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.

Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the metabolic syndrome.

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2 years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone < 10 nmol/L and/or LH > 10 IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10 mIU/L; p = 0.002) and HOMAir (mean difference: 0.792; p = 0.007) were detected. Hypogonadism group presented with increased risk (OR = 4.4; p = 0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients.

Parametric quantification of myocardial ischaemia using real-time perfusion adenosine stress echocardiography images, with SPECT as reference method.

SUMMARY BACKGROUND: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast((R))-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. METHODS: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast-generated A, beta and Axbeta images, at different time points during rest and stress, were blindly compared to SPECT. RESULTS: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, beta and Axbeta image interpretation significantly identified ischaemia in all territories (area under the curve 0.66-0.80, P = 0.001-0.05). Combined A, beta and Axbeta image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0.63; P<0.001. CONCLUSION: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast-generated images, especially by combined A, beta and Axbeta image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.

Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease.

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography using low mechanical index power modulation technique allows for simultaneous myocardial perfusion and wall motion analysis. RTP-adenosine stress echocardiography (ASE) could be an alternative to dobutamine-atropine stress echocardiography; more tolerable for the patients and possibly similarly accurate. We aimed to evaluate RTP-ASE for the detection of myocardial ischaemia, compared to 99mTc-sestamibi single-photon emission computed tomography (SPECT). METHODS: Patients with suspected coronary artery disease, admitted to SPECT evaluation, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using infusion of Sonovue (Bracco, Milano, Italy) before and during ASE. Two separate readers performed off-line analysis of myocardial perfusion and wall motion by RTP-ASE. A perfusion defect was the principal marker of ischaemia. Wall motion assessment was used to evaluate ischaemia in segments with perfusion artefacts. Each segment was attributed to one of the three main coronary vessel areas of interest: the left anterior descending (LAD); the left circumflex (LCx) and the right posterior descending (RPD). Normal SPECT at stress was judged normal at rest. RESULTS: In 33 patients, 99 coronary territories were analysed by SPECT and RTP-ASE. SPECT showed evidence of ischaemia in 9 of 33 patients. For the detection of ischaemia, the overall level of agreement between RTP-ASE and SPECT was 92% in all segments. The level of agreement was 88% in LAD, 97% in LCx and 91% in RPD segments. CONCLUSION: Real-time perfusion-adenosine stress echocardiography using power modulation could be an accurate and feasible tool for evaluation of ischaemia in patients with suspected coronary artery disease. The results from this study need confirmation by a study of a larger patient sample.

[Evaluation of magnesium cation levels in serum of patients with mitral valve prolapse syndrome]. / Ocena stezenia kationów magnezowych w surowicy krwi u chorych z zespolem wypadania platka zastawki dwudzielnej.

Magnesium deficiency has been suggested to be related to the mitral valve prolapse syndrome (MVPS). The aim of the present study was to analyse the concentration of magnesium in blood plasma of patients (pts) with MVPS. In the group of 80 subjects, including 50 pts with MVPS and 30 healthy people matched for age and gender, who comprised the control group (CG), concentration of magnesium in blood plasma was estimated. Magnesium levels were measured by atomic absorption spectrophotometry. Mean concentration of magnesium cation in plasma in pts with MVPS was 0.74 +/- 0.12 mmol/l (range 0.47-1.02 mmol/l). It was only 1.02% lower than in the CG (x = 0.76 +/- 0.07 mmol/l; range 0.67-0.97 mmol/l). However evaluation of the magnesium concentration in blood plasma did not prove magnesium deficiency in the mitral valve prolapse syndrome. Moreover the study revealed that histograms of magnesium concentration values in both investigated groups were divergent.

[Variability of heart auscultation in patients with mitral valve prolapse]. / Zmiennosc zmian osluchowych serca u pacjentów z zespolem wypadania platka zastawki dwudzielnej.

The aim of the study was to analyze the auscultatory findings and its variability in 84 patients (pts) with mitral valve prolapse syndrome (MVPS) who were examined in the different body positions. All the pts underwent the echocardiographical examination and in 32 subjects (38%) prolapse of the anterior mitral leaflet was found, in 40 pts (48%) prolapse of the posterior mitral leaflet and in 12 (14%) pts prolapse of the both mitral leaflets. The auscultation of the heart was done in the supine position, in the lying position on the left side and in the upright position of the patient's body. Characteristic for the mitral valve prolapse (MVP) auscultatory findings (midsystolic murmur, late-systolic murmur and/or mid-systolic "non ejection" click) were demonstrated by 43 pts (51%) in the supine position. During the auscultation in the lying position of the pts on the left side, the auscultatory findings were found in 57 pts (68%) while in the upright position in 64 pts with MVPS (76%). The study showed that the auscultatory findings in pts with MVPS were demonstrated more frequently in the lying position of the body on the left side or in the upright position compared with the supine position. Moreover we found that 20 pts with MVPS (24%) did not demonstrate the characteristic auscultatory findings of MVP.

[Myocardial bridge of the coronary arteries and its clinical significance]. / Mosty miesniowe naczyn wiencowych i ich znaczenie kliniczne.

Myocardial bridge is a congenital anomaly of the coronary artery and appears on an angiogram as a systolic narrowing. Major coronary veins are rarely covered by myocardial bridges. The functional significance of coronary bridging remains controversial. Generally, bridging is not though to result in symptoms, as the coronary narrowing occurs during systole and most coronary flow occurs during diastole. Some authors reported this condition in association with angina pectoris, myocardial infarction, cardiac arrhythmias and sudden cardiac death. The mechanism of ischemia, connection with atherosclerosis are not clear. The symptomatic compressive myocardial bridge is in itself an indication for operation by simple section of the bridge. But if there exist associated atheromatous lesions, the surgeon should combine aortocoronary bypass with section or coronary angioplasty.

Fetal hemoglobin as a possible marker of susceptibility to working conditions for certain men exposed to industrial pollutants.

In 43 from 222 men (19.4%) employed in a coking plant a higher than normal concentration of fetal hemoglobin (HbF) was found, whereas an elevated level of HbF was detected in only two from 87 persons (2.3%) working in the cold rolling mill of the steel mill 'Huta Sendzimira', Krakow, Poland. Subjects employed in the coking mill worked in a much more polluted atmosphere than those in the cold rolling mill. It is speculated that synthesis of HbF may be a marker of the effect of unfavorable working conditions on some susceptible persons.

[Current views on the clinical significance of coronary artery spasm]. / Wspólczesne poglady na znaczenie kliniczne skurczu tetnic wiencowych.

Current views about etiology, pathogenesis, diagnostics and treatment of coronary artery spasm have been presented. A lot of researches show complexity of factors, which are responsible for coronary artery spasm. The most important are: a local hypersensitivity of vessels wall, neurogenic factors and humoral factors. The lack of magnesium plays also important role. Clinical manifestations of coronary artery spasm are: Printzmetal's angina, arrhythmia, acute myocardial infarction, atypical chest pain and cardiac sudden death. Among diagnostic examination the main importance have provocative tests with ergonovine and acetylcholine, rarely hyperventilation and cold are used. Calcium channel blockers, nitrate, molsidomine are employed in treatment patients with coronary artery spasm. There are taken modern examinations of new drugs like beta-1 adrenergic agonists and derived molsidomine agents. Beta-adrenergic blocking agents are contraindicated. It has been emphasized, that early diagnostics and pharmacologic treatment improve long-term prognosis in this group of patients.

Reference values for fetal hemoglobin concentration in blood of steel-mill workers.

The concentration of fetal hemoglobin (HbF) in blood of 195 healthy men and 39 women was measured by alkali denaturation method of Singer et al. Arithmetic mean in the group of men was 0.325% whereas in women it was 0.399%. The difference between the means was statistically significant. Frequency histograms showed two unlike subpopulations with wider span of values in women, different standardised skewness and kurtosis. Kolmogorov-Smirnoff test revealed a significant abnormality of both distributions. The data presented may serve for the comparison of HbF values obtained in persons living and working in similar microclimatic conditions.

[Arrhythmias in patients with mitral valve prolapse]. / Zaburzenia rytmu serca u chorych z zespolem wypadania platka zastawki dwudzielnej.

The aim of the study was to analyse rhythm disturbances in 92 patients with mitral valve prolapse syndrome (52 women and 40 men). The patients were examined by resting electrocardiograms monitoring, exercise electrocardiogram (submaximal exercise test), phonocardiograms and echocardiograms. We found tachycardia sinusalis in 72 patients (78%), supraventricular premature beats in 23 (25%) and ventricular premature beats in 54 patients (59%). There was no correlation between dizziness and syncope and ventricular rhythm disturbances in those patients.

Ventricular arrhythmias and the autonomic tone in patients with mitral valve prolapse.

The aim of this study was to evaluate a possible relation between the autonomic tone determined by daily urine catecholamine excretion and the incidence of ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP). The study included 53 patients (31 women and 22 men) aged 19-52 years (mean age 32.7). The diagnosis of MVP was based on medical history, physical examination, and echocardiography. Cardiac arrhythmias were detected by Holter monitoring and classified according to Lown grades. Daily heart rate and duration of corrected QT interval using Basett's formula were also analyzed. Daily urine adrenaline and noradrenaline levels were determined fluorometrically by Von Euler and Lishajko's method. The patients with Lown's grade III-V VA were evaluated with particular consideration. Student's t-test was used for statistical analysis. On Holter monitoring 26 patients showed VA, including 6 with grade I, 11 with grade II, 2 with grade III, 4 with grade IV, and 3 with grade V according to Lown's classification. The remaining 27 patients were free of cardiac arrhythmias. Mean daily heart rate ranged from 54-93 beats/min (73 +/- 8.44, mean +/- SD) and corrected QT from 336-494 ms (411 +/- 37.17). Daily adrenaline and noradrenaline excretion for the whole group of patients were 0.01-16.2 micrograms (2.1 +/- 2.38) and 1.6-31.0 micrograms (13.1 +/- 7.27), respectively, which was within normal range. However, the patients with serious ventricular arrhythmias showed significantly higher daily adrenaline excretion. Individual analysis of two-thirds of patients with ventricular arrhythmias grade III-V showed daily urine noradrenaline levels exceeding mean values for the whole group.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial vascularization of the vermiform appendix in human fetus.

In 50 human fetuses of the crown-rump length ranging from 88 mm to 185 mm (12 to 20 weeks), the variability of the arterial vascularization of the vermiform appendix was investigated using the injection method. 3 vascularization types were distinguished on the basis of the size and number of the supplying arteries. The obtained results were compared with those reported by other authors who studied vermiform appendix vascularization in adults. In most cases the vermiform appendix is supplied by single ramus arising from ileocolic artery.