https://e-lactancia.org/media/papers/ComposicionBF-PedCliMA2013.pdf

Human milk composition: nutrients and bioactive factors

ContextDespite improved understanding of atherothrombosis, cardiovascular prediction algorithms for women have largely relied on traditional risk factorsObjectiveTo develop and validate cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factorsDesign, Setting, and ParticipantsThirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 102 years (through March 2004) for incident cardiovascular events (an adjudicated composite of myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death) We used data among a random two thirds (derivation cohort, n = 16 400) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women (validation cohort, n = 8158)Main Outcome MeasureMinimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models In the validation cohort, we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk scoreResultsIn the derivation cohort, a best-fitting model (model A) and a clinically simplified model (model B, the Reynolds Risk Score) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III In the validation cohort, all measures of fit, discrimination, and calibration were improved when either model A or B was used For example, among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5% to less than 10% (n = 603) or 10% to less than 20% (n = 156), model A reclassified 379 (50%) into higher- or lower-risk categories that in each instance more accurately matched actual event rates Similar effects were achieved for clinically simplified model B limited to age, systolic blood pressure, hemoglobin A1c if diabetic, smoking, total and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and parental history of myocardial infarction before age 60 years Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III scoreConclusionWe developed, validated, and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40% to 50% of women at intermediate risk into higher- or lower-risk categories

https://jamanetwork.com/journals/jama/articlepdf/205528/joc70004_611_619.pdf

Development and Validation of Improved Algorithms for the Assessment of Global Cardiovascular Risk in Women: The Reynolds Risk Score

Endometriosis

Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.

In a healthy body, ROS (reactive oxygen species) and antioxidants remain in balance When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS) occurs OS influences the entire reproductive lifespan of a woman and even thereafter (ie menopause) OS results from an imbalance between prooxidants (free radical species) and the body's scavenging ability (antioxidants) ROS are a double-edged sword – they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy It has been suggested that OS modulates the age-related decline in fertility It plays a role during pregnancy and normal parturition and in initiation of preterm labor Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants There is growing literature on the effects of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions Numerous studies have shown that OS plays a role in the pathoysiology of infertility and assisted fertility There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal embryopathies, preterm labour and preeclampsia and gestational diabetes The review also addresses the growing literature on the role of nitric oxide species in female reproduction The involvement of nitric oxide species in regulation of endometrial and ovarian function, etiopathogenesis of endometriosis, and maintenance of uterine quiescence, initiation of labour and ripening of cervix at parturition is discussed Complex interplay between cytokines and oxidative stress in the etiology of female reproductive disorders is discussed Oxidant status of the cell modulates angiogenesis, which is critical for follicular growth, corpus luteum formation endometrial differentiation and embryonic growth is also highlighted in the review Strategies to overcome oxidative stress and enhance fertility, both natural and assisted are delineated Early interventions being investigated for prevention of preeclampsia are enumerated Trials investigating combination intervention strategy of vitamin E and vitamin C supplementation in preventing preeclampsia are highlighted Antioxidants are powerful and there are few trials investigating antioxidant supplementation in female reproduction However, before clinicians recommend antioxidants, randomized controlled trials with sufficient power are necessary to prove the efficacy of antioxidant supplementation in disorders of female reproduction Serial measurement of oxidative stress biomarkers in longitudinal studies may help delineate the etiology of some of the diosorders in female reproduction such as preeclampsia

/pdf/role-of-oxidative-stress-in-female-reproduction-2fcw0uqz6p.pdf

Role of oxidative stress in female reproduction

Only one third of the in vitro fertilization treatments result in successful delivery following morphological viability assessment worldwide. A paper by Montsko et al. (2015) describes the identification of the alpha-1 chain of human haptoglobin as a potential marker of embryo viability. Using mass spectrometry, the concentration of the haptoglobin alpha-1 chain was determined in spent culture media samples of in vitro fertilized embryos and correlation was found with the outcome of the respective transfer. In the present study we investigated, whether the concentration of haptoglobin alpha-1 chain shows any correlation with morphological scores to clarify whether levels of the alpha-1 chain provide additional information on embryo viability unnoticed by the morphological assessment. In the study, pregnancy and live birth rates were examined in 143 transferred samples of 86 patients, retrospectively. Two sample groups were created. The control group contained embryos classified as ‘good’ or ‘fair’...

https://www.tandfonline.com/doi/pdf/10.1080/19396368.2018.1518499

Alpha-1 chain of human haptoglobin as viability marker of in vitro fertilized human embryos: information beyond morphology

JAR choriocarcinoma cells have retained several characteristics of normal trophoblasts and have been used as an in vitro trophoblast model. The superfusion system is suitable for the study of hormone synthesis and/or secretion. JAR cells were cultured and transferred to the superfusion system in order to evaluate the spontaneous hCG secretion and the effect of GnRH. The spontaneous hCG release showed a periodic pattern with a 48 min phase interval. In our system single cells and cell-clusters were superfused and there is a possibility that cell to cell connections might have an influence on the regulation of hormone synthesis and/or secretion. GnRH in 4×10−7 M and 4×10−6 M concentrations or 100 mM KCl caused an immediate hCG release from the JAR cells Repeated administration of GnRH resulted in a delayed hCG release which is probably related to the relatively small amount of hCG available from the storage granules or to the phase of spontaneous secretion.

Spontaneous and gonadotropin-releasing hormone induced human chorionic gonadotropin release from superfused JAR choriocarcinoma cells

Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF centre have not been started in the absence of a recommendation. Our objective in this study was to provide a comprehensive workflow for a clinically applicable strategy for NIPGT-A based on next-generation sequencing (NGS) technology with the corresponding bioinformatic pipeline. In a retrospective study, we performed NGS on spent blastocyst culture media of Day 3 embryos fertilised with intracytoplasmic sperm injection (ICSI) with quality score on morphology assessment using the blank culture media as background control. Chromosomal abnormalities were identified by an optimised bioinformatics pipeline applying copy number variation (CNV) detecting algorithm. In this study, we demonstrate a comprehensive workflow covering both wet- and dry-lab procedures supporting a clinically applicable strategy for NIPGT-A that can be carried out within 48 h, which is critical for the same-cycle blastocyst transfer. The described integrated approach of non-invasive evaluation of embryonic DNA content of the culture media can potentially supplement existing pre-implantation genetic screening methods.

https://www.mdpi.com/1422-0067/22/5/2443/pdf

NGS-Based Application for Routine Non-Invasive Pre-Implantation Genetic Assessment in IVF.

Successful treatment of FIGO stage IV gestational choriocarcinoma occurring 2 months after delivery.

This cross-sectional clinical study was designed to explore the impact of tryptophan-kynurenine and tryptophan-serotonin (5 HT) pathways on reproductive performance during in vitro fertilization (IVF). Paired serum and follicular fluid (FF) samples were obtained from 64 consecutive IVF patients. The analysis was done by using LC-MS/MS. Ovarian hyperstimulation resulted in decreased serum tryptophan (p<0.004), 5-HT (p<0.049) and kynurenine (p<0.001). FF levels of tryptophan (R=0.245, p<0.051), kynurenine (R=0.556, p<0.001) and 5-HT (R=0.523, p<0.001) were positively related to their respective serum levels. Clinical pregnancy was associated with higher serum 5-HT (p<0.045) and FF 5-HT (p<0.020) and lower kynurenine to 5-HT ratio (p<0.024). Chemical pregnancy was also positively related to FF 5-HT (R=0.362, p<0.024). Moreover, there was a direct relationship of the number of mature oocytes to the FF 5-HT (R=0.363, p<0.020) but it was inversely related to FF tryptophan to 5-HT and FF kynurenine to 5-HT ratios (R=-0.389, p<0.016 and R=-0.337, p<0.036, respectively). Multivariate logistic regression revealed that the number of mature oocytes was significantly influenced by FF 5-HT (?=0.473, p<0.001). In IVF patients ovarian hyperstimulation results in a reduction of the availability of tryptophan to catabolic pathways to kynurenine and 5-HT. Outcome measures improved significantly when 5-HT predominated over kynurenine.

/pdf/tryptophan-catabolism-to-serotonin-and-kynurenine-in-women-ta5csek31b.pdf

József Bódis

Papers

Alpha-1 chain of human haptoglobin as viability marker of in vitro fertilized human embryos: information beyond morphology

Spontaneous and gonadotropin-releasing hormone induced human chorionic gonadotropin release from superfused JAR choriocarcinoma cells

NGS-Based Application for Routine Non-Invasive Pre-Implantation Genetic Assessment in IVF.

Successful treatment of FIGO stage IV gestational choriocarcinoma occurring 2 months after delivery.

Tryptophan catabolism to serotonin and kynurenine in women undergoing in-vitro fertilization.