposes and a battery of cognitive tests was administered to understand the relation between CSC and established cognitive concepts. The aims of the thesis were to investigate how CSC is influenced by 1) different executive demands and memory loads; 2) background noise; 3) visual cues; 4) aging and concomitant hearing loss. The results showed that 1) CSC was sensitive to memory load, and updating demands reduced CSC more than inhibition demands; 2) CSC was reduced in background noise compared to quiet; 3) visual cues enhanced CSC especially in noise; 4) CSC was reduced with ageing and concomitant hearing loss especially when visual cues were absent, memory demands were increased and background noise was speech-like. The main finding of this thesis was that visual cues enhanced CSC for older individuals with hearing loss, specifically in adverse listening conditions. This demonstrates the importance of audiovisual testing in audiological assessment. Further, specific cognitive resources depleted during listening in noise were at least partially compensated by other cognitive functions. This thesis is the first step towards a theoretical understanding of CSC and in future, tests of CSC may play a crucial role in planning rehabilitation of persons with hearing loss.
|
|
| 9. |
- Rönnberg, Jerker, et al.
(författare)
-
Speech in noise and ease of language understanding : When and how working memory capacity plays a role
- 2012
-
Ingår i: The Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966.
-
Konferensbidrag (refereegranskat)abstract
- A working memory based model for Ease of Language Understanding (ELU) has been developed (Rönnberg, 2003; Rönnberg et al., 2008; Rönnberg et al., 2011). It predicts that speech understanding in adverse, mismatching noise conditions is dependent on explicit processing resources such as working memory capacity (WMC). This presentation will examine the details of this prediction by addressing some recent data on (1) how brainstem responses are modulated by working memory load and WMC, (2) how cortical correlates of speech understanding in noise are modulated by WMC, and (3) how WMC determines episodic long-term memory for spoken discourse masked by speech.
|
|
| 10. |
- Stenfelt, C., et al.
(författare)
-
Effects of the colour and design of a new pelvic examination chair on comfort during gynaecological examination
- 2020
-
Ingår i: CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY. - : IMR PRESS. - 0390-6663. ; 47:4, s. 556-559
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The main question was whether the colour of a new design of pelvic examination chair could affect how the examination procedure was perceived. A prototype was constructed without vertical leg support and with built-in heating in the upholstery. To improve integrity, the perineum was exposed only during the examination. Main Outcome Measures: The patients were invited to evaluate the two different chair colours used, light blue and off-white, respectively. After vaginal ultrasound, the patients answered an anonymous questionnaire about their experience of the examination and how they perceived the comfort, warmth, integrity and colour of the chair. There were also questions regarding the absence of vertical leg support. Results: The questionnaire evaluation demonstrated the importance of colour since integrity was rated significantly higher in the light-blue chair than in the off-white. Similarly, the blue chair was experienced as significantly more comfortable than the white. Conclusions: The effect of colour was investigated in a new pelvic examination chair without vertical leg support, developed to suit men, women and also non-binary and transgender persons. It was also designed for increased comfort and integrity. The experience of colour had a significant positive (p < 0.001) effect on how the comfort, integrity and the absence of vertical leg support were perceived.
|
|
