bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproduction misconceived: why there is no right to reproduce and the implications for ART access
Authors: Hall Georgina Antonia 
Published: November 2022

Reproduction is broadly recognised as fundamental to human flourishing. The presumptive priority of reproductive freedom forms the predominant position in the literature, translating in the non-sexual reproductive realm as an almost inviolable right to access assisted reproductive technology (ART). This position largely condemns refusal or restriction of ART by clinicians or the state as discriminatory. In this paper, I critically analyse the moral rights individuals assert in reproductive pursuit to explore whether reproductive rights entitle hopeful parents to ART. I demonstrate that none of the protected actions performed, or entitlements generated are sui generis ‘reproductive’ rights, leading to the claim that there is no such thing as a right to reproduce. Under scrutiny, the reproductive right is a far narrower and weaker rights assertion than is recognised in the literature. I argue that the predominant position is grounded in a fundamental misunderstanding of the scope and strength of reproductive claims.I also highlight a significant conceptual inconsistency in the literature. On one hand, there is broad consensus that reproductive rights are predominantly negative, yet access to fertility treatment is framed as a component of the right. This wrongly contorts the negative nature of reproductive rights into a positive claim-right to ART. I conclude that this mistakenly frames ART access as sitting within the scope of reproductive freedom. I offer a revised conceptual paradigm of reproductive rights that has important clinical and policy implications for the provision and regulation of ART.
Prospective validation of the 4C prognostic models for adults
hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation
Protocol
Authors: Knight Stephen R , Gupta Rishi K , Ho Antonia , Pius Riinu , Buchan Iain , Carson Gail , Drake Thomas M , Dunning Jake , Fairfield Cameron J , Gamble Carrol , Green Christopher A , Halpin Sophie , Hardwick Hayley E , Holden Karl A , Horby Peter W , Jackson Clare , Mclean Kenneth A , Merson Laura , Nguyen-Van-Tam Jonathan S , Norman Lisa , Olliaro Piero L , Pritchard Mark G , Russell Clark D , Shaw Catherine A , Sheikh Aziz , Solomon Tom , Sudlow Cathie , Swann Olivia V , Turtle Lance C W , Openshaw Peter J M , Baillie J Kenneth , Docherty Annemarie , Semple Malcolm G , Noursadeghi Mahdad , Harrison Ewen M 
Published: November 2022

Purpose
To prospectively validate two risk scores to predict mortality (4C
Mortality) and in-hospital deterioration (4C Deterioration) among adults
hospitalised with COVID-19.

Methods
Prospective observational cohort study of adults (age ≥18 years)
with confirmed or highly suspected COVID-19 recruited into the
International Severe Acute Respiratory and emerging Infections
Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK)
study in 306 hospitals across England, Scotland and Wales. Patients were
recruited between 27 August 2020 and 17 February 2021, with at least
4 weeks follow-up before final data extraction. The main outcome
measures were discrimination and calibration of models for in-hospital
deterioration (defined as any requirement of ventilatory support or
critical care, or death) and mortality, incorporating predefined
subgroups.

Results
76 588 participants were included, of whom 27 352 (37.4%)
deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77
to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI
0.75 to 0.77)) demonstrated consistent discrimination across all nine
National Health Service regions, with similar performance metrics to the
original validation cohorts. Calibration remained stable (4C Mortality:
pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C
Deterioration: 1.00, –0.04), with no need for temporal recalibration
during the second UK pandemic wave of hospital admissions.

Conclusion
Both 4C risk stratification models demonstrate consistent
performance to predict clinical deterioration and mortality in a large
prospective second wave validation cohort of UK patients. Despite recent
advances in the treatment and management of adults hospitalised with
COVID-19, both scores can continue to inform clinical decision
making.

Trial registration number
NCT66726260.
COVID-19 Impact on Fertility and Pregnancy
Authors: FEINBERG Eve C. 
Published: November 2022

Background: The emergence of the COVID-19 global pandemic has posed significant challenges to the field of reproductive medicine. Aim: This talk will update the audience on the timeline of the pandemic, emergence of recommendations regarding fertility and reproductive medicine care, present state of the pandemic, vaccine development, data on vaccination in pregnancy, and combatting misinformation/vaccine hesitancy. Method: Review of current literature, review of guidance documents from international societies Results: Maternal morbidity with COVID-19 is greater than that seen in non-pregnant counterparts. This skews the risk/benefit profile in favor of vaccination, even in the absence of randomized clinic trials that did not include pregnant women. Emerging vaccination data are showing a favorable safety profile of the vaccine and vaccination should be encouraged in all women who are pregnant or considering pregnancy. Conclusion: Lessons learned from the COVID-19 pandemic should help to guide provision of reproductive care in future pandemics.
Blurring the Lines Between Life and Death — Ethical and Psychological Considerations in Posthumous Conception
Authors: LAWSON Angela 
Published: November 2022

ART practitioners routinely offer embryo and oocyte/sperm cryopreservation services to patients and couples who are interested in future family building. Unfortunately, some patients, whether due to disease or accident, die after cryopreserving their genetic material. In the event of a patient’s death, their partner or other family members may desire to use those materials to achieve pregnancy. However, posthumous reproduction (reproductive attempts after the death of a partner) has resulted in a number of ethical issues regarding pre-death consent from the deceased patient and ambiguous legal and social status for the resulting child(ren). Multiple psychological issues also arise during the course of posthumous reproduction. This includes decision making in the context of grieving the death of a loved one, family disagreements about posthumous reproduction, and coping with potential pregnancy-related adverse events. Further, it is unknown what if any psychological burden posthumously conceived children or their family members will bear as the child grows. From an ethical standpoint, it is often unclear as to who should have rights to these gametes or embryos as pre-death consent forms have often not been completed. Because of the psychological and ethical concerns regarding posthumous reproduction many practitioners have concerns about facilitating such treatment. This presentation will address the psychological and ethical issues in posthumous reproduction and will provide direction to providers for how to address these issues with surviving loved ones.
Practical Tips with Posthumous Use
Authors: PAGE Stephen 
Published: November 2022

Background: Posthumous use remains a controversial topic. Far too often, posthumous sperm retrieval occurs following the making of urgent Supreme Court orders-when both case law and statute say that such urgent orders are neither necessary or are legally dubious. The surviving parent then is often told to commence court proceedings in order to be able to either use or export the gamete-when often the best approach is not to go to court, but instead demonstrate to the clinics concerned that there has been full compliance with the law and the Ethical Guidelines’ requirements as to posthumous use. In recent years there have been many cases concerning posthumous use, most of which point the way to making the process easier-either in that State or by cross-border reproduction. Aim: To demystify law and practice about posthumous use. Method: To set out the law concerning posthumous use in each Australian State and Territory (both statute and case law) in the accompanying paper, set out practical tips for practitioners about what to look for, and to provide flowcharts for each State and Territory about what needs to be covered in any posthumous case. Results: Too often widows are told to spend considerable sums in unnecessary court cases. Court cases are usually not required in order to lawfully undertake posthumous use. A leading case about posthumous use from Queensland, for example, omitted in all its numerous citations a significant High Court of Australia case about gametes. A significant Western Australian case about who is a donor may also have implications in other States. Conclusion: As per the method.
Reproductive Health of Adults Conceived by IVF and GIFT
Authors: LEWIS Sharon , KENNEDY Joanne , GLYNN Anne , HAMMARBERG Karin , AMOR David , HICKEY Martha , MCBAIN John , BIGGS Sarah , HALLIDAY Jane 
Published: November 2022

Background: We have an established cohort of singleton adults conceived by IVF and GIFT born from January 1982 to December 1992, and matched controls conceived without assisted reproduction (non-ART). They have participated in two previous studies: 1) a telephone interview study when aged 21 years on average and 2) a clinical review 6 years later. As these adults are reaching the average age of first-time parents, it is important to determine their reproductive health. Aim: To examine the reproductive health of IVF/GIFT-conceived adults compared to non-ART controls. Method: Contact details were confirmed via email or the Australian Electoral Roll. Participants were asked to complete a 15-minute online questionnaire hosted in REDCap with questions about fertility and reproductive health, well-being, self-reported health status, demographics and important potential outcome modifiers. Data were analysed using chi-squared and [Formula: see text]-tests. Results: 231 IVF (60%), 74 GIFT (65%) and 153 non-ART (41%) control participants completed the questionnaire. As there were no outcome differences between IVF and GIFT, their results are combined. The overall median age of the IVF/GIFT group and controls was 31.3 years, and 63% were female in both groups. In both groups just over a third had already given birth, with 15% and 18% respectively reporting having had medical advice for fertility concerns. Endometriosis was the only condition more common in IVF/GIFT-conceived females compared to female controls (16% versus 8%, p=0.07). There were no differences between IVF/GIFT and non-ART conceived women on other female reproductive conditions such as PCOS (18% and 16% respectively) and painful periods (26% and 30% respectively). All male conditions such as undescended testes, sperm parameters or erectile disorders were rare in both groups. Conclusion: As IVF/GIFT-conceived individuals reach the average childbearing age of 31 years, they appear to have no substantial adverse outcomes related to their reproductive health or fertility.
Are Clinical Outcomes of Microdissection Testicular Sperm Extraction in Non-Obstructive Azoospermic Men Affected by the Use of Fresh or Frozen Gametes?
Authors: ROMBAUTS Luk , HORTA Fabrizzio , HOLDEN Sandra , KATZ Darren , GREEN Mark , ZANDER-FOX Deirdre 
Published: November 2022

Background: Non-obstructive azoospermia (NOA) is a severe form of male factor infertility, evident in approximately 5% of infertile couples seeking fertility treatment. The combination of microsurgical testicular sperm extraction (mTESE) and ICSI has become one of the treatment options, with sperm motility positively associated with outcome success rates. Few studies have investigated whether use of fresh or thawed gamete combinations affect clinical outcomes. Aim: To determine the clinical outcomes of ICSI cycles using mTESE recovered testicular sperm of NOA patients and whether these are affected by the use of fresh or thawed gametes. Method: A retrospective study of NOA patients who underwent mTESE between March 2017 and September 2020. Clinical outcomes investigated included successful surgical sperm retrieval (SSR), sperm motility, fertilisation, embryo utilisation and live-birth/ongoing pregnancy rates. Results: A total of 105 NOA patients underwent mTESE, with a 65.7% successful SSR. In total 58 patients contributed to 72 ICSI cycles, with a 37.5% 2PN fertilisation rate and 29.4% live-birth/ongoing pregnancy rate. Cycles using only motile sperm had a greater fertilisation rate than those using a motile/non-motile sperm combination (51.7% vs 31.1%, p[Formula: see text]0.05). Compared with fresh, thawed testicular spermatozoa didn’t affect clinical outcomes, including live-birth/ongoing pregnancy rates (Fresh 18.2%; Thawed 17.9%; Odds ratio (OR) 1.02 (0.34-2.86) p=0.98). In contrast, use of thawed oocytes decreased fertilisation rate [Fresh-oocytes: 45.0%; Vitrified-oocytes: 35.5%; OR 1.47(1.03-2.10), p=0.03] but had no differences for other clinical outcomes, including live-birth/ongoing pregnancy rate (p=0.74). Importantly, injection of exclusively non-motile-spermatozoa (n=26 cycles) resulted in a very low fertilisation rate (2.7%) and no live-birth/ongoing pregnancies were recorded. Conclusion: Microdissection TESE is an effective treatment for NOA patients, with no clear negative effects of using thawed spermatozoa, however, the use of vitrified oocytes requires further investigation. The use of non-motile spermatozoa in mTESE ICSI cycles is discouraged.
Antioxidants in Mouse Embryo Culture and Vitrification Media Maintain an In Vivo Like Gene Expression Profile
Authors: TRUONG Thi T. , HARVEY Alexandra J. , GARDNER David K. 
Published: November 2022

Background: Embryo culture and cryopreservation causes detrimental effects on blastocyst gene expression. While combined antioxidants (acetyl-L-carnitine/N-acetyl-L-cysteine/[Formula: see text]-lipoic acid (A3)) in culture and vitrification media have beneficial effects on embryo and fetal development, their impact on fetal gene expression has not been assessed. Therefore, the effects of antioxidants on global gene expression were examined from fetal and placental tissue of transferred blastocysts and compared to in vivo derived embryos. Aim: To determine the effect of A3 in culture and vitrification media on mouse blastocyst, fetal and placental gene expression. Method: Embryo transfers were conducted on in vivo flushed blastocysts or blastocysts cultured or vitrified with and without A3. Transcriptional profiles of E14 fetal liver and placental tissue in all groups were quantified using RNAseq and functional analyses (KEGG). Results: Compared to in vivo derived embryos, in vitro culture altered the expression of 3601 fetal liver and 408 placental genes. Functional analysis showed upregulation/enrichment of oxidative phosphorylation and mitochondrial function and activity. Similarly, vitrification led to 2018 liver and 216 placental differentially expressed genes (DEGs). Upregulated KEGG pathways were enriched for cell and tissue development and cell cycle regulation. Down regulated pathways were associated with metabolism and immune response. Interestingly, exposure to A3 during development significantly reduced the number of DEGs with 1855 and 4 identified in liver and placentae respectively with no KEGG pathways identified. Correspondingly, exposure to A3 during vitrification reduced the number of DEGs to 1017 in liver and 206 in placentae. Functional pathway enrichment was similar to embryos vitrified without A3, although with decreased expression. Conclusion: Supplementation with antioxidants reduce the number of DEGs and biological processes altered by in vitro culture and vitrification, in fetal liver and placentae, establishing a more in vivo like gene expression profile which may help maintain the viability of vitrified human embryos.
Short-Term Exposure with Long-Term Effects: The Ketone Body, Beta-Hydroxybutyrate, Alters Mouse Embryo Developmental Programming and Reduces Viability
Authors: WHATLEY Emma G. , HARVEY Alexandra J. , GARDNER David K. 
Published: November 2022

Background: Diet-induced nutritional changes in the maternal reproductive tract stimulate embryonic adaptations to maintain growth and survival, directly impacting child and adult health via developmental programming. This is plausibly facilitated by an interrelationship between metabolism and epigenetic control of gene expression, termed ‘metaboloepigenetics’, resulting in heritable modifications that affect long-term offspring health and viability. The ketogenic diet (KD) is increasingly popular amongst sub-fertile women trying to conceive, and results in elevated maternal ketone levels, including beta-hydroxybutyrate (bOHB). The impact of high bOHB levels on embryonic development, physiology, and developmental programming remains unknown. Aim: To assess how bOHB affects preimplantation mouse embryo development, metaboloepigenetic regulation, and post-transfer viability. Method: Preimplantation mouse embryos were cultured in vitro with or without 2 mM bOHB, representing serum concentrations with KD consumption. Day 5 blastocyst cell number and lineage allocation was assessed via differential nuclear stain, metabolism of bOHB and carbohydrates was assessed by ultramicrofluorescence, and acetylation of histone 3 lysine 9 (H3K9ac) and lysine 27 (H3K27ac) were assessed by immunofluorescence. Day 4 blastocysts were transferred to pseudo-pregnant females for analysis of embryonic day 14.5 placental and fetal development. Results: A reduction in total and trophectoderm cell number (P<0.05) was observed, indicating reduced viability. Blastocysts were shown to consume bOHB in vitro, with uptake increasing with bOHB concentration. Further, bOHB increased glycolytic rate (P<0.01), while epigenetic analyses revealed H3K9ac and H3K27ac were unaffected by bOHB. Of significance, post-transfer implantation rates were reduced (P<0.05), concurrent with smaller placental diameter (P<0.01) and fetal crown-rump length (P<0.05), indicating developmental programming alterations. Conclusion: These data infer that bOHB-stimulated metabolic alterations are a contributing factor to ketone-induced developmental programming, which may incorporate epigenetic components other than H3K9ac or H3K27ac. Therefore, consumption of a KD during conception and pregnancy may have negative impacts on the long-term viability and health of offspring.
How Low Can You Go? Transfer of Low-Grade Blastocysts
Authors: ZOU Haowen , KEMPER James , HAMMOND Elizabeth , LIU Yanhe , XU Fengqin , LIU Gensheng , XI Haitao , XUE Lintao , BAI Xiaohong , LIAO Hongqing , XUE Songguo , ZHAO Shuqin , ZHANG Aijun , AFNAN Masoud , WANG Rui , MOL Ben , MORBECK Dean 
Published: November 2022

Background: Low grade blastocyst (LGB) transfer results in varied live birth rates (5-39%). Only limited studies with small sample sizes (n=10-440) exist, due to LGB transfer being less desirable. Definitions of LGB and study designs are heterogenous, further confounding outcome interpretation. Aim: This study aimed to obtain sufficient LGB transfers to determine live birth rates, as well as allow subgroup analysis by blastocyst quality and maternal age. Method: This study was a multicentre, multinational retrospective cohort study across nine IVF clinics in China and New Zealand between 2012 to 2019. 6966 single blastocyst transfer cycles on days 5-7 (fresh and frozen) were collected; of these, 875 transfers were from LGBs (<3BB). Blastocysts with expansion stage 1 or 2 (early blastocysts) were excluded. The main outcome was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n=3849, AA, AB and BA), moderate-grade blastocysts (MGBs; n=2242, BB) and LGBs (n=875, AC, CA, BC, CB and CC). Live birth rates were compared using the Pearson Chi-squared test. A logistic regression analysis examined the relationship between blastocyst grade and live birth after adjustment for confounders: clinic, female age, expansion stage, and blastocyst age. Results: Live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p<0.0001). Within the LGB group, the highest live birth rates were for grade C TE (30%) and the lowest were for grade C ICM (19%). The lowest combined grade (CC) had a 15% live birth rate (n=7/48). The odds of live birth were 2.33 (95% CI = 1.88-2.89) for GGBs compared to LGBs and 1.56 (95% CI = 1.28-1.92) for MGBs compared to LGBs following fresh and frozen blastocyst transfers (p<0.0001). The odds of live birth according to ICM grade were 1.31 (A versus B; 95% CI = 1.15-1.48), 2.82 (A versus C; 95% CI = 1.91-4.18) and 2.16 (B versus C; 95% CI = 1.48-3.16; all p<0.0001). The odds of live birth according to TE grade were 1.33 (A versus B; 95% CI = 1.17-1.50, p<0.0001), 1.85 (A versus C; 95% CI = 1.45-2.34, p<0.0001) and 1.39 (B versus C; 95% CI = 1.12-1.73, p=0.0024). Conclusion: The live birth rate for LGBs is 28%, with rates ranging between 15-31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. Even those in the lowest grading tier maintain modest live birth rates (15%; CC). Thus, these can be considered for transfer in women with few other options.
Is the Ploidy Status of the Embryo Impacted by Gonadotrophin Dose?
Authors: AGRESTA Franca , GARRETT Claire , STOCK-MYER Sharyn , GARDNER David , STERN Kate 
Published: November 2022

Background: There has been much debate and concern about whether the dose of exogenous gonadotrophins used for controlled ovarian stimulation (COS) adversely affects the selection of leading follicles and potentially impacts the quality of the eggs retrieved and the embryos created. The ploidy status of the embryo, as assessed by pre-implantation genetic testing (PGT), is used as a measure of embryo quality.
Immunolocalisation of Olfactory Signalling Molecules in Spermatozoa
Authors: MAKEYEVA Y. , NICOL C. , LEACH S. T. , De GRAAF S. P. , LEDGER W. L. , RYUGO D. K. 
Published: November 2022

Olfactory receptors (ORs) expressed by mature olfactory sensory neurons (mOSNs) in the olfactory neuroepithelium detect and distinguish volatile chemicals of diverse structure. Chemoreception begins when the odorant binds to the OR, initiating a signal transduction cascade involving olfactory G-protein (Golf), adenylyl cyclase 3 (AC3), and cyclic nucleotide-gated cation channels that eventually results in odour perceptions. ORs are also present in non-olfactory systems including spermatozoa. This study examined the immunolocalisation of olfactory marker protein (OMP), OR6B2 (human OR), Golf and AC3 in spermatozoa. OMP is involved in the olfactory signal transduction pathway and is a marker for mOSNs in the olfactory system and for ORs in non-olfactory systems. If OR-chemosensing is confirmed for spermatozoa, the data would imply involvement with excitability, exocytosis, and chemotaxis. We used immunohistochemistry and microscopic analysis to examine olfactory signalling molecules in testis (rat) and spermatozoa (human, ram, rat). In human spermatozoa, we experimentally induced three modes of activation: control, activation and hyperactivation. Modes of activation affected OMP and OR6B2 co-expression. OMP was staged-expressed in the testis, and co-localised with AC3 in the acrosomal membrane and head of rat sperm. OMP was co-expressed with OR6B2, Golf, and AC3 on the head and tail of human, ram, and rat spermatozoa, implying different drivers and separate domains for target recognition (head) and motor activation (tail). The staining patterns in spermatozoa suggest OR-mediated, chemoreceptive mechanisms that control motility, facilitate the acrosomal reaction for capacitation, and promote fertilisation.