No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

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. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. TRIAL REGISTRATION NUMBER: N/A.

Effect of counterions on the micellization and monolayer behaviour of cationic gemini surfactants.

The effect of various inorganic and organic counterions on the aggregation behavior of gemini surfactants was examined to investigate the dominant influence of the anions on their micellization and aggregation behavior. This study included eight ethanediyl-α,ω-bis-(dimethylhexadecylammonium) gemini surfactants (GS, also known as 16-2-16) having counterions of chloride (Cl-), bromide (Br-), malate, tartrate, adenosine monophosphate (AMP), guanosine monophosphate (GMP), cytidine monophosphate (CMP), and uridine monophosphate (UMP). Tensiometry, conductivity and Langmuir monolayer measurements were performed to investigate the micellization and surface behaviour of each surfactant.

Caring for the carers during transplant surgery.

Staff working in theatre departments play a vital role in organ retrieval. However, many find involvement with organ donation uncomfortable and sometimes distressing. They may also have misunderstandings about what takes place before and after the retrieval operation. This article will examine the issue of organ donation from the perspective of the operating theatre staff and offer insight into the process of organ donation prior to and following the retrieval surgery.

Variable path length transmittance cell for ultraviolet, visible, and infrared spectroscopy and spectroelectrochemistry.

The design and characteristics of a transmittance cell for ultraviolet, visible, and infrared spectroscopy and spectroelectrochemistry are described. Through modification of a previously reported design, this cell employs threaded glass connectors as insertion ports for either quartz- or silicon-windowed tubes, thus permitting essentially continuous variation of the optical path length from ∼0.050 to 200 mm. Though the initial fabrication requires skillful glassblowing, once constructed, the cell's simple design allows for rapid and reproducible disassembly/reassembly between experiments. The utility of the cell for a diversity of fluid samples is demonstrated through applications to water, aqueous ferricyanide, ferrocene in methylene chloride, and acetone vapor.

Flow and antibody binding properties of hydrated fibrins prepared from plasma, platelet rich plasma and whole blood.

Previous studies, using cross-linked fibrin prepared from purified fibrinogen, showed low binding of a fibrin-specific monoclonal antibody designated T2G1 (Procyk et al., Blood 77:1469-75, 1991). In this study we investigated the binding of T2G1 and one other antibody to clots prepared from platelet poor plasma (PPP), platelet rich plasma (PRP) and whole blood. In contrast to our previous study, we used unlabelled antibodies and quantitated the level bound by ELISA, measuring antibody concentration in the non-adsorbed fraction. Antibody T2G1 bound 1.35 +/- 0.10 pmol/pmol fibrin (n = 11) to whole blood columns, 1.64 +/- 0.18 (n = 10) to PRP columns and 1.58 +/- 0.13 (n = 8) to PPP columns. The binding of T2G1 to columns made from purified fibrinogen was 0.78 +/- 0.05 pmol/pmol fibrin (n = 15). An antibody to a conformation-dependent epitope on Fragment D (Fd4-7B3) bound in comparable amounts to the different fibrins. Flow data show that whole blood columns, and also, but to a lesser extent those made with plasma, had a higher flow rate, permeability and fiber mass-length ratio than columns prepared from fibrinogen indicating a more coarse fibrin network. These data show that the presence of other proteins and blood cells, similar to what might occur in vivo, not only lead to an increase in the permeability of gels but also allow for better exposure of some epitopes.

Accessibility of epitopes on fibrin clots and fibrinogen gels.

Radiolabeled antibodies were perfused into fibrin clots and fibrinogen gels formed in vitro to assess the reactivity of selected epitopes. An antifibrinogen monoclonal antibody (MoAb) (antibody 1D4/xl-f), directed against an epitope in the A alpha-chain C-terminal region (A alpha 241-476), bound to 35% of the epitope in crosslinked fibrin clots and 37% of the same epitope in factor XIII-induced fibrinogen gel networks. A different MoAb (4-2/xl-f, anti gamma 392-406) bound to only 7% of the epitope in both fibrin and fibrinogen gels. As expected, an antifibrin MoAb (antibody T2G1, antiB beta 15-21) did not bind to fibrinogen gels, but bound to fibrin, although to only 14% of the available T2G1-reactive epitopes. An antibody that does not recognize fibrin (antibody 1-8C6, antiB beta 1-21) predictably did not bind to fibrin clots and bound to 35% of the 1-8C6 epitopes present in fibrinogen gels, a level of binding also observed with antibody T2G1 and fibrinogen gels only after the latter were treated with thrombin. T2G1 epitope expression was affected much more than 1D4/xl-f epitope expression in clots formed in buffers of high or low ionic strength, conditions known to influence clot structure. Studies on the availability, in quantitative terms, of the T2G1-reactive epitope in fibrin clots is of particular importance because this antibody is currently being used in clinical trials as a clot imaging agent.

Haematological aspects of life with an ileostomy.

The haematological aspects of life with an ileostomy have been studies in 51 patients, of whom 39 had had ulcerative colitis and 12 had Crohn's disease. The findings in these patients have been compared with those in 39 healthy volunteers who were matched for age and sex with the 39 patient who had had ulcerative colitis. There was evidence of a mild degree of iron deficiency in the patients with an ileostomy. This was partly due to a pre-existing iron deficiency resulting from their preceding illness and operation, as the abnormality was less pronounced in the patients in whom the ileostomy had been established for more than 3 years. There was some evidence of excessive iron loss and a controlled trial of ferrous fumurate showed that the iron deficiency was largely corrected by this means. Circulating levels of vitamin B12 were normal, but it is relevant that some of the Crohn's disease group were receiving parenteral supplements. The absorption of vitamin B12 wa low in the patients with Crohn's disease who had had an ileal resection of more than 17 cm. The absorption of vitamin B12 in the patients who had had ulcerative colitis was increased and possible mechanisms are discussed. All but one of the patients had normal levels of plasma folate and in all the red cell blood folate was normal, which can be taken as an indication of a good dietary intake and adequate absorption.

Long survival in acute myelogenous leukaemia: an international collaborative study.

A group of 82 adult patients with acute myelogenous leukaemia had survived in continuous first remission for more than three years was studied. These long-surviving patients were being treated at 12 referral centres in Europe and the USA, and they were compared with other patients with acute myelogenous leukaemia from 10 of these centres. There was no clear difference in the amount of induction chemotherapy or the time taken to achieve remission. Immunotherapy was not found to improve chances of long-term survival. The 82 patients were also compared with a group of 115 patients who had no appreciable difference in the number of blood or marrow myeloblasts between these two groups at presentation, but the long survivors had significantly higher initial platelet counts and were slightly younger. The long survivors also tended to have a lower total white cell count at presentation and lower granulocyte counts; there was no obvious explanation for these differences. Eight of the 82 patients relapsed from three to four years after remission and two (of 69 patients) after four to five year. Thereafter relapse was rare, and it seems likely that some of the 40 patients who have survived for five years or more are cured.

Iron absorption and loading in beta-thalassaemia intermedia.

Iron absorption and rates of iron accumulation were analysed in a group of patients with beta-thalassaemia intermedia. Iron absorption was strikingly increased and there was a progressive iron loading with increasing age. Balance studies indicated that by the time many of these patients reach the third or fourth decades their total iron loads may be of a similar magnitude to those of transfusion-dependent beta-thalassaemia homozygotes. If these patients are to be protected from cardiac, hepatic, and endocrine complications of iron overload in middle life it will be necessary to reduce gastrontestinal iron absorption, starting from early childhood.

Infiltration of central nervous system in adult acute myeloid leukaemia.

Out of 64 consecutive unselected patients with acute myeloid leukaemia studied during 1973-6, five developed clinical evidence of spread to the central nervous system (CNS). Neuroradiological examination showed cerebral deposits in three, in whom rapid symptomatic relief was obtained with radiotherapy. In two of these patients who developed solid intracranial deposits haematological remission could be reinduced or maintained; they were still alive 86 and 134 weeks later. When patients presented with spread to the CNS complicating generalised uncontrolled leukaemia they had short survivals. CNS infiltration may respond dramatically to appropriate treatment provided that it is not associated with generalised uncontrolled leukaemia, which has a poor prognosis. In view of this, routine "prophylaxis" of the CNS in adult acute myeloid leukaemia does not seem justified at present.

Prevention of iron loading in transfusion-dependent thalassaemia.

Urinary iron excretion after single intramuscular (i.m.) bolus injections or 12 h subcutaneous (s.c.) infusions of desferrioxamine (D.F.) was determined in sixteen homozygous beta-thalassaemia patients whose ages ranged from 10 months to 23 years. At all ages the s.c. infusions resulted in greater iron loss than identical i.m. doses. With doses of 0.5-1 g of D.F. as s.c. infusions eight out of nine children aged less than 6 years with a total transfusion iron load of less than 10 g excreted sufficient iron to achieve iron balance. These results suggest that iron loading in transfusion-dependent thalassaemics may be preventable by the use of an appropriate chelation regimen started early in life.

Intensive iron-chelation therapy with desferrioxamine in iron-loading anaemias.

1. Urinary iron excretion after desferrioxamine has been examined in nine patinets with different iron-loading anaemias. Particular attention has been paid to individual variation in response and the kinetics of iron removal in order to determine the most efficient and convenient method of administration. 2. Twelve-hour subcutaneous infusions of desferrioxamine were comparable with intravenous infusions and gave a mean value of 62% more iron excretion than similar intramuscular bolus doses (range 20--125%). 3. Increasing doses as 12 h subcutaneous infusions produced a linear increase in iron excretion, which was followed by a tendency to reach a plateau. Iron excretion varied greatly between patients, was not related solely to age or estimated iron load, and in most cases was increased by ascorbic acid saturation. 4. Maximum iron-excretion rates were achieved after 3--6 and then maintained throughout an infusion. With bolus injections excretion rates declined rapidly after the first 6 h, during which approximately 60% of the total iron excretion occurred. 5. The dose and method of administration should be 'tailor-made' for each patient. Overnight 12 h subcutaneous infusions can be both as effective as similar doses given over 24 h and a practical way of achieving substantial negative iron balance. 6. Since children receiving regular blood transfusions for congenital anaemias such as thalassaemia usually die at the end of the second decade, this approach to iron chelation offers the possibility of alleviating what have hitherto been fatal-iron loading states.

Absorption of inorganic and haemoglobin iron in coeliac disease.

Absorption from a 5 mg dose of iron as Fe++ or haemoglobin iron was studied using a Total Body Counter in control subjects and patients with coeliac disease. In both groups the majority of subjects were iron deficient. Thirteen control subjects, 13 patients with untreated coeliac disease and 14 on treatment with gluten-free diet had both absorption tests. Absorption of Fe++ iron was reduced in untreated coeliac disease. This was particularly significant in iron deficient patients. Absorption was improved on treatment with gluten-free diet; In contrast, the absorption of haemoglobin iron was not affected in coeliac disease, indicating that absorption of iron in this form is not dependent on the integrity of the mucosa of the proximal small bowel.