bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors for pleomorphic dermal sarcoma: analysis of 1911 cases from the SEER database
Authors: Perez Alexander N , Dashti Nooshin K , Cates Justin M M
Published: November 2022

Prognostic factors for pleomorphic dermal sarcoma, a rare undifferentiated neoplasm of the skin, are poorly defined, and typical staging systems do not appear to be appropriate for these neoplasms. We; therefore, sought to identify prognostic factors for disease-specific survival and predictors of metastasis.

Pleomorphic dermal sarcomas were identified in the Surveillance, Epidemiology and End Results database (N=1911). Multiple imputation was used to overcome inherent limitations in this dataset to assess prognostic factors using multivariable Cox proportional hazard stratified by (neo)adjuvant radiotherapy and logistic regression for presentation with metastasis.

Age, tumour size and metastasis were independent prognostic factors for cutaneous sarcoma-specific survival. Only tumour size was associated with increased odds of presentation with metastasis, with tumours >4 cm at highest risk. Metastasis is the most important factor in determining outcomes, with age and size as lesser factors. Only tumour size is predictive of metastasis, with larger tumours at highest risk.
Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma
Authors: Kiyozawa Daisuke , Kohashi Kenichi , Takamatsu Dai , Umekita Shinya , Eto Masatoshi , Kinjo Mitsuru , Nishiyama Kenichi , Taguchi Kenichi , Oshiro Yumi , Kuboyama Yusuke , Oda Yoshinao
Published: November 2022

Aims

Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells.

Methods

Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8+, CXCR2+, CD11b+, CD66b+and CD33+immune cells located in the tumour components.

Results

A number of CXCR2+(p=0.0058), CD11b+(p=0.0070) and CD66b+(p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8+lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2+, CD11b+and CD66b+immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities.

Conclusions

Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.
New species and new distributional records of the hygropetric water scavenger beetle genus Ephydrolithus Girón & Short (Coleoptera: Hydrophilidae) from the Brazilian Shield
Authors: Alencar Janderson Batista R. , Serra Myllena Bastos , Short Andrew Edward Z. , Hamada Neusa
Published: November 2022

The water scavenger beetle Ephydrolithus Girón and Short, 2019 contains five species, all occurring in the southeastern region of Brazil. In this paper, 5 new species are described from the Brazilian Shield, bringing the number of species in the genus to 10: Ephydrolithus bentoi sp. nov., Ephydrolithus cipo sp. nov., Ephydrolithus mucugensis sp. nov., Ephydrolithus serro sp. nov., and Ephydrolithus vivas sp. nov. New geographical records in the Brazilian Shield are provided for Ephydrolithus hamadae Girón and Short, 2019, Ephydrolithus spiculatus Girón and Short, 2019, and Ephydrolithus teli Girón and Short, 2019. Corroborating the previously described habitat for the genus, all new species are associated with hygropetric zones such as wet rocks, waterfalls, and seepages. An updated key to identify adults of Ephydrolithus is provided.
Emerging pollutants of water supplies and the effect of climate change
Authors: Alshamsi Aysha Mohammed Omran , Tatan Bushra Mohammad , Ashoobi Nasim Mohammad Sharif , Mortula Md Maruf
Published: November 2022

Emerging pollutants (EPs) are the contaminants of concern in water systems. These are mainly due to anthropogenic activities and are not always removed during water treatment, eventually affecting the quality of water supply systems (WSSs). These pollutants vary from organic pollutants such as pharmaceuticals, pesticides, and flame retardants to inorganic pollutants, like heavy metals or illicit drugs. Currently, there is a lack of adequate research on the chronic health effects of these pollutants. In addition, climate change plays a role in immobilizing these pollutants. Consequently, considering the increasing effects visible in many countries, the rising levels of contaminants have strained the effectiveness of water treatment facilities. As water supply is an essential service to communities, it is necessary to ensure the reliability against risks of EPs. Therefore, it is important to protect the health and safety of consumers. Climate change has brought threats to water infrastructures, like many others. This review examined the effect of climate change on EPs in water supplies by providing a detailed review of the contaminants, evaluating their potential toxicity, and determining the appropriate water treatment technologies. The role of the WSS in EP immobilization was examined in addition to the potential effect of climate change. This review of different critical and relevant literature aids with the identification of current research gaps. Based on the identified gaps, a research framework was developed for the future investigation of EPs.
Wildlife health in environmental impact assessments: are we missing a key metric?
Authors: Aleuy O. Alejandro , Kutz Susan , Mallory Mark L. , Provencher Jennifer F.
Published: November 2022

Environmental impact assessments (EIAs) aim to assess the predicted effects of future projects on the environment, human health, and the economic potential of a region. They are an instrumental tool for sustainable development and to reduce the impact of large-scale industrial projects on biodiversity. The accurate assessment of the effects of projects on wildlife populations has a variety of ecological, cultural, and economic implications. However, assessments are commonly done using indirect indicators such as the predicted impact of changes in the quantity and quality of wildlife habitat and (or) predicted changes in nonspecific wildlife population metrics (e.g., relative abundance). In recent decades, the interpretation of wildlife health has moved from the classical dichotomous state of “disease presence/absence” to a broader concept that integrates the interaction of biological, social, and environmental health determinants. We sought to determine how wildlife health metrics are used in EIA processes and propose a framework to characterize, quantify, and monitor wildlife health in future EIAs. First, we performed a targeted review of EIA documents from three jurisdictions in Canada to characterize the relevance and use of “wildlife health” in these documents. Then, we reviewed case studies and research examples to understand wildlife health in different contexts associated with conservation biology to propose a framework to incorporate wildlife health into baseline monitoring and mitigation processes in EIAs. Our targeted review illustrates that while wildlife health and related terminology is often invoked in the main and specific objectives of EIAs, it is rarely tracked and quantified in EIAs and related processes. We identified approaches that can be used to effectively incorporate wildlife health in EIAs, including context-specific wildlife health metrics, participatory epidemiology, community-based sampling, and local ecological knowledge. We illustrate case studies where wildlife health can facilitate the inclusion of communities, Indigenous governments, and local ecological knowledge into the evaluation process of projects and developments and into comanagement practices of wildlife. Our work highlights the critical need to move towards incorporating wildlife health into EIA processes to provide a more direct and holistic perspective on the potential environmental impacts and improve the opportunities for early implementation of mitigation measurements.
Stellar neutron capture reactions at low and high temperature
Authors: Rauscher Thomas
Published: November 2022

The determination of astrophysical reaction rates requires different approaches depending on the conditions in hydrostatic and explosive burning. The focus here is on astrophysical reaction rates for radiative neutron capture reactions. Relevant nucleosynthesis processes not only involve the s-process but also the i-, r- and $$\gamma $$
γ
-processes, which from the nuclear perspective mainly differ in the relative interaction energies of neutrons and nuclei, and in the nuclear level densities of the involved nuclei. Emphasis is put on the difference between reactions at low and high temperature. Possible complications in the prediction and measurement of these reaction rates are illustrated and the connection between theory and experiment is addressed.
Multiparticle production in proton–nucleus collisions beyond eikonal accuracy
Authors: Agostini Pedro , Altinoluk Tolga , Armesto Néstor , Dominguez Fabio , Milhano José Guilherme
Published: November 2022

We study the effects on multigluon production at mid-rapidity in the Color Glass Condensate of the non-eikonal corrections that stem from relaxing the shockwave approximation and giving the target a finite size. We extend previous works performed in the dilute-dilute approximation suitable for proton–proton collisions, to the dilute-dense one applicable to proton–nucleus. We employ the McLerran–Venugopalan model for the projectile averages. For the target averages, we use the Golec-Biernat–Wüsthoff model and restrict to the leading contributions in overlap area that allow a factorization of ensembles of Wilson lines into products of dipoles. We make the connection with the jet quenching formalism and compare with previous results in the literature, providing a parametrization of the so-called decorated dipoles. We show that the non-eikonal effects on single inclusive particle production, contrary to what happens in jet quenching, are only sizable, of a few percent, for modest energies $$\sqrt{s_{NN}}\le 100$$

s

NN

≤
100

GeV and central rapidities. On the other hand, we find that the effects on double inclusive gluon production are larger for the same kinematics. We show that, as found previously in the dilute-dilute situation, non-eikonal corrections break the accidental symmetry in the CGC, allowing for the existence of non-vanishing odd azimuthal harmonics.
Enhancing short-term crime prediction with human mobility flows and deep learning architectures
Authors: Wu Jiahui , Abrar Saad Mohammad , Awasthi Naman , Frias-Martinez Enrique , Frias-Martinez Vanessa
Published: November 2022

Place-based short-term crime prediction models leverage the spatio-temporal patterns of historical crimes to predict aggregate volumes of crime incidents at specific locations over time. Under the umbrella of the crime opportunity theory, that suggests that human mobility can play a role in crime generation, increasing attention has been paid to the predictive power of human mobility in place-based short-term crime models. Researchers have used call detail records (CDR), data from location-based services such as Foursquare or from social media to characterize human mobility; and have shown that mobility metrics, together with historical crime data, can improve short-term crime prediction accuracy. In this paper, we propose to use a publicly available fine-grained human mobility dataset from a location intelligence company to explore the effects of human mobility features on short-term crime prediction. For that purpose, we conduct a comprehensive evaluation across multiple cities with diverse demographic characteristics, different types of crimes and various deep learning models; and we show that adding human mobility flow features to historical crimes can improve the F1 scores for a variety of neural crime prediction models across cities and types of crimes, with improvements ranging from 2% to 7%. Our analysis also shows that some neural architectures can slightly improve the crime prediction performance when compared to non-neural regression models by at most 2%.
Conformal Ricci soliton and almost conformal Ricci soliton in paracontact geometry
Authors: Dey Santu
Published: November 2022

In this paper, we study conformal Ricci soliton and almost conformal Ricci soliton within the framework of paracontact manifolds. Here, we have shown the characteristics of the soliton vector field and the nature of the manifold if para-Sasakian metric satisfies conformal Ricci soliton. We also demonstrate the feature of the soliton vector field V and scalar curvature when the para-Sasakian manifold admitting conformal Ricci soliton and vector field is pointwise collinear with the characteristic vector field [Formula: see text]. Next, we prove that if a K-paracontact manifold confesses a gradient conformal Ricci soliton, then it is Einstein. Next, we show that a para-Sasakian metric reveals with an almost conformal Ricci soliton that is either Einstein or [Formula: see text]-Einstein metric if the soliton vector field V is an infinitesimal contact transformation. Lastly, we decorate an example of conformal Ricci soliton on para-Sasakian manifold.
Xi Jinping’s Dominance in China’s Foreign Policy
Authors: LI-OGAWA Hao
Published: November 2022

This paper analyses Xi Jinping’s role in China’s foreign policy from elitepolitics perspective focusing on first, the policy preferences and worldviews of political elites; second, balance of power among political elites; and third, the sectoral interests behind political elites. China’s foreign policies have generally developed in line with Xi’s policy preferences and worldview. The current balance of power is in Xi’s favour. His administration comprises mostly local cadres, whose developmentalist policy preferences are reflected in foreign policies.
Psychosocial Impact of the COVID-19 Pandemic on Fertility Patients
Authors: BOIVIN Jacky
Published: November 2022

COVID-19 is a challenge for fertility care. Our research shows that the key challenge for patients is managing the uncertainty that COVID-19 causes around the attainability of the parenthood goal (e.g., continued access to treatment, effects of delay on fertility, accentuated health worries about pregnancy). Patient coping strategies are often, but not always, optimised for managing uncertainty leading about 10% of patients to report extreme stress reactions in several health domains (e.g., psychological, physical, behavioural). While focus has been on patients, our research also shows that COVID-19 produces multi-causal uncertainties for staff due to unknown and unknowable futures (e.g., future threats to health, practice changes, clinic viability and finance, unstable knowledge states). Most international guidance for fertility staff focuses on mitigating risks in practice. However, staff could benefit too from learning more about uncertainty management for situations with irreducible risk such as COVID-19. Altogether COVID-19 studies in fertility care indicate that COVID-19 is distressing for patients and staff and as such welfare considerations (physical and psychological) will continue to be critical for clinics. Focusing support resources at threat and uncertainty management will help build sustainable personal and organisational resilience. Investing in uncertainty management for COVID-19 should also help manage other uncertainties in fertility care, for example per-cycle and cumulative chances of live birth.
AI, Time-lapse and Biomarkers: What Can We Expect in the Next Decade?
Authors: GARDNER David K.
Published: November 2022

For 40 years we have relied upon morphological assessment of the human embryo for its selection for transfer. With the advent of time-lapse microscopy (TLM), we have been able examine the timings of key developmental events and create algorithms to further advance embryo selection. However, such algorithms do not utilise all available data. Artificial intelligence (AI) can utilise the hundreds of successive images of each embryo as it develops to produce highly predictive rankings. This approach increases the speed of assessment, while decreasing variation typically associated with the subjective analysis of individual embryologists. Therefore, AI represents a means to increase both accuracy and standardisation of embryo selection. In the IVF laboratory, beyond its current function in embryo selection, AI will be used for gamete selection prior to fertilisation, and to increase laboratory function by its integration into Quality Control and Management systems.

Although TLM combined with AI holds great potential, it does not quantitate the physiological status of the embryo. Analysis of spent culture medium has revealed that metabolism (glucose uptake and the utilisation of amino acids) of the human blastocyst is related to pregnancy. Currently, analysis of metabolic function by individual embryos requires highly specialised technologies, but with the advent of microfluidics and microfabrication we are entering an era of novel benchtop technologies capable of rapid single embryo analysis. Subsequently, it is envisaged that AI will be used in combination with TLM and the analysis of spent culture medium (to quantitate metabolism and plausibly cell-free DNA), to identify non-invasively the healthiest embryo for transfer.
Research Outcomes Following Uterus Transplantation at Royal Prince Alfred Hospital
Authors: GEORGEVSKY Dana , LI Ying , PATHER Selvan , TEJADAS-BERGES Trevor , ROBINSON David , LAURENCE Jerome , CAMPBELL Neil , WYBURN Kate , LIYANAGAMA Keith , NARAYAN Rajit , LUTZ Tracey , CHAN Agnes , HEANEY Sally-Ann , KITZING Yu Xuan , ANDERSON Lyndal , TESTA Giuliano , JOHANNESSON Liza , MARREN Anthony
Published: November 2022

Background: Absolute Uterine Factor infertility (AUFI) can be congenital such as Mayer-Rokitansky Küster syndrome (MRKH), or acquired resulting from conditions rendering the uterus non-functional or following a hysterectomy. In 2014 the first successful uterus transplant (UT) was achieved in Sweden. This sparked widespread interest, and many countries have established UT trials. In 2019 Royal Prince Alfred hospital was the first site in Australia to receive ethical approval for a UT protocol. As part of this trial research outcomes will be collected.

Aim:

• To determine if UT is an effective, safe, and operationally viable option for women with AUFI in order to achieve live birth.

• To collect research outcomes which will contribute to an international bio-bank for future research opportunities.

Method: Approved donor/recipient pairs will be invited to participate in the research components of the trial. This will involve completing various questionnaires to assess clinical outcomes before and after the procedure, as well as providing additional blood and cervical tissue samples which will be stored for future research projects.

Conclusion: UT is a relatively new procedure, with significant scope for basic research opportunities. Due to the infancy of UT it is pivotal that all centers are diligent in collecting research outcomes and contributing to an international data registry to aid in proving the necessity of UT as a clinical treatment for woman with AUFI.
Random Families: Genetic Strangers, Sperm Donor Siblings and the Creation of New Kin
Authors: HERTZ Rosanna
Published: November 2022

Unprecedented families formed by sperm donor siblings have grown up at the intersection of new reproductive technologies, social media, and the human desire for belonging. As the Internet has expanded, parents (and their children) who shared the same donor have discovered that they can connect. When they meet, they wonder: What does it mean to be a donor sibling? Do shared genes make you family? Does “family” even describe our relationship?

In an era in which conventional families are shrinking, the idea of connecting with genetically related strangers offers opportunities and risks. Hertz will discuss the contemporary interplay of genetics, social interaction, and culture expectations in an effort to explain the emergence of web-based donor sibling networks. Funded by the U.S. National Science Foundation, her talk is based upon over 350 interviews with donor-conceived children, their parents and donors from her co-authored book, Random Families.
Why Euploid Blastocysts Fail
Authors: KEEFE David
Published: November 2022

Preimplantation genetic testing for aneuploidy improves implantation and reduces miscarriage rates, but still about 30 to 35% of euploid blastocysts fail to implant and 10 to 13% of pregnancies following euploid blastocyst transfer miscarry. Both endometrial and embryo factors may contribute to failed euploid embryo transfers. Endometrial factors include uterine structural abnormalities, altered timing of endometrial receptivity, glandular-stromal disynchrony, and inflammatory states. Recent studies question the clinical benefit of some recent assays for endometrial receptivity. Other recent studies question the value of surgical correction of uterine septae and fibroids to prevent further pregnancy loss. Embryo factors include aneuploidy, either undetected by PGT-A performed on the blastocyst trophectoderm (i.e. false negative test) or de novo non-disjunction. Sub chromosomal genetic variation, e.g. copy number variants and de novo retrotransposon insertions, may impair embryo viability. We employ a “genetics first” approach, which relies on genetic analysis of products of conception, obtained by uterine evacuation, to evaluate miscarriage after euploid blastocyst transfer. Non-invasive genetic analysis of first trimester pregnancies also may help characterize the cause of embryo loss after euploid embryo transfer. Early results suggest that analysis of cfDNA and trophoblast retrieval and isolation from the cervix (TRIC) may allow women experiencing early pregnancy loss to learn about the genetic state of their miscarriage, without an invasive surgical procedure to obtain products of conception.
Online Semen Donors — Why Not?
Authors: KERNER Rebecca
Published: November 2022

Increasing numbers of single women and couples are looking to online semen donors to help create their families. While on-line platforms may appear to provide a quicker and easier pathway to parenthood, this choice carries significant medical and legal risks.

As part of our advocacy work in patient centred care, the fertility counsellors in ANZICA believe it is important to identify and bring to attention any significant concerns that might have serious implications for individuals and couples trying to conceive. In doing this however, we also have a duty to seek out new ways to provide more accessible forms to treatment for those who may not come with an infertility problem.

This session will introduce a new patient centred resource that highlights some of the risks and pitfalls of using an online semen donor. It also offers guidance and support for those looking to create their family using home insemination and explores some new ideas on how we might better meet the needs of these women and couples. The resource aims to empower all involved to make fully informed choices, based on thorough consideration of their needs and health, and the safety and legal rights of everyone involved. Importantly the focus will include the long-term outcomes for children born through donation.
Mitochondrial Donation — Ethical Considerations
Authors: NEWSON Ainsley
Published: November 2022

Background: Mitochondrial donation is an assisted reproductive technology that can be used to avoid transmission of mitochondrially encoded mitochondrial DNA disease from women to their children. The Australian government is currently considering whether to legalise mitochondrial donation for clinical use.

Aim: This presentation will elucidate and reflect on the main ethical issues that arise in mitochondrial donation.

Method: This presentation will utilise methods of bioethics scholarship, which includes presenting concepts and/or issues and critically reflecting on them. A goal of bioethics scholarship is to come to a normative position about what should happen and how this should be justified.

Results: Ethical issues do arise in the development and clinical use of mitochondrial donation. Those particularly relevant in relation to the proposed use of mitochondrial donation in Australia include responsibility for safety, equity of access, the heritability of the changes to the germ-line, the value of genetic kinship, oocyte donor anonymity, the choice not to use this technology and follow-up of children over time.

Conclusion: Mitochondrial donation offers a promising additional reproductive option for those with a high chance of transmitting mitochondrially encoded mitochondrial disease. Ethical implementation of mitochondrial donation in Australia necessitates consideration of numerous ethical issues, not all of which have yet been given appropriate attention.
Management of Azoospermia Due to Spermatogenic Dysfunction
Authors: NIEDERBERGER Craig
Published: November 2022

When I was taking my urology boards 30 years ago, a question on the exam was how to treat an azoospermic man with an FSH level of 2 to 3 times normal, and the answer was to counsel to adopt. So much has changed in those intervening years: the most common patient that I treat today is exactly that man, and a live birth is achieved in approximately 70%. Between then and now, what made reproductive success possible in this previously hopeless clinical scenario was the introduction of intracytoplasmic sperm injection and the ability to use it with testicular sperm derived from a microsurgical systematic survey of seminiferous tubule size and quality.

However, treatment of the male lags behind that of the female for a variety of reasons, with the principle one being male gametogenesis is longer and less easily observed than the female. The quick weeks of ovulation may be followed by ultrasound, but with months long spermatogenesis and its tiny sperms, should they only exist in the testis and not in the ejaculate, the only way of knowing what’s happening in the testis is to do surgery. Fortunately, the binary outcome of sperm or not is providing us with means to test endocrine stimulatory protocols in the male similar to those in the female that have made in-vitro fertilization so successful. Cryopreservation of testicular tissue is another advance making these procedures more convenient for patients and physicians, and importantly, knowing whether biological gametes from the male are available for IVF.
Mosaicism in Human Embryos: What Do We Know?
Authors: STOCK-MYER Sharyn E.
Published: November 2022

Preimplantation Genetic Testing for Aneuploidy (PGT-A) involves performing aneuploidy testing on the small number of cells biopsied from a preimplantation embryo. It is well established that aneuploidy is a common cause of implantation failure and miscarriage. In an ideal world, a measure of the chromosome status of the cells from the embryo would produce a highly specific result that would predict the fate of that embryo. One of the difficulties with PGT-A however, has been putative chromosomal mosaicism present in a proportion of tested embryos.

Chromosome mosaicism became more widely reported following the use of Next Generation Sequencing (NGS) as a tool for performing PGT-A. This was due to the higher dynamic range of the NGS profiles that made mosaicism in the trophectoderm biopsy more visible. Around this same time the first study was published that followed the transfer of 18 mosaic embryos, resulting in the birth of six healthy babies ( Greco et al 2015 ). Since then, several publications have described the results of mosaic embryo transfers, including the work by Viotti et al 2021 which summarised the results of transferring 1000 mosaic embryos. These studies have the common theme that a mosaic embryo result does not clearly predict a negative pregnancy outcome, unlike a uniform aneuploid result. However, it may predict a reduced chance of pregnancy, and an increased chance of miscarriage, depending on the type of mosaicism.

Reassuringly, a mosaic result in an embryo also does not seem to indicate a higher chance of having a baby with an abnormality than euploid embryos. Chromosomally mosaic embryos should not be discarded and should be considered for use with appropriate counselling of the patients.
Debate: Are We Limiting the Potential of Oocytes by Not Using ICSI for All? - ICSI Should be Used for Most IVF Cycles
Authors: YOVICH John L.
Published: November 2022

Background: Following earlier studies introducing an IVF-ICSI Split model on couples with unexplained infertility to avoid the scenario of unexplained failed or poor fertilization, PIVET has adopted a high ICSI rate approaching 90%, whereas the general rate among Australian facilities is around 60%.

Aim: To compare the embryology and clinical outcomes in an IVF program where ICSI is applied beyond male-factor reasons and applies an IVF-ICSI Split protocol for IVF-naïve women with unexplained infertility.

Method: This observational study with retrospective data analysis reports on autologous IVF± ICSI procedures conducted over the period 2011 to 2019 with follow-up of ensuing pregnancies through 2020.

Results: Using autologous oocytes, 2343 women had 3434 IVF± ICSI cycles with 84.5% of women had 88.9% of initiated treatment cycles using ICSI and only 5.3% of women had 4.0% of cycles by IVF. The remaining 10.1% of women utilised the IVF-ICSI Split model for the remaining 7.2% of cycles. It was shown that oocyte fertilisation rates were significantly higher for ICSI (p<0.0001), but not significant for women >40 years. The utilisation rates of the ensuing embryos were [Formula: see text]45% across all ages with no significant differences across the ages, except for those small numbers of women [Formula: see text] 45 years who had a higher rate from IVF-generated embryos (p<0.0002). Pregnancy outcomes were higher from ICSI-generated embryos across the age groups, being especially marked among the younger women <40 years (p<0.0001). Miscarriage rates were lowest for the IVF-generated pregnancies (overall 6.7% vs 22.8%, p<0.0001) but nevertheless the final live birth productivity rates per initiated treatment cycle remained higher from the ICSI-generated pregnancies (56.5% vs 46.3%; p<0.0001).

Conclusion: Although this study does not meet the highest standards for EBM, it emanates from a pioneer facility with >40 years of published activity and which practices 90% blastocyst transfers in >90% SET cycles. The study supports a high ICSI rate of 90% and an IVF-ICSI Split rate of 10%.
Shedding Light Onto the Structural Secrets Inside Pluripotent Stem Cells of the Preimplantation Mammalian Embryo in Real-Time
Authors: ABERKANE Asma , HAWDON Azelle , STATHATOS Gemma , GREANEY Jessica , LI Yi Louise , LIU Xiaodong , PARTON Rob , POLO José , ZENKER Jennifer
Published: November 2022

The organisation of a cell’s interior, the cytoskeleton and organelles, is fundamental for every cell’s functionality. However, unlike most differentiated cells, our knowledge about the contribution of the sub-cellular architecture to embryonic development and pluripotency remains scarce. Using advanced live imaging, we discovered polarised non-centrosomal microtubules as central player for the pluripotent state of the in vivo early mammalian embryo and induced pluripotent stem cells (iPSCs). Each cell contains an apical pole highly enriched with CAMSAP3-nucleated microtubules, growing in a longitudinal direction towards the base of PSCs. These non-centrosomal microtubules initiate an asymmetry of metabolites and organelles, including mitochondria. We further establish their rearrangement upon differentiation in a germ layer-specific manner. Dissecting how intrinsic cellular regulation contributes to pluripotency will lead a revolutionary era of regenerative and reproductive medicine.
Application of Ex-Vivo In Vitro Maturation (IVM) to Fertility Preservation in Cancer Patients
Authors: GILCHRIST Robert B. , RICHANI Dulama , CULLINAN Rosemarie , DALATI Sarah , TILIA Liza , ANAZODO Antoinette , LEDGER William L. , RODGERS Rachael J.
Published: November 2022

Background: Oocyte in vitro maturation (IVM) is a reproductive technology that generates mature oocytes from patients who have received minimal or no ovarian stimulation (OS). The minimal-stimulation feature of IVM makes it a valuable option for cancer patients requiring fertility preservation (FP), before chemo- or radiotherapy. When ovarian tissue is collected for cryopreservation (OTC), only the ovarian cortex is preserved whereas the ovarian medulla containing growing follicles is discarded. To maximise the future fertility prospects for cancer patients, OTC should be coupled with a modified form of IVM, termed ex-vivo IVM, in which immature cumulus-oocyte complexes (COCs) are collected from antral follicles.

Aim: To examine the utility of emergency ex-vivo IVM for FP.

Method: A 31-year-old woman diagnosed with locally invasive appendiceal cancer required urgent FP as there was no time for conventional OS egg freeze before surgery, and OTC was contra-indicated due to the possibility of later regrafting of cancer cells. She underwent peritonectomy with bilateral oophorectomy with no prior ovarian stimulation or cycle management. Visible antral follicles were aspirated ex-vivo, the ovaries were then manually dissected, antral follicles punctured and intact COCs collected. COCs were washed and matured for 30-46h in G-2 PLUS medium supplemented with 0.1IU/mL rec-FSH, 0.5IU/mL rec-hCG, and 10% (v/v) autologous heat-inactivated patient serum.

Results: 40 COCs were collected and 18 (45%) reached metaphase II, 1 was cryopreserved and 17 were inseminated by ICSI. 13/17 oocytes fertilised (2PN; 76%) and 7/13 (54%) blastocysts were generated (D5: 1× HB-1-1, 3× B-1-1, 1× B-2-1. D6: 1× HB-1-2, 1× B-2-2). Seven blastocysts and one oocyte were vitrified for future use by the patient.

Conclusion: Ex-vivo IVM is a viable FP option for patients diagnosed with cancer. It can readily be coupled with OTC and/or a regular IVM oocyte pickup to maximise a cancer patient’s future fertility prospects.
Assessment of Oocyte Quality Using Deep Radiomic Signature of Oocyte Morphology in the Mouse
Authors: HABIBALAHI Abbas , BERTOLDO Michael J. , MAHBUB Saabah B. , CAMPBELL Jared M. , GOSS Dale M. , LEDGER William L. , GILCHRIST Robert B. , WU Lindsay E. , GOLDYS Ewa M.
Published: November 2022

Background: Technologies such as in vitro fertilization (IVF) are increasingly used to compensate for the loss of fertility associated with increasing maternal age and decline in oocyte quality. During IVF, superovulation yields more oocytes than are required, and the selection of oocytes for fertilization and implantation is based on poorly defined morphological features which are subject to user bias.

Aim: We aim to develop a deep radiomic signature based on an artificial intelligence (AI) model in order to identify oocyte morphological changes corresponding to reproductive ageing in bright field images captured by optical light microscopy. This approach has potential for application in assessment of human oocytes.

Method: Oocytes were collected from three groups of C57BL/6J female mice: young (4- to 5-week-old), aged (12-month-old) mice and aged mice treated with the NAD+ precursor nicotinamide mononucleotide (NMN), a treatment recently shown to rejuvenate aspects of fertility in aged mice. Deep learning, swarm intelligence and discriminative analysis were applied to images of mouse oocytes taken by bright field microscopy to identify a highly informative deep radiomic signature (DRS) of oocyte morphology. Approximately 25 oocyte images were derived from each group.

Results: This signature distinguished morphological changes in oocytes associated with maternal ageing, which are imperceptible to an experienced embryologist, with 92% accuracy (AUC[Formula: see text]1), reflecting the age-induced decline in oocyte quality. We then employed the DRS to evaluate the impact of the NMN treatment. The DRS signature classified 60% of oocytes from NMN-treated aged mice as having a ‘young’ morphology, demonstrating the signature’s sensitivity to improvements in quality and reinforcing its applicability for oocyte selection.

Conclusion: Our data illustrate the power of DRS for recognizing morphological features of cellular ageing, which outperforms current subjective methods relying on visual grading for the recognition and classification of oocytes based on maternal age.
School Age Developmental Outcomes of Children Conceived by IVF Compared with Controls: A Population Linkage Study
Authors: KENNEDY Amber , VOLLENHOVEN Beverley , HISCOCK Richard , STERN Catharyn , WALKER Susan , CHEONG Jeanie , QUACH Jon , HASTIE Roxanne , WILKINSON David , MCBAIN John , GURRIN Lyle , MACLACHLAN Vivien , AGRESTA Franca , BAOHM Susan , TONG Stephen , LINDQUIST Anthea
Published: November 2022

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. Our primary outcome was an AEDC score indicative of developmental vulnerability in two or more domains. We adjusted for the child’s age at assessment, sex, highest level of maternal education, maternal age, parity, SEIFA (Socio-Economic Indexes for Areas) quintile, language background other than English, and Aboriginal and Torres Strait Islander (ATSI) status.

Results: The linked dataset comprised 163,418 children, including 4,441 IVF-conceived children. The IVF conceived population had older, more highly educated mothers who lived in more affluent areas and were less likely to be from non-English speaking backgrounds or identify as ATSI. IVF-conceived children were less likely to be developmentally vulnerable, in both unadjusted (RR 0.59, 95%CI: 0.52-0.67, p<0.001) and adjusted analyses (aRR 0.72, 95%CI: 0.58-0.88, p<0.001).

Conclusion: Children conceived by IVF were less likely to be developmentally vulnerable in their first year of schooling, compared with peers conceived naturally. Further research should aim to understand if similar patterns are seen in other education and health domains and the potential mechanisms for these differences.
Non-Compliance of Fertility Patients with the Ejaculatory Abstinence Period: The Influence of Confusing Online Fertility Information
Authors: KING Amber
Published: November 2022

Background: Findings from a Western Australian fertility clinic show that male patients may often disregard ejaculatory abstinence directives prior to providing a semen sample. This practise may lead to the production of low quality spermatozoa.

Aim: This study explores the readability and accessibility of online patient information from fertility clinics across Australia as a reason why patients may not adhere to instructions surrounding this behaviour.

Method: A content analysis was conducted of patient information from the websites of 86 registered fertility clinics in Australia. The reading complexity of information found on these websites was determined through calculating the Flesch Reading Ease Scores and Flesch-Kincaid Grade Levels of excerpts retrieved. The presence and diversity of information provided in multilingual formats was recorded. Online instructions regarding ejaculatory abstinence were also compared within and between clinics to identify contradictory information.

Results: The mean Flesch Reading Ease Score across all websites was 47.54 (s.d. 8.18) and the mean Flesch-Kincaid Grade Level was 11.09 (s.d. 1.11), indicating that the information presented exceeds the average Australian’s reading abilities. Information was also rarely presented in languages other than English (1/36 clinic websites, 2.8%) and ejaculatory abstinence recommendations were frequently contradictory (11/24 clinic websites, 45.8%).

Conclusion: The provision of confusing and inaccessible online fertility information by fertility clinics to patients may represent a potential barrier to ejaculatory abstinence adherence. It is recommended that fertility clinics revise their online information to ensure readability.
Embryo Selection by “Black-Box” Artificial Intelligence: The Ethical and Epistemic Considerations
Authors: LIU Yanhe , AFNAN Michael , CONTIZER Vincent , RUDIN Cynthia , MISHRA Abhishek , SAVULESCU Julian , AFNAN Masoud
Published: November 2022

Background: The combination of time-lapse imaging and artificial intelligence (AI) offers novel potential for embryo assessment by allowing a vast quantity of image data to be analysed via machine learning. Most algorithms developed to date have used neural networks which are uninterpretable (“black-box”) and cannot be understood by doctors, embryologists and patients, which raises ethical and epistemic concerns for embryo selection in a clinical setting.

Aim: This study aims to discuss ethical and epistemic considerations surrounding clinical implementation of “black-box” based embryo selection algorithms.

Method: A scoping review was performed by evaluating publications reporting “black-box” embryo selection algorithms. Potential ethical and epistemic issues were identified and discussed.

Results: No randomised controlled trial was identified in the literature evaluating clinical effectiveness of “black-box” embryo selection algorithms. Several ethical and epistemic concerns were identified. Potential ethical issues included (1) lack of randomised controlled trials, (2) impact on the shared decision-making process in embryo selection between clinicians and patients, (3) misrepresentation of patient values due to hidden reasoning process in “black-box” algorithms, (4) social impacts if algorithm subsequently proven to be biased, and (5) unclear responsibility when algorithm makes obviously poor choices of embryos. Potential epistemic issues included (1) information asymmetries between algorithm developers and doctors, embryologists and patients; (2) risk of biased prediction due to data selection during training process; (3) inability to troubleshoot for data training purposes due to limited interpretability; and (4) the economics of buying into commercial proprietary add-ons.

Conclusion: There are significant epistemic and ethical concerns with “black-box” embryo selection. No published randomised controlled trial is available to support its clinical implementation. AI embryo selection in general, however, is potentially useful but must be done carefully and transparently. Interpretable AI would be preferred alternative in causing fewer issues.
Development of a Robust D5 Embryo Ranking System: A Retrospective Multi-Centre Study Involving 8866 Single Fresh Embryo Transfers
Authors: LIU Yanhe , ONG Kee , KORMAN Irving , TURNER Ross , SHAKER David , ZANDER-FOX Deirdre , ROMBAUTS Luk
Published: November 2022

Background: Inter-operator variation in morphology-based embryo assessment is known to be an ongoing issue in in vitro fertilisation (IVF). This includes inconsistent annotation of embryo morphology and disagreement in the predictive weightings amongst different morphological features. Although currently underexplored, subjectivity reduction using statistical tools is considered clinically valuable, and is more affordable than newer approaches such as time-lapse imaging.

Aim: This study aims to develop a robust numerical D5 embryo ranking system by incorporating several patient and embryo characteristics arising from routine static D5 assessment.

Method: A total of 8866 autologous-oocyte single fresh D5 transfers performed at 14 Monash IVF clinics during 2012-2018 were retrospectively analyzed, with repeat cycles from the same patients excluded to avoid clustering effects. The dataset was randomly split into two subsets at 60:40 ratio, including one (n=5274) used for regression analysis and model development and the other (n=3592) for validation. Multiple logistic regression was performed to evaluate live birth prediction by several variables, expressed by odds ratio (OR) and 95% confidence interval (CI). A numerical ranking system was developed based on calculated weightings of contributing factors and subsequently tested using receiver operating characteristics (ROC) as expressed by area under the ROC curve (AUC).

Results: All included variables were significantly predictive of live birth, including maternal age (OR=1.465, 1.364-1.574, P=0.000), assessment timing (OR=1.096, 1.020-1.177, P=0.012), embryo developmental stage (OR=1.341, 1.244-1.445, P=0.000) and morphological sore (OR=1.520, 1.392-1.661, P=0.000). Increments of resultant numerical ranking scores ([Formula: see text]3, 3-3.99, 4-4.99, and [Formula: see text]5) were associated with increasing live birth rates (9.4%, 27.2%, 43.6%, and 54.9%; respectively). ROC analysis indicated significantly predictive power of the numerical ranking system in both the development (AUC=0.690, 0.675-0.704, P=0.000) and validation (AUC=0.685, 0.667-0.703, P=0.000) subsets.

Conclusion: A robust numerical model can be developed for D5 embryo selection, potentially leading to improved inter-operator subjectivity for embryo assessment.