Aromatase inhibitors in post-menopausal endometriosis

Background

Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle.

Methods

AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes.

Results

AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose.

Conclusions

OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance.     

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

Objective

This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.

Methods

We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.

Results

Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.

Conclusion

Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women''s age.     

Age at Adiposity Rebound Is Associated with Fat Mass in Young Adult Males—The GOOD Study

Objective

Age at adiposity rebound (AR) is associated with obesity and Type 2 Diabetes in adults. The aim of the present study was to investigate the role of age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish cohort.

Patients and Methods

This is a retrospective cohort study. Detailed growth charts were retrieved for the men participating in the population-based GOOD (Gothenburg Osteoporosis and Obesity Determinants) study (n = 573). Body composition was analysed using dual X-ray absorptiometry and computed tomography at 18–20 years of age. Age and BMI at AR were calculated using pediatric growth charts and AR was defined as the lowest BMI between 3 and 9 years of age.

Results

Subjects were divided into early (age at AR below 5.4 years of age), middle (age at AR 5.4 to 6.8 years of age) and late (age at AR after 6.8 years of age) age at AR tertiles. Subjects in the early age at AR tertile had higher young adult BMI (+8%), whole body fat mass (+34%) and amount of subcutaneous adipose tissue (+61%) than the subjects in the middle and late tertiles (p<0.01). The early age at AR tertile had an increased risk of obesity (Odds Ratio 4.1 [95% CI 1.2–13.9]) compared with the middle and late tertiles. In addition, the early age at AR tertile had Peak Height Velocity (PHV) 7 months earlier than the late tertile.

Conclusions

Early age at AR was associated with young adult obesity as a consequence of a high amount of subcutaneous adipose tissue in men. In addition we made the novel observation that early age at AR was associated with an early puberty in men.     

Ovarian Response and Cumulative Live Birth Rate of Women Undergoing In-Vitro Fertilisation Who Had Discordant Anti-Mullerian Hormone and Antral Follicle Count Measurements: A Retrospective Study

Objective

To evaluate ovarian response and cumulative live birth rate of women undergoing in-vitro fertilization (IVF) treatment who had discordant baseline serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC).

Methods

This is a retrospective cohort study on 1,046 women undergoing the first IVF cycle in Queen Mary Hospital, Hong Kong. Subjects receiving standard IVF treatment with the GnRH agonist long protocol were classified according to their quartiles of baseline AMH and AFC measurements after GnRH agonist down-regulation and before commencing ovarian stimulation. The number of retrieved oocytes, ovarian sensitivity index (OSI) and cumulative live-birth rate for each classification category were compared.

Results

Among our studied subjects, 32.2% were discordant in their AMH and AFC quartiles. Among them, those having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate. Subjects discordant in AMH and AFC had intermediate OSI which differed significantly compared to those concordant in AMH and AFC on either end. OSI of those discordant in AMH and AFC did not differ significantly whether either AMH or AFC quartile was higher than the other.

Conclusions

When AMH and AFC are discordant, the ovarian responsiveness is intermediate between that when both are concordant on either end. Women having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate.     

Sperm quality and paternal age: effect on blastocyst formation and pregnancy rates

Background

Several studies suggest a decrease in sperm quality in men in the last decades. Therefore, the aim of this work was to assess the influence of male factors (sperm quality and paternal age) on the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

Methods

This retrospective study included all couples who underwent IVF or ICSI at Montpellier University Hospital, France, between 1 January 2010 and 31 December 2015. Exclusion criteria were cycles using surgically retrieved sperm or frozen sperm, with pre-implantation genetic diagnosis or using frozen oocytes. The primary outcomes were the blastulation rate (number of blastocysts obtained at day 5 or day 6/number of embryos in prolonged culture at day 3) and the clinical pregnancy rate. The secondary outcomes were the fertilization and early miscarriage rates.

Results

In total, 859 IVF and 1632 ICSI cycles were included in this study. The fertilization rate after ICSI was affected by oligospermia. Moreover, in ICSI, severe oligospermia (lower than 0.2 million/ml) led to a reduction of the blastulation rate. Reduced rapid progressive motility affected particularly IVF, with a decrease of the fertilization rate and number of embryos at day 2 when progressive motility was lower than 32%.Paternal age also had a negative effect. Although it was difficult to eliminate the bias linked to the woman’s age, pregnancy rate was reduced in IVF and ICSI when the father was older than 51 and the mother older than 37 years.

Conclusions

These results allow adjusting our strategies of fertilization technique and embryo transfer. In the case of severe oligospermia, transfer should be carried out at the cleaved embryo stage (day 2–3) due to the very low blastulation rate. When the man is older than 51 years, couples should be aware of the reduced success rate, especially if the woman is older than 37 years. Finally, promising research avenues should be explored, such as the quantification of free sperm DNA, to optimize the selection of male gametes.

     

Ongoing Pregnancy Rates in Women with Low and Extremely Low AMH Levels. A Multivariate Analysis of 769 Cycles

Background

The ideal test for ovarian reserve should permit the identification of women who have no real chance of pregnancy with IVF treatments consequent upon an extremely reduced ovarian reserve. The aim of the current study was to evaluate pregnancy rates in patients with low AMH levels (0.2–1 ng/ml) and extremely low AMH levels (<0.2 ng/ml) and to determine the cumulative pregnancy rates following consecutive IVF treatments.

Methods

We conducted an historical cohort analysis at a tertiary medical center. Serum AMH levels were measured at initial clinic visit and prior to all following treatment cycles in 181 women (769 cycles) with an initial AMH level ≤1 ng/ml, undergoing IVF-ICSI. Main outcome measures were laboratory outcomes and pregnancy rates.

Results

Seventy patients undergoing 249 cycles had extremely low AMH levels (≤0.2 ng/ml), whereas 111 patients undergoing 520 cycles had low AMH levels (0.21–1.0 ng/ml). Number of oocytes retrieved per cycle, fertilized oocytes and number of transferred embryos were significantly lower in the extremely low AMH levels group compared to the low AMH levels (P<0.003). Crude ongoing pregnancy rates were 4.4% for both groups of patients. Among 48 cycles of women aged ≥42 with AMH levels of ≤0.2 ng/ml no pregnancies were observed. But, in patients with AMH levels of 0.2–1.0 ng/ml, 3 ongoing pregnancies out of 192 cycles (1.6%) were observed. However, in a multivariate regression analysis adjusted for age and cycle characteristics, no significant differences in ongoing pregnancy rates per cycle between the two groups were evident. Cumulative pregnancy rates of 20% were observed following five cycles, for both groups of patients.

Conclusions

Patients with extremely low AMH measurements have reasonable and similar pregnancy rates as patients with low AMH. Therefore, AMH should not be used as the criterion to exclude couples from performing additional IVF treatments.     

Renal function is related to severity of coronary artery calcification in elderly persons: the Rotterdam study

Background

Coronary artery calcification (CAC) has been proposed to be the underlying mechanism of the increased risk of coronary heart disease with reductions in glomerular filtration rate (GFR). Since renal function diminishes with aging we examined the association between GFR and CAC in the Rotterdam Study, a population-based study of elderly individuals.

Methods

The study was performed in 1703 subjects without a history of coronary heart disease. GFR was estimated using the modification of diet in renal disease equation. We used analysis of covariance to test for mean differences in CAC between GFR tertiles.

Results

The mean CAC scores in the middle and lowest GFR tertile did not significantly differ from the mean CAC score in the highest GFR tertile (geometric mean CAC score 4.1 and 4.3 vs 4.2). In a multivariable model the mean CAC score did also not differ between the GFR tertiles. As the interaction term between age and GFR was significant (P = 0.037), we divided the population in two age categories based on median age of 70 years. Below 70 years, the mean CAC scores did not differ between the GFR tertiles. Above median age, mean CAC score in the lowest GFR tertile was significantly higher than the mean CAC score in the highest tertile in a multivariable model (CAC 4.9 vs 4.5, p = 0.010).

Conclusion

In this population-based study we observed that the association between CAC and GFR is modified by age. In participants at least 70 years of age, a decrease in GFR was associated with increased CAC.     

Discordances between follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility

Background

Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients.

Methods

We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR.

Results

Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages.

Discussion

Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF.

     

Intérêt du dosage de l’inhibine B et de l’AMH dans le plasma séminal: étude préliminaire

Objectives

The aim of this study was to establish reference values for seminal inhibin B and AMH concentrations in patients with normal and abnormal sperm parameters. Preliminary analysis was performed to evaluate the predictive value of these markers for retrieving testicular sperm in non-obstructive azoospermic men.

Methods

Seminal inhibin B and AMH concentrations were assayed by an enzyme-linked immunoassay in three groups of men: 47 patients with normal sperm parameters, 28 oligospermic men and 68 patients with azoospermia.

Results

Inhibin B and AMH concentrations varied considerably in the three groups, but were significantly higher in normospermic men (inhibin B: 714.36±522.66 ng/l, AMH: 97.08±135.15 pmol/l) than in oligospermic men (inhibin B: 417.5±386.9 ng/l, AMH: 62.02±93.33 pmol/l) and azoospermic men (59.61±2.65 ng/l et 13.12±31.94 pmol/l, respectively) (p<0.001). A significant correlation (p=0.0054) was observed between seminal inhibin B concentration and sperm production. Testicular biopsy allowed sperm retrieval in 11 out of 21 patients (52.3%). The predictive value of seminal inhibin B was analyzed using receiver operating characteristics (ROC) curve analysis. The best discriminating inhibin B concentration was 30 ng/l with an area under the curve (AUC) of 0.63.

Conclusion

This study confirms the correlation between seminal inhibin B and AMH concentrations and spermatogenesis. However, the significance of these two markers as predictors of the presence of testicular sperm in men with non-obstructive azoospermia is limited. This analysis shows that AMH and inhibin B, either alone or in combination with serum FSH, fail to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.     

Anti-Müllerian Hormone Serum Values and Ovarian Reserve: Can It Predict a Decrease in Fertility after Ovarian Stimulation by ART Cycles?

Background

A variety of indicators of potentially successful ovarian stimulation cycles are available, including biomarkers such as anti-Mullerian hormone. The aim of our study was to confirm the usefulness of serum anti-Mullerian hormone assay in predicting ovarian response and reproductive outcome in women eligible for ART cycles.

Materials

Forty-six women undergoing ART cycles at the Centre for Reproductive Medicine in Parma were recruited from March-to-June 2010. Inclusion criteria: age<42 years; body-mass-index = 20–25; regular menstrual cycles; basal serum FSH concentration <12 IU/L and basal serum estradiol concentration <70 pg/mL. The couples included in our study reported a variety of primary infertility causes. All women underwent FSH stimulation and pituitary suppression (GnRH-agonist/GnRH-antagonist protocols). Women were considered poor-responders if thay had ≤3 oocytes; normal-responders 4–9 oocytes and high-responders ≥10 oocytes. Serum samples for the AMH assays were obtained on the first and last days of stimulation. A P value ≤0.05 was considered statistically significant.

Result

FSH levels increased significantly when AMH levels decreased. The total dose of r-FSH administered to induce ovulation was not correlated to AMH. The number of follicles on the hCG, serum estradiol levels on the hCG-day, and the number of retrieved oocytes were significantly correlated to AMH. The number of fertilized oocytes was significantly correlated to the AMH levels. No significant correlation was found between obtained embryos or transferred embryos and AMH. Basal serum AMH levels were significantly higher than those measured on the hCG-day, which appeared significantly reduced. There was a significant correlation between AMH in normal responders and AMH in both high and poor responders.

Conclusions

Our data confirm the clinical usefulness of AMH in ART-cycles to customize treatment protocols and suggest the necessity of verifying an eventual permanent decrease in AMH levels after IVF.     

Increased NO bioavailability in aging male rats by genistein and exercise training: using 4, 5-diaminofluorescein diacetate

Background

Some studies have suggested that the suppression of endogenous LH secretion does not seem to affect the majority of patients who are undergoing assisted reproduction and stimulation with recombinant FSH (r-FSH). Other studies have indicated that a group of normogonadotrophic women down-regulated and stimulated with pure FSH preparations may experience low LH concentrations that compromise the IVF parameters. The present study aimed to compare the efficacy of recombinant LH (r-LH) supplementation for controlled ovarian stimulation in r-FSH and GnRH-agonist (GnRH-a) protocol in ICSI cycles.

Methods

A total of 244 patients without ovulatory dysfunction, aged <40 years and at the first ICSI cycle were divided into two groups matched by age according to an ovarian stimulation scheme: Group I (n = 122): Down-regulation with GnRH-a + r-FSH and Group II (n = 122): Down-regulation with GnRH-a + r-FSH and r-LH (beginning simultaneously).

Result(s)

The number of oocytes collected, the number of oocytes in metaphase II and fertilization rate were significantly lower in the Group I than in Group II (P = 0.036, P = 0.0014 and P = 0.017, respectively). In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were statistically lower (P = 0.0092 and P = 0.0008, respectively) in Group I than in Group II. Finally the cumulative implantation rate (fresh+thaw ed embryos) was significantly lower (P = 0.04) in Group I than in Group II. The other clinical and laboratory results analyzed did not show difference between groups.

Conclusion

These data support r-LH supplementation in ovarian stimulation protocols with r-FSH and GnRH-a for assisted reproduction treatment.     

Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort

Background

Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent.

Objective

To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants.

Methods

Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels'' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL.

Results and Conclusions

A total of 724 infants were included in the study, and among them, 631 (87%) were evaluated at two years old. The infants of the first tertile were younger and smaller than the infants of the other two tertiles, in accordance with Maisels'' recommendations for very small infants. No difference in the risk of impaired functional outcome among the three groups was observed. However, among infants weighing less than 1001 g, those in the third tertile had a poorer neurodevelopmental prognosis as compared to those in the second tertile (adjusted odds ratio = 6.8, 95% CI: 1.2–36.7, p = 0.03). Considering the results obtained, we propose 196 µmol/L (11.5 mg/dL) when birthweight varies between 1001 and 1500 g, and 170 µmol/L (9.9 mg/dL) when birthweight is less than 1001 g, as recommended max-SBLs (defined as maximal levels of 95^th percentile curves of SBLs in infants with an optimal outcome). When Maisels'' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001–1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels'' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g.     

A cytogenetic study of couples with recurrent spontaneous abortions and infertile patients with recurrent IVF/ICSI failure

PURPOSE:

This study was conducted to determine the frequency and contribution of chromosomal abnormalities in miscarriages and in couples with recurrent in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) failure.

MATERIALS and METHODS:

A total of 221 individuals; 79 with three or more recurrent spontaneous abortions and 142 with at least three IVF/ICSI failures. Chromosomal analysis from peripheral blood lymphocytes was performed according to standard cytogenetic methods using G-banding technique.

RESULTS:

Abnormal karyotype was found in 21 (9.50%) individuals. Of these 21 subjects, 4 (19.04%) exhibited sex chromosomal abnormalities and 17 (80.96%) had autosomal abnormalities. Male partners had significantly higher chromosomal abnormalities (5.88%) than of females (3.61%). These abnormalities were also higher in patients with recurrent spontaneous abortions than with IVF/ICSI failure (P < 0.05).

CONCLUSIONS:

These data may be indicative that chromosomal abnormalities are involved more in spontaneous abortions than in recurrent IVF/ICSI failure. Cytogenetic analysis could be valuable for these couples when clinical data fail to clarify the cause.     

Age paternel: apport des données épidémiologiques et d'AMP

Introduction

Maternal age over 35 years is a well known risk factor in reproduction. This effect of maternal age had been demonstrated on the risk of infertility and the risk of miscarriage on the basis of epidemiological data and ART data, especially AID sources. In contrast, the effect of paternal age has been rarely analysed. The objective of this study was to review the literature analysing the effect of paternal age on the risk of infertility and the risk of miscarriage.

Material and method

Sixteen publications analysing paternal age were selected by a MEDLINE search. Thirteen publications concerned epidemiological data, based on surveys in the general population, surveys in pregnant women, case-control studies, and birth and death certificates. Three publications concerned ART data, based on IVF with ovum donation. In IVF with ovum donation, there is no correlation between paternal age and age of the female gamete donor.

Results

Seven epidemiological studies analysed the effect of paternal age on the risk of infertility. After controlling for maternal age, five studies showed a paternal age effect, and one showed a very weak paternal age effect. The last study did not show any paternal age effect, but only considered men under the age of 33 years. Three studies analysed the effect of paternal age on pregnancy rates in IVF with ovum donation. Only one study showed a paternal age effect. The four studies analysing the effect of paternal age on the risk of miscarriage showed a paternal age effect and two of the three studies based on birth and death certificates showed a paternal age effect on late foetal death (>20 weeks of gestation).

Conclusion

There are concordant data in the literature showing an effect of paternal age on the risk of infertility and the risk of miscarriage. Paternal age over 40 years could therefore be a risk factor in reproduction in the same way as maternal age over 35 years. Moreover, the risk of infertility and the risk of miscarriage could be much higher when both partners are over the age of 35–40 years.     

The impact in older women of ovarian FMR1 genotypes and sub-genotypes on ovarian reserve

We recently associated ovarian FMR1genotypes and sub-genotypes with distinct ovarian aging patterns. How they impact older females is, however, unknown. We, therefore, investigated 217 consecutive first in vitro fertilization (IVF) cycles in women >40 assessing oocyte yields, stratified for better (anti-Müllerian hormone, AMH >1.05 ng/mL) or poorer (AMH ≤ 1.05 ng/mL) functional reserve (FOR)). Mean age was 42.4 ± 2.0 years, mean AMH 0.76 ± 0.92 ng/mL and mean oocyte yield 5.3 ± 5.4. Overall, and in women with better FOR, FMR1 did not affect oocyte yields. With poorer FOR (AMH ≤ 1.05 ng/mL) women with het-norm/high, however, demonstrated higher oocyte yields (5.0 ± 3.8) than those with het-norm/low sub-genotype 3.1 ± 2.5; P = 0.03), confirmed after log conversion. Known associated with low FOR at young age, het-norm/high, thus, appears to preserve FOR into older age, and both het sub-genotypes appear to expand female reproductive lifespan into opposite directions.     

Serum Gamma - Glutamyltransferase Is Associated with Albuminuria: A Population-Based Study

Background

Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population.

Materials and Methods

We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion.

Results

The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend <0.05). In logistic regression analysis, compared with subjects in the lowest quartile of serum GGT level, the adjusted odds ratios (ORs) in the highest quartile was 1.22 [95% confidence interval (CI), 1.04–1.43] for low-grade albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05).

Conclusion

Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese.     

Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

Background

The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD) is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA) have comparable prognostic value.

Methods

We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA) study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1). We classified patients' health status using tertiles of the Saint George Respiratory Questionnaire (SGRQ) and a MDA including functional (the 6' walking test, WT), cognitive (Mini-Mental State Examination, MMSE) and affective status (Geriatric Depression Scale, GDS). The agreement of the classification methods was calculated using the kappa statistic, and survival associated with group membership was evaluated using survival analysis.

Results

Pulmonary function, expressed by the FEV1, worsened with increasing SGRQ or MDA scores. Cognitive function was not associated with the SGRQ, while physical performance and mood status were impaired only in the highest tertile of SGRQ. A poor agreement was found between the two classification systems tested (k = 0.194). Compared to people in the first tertile of SGRQ score, those in the second tertile had a sex-adjusted HR of 1.22 (0.75 – 1.98) and those in the third tertile of 2.90 (1.92 – 4.40). The corresponding figures of the MDA were 1.49 (95% CI 1.02 – 2.18) and 2.01 (95% CI: 1.31 – 3.08). After adjustment for severity of obstruction, only a SGRQ in the upper tertile was associated with mortality (HR: 1.86; 95% CI: 1.14 – 3.02).

Conclusion

In elderly outpatients with mild-moderate COPD, a disease-specific health status index seems to be a better predictor of death compared to a MDA.     

Cardiovascular autonomic function tests in an African population

Background

Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSH_basal (TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences.

Methods

2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 – 12 months, and 1 – 5, 6 – 10, 11 – 14, and 15 – 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia^® Centaur? automated immunoassay system.

Results

The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age.

Conclusion

Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.     

Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles

Background  

This study was designed to assess the capability of ovarian reserve markers, including baseline FSH levels, baseline anti-Müllerian hormone (AMH) levels, and antral follicle count (AFC), as predictors of live births during IVF cycles, especially for infertile couples with advanced maternal age and/or male factors.