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Objective: To study childbirth and the risk of miscarriage and infertility among women who have received a diagnosis of type 2 diabetes before the start of their reproductive journey.Design: Register-based cohort study using the Skane Healthcare Register.Setting: All healthcare visits for the whole population of the southernmost region in Sweden over the past 20 years.Patient(s): All women who were aged 18-45 years between January 1, 1998 and December 31, 2019 and who received a clinical diagnosis of type 2 diabetes before their first childbirth, miscarriage, or infertility diagnosis (n = 230) were compared with a healthcareseeking population of women without any type of diabetes, matched for calendar year and age (n = 179,434).Intervention(s): None.Main Outcome Measure(s): Childbirth, miscarriage, and infertility diagnosis.Result(s): The birthrate was lower among women with type 2 diabetes (62.6% vs. 83.8%), and they were less likely to give birth (crude risk ratio [RR] = 0.73, 95% confidence interval [CI]: 0.66-0.81). They had a higher risk of experiencing a miscarriage (RR = 1.88, 95% CI: 1.50-2.36). The risk of infertility was increased (RR = 3.44, 95% CI: 2.88-4.10) as was the risk of having infertility and not giving birth (RR = 4.47, 95% CI: 3.44-5.82). All results remained the same after adjustment for polycystic ovary syndrome and obesity.Conclusion(s): Women with type 2 diabetes with onset before their reproductive journey were more often childless compared with women without diabetes and had a higher risk of experiencing both miscarriage and infertility. This patient group may be in need of targeted information regarding potential fertility issues as part of their clinical treatment. ((c) 2021 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.

Objective: To study childbirth and the risk of miscarriage and infertility among women who have received a diagnosis of type 2 diabetes before the start of their reproductive journey.Design: Register-based cohort study using the Skane Healthcare Register.Setting: All healthcare visits for the whole population of the southernmost region in Sweden over the past 20 years.Patient(s): All women who were aged 18-45 years between January 1, 1998 and December 31, 2019 and who received a clinical diagnosis of type 2 diabetes before their first childbirth, miscarriage, or infertility diagnosis (n = 230) were compared with a healthcareseeking population of women without any type of diabetes, matched for calendar year and age (n = 179,434).Intervention(s): None.Main Outcome Measure(s): Childbirth, miscarriage, and infertility diagnosis.Result(s): The birthrate was lower among women with type 2 diabetes (62.6% vs. 83.8%), and they were less likely to give birth (crude risk ratio [RR] = 0.73, 95% confidence interval [CI]: 0.66-0.81). They had a higher risk of experiencing a miscarriage (RR = 1.88, 95% CI: 1.50-2.36). The risk of infertility was increased (RR = 3.44, 95% CI: 2.88-4.10) as was the risk of having infertility and not giving birth (RR = 4.47, 95% CI: 3.44-5.82). All results remained the same after adjustment for polycystic ovary syndrome and obesity.Conclusion(s): Women with type 2 diabetes with onset before their reproductive journey were more often childless compared with women without diabetes and had a higher risk of experiencing both miscarriage and infertility. This patient group may be in need of targeted information regarding potential fertility issues as part of their clinical treatment. ((c) 2021 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.

Aims: a) To analyze the relationship of known and emerging biomarkers/indicators for early risk identification of cardiometabolic health risk; b) to identify early risk markers to be used in both clinical and nonclinical settings; and c) to propose a definition of early risk identification in terms of pre-metabolic syndrome (PreMetSyn). Data synthesis: Pubmed/Medline, Web of Science, Embase, and Cochrane were searched for Systematic Reviews and Meta-analysis. Selected studies were evaluated, and relevant data were extracted and synthesized. Conclusions: Serum uric acid is a good predictive biomarker of metabolic syndrome (MetSyn) and has been associated with non-alcoholic liver fat disease (NAFLD) and type 2 diabetes. NAFLD emerges as an early risk indicator of PreMetSyn by itself. Muscle strength should also be included as an early risk marker of cardiometabolic health. High serum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/proinflammatory status usually linked to MetSyn showed limited evidence as robust biomarkers for PreMetSyn. Authors suggest defining PreMetSyn related to cardiometabolic risk. It is also necessary to determine how close people are to the cut-off point of MetSyn components, including emerging indicators proposed by our review. Some biomarkers could be used as indicators of PreMetSyn, before any of the MetSyn components appear, allowing early health interventions to prevent its development. Defining a PreMetSyn status might consider both emerging indicators and those variables already included in the definition of MetSyn. New indicators should be considered to create a new risk score specifically meant for PreMetSyn. (c) 2021 The Authors. Published by Elsevier B.V. on beh

Our understanding of the intracrine (or local) regulation of estrogen and other steroid synthesis and degradation expanded in the last decades, also thanks to recent technological advances in chromatography mass-spectrometry. Estrogen responsive tissues and organs are not passive receivers of the pool of steroids present in the blood but they can actively modify the intra-tissue steroid concentrations. This allows fine-tuning the exposure of responsive tissues and organs to estrogens and other steroids in order to best respond to the physiological needs of each specific organ. Deviations in such intracrine control can lead to unbalanced steroid hormone exposure and disturbances. Through a systematic bibliographic search on the expression of the intracrine enzymes in various tissues, this review gives an up-to-date view of the intracrine estrogen metabolisms, and to a lesser extent that of progestogens and androgens, in the lower female genital tract, including the physiological control of endometrial functions, receptivity, menopausal status and related pathological conditions. An overview of the intracrine regulation in extra gynecological tissues such as the lungs, gastrointestinal tract, brain, colon and bone is given. Current therapeutic approaches aimed at interfering with these metabolisms and future perspectives are discussed.

Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs. Methods: The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese. Results: OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance. Conclusions: We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

Objective Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs) have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). Materials and methods The bmMSCs were isolated from bone marrow aspirates through culturing, whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their surface marker, proliferation profiles and migration properties towards serum and inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets was analysed in each cell type at basal level along with lipopolysaccharide (LPS)-induced state. Results Both stem cell types, bmMSCs and eMSCs, presented with similar stem cell surface marker profiles as well as possessed high proliferation and migration potential compared to eSFs. In multiplex assays, the secretion of 16 cytokine targets was detected and LPS stimulation expanded the cytokine secretion pattern by triggering the secretion of several targets. The bmMSCs exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)A, stromal cell-derived factor-1 alpha (SDF)-1 alpha, interleukin-1 receptor antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte chemoattractant protein (MCP)1, macrophage inflammatory protein (MIP) 1 alpha and RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8 secretion was higher in both endometrial cell types compared to bmMSCs. Conclusion Our results highlight that similar to bmMSCs, the eMSCs possess high migration activity while the different

(1) Background: Medical interventions including assisted reproductive technologies have improved fertility outcomes for many sub-fertile couples. Increasing research interest has investigated the effect of low carbohydrate diets, with or without energy restriction. We aimed to systematically review the published literature to determine the extent to which low carbohydrate diets can affect fertility outcomes; (2) Methods: The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42016042669) and followed Preferred Reporting Items For Systematic Reviews and Meta-Analyses guidelines. Infertile women were the population of interest, the intervention was low carbohydrate diets (less than 45% total energy from carbohydrates), compared to usual diet (with or without co-treatments). Four databases were searched from date of commencement until April 2016; a supplementary Google scholar search was also undertaken. Title and abstract, then full text review, were undertaken independently and in duplicate. Reference lists of included studies and relevant systematic reviews were checked to ensure that all relevant studies were identified for inclusion. Quality assessment was undertaken independently by both authors using the Quality Criteria Checklist for Primary Research. Outcome measures were improved fertility outcomes defined by an improvement in reproductive hormones, ovulation rates and/or pregnancy rates; (3) Results: Seven studies fulfilled the inclusion criteria and were included in the evidence synthesis. Interventions were diverse and included a combination of low carbohydrate diets with energy deficit or other co-treatments. Study quality was rated as positive for six studies, suggesting a low risk of bias, with one study rated as neutral. Of the six studies which reported changes in reproductive hormones, five reported significant improvements post intervention; (4) Conclusion: The findings of these stud

Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs. Methods: The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese. Results: OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance. Conclusions: We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

Background: The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs. Methods: The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese. Results: OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance. Conclusions: We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

Excessive daytime sleepiness (EDS) is often associated with increased adiposity, particularly when assessed in the context of samples of sleep-disordered patients; however, it is unclear if this relationship is sustained among non-clinical, population-based cohorts. This study aimed to investigate the relationship between EDS and a number of body composition markers among a population-based sample of men and women.

Context: Previous studies have suggested that antimullerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective: The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design: The study was a prospective cohort study between April 2008 and June 2011. Setting: The study was done at a university-affiliated private infertility center. Patients: The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s): AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures: Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), P-trend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions: AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

To assess whether the common rs8111699 (C528G) variant in STK11 is related to metabolic risk markers in pregnant women and to gestational diabetes mellitus (GDM).Cross-sectional study.Hospital.A total of 561 pregnant women: 318 without and 243 with GDM (National Diabetes Data Group criteria).None.rs8111699 variant in STK11 (Taqman technology). Fasting glucose, insulin (homeostatic model assessment of insulin resistance and ?-cell function [HOMA-IR and -?]) and C-peptide assessed at 24-28 weeks' gestation.In non-GDM women, the G allele in rs8111699 was associated with lower HOMA-IR (CC: 1.3 ± 0.1 mIU/L; GG: 0.9 ± 0.1 mIU/L) and HOMA-? (CC: 165 ± 20 mIU/L; GG: 118 ± 10 mIU/L). In GDM women, the G allele was related to lower body mass index (BMI; CC: 27.9 ± 1.0 kg/m(2); GG: 24.5 ± 0.6 kg/m(2)) and C-peptide (CC: 2.3 ± 0.1 ng/mL; GG: 1.6 ± 0.1 ng/mL). The GG genotype was less frequently observed in GDM women (18% vs. 26%), particularly in heavier GDM women (BMI > median: 14% vs. 28%).In pregnant women, the G allele for the rs8111699 variant in STK11 is associated with a more favorable metabolic phenotype and may protect against the development of GDM, particularly in heavier women.Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression.We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function.Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group.In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.

Background: High throughput microarray analyses result in many differentially expressed genes that are potentially responsible for the biological process of interest. In order to identify biological similarities between genes, publications from MEDLINE were identified in which pairs of gene names and combinations of gene name with specific keywords were co-mentioned. Results: MEDLINE search strings for 15,621 known genes and 3,731 keywords were generated and validated. PubMed IDs were retrieved from MEDLINE and relative probability of cooccurrences of all gene-gene and gene-keyword pairs determined. To assess gene clustering according to literature co-publication, 150 genes consisting of 8 sets with known connections (same pathway, same protein complex, or same cellular localization, etc.) were run through the program. Receiver operator characteristics (ROC) analyses showed that most gene sets were clustered much better than expected by random chance. To test grouping of genes from real microarray data, 221 differentially expressed genes from a microarray experiment were analyzed with CoPub Mapper, which resulted in several relevant clusters of genes with biological process and disease keywords. In addition, all genes versus keywords were hierarchical clustered to reveal a complete grouping of published genes based on co-occurrence. Conclusion: The CoPub Mapper program allows for quick and versatile querying of co-published genes and keywords and can be successfully used to cluster predefined groups of genes and microarray data

OBJECTIVE To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in - obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and I I pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S-i measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS There was a significant negative correlation between HOMA-IR and S-i (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S-i (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S-i (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S-i (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S-i assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β% FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for a