An improved vitrification protocol for equine immature oocytes, resulting in a first live foal

Background: The success rate for vitrification of immature equine oocytes is low. Although vitrified-warmed oocytes are able to mature, further embryonic development appears to be compromised. Objectives: The aim of this study was to compare two vitrification protocols, and to examine the effect of the number of layers of cumulus cells surrounding the oocyte during vitrification of immature equine oocytes. Study design: Experimental in vitro and in vivo trials. Methods: Immature equine oocytes were vitrified after a short exposure to high concentrations of cryoprotective agents (CPAs), or a long exposure to lower concentrations of CPAs. In Experiment 1, the maturation of oocytes surrounded by multiple layers of cumulus cells (CC oocytes) and oocytes surrounded by only corona radiata (CR oocytes) was investigated. In Experiment 2, spindle configuration was determined for CR oocytes vitrified using the two vitrification protocols. In Experiment 3, further embryonic development was studied after fertilisation and culture. Embryo transfer was performed in a standard manner. Results: Similar nuclear maturation rates were observed for CR oocytes vitrified using the long exposure and nonvitrified controls. Furthermore, a lower maturation rate was obtained for CC oocytes vitrified with the short exposure compared to control CR oocytes (P = 0.001). Both vitrification protocols resulted in significantly higher rates of aberrant spindle configuration than the control groups (P<0.05). Blastocyst development only occurred in CR oocytes vitrified using the short vitrification protocol, and even though blastocyst rates were significantly lower than in the control group (P<0.001), transfer of five embryos resulted in one healthy foal. Main limitations: The relatively low number of equine oocytes and embryo transfer procedures performed. Conclusions: For vitrification of immature equine oocytes, the use of 1) CR oocytes, 2) a high concentration of CPAs, and 3) a short exposure time may be key factors for maintaining developmental competence

Variation and ethnic inequalities in treatment of common mental disorders before, during and after pregnancy : combined analysis of routine and research data in the Born in Bradford cohort

BACKGROUND: Common mental disorders (CMD) such as anxiety and depression during the maternal period can cause significant morbidity to the mother in addition to disrupting biological, attachment and parenting processes that affect child development. Pharmacological treatment is a first-line option for moderate to severe episodes. Many women prescribed pharmacological treatments cease them during pregnancy but it is unclear to what extent non-pharmacological options are offered as replacement. There are also concerns that treatments offered may not be proportionate to need in minority ethnic groups, but few data exist on treatment disparities in the maternal period. We examined these questions in a multi-ethnic cohort of women with CMD living in Bradford, England before, during and up to one year after pregnancy. METHODS: We searched the primary care records of women enrolled in the Born in Bradford cohort for diagnoses, symptoms, signs ('identification'), referrals for treatment, non-pharmacological and pharmacological treatment and monitoring ('treatment') related to CMD. Records were linked with maternity data to classify women identified with a CMD as treated prior to, and one year after, delivery. We examined rates and types of treatment during pregnancy, and analysed potential ethnic group differences using adjusted Poisson and multinomial logistic regression models. RESULTS: We analysed data on 2,234 women with indicators of CMD. Most women were discontinued from pharmacological treatment early in pregnancy, but this was accompanied by recorded access to non-drug treatments in only 15 % at the time of delivery. Fewer minority ethnic women accessed treatments compared to White British women despite minority ethnic women being 55-70 % more likely than White British women to have been identified with anxiety in their medical record. CONCLUSIONS: Very few women who discontinued pharmacological treatment early in their pregnancy were offered other non-pharmacological treatments as replacement, and most appeared to complete their pregnancy untreated. Further investigation is warranted to replicate the finding that minority ethnic women are more likely to be identified as being anxious or having anxiety and understand what causes the variation in access to treatments

Bright light therapy in pregnant women with major depressive disorder: Study protocol for a randomized, double-blind, controlled clinical trial

Background: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. Methods: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. Discussion: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. Trial registration: Netherlands Trial Register NTR5476. Registered 5 November 2015

Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Drug dosing during pregnancy—opportunities for physiologically based pharmacokinetic models

Drugs can have harmful effects on the embryo or the fetus at any point during pregnancy. Not all the damaging effects of intrauterine exposure to drugs are obvious at birth, some may only manifest later in life. Thus, drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus. Dosing of drugs during pregnancy is often empirically determined and based upon evidence from studies of non-pregnant subjects, which may lead to suboptimal dosing, particularly during the third trimester. This review collates examples of drugs with known recommendations for dose adjustment during pregnancy, in addition to providing an example of the potential use of PBPK models in dose adjustment recommendation during pregnancy within the context of drug-drug interactions. For many drugs, such as antidepressants and antiretroviral drugs, dose adjustment has been recommended based on pharmacokinetic studies demonstrating a reduction in drug concentrations. However, there is relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Examples of using pregnancy PBPK models to predict feto-maternal drug exposures and their applications to facilitate and guide dose assessment throughout gestation are discussed

Which anthropometric indicators identify a pregnant woman as acutely malnourished and predict adverse birth outcomes in the humanitarian context?

Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts

Operational consistency of medical linear accelerators manufactured and commissioned in series

The purpose of this study was to determine if medical linear accelerators (linac) produced by the same manufacturer exhibit operational consistency within their subsystems and components. Two linacs that were commissioned together and installed at the same facility were monitored. Each machine delivered a daily robust quality assurance (QA) irradiation. Linacs and their components operate consistently, but have different operational parameter levels even when produced by the same manufacturer and commissioned in series. These findings have implications on the feasibility of true clinical beam matching. Keywords: Statistical process control, Medical linear accelerator, Performance, Quality assuranc