Beverley Vollenhoven - Academia.edu (original) (raw)
Papers by Beverley Vollenhoven
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.
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.
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,
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...
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. ...
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...
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,...
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...
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...
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...
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...
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...
PROTEOMICS, 2021
Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biolog... more Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry‐based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL‐sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion‐related proteins (LGALS1/3, S100A4/11) in fertile UL‐sEVs in the secretory (estrogen plus progesterone‐driven, EP) versus proliferative (estrogen‐driven, E) phase, with several players downregulated in infertile UL‐sEVs. Consistent with this, sEVs from EP‐ ve...
BACKGROUND A recent surge in interest at understanding alternative options to pharmacological ana... more BACKGROUND A recent surge in interest at understanding alternative options to pharmacological analgesia for managing acute pain has resulted in the development of a new research field that explores the feasibility of using Virtual Reality (VR) in pain relief regimes within clinical environments. OBJECTIVE To review the current evidence for the efficacy of VR as an analgesic in the management of acute pain in an inpatient setting. METHODS A comprehensive search was conducted till January 2019 on PubMed, Ovid Medline, EMBASE, and Cochrane Database of Systematic reviews as per the PRISMA guidelines. Search terms included ‘virtual reality', ‘vr’, and 'pain'. Primary articles with a focus on acute pain in the clinical setting were considered for the following review. Primary and secondary outcome measures: Quantification of outcomes for acute pain patients in relation to analgesic and anxiolytic effect, modulation of physiological indicators of pain, and adverse effects resul...
Human Reproduction, 2019
STUDY QUESTIONDoes female ageing have a negative effect on the DNA repair capacity of oocytes fer... more STUDY QUESTIONDoes female ageing have a negative effect on the DNA repair capacity of oocytes fertilised by spermatozoa with controlled levels of DNA damage?SUMMARY ANSWERCompared to oocytes from younger females, oocytes from older females have a reduced capacity to repair damaged DNA introduced by spermatozoa.WHAT IS KNOWN ALREADYThe reproductive lifespan in women declines with age predominantly due to poor oocyte quality. This leads to decreased reproductive outcomes for older women undergoing assisted reproductive technology (ART) treatments, compared to young women. Ageing and oocyte quality have been clearly associated with aneuploidy, but the range of factors that influence this change in oocyte quality with age remains unclear. The DNA repair activity prior to embryonic genomic activation is considered to be of maternal origin, with maternal transcripts and proteins controlling DNA integrity. With increasing maternal age, the number of mRNAs stored in oocytes decreases. This ...
Cochrane Database of Systematic Reviews, 2017
Analysis 2.12. Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy... more Analysis 2.12. Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 12 Duration of hospital stay (data table
Journal of Endometriosis and Pelvic Pain Disorders, 2019
Hysteroscopy is one of the most frequent procedures that a gynecologist will perform over their c... more Hysteroscopy is one of the most frequent procedures that a gynecologist will perform over their career. It is also one of the safest procedures. Operative hysteroscopy has an increased risk profile due to the nature of the surgery. The following review will address the issue of gas embolism in hysteroscopy. This review will look at the evidence regarding the likely causation, rates, and potential methods of minimizing risk to patients as well as treatment options available should this complication arise.
Human Reproduction, 2019
STUDY QUESTION Does IVF using donor sperm increase the risk of hypertensive disorders of pregnanc... more STUDY QUESTION Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)? SUMMARY ANSWER IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR. WHAT IS KNOWN ALREADY It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner—the concept of ‘primipaternity’. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR. STUDY DESIGN, SIZE, DURATION Theories about th...
Journal of the National Comprehensive Cancer Network, 2018
Background: Currently, no studies have attempted to validate the AJCC tumor (T) class for vulvar ... more Background: Currently, no studies have attempted to validate the AJCC tumor (T) class for vulvar cancer or examine its performance via clinical data. The goal of this study was to identify risk factors associated with poor outcomes in vulvar squamous cell carcinoma (vSCC) and compare prognostic discrimination of these outcomes between the AJCC T-classification system and the newly developed Brigham and Women's Vulvar Tumor Classification system (BWVTC). Methods: A 15-year, 2-center retrospective cohort study of primary vSCCs (N=226) was undertaken. Risk factors for poor outcomes, including local recurrence (LR), nodal and distant metastasis (NM and DM, respectively), disease-specific death (DSD), and overall death (OD) were determined using competing risks models. Poor outcomes were analyzed by T stage with regard to each classification system's distinctiveness, homogeneity, and monotonicity. Results: AJCC T stages were indistinct, with overlapping 95% confidence intervals for 10-year cumulative incidences of poor outcomes. Most poor outcomes occurred in low AJCC T stages: T1a/T1b contained 77% of LR, 79% of NM, 66% of DM/DSD, and 78% of OD, indicating poor homogeneity and monotonicity. Five risk factors were independent predictors of poor outcomes: history of lichen sclerosus, tumor diameter ≥2.0 cm, tumor depth ≥3.0 mm, poor differentiation, and mucosal involvement, and these were used to develop the BWVTC (BWVTC BWT1 = 0 risk factors; BWT2 = 1 risk factor; BWT3 = 2 risk factors; and BWT4 = ≥3 risk factors). The BWVTC displayed superior homogeneity and monotonicity, with most poor outcomes occurring in high T stages: T3/T4 contained 87% of LR, 92% of NM, 91% of DM/DSD, and 78% of OD (P<.001), although not all T stages were statistically distinct in this small cohort. Conclusions: The BWVTC offers improved prognostic discrimination over the AJCC T-classification system. Validation in population-based cohorts and in vulvar cancers other than SCC is needed.
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.
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.
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,
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...
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. ...
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...
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,...
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...
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...
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...
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...
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...
PROTEOMICS, 2021
Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biolog... more Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry‐based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL‐sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion‐related proteins (LGALS1/3, S100A4/11) in fertile UL‐sEVs in the secretory (estrogen plus progesterone‐driven, EP) versus proliferative (estrogen‐driven, E) phase, with several players downregulated in infertile UL‐sEVs. Consistent with this, sEVs from EP‐ ve...
BACKGROUND A recent surge in interest at understanding alternative options to pharmacological ana... more BACKGROUND A recent surge in interest at understanding alternative options to pharmacological analgesia for managing acute pain has resulted in the development of a new research field that explores the feasibility of using Virtual Reality (VR) in pain relief regimes within clinical environments. OBJECTIVE To review the current evidence for the efficacy of VR as an analgesic in the management of acute pain in an inpatient setting. METHODS A comprehensive search was conducted till January 2019 on PubMed, Ovid Medline, EMBASE, and Cochrane Database of Systematic reviews as per the PRISMA guidelines. Search terms included ‘virtual reality', ‘vr’, and 'pain'. Primary articles with a focus on acute pain in the clinical setting were considered for the following review. Primary and secondary outcome measures: Quantification of outcomes for acute pain patients in relation to analgesic and anxiolytic effect, modulation of physiological indicators of pain, and adverse effects resul...
Human Reproduction, 2019
STUDY QUESTIONDoes female ageing have a negative effect on the DNA repair capacity of oocytes fer... more STUDY QUESTIONDoes female ageing have a negative effect on the DNA repair capacity of oocytes fertilised by spermatozoa with controlled levels of DNA damage?SUMMARY ANSWERCompared to oocytes from younger females, oocytes from older females have a reduced capacity to repair damaged DNA introduced by spermatozoa.WHAT IS KNOWN ALREADYThe reproductive lifespan in women declines with age predominantly due to poor oocyte quality. This leads to decreased reproductive outcomes for older women undergoing assisted reproductive technology (ART) treatments, compared to young women. Ageing and oocyte quality have been clearly associated with aneuploidy, but the range of factors that influence this change in oocyte quality with age remains unclear. The DNA repair activity prior to embryonic genomic activation is considered to be of maternal origin, with maternal transcripts and proteins controlling DNA integrity. With increasing maternal age, the number of mRNAs stored in oocytes decreases. This ...
Cochrane Database of Systematic Reviews, 2017
Analysis 2.12. Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy... more Analysis 2.12. Comparison 2 GnRHa treatment versus no pretreatment or placebo before hysterectomy (operative and postoperative), Outcome 12 Duration of hospital stay (data table
Journal of Endometriosis and Pelvic Pain Disorders, 2019
Hysteroscopy is one of the most frequent procedures that a gynecologist will perform over their c... more Hysteroscopy is one of the most frequent procedures that a gynecologist will perform over their career. It is also one of the safest procedures. Operative hysteroscopy has an increased risk profile due to the nature of the surgery. The following review will address the issue of gas embolism in hysteroscopy. This review will look at the evidence regarding the likely causation, rates, and potential methods of minimizing risk to patients as well as treatment options available should this complication arise.
Human Reproduction, 2019
STUDY QUESTION Does IVF using donor sperm increase the risk of hypertensive disorders of pregnanc... more STUDY QUESTION Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)? SUMMARY ANSWER IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR. WHAT IS KNOWN ALREADY It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner—the concept of ‘primipaternity’. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR. STUDY DESIGN, SIZE, DURATION Theories about th...
Journal of the National Comprehensive Cancer Network, 2018
Background: Currently, no studies have attempted to validate the AJCC tumor (T) class for vulvar ... more Background: Currently, no studies have attempted to validate the AJCC tumor (T) class for vulvar cancer or examine its performance via clinical data. The goal of this study was to identify risk factors associated with poor outcomes in vulvar squamous cell carcinoma (vSCC) and compare prognostic discrimination of these outcomes between the AJCC T-classification system and the newly developed Brigham and Women's Vulvar Tumor Classification system (BWVTC). Methods: A 15-year, 2-center retrospective cohort study of primary vSCCs (N=226) was undertaken. Risk factors for poor outcomes, including local recurrence (LR), nodal and distant metastasis (NM and DM, respectively), disease-specific death (DSD), and overall death (OD) were determined using competing risks models. Poor outcomes were analyzed by T stage with regard to each classification system's distinctiveness, homogeneity, and monotonicity. Results: AJCC T stages were indistinct, with overlapping 95% confidence intervals for 10-year cumulative incidences of poor outcomes. Most poor outcomes occurred in low AJCC T stages: T1a/T1b contained 77% of LR, 79% of NM, 66% of DM/DSD, and 78% of OD, indicating poor homogeneity and monotonicity. Five risk factors were independent predictors of poor outcomes: history of lichen sclerosus, tumor diameter ≥2.0 cm, tumor depth ≥3.0 mm, poor differentiation, and mucosal involvement, and these were used to develop the BWVTC (BWVTC BWT1 = 0 risk factors; BWT2 = 1 risk factor; BWT3 = 2 risk factors; and BWT4 = ≥3 risk factors). The BWVTC displayed superior homogeneity and monotonicity, with most poor outcomes occurring in high T stages: T3/T4 contained 87% of LR, 92% of NM, 91% of DM/DSD, and 78% of OD (P<.001), although not all T stages were statistically distinct in this small cohort. Conclusions: The BWVTC offers improved prognostic discrimination over the AJCC T-classification system. Validation in population-based cohorts and in vulvar cancers other than SCC is needed.