bluuebunny/crossref_metadata_2025 huggingface dataset:
NMN Supplementation Rescues Fertility and Bone Strength in Chemotherapy-Treated Mice
Authors: MARINOVA Maria B. , HO Wing-Hong Jonathan , BERTOLDO Michael J. , LOVRIC Vedran , SELESNIEMI Kaisa , WALSH William R. , SINCLAIR David A. , WALTERS Kirsty , GILCHRIST Robert B. , WU Lindsay E.
Published: November 2022

Background: Cancer survivors often face infertility as a result of ovarian toxicity from cytotoxic chemotherapy drugs, which trigger a cascade of events ultimately causing follicular reserve exhaustion and endocrine disruption. Apart from infertility, this can have severe consequences on women’s health with early-onset menopause and a decline in bone health. For girls with cancer, ovarian tissue cryopreservation (OTC) is the only option for fertility preservation. OTC + transplantation may provide future fertility potential, but it provides minimal/no protection from endocrine failure and osteoporosis.

Aim: To assess the effects of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) on ovarian function, fertility, and late-life bone health.

Method: 7-day old female mice were treated +/- cisplatin (2mg/kg). Two weeks later, +/- NMN was delivered in drinking water (2g/L) and sustained throughout life. A breeding trial was conducted at 6 weeks, and to assess late-life effects on bone structure, mice were maintained until euthanasia at 24 months of age.

Results: Cisplatin caused a dramatic decline in all fertility endpoints. NMN supplementation rescued breeding performance in cisplatin treated animals by 5-fold (p=0.015), as measured by the cumulative number of pups/female. Given the importance of ovarian function to estrogen release and the risk of osteoporosis, we sought to determine the impacts of these interventions on late-life bone health. Bones were subject to mechanical and structural analysis to assess differences in the onset of osteoporosis. In cisplatin treated animals, NMN rescued cortical bone thickness (femur diaphysis p[Formula: see text]0.0001, femur metaphysis p=0.0081, tibia p=0.0072), bone volume (femur p=0.0015, tibia p=0.0102), and bone density (femur p=0.0463) to control levels, and increased mechanical strength (tibia, p=0.0024).

Conclusion: Long-term NMN treatment delivered following chemotherapy protected against subsequent ovarian failure and infertility, and notably improved late-life bone health, possibly due to the prevention of premature ovarian failure.
Mitochondrial Donation and Egg Donor Consent in Australia
Authors: MILLS Catherine , SUTTON Elizabeth , KOPLIN Julian , KNEEBONE Ezra , LUDLOW Karinne , NEWSON Ainsley
Published: November 2022

Background: Legislation to permit mitochondrial donation (MD) in Australia was introduced into Federal Parliament in early 2021, and the techniques may be legalized and made available soon. MD enables women affected by disease-causing mutations in their mitochondrial DNA to have a genetically related child who is unlikely to inherit these mutations.

MD relies on the donation of oocytes. Australia’s oocyte donation system does not meet current demand for oocytes and MD would add to this. Consequently, the implementation of MD would raise critical questions about the system of procuring donors and using their oocytes. The proposed model for implementing MD in Australia does not address these issues. We address two key inter-related concerns – oocyte availability and donor consent – in how best to meet current and future demand for donor oocytes.

Aim: To consider ethical, social, and regulatory issues arising from the proposed implementation of MD in Australia, particularly oocyte availability and donor consent issues.

Method: We discuss the current system of oocyte donation in Australia and consider likely impacts of MD on this. We review alternative systems that have been proposed to enhance the availability of oocytes, focusing on ethical aspects of these with reference to specific features of the Australian context, donor consent, and MD.

Results: MD will increase demand for oocytes if introduced in Australia. Alternative procurement systems to address the shortage of oocytes may be required. Refining the system of consent used for oocyte donation may be an important feature of increasing oocyte availability for MD.

Conclusion: As Australia presses ahead with the potential implementation of MD, consideration should be given as to whether the current system for oocyte donation is adequate. We conclude that it is necessary to consider alternative systems for enhancing oocyte availability in Australia, which, in some circumstances, may include changing consent procedures.
Inter-Cycle Variation in Endometrial Thickness in Fresh Embryo Transfer Cycles: Predictors and Association with Pregnancy Outcome
Authors: HUNT Sarah , LI Xiaohong , LUO Shan , HUANG Wei , MOL Ben
Published: November 2022

Background: The use of intracytoplasmic sperm injection (ICSI) has increased substantially worldwide, primarily in couples with non-male factor infertility. We recently published the results of a large randomised controlled trial (RCT) comparing ICSI and IVF showing no significant improvement of ICSI over IVF in couples with normal semen concentration and motility. Here, we assess the cost-effectiveness of ICSI in these couples, with additional attention for subgroups.

Aim: To evaluate the inter-cycle variation in endometrial combined thickness (ECT) in fresh embryo transfer cycles

Method: This was a retrospective cohort study in a single university affiliated fertility clinic in Chengu, China. We studied women undergoing IVF/ ICSI treatment in a fresh stimulated cycle, and measured endometrial combined thickness on the day of HCG trigger in consecutive stimulated IVF/ICSI cycles. Inter-cycle variation in ECT was the main outcome measure. Secondary outcomes were the relationship between ECT and treatment outcomes clinical pregnancy, live birth and miscarriage.

Results: The mean ECT in consecutive fresh stimulated cycles was 10.28 ⊠ 2.15mm in cycle 1 (n=7038), 9.93 ⊠ 2.11mm in cycle 2 (n=1287), 9.49 ⊠ 2.22mm in cycle 3 (n=148) and 8.63 ⊠ 1.82mm in cycle 4 (n=17) (p [Formula: see text]0.01.). An incremental increase in the clinical pregnancy rate was demonstrated for each additional millimetre in ECT up to a threshold level of 12-15mm. There was no evidence of systematic bias on the visual assessment of the Bland Altman plot in women undergoing 2 consecutive cycles of treatment (mean bias 0.46, (95% limits of agreement -5.62 to 5.65)). Multivariate predictors of ECT were the number of previous treatment cycles, secondary infertility, infertility diagnoses of anovulation, endometriosis, male factor or unexplained infertility and the number of follicles greater than 14mm on the day of HCG trigger. There was a small, significant interaction between female age and ECT on the outcome clinical pregnancy.

Conclusion: There is a slight decrease in mean ECT in women undergoing consecutive stimulated IVF/ICSI cycles which is potentially explained by the increased occurrence of pregnancy with thicker ECT. Each millimetre increase in late follicular ECT increases the odds ratio of clinical pregnancy to a threshold level of 12-15mm.
Pharmacological Antagonism of the Kisspeptin-Neurokinin System Improved Adverse Metabolic Traits in a PCOS Mouse Model
Authors: SUCQUART Irene E. , NAGARKAR Ruchi , EDWARDS Melissa C. , PARIS Valentina RODRIGUEZ , AFLATOUNIAN Ali , BERTOLDO Michael J. , CAMPBELL Rebecca E. , BEGG Denovan P. , HANDELSMAN David J. , PADMANABHAN Vasantha , ANDERSON Richard A. , GILCHRIST Robert B. , WALTERS Kirsty A.
Published: November 2022

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine condition affecting up to 20% of reproductively aged women worldwide. Owing to an ambiguous etiology and complicated pathophysiology, current PCOS treatments remain purely symptomatic. Aberrations in androgen receptor driven neuroendocrine pathways are reportedly involved in the pathogenesis of PCOS. A clinical trial, focusing on the androgen regulated kisspeptin-neurokinin B-dynorphin system, treated women with PCOS with a neurokinin B receptor (neurokinin 3 receptor, NK3R) antagonist and reported improvements in LH secretion, LH pulses and testosterone levels.

Aim: To investigate if pharmacological antagonism of NK3R can ameliorate PCOS traits in a mouse model.

Method: Reproductive and metabolic features of PCOS were evaluated in control and dihydrotestosterone (DHT)-induced PCOS mice, treated +/-NK3R antagonist (MLE4901) for 28 days at a dose of 25mg/kg/day.

Results: PCOS-like mice were acyclic and exhibited ovulatory dysfunction, which were not rescued by NK3R antagonist treatment. Compared to control mice, the PCOS-like mice displayed a significant increase in total body weight and inguinal, parametrial, mesenteric, retroperitoneal, and brown fat pad weights (all P[Formula: see text]0.01). NK3R antagonism partially reversed the total body weight and fat pad weight gains (all P[Formula: see text]0.01) in all white fat depots of PCOS-like mice. PCOS-like mice also displayed adipocyte hypertrophy and increased leptin levels compared to control mice (both P[Formula: see text]0.01), which were improved with NK3R antagonism treatment (P[Formula: see text]0.01 and P[Formula: see text]0.05, respectively). Moreover, DHT exposure significantly reduced the respiratory exchange ratio (RER) (P[Formula: see text]0.01), whereas NK3R antagonism significantly increased RER compared to control mice (P[Formula: see text]0.01), suggesting a metabolic shift in the PCOS-like mice treated with the NKR3 antagonist.

Conclusion: These findings show that pharmacological antagonism of the kisspeptin-neurokinin system may be a beneficial treatment for adverse metabolic features of PCOS. This study also reveals important new insights into neuroendocrine androgen actions in the pathogenesis of PCOS.
The Complexity Around Mosaic Embryo Decision Making– A Genetic Counselling Perspective
Authors: TEED Maddie , JEDWAB Abbie , STUTTERD Chloe , SORBY Kelli , WEEKS Alice
Published: November 2022

Background: In recent years there is an evident increase in the interest of transferring mosaic embryos. Our genetic counselling team have reported mosaic results to over 250 patients since the beginning of 2020, and there is an upward trend in patient interest, and willingness to consider transfer. As patients continue to request the transfer of mosaic embryos, and research advances regarding transfer outcomes, it is critical that the genetic/medical professionals who counsel these patients are aware of the complex factors that feed into important decision making.

Aim: To explore the genetic counselling perspectives on counselling issues for patients considering transfer of a mosaic embryo, including barriers, commonalities, and themes that impact their decision pathway.

Method: Fundamental thematic analysis on genetic counselling consultation notes detailing questions, concerns, motivations, and decision outcomes was utilized for gaining a preliminary perspective. Specific case vignettes help highlight the complexity in these decisions.

Results: Depending on the result, patients with PGT-A NGS reported mosaic embryo(s) have the option to consider transfer, retaining, or discarding these embryos. Thematic analysis revealed themes regarding factors that influence decision making. Patients less likely to proceed with embryo transfer: highly risk averse, poor management of uncertainty, perceived limited options, lived experience of unhealthy pregnancy or birth (ie. family/friend), complex reproductive history (ie. multiple miscarriages), and high emotional burden of the decision. Patients more likely to proceed with transfer: extensive fertility journey, high level of information comprehension, encouraging community support, low emotional burden of the decision, and awareness of age-related limitations.

Conclusion: Our work highlights potential benefits of a genetic counselling guideline of factors to present/challenge to patients, as each patient has their own journey.
Expectations and Experiences of Australian Online Sperm Donors Who Have Early Contact with Recipient Parents and Donor Conceived Children
Authors: VOLKS Cal , KELLY Fiona
Published: November 2022

Background: In recent years there has been an increase in the offering and uptake of informal online sperm donation in Australia. While there are a handful of survey-based studies exploring the motives of online sperm donors in Holland and the UK, (Graham et al 2019; Whyte 2018; Freeman et al 2016; Woetsneburg et al 2016) there is little qualitative research that enables a detailed analysis of the experiences of online donors.

Aim: This paper aimed to explore the motivations experiences and outcomes of Australian and New Zealand online sperm donors who have had early contact (before the age of 18) with their donor conceived children and recipient parents.

Method: Six semi-structured qualitative interviews were conducted with Australian online sperm donors who have had early contact with their donor conceived children. Additional data has been drawn from an analysis of a variety of media sources about online donors, including interviews with online sperm donors from the podcast Sperm Donation World and from newspaper stories about online sperm donors in Australia and New Zealand.

Results: There was no universal experience or set of motivations among the donors. Some online sperm donors wanted to co-parent, while others wanted only limited contact with their donor conceived children. However, intentions did not always remain stable. Initial preferences changed during the process of donating and relating to the recipients and donor conceived children. Some study participants’ role preference aligned with what the RPs wanted, while others reported discord in their relationships with RPs, including around contact with their DCC.

Conclusion: Our findings suggest that there is the potential for a mismatch of expectations between online sperm donors and recipient parent(s).
Ovarian Stimulation Strategies for Intrauterine Insemination in Couples with Unexplained Infertility - A Systematic Review and Individual Participant Data Meta-analysis
Authors: WESSEL J.A. , DANHOF N.A. , VAN EEKELEN R. , DIAMOND M.P. , LEGRO R.S. , PEERAER K. , ERDEM M. , DANKERT T. , ECOCHARD R. , MOL B.W. , VAN WELY M. , MOCHTAR M.H. , WANG R.
Published: November 2022

Background: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for couples with unexplained infertility. Individual participant data meta-analysis (IPD-MA) is the gold standard for evidence synthesis.

Aim: To compare the effectiveness and safety of ovarian stimulation with gonadotrophin, Letrozole and clomiphene citrate (CC) and to explore treatment-covariate interactions for important baseline characteristics in women undergoing IUI.

Method: We searched electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). We included randomised controlled trials (RCTs) comparing IUI-OS with gonadotropins, Letrozole or CC among couples with unexplained infertility. We excluded dose comparing studies of the same drug. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. We used a one-stage approach using a random effects model.

Results: Six RCTs (n= 2299) provided IPD. Gonadotropins increased the chance of a live birth compared to both CC (5 RCTs, 1946 women, RR 1.28, 95%CI 1.10 to 1.49, I2 = 25%, moderate-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.77 95%CI 0.58 to 1.03). Gonadotropins increased the risk of a multiple pregnancy compared to both CC (4 RCTs, 1696 women, RR 2.17, 95%CI 1.33 to 3.55, I2 = 69%, low-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.71, 95%CI 0.33 to 1.56). No strong evidence on the treatment-covariate interactions (female age, BMI or primary versus secondary infertility) was found.

Conclusion: Gonadotropins increased the chance of a live birth compared to both CC and Letrozole but also increased the chance of a multiple pregnancy. Further RCTs comparing Letrozole and other interventions in couples with unexplained infertility are needed.
Scoping Appropriate Quality of Life Dimensions for the Development of a Meaningful Quality of Life Tool for PCOS. The “HERAQoL-P”
Authors: AVERY Jodie , PIROTTA Stephanie , JISKOOT Geranne , GIBSON-HELM Melanie
Published: November 2022

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine condition in women, with a range of symptoms related to problems with fertility, weight gain, mental health and sleep, and is not a stable condition over the life course. Women with PCOS have different experiences of Quality of Life (QoL) depending on their age, ethnicity, socio economic status, severity and phenotype. QoL is an important health outcome, yet measures include predefined items, that may be unimportant to individuals. Existing PCOS QoL measures may not capture the full physical, emotional, and social impact of PCOS, all of which need to be addressed within person-centred care in order to achieve the best possible health outcomes in both the short and long term.

Aim: We aim to scope and understand priorities for quality of life (QoL) dimensions from women with PCOS throughout life, to provide a conceptual framework for the creation of a meaningful, scientifically validated quality of life tool in the future.

Method: Based on the Schedule for the Evaluation of Individual Quality of Life (SEIQoL) questionnaire, we are surveying 200 women and interviewing 20-30 women diagnosed with PCOS about aspects of life important for their quality of life.

Questions in the interview include the impact of this condition on physical, mental and emotional health, and understand whether PCOS affects women differently according to their profile of symptoms and background.

Results: This work provides the basis for developing a new QoL tool, reflecting the diverse PCOS features with the greatest impact, enabling better evaluation of Patient Reported Outcomes.

Conclusion: A high-quality QoL questionnaire could highlight women’s specific priorities, and then measure whether their healthcare addresses such priorities. We will then create the HERAQol-P, with extensive potential to have impact, in both research and clinical care, adding to the evidence base for PCOS.
ANZARD Data Linkage – Agreement Between Births Recorded by Clinics and in NSW Perinatal Data Collection
Authors: CHAMBERS Georgina M. , CHOI Stephanie K.Y. , IRVINE Katie , VENETIS Christos , HARRIS Katie , HAVARD Alys , NORMAN Robert J. , LUI Kei , LEDGER William , JORM Louisa R.
Published: November 2022

Background: Fertility clinics submit treatment data on all ART cycles to the Australian and New Zealand Assisted Reproductive Technology Database (ANZARD) as part of their accreditation. The National Perinatal Epidemiology and Statistics Unit (NPESU), who manages ANZARD, is undertaking a study involving the linkage of ANZARD to state and commonwealth datasets to investigate health outcomes of infants born from fertility treatments.

Aim: To describe the creation and performance of the linked dataset and to evaluate the agreement between births recorded by clinics and those recorded in state perinatal data collections (PDC).

Method: The linked dataset was created by linking the ANZARD to NSW and ACT administrative datasets (performed by NSW Centre for Health Record Linkage (CHeReL)) and to Medicare Benefits Scheme and Pharmaceutical Benefits Schedule (performed by AIHW). The CHeReL’s Master Linkage Key (MLK) was used as a bridge between ANZARD’s statistical linkage key and state administrative datasets. Linkage rates and concordance between births recorded in ANZARD and PDCs was evaluated.

Results: A 96.7% linkage rate was achieved between women recorded in ANZARD and CHeReL’s MLKs. A reconciliation of ANZARD-recorded births among NSW residents found that 94.2% (95% CI: 93.9-94.4%) of births were also recorded in NSW/ACT PDCs. A proportion of the missing births could be to women who had ART treatment in NSW but birthed in a different Australian state or country. A high concordance rate (>99%) was found in plurality status and birth outcome between ANZARD and PDCs.

Conclusion: High linkage rates can be achieved with partially identifiable data and population spines, such as the CHeReL’s MLK, can be successfully used to link clinical registries and administrative datasets. This linkage resource will provide invaluable information on the safety of the ART and non-ART treatment, and the role of subfertility on the fertility treatments for Australia and beyond.
Developing and Implementing a Core Outcome Set for Ectopic Pregnancy
Authors: CHONG Krystle , MOL Ben
Published: November 2022

Background: Diagnosis of ectopic pregnancy (EP) has improved significantly in the last few decades, and RCTs remain the mainstay of assessing the effectiveness and safety of treatments. The pooling of individual RCT data is likely to provide the best evidence to inform clinical practice. However, currently published data in ectopic pregnancy has reported many different outcomes, which are themselves often defined and measured in distinct ways.

The lack of consensus and level of variation results in an inability to compare the results of individual RCTs, and consequently directly impacts the usefulness of research to inform patients and clinicians in clinical practice.

Aim: The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy.

Methods and Analysis: We have established an international steering group of stakeholders, including healthcare professionals, researchers, and individuals with lived experience with EP. We have identified potential outcomes from a comprehensive literature review of published randomised controlled trials. We have utilised a modified Delphi method to prioritize outcomes.

Results: Key stakeholders have been invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). 424 enrolled participants, with 86% completing round 1, comprising of 117 (32%) healthcare professionals, 237(64%) individuals with lived experience, 14(4%) researchers. Highly rates outcomes included the resolution of EP, psychological impact, and future fertility outcomes.

Conclusion: Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes over 3 rounds. Implementation of a core outcome set will enable collection and reporting of data in a standardised fashion. This will allow standardisation of research to guide and inform clinical practice and enhance patient centred care.
Merging Motherhood and Medicine: A Qualitative Study Exploring Barriers and Enablers to Motherhood Among Australian Female Doctors
Authors: COLLIE Erika , LEW Raelia , PEATE Michelle
Published: November 2022

Background: Despite the increasing ‘feminisation’ of the Australian medical workforce, female doctors remain under-represented in leadership positions, many specialty areas, and renumeration levels. A key factor implicated in this disparity is the unequal impact of parenthood on mothers. Australian research on this issue is lacking.

Aim: To identify the barriers and enablers experienced by Australian female doctors, when combining motherhood with a medical career.

Method: Semi-structured telephone interviews were conducted with 18 female Australian physician mothers, during March and May 2020. Interview data were examined using thematic analysis to extract key themes.

Results: Six key barriers and seven key enablers were identified. Barriers (B1-6) largely reflected structural and cultural issues operating within health services and the wider medical profession, specifically the (B1) experience of working in medicine; (B2) demands of postgraduate specialty training; (B3) attitudes towards mothers in medicine; (B4) gender inequality; (B5) insufficient entitlements and support; and (B6) competing priorities, conflicting roles. Enablers (E1-7) were predominantly personal and interpersonal supports relating to (E1) supportive partnerships; (E2) non-traditional gender roles; (E3) capacity to outsource; (E4) doctors supporting doctors; (E5) flexible work arrangements; (E6) increasing acceptance and support; and (E7) capacity to combine career and family.

Conclusion: This was the first Australian qualitative study to explore motherhood experiences among female doctors. The results indicate that Australian physician-mothers encounter considerable structural and cultural barriers during all stages of motherhood. To facilitate motherhood in medicine, further research is needed to inform policy development and support provisions within Australian health systems.
pHantastic Embryos and Where to Find Them: Can a Real-Time pH Monitoring System Represent the pH Environment of Culture Media?
Authors: DEAN Casey , GUNASEGARAN Kavyadharshini , GABRIEL Justine , IACOBELLI Daniela , SORBY Kelli
Published: November 2022

Background: Maintaining optimal pH of culture media reduces environmental stressors on gametes and embryos, which has been shown to be critical in supporting embryo development. There are many options to determine pH but none are ideal for use in a laboratory setting. SignipHy™ is a system that monitors pH in real-time within the incubator environment without disturbing the incubator or exposing the media.

Aim: To determine if SignipHy can provide an accurate representation of the dynamic pH in culture media across a range of environmental conditions.

Method: pH of G1+ under Ovoil in a 5-well dish was measured using a blood gas analyser at regular intervals under multiple experimental conditions.

Statistical analyses used repeated measures ANOVA, Pearson’s Correlation and Linear regression.

Results: pH of media undergoing initial equilibration was found to decrease more rapidly in culture dishes (ΔpH 0.228/hr) than SignipHy cuvettes (ΔpH 0.160/hr) over a 6 hour period (p=0.0005). Full equilibration was achieved in the culture dishes after 4 hours, while the SignipHy cuvettes stabilised after 6 hours.

When fully equilibrated dishes were exposed to 4% CO2, pH in the culture dishes increased more rapidly (ΔpH 0.098/hr) than SignipHy cuvettes (ΔpH 0.060/hr). Similarly, equilibrated media exposed to 2% CO2 showed an increase of pH in culture dishes of 0.171/hr compared with SignipHy cuvettes at 0.150/hr.

Unsurprisingly when media in a culture dish without oil was exposed to a humified CO2 incubator the pH shift was rapid (ΔpH 0.258/hr). Laboratories should be conscious of rapid pH shifts in culture media without oil. Which can be optimal when needing to equilibrate media quickly, but of concern when handling dishes.

Conclusion: SignipHy was found to be a viable representation of pH under multiple experimental conditions, however, the rate of change was found to be slower compared to culture dishes.
Biomarkers of Endometriosis
Authors: GARRETT Kerryn L. , KILLEEN Aideen P. , CASEY Tammy M. , ITO Jun , ISMAIL Deem , CHEN Lianzhi , RAJU Mufaidha , ANDRONIS Christina , BRINGANS Scott , LISPCOMBE Richard J. , ROGERS Peter A.W. , HOLDSWORTH-CARSON Sarah J.
Published: November 2022

Background: Endometriosis is an under-recognised and often misdiagnosed chronic disease that affects one in ten women. It occurs when cells similar to those that line a uterus grow in other parts of the body, usually around the pelvis. The current gold standard for diagnosis of endometriosis is direct visualisation by histological analysis which can only be achieved by an invasive laparoscopy. It is estimated 176 million women and girls around the world are living with endometriosis. The condition costs $7.7 billion a year in direct medical expenses and lost productivity in Australia alone.

Aim: To analyse a series of plasma samples from patients with clinically diagnosed endometriosis, others with gynaecological symptoms without endometriosis and otherwise healthy controls to identify biomarkers to differentiate these groups and potentially aid in endometriosis diagnosis.

Method: A standard proteomic discovery workflow was used to search for unique biomarkers of endometriosis. Initially, pooled plasma samples from three distinct groups of patients were tested. The first group had symptoms of endometriosis with a laparoscopic/histology confirmed diagnosis. The second group also had symptoms, but the laparoscopy confirmed no endometriosis or an alternate diagnosis. The third group were healthy matched controls. The pooled plasma samples were quantitatively profiled against each other with a triplicate experiment.

A validation of the biomarkers identified as significant in the discovery phase, was then undertaken in a larger clinical cohort (n=902) using a targeted multiplex mass spectrometry assay using multiple reaction monitoring (MRM). Statistical analyses were caried out using Stata and logistical regression was used to evaluate associations of biomarkers with binary clinical outcomes.

Results: Out of the 943 proteins identified with [Formula: see text] 2 significant peptides in the initial discovery workflow, 47 were determined as being differential biomarkers across the three clinical groups.

The derived targeted MRM assay was tested on the clinical validation cohort, and a number of candidate biomarkers were significantly associated, thereby indicating their potential for use in the diagnosis of endometriosis.
Non-Invasive Metabolic Live Cell Imaging of Early Embryo Development Using Novel Adapted Confocal Microscopy in Ageing
Authors: HORTA Fabrizzio , NEWMAN Hope , VARGAS-ORDAZ Erick J. , CADARSO Victor J. , NOSRATI Reza , NEILD Adrian , VOLLENHOVEN Beverly , CATT Sally
Published: November 2022

Background: Developing non-invasive methods that are reliable to assess embryo quality has been a significant aim for assisted reproductive technologies. Changes in metabolic activity could lead to abnormal embryo development and implantation potential which could be potentially predicted by incorporating non-invasive measurements of metabolism. Metabolic imaging of nicotinamide adenine dinucleotide (NADH) has been well studied in cell lines, however, evidence for its use in embryo development is limited. Measurements of NADH during advanced-reproductive-age could be a useful tool as the auto-fluorescence of NADH is a straightforward representation of mitochondrial function and cellular redox status.

Aim: To determine potential differences in NADH levels associated in early embryo development from young and old mice using novel adapted confocal microscopy.

Methods: Oocytes from two groups of 20 super-ovulated female mice (Young: 5-8 weeks old, n=10; Old: 45-52 weeks old, n=10) were inseminated through in-vitro fertilisation (IVF). Inseminated oocytes (Young:93; Old:64) were assessed for fertilisation and embryo development to the blastocyst stage. Early embryos (Young:44; Old:34) from both young and old groups were assessed for NADH levels during embryo development every 2 and 3 hours respectively in separated experiments, using arbitrary units of auto-fluorescence (AU).

Results: IVF experiments showed no significant differences in fertilisation rates between age groups but with significant differences in blastocyst formation (Young: 90.9%; Old: 66.7%; p[Formula: see text]0.05). Embryos from young and old females showed significantly different NADH levels during embryo development (Young: 29,889 ±864AU; Old: 25,972 ±260AU; p[Formula: see text]0.0001). Zygotes that reached the blastocyst stage in old females had significantly decreased NADH levels compared to young females (Young: 31,508 ±853AU, Old: 26,417 ±186AU; p=0.0002).

Conclusion: Our study indicates different levels of NADH activity during early embryo development associated to ageing and blastocyst formation. Non-invasive measurements of NADH could be applied to determine embryo metabolic activity associated to ageing using simple technology.
Validation of sORP, a Measure of Oxidative Stress, in Australian Population
Authors: SHIH Yu-Cih , ELLIOT Peter , AN Jing , LEUNG Pui Ying , KILLEEN Aideen
Published: November 2022

Background: Excessive reactive oxygen species are normally eliminated by seminal plasma free radical antioxidant scavengers and enzymes. Assessing the oxidation reduction potential of seminal fluid (mV/million sperm/mL) enables the detection of an imbalance in this biological mechanism, and identifies patients exhibiting oxidative stress (OS). A novel technology, MiOX[Formula: see text], detects static Oxidation-Reduction Potential (sORP), providing a comprehensive measure of oxidants and reductants in semen, with the advantages of rapid, simple and less sample volume compared to the conventional chemiluminescence assay.

Aim: This study aims to validate the MiOX[Formula: see text] analyser for the detection of OS in seminal fluid, in the Australian population.

Method: Samples were collected from consenting patients attending the Royal Women’s Hospital Andrology Unit for semen analysis (n=144); those with [Formula: see text]1 million/ml were excluded. Semen analysis was carried out as per WHO 2010 guidelines, and replicate sORP measurements taken within 60 minutes of ejaculation.

Results: Replicate sORP measurements from semen samples (n=20) demonstrated no significant differences between and within operators, and across days. sORP did not vary between samples incubated at 4[Formula: see text]C, room temperature, and 37[Formula: see text]C, or samples subjected to mechanical agitation. Freeze-thaw resulted in a significant increase in sORP (p=0.031). The stability of sORP measurements was demonstrated up to 4 hours after ejaculation, however, significant increases were observed after 24 and 48 hours (p[Formula: see text]0.05).

Patients grouped according to normal and abnormal total motile sperm count (TMSC) demonstrated significantly different sORP (0.75 ± 0.86, 5.02 ± 5.32, p[Formula: see text]0.001). A preliminary ROC analysis, using TMSC, revealed a cut-off value of 1.07 mV/106 sperm/mL (AUC=0.904) with 81.1% sensitivity and 81.3% specificity.

Conclusion: Results from the technical validation are consistent with other studies. The clinical reference range validation requires further patient samples to better reflect the distribution of results observed in the low TMSC group.
Post-Thaw Sperm Recovery Rates; A Retrospective Study
Authors: LEUNG Pui Ying , ELLIOT Peter , AN Jing , SHIH Yu-Cih , KILLEEN Aideen
Published: November 2022

Background: Cryopreservation is currently the only fertility preservation option available to patients undergoing gonadotoxic treatment. Much research in the field focusses on techniques, media and equipment employed to cryopreserve cells, and demonstrating cell viability after using such. Comparatively, there is a death of information available on the procedures and equipment used to thaw cryopreserved cells, or estimates for post-thaw recovery.

Aim: This is a retrospective study assessing semen parameters in post-thawed specimen from patients who attended the Royal Women’s Hospital Andrology Unit for sperm cryopreservation prior to gonadotoxic or other treatments. The study aims to examine the relationship between sperm cryopreservation technique, media and period of storage with post-thaw sperm parameters.

Method: Patients with written consent to discard their stored semen were selected for inclusion in the study (n=59); samples with sperm concentration [Formula: see text]1 million/ml prior to freezing (n=11) were excluded. Semen samples were thawed accordingly: 5 minutes at room temperature followed by incubation at 37[Formula: see text]C for sperm straws; vials were transferred directly to a mixer incubator at 37[Formula: see text]C. All samples were immediately assessed for sperm concentration and motility. Recovery rates were calculated and data were analysed using SPSS (IBM, USA) version 25.

Results: Progressive motility recovery was 32.4% ± 20.6. Patients were divided into groups according to period of storage, and showed no significant differences for recovery of motility and concentration (p=0.44, 0.96, respectively). Furthermore, progressive motility recovery rates were not significantly different between freezing techniques (p=0.116) and media (p=0.099).

Conclusion: Data from this study are preliminary and further study is warranted to fully extrapolate the relationship between sperm cryopreservation protocols and period of storage on recovery rates. The lack of relationship between these factors exhibited in the data could suggest that research and development in thaw technologies may be more pertinent to improving sperm recovery rates.
Surrogates’ and Intended Parents’ Experiences of Surrogacy: A Systematic Review
Authors: KNEEBONE Ezra , BEILBY Kiri , HAMMARBERG Karin
Published: November 2022

Background: Surrogacy arrangements can be conducted domestically, where the surrogate and intended parents live in the same country, or internationally, where the intended parents engage a surrogate in a foreign destination. Understanding the experiences of people participating in surrogacy arrangements can inform policy to protect the best interests of all parties.

Aim: To review the evidence relating to surrogates’ and intended parents’ experiences of surrogacy arrangements.

Method: Studies of surrogates’ and intended parents’ experiences of a surrogacy arrangement, published since 2005 in English language peer reviewed journals were identified by searching Embase, Medline, PsycInfo and Scopus. Data relating to each participant group were synthesised separately using thematic analysis. Methodological quality of the studies was assessed using the QualSyst scoring system.

Results: 67 articles were included in the synthesis. The mean QualSyst score was 0.78/1. Four themes relating to surrogates’ (exercising agency, making sense of their maternal identity, forming a relationship with the intended parents’, and accessing information and support) and intended parents’ experiences (navigating the law, rationalising the financial transaction, forming a relationship with the surrogate, and accessing information and support) were identified. Intended parents faced legal barriers when seeking domestic arrangements and difficulties when obtaining legal parenthood and citizenship for their child after an international arrangement. Having a close relationship between participants contributed to a positive experience for both parties. Conversely, a distant relationship, whether emotionally or geographically, negatively impacted participants’ experiences.

Conclusion: Legal barriers in the home country lead some to seek international surrogacy which limits opportunities for intended parents and surrogates to form a close relationship and poses legal challenges when they return home. Removing the legal barriers to domestic surrogacy would allow more arrangements to be conducted where participants have a better prospect of forming close relationships and can avoid the challenges inherent in international arrangements.
National Ovarian and Testicular Tissue Transport and Cryopreservation Service (NOTTCS)
Authors: MARTIN Andrea , TORO Marcela , ROZEN Genia , AGRESTA Franca , GOOK Debra , STERN Kate
Published: November 2022

Background: Recognised female fertility preservation strategies include oocyte and embryo cryopreservation. Ovarian tissue cryopreservation is no longer experimental, and the only option for children and pre-pubertal girls. Although testicular cryopreservation remains experimental for boys, it has the potential to evolve and provide a realistic opportunity for fertility in the future. The RWH/MIVF fertility preservation service has been preserving ovarian tissue since 1995. This service has been available to children, adolescent young adults (AYA) and adults about to receive gonadotoxic treatment for malignant and non-malignant conditions. In 2013, this service was extended to freezing testicular tissue for pre-pubertal and peri-pubertal males. Until 2019 these fertility preservation options have only been available to those undergoing procedures at Melbourne metropolitan hospitals. Young cancer patients seeking fertility preservation in regional or interstate areas, did not have this opportunity due to lack of access and resources. One approach to increasing patient access to Gonadal Tissue Cryopreservation (GTC), was to establish a national tissue retrieval and transport service.

Aim: This paper describes the uptake of a GTC transport program at RWH, allowing rural and interstate oncology referral for transport, processing and storage of gonadal tissue in an acknowledged centre of excellence.

Method: An information/education/instruction resource package was developed for fertility units Australia-wide, supported by a centralised GTC program coordinator. Referrals are fast tracked to eliminate any delay in treatment. Gonadal tissue is harvested at the referring hospital and transported to RWH for cryopreservation and storage, following methods established in other countries with a centralised service 1 – 3 .

Results: To date, 40 ovarian and testicular tissue has been transported from all Australian states, and Northern Territory to RWH, including semen transported from a regional hospital where no fertility service was available. This service was made possible, and free of charge to those patients 13–30 yo with a cancer diagnosis, through a generous donation by Sony Foundation.

Conclusion: Provision of a comprehensive fertility preservation service, including GTC, for young people, was not widely available until 2019. Gonadal tissue transport facilitates engagement and upskilling in oncofertility with extensive support from a centre of excellence, allowing expansion of patient and provider access to best-practice fertility preservation options, regardless of their geographic location and socio-economic status.
Can we Make SpermFAST? Improving Sperm Function to Increase Fertilisation Rates after in vitro Fertilisation
Authors: MCPHERSON Nicole O. , HAMILTON Hamish , ZANDER-FOX Deirdre , ARCHER Emily , BAKOS Hassan W.
Published: November 2022

Background: Intracytoplasmic sperm injection (ICSI) usage ([Formula: see text]64% of autologous cycles) has increased in Australia as an attempt to avoid low fertilisation and total fertilisation failure after standard in vitro fertilization (IVF). ICSI and to a lesser extent IVF, bypass key sperm maturation (hyperactivation, capacitation/acrosome reaction) events that naturally occur in the female tract and are vital for successful fertilisation. Current commercial sperm preparation media are not fully designed to induce these changes in sperm prior to insemination.

Aim: To improve fertilisation rates following IVF by increasing sperm capacitation and hyperactivation between sperm preparation and insemination ultilising a new sperm medium (SpermFAST).

Method: Sperm from 12 consenting normospermic men were incubated in either G-IVF+ (Vitrolife) or SpermFAST (UoA/Monash IVF) following a direct swim-up. Measures of capacitation, hyperactivation, sperm binding, acrosome reaction and oxidative DNA damage were assessed. Further, sperm from male CBAF1 mice (N=8) were incubated in either G-IVF+ or SpermFAST prior to IVF insemination. Fertilisation rates, embryo development, blastocyst cell numbers and DNA damage were assessed.

Results: Incubation of human sperm in SpermFAST increased tyrosine phosphorylation (15.8% vs 9.5%, P[Formula: see text]0.05), hyperactive motility (38.3% vs 14.9%, P[Formula: see text]0.01), sperm binding (73.1% vs 47.7%, P[Formula: see text]0.01), while having no impact on sperm acrosomal status or oxidative DNA damage levels. Following IVF in the mouse, sperm incubated in SpermFAST increased fertilisation rates (94% vs 88%, P[Formula: see text]0.05), blastocyst total cell (92.2% vs 77.4%, P[Formula: see text]0.05), inner cell mass (14.9% vs 18.9%, P[Formula: see text]0.01) and epiblast cell numbers (3.7% vs 1.6%, P[Formula: see text]0.01), while the proportion of DNA damaged cells decreased in blastocysts (2.3% vs 4.8%, P[Formula: see text]0.001).

Conclusion: Sperm function and fertilisation rates are improved when the sperm medium better mimics the environment of the female reproductive tract during natural conception. Improving IVF culture media to better meet the physiological needs of sperm could potentially improve outcomes following IVF.
Diet, Fertility and the Australian Primary Health Care Setting — A Review
Authors: PANDELIOS Georgia , LAWS Rachel , MORAN Lisa , CAMPBELL Karen
Published: November 2022

Background: The relationship between diet and fertility continues to emerge, yet interventions underutilise this evidence within Australian primary health care (PHC). Infertility affects approximately 9% of the world’s population and 16% of Australian couples trying to conceive naturally. Current PHC practices do not address nor encourage improved diet for sperm and oocyte quality, ovulation and sperm production. Due to a lack of resources and training, general practitioners typically refer these individuals to fertility clinics for medical management. As a result, Australia ranks as the 6th highest global utiliser of assisted reproductive technology, with annual costs to treat infertility exceeding $46,000,000.

Aim: To synthesise current evidence for the diet-fertility relationship and identify suitable PHC interventions for improving fertility related lifestyle risk factors.

Method: A database search for published peer reviewed articles using MEDLINE, Scopus, Google Scholar, PubMed and Global Health was carried out, and narratively synthesised.

Results: Poor diet, central adiposity and unhealthy weight are modifiable risk factors impacting fertility, and common amongst the Australian adult population. There are opportunities to address these risk factors by modifying existing lifestyle modification programs to improve the overall fertility profile of this demographic within PHC.

Conclusion: It is possible to optimise fertility through lifestyle interventions that encompass dietary modification. Health and fertility treatment costs can potentially be improved if changes to diet and lifestyle are consistently addressed as first line management for infertility within PHC for appropriate individuals. Understanding evidence for interventions have importuning implications for policy and practice. Further work needs to describe how fertility lifestyle interventions can successfully translate into PHC practice.