Culture media affect sex after IVF treatment-a detailed analysis of explanatory variables.

PURPOSE: The purpose of this study was to provide a detailed analysis of clinical and laboratory factors associated with skewed secondary sex ratio (SSR) after ART. METHOD: Retrospective cohort study of embryos resulting in live births, from frozen and fresh single blastocyst transfers. Embryos were cultured in either G-TL (n = 686) or Sage media (n = 685). Data was analyzed using a multivariate logistic regression model and a mixed model analysis. RESULTS: Significantly more male singletons were born after culture in Sage media compared to G-TL media (odds ratio (OR) 1.34, 95% CI (1.05, 1.70), P = 0.02). Inner cell mass grade B vs A (OR 1.36 95% CI (1.05, 1.76), P = 0.02) and one previous embryo transfer (OR 1.49, 95% CI (1.03, 2.16), P = 0.03) were associated with a significantly higher probability of male child at birth. Factors associated with a reduced probability of male child were expansion grade 3 vs 5 (OR 0.66, 95% CI (10.45, 0.96), P = 0.03) and trophectoderm grade B vs A (OR 0.57, 95% CI (0.44, 0.74), P = 0.00). Male embryos developed significantly faster in Sage media compared to G-TL media for the stages of blastocyst (- 1.12 h, 95% CI (- 2.12, - 0.12)), expanded blastocyst (- 1.35 h, 95% CI (- 2.34, - 0.35)), and hatched blastocyst (- 1.75 h, 95% CI (- 2.99, - 0.52)). CONCLUSION: More male children were born after culture in Sage media compared to G-TL media. Male embryo development was affected by culture media. Our observations suggest that culture media impact male embryo quality selectively, thus potentially favoring the selection of male embryos.

Developmental stage and morphology of the competent blastocyst are associated with sex of the child but not with other obstetric outcomes: a multicenter cohort study.

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child? SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed. WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting. STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833). MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)). LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

New candidate genes for ST-elevation myocardial infarction.

BACKGROUND: Despite extensive research in atherosclerosis, the mechanisms of coronary atherothrombosis in ST-elevation myocardial infarction (STEMI) patients are undetermined. OBJECTIVES: Our aim was to find candidate genes involved in STEMI by analysing leucocyte gene expression in STEMI patients, without the influence of secondary inflammation from innate immunity, which was assumed to be a consequence rather than the cause of coronary atherothrombosis. METHODS: Fifty-one patients were included at coronary angiography because of STEMI. Arterial blood was sampled in the acute phase (P1), at 24-48 h (P2) and at 3 months (P3). Leucocyte RNA was isolated and gene expression analysis was performed by Affymetrix Human Transcriptome Array 2.0. By omission of up- or downregulated genes at P2, secondary changes from innate immunity were excluded. Genes differentially expressed in P1 when compared to the convalescent sample in P3 were determined as genes involved in STEMI. RESULTS: Three genes were upregulated at P1 compared to P3; ABCG1 (P = 5.81 × 10-5 ), RAB20 (P = 3.69 × 10-5 ) and TMEM2 (P = 7.75 × 10-6 ) whilst four were downregulated; ACVR1 (P = 9.01 × 10-5 ), NFATC2IP (P = 8.86 × 10-5 ), SUN1 (P = 3.87 × 10-5 ) and TTC9C (P = 7.18 × 10-6 ). These genes were also highly expressed in carotid atherosclerotic plaques. CONCLUSIONS: We found seven genes involved in STEMI. The study is unique regarding the blood sampling in the acute phase and omission of secondary expressed genes from innate immunity. However, the results need to be replicated by future studies.

Gene expression signatures, pathways and networks in carotid atherosclerosis.

BACKGROUND: Embolism from unstable atheromas in the carotid bifurcation is a major cause of stroke. Here, we analysed gene expression in endarterectomies from patients with symptomatic (S) and asymptomatic (AS) carotid stenosis to identify pathways linked to plaque instability. METHODS: Microarrays were prepared from plaques (n = 127) and peripheral blood samples (n = 96) of S and AS patients. Gene set enrichment, pathway mapping and network analyses of differentially expressed genes were performed. RESULTS: These studies revealed upregulation of haemoglobin metabolism (P = 2.20E-05) and bone resorption (P = 9.63E-04) in S patients. Analysis of subgroups of patients indicated enrichment of calcification and osteoblast differentiation in S patients on statins, as well as inflammation and apoptosis in plaques removed >1 month compared to <2 weeks after symptom. By prediction profiling, a panel of 30 genes, mostly transcription factors, discriminated between plaques from S versus AS patients with 78% accuracy. By meta-analysis, common gene networks associated with atherosclerosis mapped to hypoxia, chemokines, calcification, actin cytoskeleton and extracellular matrix. A set of dysregulated genes (LMOD1, SYNPO2, PLIN2 and PPBP) previously not described in atherosclerosis were identified from microarrays and validated by quantitative PCR and immunohistochemistry. CONCLUSIONS: Our findings confirmed a central role for inflammation and proteases in plaque instability, and highlighted haemoglobin metabolism and bone resorption as important pathways. Subgroup analysis suggested prolonged inflammation following the symptoms of plaque instability and calcification as a possible stabilizing mechanism by statins. In addition, transcriptional regulation may play an important role in the determination of plaque phenotype. The results from this study will serve as a basis for further exploration of molecular signatures in carotid atherosclerosis.

HLA-alleles associated with increased risk for extra-pulmonary involvement in sarcoidosis.

Genetic factors influence the risk for disease as well as the clinical picture seen in sarcoidosis and especially the genes localized to the human leukocyte antigen (HLA) region on chromosome 6 are of importance. The aim of this study was to further investigate associations between HLA-DRB1 alleles and the risk for extra-pulmonary manifestations (EPMs), i.e. engagement of the skin, superficial lymph nodes, eyes, nervous system, kidneys, hypercalcemia, parotid and salivary glands, heart, liver, spleen and bone marrow in Scandinavian sarcoidosis patients. One thousand patients with together with a group of 2000 healthy individuals, matched for sex and age. HLA-DRB1 alleles were determined for all patients and controls. Excluding erythema nodosum and ankle arthritis, we found 288 of 1000 patients to have EPMs. There were 383 patients with Löfgren's syndrome (LS), and among them EPM were relatively uncommon and diagnosed in only 31 (8.1%) of the patients. In contrast, among the 617 non-LS patients, 257 (41.6%) had EPM (P < 0.0001). In LS patients, the absence of HLA-DRB1*03 substantially increased the risk factor for EPM (erythema nodosum and ankle arthritis excluded) (P < 0.0001). A distinct HLA allele combination, HLA-DRB1*04/*15, was identified as a risk factor for EPM in all patients (25 of 50 with DRB1*04/15 had EPM). In conclusion, EPM are common in non-LS sarcoidosis. Furthermore, HLA-typing of sarcoidosis patients can be used in the clinic to identify patients with an increased risk for EPM.

Pulmonary function and blood gases after gastric bypass and lifestyle intervention: a comparative study.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study to compare the effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary function improved to a greater extent after gastric bypass than after lifestyle intervention. The superiority of surgical treatment might be mediated by greater weight loss after gastric bypass. Impaired lung function associated with obesity improves with weight loss. The effects of obesity surgery and intensive lifestyle intervention on pulmonary function and arterial blood gases have not previously been subjected to comparative examination. In this 1-year non-randomized controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139 morbidly obese subjects (19-66 years, mean [standard deviation] body mass index [BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes, gas diffusing capacity and arterial blood gases were measured. Compared with lifestyle intervention, surgery resulted in a significantly greater increase in forced vital capacity (mean [95% confidence interval] between-group difference, 7 [4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1-8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%), expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or diminished after adjusting for weight loss. Reduced central adiposity (waist circumference and waist-to-hip ratio) and systemic inflammation (C-reactive protein and adiponectin) had no effect on pulmonary function beyond the effect of reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass surgery is more effective than lifestyle intervention at improving arterial oxygenation and pulmonary function. The effect might be mediated by greater weight loss after surgical treatment.

Correlations between clinical variables and gene-expression profiles in carotid plaque instability.

OBJECTIVE: Strokes, a major cause of disability, are often caused by embolism from unstable carotid plaques. The aim of this study was to validate a biobank of human carotid endarterectomies as a platform for further exploration of pathways for plaque instability. For this purpose, we investigated the relationship between clinical parameters of plaque instability and expression of genes previously shown to be associated with either plaque instability or healing processes in the vessel wall. METHODS: A database of clinical information and gene-expression microarray data from 106 carotid endarterectomies were used. RESULTS: Expression of matrix metalloproteinase (MMP)-9 and MMP-7 was 100-fold higher in plaques than in normal artery. In general, genes associated with inflammation (such as RANKL and CD68) were overexpressed in symptomatic compared with asymptomatic plaques. Plaques obtained from patients undergoing surgery within 2 weeks after an embolic event showed up-regulation of genes involved in healing reactions in the vessel wall (including elastin and collagen). Statin treatment, as well as echodense lesions, were associated with a more stable phenotype. CONCLUSION: Here, we demonstrate that gene-expression profiles reflect clinical parameters. Our results suggest that microarray technology and clinical variables can be used for the future identification of central molecular pathways in plaque instability.

Expression of fatty acid-binding protein 4/aP2 is correlated with plaque instability in carotid atherosclerosis.

OBJECTIVE: the molecular basis for atherosclerotic plaque vulnerability with high risk of plaque rupture and thromboembolism is complex. We investigated whether clinical estimates of plaque stability correlate with differentially expressed mRNA transcripts within the lesion. METHODS AND RESULTS: endarterectomy samples from patients undergoing surgery for symptomatic and asymptomatic carotid stenosis were prospectively collected and clinical parameters recorded in the Biobank of Karolinska Carotid Endarterectomies. mRNA expression profiling (n = 40) and quantitative RT-PCR (n = 105) revealed increased levels of fatty acid-binding protein 4 (FABP4/aP2) in lesions from patients with recent symptoms of plaque instability compared to asymptomatic patients (array: FC = 2, P < 0.05; RT-PCR: P < 0.05). At the mRNA level, FABP4/aP2 correlated with the cell markers CD36, CD68 and CD163 of monocyte/macrophage lineage as well as with CD4-positive T cells. FABP4/aP2 mRNA expression was also correlated with enzymes of the leukotriene pathway, 5-lipoxygenase and leukotriene A4 hydrolase. In addition, analysis of transcript profiles identified CD52 and adipophilin as the mRNAs with the highest correlation with FABP4/aP2. Expression of FABP4/aP2 by macrophages and CD52 by T cells in the lesion was confirmed by immunohistochemistry. CONCLUSIONS: expression of FABP4/aP2 is increased at the mRNA level in unstable carotid plaques. Immunohistochemical analyses showed localization of FABP4/aP2 to macrophage populations. These FABP4/aP2-positive macrophages constitute an important and prevalent phenotype and could provide a new link between scavenging-mediated lipid uptake and cellular metabolic stress in plaque. In addition FABP4/aP2 correlates with other important signs of inflammation and plaque instability, such as T cells and leukotriene enzymes. Taken together, these results indicate that FABP4/aP2 is a key factor connecting vascular and cellular lipid accumulation to inflammation.

Continuous hypoxic culturing maintains activation of Notch and allows long-term propagation of human embryonic stem cells without spontaneous differentiation.

OBJECTIVE: The maintenance of pluripotency of human embryonic stem cells (hESCs) requires a high efficiency of self-renewal. During in vitro propagation, however, hESCs have a propensity to differentiate spontaneously. In this study, we assessed the nature of hESC responses to hypoxic conditions. MATERIALS AND METHODS: Human embryonic stem cells were grown in normoxic and hypoxic conditions, and the cells expressing Oct4 and stage-specific embryonic antigen-1 were identified by indirect immunofluorescence. The transcriptional expression of Nanog, Notch1, and Oct4 was determined by a real-time reverse transcription-polymerase chain reaction, and the inhibition of Notch-mediated signalling was achieved with a gamma-secretase inhibitor. RESULTS: In contrast to culture at 21% oxygen, where the colonies displayed a marked degree of differentiation, we found that during exposure to 5% oxygen, the hESC colonies displayed a homogenous and flat morphology that was consistent with the presence of Oct4-positive phenotype, indicating no spontaneous differentiation. When cultured at 5% oxygen for either 4 weeks or up to 18 months, high levels of Nanog and Notch1 transcriptional expression were detected, albeit the expression was significantly lower during longer exposure. The suppression of differentiation was rapidly reversed on transfer of the hypoxic cultures to normoxic conditions. Looking into the molecular mechanisms of the maintenance of self-renewal at low oxygen tensions, we found that inhibition of Notch signalling fully abrogated the hypoxic induction of undifferentiated phenotype. CONCLUSION: Our data, thus, indicate that hypoxic exposure has the capacity to sustain long-term self-renewal of hESCs and that this effect is mediated through activation of Notch.

Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm.

BACKGROUND: Follow-up studies of children conceived after ICSI using epididymal or testicular sperm are important due to a still more extensive use of immature male germ cells for ICSI. It is, however, difficult to evaluate the potential risks of malformations of children born after ICSI, overcoming the natural fertilization processes, due to methodological limitations. METHODS: Follow-up study including all children born in Denmark and Norway following ICSI in Denmark, using epididymal or testicular sperm, was done. A questionnaire was sent to the parents between 3 months and 7 years after delivery. RESULTS: Of 341 couples, 329 returned the questionnaire giving a response rate of 96.5%. The study included 412 children, 225 girls and 187 boys, giving a sex ratio (males/males + females) of 45.4% compared with 53.1% in Danish children conceived after conventional IVF without ICSI (P < 0.005). Among a total of 14 (3.4%; 95% confidence interval (CI): 1.9%-5.7%) major malformations, three boys with hypospadias were the most remarkable finding (1.6%; 95% CI: 0.33-4.7%). CONCLUSIONS: An increased frequency of hypospadias in the male offsprings was seen compared with the general population. Apart from this, no increased major malformation rate was detected in ICSI children conceived with epididymal or testicular sperm when compared with malformation rates for IVF or spontaneously conceived children reported in the literature. The sex ratio was significantly lower for ICSI children conceived with epididymal or testicular sperm when compared with children conceived with conventional IVF.

Parameters predicting the implantation rate of thawed IVF/ICSI embryos: a retrospective study.

Single embryo transfer is becoming increasingly popular in IVF/ICSI. More IVF/ICSI cycles therefore include freezing of high quality embryos, and the cumulative effect of such cycles becomes more important. To improve the results obtained using frozen-thawed embryos, the predictive value of embryo and patient characteristics was analysed retrospectively. Excess embryos were frozen on day 2 according to routine procedures and thawed 24 h before transfer. The women were either treated with oestradiol/progesterone, or the transfer took place after a natural cycle. Of 1777 embryos thawed, 1360 survived (survival rate 76.5%). In the 410 transfer cycles, 819 embryos were transferred, giving 109 positive serum HCG tests and 69 clinical pregnancies. The implantation rate was 10.4%. Five parameters were positively related to implantation: (i) four or more cells at the freezing time (day 2); (ii) resumption of mitosis after thawing; (iii) more than six cells at transfer (day 3); (iv) assisted hatching and (v) child in a previous fresh cycle. The relative predictive value of these parameters may be a guideline for the selection of embryos used for transfer. Assisted hatching may become routine in freeze-thaw cycles if its utility is confirmed in subsequent studies.

Assisted hatching improves implantation rates on cryopreserved-thawed embryos. A randomized prospective study.

BACKGROUND: Focus on the hatching process has so far been in the field of fresh embryos. Cryopreserved-thawed embryos have a lower rate of pregnancy than fresh embryos, which might be due to hardening of the zona pellucida. METHODS: During a 2 year period, a prospective randomized study enrolling 253 cryopreserved-thawed cycles was performed on day 2 embryos. Pseudorandomization to assisted hatching or a control group was done on the basis of even and odd dates for thawing. One hour before embryo transfer, hatching was carried out using acidic Tyrode's solution. RESULTS: Among 136 embryos exposed to assisted hatching, 11.4% (30) were implanted compared with only 5.8% (13) of 117 embryos not exposed to assisted hatching (P<0.05, chi(2) test). No difference in the rate of clinical pregnancy and positive serum HCG was observed between the two groups. Very few women >38 years old were included in the study, and no significant difference according to age could be found between the groups. CONCLUSIONS: These results show that assisted hatching using acidic Tyrode's solution increases the implantation rate of cryopreserved-thawed embryos (P<0.05).

Systemic vascular resistance during brief withdrawal of angiotensin converting enzyme inhibition in heart failure.

We tested the hypothesis that moderate increases in endogenous angiotensin II (Ang II) concentrations, induced by withdrawal of angiotensin converting enzyme inhibition (ACE-I) in patients with compensated heart failure (HF) on chronic medical therapy, do not increase or impair control of systemic vascular resistance (SVR). SVR was determined in supine and seated positions in 12 HF patients [NYHA class II-III; ejection fraction=0.29 +/- 0.03 (mean +/- SE)] and 9 control subjects. HF patients were investigated during high (n=11; withdrawal of ACE-I treatment for 24 h) and low (n=9; sustained ACE-I therapy) endogenous plasma Ang II concentrations. Withdrawal of ACE-I therapy in HF caused moderately increased Ang II concentrations of 30 +/- 5 pg/ml compared with 12 +/- 2 pg/ml in controls (p<0.05 vs. HF patients). Despite this, SVR was similar in HF (supine: 1503 +/- 159; seated: 1957 +/- 262 dyn s/cm5, p<0.05 vs. supine) and controls (supine: 1438 +/- 104; seated: 1847 +/- 127 dyn s/cm5, p<0.05 vs. supine). During sustained ACE-I therapy in HF, plasma Ang II concentrations were lower (6 +/- 2pg/ml, p<0.05 vs. withdrawal of ACE-I in HF) with no effect on supine SVR. However, the posture-induced increase in SVR in response to the seated position was attenuated. In conclusion, brief moderate increases in circulating plasma Ang II concentrations in compensated HF do not increase SVR compared to control subjects or impair control of SVR in response to a posture change.

Atrial distension, haemodilution, and acute control of renin release during water immersion in humans.

We tested the hypothesis that atrial distension (stimulation of cardiopulmonary baroreceptors) is not the single pivotal stimulus for the acute suppression of renin release during water immersion in humans and that immersion-induced haemodilution constitutes an important additional stimulus. In nine healthy male subjects, identical increases in atrial distension were induced by two immersion procedures (of 30 min each); one without (WI) and one with attenuation (WI + cuff) of the concomitant haemodilution (estimated from changes in plasma protein concentration) by inflating thigh cuffs during immersion. During WI, central venous pressure (CVP) and left atrial diameter (LAD) increased (P < 0.05) by 5.5 +/- 0.4 mmHg and 4.6 +/- 0.5 mm, respectively, and plasma protein concentration and plasma renin activity (PRA) progressively decreased (P < 0.05) by 4.8 +/- 0.5 g L(-1) and 1.6 +/- 0.2 ng mL(-1) h(-1) (to 49 +/- 4% of baseline values), respectively. The WI + cuff caused similar atrial distension as WI (CVP and LAD increased by 6.9 +/- 0.5 mmHg and 5.5 +/- 0.5 mm, respectively), attenuated haemodilution (plasma protein concentration decreased by 1.9 +/- 0.4 g L(-1), P < 0.05 vs. WI), and markedly inhibited suppression of PRA, which decreased by 0.4 +/- 0.1 ng mL(-1) h(-1) (to 87 +/- 4% of baseline values, P < 0.05 vs. WI). Differences in renin release could not be accounted for by differences in mean arterial pressure. In conclusion, baroreceptor stimulation induced by atrial distension is not the single pivotal stimulus for the acute suppression of renin release in response to intravascular volume expansion by water immersion in humans. Haemodilution constitutes a significant and conceivably the principal stimulus for the acute immersion-induced suppression of renin-angiotensin system activity.

The impact of the zona pellucida thickness variation of human embryos on pregnancy outcome in relation to suboptimal embryo development. A prospective randomized controlled study.

BACKGROUND: The study represents a prospective randomized controlled study evaluating zona pellucida thickness variation (ZPTV) measurements versus conventional selection of embryos using classic embryo score criteria, prior to embryo transfer in human IVF/intracytoplasmatic sperm injection (ICSI). METHODS: Eighty-six patients having > or =3 embryos, with a classic embryo score of < or =2.2, were allocated to either ZPTV measurement or classic embryo morphology score before embryo transfer. The technician selecting embryos using classic embryo scoring was not aware of the ZPTV measurement results. Of the embryos allocated to ZPTV measurements, only the embryos with the highest ZPTV were transferred. RESULTS: We found no differences in the pregnancy rate per embryo transfer between the two groups (34.4 versus 35.7%). Neither did the implantation rates differ. However, significantly better results were obtained when ZPTV was used as the selection criteria in cases where all embryos had an asynchrony in development or a high embryo score (i.e. were of poorer quality) by classical evaluation (odds ratio = 2.51, confidence interval = 0.33-198). CONCLUSIONS: Using a normally-developed embryo with an optimal embryo score, no beneficial effect of using ZPTV measurement was seen. However, when only less optimal embryos were available to select for transfer, ZPTV provided a x 2.5 increase in the chance of achieving a clinical pregnancy.

Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans.

During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (-9 to -24 mmHg) from between 30 and 31 +/- 1 to 34 +/- 1 mm (P < 0.05). The increase in PP from 38 +/- 2 to 44 +/- 2 mmHg (P < 0.05) was sustained during the posture change but only increased during the initial 5 min of negative pressure breathing from 36 +/- 3 to 42 +/- 3 mmHg (P < 0.05). Aortic transmural pressure decreased during the posture change and increased during negative pressure breathing. Plasma AVP was suppressed to a lower value during the posture change (from 1.5 +/- 0.3 to 1.2 +/- 0.2 pg/ml, P < 0.05) than during negative pressure breathing (from 1.5 +/- 0.3 to 1.4 +/- 0.3 pg/ml). Plasma norepinephrine was decreased similarly during the posture change and negative pressure breathing compared with seated control. In conclusion, the results are in compliance with the hypothesis that during maneuvers with similar cardiac distension, suppression of AVP release is dependent on the increase in PP and, furthermore, probably unaffected by static aortic baroreceptor stimulation.

Central volume expansion is pivotal for sustained decrease in heart rate during seated to supine posture change.

During prolonged, static carotid baroreceptor stimulation by neck suction (NS) in seated humans, heart rate (HR) decreases acutely and thereafter gradually increases. This increase has been explained by carotid baroreceptor adaptation and/or buffering by aortic reflexes. During a posture change from seated to supine (Sup) with similar carotid stimulation, however, the decrease in HR is sustained. To investigate whether this discrepancy is caused by changes in central blood volume, we compared (n = 10 subjects) the effects of 10 min of seated NS (adjusted to simulate carotid stimulation of a posture change), a posture change from seated to Sup, and the same posture change with left atrial (LA) diameter maintained unchanged by lower body negative pressure (Sup + LBNP). During Sup, the prompt decreases in HR and mean arterial pressure (MAP) were sustained. HR decreased similarly within 30 s of NS (65 +/- 2 to 59 +/- 2 beats/min) and Sup + LBNP (65 +/- 2 to 58 +/- 2 beats/min) and thereafter gradually increased to values of seated. MAP decreased similarly within 5 min during Sup + LBNP and NS (by 7 +/- 1 to 9 +/- 1 mmHg) and thereafter tended to increase toward values of seated subjects. Arterial pulse pressure was increased the most by Sup, less so by Sup + LBNP, and was unchanged by NS. LA diameter was only increased by Sup. In conclusion, static carotid baroreceptor stimulation per se causes the acute (<30 s) decrease in HR during a posture change from seated to Sup, whereas the central volume expansion (increased LA diameter and/or arterial pulse pressure) is pivotal to sustain this decrease. Thus the effects of central volume expansion override adaptation of the carotid baroreceptors and/or buffering of aortic reflexes.

Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure.

To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits a natriuresis. In HF, WI suppressed ANG II and aldosterone (Aldo) concentrations, increased the release of atrial natriuretic peptide (ANP), and elicited a natriuresis (P < 0.05 for all) compared with seated control. Compared with control subjects (n = 9), ANG II, Aldo, and ANP concentrations were increased (P < 0.05) in HF, whereas absolute and fractional sodium excretion rates were attenuated [47 +/- 16 vs. 88 +/- 15 micromol/min and 0.42 +/- 0.18 vs. 0.68 +/- 0.12% (mean +/- SE), respectively, both P < 0.05]. When ANG II and Aldo concentrations were further suppressed (P < 0.05) during WI in HF (by sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P < 0.05) to the level of control subjects (108 +/- 34 micromol/min and 0.70 +/- 0.23%, respectively). Renal free water clearance increased during WI in control subjects but not in HF, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast, renal free water clearance is attenuated in response to volume expansion in compensated HF despite normalized plasma AVP concentrations.

Mechanisms of hypotensive effects of a posture change from seated to supine in humans.

The hypothesis tested was that the hydrostatic stimulation of carotid baroreceptors is pivotal to decrease mean arterial pressure at heart level during a posture change from seated to supine. In eight males, the cardiovascular responses to a 15-min posture change from seated to supine were compared with those of water immersion to the xiphoid process and to the neck, respectively. Left atrial diameter and cardiac output (rebreathing) increased similarly during the posture change and water immersion to the xiphoid process and further so during neck immersion. Mean arterial pressure decreased by 12 +/- 2 mmHg during the posture change, by 5 +/- 1 mmHg during xiphoid immersion, and was unchanged during neck immersion. Arterial pulse pressure increased by 12 +/- 3 mmHg during the posture change (P < 0.05) and less during xiphoid and neck immersion by 7 +/- 3 mmHg (P < 0.05). Total peripheral vascular resistance decreased similarly during the posture change and neck immersion and slightly less during xiphoid immersion (P < 0.05). In conclusion, the hydrostatic stimulation of carotid baroreceptors combined with some additional increase in arterial pulse pressure, which also stimulates aortic baroreceptors, accounts for more than half of the hypotensive response at heart level to a posture change from seated to supine.

Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans.

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (-22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 +/- 1 mmHg, P < 0.05) and less during WI + NS (4 +/- 1 mmHg) and NS (3 +/- 1 mmHg). The decrease in heart rate (HR) by 13 +/- 1 beats/min (P < 0.05) and the increase in arterial pulse pressure (PP) by 17 +/- 4 mmHg (P < 0.05) during supine was more pronounced (P < 0.05) than during WI + NS (10 +/- 2 beats/min and 7 +/- 2 mmHg, respectively) and WI (8 +/- 2 beats/min and 6 +/- 1 mmHg, respectively, P < 0.05). Plasma vasopressin decreased only during supine and WI, and plasma norepinephrine, in addition, decreased during WI + NS (P < 0.05). In conclusion, WI + NS is not sufficient to decrease MAP and HR to a similar extent as a 15-min seated to supine posture change. We suggest that not only static carotid baroreceptor stimulation but also the increase in PP combined with low-pressure receptor stimulation is a possible mechanism for the more-pronounced decrease in MAP and HR during the posture change.