Obstetrics and Gynaecology - Research Publications
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ItemConsequences of β-Thalassemia or Sickle Cell Disease for Ovarian Follicle Number and Morphology in Girls Who Had Ovarian Tissue Cryopreserved.(Frontiers Media SA, 2020)Women with β-thalassemia (BT) and sickle cell disease (SCD) have a high risk of infertility and premature ovarian insufficiency. Different fertility preserving strategies, including ovarian tissue cryopreservation (OTC) and oocyte cryopreservation has been considered, and healthy babies have been born after successful OTC and transplantation. We evaluated follicle number and follicle health in ovarian tissue from a cohort of BT and SCD patients who underwent OTC before the age of 18 years. Patients undergoing OTC from 2002 to 2019 were included. A total of 14 girls and adolescents with BT and four with SCD, aged 2.8-17.4 years at OTC were included together with a reference group of 43 girls and adolescents with non-anemia diseases considered to have normal ovaries aged 0.6-17.9 years at OTC. Ovarian follicle density was measured in cortex biopsies and compared to the reference group. Expression of proteins associated with follicular health was evaluated using immunohistochemistry. Follicles were detected in the ovarian cortex biopsies from all patients with BT and SCD. The follicle densities were within the 95% prediction interval of the reference group in all cases. A similar expression of six proteins essential for follicular health was detected using immunohistochemistry in BT, SCD, and references. OTC should be considered an option for young girls and adolescents with BT and SCD.
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ItemDelineating a role for the mitochondrial permeability transition pore in diabetic kidney disease by targeting cyclophilin D(PORTLAND PRESS LTD, 2020-01)Mitochondrial stress has been widely observed in diabetic kidney disease (DKD). Cyclophilin D (CypD) is a functional component of the mitochondrial permeability transition pore (mPTP) which allows the exchange of ions and solutes between the mitochondrial matrix to induce mitochondrial swelling and activation of cell death pathways. CypD has been successfully targeted in other disease contexts to improve mitochondrial function and reduced pathology. Two approaches were used to elucidate the role of CypD and the mPTP in DKD. Firstly, mice with a deletion of the gene encoding CypD (Ppif-/-) were rendered diabetic with streptozotocin (STZ) and followed for 24 weeks. Secondly, Alisporivir, a CypD inhibitor was administered to the db/db mouse model (5 mg/kg/day oral gavage for 16 weeks). Ppif-/- mice were not protected against diabetes-induced albuminuria and had greater glomerulosclerosis than their WT diabetic littermates. Renal hyperfiltration was lower in diabetic Ppif-/- as compared with WT mice. Similarly, Alisporivir did not improve renal function nor pathology in db/db mice as assessed by no change in albuminuria, KIM-1 excretion and glomerulosclerosis. Db/db mice exhibited changes in mitochondrial function, including elevated respiratory control ratio (RCR), reduced mitochondrial H2O2 generation and increased proximal tubular mitochondrial volume, but these were unaffected by Alisporivir treatment. Taken together, these studies indicate that CypD has a complex role in DKD and direct targeting of this component of the mPTP will likely not improve renal outcomes.
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ItemNo Preview AvailableThe New Generation Antiplatelet Agent Prasugrel Represents an Exciting Novel Candidate Therapy for Preeclampsia.(SPRINGER HEIDELBERG, 2020-03)
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ItemLong-term trends of Chlamydia trachomatis in a clinic population at the Royal Women's Hospital, Melbourne(WILEY, 2020-02)BACKGROUND: Chlamydia trachomatis (C. trachomatis) prevalence has been reported to be increasing. Whether this is a true increase over time or confounded by increases in testing and/or use of more sensitive assays is to be determined. MATERIALS AND METHODS: One laboratory service has been detecting C. trachomatis for the past 30 years within the Royal Women's Hospital Melbourne. We conducted a retrospective audit of records over the period 1986-2016 from a clinic population routinely offered chlamydia screening. These were women presenting for family planning advice (termination of pregnancy, intrauterine device insertion or considered at high risk), who underwent chlamydia testing in the context of various diagnostic assays used over this time period. Assays utilised included culture, enzyme immunoassay (EIA), DNA probe, and nucleic acid amplification testing (NAAT). Non-parametric test for trend was used to determine significant differences between prevalence estimates across ordered groups. Least squares regression was conducted to describe a linear trend matching known data points. RESULTS: Overall, there was no significant change for chlamydia prevalence which was 2.2%, in the 30-year study period (P = 0.7). Over time diagnostic assays changed from culture, to EIA, DNA probe, to the more sensitive NAAT. The bulk of the positives were in women under 25 years of age (57%). CONCLUSION: Chlamydia prevalence has been stable over 30 years, remaining a problem in young women. Screening for those at risk needs underscoring in a national sexual health program.
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ItemFetal fraction and noninvasive prenatal testing: What clinicians need to know(WILEY, 2020-01)The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of samples with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice.
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ItemCombination methotrexate and gefitinib: A potential medical treatment for inoperable nontubal ectopic pregnancy(WILEY, 2020-03)Nontubal ectopic pregnancies present as a therapeutic challenge. A 35-year-old primigravida at 7 weeks gestation had a live interstitial ectopic pregnancy and contraindications to surgery. The patient was treated with a multidose methotrexate regimen combined with oral gefitinib (250 mg daily for 7 days). The peak human chorionic gonadotropin (hCG) of the patient was recorded at 19 510 IU/L and began declining from day 4 of combination therapy (day 6 of initial treatment). Successful resolution of the ectopic was demonstrated by cessation of the fetal heart by day 15 and hCG falling to 23 IU/L by day 42. A 10-year review of all nontubal ectopic pregnancies treated with methotrexate identified 46 cases, which had a comparable time to resolution to combination therapy. However, for cases where cardiac activity was present, the median time to resolution following methotrexate treatment was 64 days (47-87 days), 22 days longer than combination therapy. Combination therapy may provide a safe medical treatment for inoperable nontubal ectopic pregnancy.
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ItemThe Vulval Disease Quality of Life Index in women with vulval lichen sclerosus correlates with clinician and symptom scores(WILEY, 2020-05)BACKGROUND/OBJECTIVES: The Vulval disease Quality of Life Index (VQLI) is a new tool that assesses the burden of vulval disease on quality of life (QoL). Our objective was to assess the correlation between VQLI score and clinician-rated severity scores, overall patient itch/discomfort, disease duration, sexual activity, and age, in vulval lichen sclerosus (VLS) at a vulval disorders clinic. METHODS: A retrospective case note review, including consecutive women with VLS who attended the clinic between April and October 2018. Outcome measures include the VQLI score, clinician-rated severity score, and patient symptom score. RESULTS: A total of 109 women with VLS were included. On multivariable analysis, there was evidence of a positive relationship between VQLI scores and the total clinician-rated score (mean increase in VQLI score per unit increase in clinician score 1.34, 95% confidence interval [CI] 0.31, 2.38; P = 0.01); the relationship was stronger for the cutaneous component. There was little evidence for relationships of the VQLI with the patient's age, sexual activity or time since onset of symptoms. There was strong evidence for a positive relationship between VQLI score and overall itch/discomfort score (mean increase 2.38, 95% CI 1.88, 2.88; P < 0.001). New and follow-up data were obtained on sequential visits for 12 women, among whom the VQLI score dropped a mean -2.75 points between visits (95% CI -6.05, 0.55; P = 0.094). CONCLUSION: The clinician-rated severity correlates with the impact of VLS on QoL. The VQLI captures information included in a patient itch/discomfort score, which can be easily incorporated into routine assessment.
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ItemChanges in the modes of twin birth in Victoria, 1983-2015(WILEY, 2020-02)OBJECTIVES: To examine changes in the modes of delivery of twins in Victoria over 33 years. DESIGN: Retrospective population-based study. SETTING, PARTICIPANTS: All twin births in Victoria, 1 January 1983 - 31 December 2015. MAJOR OUTCOMES: Mode of birth (vaginal, planned or unplanned caesarean delivery); indications for caesarean delivery. RESULTS: During 1983-2015, 32 187 twin pregnancies ended in live or stillbirths in Victoria. The proportion of twins born by caesarean delivery increased from 24% (156 twin deliveries) in 1983 to 71% (782 deliveries) in 2015. The proportion of twin births by planned caesarean delivery with twin pregnancy as the sole indication for caesarean delivery increased across this period from 1.8% (12 twin deliveries) to 21% (231 deliveries). The proportion of twin births by caesarean delivery and the proportion of caesarean twin deliveries with twin pregnancy as the principal indication each differed between Victorian regions. CONCLUSION: During 1983-2015, the proportion of twins born in Victoria by caesarean delivery increased almost threefold, mostly because caesarean delivery has become the preferred mode of birth for twin pregnancies. Regional differences in the delivery of twins suggest that the number of caesarean deliveries can be reduced with appropriate system and training support.
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ItemMovement-based interventions for preschool-age children with, or at risk of, motor impairment: a systematic review(WILEY, 2020-03)AIM: To explore the efficacy of movement-based interventions to improve motor skills in preschool-age children with, or at risk of, motor impairment, including those with a diagnosis of cerebral palsy, autism spectrum disorder, and developmental coordination disorder. METHOD: Relevant electronic databases were searched for randomized or quasi-randomized controlled trials. Outcomes were classified using domains of the International Classification of Functioning, Disability and Health: Children & Youth version. Quality was assessed using the Physiotherapy Evidence Database scale. Risk of bias was assessed using the Cochrane Risk of Bias tool. Effect sizes were calculated using Cohen's d. RESULTS: Seventeen articles exploring a heterogeneity of intervention types, population groups, and outcome measures met the inclusion criteria. Movement-based interventions did not significantly improve outcomes in either the body structure and function or activity domains in most studies. No studies used a participation outcome measure. INTERPRETATION: There is a paucity of evidence exploring movement-based interventions in the preschool-age group. Although movement-based interventions showed potential for improving body structure and function and activity outcomes for children with motor impairment, results were mostly not significant. Small sample sizes, variable study quality, and risk of bias limit confidence in the results. WHAT THIS PAPER ADDS: The evidence is inconclusive to support movement-based interventions in this group. No studies used outcome measures assessing participation. Variability in intervention type and study quality limit confidence in results.
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ItemPostnatal probiotics and allergic disease in very preterm infants: Sub-study to the ProPrems randomized trial(WILEY, 2020-01)BACKGROUND: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. METHODS: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. RESULTS: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. CONCLUSION: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.