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Nuffield Department of Women's & Reproductive Health sits within the Medical Sciences Division of the University of Oxford. The department encompasses multi-disciplinary research across four overarching themes; Cancer, Global Health, Maternal & Fetal Health and Reproductive Medicine & Genetics
Suppression and enhancement of the T cell-dependent production of antibody to SRBC in vitro by bacterial lipopolysaccharide.
LPS induced the production of antibody to sheep red blood cells (SRBC) in cultures of spleen cells from normal and T cell-depleted mice, and addition of SRBC to the cultures enchanced this T cell-independent response very little. By contrast, the T cell-dependent production of antibody to SRBC in vitro was suppressed when lipopolysaccharide (LPS) was added at the time when the spleen cells were cultured. Later addition of LPS to spleen cell cultures caused enhancement of antibody production, but only when LPS had not been added before. Addition of T cells that had been primed with SRBC in vivo did not reverse the LPS-induced suppression of antibody production. The data are interpreted to mean that either B cells are rendered incapable of receiving T cell signals in the presence of LPS or that LPS interferes with the appropriate association of cellular components which cooperate in the immune response to SRBC.
Standardization and quality control of the introduction of a noninvasive cardiac output monitor for pregnancy measurements in a low- and middle-income country.
INTRODUCTION: There is increasing awareness of the role of the maternal cardiovascular system in complicated pregnancies. Despite the high disease burden, noninvasive cardiac output monitors have not been used extensively in low- and middle-income countries. The aim of this study was to evaluate the quality control of the use of the ultrasonic cardiac output monitor (USCOM) 1A® in a LMIC. MATERIAL AND METHODS: This was a quality assessment study of the introduction of the USCOM 1A® to measure maternal hemodynamic indices. Inter-observer agreement was assessed across all four study sites by intraclass correlation coefficient. Quality control was assessed using pre-defined acceptability criteria, rated by 2 independent scorers. RESULTS: On average, nurses or midwives needed to obtain 30.4 (range 24-36) Doppler waveform recordings to be deemed competent to undertake USCOM 1A® measurements. There was very good inter-observer agreement across all 4 sites (intraclass correlation coefficient 0.86-0.93, all p
The efficacy of sildenafil therapy in dismal prognosis early-onset intrauterine growth restriction: the STRIDER RCT
BackgroundSevere early-onset intrauterine growth restriction is associated with stillbirth, neonatal death and neurodevelopmental impairment. There is no treatment for intrauterine growth restriction with timely delivery being the only management option. Placentas from intrauterine growth restriction pregnancies often show failure to remodel maternal spiral arteries leading to a persistent vasoactive responsiveness. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates naturally occurring nitrous oxide, encouraging vasodilation of vasoactive vessels. Previous studies in animal models and humans show recovery of placental function and improvement in fetal growth. The STRIDER trial aimed to address whether treatment with sildenafil is beneficial to fetal growth and perinatal and toddler outcomes.MethodsThe STRIDER trial was a superiority, randomised double-blind placebo-controlled trial that was carried out in 19 fetal medicine units in the United Kingdom. Women with a singleton pregnancy between 22+0 and 29+6 weeks’ gestation, with severe early-onset intrauterine growth restriction, were asked to participate. Women were randomised (1 : 1) to receive either sildenafil 25-mg three times daily or placebo until 31+6 weeks’ gestation or delivery. Women were stratified by site and their gestational age at randomisation (before 26+0 or at 26+0 weeks or later). Severe intrauterine growth restriction was defined as a combination of estimated fetal weight or abdominal circumference below the 10th percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days with a 1-week difference deemed to be clinically significant. The phase 2 study followed up all babies alive at discharge to assess for cardiovascular function and neurodevelopment at 2 years of age.ResultsBetween 21 November 2014 and 6 July 2016, a total number of 135 women were recruited to the study, of these 70 were assigned to sildenafil and 65 to the placebo. No difference was found in the median randomisation to delivery interval between sildenafil [17 days (interquartile range 7–24)] and placebo [18 days (8–28), p = 0.23]. Live births [relative risk 1.06, 95% confidence interval 0.84 to 1.33; p = 0.62], fetal deaths (relative risk 0.89, 95% confidence interval 0.54 to 1.45; p = 0.64), neonatal deaths (relative risk 1.33, 95% confidence interval 0.54 to 3.28; p = 0.53), and birthweight [mean difference −14 g (95% confidence interval −100 to 126); p = 0.81] did not differ between the treatment arms and no differences were found for other maternal or perinatal secondary outcomes. Eight serious adverse events were reported during the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Seventy-five babies were discharged alive from the neonatal unit and of those 61 were available for follow-up with 32 treated with sildenafil and 29 with placebo. Of those that did not have a follow-up 1 baby died (placebo) and 3 declined follow-up and 10 were uncontactable. There was no difference in neurodevelopment, or blood pressure for infants treated with sildenafil versus placebo. Infants who received sildenafil had a greater head circumference compared to those who received placebo (median difference 49.25 cm, interquartile range 46.4–50.26 vs. 47.17 cm, 95% confidence interval 44.71 to 48.95).ConclusionSildenafil did not prolong pregnancy or improve pregnancy outcomes. There was no effect from sildenafil treatment on infant neurodevelopment. Our data show that sildenafil should not be prescribed for fetal growth restriction.Trial registrationThis trial is registered as ISRCTN39133303.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/62/109) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 18. See the NIHR Funding and Awards website for further award information.
The evolution of preimplantation genetic testing: where is the limit?
Preimplantation genetic testing (PGT) has revolutionized reproductive medicine over the past 30 years, providing a reliable method for reducing the risk of transmitting severe inherited conditions and offering the possibility of improved IVF outcomes. Today, PGT is widely accepted and integrated into fertility care in many countries around the world. Its history, however, has not been without controversy, with debate around its application to the diagnosis of late-onset disorders, conditions with incomplete penetrance and its use for embryo selection based upon human leukocyte antigen status. Nonetheless, PGT has progressively broadened its scope, and the number of embryos undergoing genetic testing continues to grow each year. Preimplantation genetic testing is most often used for the detection of chromosomal abnormalities, assisting in the identification of embryos affected by lethal aneuploidy. This application has generated the greatest debate of all, owing, in part, to difficulties delivering effective embryo testing using earlier methods. In recent years, advances in technology and rigorous validation studies have helped to improve accuracy, although variability among methods underscores the need for greater standardization and transparency. Emerging technologies, such as whole genome sequencing (WGS) and genome editing, hold promise for further advancements but introduce complex ethical, privacy and consent challenges that demand careful consideration, public engagement and thorough clinical research before implementation. Given its current trajectory, it seems likely that the use of PGT will continue to grow, offering reduced reproductive risks and the possibility of enhanced fertility treatment outcomes for ever greater numbers of patients, ultimately becoming an accepted cornerstone of reproductive care.