bluuebunny/crossref_metadata_2025_split huggingface dataset:
O-172 Live imaging reveals key events in preimplantation embryo development
Authors: Skory R 
Published: July 2024

Abstract
Preimplantation development encompasses the zygote to blastocyst stages, occurring in vivo within the Fallopian tube and in vitro within embryology labs worldwide. During these first five days of life, several key morphologic changes take place facilitating cell fate specification and resulting in blastocyst assembly containing ICM and trophectoderm lineages. These include cell polarization, embryo compaction and inner-outer segregation, which transform the collection of blastomeres into a morula. Subsequently, the blastocoel cavity forms and expands followed by hatching from the zona pellucida prior to implantation. This ability to self-organize has enabled live imaging of these events within intact embryos. Moreover, this has revealed the dynamics of early mitoses, nuclear morphology and cytoskeletal changes driving early development. Although a great deal has been learned in the mouse, events in the human embryo remain relatively unknown. Recent achievements in stem cell-based embryoid models and non-invasive live imaging now poise researchers to make significant advancements unveiling human embryo development. Furthermore, a comprehensive understanding of human embryogenesis is essential to improving IVF efficiency and outcomes. Preimplantation development in mouse and human will be reviewed with a focus on recent discoveries made possible by live imaging.
O-175 Ethical practices and policies for ART carbon reduction
Authors: Richie C 
Published: July 2024

Abstract

Background
The carbon emissions of global health care activities make up 4-5% of total world emissions, placing the health care industry on par with the food sector. Health care contributes to climate change and climate change health hazards. Safe amounts of carbon in the atmosphere have been exceeded—in part because of medical lifestyles in the industrialized world.
A significant proportion of health care carbon comes from pharmaceuticals and clinical services in the developed world, including reproductive technologies. Since 1978, approximately 12 million babies have been born through IVF alone.

Problem statement
Reproductive technologies have an exceptional impact on the environment as they 1. expend carbon in the medical process, 2. increase population growth in mostly high-carbon countries, 3. impact earth’s carrying capacity, and 4. create a carbon legacy. This would not necessarily be ethically problematic, but in a climate crisis carbon emissions must be reduced in all areas of life.

Objectives
This presentation by an ethicist (PhD) will:
1. Highlight aspects of environmental ethics for reproductive technologies
2. Offer practices and policies to make reproductive technologies more sustainable.

Takeaways
• Prevention of infertility fits within basic health care.
• Carbon emissions from reproductive technologies can be reduced by life cycle assessments (LCA) of the procedures and components.
• Clinical evidence can inform ethical policies to reduce the number and kind of reproductive technologies, thereby lowering fertility industry carbon emissions.
• New scientific and technological developments in reproduction must consider sustainability proactively, not reactively, thus putting ethics in the pipeline of reproductive medicine.

Further Reading
Bhopal A, and Norheim O. Priority setting and net zero healthcare: how much health can a tonne of carbon buy?. BMJ 2021; 375:e067199.
Pichler, P.-P. et al., “International Comparison of Health Care Carbon Footprints,” Environmental Research Letters 14, no. 6 (2019): 064004.
Richie, Cristina. Environmental Ethics and Medical Reproduction (Oxford University Press, 2024.
O-177 Emotional experiences of staff caring for parents suffering a pregnancy loss
Authors: Judith J 
Published: July 2024

Abstract
Experiencing pregnancy loss can have devastating emotional impacts on expectant parents, leading them to experience depression, anxiety and post-traumatic stress. There is now a well-established literature into the experiences of expectant parents, with dozens of studies conducted since the 1990s. However, over this period there has been notably less research conducted into the experiences of the professionals who care for these women. Addressing this is crucial; healthcare professionals are the greatest asset that healthcare systems have. Providing better support for them is the best route to improving care for expectant parents. The studies which have been conducted suggest the emotional toll on professionals can be significant. Emotions described can reflect those of expectant parents, including sadness, grief, and anger. One study suggested that delivering this care can be like ‘working in darkness’; another found that delivering news of losses to expectant parents on a regular basis can cause an emotional ‘repetitive strain injury’ for some.
This talk will tackle this topic, providing updates and insights from recent studies which have investigated the experiences of healthcare professionals who undertake the emotional work of caring for expectant parents who are experiencing loss. It will take an interactive approach, using audience feedback to understand and learn from the experiences shared by those in the room. The importance and value of professionals who work in this area will be highlighted; coping strategies and self-care activities will be considered.
P-196 Early blastocyst formation on day 4 is associated with improved clinical outcome and advocates for embryo quailty assessment on day 4
Authors: Lammers J , Loubersac S , Reignier A , Freour T 
Published: July 2024

Abstract

Study question
Is early cavitation on day 4 associated with improved clinical outcome?

Summary answer
Early blastulation on day 4 is a positive predictor of implantation after single blastocyst transfer on day 5.

What is known already
In order to select the blastocyst with the highest implantation potential for transfer or freezing, several morphological and/or morphokinetic parameters have been proposed. For instance, early compaction on day 3 (D3) or blastocyst expansion on day 5 (D5) have been reported to be relevant when selecting embryos for transfer. However, day 4 has often been overlooked and very few studies focused on early blastulation on day 4 (D4). Indeed, data on early blastulation on day 4 is scarce. It was however recently demonstrated that embryos transferred on day 4 could provide acceptable pregnancy rates.

Study design, size, duration
This monocentric retrospective cohort study was conducted in all consecutive couples undergoing IVF cycles in 2017-2022 with single blastocyst transfer and observation on day 4.

Participants/materials, setting, methods
Morphological and morphokinetic assessment was performed by 2 operators at 93±2h, 116±2h (and 140±2h) post insemination, on day 4, 5 (and 6) respectively. A total of 26 507 D4 embryos were included in this study and grouped according to the observation of early cavitation or not : 23 244 were in the D4 control group (absence of early cavitation on D4) and 3263 were in the D4 blastocyst group (observation of early cavitation on D4).

Main results and the role of chance
The proportion of embryos used clinically for either transfer or freezing on day 5 or 6 was significantly higher in the D4 blastocyst group than in D4 control group (86.7% vs 50.1% respectively, p &lt; 0.05).
Concerning pregnancy rate, cinical pregnancy rate was significantly higher in the D4 blastocyst group than in D4 control group (p &lt; 0.05). In the D4 control group, 5051 embryos were transferred and clinical pregnancy rate is 28.7%. In the D4 blastocyst group, 1286 embryos were transferred (fresh or frozen) and clinical pregnancy rate is 40.2%.

Limitations, reasons for caution
The retrospective and monocentric design calls for caution when considering the generalizability of our findings.

Wider implications of the findings
We postulate that D4 embryo quality assessment should be widely implemented in any blastocyst program in order to improve embryo quality assessment and subsequently clinical outcome.

Trial registration number
not applicable
P-236 Simulated cohort ranking analysis estimates the number of IVF cycles needed to reach fetal heartbeat with and without artificial intelligence (AI) embryo triage
Authors: Shapiro M , Amar Y , Tauber Y , Seidman D , Gilboa D 
Published: July 2024

Abstract

Study question
What is the impact of AI-based embryo triage on the number of IVF cycles needed to reach fetal heartbeat (FH)?

Summary answer
Simulated cohort ranking via the AIVF Day-5 AI model demonstrates a 27.5% reduction in the number of IVF cycles needed to achieve FH.

What is known already
Published reports show FH rates per first-time IVF/single euploid embryo transfer ranging from 26-43% (age &lt;38 yrs). Likewise, the average number of autologous retrieval cycles required for FH is 2.25±0.8, depending on oocyte age and demographic. While conventional embryo morphology ranking is used as a proxy indicator for IVF success, its use is associated with observer variability and manual workflow. This leads to a non-efficient cycle number-per-FH ratio, preventing the clinic’s ability to service more patients.

Study design, size, duration
A single center database (N = 10,000 embryos) was used to generate 1,288 simulated cohorts reflecting known maternal age/cohort size distributions. Only cohorts containing ≥1 FH+ embryo(s) were included. The model ranked embryos within each cohort by scalar output (1-9.9). The position of the first FH+ embryo within each AI-ranked cohort was calculated and averaged across cohorts to compute number of cycles required to reach FH.

Participants/materials, setting, methods
Data was stratified into 5 age categories; the prevalence of top/good/fair graded embryos per cohort were included according to their known (%) prevalences per stratified age group. Data was randomized into 1,288 cohorts; positions of the first FH+ embryo in each cohort was calculated (for example, if the 2nd AI-ranked embryo was FH+, a value of 2 was assigned, respectively). Values were averaged and compared to conventional IVF.

Main results and the role of chance
A mean ± SD of 1.63 ±1.06 cycles was needed to reach the first FH+ embryo with AI cohort ranking (pooled mean across all age groups &lt;38 years) with a mean cohort size N = 7.8 embryos. The relative percent reduction in cycles needed to reach FH when compared to conventional IVF without AI ranking (2.25±0.8; age &lt;38 yrs) was 27.5%. Ranking and electronic recording time for ranking per embryo with/without AI implementation was 186.0 versus 30.9 seconds per embryo, respectively. Relative ranking time reduction was 83%.

Limitations, reasons for caution
Results were pooled across age groups and not stratified per age. Prospective validation is ongoing to show the influence of demographics/clinical characteristics on AI utility.

Wider implications of the findings
This study demonstrates the potential of shortening the time to pregnancy by using AI-based quantitative embryo assessment for cohort ranking.

Trial registration number
Not applicable
P-621 Rekovelle® vs Gonal-F®: in vitro characterization of intracellular signals induced by the two FSH preparations
Authors: Lazzaretti C , Baschieri L , Mascolo E , Sperduti S , Perri C , Fusco C , Simoni M , Casarini L 
Published: July 2024

Abstract

Study question
Do Rekovelle® and Gonal-F® modulate preparation-specific signalling?

Summary answer
Gonal-F® and Rekovelle® induce preparation-specific pattern of intracellular signalling.

What is known already
Rekovelle® and Gonal-F® are two commercial preparations of recombinant FSH used in assisted reproduction. These preparations differ in originator cells (PER.C6® cell line of human fetal retinal origin for Rekovlle®; modified Chinese Hamster Ovary cell line for Gonal-F®), likely reflecting glycosylation profiles impacting their mode of action.

Study design, size, duration
3-year in vitro functional comparison of Rekovelle® and Gonal-F®, using the transfected HEK293 cell line expressing FSH receptor (FSHR).

Participants/materials, setting, methods
FSHR-expressing HEK293 cells were treated with increasing concentrations of GonalF® and Rekovelle® (pM-µM) to evaluate receptor-receptor interaction and trafficking, intracellular cyclic adenosine monophosphate (cAMP) and Ca2+ increase by bioimaging techniques, as well as phospho-protein by Western blotting, and genomic effects by CRE-luciferase reporter gene activity.

Main results and the role of chance
Both the preparations induced similar, dose-dependent increase of receptor trafficking through intracellular organelles. These data were obtained by evaluation of the interaction between FSHR and endosomal markers RAB-GTPases (Rab) 5 and 7. Rekovelle® induced more pronounced steroifogenic signals than Gonal-F®, detected as FSHR-FSHR interactions at the cell membrane, cAMP accumulation, cAMP-responsive elements binding protein (CREB) phosphorylation and CRE promoter activity. Interestingly, while cell treatment by Gonal-F® mediated complete dose-response of cAMP, consisting in the continuous increase of the second messenger together with the increase of FSH concentration, Rekovelle® had biphasic action where cAMP increased from 0 to 100 nM although decreased at 1 µM Rekovelle® dose. Moreover, Rekovelle® was 10-times more potent than Gonal-F® in activating intracellular Ca2+ activation. The two preparations induced similar pattern of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation. In conclusion, Rekovelle® has higher potency than Gonal-F® in activating cAMP- and Ca2+-dependent intracellular events, potentially resulting in preparation-specific steroidogenic pattern.

Limitations, reasons for caution
Experiments were performed in the transfected HEK293 cell line in vitro and should be confirmed by clinical observations.

Wider implications of the findings
We described different intracellular events mediated by Gonal-F® and Rekovelle® in vitro, likely originated by different glycan profiles and possibly impacting the ovarian response during assisted reproduction.

Trial registration number
Not Applicable
P-651 Neither high nor low serum progesterone levels affect clinical outcomes in Artificially prepared-frozen embryo transfer cycles using intramuscular progesterone
Authors: Sharma G , Roque M , Bhoi N , Chandra V , Murdia K , Murdia N 
Published: July 2024

Abstract

Study question
Does serum progesterone level on the day of frozen-thawed embryo-transfer (FET) correlate with the likelihood of achieving pregnancy in artificial FET cycles utilizing intramuscular progesterone?

Summary answer
Serum progesterone levels on the day of FET do not correlate with the likelihood of achieving a pregnancy in artificial FET cycles employing intramuscular progesterone.

What is known already
There is scientific evidence suggesting that serum progesterone levels under a specific cutoff level on the day of FET significantly decrease the clinical outcomes in patients under artificial endometrial preparation using micronized vaginal progesterone. However, no substantial evidence exists in patients under artificial endometrial preparation using intramuscular progesterone.

Study design, size, duration
This prospective cohort study was conducted from February to December 2022 and enrolled 353 patients undergoing FET in hormone replacement therapy (HRT) cycles using intramuscular progesterone until the day of embryo transfer.

Participants/materials, setting, methods
The study included women aged 21-40 years old undergoing FET, triple layer endometrium &gt;7mm, and ≥2 high-quality embryos (Gardner’s grade 3/4/5/AA/AB/BA/BB) available. Exclusion criteria included patients with uncontrolled diabetes, hypertension, heart disease, known autoimmune diseases, uterine infertility factor, severe male factor infertility (total sperm count &lt; 5 million/ml), and cases requiring surgically retrieved sperm for ICSI.

Main results and the role of chance
The cohort had an average age of 32.09 ± 4.19 years, BMI of 24.70 ± 3.07 kg/m², and endometrial thickness of 8.87 ± 1.06 mm on the day of embryo transfer. The mean serum progesterone level was 31.36 ± 13.78 ng/ml. Participants were categorized into quartiles based on serum progesterone levels. :Q1 (&lt;21.7 ng/ml), Q2 (21.7-28.1 ng/ml), Q3 (28.2-40.0 ng/ml), and Q4 (≥40.0 ng/ml). No significant difference in Clinical Pregnancy Rate (CPR), Ongoing Pregnancy Rates (OPR), and first-trimester miscarriage rates were observed across quartiles. The OPRs according to serum progesterone quartiles were: Q1: 57.5%; Q2: 62.6%; Q3: 59.6%; Q4:62.8%, with no statistical difference among the groups. Binary logistic regression revealed no statistically significant differences in clinical pregnancy and ongoing odds among the quartiles.

Limitations, reasons for caution
Although a prospective study, its relatively small sample size may affect the results’ robustness and generalizability.

Wider implications of the findings
These findings suggest that when using intramuscular progesterone before embryo transfer in FET under HRT, serum progesterone testing may not be necessary before embryo transfer, as progesterone levels have no impact on clinical outcomes in this group of patients.

Trial registration number
CTRI/2022/11/046995
Breast Cancer Screening With Automated Breast US and Mammography vs Handheld US and Mammography in Women With Dense Breasts in a Real-World Clinical Setting
Authors: Winkelman Andrew J , Tulenko Kassandra , Epstein Samantha H , Nguyen Jonathan V , Ford Clay , Miller Matthew M 
Published: June 2024

Abstract

Objective
We compared the performance of 2 breast cancer screening approaches, automated breast US (ABUS) with same-day mammography (ABUS/MG) and handheld US (HHUS) with same-day mammography (HHUS/MG), in women with dense breasts to better understand the relative usefulness of ABUS and HHUS in a real-world clinical setting.

Methods
In this institutional review board–approved, retrospective observational study, we evaluated all ABUS/MG and HHUS/MG screening examinations performed at our institution from May 2013 to September 2021. BI-RADS categories, biopsy pathology results, and diagnostic test characteristics (eg, sensitivity, specificity) were compared between the 2 screening approaches using Fisher’s exact test.

Results
A total of 1120 women with dense breasts were included in this study, with 852 undergoing ABUS/MG and 268 undergoing HHUS/MG. The sensitivities of ABUS/MG and HHUS/MG were 100% (5/5) and 75.0% (3/4), respectively, which was not a statistically significant difference (P  = .444). The ABUS/MG approach demonstrated a slightly higher specificity (97.4% [825/847] vs 94.3% [249/264]; P = .028), higher accuracy (97.4% [830/852] vs 94.0% [252/268]; P = .011), and lower biopsy recommendation rate (3.2% [27/852] vs 6.7% [18/268]; P = .019) than the HHUS/MG approach in our patient population.

Conclusion
Our findings suggest that ABUS/MG performs comparably with HHUS/MG as a breast cancer screening approach in women with dense breasts in a real-world clinical setting, with the ABUS/MG approach demonstrating a similar sensitivity and slightly higher specificity than the HHUS/MG approach. Additional variables, such as patient experience and physician time, may help determine which imaging approach to employ in specific clinical settings.
Patient characteristics and antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae infections in international travellers: a GeoSentinel analysis
Authors: McGuinness Sarah L , Muhi Stephen , Nadimpalli Maya L , Babiker Ahmed , Theunissen Caroline , Stroffolini Giacomo , Motta Leonardo , Gobbi Federico , Huits Ralph , Libman Michael , Leder Karin ,   for the GeoSentinel Network
Published: June 2024

Abstract

Background
Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales, including Escherichia coli and Klebsiella pneumoniae, playing significant roles. While international travel to low- and middle-income countries is linked to colonization with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterize E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates.

Methods
We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes.

Results
Over the 8-year period, we included 655 patients (median age 41 years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72 K. pneumoniae infections. Common travel regions included sub-Saharan Africa, Southeast Asia and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalized. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time.

Conclusions
E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasizes the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition.
Night shift work and myocardial infarction in the UK Biobank
Authors: Yang M J , Jia Z W , Wang E , Li J C , Tang A M , Song Z B , Zhang Z 
Published: June 2024

Abstract

Background
Shift work has become popular along with adverse effects such as disrupted biological rhythms, metabolic changes, sleep disorders and myocardial infarction. Studies have shown a link between myocardial infarction and shift work, but evidence is still lacking.

Aims
We aim to explore the association between present and past shift work and risk of myocardial infarction in a large population of European workers.

Methods
We analysed data from the UK Biobank with &gt;500 000 participants and an average 12-year follow-up duration. Cox proportional hazard models were employed to analyse the relationship between present shift work (n = 265 064), lifetime duration or frequency of shift work (n = 71 428) and the risk of myocardial infarction, as well as the association between rest day during shift work and myocardial infarction incidents in night shift workers (n = 14 588).

Results
Night shift workers had a higher risk of myocardial infarction compared to day workers, including ‘shift but never/rarely night shifts’ (hazard ratio [HR] = 1.09, 95% confidence interval [CI] 1.00–1.20), ‘some night shifts’ (HR = 1.13, 95% CI 1.01–1.27) and ‘usual/permanent night shifts’ (HR = 1.21, 95% CI 1.07–1.37), respectively. Similarly, higher frequency and longer duration of night shift work were associated with the increased risk of myocardial infarction (&lt;10 years: HR = 1.20, 95% CI 1.01–1.42; ≥10 years: HR = 1.51, 95% CI 1.28–1.77; or an average of more than eight nights per month: HR = 1.45, 95% CI 1.23–1.71). However, longer rest days couldn’t decrease myocardial infarction risk compared to those who rest 1 day.

Conclusions
Present and lifetime exposure to night shifts were associated with a risk of myocardial infarction and did not benefit from longer rest days.