Cycle-specific Factors Research Articles

Patient- and cycle-specific factors affecting the outcome of frozen–thawed embryo transfers

PurposeThis study attempted at identifying the main parameters influencing the outcome of frozen embryo transfers.MethodsThis is a single-center retrospective cohort study of 830 frozen-embryo-transfer cycles performed at a German university hospital from January 2012 to December 2016. Main outcome parameters were the clinical pregnancy and live birth rate. Twelve patient- and cycle-dependent factors were analyzed in terms of their influence on the outcome of frozen embryo transfers. Multivariate logistic regression analysis was used for the modelling of the dependency of the different parameters on outcomes.ResultsThe clinical pregnancy rate in our study was 25.5%, the live birth rate was 16.1% with an average maternal age of 34.2 years at the time of the oocyte retrieval. In the univariate analysis age, number of transferred embryos, blastocyst versus cleavage stage transfer, embryo quality and mode of endometrial preparation affected the birth rate significantly. The birth rate after artificial endometrial preparation was significantly lower than the birth rate after transfers in modified natural cycles (12.8 versus 20.6% with p = 0.031). The multivariate logistic regression analysis showed a significant independent influence of age, number of transferred embryos, culture duration and mode of endometrial preparation on the frozen embryo transfer success rates. Body mass index, nicotine abuse, a history of PCO syndrome or endometriosis and the co-transfer of a second poor-quality embryo to a good-quality embryo appeared to be irrelevant for the outcome in our collective.ConclusionAge, number of transferred embryos, embryo culture duration and the mode of endometrial preparation are independent predictive factors of frozen embryo transfer outcomes.

Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation

Post-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods relying on pulsed metabolic labeling are popular to quantify turnover rates on a proteome-wide scale. Such data have traditionally been interpreted in the context of protein proteolytic stability. Here, we combine theoretical kinetic modeling with experimental pulsed stable isotope labeling of amino acids in cell culture (pSILAC) for the study of protein phosphorylation. We demonstrate that metabolic labeling combined with PTM-specific enrichment does not measure effects of PTMs on protein stability. Rather, it reveals the relative order of PTM addition and removal along a protein’s lifetime—a fundamentally different metric. This is due to interconversion of the measured proteoform species. Using this framework, we identify temporal phosphorylation sites on cell cycle-specific factors and protein complex assembly intermediates. Our results thus allow tying PTMs to the age of the modified proteins.

FACTORS ASSOCIATED WITH PREGNANCY LOSS AFTER SINGLE EUPLOID EMBRYO TRANSFER

Clinical pregnancy loss (CPL) is often attributed to chromosomal copy number errors in the human embryo. When undergoing in vitro fertilization (IVF), preimplantation genetic testing for aneuploidy (PGT-A) can be utilized to select euploid embryos for transfer, thus significantly decreasing the risk of miscarriage. Surprisingly, pregnancy loss after single euploid embryo transfer (SEET) can still occur. This study sought to identify patient and cycle-specific factors associated with CPL after a SEET.

Risk Factors for Different Types of Pregnancy Losses: Analysis of 15,210 Pregnancies After Embryo Transfer.

ObjectiveTo evaluate the risk factors for different types of pregnancy losses after embryo transfer (ET).DesignRetrospective cohort study.SettingReproductive medicine center.ParticipantsA total of 15,210 pregnancies after fresh and frozen-thawed embryo transfer between January 2014 and June 2019.Main Outcome MeasuresThe primary outcome was pregnancy loss (PL) throughout the entire pregnancy. Secondary outcomes were non-visualized PL, early miscarriage, late miscarriage, and stillbirth.MethodsThe effect of patients’ baseline characteristics and IVF/ICSI cycle-specific factors on the risk of PL after fresh and frozen-thawed ET was determined by multivariate logistic regression analysis.ResultsCompared to women under 35 years old, those between 35 and 40 had an increased risk of early miscarriage [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.22-1.83], while those after 40 appeared to have an increased risk of both early miscarriage (OR 3.82, 95% CI 2.65-5.51) and late miscarriage (OR 2.79, 95% CI 1.64-4.77). Overweight patients were observed to have a higher risk of late miscarriage (OR 1.38, 95% CI 1.16-1.65), while obese patients showed a higher risk of both early miscarriage (OR 1.47, 95% CI 1.14-1.91) and late miscarriage (OR 1.80, 95% CI 1.33-2.44). Polycystic ovary syndrome (PCOS) was an independent risk factor for late miscarriage (OR 1.58, 95% CI 1.28-1.96), and the detrimental effect of PCOS was independent of obesity status. Women with uterine factors had a higher risk of early miscarriage (OR 1.77 (95% CI 1.32-2.38) than women without uterine factors. A negative correlation was observed between the thickness of the endometrium and PL (OR 0.95 95% CI 0.92-0.97). There was an increased risk of PL after frozen-thawed ET versus fresh ET (OR 1.12, 95% CI 1.01-1.24). Women who transferred ≥2 embryos showed lower risk of overall PL than women who transferred a single embryo, with adjusted ORs ranged from 0.57~0.94. However, women who transferred three embryos demonstrated a higher risk of late miscarriage than women who transferred a single embryo (OR 2.23, 95% CI 1.36-3.66).ConclusionsPatients with uterine factors demonstrated higher risk of early miscarriage and stillbirth. Being overweight, PCOS, and transferring three embryos was associated with late miscarriage. Being aged 40 and over, obese, and using frozen embryo transfer was associated with early and late miscarriage.

Robotic chemotherapy compounding: A multicenter productivity approach.

The aim of this study is to compare productivity of the KIRO Oncology compounding robot in three hospital pharmacy departments and identify the key factors to predict and optimize automatic compounding time. The study was conducted in three hospitals. Each hospital compounding workload and workflow were analyzed. Data from the robotic compounding cycles from August 2017 to July 2018 were retrospectively obtained. Nine cycle specific parameters and five productivity indicators were analysed in each site. One-to-one differences between hospitals were evaluated. Next, a correlation analysis between cycle specific factors and productivity indicators was conducted; the factors presenting a highest correlation to automatic compounding time were used to develop a multiple regression model (afterwards validated) to predict the automatic compounding time. A total of 2795 cycles (16367 preparations) were analysed. Automatic compounding time showed a relevant positive correlation (ǀrs|>0.40) with the number of preparations, number of vials and total volume per cycle. Therefore, these cycle specific parameters were chosen as independent variables for the mathematical model. Considering cycles lasting 40 minutes or less, predictability of the model was high for all three hospitals (R2:0.81; 0.79; 0.72). Workflow differences have a remarkable incidence in the global productivity of the automated process. Total volume dosed for all preparations in a cycle is one of the variables with greater influence in automatic compounding time. Algorithms to predict automatic compounding time can be useful to help users in order to plan the cycles launched in KIRO Oncology.

Goods Inflation, Asset Inflation, and the Greatest Peacetime Inflation in the US

In every episode of global monetary inflation originating in the Federal Reserve, we find both asset price inflation and goods inflation. The interrelationship between these two types of inflation depends both on cycle-specific factors and more general factors which transcend the cycle and stem from essential aspects of monetary disorder. The purpose of this article is to analyse the nature of this interrelationship and elaborate on the concepts of monetary disorder, goods inflation, and asset inflation. In today’s world of monetary systems where there is no stable demand for high-powered money (which itself is no longer a highly distinct asset) monetary disorder can be hard to recognize until quite late in the inflationary process. Asset price inflation now has a popular meaning quite different from the original found in Austrian business cycle theory. Two decades of widespread inflation targeting at around 2% per annum have encouraged us to ignore an old lesson. In a well-functioning capitalist economy under a sound money order, prices would fluctuate considerably upwards and downwards with a tendency to revert to the mean over the very long run. Finally the principles and hypotheses developed here are analysed in the laboratory of history, specifically for the greatest peacetime inflation in the U.S. (1963–80).

Frozen-thawed embryo transfer (FET) versus fresh embryo transfer in clinical pregnancy rate during in vitro fertilization-embryo transfer

To investigate whether frozen-thawed embryo transfer (FET) instead of fresh embryo transfer for the first embryo transfer (ET) in a controlled ovarian hyperstimulation (COH) cycle improves the in vitro fertilization-ET clinical pregnancy rate. The investigators retrospectively analyzed the clinical data of 1341 IVF-ET cycles under COH, including 1169 fresh ET cycles (Group T1) and 172 FET cycles as the first embryo transfer in COH cycle (Group C1). Logistic regression was used to model the probability of clinical pregnancy rate based on age, ET method and other cycle-specific factors. The clinical pregnancy rate was significantly higher in Group C1 than in Group T1 (63.4% vs 49.4%, P < 0.01). Multivariate logistic regression analysis revealed significant associations between the number of high-quality embryos transferred, patient age and ET method in clinical pregnancy rate. After adjusting for the number of high-quality embryos transferred and age, the clinical pregnancy rate remained significantly higher in Group C1 than in Group T1 (odds ratio: 1.75, 95% confidence interval: 1.25 - 2.46; P < 0.01). Significant differences were found in age (< 35 years old) and the number of retrieved oocytes (> or = 15). Using FET instead of fresh embryo transfer can improve the clinical pregnancy rate and the efficiency of IVF-ET.

Hyperstimulation With Interleukin 6 Inhibits Cell Cycle Progression After Hepatectomy in Mice

Interleukin 6 (IL-6) is an important mediator of hepatocyte proliferation after hepatectomy. However, elevated IL-6 levels are found in patients with chronic liver disease. Therefore, it is unclear if hyperstimulation with IL-6 may have an influence on liver regeneration. We investigated whether a strong activation of IL-6–dependent pathways may change the course of hepatocyte proliferation after hepatectomy. Transgenic mice overexpressing the human soluble IL-6 receptor/gp80 (hsgp80) in hepatocytes were stimulated with or without hepatectomy with human IL-6 (hIL-6). Nuclear extracts were prepared and activation of gp130-dependent pathways was studied by Western blot and gel shift experiments. Cell cycle progression of hepatocytes after hepatectomy was investigated by monitoring cell cycle-specific factors. hIL-6 strongly activates Stat3 for more than 48 hours in human soluble hsgp80 transgenic mice. In contrast, no major differences were evident in the regulation of the Ras/MAP kinase pathway compared with wild-type (wt) mice. Also when hsgp80 mice were stimulated with hIL-6 3 hours before hepatectomy Stat3 is activated for more than 72 hours, whereas in unstimulated mice this event is restricted to the early hours. Strong activation of Stat3 resulted in a delay and inhibition of hepatocyte proliferation as measured by 5-bromo-2′-deoxyuridine (BrdU) staining and Cyclin A and E expression. This observation directly correlates with the induction of the cell cycle inhibitor p21. In summary, strong IL-6–dependent activation of Stat3 before hepatectomy results in delay and inhibition of cell cycle progression after hepatectomy. Therefore our results suggest that hyperstimulation with IL-6 can inhibit liver regeneration.(Hepatology 2000;32:514-522.)

Will biomass be the environmentally friendly fuel of the future?

Many influential organisations foresee biomass playing a key role in a future, more sustainable, global energy supply matrix. Countries such as Austria, Brazil, Denmark, Finland, Sweden, India, the USA and the UK are actively encouraging the use of biomass for energy, and pushing forward the development of the necessary knowledge and technology for modern biomass energy systems. There is a growing consensus that renewable energy must progressively displace the use of fossil fuels, with fears of global climate change adding urgency to this need. Among the available types of renewable energy biomass is unique in its ability to provide solid, liquid and gaseous fuels which can be stored and transported. The potential resource for bioenergy is large, especially in forest-rich nations, in richer countries where there is a surplus of agricultural land, and in many low latitude countries where high biomass yields are possible. Therefore we expect biomass to be an important fuel of the future, but this cannot be taken for granted. The systems adopted must demonstrate clear environmental and social benefits relative to alternatives if the potential is to be realised. These benefits are not inherent to biomass energy, but depend on site- and fuel cycle-specific factors. Life-cycle analysis and evaluation of external costs are important means for assessing the social and environmental pros and cons of bioenergy systems.

Regulation of Synthesis of Ribonucleotide Reductase and Relationship to DNA Replication in Various Systems

This chapter discusses the nature of ribonucleotide reductase enzyme and reaction. Ribonucleotide reductase is a central and crucial enzyme in all cells. It catalyzes an irreversible step, the first in the only de novo pathway to deoxyribonucleotides, and it follows a large number of enzymes that form pyrimidine and purine ribonucleotide precursors. The classical ribonucleotide reductase is the ribonucleoside diphosphate reductase of aerobically grown Escherichia coli . The biosynthesis of the subunits of ribonucleotide reductases in several diverse systems is examined and their controls are described and compared in the chapter. Escherichia coli present a sophisticated combination of systems regulating the initiation of ribonucleotide reductase and tying its activity to the cell cycle. In prokaryotic cells, many genes may be expressed in a coordinated manner on single, multigenic transcripts. Although mouse nrdA and nrdB genes are on separate chromosomes, in some conditions the expression of the two genes or the formation of their protein products appears to be coordinated. Numerous links between cell cycle-specific factors and the regulatory sequences of the nrd genes are evident.