Time-dependent O2 consumption patterns determined optimal time ranges for selecting viable human embryos

Tejera, A.; Herrero, Javier; Viloria, Thamara; Romero, Josep Lluís; Gámiz, Pilar; Meseguer, Marcos

doi:10.1016/j.fertnstert.2012.06.040

Cited by 53 publications

(32 citation statements)

References 74 publications

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“…High-quality blastocysts lead to high pregnancy and implantation rates, but some still do not implant into the uterus; this is related to embryonic biochemical factors such as O 2 consumption [39, 40], pyruvate and glucose uptake [34, 41], lactate production [42], the secretion of factors such as platelet-activating factor and insulin-like growth factor [43], and the activity of the enzymes involved in acid and carbohydrate metabolism pathways [44, 45]. However, measuring these parameters typically requires special instruments and training, limiting their practical application.…”

Section: Discussionmentioning

confidence: 99%

Prediction of blastocyst development and implantation potential <i>in utero</i> based on the third cleavage and compaction times in mouse pre-implantation embryos

Kim

Jun

2017

Journal of Reproduction and Development

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Cytokinesis and cell division during pre-implantation embryonic development occur as an orchestrated spatiotemporal program. Cleavage, compaction, and blastulation in pre-implantation embryos are essential for successful implantation and pregnancy. Their alteration is associated with chromosomal imbalance and loss of developmental competence. In this study, we evaluated the time of cleavage and compaction as predictors for in vitro pre- and peri-implantation development and in utero implantation potential by time-lapse monitoring. Mouse 2-cell embryos were collected on 1.5 days post coitum (dpc) and were individually cultured to the outgrowth (OG) stage (7.5 dpc). Developmental stages were classified as 3-cell, 4-cell, 8-cell, morula, blastocyst, and OG. Cut-off times for successful blastocyst development were determined by receiver operating characteristic curve analysis. When cut-off times were set as 9 h for the third cleavage from the 2- to 4-cell stage, and 40 h for compaction from the 2-cell to morula stage, blastocyst and OG development rates, respectively, were significantly higher (P < 0.0001). Embryos were grouped according to the above cut-off time and transferred to the contralateral uterine horn on 3.5 dpc. Implantation rates in utero on 5.5 dpc were significantly higher in early third cleaved (≤ 9 h from 2- to 4-cell) and early compacted embryos (≤ 40 h from 2-cell to morula) than those in delayed embryos (P < 0.05). Therefore, the time of the third cleavage from 2- to the 4-cell stage and compaction from 2-cell to morula stage may be a useful morphokinetic parameter for predicting developmental potential, including successful implantation and pregnancy in human in vitro fertilization-embryo transfer programs.

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Section: Discussionmentioning

confidence: 99%

Prediction of blastocyst development and implantation potential <i>in utero</i> based on the third cleavage and compaction times in mouse pre-implantation embryos

Kim

Jun

2017

Journal of Reproduction and Development

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“…However, several studies do not support this hypothesis Gardner et al 2011); rather, they infer that viability is actually associated with increased metabolic rate. Indeed, oxygen consumption by cleavage stage human embryos indicates that viability is associated with an increased oxygen consumption rate, reflecting an increase in respiration rate (Tejera et al 2012). So how can this paradox be resolved?…”

Section: Relationship Between Metabolism and Blastocyst Viabilitymentioning

confidence: 99%

Blastocyst metabolism

Gardner¹,

Harvey²

2015

Reprod. Fertil. Dev.

130

108

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The mammalian blastocyst exhibits an idiosyncratic metabolism, reflecting its unique physiology and its ability to undergo implantation. Glucose is the primary nutrient of the blastocyst, and is metabolised both oxidatively and through aerobic glycolysis. The production of significant quantities of lactate by the blastocyst reflects specific metabolic requirements and mitochondrial regulation; it is further proposed that lactate production serves to facilitate several key functions during implantation, including biosynthesis, endometrial tissue breakdown, the promotion of new blood vessel formation and induction of local immune-modulation of the uterine environment. Nutrient availability, oxygen concentration and the redox state of the blastocyst tightly regulate the relative activities of specific metabolic pathways. Notably, a loss of metabolic normality is associated with a reduction in implantation potential and subsequent fetal development. Even a transient metabolic stress at the blastocyst stage culminates in low fetal weights after transfer. Further, it is evident that there are differences between male and female embryos, with female embryos being characterised by higher glucose consumption and differences in their amino acid turnover, reflecting the presence of two active X-chromosomes before implantation, which results in differences in the proteomes between the sexes. In addition to the role of Hypoxia-Inducible Factors, the signalling pathways involved in regulating blastocyst metabolism are currently under intense analysis, with the roles of sirtuins, mTOR, AMP-activated protein kinase and specific amino acids being scrutinised. It is evident that blastocyst metabolism regulates more than the production of ATP; rather, it is apparent that metabolites and cofactors are important regulators of the epigenome, putting metabolism at centre stage when considering the interactions of the blastocyst with its environment.

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“…The authors reported that measurements of the oxygen consumption rate of individual blastocysts before freezing provides important information regarding their viability after warming from the view point of blastocoel reexpansion . Another study demonstrated that oxygen consumption from individual embryos revealed significant differences, mainly close to the time of transfer, when the oxygen consumption pattern was associated with successful implantation . In recent years, automated devices that measure embryo oxygen consumption have been manufactured and are reported to correlate with SECM functions.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, measuring the oxygen consumption pattern of human embryos in culture for ≤72 hours could be used to select the embryo with the best developmental potential. One of the previous studies concluded that the measurement of oxygen consumption rates for individual oocytes before fertilization provides an uninvasive marker of oocyte quality and hence a quantitative assessment of the reproductive potential of the oocyte . Combining embryo respiration activity measurement with morphological evaluation can provide new information regarding the quality of human embryos and improve the selection rate of superior embryos before transfer in IVF‐e‐SET.…”

Section: Discussionmentioning

confidence: 99%

Prediction of the in vitro developmental competence of early‐cleavage‐stage human embryos with time‐lapse imaging and oxygen consumption rate measurement

Goto¹,

Kumasako²,

Koike³

et al. 2018

Reprod Medicine & Biology

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PurposeTo assess an embryo's ability to develop into a good‐quality blastocyst during the early‐cleavage stage using time‐lapse imaging and the oxygen consumption rate.MethodsIn total, 942 zygotes had their oxygen consumption rates measured. In total, 282 zygotes were assessed by using time‐lapse imaging. In total, 121 zygotes were examined by using both their oxygen consumption rate and time‐lapse imaging.ResultsThe embryos with moderate respiration rates of between 0.41 and 0.61 (×1014/mol s−1) on day 3 had a 22.1% chance of becoming good‐quality blastocysts; those outside that range had a 14.3% chance. With the time‐lapse system, when the first division was within 24 hours, 22.3% of the embryos grew to good blastocysts. After 24 hours, the rate dropped to 8.6%. The intervals between two consecutive cleavages were calculated and the duration of the second cell cycle was defined. When the time was between nine hours and 13 hours, there was a higher rate of good blastocysts. Regarding both criteria, when the embryos had progressed in the optimal range, a high percentage of them had become good blastocysts; it was 8.0% outside of that range.ConclusionIndividual embryos with the potential to develop into good‐quality blastocysts could be selected at day 3 of culture using these systems.

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Time-dependent O2 consumption patterns determined optimal time ranges for selecting viable human embryos

Cited by 53 publications

References 74 publications

Prediction of blastocyst development and implantation potential <i>in utero</i> based on the third cleavage and compaction times in mouse pre-implantation embryos

Prediction of blastocyst development and implantation potential <i>in utero</i> based on the third cleavage and compaction times in mouse pre-implantation embryos

Blastocyst metabolism

Prediction of the in vitro developmental competence of early‐cleavage‐stage human embryos with time‐lapse imaging and oxygen consumption rate measurement

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