Good practice recommendations for the use of time-lapse technology†

STUDY QUESTION: What recommendations can be provided on the approach to and use of time-lapse technology (TLT) in an IVF laboratory?SUMMARY ANSWER: The present ESHRE document provides 11 recommendations on how to introduce TLT in the IVF laboratory. WHAT IS KNOWN ALREADY: Studies have been published on the use of TLT in clinical embryology. However, a systematic assessmentof how to approach and introduce this technology is currently missing.STUDY DESIGN, SIZE, DURATION: A working group of members of the Steering Committee of the ESHRE Special Interest Group in Embryology and selected ESHRE members was formed in order to write recommendations on the practical aspects of TLT for the IVF laboratory.PARTICIPANTS/MATERIALS, SETTING, METHODS: The working group included 11 members of different nationalities with internationally recognized experience in clinical embryology and basic science embryology, in addition to TLT. This document is developed according to the manual for development of ESHRE recommendations for good practice. Where possible, the statements are supported by studies retrieved from a PUBMED literature search on ‘time-lapse’ and ART.MAIN RESULTS AND THE ROLE OF CHANCE: A clear clinical benefit of the use of TLT, i.e. an increase in IVF success rates, remains to be proven. Meanwhile, TLT systems are being introduced in IVF laboratories. The working group listed 11 recommendations on what to do before introducing TLT in the lab. These statements include an assessment of the pros and cons of acquiring a TLT system, selection of relevant morphokinetic parameters, selection of an appropriate TLT system with technical and customer support, development of an internal checklist and education of staff. All these aspects are explained further here, based on the current literature and expert opinion.LIMITATIONS, REASONS FOR CAUTION: Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. The paper provides technical advice, but leaves any decision on whether or not to use TLT to the individual centres.WIDER IMPLICATIONS OF THE FINDINGS: This document is expected to have a significant impact on future developments of clinical embryology, considering the increasing role and impact of TLT

The impact of RIPK1 kinase inhibition on atherogenesis : a genetic and a pharmacological approach

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) enzymatic activity drives both apoptosis and necroptosis, a regulated form of necrosis. Because necroptosis is involved in necrotic core development in atherosclerotic plaques, we investigated the effects of a RIPK1(S25D/S25D) mutation, which prevents activation of RIPK1 kinase, on atherogenesis in ApoE(−/−) mice. After 16 weeks of western-type diet (WD), atherosclerotic plaques from ApoE(−/−) RIPK1(S25D/S25D) mice were significantly larger compared to ApoE(−/−) RIPK1(+/+) mice (167 ± 34 vs. 78 ± 18 × 10(3) µm(2), p = 0.01). Cell numbers (350 ± 34 vs. 154 ± 33 nuclei) and deposition of glycosaminoglycans (Alcian blue: 31 ± 6 vs. 14 ± 4%, p = 0.023) were increased in plaques from ApoE(−/−) RIPK1(S25D/S25D) mice while macrophage content (Mac3: 2.3 ± 0.4 vs. 9.8 ± 2.4%, p = 0.012) was decreased. Plaque apoptosis was not different between both groups. In contrast, pharmacological inhibition of RIPK1 kinase with GSK’547 (10 mg/kg BW/day) in ApoE(−/−) Fbn1(C1039G+/−) mice, a model of advanced atherosclerosis, did not alter plaque size after 20 weeks WD, but induced apoptosis (TUNEL: 136 ± 20 vs. 62 ± 9 cells/mm(2), p = 0.004). In conclusion, inhibition of RIPK1 kinase activity accelerated plaque progression in ApoE(−/−) RIPK1(S25D/S25D) mice and induced apoptosis in GSK’547-treated ApoE(−/−) Fbn1(C1039G+/−) mice. Thus, without directly comparing the genetic and pharmacological studies, it can be concluded that targeting RIPK1 kinase activity does not limit atherogenesis

The Impact of RIPK1 Kinase Inhibition on Atherogenesis: A Genetic and a Pharmacological Approach

RIPK1 (receptor-interacting serine/threonine-protein kinase 1) enzymatic activity drives both apoptosis and necroptosis, a regulated form of necrosis. Because necroptosis is involved in necrotic core development in atherosclerotic plaques, we investigated the effects of a RIPK1(S25D/S25D) mutation, which prevents activation of RIPK1 kinase, on atherogenesis in ApoE(- /-) mice. After 16 weeks of western-type diet (WD), atherosclerotic plaques from ApoE(-/-) RIPKS25D/S25D mice were significantly larger compared to ApoE(-/- )RIPK1(+/+) mice (167 +/- 34 vs. 78 +/- 18 x 10(3) mu m(2), p = 0.01). Cell numbers (350 +/- 34 vs. 154 +/- 33 nuclei) and deposition of glycosaminoglycans (Alcian blue: 31 +/- 6 vs. 14 +/- 4%, p = 0.023) were increased in plaques from ApoE(-/-)RIPK1(S25D/S25D) mice while macrophage content (Mac3: 2.3 +/- 0.4 vs. 9.8 +/- 2.4%, p = 0.012) was decreased. Plaque apoptosis was not different between both groups. In contrast, pharmacological inhibition of RIPK1 kinase with GSK'547 (10 mg/kg BW/day) in ApoE(-/-) RIPK1(S25D/S25D) mice, a model of advanced atherosclerosis, did not alter plaque size after 20 weeks WD, but induced apoptosis (TUNEL: 136 +/- 20 vs. 62 +/- 9 cells/mm(2), p = 0.004). In conclusion, inhibition of RIPK1 kinase activity accelerated plaque progression in ApoE(-/-)RIPK1(S25D/S25D) mice and induced apoptosis in GSK'547-treated ApoE(-/-) Fbn1(C1039G+/-) mice. Thus, without directly comparing the genetic and pharmacological studies, it can be concluded that targeting RIPK1 kinase activity does not limit atherogenesis