Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

The Role of TSHR, PTEN and RASSF1A Promoters' Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma.

Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in TSHR, PTEN and RASSF1A genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of TSHR was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (p = 0.040). TSHR methylation levels in the PTC group plasma samples were significantly higher compared to HC (p = 0.022). After surgery, PTC plasma samples showed lower TSHR and PTEN methylation levels compared to the levels before surgery (p = 0.003, p = 0.031, respectively). The TSHR methylation level was significantly higher in PTC with larger tumor size (>2 cm) (p < 0.001), and lymph node metastases (p = 0.01), lymphovascular invasion (p = 0.02) and multifocality (p = 0.013) 0ROC analysis revealed that the TSHR methylation level provides high accuracy in distinguishing PTC from HC (p = 0.022, AUC of 0.616). Conclusion: TSHR methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.

Cardiometabolic Health in Adolescents and Young Adults with Congenital Adrenal Hyperplasia.

Background and objectives: Data on long-term cardiometabolic consequences in patients with congenital adrenal hyperplasia (CAH) are controversial. The aim of our study was to evaluate body mass index (BMI), body composition, blood pressure (BP) and insulin sensitivity in adolescents and young adults with CAH in comparison with healthy controls. Methods: Thirty-two patients with classical CAH (13 males; mean of age 26.0 ± 7.1, years (14.0−37.3) were compared to 32 healthy sex and age-matched controls (13 males; mean of age 28.7 ± 4.6 years (14.1−37.2), p = 0.13). Body composition was evaluated in all subjects with DXA (Hologic Inc., Bedford, MA, USA). Elevated BP was defined as BP > 95th percentile in adolescents, and >140/90 mmHg in adults. Comparisons between the two groups were adjusted for age, gender, pubertal stage and height. An oral glucose tolerance test was performed, and fasting insulin levels were evaluated. Insulin sensitivity was determined using a homeostasis model assessment of insulin resistance index (HOMA-IR). Results: The median BMI was significantly higher in subjects with CAH (1.63 (0.3−2.4) SDS and 0.41 (−0.63−1.19) SDS, respectively, p < 0.001). Visceral adipose tissue (VAT) in grams was significantly higher in CAH females versus control females (467 (231−561) vs. 226 (164−295), p = 0.002). Elevated BP was identified in 34% of CAH patients (nine SW and two SV) and 12.5% (n = 4) of controls (p = 0.038). Impaired fasting glycemia was detected in one SW CAH patient and impaired glucose tolerance in three SV CAH patients; normal glucose tolerance was found in all controls. A strong positive correlation was found between median cumulative hydrocortisone (HC) dose equivalents and LDL-cholesterol and a negative association with lean body mass (r = −0.79, p = 0.036) in females with CAH. BMI, VAT, BP and HOMA-IR were not related to median cumulative HC dose equivalents. Conclusions: CAH patients had higher BMI, VAT and frequency of elevated BP compared to controls. Doses of glucocorticoids were related directly to LDL-cholesterol and inversely to lean body mass in CAH females, but not associated with body composition, insulin sensitivity and BP in the whole cohort of CAH patients.

Diagnostic Value of Circulating Cell-free DNA in Patients With Papillary Thyroid Cancer.

AIM: We investigated whether the occurrence and development of papillary thyroid cancer (PTC) might be predicted using levels of circulating cell-free DNA (cfDNA). MATERIALS AND METHODS: The peripheral blood samples were collected from 68 patients with PTC, 31 patients with nodular goiter (NG), and 86 healthy controls (HC). The concentration of cfDNA was measured by qPCR using three primer sets: ß-actin99, ß-actin394 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in plasma samples. RESULTS: It was demonstrated that plasma ß-actin99 and ß-actin394 in the PTC group were significantly higher compared to HC (p<0.05 and p<0.001, respectively). The cfDNA integrity index was significantly higher in the PTC patients compared to HC and NG (p<0.001, p<0.05, respectively). The cfDNA concentration in the NG group was significantly higher than in the PTC (p<0.05 and p<0.001, respectively). Moreover, in most PTC patients with suppressed thyroglobulin, the ß-actin394 and cfDNA integrity index was significantly decreased after surgery (p<0.05 and p<0.001, respectively). ROC analysis revealed that cfDNA integrity index can be used as a potential marker in distinguishing PTC from HC (AUC 0.901, p<0.001) and NG (AUC 0.629, p<0.05). CONCLUSION: Increased concentration of cfDNA ß-actin99 and ß-actin394 may be a valuable biomarker that differentiates PTC patients from HC. Also, an increased cfDNA integrity index may be a suitable parameter which differentiates PTC patients from NG and HC.

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices.

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices.

PURPOSE: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. MATERIALS AND METHODS: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. RESULTS: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. CONCLUSIONS: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.

Papillary Thyroid Carcinoma Tissue miR-146b, -21, -221, -222, -181b Expression in Relation with Clinicopathological Features.

We analyzed miR-146b, miR-21, miR-221, miR-21, and miR-181b in formalin fixed paraffin-embedded papillary thyroid carcinoma (PTC) tissue samples of 312 individuals and evaluated their expression relationship with clinicopathological parameters. A higher expression of miR-21 was related to unifocal lesions (p < 0.011) and autoimmune thyroiditis (0.007). miR-221, miR-222 expression was higher in the PTC tissue samples with extrathyroidal extension (p = 0.049, 0.003, respectively). In a group of PTC patients with pT1a and pT1b sized tumors, the expression of miR-146b, miR-21, miR-221, and miR-222 in PTC tissue samples was lower than in patients with pT2, pT3, and pT4 (p = 0.032; 0.0044; 0.003; 0.001; 0.001, respectively). Patients with lymph node metastases had higher expression of miR-21, -221, -222, and -181b (p < 0.05). A high expression of miR-146b, miR-21, miR-221 panel was associated with decreased overall survival (OS) (Log rank p = 0.019). Univariate analysis revealed that presence of metastatic lymph nodes and high expression of miR-146b, miR-21, and miR-221 panels were associated with increased hazard of shorter OS. After multivariate analysis, only sex (male) and age (≥55 years) emerged as independent prognostic factors associated with shorter OS (HR 0.28 (95% CI 0.09-0.86) and HR 0.05 (95% CI 0.01-0.22), respectively). In conclusion, 5 analyzed miRs expression have significant relations to clinicopathologic parameters so further investigations of these molecules are expedient while searching for prognostic PTC biomarkers.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

Different stability of miRNAs and endogenous control genes in archival specimens of papillary thyroid carcinoma.

BACKGROUND: The most popular miRNA quantitation technique is RQ-PCR with relative gene expression method that requires an endogenous control (EC) gene for data normalization. However, there are insufficient data and selection criteria on the most suitable ECs for miRNA expression studies in many cancer types including papillary thyroid carcinoma (PTC). Therefore, in this study we evaluated the impact of chosen EC and archival formalin-fixed, paraffin-embedded (FFPE) PTC tissue age on estimated target miRNA expression. METHODS: RQ-PCR was used to determine expression levels of five miRNAs (miR-146b, miR-222, miR-21, miR-221 and miR-181b) and three different endogenous controls (RNU48, let-7a, miR-16), which were used to normalize the data. In total, 400 FFPE PTC tissues were analyzed that have been stored from 1 to 15 years. RESULTS: The stability of commonly used ECs RNU48 and let-7a significantly differs from the stability of target miRNA in archival FFPE PTC tissues. Moreover, these differences have a great impact on miRNA expression results when FFPE tissue samples have been stored for a different period of time. CONCLUSIONS: It is important to select an ECs not only stable in the tissue of interest but also with similar stability to target miRNA, especially when working with samples of different age.

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer.

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression (n = 49) was compared with plasma miRNA in the HC group (n = 57) and patients with NG (n = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC (p < 0.0001; p < 0.0001; p < 0.0001; p < 0.0001; p < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy (p = 0.004; p = 0.001; p = 0.03; p = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group (p = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; p = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.

Association of MicroRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer.

Many miRNAs and cancer-related mutations have been proposed as promising molecular markers of papillary thyroid carcinoma (PTC). However, there are limited data on the correlation between miRNA expression, BRAFV600E mutation, and PTC recurrence. Therefore, to evaluate the potential of BRAFV600E mutation and five selected miRNAs (-146b, -222, -21, -221, -181b) in predicting PTC recurrence, these molecular markers were analyzed in 400 formalin-fixed, paraffin-embedded PTC tissue specimens. The expression levels of miRNAs were measured using qRT-PCR. It was demonstrated that expression levels of all analyzed miRNAs are significantly higher in recurrent PTC than in non-recurrent PTC (p < 0.05). Moreover, higher expression levels of miR-146b, miR-222, miR-21, and miR-221 were associated with other clinicopathologic features of PTC, such as tumor size and lymph node metastases at initial surgery (p < 0.05). No significant differences in the frequency of BRAFV600E mutation in recurrent PTC and non-recurrent PTC were determined. Our results suggest that miRNA expression profile differs in PTC that is prone to recurrence when compared to PTC that does not reoccur after the initial surgery while BRAFV600E mutation frequency does not reflect the PTC recurrence status. However, the prognostic value of the analyzed miRNAs is rather limited in individual cases as the pattern of miRNA expression is highly overlapping between recurrent and non-recurrent PTC.

Relationship between Echocardiographic and Magnetic Resonance-Derived Measurements of the Thoracic Aorta in Turner Syndrome Patients.

INTRODUCTION: Turner syndrome (TS) is assigned to the rare diseases group. Morbidity and mortality of TS patients are high, particularly due to the cardiovascular disorders, so monitoring for cardiovascular complications must be ensured. The data demonstrate a strong correlation between 2-dimensional echocardiographic (2Decho) evaluation and magnetic resonance imaging (MRI); still, according to recent guidelines, MRI remains a gold standard. In this study, we aimed to compare aortic dimensions on MRI and 2Decho in TS patients. METHODS: 50 TS patients (≥18 years) were enrolled into the cross-sectional study. 2Decho and MRI were performed. The measurements of the aorta were assessed in five standard positions on 2Decho and in 9 standard positions on MRI; ASI (aortic size index) of the ascending aorta was calculated since reduced adult height is observed in TS patients. RESULTS: ASI on echocardiography strongly correlated with ASI on MRI in all positions of the ascending aorta, but significantly larger medians of ASI were found on 2Decho in all positions of the ascending aorta and arch when compared with MRI measurements. Still, the prevalence of aortic sinus dilation was significantly and more frequently (52% vs. 38%, p < 0.001) observed on MRI when compared with 2Decho. CONCLUSION: The relation of aortic size was significant in all positions when comparing the MRI and 2Decho methods; still, the dilatation of the sinus of aorta was more frequently found on MRI compared with echocardiography.

SGLT2 inhibitors in T2D and associated comorbidities - differentiating within the class.

BACKGROUND: For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. EXPERT OPINION: To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. CONCLUSION: CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

Corrigendum to "Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects".

[This corrects the article DOI: 10.1155/2017/8401518.].

The Link between Thyroid Autoimmunity, Depression and Bipolar Disorder.

Depression and bipolar disorder are two major psychiatric illnesses whose pathophysiology remains elusive. Newly emerging data support the hypothesis that the dysfunction of the immune system might be a potential factor contributing to the development of these mental disorders. The most common organ affected by autoimmunity is the thyroid; therefore, the link between autoimmune thyroid disorders and mental illnesses has been studied since the 1930s. The aim of this review is to discuss the associations between thyroid autoimmunity, depression and bipolar disorder.

The main predictors of the enlargement of ascending aorta in Turner syndrome: a cross-sectional contrast-enhanced magnetic resonance angiography study.

BACKGROUND: The aim of this study was to identify the main predictors of the enlargement of ascending aorta and to assess the possible relation between reduced bone mineral density and a diameter of ascending aorta in the specific Turner syndrome (TS) population. METHODS: Fifty adult females diagnosed with TS have been enrolled into the cross-sectional study. Dimensions of ascending aorta have been measured in four positions using thoracic magnetic resonance imaging, Aortic Size Index (ASI) has been calculated. BMD has been assessed on dual-energy-X ray absorptiometry (DXA) in 1-4 lumbar vertebrae and neck of the femur. According to Z Score on DXA two groups have been formed: a group of patients with normal BMD and a group with reduced BMD. Metabolic parameters and the measurements of ascending aorta have been compared between the two groups. RESULTS: Extremely high rate of the dilatation of the root of aorta (up to 50%) was identified in this study. The larger ASI has been found in patients with reduced BMD, negative relation between BMD and ASI has been identified, although after the adjustment for SHRT this correlation remained insignificant. In the multivariate analysis, the main factors affecting ASI were age, body surface area and bicuspid aortic valve. CONCLUSIONS: The main factors associated with the enlargement of ascending aorta in Turner syndrome were age, body surface area and bicuspid aortic valve, the relation between diameter of ascending aorta and bone mineral density was not identified.

The impact of FSH receptor polymorphism on time-to-pregnancy: a cross-sectional single-centre study.

BACKGROUND: Single nucleotide polymorphism of the follicle-stimulating hormone (FSH) receptor (FSHR) is an important marker of ovarian function. However, its role in female fecundity remains debatable. The aim of the study to assess the relationship of FSHR polymorphism of Serine/Serine, Asparagine/Asparagine and Asparagine/Serine variants directly against the time-to-pregnancy (TTP) in women. METHODS: Data were collected from 291 consecutive selected post-partum Caucasians using this criterion: ethnicity, age between 21 and 34-year-old new mothers and, 0-3 days after delivery of newborns in the Klaipeda University Hospital, Lithuania. Questionnaires on factors associated with conception were given to patients, and blood samples were collected for genomic DNA extractions as well as for analysis of follicle-stimulating hormone receptor gene polymorphism. Odds ratios (OR) and 95% confidence intervals (CI) for time-to-pregnancy were estimated by multivariate logistic regression. Women with unplanned pregnancies and those who received assisted reproductive technologies were not included in the study. RESULTS: After adjustment for other possible factors, increased risk for time-to-pregnancy of 12 or more months was associated with: Serine/Serine polymorphism variant (OR = 1.38, 95% CI 1.56-2.71, p = 0.007), age of 30 or more years (OR = 1.95, 95% CI 1.25-2.71, p = 0.015), gynaecological diseases in the past (OR = 2.21, 95% CI 1.12-5.74, p = 0.027), prior contraception use (OR = 1.87, 95% CI 1.14-3.64, p = 0.016), and fertility problems in the past (OR = 1.57, 95% CI 1.16-4.76, p = 0.019). CONCLUSION: The results suggest a possible relationship of FSH receptor gene Serine/Serine variant for the lower possibility of conception during the first 12 months of planned conception.

Semen quality of young men from the general population in Baltic countries.

STUDY QUESTION: What are the parameters of semen quality in Baltic men? SUMMARY ANSWER: Combined parameters of sperm concentration, motility and morphology revealed that 11-15% of men had low semen quality, 37-50% intermediate and 38-52% high semen quality. WHAT IS KNOWN ALREADY: Previous studies have revealed regional differences in semen parameters, and semen quality of Baltic men has been suggested to be better than that of other European men. STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study of 1165 men aged 16-29 years from Estonia (N = 573), Latvia (N = 278) and Lithuania (N = 314) conducted in 2003-2004. PARTICIPANTS/MATERIALS SETTING METHODS: Men from the general population, median age 19.8 years, provided one semen sample each, had blood samples taken, had testis size determined, and provided information on lifestyle. Based on combined data of sperm concentration, sperm motility and morphology the cohort was classified into three categories: low, intermediate or high semen quality. Comparisons between groups (including subgroups of Estonian men of Russian versus Estonian ethnicity) were tested, adjusting for ejaculation abstinence and age. MAIN RESULTS AND THE ROLE OF CHANCE: The median sperm concentration of the Estonian, Latvian and Lithuanian populations of Baltic men was 63 mill/ml. Low semen quality was detected in 11-15% of the men, intermediate in 37-50% and high in 38-52%. No crucial differences between national subgroups were detected, except that a higher percentage (9.6%) of the subgroup of Russian Estonians reported having had cryptorchidism compared to the other men (2.5-3.6%, P < 0.001). Smoking had an adverse impact on both sperm concentration and total sperm counts (P < 0.001). LIMITATIONS REASONS FOR CAUTION: The semen quality data were collected >10 years ago. Thus, a recent change in semen quality cannot be excluded. Owing to the study design, it is assumed, but unproven, that the men were representative of the general populations. Some men were very young (16 years), however, this was also the case for other European studies of similar populations. Assessment of sperm motility is associated with inter-observer variation, and no quality control was undertaken for sperm motility assessment to account for that. Thus, estimates of sperm motility should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Analysis of the semen variables separately did not identify that a considerable percentage of Baltic men had low semen quality. The combined analysis, however, showed that more than one out of nine men had semen quality at a level indicating reduced fertility chances. We suggest that future studies of semen quality should be carried out reporting both results of single semen parameters and estimates that combine the most frequently assessed variables. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the EU fifth framework project Number QLK4-1999-01422 'Envir.Repro.Health' extension to Baltic countries Number QLRT-2001-02911; Estonian Science Foundation, grant numbers 2991 and PUT181. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Factors Associated with the Prevalence of Thyroid Nodules and Goiter in Middle-Aged Euthyroid Subjects.

The aim of the present study was to determine associations of thyroid hormone levels and different metabolic parameters and anthropometric measurements with volume of nodular and nonnodular thyroid as well as with prevalence of goiter and thyroid nodules in middle-aged euthyroid subjects. Methods. The study consisted of 317 euthyroid subjects aged 48-49 from the Kaunas Cardiovascular Risk Cohort study. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and antithyroid peroxidase antibody (ATPO) levels, as well as anthropometric and metabolic parameters and smoking information, were evaluated. Results. In subjects with and without thyroid nodules, thyroid volume correlated with components of metabolic syndrome, body mass index (BMI), smoking, and TSH levels. In the nonnodular thyroid group, thyroid volume was also positively related to serum insulin and HOMA-IR, whereas a negative correlation between thyroid volume and leptin was identified in the nodular thyroid group. The goiter was identified in 12.3% of subjects. Female gender, thyroid nodules, smoking, BMI, and levels of TSH were independent predictors for goiter. Thyroid nodules were found in 31.2% of participants. Female gender, higher TSH levels, and thyroid volume were independent risk factors for thyroid nodules. Conclusions. Female gender, thyroid nodules, smoking, BMI, and TSH levels were identified as potential predictors of goiter. Female gender, TSH levels, and thyroid volume predicted the presence of thyroid nodules.