Beverley Vollenhoven - Profile on Academia.edu (original) (raw)

Papers by Beverley Vollenhoven

Research paper thumbnail of Pelvic inflammatory disease and infertility

Research paper thumbnail of Faculty of 1000 evaluation for Ovarian ageing: the role of mitochondria in oocytes and follicles

Faculty of 1000 evaluation for Ovarian ageing: the role of mitochondria in oocytes and follicles

F1000 - Post-publication peer review of the biomedical literature, 2018

Research paper thumbnail of Depot Medroxyprogesterone Acetate and Bone Mineral Density

Journal of clinical gynecology and obstetrics, 2018

Background: Previous studies have suggested that depot medroxyprogesterone acetate (DMPA) may res... more Background: Previous studies have suggested that depot medroxyprogesterone acetate (DMPA) may result in a reduction in bone mineral density (BMD). This study further explores this relationship. This study was undertaken to assess the association between long-term DMPA use and areal BMD (aBMD) in a uniform manner in a single private specialist practice over two decades. Methods: Of 1,046 consecutive patients using DMPA in a single Melbourne specialist's practice between 1981 and 2013, from 1992 102 were referred for dual-energy X-ray absorptiometry (DXA) scans. Each was matched for age and body mass index with two participants from a reference group of 1,416 healthy female volunteers who underwent DXA scans at the Royal Melbourne Hospital. Results: A total of 306 participants were included in this study, 102 cases and 204 referents. DMPA users had lower aBMD at first testing (median duration of DMPA use 4.3 years (IQR 2.6 -6.7 years) compared with the reference group, and lower aBMD persisted in users 2 -5 years post cessation of DMPA. These differences from the reference group were statistically and potentially clinically significant. There was no evidence of accelerated bone loss at any site in the DMPA users during longitudinal observations on treatment, but the study had limited power to detect such an effect. Conclusions: DMPA use was associated with aBMD deficits during and after treatment. The findings demonstrate that long-term, controlled, prospective studies with adequate sample size are required to evaluate the potential clinical impact of DMPA use on bone health outcomes.

Research paper thumbnail of Faculty of 1000 evaluation for Can an educational DVD improve the acceptability of elective single embryo transfer? A randomized controlled study

Faculty of 1000 evaluation for Can an educational DVD improve the acceptability of elective single embryo transfer? A randomized controlled study

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle

Faculty of 1000 evaluation for Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

Faculty of 1000 evaluation for Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials

Faculty of 1000 evaluation for Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials

F1000 - Post-publication peer review of the biomedical literature, 2009

Research paper thumbnail of A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol

BMJ Open, Sep 1, 2014

Introduction: High levels of oxidative stress can have considerable impact on the outcomes of in ... more 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 0deoxyguanosine 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 peerreviewed journals. Trial registration number: ACTRN12613001317785.

Research paper thumbnail of When only one embryo is available, is it better to transfer on Day 3 or to grow on?

When only one embryo is available, is it better to transfer on Day 3 or to grow on?

Reproductive BioMedicine Online, 2019

RESEARCH QUESTION In patients with only one embryo on Day 3 post-IVF treatment, does transferring... more RESEARCH QUESTION In patients with only one embryo on Day 3 post-IVF treatment, does transferring the embryo into the uterine environment achieve a higher pregnancy rate than growing the embryo on with a plan to transfer at Day 4-6? DESIGN This was a retrospective cohort study conducted in patients with only one viable embryo on Day 3 post-IVF treatment. Data were extracted from a standardized IVF database and included 1384 women who fulfilled this study's selection criteria. Outcomes of these embryos were followed up and stratified into two groups: embryos transferred on Day 3 and those grown on to Day 4-6. Pregnancy rate (biochemical and clinical) and live birth rates were analysed with logistic regression and adjusted using a parsimonious model for baseline patient characteristics. RESULTS Biochemical pregnancy (16.7% versus 9.5%, odds ratio [OR] 1.9, P = 0.001), clinical pregnancy (14.7% versus 6.8%, OR 2.35, P < 0.001) and live birth rates (9.7% versus 4.4%, OR 2.37, P = 0.002) were significantly higher in the Day 3 group than those in the group grown on to Day 4-6. These differences were still significant after adjusting for potential confounders (adjusted OR 2.60, 3.71, 4.08, respectively, P < 0.001). CONCLUSIONS These findings support Day 3 cleavage-stage embryo transfer instead of growing on to Day 4-6 for blastocyst-stage transfer when only a single embryo is available.

Research paper thumbnail of Associations between embryo grading and congenital malformations in IVF/ICSI pregnancies

Reproductive BioMedicine Online, 2019

The aim was to determine whether the quality of transferred embryos has an impact on the rate of ... more The aim was to determine whether the quality of transferred embryos has an impact on the rate of congenital malformations in IVF/ICSI-conceived babies. Design: The retrospective cohort study involved 6637 pregnancies ≥20 weeks gestation from women who underwent embryo transfer with a single day 5 embryo at a private multisite IVF clinic between 2005 and 2015. Embryos were classified as good quality (n=5537) or poor quality (n=1100) based on an internal grading system of morphological parameters; malformation rates were compared. Results: In pregnancies proceeding to delivery (≥ 20 weeks gestation), poor quality embryos were associated with increased odds of at least one anomaly, (aOR 1.33, 95% CI 1.03-1.71), major anomalies (aOR 1.42, 95% CI 1.05-1.91), musculoskeletal anomalies (aOR 2.09, 95% CI 1.35-3.22), particularly talipes (aOR 2.88, 95% CI 1.33-6.25), and the International Classification of Diseases (ICD) classification "Other Congenital Malformations" (aOR 2.34, 95% CI 1.34-4.34). Furthermore, for pregnancies ≥ 9 weeks gestation, poor embryos had more than double the odds of chromosomal anomalies than good embryos (aOR 2.33, 95% CI 1.30-4.18, p=0.005). Conclusions: This is the first study comparing the rates of individual congenital malformations for good and poor quality embryos. It provides insight into potential risks of transferring poor quality embryos. In pregnancies ≥ 20 weeks gestation, poor grade day 5 embryos are associated with major malformations, at least one anomaly, musculoskeletal anomalies, talipes and the ICD classification "Other Congenital Malformations". In pregnancies ≥ 9 weeks gestation, poor grade day 5 embryos are associated with chromosomal anomalies. KEY MESSAGE This is the first study comparing the rates of individual congenital malformations for good and poor embryos. It assists clinicians in counselling patients about the risks of transferring poor quality embryos. Poor grade day 5 embryos are associated with a higher rate of congenital malformations.

Research paper thumbnail of School-age outcomes among IVF-conceived children: A population-wide cohort study

PLOS Medicine, Jan 24, 2023

Background AU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: In vitro fertilisation ... more Background AU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. TheAU : KindlycheckifthechangesmadeinthesentenceTheaimo aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. Methods and findings Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in �2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation,

Research paper thumbnail of Slow Development of a Day 5 Fresh Transferred Embryo Leads to Reduced Live Birth Rate but Not Birthweight: A Multicenter Retrospective Cohort Study

Fertility & Reproduction

Objective: This study aims to investigate the impact of slow embryo development on the subsequent... more Objective: This study aims to investigate the impact of slow embryo development on the subsequent live birth rate and birthweight outcomes following a fresh day 5 transfer. Study design: This retrospective multicenter cohort study included 1,213 consecutive patients undergoing autologous oocyte in vitro fertilization (IVF) treatment at four associated private clinics during 2016–2019. Only fresh single day 5 transfers were included for analysis. Results: No implantation was achieved by embryos that failed to reach the early blastocyst stage on day 5 ([Formula: see text]). After adjusting for potential confounding factors, multivariate logistic regression (expressed as adjusted odds ratio or aOR and [Formula: see text] confidence interval) showed a significantly reduced live birth rate in early blastocysts ([Formula: see text]) in reference to those at the expanding (aOR = 0.584, [Formula: see text], [Formula: see text], [Formula: see text]), expanded (aOR = 0.322, [Formula: see text...

Research paper thumbnail of School Age Developmental Outcomes of Children Conceived by IVF Compared with Controls: A Population Linkage Study

Fertility & Reproduction

Background: There has been increasing interest in assessing longer term developmental and health ... more Background: There has been increasing interest in assessing longer term developmental and health outcomes in IVF-conceived offspring compared with those born after natural conception. So far, the findings have been conflicting. The Australian Early Developmental Consensus (AEDC) assesses children in their first year of primary school across five domains; physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, and communication skills and general knowledge. Aim: To compare school entry (5-7 years of age) outcomes in IVF-conceived children in Victoria with naturally conceived controls. Method: We undertook a statewide data linkage study, with perinatal data (births 2005-2014) linked to data from major IVF providers in Victoria and the AEDC. Our approach to analysis included: complete case analysis, multiple imputation of missing data, consideration of clustering (siblings) and inverse probability weighted modeling to adjust for covariates. ...

Research paper thumbnail of Slow Development of Day 5 Embryo Leads to Compromised Live Birth But Not Birthweight Outcomes

Fertility & Reproduction

Background: There is currently no consensus regarding developmental cutoff for fresh transfer of ... more Background: There is currently no consensus regarding developmental cutoff for fresh transfer of slow developing day 5 embryos on. Literature is sparse regarding true prognosis of such embryos. Aim: To investigate live birth and birthweight outcomes of slow developing day 5 transferred embryos. Method: This retrospective multi-center study included 1213 consecutive autologous-oocyte single fresh day 5 transfers performed at 4 Monash IVF clinics during 2016-2019. Repeat cycles by same patients were excluded to avoid clustering effects. Live birth and birthweight were followed up in all pregnancies. Multiple regression was performed to investigate associations between slow day 5 development (defined as ≤ early blastocyst) and (a) live birth, (b) birthweight, and (c) gestation-adjusted birthweight (Z score) to account for gestational age and gender. Results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). Results: No implantation was achieved when day 5 em...

Research paper thumbnail of Virtual reality and its use in post-operative pain following laparoscopy: a feasibility study

Scientific Reports

Pain following laparoscopic surgery remains a neglected healthcare issue. Virtual reality-mediate... more Pain following laparoscopic surgery remains a neglected healthcare issue. Virtual reality-mediated therapy’s (VRT) analgesic potential could address this. However, its effect in this setting remains unexplored. We aimed to establish the feasibility and safety of VRT as an adjunct analgesic following gynaecological laparoscopy and explore differences between active distraction and passive meditation content. 35 women were enrolled into an open crossover pilot and randomised to either intervention group 1 (active then passive content) or intervention group 2 (passive then active content) following surgery. VRT was administered in two 10-min segments with a 10-min washout period in between. Pain scores, opioid requirements and side effects were recorded before and after each segment whilst questionnaires evaluated acceptability. We observed a significant reduction in pain over time for the entire study population (F = 8.63, p < 0.0005) but no differences between intervention groups,...

Research paper thumbnail of P-237 Non-invasive metabolic live cell imaging of early embryo development using adapted confocal microscopy; a safety study

Human Reproduction

Study question Is it safe to use metabolic imaging to measure nicotinamide adenine dinucleotide (... more Study question Is it safe to use metabolic imaging to measure nicotinamide adenine dinucleotide (NADH) associated auto-fluorescence during embryo development using adapted confocal microscopy? Summary answer Non-invasive metabolic imaging is safe as no differences were observed between controls and illuminated embryos in terms of embryo development, blastocyst formation and implantation potential. What is known already Developing non-invasive methods that are reliable to assess oocyte and embryo quality has been a significant aim for assisted reproductive technologies. Changes in metabolic activity could lead to cell death or abnormal embryo development and low implantation potential. This could potentially be predicted by incorporating non-invasive measurements of metabolism. Metabolic imaging in embryos has been investigated through complex methodologies, however, scientific evidence for its utility during embryo development using simple technology remains unexplored. Measurements...

Research paper thumbnail of Uterine Fibroids (Leiomyomata) and Heavy Menstrual Bleeding

Frontiers in Reproductive Health, 2022

Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 7... more Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 75% within women of reproductive age. In ~30% of patients, uterine fibroids cause menorrhagia, or heavy menstrual bleeding, and more than half of the patients experience symptoms such as heavy menstrual bleeding, pelvic pain, or infertility. Treatment is symptomatic with limited options including hysterectomy as the most radical solution. The genetic foundations of uterine fibroid growth have been traced to somatic driver mutations (MED12, HMGA2, FH−/−, and COL4A5-A6). These also lead to downstream expression of angiogenic factors including IGF-1 and IGF-2, as opposed to the VEGF-driven mechanism found in the angiogenesis of hypoxic tumors. The resulting vasculature supplying the fibroid with nutrients and oxygen is highly irregular. Of particular interest is the formation of a pseudocapsule around intramural fibroids, a unique structure within tumor angiogenesis. These aberrations in vas...

Research paper thumbnail of P–790 Effects of COVID–19 quarantine period on Fertility Treatment and IVF Clinic management

Human Reproduction, 2021

Study question What are the effects of the initial COVID–19 response on the management of fertili... more Study question What are the effects of the initial COVID–19 response on the management of fertility clinics and clinical practice around the world? Summary answer In the COVID–19 outbreak, the large majority of fertility clinics worldwide suspended fertility treatments. In cycles that continued, there was a shift to frozen embryo-transfer. What is known already After the initial months of 2020 showed a rapid spread of the new Coronavirus SARS-CoV–2, the World Health Organisation declared a global pandemic on 11 March 2020. Occupation of health care facilities with acutely sick patients and the need to reduce infection transmission led to a reduction in capacity to perform elective medical procedures. Little was known on the global impact of COVID–19 on fertility care. With the implication of ‘lockdowns’ in different countries around the world to stop the spread of the virus, the question was posed on how fertility clinics and treatments would proceed moving forward. Study design, si...

Research paper thumbnail of 1295School age outcomes in IVF-conceived children compared with controls: a population linkage study

International Journal of Epidemiology, 2021

Background There is interest in longer term outcomes in IVF-conceived offspring compared with tho... more Background There is interest in longer term outcomes in IVF-conceived offspring compared with those conceived naturally. So far, the findings have been conflicting. The Australian Early Developmental Consensus (AEDC) assesses children in their first year of primary school across five domains. Methods To compare school entry outcomes in IVF-conceived children with naturally conceived controls, we undertook a statewide data linkage study, with perinatal data (2005-2014) linked to data from IVF providers in Victoria and the AEDC. Our approach to analysis included: complete case analysis, multiple imputation of missing data, consideration of clustering (siblings) and inverse probability weighted modeling to adjust for covariates. Our primary outcome was an AEDC score indicative of developmental vulnerability in two or more domains. We adjusted for confounders: child’s age at assessment, sex, highest level of maternal education, maternal age, parity, SEIFA (Socio-Economic Indexes for Are...

Research paper thumbnail of An evaluation of strategies to achieve greater than 90% coverage of maternal influenza and pertussis vaccines including an economic evaluation

BMC Pregnancy and Childbirth, 2021

Background Maternal immunisation is an essential public health intervention aimed at improving th... more Background Maternal immunisation is an essential public health intervention aimed at improving the health outcomes for pregnant women and providing protection to the newborn. Despite international recommendations, safety and efficacy data for the intervention, and often a fully funded program, uptake of vaccines in pregnancy remain suboptimal. One possible explanation for this includes limited access to vaccination services at the point of antenatal care. The aim of this study is to evaluate the change in vaccine coverage among pregnant women following implementation of a modified model of delivery aimed at improving access at the point of antenatal care, including an economic evaluation. Methods This prospective multi-centre study, using action research design, across six maternity services in Victoria, Australia, evaluated the implementation of a co-designed vaccine delivery model (either a pharmacy led model, midwife led model or primary care led model) supported by provider educ...

Research paper thumbnail of Pelvic inflammatory disease and infertility

Research paper thumbnail of Faculty of 1000 evaluation for Ovarian ageing: the role of mitochondria in oocytes and follicles

Faculty of 1000 evaluation for Ovarian ageing: the role of mitochondria in oocytes and follicles

F1000 - Post-publication peer review of the biomedical literature, 2018

Research paper thumbnail of Depot Medroxyprogesterone Acetate and Bone Mineral Density

Journal of clinical gynecology and obstetrics, 2018

Background: Previous studies have suggested that depot medroxyprogesterone acetate (DMPA) may res... more Background: Previous studies have suggested that depot medroxyprogesterone acetate (DMPA) may result in a reduction in bone mineral density (BMD). This study further explores this relationship. This study was undertaken to assess the association between long-term DMPA use and areal BMD (aBMD) in a uniform manner in a single private specialist practice over two decades. Methods: Of 1,046 consecutive patients using DMPA in a single Melbourne specialist's practice between 1981 and 2013, from 1992 102 were referred for dual-energy X-ray absorptiometry (DXA) scans. Each was matched for age and body mass index with two participants from a reference group of 1,416 healthy female volunteers who underwent DXA scans at the Royal Melbourne Hospital. Results: A total of 306 participants were included in this study, 102 cases and 204 referents. DMPA users had lower aBMD at first testing (median duration of DMPA use 4.3 years (IQR 2.6 -6.7 years) compared with the reference group, and lower aBMD persisted in users 2 -5 years post cessation of DMPA. These differences from the reference group were statistically and potentially clinically significant. There was no evidence of accelerated bone loss at any site in the DMPA users during longitudinal observations on treatment, but the study had limited power to detect such an effect. Conclusions: DMPA use was associated with aBMD deficits during and after treatment. The findings demonstrate that long-term, controlled, prospective studies with adequate sample size are required to evaluate the potential clinical impact of DMPA use on bone health outcomes.

Research paper thumbnail of Faculty of 1000 evaluation for Can an educational DVD improve the acceptability of elective single embryo transfer? A randomized controlled study

Faculty of 1000 evaluation for Can an educational DVD improve the acceptability of elective single embryo transfer? A randomized controlled study

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle

Faculty of 1000 evaluation for Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

Faculty of 1000 evaluation for Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

F1000 - Post-publication peer review of the biomedical literature, 2010

Research paper thumbnail of Faculty of 1000 evaluation for Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials

Faculty of 1000 evaluation for Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials

F1000 - Post-publication peer review of the biomedical literature, 2009

Research paper thumbnail of A pilot double-blind randomised placebo-controlled dose-response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol

BMJ Open, Sep 1, 2014

Introduction: High levels of oxidative stress can have considerable impact on the outcomes of in ... more 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 0deoxyguanosine 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 peerreviewed journals. Trial registration number: ACTRN12613001317785.

Research paper thumbnail of When only one embryo is available, is it better to transfer on Day 3 or to grow on?

When only one embryo is available, is it better to transfer on Day 3 or to grow on?

Reproductive BioMedicine Online, 2019

RESEARCH QUESTION In patients with only one embryo on Day 3 post-IVF treatment, does transferring... more RESEARCH QUESTION In patients with only one embryo on Day 3 post-IVF treatment, does transferring the embryo into the uterine environment achieve a higher pregnancy rate than growing the embryo on with a plan to transfer at Day 4-6? DESIGN This was a retrospective cohort study conducted in patients with only one viable embryo on Day 3 post-IVF treatment. Data were extracted from a standardized IVF database and included 1384 women who fulfilled this study's selection criteria. Outcomes of these embryos were followed up and stratified into two groups: embryos transferred on Day 3 and those grown on to Day 4-6. Pregnancy rate (biochemical and clinical) and live birth rates were analysed with logistic regression and adjusted using a parsimonious model for baseline patient characteristics. RESULTS Biochemical pregnancy (16.7% versus 9.5%, odds ratio [OR] 1.9, P = 0.001), clinical pregnancy (14.7% versus 6.8%, OR 2.35, P < 0.001) and live birth rates (9.7% versus 4.4%, OR 2.37, P = 0.002) were significantly higher in the Day 3 group than those in the group grown on to Day 4-6. These differences were still significant after adjusting for potential confounders (adjusted OR 2.60, 3.71, 4.08, respectively, P < 0.001). CONCLUSIONS These findings support Day 3 cleavage-stage embryo transfer instead of growing on to Day 4-6 for blastocyst-stage transfer when only a single embryo is available.

Research paper thumbnail of Associations between embryo grading and congenital malformations in IVF/ICSI pregnancies

Reproductive BioMedicine Online, 2019

The aim was to determine whether the quality of transferred embryos has an impact on the rate of ... more The aim was to determine whether the quality of transferred embryos has an impact on the rate of congenital malformations in IVF/ICSI-conceived babies. Design: The retrospective cohort study involved 6637 pregnancies ≥20 weeks gestation from women who underwent embryo transfer with a single day 5 embryo at a private multisite IVF clinic between 2005 and 2015. Embryos were classified as good quality (n=5537) or poor quality (n=1100) based on an internal grading system of morphological parameters; malformation rates were compared. Results: In pregnancies proceeding to delivery (≥ 20 weeks gestation), poor quality embryos were associated with increased odds of at least one anomaly, (aOR 1.33, 95% CI 1.03-1.71), major anomalies (aOR 1.42, 95% CI 1.05-1.91), musculoskeletal anomalies (aOR 2.09, 95% CI 1.35-3.22), particularly talipes (aOR 2.88, 95% CI 1.33-6.25), and the International Classification of Diseases (ICD) classification "Other Congenital Malformations" (aOR 2.34, 95% CI 1.34-4.34). Furthermore, for pregnancies ≥ 9 weeks gestation, poor embryos had more than double the odds of chromosomal anomalies than good embryos (aOR 2.33, 95% CI 1.30-4.18, p=0.005). Conclusions: This is the first study comparing the rates of individual congenital malformations for good and poor quality embryos. It provides insight into potential risks of transferring poor quality embryos. In pregnancies ≥ 20 weeks gestation, poor grade day 5 embryos are associated with major malformations, at least one anomaly, musculoskeletal anomalies, talipes and the ICD classification "Other Congenital Malformations". In pregnancies ≥ 9 weeks gestation, poor grade day 5 embryos are associated with chromosomal anomalies. KEY MESSAGE This is the first study comparing the rates of individual congenital malformations for good and poor embryos. It assists clinicians in counselling patients about the risks of transferring poor quality embryos. Poor grade day 5 embryos are associated with a higher rate of congenital malformations.

Research paper thumbnail of School-age outcomes among IVF-conceived children: A population-wide cohort study

PLOS Medicine, Jan 24, 2023

Background AU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: In vitro fertilisation ... more Background AU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. TheAU : KindlycheckifthechangesmadeinthesentenceTheaimo aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. Methods and findings Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in �2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation,

Research paper thumbnail of Slow Development of a Day 5 Fresh Transferred Embryo Leads to Reduced Live Birth Rate but Not Birthweight: A Multicenter Retrospective Cohort Study

Fertility & Reproduction

Objective: This study aims to investigate the impact of slow embryo development on the subsequent... more Objective: This study aims to investigate the impact of slow embryo development on the subsequent live birth rate and birthweight outcomes following a fresh day 5 transfer. Study design: This retrospective multicenter cohort study included 1,213 consecutive patients undergoing autologous oocyte in vitro fertilization (IVF) treatment at four associated private clinics during 2016–2019. Only fresh single day 5 transfers were included for analysis. Results: No implantation was achieved by embryos that failed to reach the early blastocyst stage on day 5 ([Formula: see text]). After adjusting for potential confounding factors, multivariate logistic regression (expressed as adjusted odds ratio or aOR and [Formula: see text] confidence interval) showed a significantly reduced live birth rate in early blastocysts ([Formula: see text]) in reference to those at the expanding (aOR = 0.584, [Formula: see text], [Formula: see text], [Formula: see text]), expanded (aOR = 0.322, [Formula: see text...

Research paper thumbnail of School Age Developmental Outcomes of Children Conceived by IVF Compared with Controls: A Population Linkage Study

Fertility & Reproduction

Background: There has been increasing interest in assessing longer term developmental and health ... more Background: There has been increasing interest in assessing longer term developmental and health outcomes in IVF-conceived offspring compared with those born after natural conception. So far, the findings have been conflicting. The Australian Early Developmental Consensus (AEDC) assesses children in their first year of primary school across five domains; physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, and communication skills and general knowledge. Aim: To compare school entry (5-7 years of age) outcomes in IVF-conceived children in Victoria with naturally conceived controls. Method: We undertook a statewide data linkage study, with perinatal data (births 2005-2014) linked to data from major IVF providers in Victoria and the AEDC. Our approach to analysis included: complete case analysis, multiple imputation of missing data, consideration of clustering (siblings) and inverse probability weighted modeling to adjust for covariates. ...

Research paper thumbnail of Slow Development of Day 5 Embryo Leads to Compromised Live Birth But Not Birthweight Outcomes

Fertility & Reproduction

Background: There is currently no consensus regarding developmental cutoff for fresh transfer of ... more Background: There is currently no consensus regarding developmental cutoff for fresh transfer of slow developing day 5 embryos on. Literature is sparse regarding true prognosis of such embryos. Aim: To investigate live birth and birthweight outcomes of slow developing day 5 transferred embryos. Method: This retrospective multi-center study included 1213 consecutive autologous-oocyte single fresh day 5 transfers performed at 4 Monash IVF clinics during 2016-2019. Repeat cycles by same patients were excluded to avoid clustering effects. Live birth and birthweight were followed up in all pregnancies. Multiple regression was performed to investigate associations between slow day 5 development (defined as ≤ early blastocyst) and (a) live birth, (b) birthweight, and (c) gestation-adjusted birthweight (Z score) to account for gestational age and gender. Results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). Results: No implantation was achieved when day 5 em...

Research paper thumbnail of Virtual reality and its use in post-operative pain following laparoscopy: a feasibility study

Scientific Reports

Pain following laparoscopic surgery remains a neglected healthcare issue. Virtual reality-mediate... more Pain following laparoscopic surgery remains a neglected healthcare issue. Virtual reality-mediated therapy’s (VRT) analgesic potential could address this. However, its effect in this setting remains unexplored. We aimed to establish the feasibility and safety of VRT as an adjunct analgesic following gynaecological laparoscopy and explore differences between active distraction and passive meditation content. 35 women were enrolled into an open crossover pilot and randomised to either intervention group 1 (active then passive content) or intervention group 2 (passive then active content) following surgery. VRT was administered in two 10-min segments with a 10-min washout period in between. Pain scores, opioid requirements and side effects were recorded before and after each segment whilst questionnaires evaluated acceptability. We observed a significant reduction in pain over time for the entire study population (F = 8.63, p < 0.0005) but no differences between intervention groups,...

Research paper thumbnail of P-237 Non-invasive metabolic live cell imaging of early embryo development using adapted confocal microscopy; a safety study

Human Reproduction

Study question Is it safe to use metabolic imaging to measure nicotinamide adenine dinucleotide (... more Study question Is it safe to use metabolic imaging to measure nicotinamide adenine dinucleotide (NADH) associated auto-fluorescence during embryo development using adapted confocal microscopy? Summary answer Non-invasive metabolic imaging is safe as no differences were observed between controls and illuminated embryos in terms of embryo development, blastocyst formation and implantation potential. What is known already Developing non-invasive methods that are reliable to assess oocyte and embryo quality has been a significant aim for assisted reproductive technologies. Changes in metabolic activity could lead to cell death or abnormal embryo development and low implantation potential. This could potentially be predicted by incorporating non-invasive measurements of metabolism. Metabolic imaging in embryos has been investigated through complex methodologies, however, scientific evidence for its utility during embryo development using simple technology remains unexplored. Measurements...

Research paper thumbnail of Uterine Fibroids (Leiomyomata) and Heavy Menstrual Bleeding

Frontiers in Reproductive Health, 2022

Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 7... more Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 75% within women of reproductive age. In ~30% of patients, uterine fibroids cause menorrhagia, or heavy menstrual bleeding, and more than half of the patients experience symptoms such as heavy menstrual bleeding, pelvic pain, or infertility. Treatment is symptomatic with limited options including hysterectomy as the most radical solution. The genetic foundations of uterine fibroid growth have been traced to somatic driver mutations (MED12, HMGA2, FH−/−, and COL4A5-A6). These also lead to downstream expression of angiogenic factors including IGF-1 and IGF-2, as opposed to the VEGF-driven mechanism found in the angiogenesis of hypoxic tumors. The resulting vasculature supplying the fibroid with nutrients and oxygen is highly irregular. Of particular interest is the formation of a pseudocapsule around intramural fibroids, a unique structure within tumor angiogenesis. These aberrations in vas...

Research paper thumbnail of P–790 Effects of COVID–19 quarantine period on Fertility Treatment and IVF Clinic management

Human Reproduction, 2021

Study question What are the effects of the initial COVID–19 response on the management of fertili... more Study question What are the effects of the initial COVID–19 response on the management of fertility clinics and clinical practice around the world? Summary answer In the COVID–19 outbreak, the large majority of fertility clinics worldwide suspended fertility treatments. In cycles that continued, there was a shift to frozen embryo-transfer. What is known already After the initial months of 2020 showed a rapid spread of the new Coronavirus SARS-CoV–2, the World Health Organisation declared a global pandemic on 11 March 2020. Occupation of health care facilities with acutely sick patients and the need to reduce infection transmission led to a reduction in capacity to perform elective medical procedures. Little was known on the global impact of COVID–19 on fertility care. With the implication of ‘lockdowns’ in different countries around the world to stop the spread of the virus, the question was posed on how fertility clinics and treatments would proceed moving forward. Study design, si...

Research paper thumbnail of 1295School age outcomes in IVF-conceived children compared with controls: a population linkage study

International Journal of Epidemiology, 2021

Background There is interest in longer term outcomes in IVF-conceived offspring compared with tho... more Background There is interest in longer term outcomes in IVF-conceived offspring compared with those conceived naturally. So far, the findings have been conflicting. The Australian Early Developmental Consensus (AEDC) assesses children in their first year of primary school across five domains. Methods To compare school entry outcomes in IVF-conceived children with naturally conceived controls, we undertook a statewide data linkage study, with perinatal data (2005-2014) linked to data from IVF providers in Victoria and the AEDC. Our approach to analysis included: complete case analysis, multiple imputation of missing data, consideration of clustering (siblings) and inverse probability weighted modeling to adjust for covariates. Our primary outcome was an AEDC score indicative of developmental vulnerability in two or more domains. We adjusted for confounders: child’s age at assessment, sex, highest level of maternal education, maternal age, parity, SEIFA (Socio-Economic Indexes for Are...

Research paper thumbnail of An evaluation of strategies to achieve greater than 90% coverage of maternal influenza and pertussis vaccines including an economic evaluation

BMC Pregnancy and Childbirth, 2021

Background Maternal immunisation is an essential public health intervention aimed at improving th... more Background Maternal immunisation is an essential public health intervention aimed at improving the health outcomes for pregnant women and providing protection to the newborn. Despite international recommendations, safety and efficacy data for the intervention, and often a fully funded program, uptake of vaccines in pregnancy remain suboptimal. One possible explanation for this includes limited access to vaccination services at the point of antenatal care. The aim of this study is to evaluate the change in vaccine coverage among pregnant women following implementation of a modified model of delivery aimed at improving access at the point of antenatal care, including an economic evaluation. Methods This prospective multi-centre study, using action research design, across six maternity services in Victoria, Australia, evaluated the implementation of a co-designed vaccine delivery model (either a pharmacy led model, midwife led model or primary care led model) supported by provider educ...