RESUMEN
STUDY QUESTION: Do embryos displaying abnormal cleavage (ABNCL) up to Day 3 have compromised live birth rates and neonatal outcomes if full blastulation has been achieved prior to transfer? SUMMARY ANSWER: ABNCL is associated with reduced full blastulation rates but does not impact live birth rates and neonatal outcomes once full blastulation has been achieved. WHAT IS KNOWN ALREADY?: It is widely accepted that ABNCL is associated with reduced implantation rates of embryos when transferred at the cleavage stage. However, evidence is scarce in the literature reporting birth outcomes from blastocysts arising from ABNCL embryos, likely because they are ranked low priority for transfer. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 1562 consecutive autologous in vitro fertilization cycles (maternal age 35.1 ± 4.7 years) performed at Fertility North, Australia between January 2017 and June 2022. Fresh transfers were performed on Day 3 or 5, with remaining embryos cultured up to Day 6 before vitrification. A total of 6019 embryos were subject to blastocyst culture, and a subset of 664 resulting frozen blastocysts was included for live birth and neonatal outcome analyses following single transfers. PARTICIPANTS/MATERIALS, SETTING, METHODS: ABNCL events were annotated from the first mitotic division up to Day 3, including direct cleavage (DC), reverse cleavage (RC) and <6 intercellular contact points at the 4-cell stage (<6ICCP). For DC and RC in combination, the ratios of affected blastomeres over the total number of all blastomeres up to Day 3 were also recorded. All pregnancies were followed up until birth with gestational age, birthweight, and sex of the baby being recorded. MAIN RESULTS AND THE ROLE OF CHANCE: Full blastulation rates for embryos showing DC (19.5%), RC (41.7%), <6ICCP (58.8%), and mixed (≥2) ABNCL types (26.4%) were lower than the rates for those without ABNCL (67.2%, P < 0.01 respectively). Subgroup analysis showed declining full blastulation rates with increasing ratios of combined DC/RC affected blastomeres over all blastomeres up to the 8-cell stage (66.2% when 0 affected, 47.0% when 0.25 affected, 27.4% when 0.5 affected, 14.5% when 0.75 affected, and 7.7% when all affected, P < 0.01). However, once full blastulation had been achieved, no difference was detected between DC, RC, <6ICCP, and no ABNCL blastocysts following single frozen transfers in subsequent live birth rates (25.9%, 33.0%, 36.0% versus 30.8%, P > 0.05, respectively), gestational age (38.7 ± 1.6, 38.5 ± 1.2, 38.3 ± 3.5 versus 38.5 ± 1.8 weeks, P > 0.05, respectively) and birthweight (3343.0 ± 649.1, 3378.2 ± 538.4, 3352.6 ± 841.3 versus 3313.9 ± 509.6 g, P > 0.05, respectively). Multiple regression (logistic or linear as appropriate) confirmed no differences in all of the above measures after accounting for potential confounders. LIMITATIONS, REASONS FOR CAUTION: Our study is limited by its retrospective nature, making it impossible to control every known or unknown confounder. Embryos in our dataset, being surplus after selection for fresh transfer, may not represent the general embryo population. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the incremental impact of ABNCL, depending on the ratio of affected blastomeres up to Day 3, on subsequent full blastulation. The reassuring live birth and neonatal outcomes of ABNCL blastocysts imply a potential self-correction mechanism among those embryos reaching the blastocyst stage, which provides valuable guidance for clinical practice and patient counseling. STUDY FUNDING/COMPETTING INTEREST(S): This research is supported by an Australian Government Research Training Program (RTP) Scholarship. All authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
Asunto(s)
Transferencia de Embrión , Nacimiento Vivo , Humanos , Femenino , Estudios Retrospectivos , Embarazo , Adulto , Transferencia de Embrión/métodos , Fase de Segmentación del Huevo , Técnicas de Cultivo de Embriones , Fertilización In Vitro/métodos , Blastocisto , Resultado del Embarazo , Implantación del Embrión/fisiología , Recién Nacido , Índice de Embarazo , Tasa de Natalidad , CriopreservaciónRESUMEN
Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2-2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01-10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP-mediated signaling pathways. This protection was prevented by a 67LR-blocking antibody, suggesting a role for this cell-surface receptor in neuroprotection by resveratrol metabolites.
Asunto(s)
Fármacos Neuroprotectores , Receptores de Laminina , Resveratrol , Resveratrol/farmacología , Resveratrol/metabolismo , Resveratrol/química , Receptores de Laminina/metabolismo , Receptores de Laminina/genética , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/metabolismo , Simulación del Acoplamiento Molecular , Animales , Unión Proteica , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Estilbenos/farmacología , Estilbenos/metabolismo , Estilbenos/química , Neuroprotección/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sitios de Unión , Glucurónidos/metabolismo , Glucurónidos/química , Proteínas RibosómicasRESUMEN
Food-based learning (FBL) is the use of food as a teaching tool in the classroom, which can expose children to healthy foods to improve preference and consumption. However, more research is needed on the use and perception of FBL in the Head Start (HS) preschool classroom. In an online survey, we explored associations between North Carolina HS teachers' (n = 168) experiences (e.g., resources, challenges, needs, and preferences) with FBL, how frequently teachers implemented it, and how much they prioritized it. We used frequencies and chi-square tests of independence to assess associations between study variables. Teachers reported using FBL regularly with access to FBL resources (e.g., books and center play materials) and experiencing challenges (e.g., lack of funding and material resources). Teachers partnered with parents and farmers markets and expressed a need for additional FBL professional development. Our needs assessment findings revealed specific resources, challenges, and perceptions significantly associated with how often teachers used FBL and their priority level. Additional research should investigate how to alleviate FBL challenges and strategies to create policy and environmental changes that facilitate early FBL.