Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

PURPOSE: To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. METHODS: A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35 years, 198 embryos) and AMA (≥ 35 years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. RESULTS: Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). CONCLUSION: Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

Perinatal outcomes in 6640 singleton pregnancies after donor oocyte IVF across three continents over 7 years.

PURPOSE: Are trends in singleton donor oocyte IVF perinatal outcomes consistent over time among four international ethnically diverse infertility centers? METHODS: This retrospective cohort consisted of an infertility network of four international IVF centers across three continents. Singleton live births resulting from fresh and frozen donor oocyte embryo transfers from January 1, 2012 to December 31, 2018 were included. The main outcome measures were birth weight (BW), preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA) and gestational age (GA) at delivery. RESULTS: The entire cohort (n = 6640) consisted of 4753 fresh and 1887 frozen donor oocyte embryo transfers. Maternal age, parity, body mass index, neonatal sex and GA at delivery were similar for fresh and frozen donor oocyte embryo transfers in the entire cohort and within each infertility center. All four centers had a trend of decreased BW and rates of PTB before 32 weeks annually, although significance was not reached. Three of the four centers had annual increased trends of PTB before 37 weeks and LGA newborns, although significance was not reached. BWs for the entire cohort for fresh and frozen donor embryo transfers were 3166 g ± 601 g and 3137 g ± 626 g, respectively. CONCLUSION: Similar trends in perinatal outcomes were present across four international infertility centers over 7 years. The overall perinatal trends in donor oocyte IVF may be applicable to centers worldwide, but further studies in more geographic regions are needed.

Perinatal outcomes in 13,626 singleton pregnancies after autologous IVF across three continents over 7 years.

PURPOSE: Are trends in singleton autologous IVF perinatal outcomes consistent over time among five international infertility centers? METHODS: This was a retrospective cohort study from January 1, 2012, to December 31, 2018. This study was performed through a large infertility network at five international infertility centers in which patients who had a singleton live birth resulting from fresh and frozen autologous IVF cycles were included. The primary outcome was live birth weight (BW) with secondary outcomes of preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA), and gestational age at delivery. RESULTS: The entire cohort (n = 13,626) consisted of 6941 fresh and 6685 frozen autologous IVF cycles leading to singleton deliveries. Maternal age, parity, body mass index, neonatal sex, and GA at delivery were similar for fresh and frozen IVF cycles in the entire cohort and within each infertility center. Four centers had a trend of decreased BW and three centers had decreased rates of PTB before 32 and 28 weeks and LGA newborns annually, although significance was not reached. Three IVF centers had annual increased trends of PTB before 37 weeks and four centers had increased rates of SGA newborns, although significance was not reached. CONCLUSION: Similar trends in perinatal outcomes were present across five international infertility centers over 7 years. Additional studies are crucial to further assess and optimize perinatal outcomes at an international level.

Correlation between morphokinetic parameters and standard morphological assessment: what can we predict from early embryo development? A time-lapse-based experiment with 2085 blastocysts.

OBJECTIVES: To evaluate the association between morphology grading and morphokinetic parameters in blastocyst stage embryos cultured in a time-lapse system. METHODS: This retrospective cohort study included patients offered fertility treatment with autologous oocytes in our clinic between October 2017 and May 2019 using a time-lapse system. The embryos were morphologically graded according to the criteria developed by Gardner and Schoolcraft and their morphokinetic parameters were recorded. RESULTS: Our results indicated that the time of pronuclei fading (tPNf), time to cleavage into two (t2), four (t4), and eight (t8) cells, and time to start of blastulation (tB) were significantly different according to the morphological quality of the blastocysts formed. In the early development stage, tPNf, t2 and t4 differed between good (AA, AB, BA, BB) and poor (CC) quality potential blastocysts. The 8-cell stage time separated embryos graded as AA blastocysts in terms of morphology from embryos graded as BB. Earlier tB correlated with higher quality embryos (AA, AB, BA). CONCLUSION: Our results showed that the first kinetic parameters (tPNf, t2, and t4) distinguished top-graded from low-graded blastocysts. Between top-graded blastocysts, t8 separated BB blastocysts from AA blastocysts. And finally, tB also told apart BB blastocysts from AA, AB, and BA blastocysts. These time-related parameters may be applied even in centers without time-lapse systems.

Attachment style, loneliness and depression in older age women.

Older adults tend to have more avoidant attachment styles, which may make them more vulnerable to becoming isolated and lonely and increase the risk for developing mental health problems. This study used intensive interviews and logistic regression to explore how insecure attachment styles were associated with poor social support, isolation, loneliness and depression. Avoidantly, attached adults were at an increased risk for social isolation. Specifically, older adults with an Angry-Dismissive style were more likely to be lonely and experience mental health problems. Attachment style should be taken into consideration when promoting healthy aging.

In Vivo Viscoelastic Response (VisR) Ultrasound for Characterizing Mechanical Anisotropy in Lower-Limb Skeletal Muscles of Boys with and without Duchenne Muscular Dystrophy.

Our group has previously found that in silico, mechanical anisotropy may be interrogated by exciting transversely isotropic materials with geometrically asymmetric acoustic radiation force excitations and then monitoring the associated induced displacements in the region of excitation. We now translate acoustic radiation force-based anisotropy assessment to human muscle in vivo and investigate its clinical relevance to monitoring muscle degeneration in Duchenne muscular dystrophy (DMD). Clinical anisotropy assessments were performed using Viscoelastic Response ultrasound, with a degree of anisotropy reflected by the ratios of Viscoelastic Response relative elasticity (RE) or relative viscosity (RV) measured with the asymmetric radiation force oriented parallel versus perpendicular to muscle fiber alignment. In vivo results from rectus femoris and gastrocnemius muscles of boys aged ∼7.9-10.4 y indicate that RE and RV anisotropy ratios in rectus femoris muscles of boys with DMD were significantly higher than those of healthy control boys (RE: DMD = 1.51 ± 0.87, control = 0.99 ± 0.69, p = 0.04, Wilcoxon rank sum test; RV: DMD = 1.04 ± 0.71, control = 0.74 ± 0.22, p = 0.02). In the gastrocnemius muscle, only the RV anisotropy ratio was significantly higher in dystrophic than control patients (DMD = 1.23 ± 0.35, control = 0.88 ± 0.31, p = 0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope = -0.03/lbf, r = -0.43, p = 0.07, Pearson correlation) with quantitative muscle testing functional output measures but was not correlated with quantitative muscle testing in the dystrophic gastrocnemius. These results suggest that Viscoelastic Response RE and RV measures reflect differences in mechanical anisotropy associated with functional impairment with dystrophic degeneration that are relevant to monitoring DMD clinically.

Homeostatic unbalance via HSPA5 gene expression in HepG2C3A cells exposed to alpha-tomatine / Desequilíbrio homeostático através da expressão do gene HSPA5 em células HepG2C3A exposto a alpha-tomatine

The α-tomatine is a glycoalkaloid found in immature tomatoes (Lycopersicon esculetum). Currently, α-tomatine has shown anticancer effects due to its anti-proliferative property. Stressors are one of the factors contributing to the antiproliferative activity of α-tomatine that can modify cellular homeostasis.Among the cell stressors are the endoplasmic reticulum stress response elements, which can be alteredleading to cell death. In the course of this study, we verified the expression of genes involved in the stress response of the endoplasmic reticulum in HepG2/C3A cells. The α-tomatine reduced the viability of HepG2/C3A cells in a dose-dependent manner. Thus, we selected 2µg/mL of α-tomatine (62% incell viability) to evaluate the gene expressions. After 24 hours of exposure to α-tomatine, the level of HSPA5 transcripts was reduced. The HSPA5 chaperone reduced marker is an indicative of homeostasisunbalance with the consequent lack of cellular resistance and, probably, cell death. Our results indicate the involvement of oxidative stress mechanisms in the death of HepG2/C3A cells exposed to α-tomatine.

A α-tomatina é um glicoalcaloide encontrado no tomate imaturo (Lycopersicon esculetum). Atualmente,a α-tomatina tem mostrado efeito anticancerígeno devido sua propriedade antiproliferativa. O estresse celular é um dos fatores que contribui para a atividade antiproliferative da α-tomatina que pode modificara homeostase celular. Entre os estressores celulares esta os elementos de resposta ao estresse do retículo endoplasmático, que podem ser alterados, levando à morte celular. No decorrer deste estudo, verificamos que a expressão de genes envolvidos na resposta ao estresse do retículo endoplasmático em célulasHepG2/C3A. A α-tomatina reduziu a viabilidade das células HepG2/C3A de forma dose-dependente.Assim, selecionamos a concentração de 2μg/mL de α-tomatina (viabilidade celular de 62%) para avaliara expressão gênica. Após 24 horas de exposição a α-tomatina, o nível de transcrição de HSPA5 foireduzido. A redução de HSPA5 é um indicativo de desequilíbrio da homeostase, com a consequente falta de resistência celular e, provavelmente, a morte celular. Nossos resultados indicam o envolvimento de mecanismos de estresse oxidativo na morte de células HepG2/C3A exposto a α-tomatina e mostram a eficácia do sistema como um futuro candidato para os estudos de terapia de câncer.

Problem parental care and teenage deliberate self-harm in young community adults.

Deliberate self-harm (DSH) in young people is a clinical and social problem related to early maltreatment but with little specificity in type of care or abuse determined. A community sample of 160 high-risk young people (aged 16-30) were the offspring of mothers' previously interviewed as vulnerable to major depression. The youth were interviewed to determine DSH (both suicidal and nonsuicidal), childhood maltreatment (using the Childhood Experience of Care and Abuse interview) and major depression (using SCID for DSMIV) before age 17. Around one fifth reported DSH; equal proportions were suicidal and nonsuicidal with a fourth of these with both. DSH was highly related to family context (single mother upbringing and family discord) and poor parental care (including antipathy, neglect, inadequate supervision, and role reversal). Highest odds ratios were for role reversal (OR = 17) and neglect (OR = 11). DSH was unrelated to any type of abuse. Logistic regression showed that role reversal, inadequate supervision, and teenage depression all modeled DSH. There was some specificity, with single mother upbringing, role reversal, and inadequate supervision predicting nonsuicidal DSH, and neglect and role reversal alone predicting suicidal DSH. Role reversal remained a key predictor for both types of DSH when controls were applied. Poor childhood care, which has implications for problematic emotion regulation and empoverished social development, needs to be understood to improve interventions and treatment for DSH in young people.

Problem partners and parenting: exploring linkages with maternal insecure attachment style and adolescent offspring internalizing disorder.

An intergenerational study examined mothers' insecure attachment style using the Attachment Style Interview (ASI; Bifulco et al., 2002a) in relation to her history of partner relationships, her parenting competence, and depression or anxiety disorder in her offspring. The sample comprised 146 high-risk, mother-adolescent offspring pairs in London, who were recruited on the basis of the mothers' psychosocial vulnerability for depression. Retrospective, biographical, and clinical interviews were undertaken independently with mother and offspring. A path model was developed, which showed that mothers' insecure attachment style had no direct link to either recalled child neglect/abuse or currently assessed disorder in their adolescent and young adult offspring. The connections appeared to be indirect, through the quality of relationships in the family system: mothers' insecure attachment and their partners' problem behavior accounted for variance in mothers' incompetent parenting as rated by interviewers. These variables predicted her neglect/abuse of the child, which was the only variable directly associated with internalizing disorder in her offspring. Mother's lifetime depression did not add to the model. It is argued that an ecological approach (emphasizing social adversity and different role domains) and a lifespan approach (emphasizing a history of adverse relationships a different life stages) is important in understanding the mechanisms by which parental insecure attachment style influences transmission of risk to the next generation.

Adult attachment style as mediator between childhood neglect/abuse and adult depression and anxiety.

BACKGROUND: There has been little prospective investigation of the relationship between adult attachment style and clinical levels of anxiety and major depression. This paper seeks to address this, as well as examining the potentially mediating role of adult insecure attachment styles in the relationship between childhood adverse experience and adult disorder. METHODS: 154 high-risk community women studied in 1990-1995, were followed-up in 1995-1999 to test the role of insecure attachment style in predicting new episodes of anxiety and/or major depressive disorder. The Childhood Experience of Care and Abuse (CECA) and the Attachment Style Interview (ASI) were administered at first interview and the Structured Clinical Interview for DSM-IV (SCID) administered at first and follow-up interview. Major depression and clinical level anxiety disorders (GAD, Social Phobia or Panic and/or Agoraphobia) were assessed at first contact and for the intervening follow-up period. RESULTS: 55% (85/154) of the women had at least one case level disorder in the follow-up period. Only markedly or moderately (but not mildly) insecure attachment styles predicted both major depression and case anxiety in follow-up. Some specificity was determined with Fearful style significantly associated both with depression and Social Phobia, and Angry-Dismissive style only with GAD. Attachment style was unrelated to Panic Disorder and/or Agoraphobia. In addition, Fearful and Angry-Dismissive styles were shown to partially mediate the relationship between childhood adversity and depression or anxiety. CONCLUSION: In order to correctly interpret lifespan models of adult psychiatric disorder, it is necessary to test for mediating factors. Attachment theory provides a framework for explaining how dysfunctional interpersonal style arising from early childhood perpetuates vulnerability to affective disorders. This has implications for intervention and treatment to break cycles of risk.

Maternal expressed emotion predicts children's antisocial behavior problems: using monozygotic-twin differences to identify environmental effects on behavioral development.

If maternal expressed emotion is an environmental risk factor for children's antisocial behavior problems, it should account for behavioral differences between siblings growing up in the same family even after genetic influences on children's behavior problems are taken into account. This hypothesis was tested in the Environmental Risk Longitudinal Twin Study with a nationally representative 1994-1995 birth cohort of twins. The authors interviewed the mothers of 565 five-year-old monozygotic (MZ) twin pairs and established which twin in each family received more negative emotional expression and which twin received more warmth. Within MZ pairs, the twin receiving more maternal negativity and less warmth had more antisocial behavior problems. Qualitative interviews were used to generate hypotheses about why mothers treat their children differently. The results suggest that maternal emotional attitudes toward children may play a causal role in the development of antisocial behavior and illustrate how genetically informative research can inform tests of socialization hypotheses.

Exploring psychological abuse in childhood: I. Developing a new interview scale.

Definitions of psychological abuse are reviewed and a new definition proposed, operationalized as an extension of an existing measure of childhood, the Childhood Experience of Care and Abuse (CECA). This semistructured, investigator-based interview is designed for use with adults to collect retrospective accounts of childhood adverse experience. The CECA extension identifies nine subtypes of psychological abuse, with a single global severity rating. The definition is clearly differentiated from other adverse experiences with emotionally abusive elements such as parental antipathy (hostile parenting), neglect, and role reversal. Examples are given. A community-based series of 301 women were interviewed using the extended CECA to gather a range of experiences of childhood maltreatment on which to devise the new measure. Interrater reliability was satisfactory, and several features of psychological abuse were examined, including its prevalence, frequency, and the characteristics of the abused child and perpetrator. The new scale is discussed in terms of its potential use not only by researchers but also by practitioners such as clinicians and social workers in the child protection field in order to more accurately identify and assess multiples of abuse in childhood. A companion article (Bifulco, Moran, Baines, Bunn, & Stanford, 2002) examines the relationship of psychological abuse to adult major depression.

Effects of social support during weekend leave on cortisol and depression ratings: a pilot study.

BACKGROUND: The biological mechanism by which social support influences the course of a depressive episode may involve the stress response which is reflected and/or mediated by cortisol. The study took advantage of the weekend leave that inpatients receive towards the end of an admission to investigate the inter-relationship between social support, cortisol secretion, and the severity of depression. METHOD: For 23 inpatients with a major depressive episode (DSM IV) differences between ward and home in social support, depression ratings, and cortisol secretion were compared. The effect of hassles on cortisol secretion was also assessed. RESULTS: An inverse linear relationship was found between changes in social support and depression ratings across the two settings. No relationship was found between changes in the other two sets of variables. Hassles resulted in increased cortisol secretion. LIMITATIONS: The small sample limits the analysis of hypotheses of interest. Findings are restricted to an inpatient tertiary referral sample. CONCLUSIONS: Weekend leave is an appropriate paradigm to study the effect of social influences on cortisol secretion, and the severity of depression. It is feasible for depressed inpatients to accurately collect timed saliva samples both on the ward and when at home, and for research workers to measure social support provided by a ward. The relationship between social support and depression has clinical implications in terms of interpreting mood changes following weekend leave. Hassles are associated with increased secretion of cortisol in depressed patients, which extends similar previous findings in normal subjects.