Value of two-dimensional shear wave elastography quantitative analysis for evaluation of thyroid function in first trimester pregnancy

Two-dimensional (2D) ultrasound shear wave elastography (SWE) has been widely used for soft tissue properties assessment. Given that shear waves propagate in three dimensions (3D), extending SWE from 2D to 3D is important for comprehensive and accurate stiffness measurement. However, implementation of 3D SWE on a conventional ultrasound scanner is challenging due to the low volume rate (tens of Hertz) associated with limited parallel receive capability of the scanner’s hardware beamformer. Therefore, we developed an external mechanical vibration-based 3D SWE technique allowing robust 3D shear wave tracking and speed reconstruction for conventional scanners. The aliased shear wave signal detected with a sub-Nyquist sampling frequency was corrected by leveraging the cyclic nature of the sinusoidal shear wave generated by the external vibrator. Shear wave signals from different sub-volumes were aligned in temporal direction to correct time delays from sequential pulse-echo events, followed by 3D speed reconstruction using a 3D local frequency estimation algorithm. The technique was validated on liver fibrosis phantoms with different stiffness, showing good correlation (r = 0.99, p < 0.001) with values measured from a state-of-the-art SWE system (GE LOGIQ E9). The phantoms with different stiffnesses can be well-differentiated regardless of the external vibrator position, indicating the feasibility of the 3D SWE with regard to different shear wave propagation scenarios. Finally, shear wave speed calculated by the 3D method correlated well with magnetic resonance elastography performed on human liver (r = 0.93, p = 0.02), demonstrating the in vivo feasibility. The proposed technique relies on low volume rate imaging and can be implemented on the widely available clinical ultrasound scanners, facilitating its clinical translation to improve liver fibrosis evaluation.

In veterinary medicine, previous studies regarding the diagnostic performance of shear wave elastography (SWE) in chronic kidney disease (CKD) are not consistent with each other. Moreover, there has been no study evaluating the relationship between symmetric dimethyl arginine (SDMA) concentration and renal shear wave velocity (SWV) using two-dimensional SWE (2D SWE) in dogs with CKD. This study aimed to evaluate the diagnostic capability of 2D SWE in dogs with CKD and to assess the relationship between renal SWV and SDMA concentration. Dogs with healthy kidneys and dogs with CKD underwent 2D SWE and SDMA assay. Renal stiffness was estimated as renal SWV in m/s. SDMA concentration had a weak positive correlation with the left (r = 0.338, p = 0.022) and right renal SWV (r = 0.337, p = 0.044). Renal SWV was not significantly different between healthy kidney and CKD groups in the left (p = 0.085) and right (p = 0.171) kidneys. 2D SWE may could not distinguish between dogs with healthy kidney and dogs with early stage of CKD, but it would be useful for assessing the serial change of renal function in dogs.

To explore the association between levels of thyroid-stimulating hormone (TSH) on admission and prognosis of patients admitted to intensive care unit (ICU). The data were collected from patients who were admitted to the ICU of the Beth Israel Deaconess Medical Center in the United States from 2001 to 2012 with available TSH test records within 24 hours after the ICU admission via the Medical Information Mart for Intensive Care-III v1.4 (MIMIC-III v1.4). Information including gender, age, ethnicity, type of admission, mechanical ventilation (MV) or renal replacement therapy (RRT) received on admission, comorbidities, and TSH test records within 24 hours after the ICU admission were collected. The sequential organ failure assessment (SOFA) score, simplified acute physiology score II (SAPS II) and the comorbidities index Elixhauser (SID30) score were calculated according to the parameters. The primary outcome was hospital mortality. Differences in baseline characteristics and prognosis were examined between patients with normal TSH levels and abnormal TSH levels which was determined according to a dichotomous variable provided by the data. Multivariable Logistic regression was used to analyze the association between TSH levels and prognosis after adjusting for confounding factors. A sensitivity analysis was conducted which categorized the study population as three groups (i.e., decreased, normal, and elevated TSH levels) using the range of 0.30-3.00 mU/L as the normal range of TSH. A total of 3 425 ICU patients were enrolled in the study, of which 2 692 (78.60%) were with normal TSH and 733 (21.40%) were with abnormal TSH. There was no statistically significant difference in gender, age, ethnicity, type of admission and the ratio of MV between the normal TSH and abnormal TSH groups. Compared with normal TSH group, the patients in abnormal TSH had a higher SOFA, SAPS II and SID30 scores as well as the ratio of RRT [SOFA score: 4 (2, 7) vs. 4 (2, 6), SAPS II score: 38.02±13.76 vs. 36.53±13.75, SID30 score: 11 (4, 22) vs. 11 (0, 20), RRT ratio: 5.32% (39/733) vs. 3.49% (94/2 692), all P < 0.05]. The hospital mortality of patients in normal TSH was significantly higher than that of those in abnormal TSH [9.82% (72/733) vs. 5.94% (160/2 692), P < 0.01]. After adjusting for confounding factors, abnormal TSH was significantly associated with hospital mortality [odds ratio (OR) = 1.71, 95% confidence interval (95%CI) was 1.24-2.35, P = 0.001]. In the sensitivity analysis in which the range of 0.30-3.00 mU/L was used as the normal range of TSH, compared with normal TSH, decreased TSH (OR = 2.36, 95%CI was 1.40-3.97, P = 0.001) and elevated TSH (OR = 1.44, 95%CI was 1.05-1.98, P = 0.023) were both significantly associated with increased hospital mortality. An abnormal level of TSH within 24 hours after admitted to ICU is an independent risk factor for hospital mortality among ICU patients.

Background and Aims Current assessment of diabetic kidney disease (DKD) is limited to estimated glomerular filtration rate (eGFR) and albuminuria. These are inadequate as DKD often has heterogenous clinical phenotypes. There is need for a marker of intra-renal fibrosis. Native kidney biopsy remains the only reference method in clinical practice for this purpose, but is invasive and impractical for repeated evaluations. Recently, two-dimensional ultrasound shear wave elastography (SWE) has emerged as a non-invasive technique to assess renal parenchymal stiffness with renal fibrosis. We aim to investigate SWE-derived estimates of tissue stiffness with different DKD stages in an Asian population. Method In this cross-sectional pilot study, 58 patients with DKD were recruited from a single centre ambulatory Nephrology clinic. Laboratory values were taken within 1 week of undergoing SWE, with DKD staging by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines and eGFR calculated using the CKD-EPI equation. 13 patients had histological diagnoses of DKD; 2 (15.3%) Stage G1-2; 5 (38.5%) Stage G3; 5 (38.5%) Stage G4 and 1 (7.7%) Stage G5 subjects, with native kidney biopsies performed within 4 months of study recruitment. 2D SWE was performed with a 2-5 MHz transducer on an Axiplorer© ultrasound system (Supersonic Imagine, Paris) by a single Nephrologist blinded to laboratory results. Using a previously described protocol, 6 SWE measurements were taken from the cortical mid-pole of bilateral kidneys, and renal elasticity estimated as Young’s Modulus (YM) in kilopascals (kPa), (Figure 1). Results Study population were 62.1% male (36/58) and 62.1% ethnic Chinese (36/58), with diabetes duration of 11.7 ± 9.2 years. Median eGFR was 35.0 (40-101) mL/min per 1.73 m2, with 6 (10.3%) DKD Stage G1-2; 34 (58.6%) Stage G3; 13 (22.4%) Stage G4 and 5 (8.6%) Stage G5 patients. There were moderate correlations between YM values in bilateral kidneys. Left kidney maximal YM generally increased in accordance with DKD stage (Stage G1-2: 20.6 kPa, Stage G3A: 13.5 kPa, Stage G3B: 22.4 kPa, Stage G4-5: 30.9 kPa, p &amp;lt;0.01). Kidney depth correlated moderately with body mass index (BMI). After controlling kidney depth and BMI, there was a moderately positive correlation between right kidney YM and DKD stage (Maximal YM; r = 0.4, p &amp;lt; 0.01, Mean YM; r = 0.31, p = 0.02). eGFR negatively correlated with bilateral kidney maximal YM (right r = -0.2, p = 0.04, and left r = -0.3, p = 0.03, respectively). Importantly, there was a strong correlation between right kidney mean YM and histological grading of interstitial fibrosis and tubular atrophy (r = 0.9, p = 0.01). There is no correlation between kidney elasticity and percentage of sclerosed glomeruli. Using a cut-off of 13.5 kPa for mean estimated tissue YM, the area under the receiver operator curve was 0.8 to distinguish DKD Stage G1 and G2 from G3A (sensitivity 83.3%, specificity 80.0%). Conclusion SWE-derived estimates of renal stiffness appear to increase with DKD stage. The strong correlation with histological markers of fibrosis indicate that observed differences are due to renal parenchymal stiffness. SWE shows promise as a non-invasive marker of renal fibrosis, although large multi-centre studies are required to validate these findings.

ObjectivesTo quantify and model normal foetal lung and liver elasticities between 24 and 39 weeks of gestation (WG) using two-dimensional shear wave elastography (2D-SWE). To assess the impact of the distance between the probe and the target organ on the estimation of elasticity values.MethodsMeasurements of normal foetal lungs and liver elasticity were prospectively repeated monthly between 24 and 39 WG in 72 foetuses using 2D-SWE. Elasticity was quantified in the proximal lung and in the region inside the hepatic portal sinus. The distance between the probe and the target organ was recorded. Trajectories representing foetal lung and liver maturation from at least 3 measurements over time were modelled.ResultsThe average elasticity for the lung and liver was significantly different from 24 WG to 36 WG (p < 0.01). Liver elasticity increased during gestation (3.86 kPa at 24 WG versus 4.45 kPa at 39 WG). From 24 WG to 32 WG, lung elasticity gradually increased (4.12kPa at 24 WG, 4.91kPa at 28 WG, 5.03kPa at 32 WG, p < 0.002). After 32 WG, lung elasticity decreased to 4.54kPa at 36 WG and 3.94kPa at 39 WG. The dispersion of the average elasticity values was greater for the lung than for the liver (p < 0.0001). Variation in the elasticity values was less important for the liver than for the lung. The values were considered valid and repeatable except for a probe-lung distance above 8cm.ConclusionFoetal lung and liver elasticities evolve differently through gestation. This could reflect the tissue maturation of both organs during gestation.Trial registrationclinicaltrials.gov identifier: NCT03834805Key Points• Prenatal quantification of foetal lung elasticity using 2D shear wave elastography could be a new prenatal parameter for exploring foetal lung maturity.• Liver elasticity increased progressively from 24 weeks of gestation (WG) to 39 WG, while lung elasticity increased first between 24 and 32 WG and then decreased after 32 WG.• The values of elasticity are considered valid and repeatable except for a probe-lung distance above 8cm.

Objective To explore the correlation of the gene polymorphism of the two single nucleotide polymorphisms(SNPs)rs1443434 and rs925489 on forkhead box El(FOXE1)with the high normal thyroid stimulating hormone(TSH)level in Chinese Han population. Methods 1 400 subjects with normal serum TSH and thyroid peroxidase antibody(TPOAb)levels were included. According to TSH or TPOAb levels, the subjects were divided into high normal TSH group(H-TSH group, n=195)and normal TSH control group(TSH control group, n=1 205)or high normal TPOAb group(H-TPOAb group, n=711)and low normal TPOAb group(L-TPOAb group, n=689), respectively. The genotypes on the two SNPs of all the subjects were performed by whole-genome genotyping chips. Results There were significant differences in rs925489 genotypic distributions and allele frequencies between H-TSH group and TSH control group(both P<0.05). The genotype TT and allele T in H-TSH group were significantly higher than those in TSH control group(89.75% vs 83.15%, 94.62% vs 91.29%). The normal TSH levels were positively associated with rs925489 genotypic distributions after adjustment for sex, age, and high density lipoprotein cholesterol(P<0.01). There were no significant differences in rs1443434 genotypic distributions and allele frequencies between two TSH groups or two TPOAb groups. Conclusion FOXE1 rs925489 gene polymorphism may be correlated with the high normal TSH level in Chinese Han population. Key words: Forkhead box El; rs925489; Polymorphism, single nucleotide; TSH

This study examined whether a mild elevation in serum Thyroid Stimulating Hormone (TSH) in normal older individuals was associated with a cognitive impairment. Participants consisted of 15 individuals with a high- TSH level and 82 with a normal TSH. The high-TSH group performed significantly worse than the normal- TSH group on tests of immediate and delayed verbal recall and on the Mini-Mental State Exam. This decrement was not due to group differences in processing resources nor was it explained by comorbid cerebrovascular disease, depression or anticholinergic drug usage. These results suggest that undetected mild thyroid dysfunction may contribute to the cognitive decrements found in older adults.

Objectives: 1) to determine the elasticity of normal breast tissue (parenchyma and premammary adipose tissue) in healthy women using ultrasound two-dimensional shear wave elastography (2D-SWE); 2) to reveal a possible correlation between increased stiffness of the breast parenchyma and hyperprolactinemia in patients with mastodynia and mastopathy; 3) to evaluate the ability of the Vitex agnus-castus drug to reduce the stiffness of the breast glandular tissue; 4) to objectify the ability of the Vitex agnus-castus drug to affect the thickness of the breast parenchyma, the condition of the milk ducts and cystic changes.Materials and methods. Breast tissue stiffness was investigated using 2D shear wave elastography (2D-SWE) in 32 women aged 18–52 with cyclic mastalgia/mastopathy before and after treatment with Vitex agnus-castus drug. A correlation was made with laboratory parameters (prolactin level), the general condition of the breast according to the results of ultrasonography in gray scale mode. The control group consisted of 78 women without complaints, without signs of diffuse and focal pathology of the mammary glands.Results. The 2D-SWE elastography showed normal values of breast tissue stiffness in women without pathology. 2D-SWE in symptomatic women made it possible to detect increased stiffness of the breast parenchyma, thereby screening for its diffuse changes. At the same time, dynamic changes in the softbreast tissue as a result of the treatment (parenchyma thickness, dilatation of the milk ducts, the presence of simple cystic foci (BI-RADS 2)) were diagnosed, analyzed and compared in grayscale mode ultrasonography (2D). The majority of patients (90,6%) noted a decrease in the level of prolactin after treatment. Statistical evidence of the positive effect of the Vitex agnus-castus drug in the treatment of mastodynia/mastopathy has been proven.Conclusions. Assessment of the basic breast tissue stiffness using 2D-SWE makes it possible to screen patients with its elevated values. This fact makes it possible to assign these women to the risk group of developing breast cancer. Evaluation of changes in the mechanical stiffness properties of the breast soft tissues makes it possible to evaluate and objectify the effectiveness of the treatment.

To date, no study has investigated the comparability between point shear wave elastography (pSWE) and 2D-shear wave elastography (2D-SWE) in assessing patellar tendon (PT) stiffness. In addition to comparing shear wave velocities, this study also evaluated intra- and interrater reliability, as well as measurement time. Forty healthy subjects (20 females, 20 males; age: 23.3±2.4 years, BMI: 22.46±2.23kg/m2) were recruited as participants. Each participant underwent a standardized multimodal ultrasound protocol that included B-mode ultrasound (B-US), Color Doppler ultrasound (CD-US), and a shear wave elastography (SWE) examination of the bilateral patellar tendon using both pSWE and 2D-SWE. Stiffness values and examination times were recorded. Intra- and interrater reliability were assessed across two different measurement time points with two investigators for both pSWE and 2D-SWE. Elastography values were slightly higher for pSWE compared to 2D-SWE (pSWE: 4.02±1.07m/s, 2D-SWE: 3.82±0.73m/s; p<0.001). 2D-SWE10 measurements took significantly more time than pSWE (2D-SWE10: 69.89±13.46s vs. pSWE: 54.85±8.34s, p<0.001). However, the time required for 2D-SWE1 was significantly shorter than for pSWE (2D-SWE1: 47.20±8.23s vs. pSWE: 54.85±8.34s, p<0.001). Both interrater and intrarater reliability reached excellent levels for all SWE measurements, with the highest interrater and intrarater ICC values obtained for 2D-SWE1. This is the first study to evaluate and compare pSWE and 2D-SWE in the assessment of patellar tendon stiffness. These findings could have important implications for the clinical use of musculoskeletal SWE, providing insights into measurement time, reliability, and the potential benefits of using 2D-SWE in clinical practice.

To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis. Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance. MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.

The estimation of viscosity by measuring the shear-wave dispersion (SWD) using ultrasound 2D shear-wave elastography (SWE) is becoming more and more popular. Recent research suggests that SWD can be used in addition to 2D-SWE (shear-wave speed) to diagnose diffuse liver disease. Viscosity was studied for the assessment of normal thyroid tissue. This study aims to evaluate the use of viscosity measurements in patients with chronic autoimmune thyroiditis using the SuperSonic MACH®30 ultrasound machine (Hologic SuperSonic Imagine, Aix-en-Provence, France) which provides the Vi PLUS mode for viscosity and the 2D SWE PLUS mode for shear-wave speed measurements. Valid measurements were obtained in 308 cases, 153 with chronic autoimmune thyroiditis (CAT) and 155 with no thyroid pathology (95.95% feasibility of the methods). The differences between the healthy group and the CAT group were statistically significant both for Vi PLUS (2.5 ± 0.4 vs. 2.8 ± 0.5, p < 0.0001) and for 2D-SWE PLUS (13.5 ± 3.3 vs. 23.1 ± 8.3, p < 0.0001). The diagnostic performance was poor for Vi PLUS alone (AUC = 0.69; cut-off > 2.5 Pa·s, se = 68.6%; sp = 64.52%) and good for 2D-SWE PLUS alone (AUC = 0.861; cut-off > 18.4 kPa, se = 69.9%; sp = 92.2%). Vi PLUS correlated with 2D-SWE PLUS, with the presence of CAT, the thyroid volume, levothyroxine replacement therapy and age. Statistically significant differences were found between the CAT subgroup receiving thyroid replacement therapy and the subgroup without therapy: 24.74 ± 8.33 vs. 21.93 ± 8.12 kPa for 2D-SWE (p = 0.0380) and 3 ± 0.5 vs. 2.7 ± 0.4 Pa·s for Vi PLUS (p = 0.0193). Elastography-based methods improve the classic ultrasound evaluation: 2D-SWE PLUS performed somewhat better in distinguishing CAT from normal thyroid tissue, while Vi PLUS made a slightly better assessment regarding the functional status.

Ultrasound shear wave elastography is well established in diagnostics of several parenchymatous organs and is recommended by respective guidelines. So far, research about applications in relevant neurological conditions is missing, especially in adults. Here we aimed to examine the method for the differentiation of ischemic (IS) and hemorrhagic strokes (HS) and cerebral mass effects. 50 patients with a confirmed diagnosis of HS or IS were enrolled in this prospective study. 2D shear wave elastography was performed on the ipsilateral and the contralateral side with a modified acoustic radiation force impulse (ARFI) technique (ElastPQ mode, Philips). Lesion volumetry was conducted based on computed tomography data for correlation with elastography results. Elastography measurements (EM) revealed a highly significant difference between IS and HS with mean values of 1.94 and 5.50 kPa, respectively (p < 0.00 001). Mean values of brain tissue on the non-affected side were almost identical (IS3.38 (SD = 0.63); HS 3.35 (SD = 0.66); p = 0.91). With a sensitivity of 0.98 and a specificity of 0.99, a cut-off value of 3.52 kPa for discrimination could be calculated. There was a significant correlation of mass effect represented by midline shift and EM values on the contralateral side (Pearson correlation coefficient = 0.68, p < 0.0003). Ultrasound brain parenchyma elastography seems to be a reliable sonographic method for discriminating between large IS and HS and for detecting and tracking conditions of intracerebral mass effects.

Objectives The aim of the study was to compare elastographic means in parathyroid adenomas, using shear wave elastography and strain elastography. Methods This prospective study examined 20 consecutive patients diagnosed with primary hyperparathyroidism and parathyroid adenoma, confirmed by biochemical assay, technetium-99 sestamibi scintigraphy, and pathology report, after parathyroid surgery. All patients were examined on conventional 2B ultrasound, 2D shear wave elastography, and strain elastography. We determined using 2D shear wave elastography (SWE) the elasticity index (EI) in parathyroid adenoma, thyroid parenchyma, and surrounding muscle and examined using strain elastography the parathyroid adenoma, and determined the strain ratio with the thyroid tissue and muscle tissue. Results All patients had positive sestamibi scintigraphy and underwent surgery, with confirmation of parathyroid adenoma in all cases. The mean parathormone (PTH) value before surgery was 153.29 pg/ml (36.5, 464.8) and serum calcium concentration was 10.5 mg/dl (9, 11.5). We compared using 2D-SWE and strain elastography parathyroid adenoma with thyroid tissue and with surrounding muscle. The mean EI measured by SWE in parathyroid adenoma was 4.74 ± 2.74 kPa and in thyroid parenchyma was 11.718 ± 4.206 kPa (mean difference = 6.978 kPa, p < 0.001), and the mean EI value in muscle tissue was 16.362 ± 3.829 kPa (mean difference = 11.622, p < 0.001). Using ROC analysis, we found that an EI below 7 kPa correctly identifies parathyroid tissue. We evaluated parathyroid adenomas using strain elastography by color mapping and strain ratio as a semiquantitative measurement; however, we could not find any statistical correlation comparing the strain ratio obtained from the parathyroid adenoma with the thyroid tissue (p=0.485). Conclusion Ultrasound elastography is a helpful tool in identifying parathyroid adenomas. A cutoff value below 7 kPa can be used in 2D-SWE. Color maps in strain elastography without adding strain ratio can be used, parathyroid adenoma being identified as score 1 in the Rago criteria.

STUDY QUESTIONDoes lower quartile normal range thyroid stimulating hormone (TSH) compared to higher quartile normal range in women without thyroid hormone substitution affect live birth rate after a complete IUI treatment series?SUMMARY ANSWERLower quartile normal range TSH, in women without thyroid hormone substitution, does not affect live birth rate after a complete intrauterine insemination treatment series compared to higher quartile normal range TSH.WHAT IS KNOWN ALREADYTSH is historically seen as the most sensitive test for thyroid function. Its distribution is right-skewed. Whether the preconceptional upper reference TSH values in subfertile women should be 2.5 or 4.5 mIU/L is under debate. Studies have shown that IUI patients treated with levothyroxine for TSH levels above 2.5 mIU/L show higher pregnancy rates. However, no adverse outcome is associated with untreated high normal TSH levels studied in first IUI cycles. Thyroid peroxidase antibodies have also impaired outcomes in some studies whereas others have shown an effect only in combination with high normal TSH levels. As a subgroup, patients with unexplained infertility showed increased levels of TSH. This article adds to the value of TSH evaluation and fertility outcome in four quartiles and in the context of a completed IUI treatment modus of a maximum of six inseminations.STUDY DESIGN, SIZE, DURATIONThis is a retrospective cohort study in 909 women undergoing 3588 IUI cycles starting treatment between the first of January 2008 and the first of March 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen aged 22–45 years with TSH 0.3–4.5 mIU/L without thyroid hormone substitution were included at Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands, an Iodine-sufficient area. The primary endpoint was live birth. Clinical pregnancy, pregnancy loss and ongoing pregnancy were secondary endpoints. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Chi-square tests and logistic regression were used to compare groups of patients based on TSH values in four quartile TSH groups (0.3–1.21 mIU/L; 1.22–1.75 mIU/L; 1.76–2.34 mIU/L; 2.35–4.5 mIU/L) on basic characteristics and on the endpoints while adjusting for confounders.MAIN RESULTS AND THE ROLE OF CHANCEAnalysis with the natural logarithm of TSH as a continuous variable showed no association with live birth, pregnancy chance or pregnancy loss. There were no differences in any of the outcomes across the quartile TSH level ranges after regression analysis before and after adjusting for age, BMI, use of alcohol, tobacco, use or gonadotrophins, sperm count, diminished ovarian reserve, unexplained infertility and primary or secondary subfertility.The distribution of primary and secondary subfertility and smoking characteristics were remarkably different across the four groups, with proportionally the lowest prevalence of primary subfertility and the highest rate of smoking in the lowest TSH group (0.3–1.20 mIU/L).LIMITATIONS, REASONS FOR CAUTIONUnknown values of free thyroxine and thyroid peroxidase antibodies, as well as the retrospective character of the study, limit the clinical interpretability.WIDER IMPLICATIONS OF THE FINDINGSTSH in the highest quartile range (2.35–4.5 mIU/L) in subfertile women preceding IUI is not associated with a lower live birth rate or rate of clinical and ongoing pregnancy, or with loss of pregnancies, compared to subfertile women with TSH in the lower three quartile groups after complete intrauterine insemination treatment.STUDY FUNDING/COMPETING INTEREST(s)The department of Obstetrics and Gynaecology, division of Reproductive Medicine, and of Internal Medicine, division of Endocrinology provided support. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

To analyse the intra- and interobserver variability of two elastographic methods of quantification available on thesame machine, the technical factors that may influence variability as well as the intra- and interobserver variability for thesame indices between two different ultrasound machines in an in vitro experimental setting. Threedifferent types of silicone experimental devices (ED) were conceived for the purpose of this study. Two observers performedrepeated measurements on two ultrasound machines. Strain elastography, with strain ratio determination between the ED wasperformed on both machines. Shear wave ratio was also assessed. The data obtained were used to calculate intra- and interobservervariability. Reproducibility was assessed in relation to the size of the elastographic region of interest (ROI) and tothe difference in stiffness between the ED, through the value of the ICCs (Intraclass Correlation Coefficient). Strainratio had high inter- and intraobserver reproducibility, regardless of the machine used, on a large number of determinations.The choice of a small ROI diameter (5 mm) over a large ROI diameter (15mm) increased reproducibility (ICC = 0.87 vs 0.78,p=0.000). It is observed that, by Shear Wave Elastography, only when analysing structures with a large difference in hardness,significance is obtained in terms of interobserver reproducibility (ICC = 0.75, p=0.000). On a large number ofdeterminations, both techniques are inter- and intraobserver reproducible. It is preferable to opt for a smaller ROI diameter inorder to increase interobserver reproducibility. SWE Ratio provides significant reproducibility only when analysing structureswith large difference in hardness.