Shavi Fernando

Background: The performance of cell‐free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear.Objectives: This was a systematic review and meta‐analysis to investigate the sensitivity, specificity and positive predictive value (PPV) of cfDNA screening for CNVs.Search Strategy: Articles published in EMBASE, PubMed or Web of Science before November 2022 were screened for inclusion. This protocol was registered with PROSPERO (23 March 2021, CRD42021250849) prior to initiation.Selection Criteria: Articles published in English, detailing diagnostic outcomes for at least 10 high‐risk CNV results with cfDNA were considered for inclusion.Data Collection and Analysis: The PPV was calculated and pooled with random‐effects models for double‐arcsine transformed proportions, using cases with diagnostic confirmation. Overall sensitivity, specificity and a summary receiver‐operating characteristics (ROC) curve were calculated using bivariate models. The risk of bias was assessed using QUADAS‐2.Main Results: In all, 63 articles were included in the final analysis, detailing 1 591 459 cfDNA results. The pooled PPV was 37.5% (95% confidence interval [CI] 30.6–44.8), with substantial statistical heterogeneity (I² = 93.9%). Bivariate meta‐analysis estimated sensitivity and specificity to be 77.4% (95% CI 65.7–86.0) and 99.4% (95% CI 98.0–99.8), respectively, with an area under the summary ROC curve of 0.947 (95% CI 0.776–0.984).Conclusions: Approximately one‐third of women who screen high‐risk for CNVs with cfDNA will have an affected fetus. This value is of importance for screening counselling.

Background: Blended teaching combines traditional in‐person components (simulation‐based training and clinical‐based placement) with online resources. Due to the COVID‐19 pandemic, we modified our Women's Health Interprofessional Learning through Simulation (WHIPLS) program – to develop core obstetric and gynaecological skills – into a blended teaching program. There is limited literature reporting the observations of blended teaching on learning.Aims: To qualitatively evaluate the blended teaching program and explore how it contributes to learning.Materials and Methods: This study was performed at Monash University in Melbourne, Australia. A total of 98 medical students and 39 midwifery students participated. Data were collected by written survey and analysed by authors using a thematic analysis framework.Results: Students reported that in‐person teaching remains a vital aspect of their curriculum, contributing an averaged 63.2% toward an individual's learning, compared with online. Five substantial themes demonstrate how students learnt and maximised education opportunities using a blended teaching program: ‘low‐pressure simulation environments’, ‘peer‐assisted learning’, ‘haptic learning’, ‘scaffolded learning’ and ‘the impact of online discourse’.Discussion: In‐person teaching remains a cornerstone of obstetric and gynaecological clinical skills education, of which interprofessional simulation and clinical‐based placement are key components. Teaching via online discourse alone, is not sufficient to completely replace and provide comparable learning outcomes, but certainly plays an important role to prime students' learning and to maximise in‐person opportunities and resources. Our study reveals key pedagogies of a blended (online and in‐person) learning program, providing further evidence to support its ongoing utility as a feasible and warranted approach to learning.

Background: Medical and nursing students may feel under‐prepared to perform basic surgical and gynaecology procedural skills. There also remains scope within undergraduate programs to integrate interprofessional education, and better prepare students for interprofessional collaboration to improve patient care.Aims: A simulation‐based gynaecology surgical skills workshop program was introduced for undergraduate medical and nursing students. The aim of this study was to explore students’ perceptions of a simulation‐based interprofessional gynaecological skills program, using students’ pre‐ and post‐workshop confidence in taught skills reported in a post‐workshop questionnaire as an outcome measure.Materials and methods: One hundred and sixty undergraduate medical (n = 133) and nursing (n = 27) students attended the workshop program at a tertiary university in Melbourne, Australia. A survey was completed by all students immediately after the workshop, addressing students’ perceptions of surgical education, the four skill‐stations (gowning/gloving, suturing, intrauterine device insertion, and urethral catheterisation), and interprofessional education. A Wilcoxon signed‐rank test was performed to compare students’ pre‐ and post‐workshop confidence scores.Results: Most medical and nursing students (86%) agreed their course should provide more structured surgical education. There was a statistically significant increase in post‐workshop self‐reported confidence scores for medical and nursing students in all four taught skills. Confidence in interprofessional behaviours also improved in both cohorts, but the improvement in nursing students did not reach statistical significance.Conclusions: Simulation‐based, interprofessional, gynaecological surgery skills workshops are practical and valuable additions to undergraduate medical and nursing curricula. Further research should explore long‐term retention of procedural skills and changes in interprofessional attitudes in clinical practice.

Background: Melatonin is a potent oxygen scavenger and is capable of altering blood flow in various vascular beds.Aims: We aimed to determine the effect of melatonin on ovarian vascular indices during ovarian stimulation for in vitro fertilisation (IVF).Materials and Methods: This is a pilot double‐blind placebo‐controlled randomised trial. Sixty‐nine women (mean age 35.8 ± 4.3 years) undergoing their first cycle of IVF were randomised to receive either placebo, 2, 4 or 8 mg of melatonin, twice a day. Each participant underwent a transvaginal ultrasound at days 6–10 assessing follicular number and size. The vascularisation index (VI), flow index (FI) and vascularisation‐flow index (VFI) were measured. These indices were then correlated with embryological outcomes. Informed consent was obtained from participants. This trial was registered with the Australia New Zealand Clinical Trials Registry (ACTRN12613001317785).Results: The number of follicles did not differ between groups (P = 0.4). There were no differences in the VI (P = 0.4), FI (P = 0.1) or VFI (P = 0.3) in the right ovary or the FI (P = 0.3) or VFI (P = 0.3) in the left ovary between groups. When comparing placebo to any dose of melatonin, there were no differences in any measured parameter. While there was correlation between the number of follicles on ultrasound and all measured embryological outcomes, there was no correlation between ovarian vascular indices and these important clinical outcomes.Conclusions: Melatonin does not appear to change ovarian vascular indices during ovarian stimulation. In addition, such vascular indices cannot predict the number or quality of oocytes or embryos obtained in an IVF cycle. These findings require confirmation in future larger studies.

How to Prepare the Egg and Embryo to Maximize IVF Success - edited by Gabor Kovacs January 2019

Does melatonin result in a dose–response effect on sleep quality and daytime sleepiness in women undergoing IVF? Melatonin, even when given at high doses twice per day, does not cause significant daytime sleepiness or change night time sleep quantity or quality. Melatonin is being increasingly used as an adjuvant therapy for women undergoing IVF owing to its antioxidative effects. It is widely considered to be sedative but there are scant objective data on the effects of melatonin on sleep in the setting of IVF. The study was a double-blind placebo-controlled randomized trial of 116 women recruited between September 2014 and September 2016. Women who were undergoing their first cycle of IVF at private IVF centers were recruited into the RCT and randomized to receive either placebo, 2 mg, 4 mg or 8 mg of melatonin, twice per day (BD) from Day 2 of their cycle until the day before oocyte retrieval. Each participant wore an accelerometer that provides an estimate of sleep and wake activity for up to 1 week of baseline and throughout treatment (up to 2 weeks). They also kept sleep diaries and completed a Karolinska sleepiness score detailing their night time sleep activity and daytime sleepiness, respectively. In total, 116 women were included in the intention-to-treat analysis (placebo BD (n = 32), melatonin 2 mg BD (n = 29), melatonin 4 mg BD (n = 26), melatonin 8 mg BD (n = 29)). There were no significant differences in daytime Karolinska sleepiness score between groups (P = 0.4), nor was there a significant dose–response trend (β=0.05, 95% CI −0.22–0.31, P = 0.7). There were no differences in objective measures of sleep quantity or quality, including wake after sleep onset time, sleep onset latency, and sleep efficiency before and after treatment or between groups. There was an improvement in subjective sleep quality scores from baseline to during treatment in all groups, except 8 mg BD melatonin: placebo (percentage change −13.3%, P = 0.01), 2 mg (−14.1%, P = 0.03), 4 mg (−8.6%, P = 0.01) and 8 mg (−7.8%, P = 0.07). As this was a subset of a larger trial, the melatonin in ART (MIART) trial, it is possible that the sample size was too small to detect statistically significant differences between the groups. While this study suggests that melatonin can be used twice per day at high doses to achieve sustained antioxidation effects, with the reassurance that this will not negatively impact daytime sleepiness or night time sleep habits, the sample size is small and may have missed a clinically significant difference. Nevertheless, our findings may have implications not only for future studies of fertility treatments (including meta-analyses), but also in other medical fields where sustained antioxidation is desired. This study was funded by the Monash IVF Research and Education Foundation (PY12_15). S.F. is supported by the National Health and Medical Research Council (Postgraduate Scholarship APP1074342) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists Ella Macknight Memorial Scholarship. E.W. is supported by an National Health and Medical Research Council Program Grant (APP1113902). S.F., E.W., R.H., B.V., N.L., N.H., M.W., M.L., A.L., P.T., K.L. have nothing to declare. L.R. is a Minority shareholder in Monash IVF Group, has unrestricted grants from MSD®, Merck-Serono® and Ferring® and receives consulting fees from Ferring®. S.N.B. reports consulting fees from Johnson & Johnson Consumer Inc®, outside the submitted work. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (Project ID: ACTRN12613001317785). 27/11/2013 1/9/2014

Introduction: High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3–4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose–response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. Methods and analyses: We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2′-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethics and dissemination: Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. Trial registration number: ACTRN12613001317785.