bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.