CLINICAL PROFILES OF PATIENTS UNDERGOING PACEMAKER IMPLANTATION

Background and Objective: The implantation of a permanent cardiac pacemaker for the treatment of bradyarrhythmia is one of the most popular cardiac interventions. The goal of this study is to look at the clinical profiles of individuals who have permanent pacemakers implanted Material and Methods: The study was conducted using observational methods. The study included patients who received a permanent pacemaker for bradyarrhythmias between November 2019 and November 2021. A thorough review of the demographic profile and indications was performed. Results: The vast majority of the 312 patients were older, with the majority being between the ages of 56 and 88 years old (75 % ). Pacemakers were implanted in more men than in women. Complete heart block was the most common ECG finding and the most common presenting symptom was syncope. The most prevalent sign of pacing was acquired A-V block, and the most common pacemaker mode was single chamber (VVI/VVIR). Conclusion: Acquired A-V block and SSS were found to be the most common reasons for pacemaker implantation in our study. Higher implantation rates were linked to advanced age and male gender.

Randomized allocation of oocytes to IVF or ICSI for IVF-naïve cases with unexplained infertility in an IVF-ICSI Split protocol favors ICSI to optimize live birth outcomes

In assisted reproduction treatments (ART), applying the ICSI method for fertilization of oocytes rather than traditional IVF method, is regarded as controversial for two reasons, namely utility and safety. Our study examines an IVF-ICSI Split model for couples with unexplained infertility, where male factor is meticulously excluded and ART is conducted by a strict algorithm, a commitment to blastocyst culture, along with single embryo transfers and a high commitment to cryopreservation. From 242 treatment cycles, 3346 oocytes recovered (13.8 per OPU) were randomly allocated to IVF or ICSI and the fertilization rates standardized to the number of 2PNS arising from each group applying the metaphase II oocyte number identified for the ICSI group, as the denominator for both groups. The fertilization rates were significantly higher overall for ICSI (83.2% vs 65.4%; p<0.0001), being most pronounced for women under 40 years. The resultant embryos had equivalent implantation rates in both fresh ET and frozen (FET) cycles with no significant differences in pregnancy rates, miscarriage rates or live birth outcomes indicating equivalent embryo quality. However, there were significantly higher numbers of ICSI-generated embryos cryopreserved and subsequent FET procedures showed higher live birth rates (21 births vs 6 births; p<0.005) and potential livebirths (214 births vs 104 births; p<0.0001). No congenital fetal abnormalities were detected in any of the 199 babies delivered during the study period to December 2020, neither IVF-generated nor ICSI-generated. Whilst the data strongly favors ICSI, there were 2 women (from 26 with fertilization in one arm only) who demonstrated fertilization only in the IVF arm of the study. We conclude that the IVF-ICSI Split model should be undertaken on all IVF-naïve women with unexplained infertility to determine the appropriate fertilization mode, albeit ICSI will be safely preferred for >90% of cases.

Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy

Aims Risk stratification algorithms for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) and regional differences in clinical practice have evolved over time. We sought to compare primary prevention implantable cardioverter defibrillator (ICD) implantation rates and associated clinical outcomes in US vs. non-US tertiary HCM centres within the international Sarcomeric Human Cardiomyopathy Registry. Methods and results We included patients with HCM enrolled from eight US sites (n = 2650) and five non-US (n = 2660) sites and used multivariable Cox-proportional hazards models to compare outcomes between sites. Primary prevention ICD implantation rates in US sites were two-fold higher than non-US sites (hazard ratio (HR) 2.27 [1.89–2.74]), including in individuals deemed at high 5-year SCD risk (≥6%) based on the HCM risk-SCD score (HR 3.27 [1.76–6.05]). US ICD recipients also had fewer traditional SCD risk factors. Among ICD recipients, rates of appropriate ICD therapy were significantly lower in US vs. non-US sites (HR 0.52 [0.28–0.97]). No significant difference was identified in the incidence of SCD/resuscitated cardiac arrest among non-recipients of ICDs in US vs. non-US sites (HR 1.21 [0.74–1.97]). Conclusion Primary prevention ICDs are implanted more frequently in patients with HCM in US vs. non-US sites across the spectrum of SCD risk. There was a lower rate of appropriate ICD therapy in US sites, consistent with a lower-risk population, and no significant difference in SCD in US vs. non-US patients who did not receive an ICD. Further studies are needed to understand what drives malignant arrhythmias, optimize ICD allocation, and examine the impact of different ICD utilization strategies on long-term outcomes in HCM.

Improving Sperm Oxidative Stress and Embryo Quality in Advanced Paternal Age Using Idebenone In Vitro—A Proof-of-Concept Study

Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm from men aged >40 years and older CBAF1 mice (12–18 months), were treated with 5 µM and 50 µM of idebenone and intracellular and superoxide ROS concentrations assessed. Following in vitro fertilization (IVF), embryo development, blastocyst differentiation, DNA damage and cryosurvival, pregnancy and implantation rates and fetal and placental weights were assessed. Five µM of idebenone given to aged human and mouse sperm reduced superoxide concentrations ~20% (p < 0.05), while both 5 and 50 µM reduced sperm intracellular ROS concentrations in mice ~30% (p < 0.05). Following IVF, 5 µM of idebenone to aged sperm increased fertilization rates (65% vs. 60%, p < 0.05), blastocyst total, trophectoderm and inner cell mass cell numbers (73 vs. 66, 53 vs. 47 and 27 vs. 24, respectively, p < 0.01). Treatment with idebenone also increased blastocyst cryosurvival rates (96% vs. 78%, p < 0.01) and implantation rates following embryo transfer (35% vs. 18%, p < 0.01). Placental weights were smaller (107 mg vs. 138 mg, p < 0.05), resulting in a larger fetal to placental weight ratio (8.3 vs. 6.3, p = 0.07) after sperm idebenone treatment. Increased sperm ROS concentrations associated with advanced paternal age are reduced with the addition of idebenone in vitro, and are associated with improved fertilization rates, embryo quality and implantation rates after IVF.

P–183 Air quality oscillations inside the IVF laboratory do not affect clinical outcomes

Study question Do air contaminant oscillations impair in vitro fertilization clinical results? Summary answer Oscillations of the main air contaminants (SO2, NO, NO2, O3, CO, PM10, C6H6) inside the IVF laboratory do not impair success rates. What is known already Pollution is a challenge that as humans we face around the world. Given the limited number of studies that demonstrate the effect of pollution into IVF treatments, the effect that air contaminants have on in vitro human gametes/embryos is not clear. IVF laboratories are designed to limit the stress that gametes and embryos suffer during culture and manipulation. Controlling temperature, humidity, light, and filtering the air is essential to have a successful IVF program. However, HEPA and active carbon filters are not enough to ensure that gametes/embryos are not exposed to contaminants, exposing them to potentially harmful gases and particles. Study design, size, duration Prospective study comprising treatments throughout 2019, recording levels of the main air contaminants (SO2, NO, NO2, O3, CO, PM10, C6H6) every 10 minutes inside the IVF laboratory in order to assess the effect of these pollutants. We included egg donor cycles without PGT-A. Participants/materials, setting, methods A total of 724 egg donation treatments were included. Using uninterrupted culture (Global, CooperSurgical) in time lapse incubators (Embryoscope, Vitrolife). A mean concentration of every pollutant during the 6 days of every treatment was calculated. We analyzed success rates such as fertilization rates, blastocyst rates, pregnancy rates, implantation rates, miscarriage rates, and live birth rates. Main results and the role of chance Our results show that no contaminant affects neither fertilization rates nor good quality blastocyst rates. The only pollutants that have an association with pregnancy rates are NO and CO (p = 0.014 y p = 0.021) in both the univariate and the multivariate statistical analysis. Still, this association is week and could be explained due to the large data set. When analyzing further data we do not find any association between the dose of contaminants and implantation rates, miscarriage rates nor live birth rates (p &gt; 0.01) demonstrating that oscillations in levels of these contaminants do not affect clinical results. Our results differ with the results from a previous study where they detected an effect of SO2 and O3 when analyzing frozen embryo transfer results. This might be explained because the levels of these gases were lower in our clinic and the pregnancy and live birth rates are higher. Limitations, reasons for caution Although we measured the levels of the contaminants inside the IVF laboratory, we did not measure the levels inside the incubators. Wider implications of the findings: This results show that IVF success rates are not impaired by oscillations in air quality if the laboratory does use the necessary HEPA and active-carbon air filter systems. Trial registration number Not applicable

O-123 Calibration of artificial intelligence (AI) models is necessary to reflect actual implantation probabilities with image-based embryo selection

Study question Do AI models for embryo selection provide actual implantation probabilities that generalise across clinics and patient demographics? Summary answer AI models need to be calibrated on representative data before providing reasonable agreements between predicted scores and actual implantation probabilities. What is known already AI models have been shown to perform well at discriminating embryos according to implantation likelihood, measured by area under curve (AUC). However, discrimination performance does not relate to how models perform with regards to predicting actual implantation likelihood, especially across clinics and patient demographics. In general, prediction models must be calibrated on representative data to provide meaningful probabilities. Calibration can be evaluated and summarised by “expected calibration error” (ECE) on score deciles and tested for significant lack of calibration using Hosmer-Lemeshow goodness-of-fit. ECE describes the average deviation between predicted probabilities and observed implantation rates and is 0 for perfect calibration. Study design, size, duration Time-lapse embryo videos from 18 clinics were used to develop AI models for prediction of fetal heartbeat (FHB). Model generalisation was evaluated on clinic hold-out models for the three largest clinics. Calibration curves were used to evaluate the agreement between AI-predicted scores and observed FHB outcome and summarised by ECE. Models were evaluated 1) without calibration, 2) calibration (Platt scaling) on other clinics’ data, and 3) calibration on the clinic’s own data (30%/70% for calibration/evaluation). Participants/materials, setting, methods A previously described AI algorithm, iDAScore, based on 115,842 time-lapse sequences of embryos, including 14,644 transferred embryos with known implantation data (KID), was used as foundation for training hold-out AI models for the three largest clinics (n = 2,829;2,673;1,327 KID embryos), such that their data were not included during model training. ECEs across the three clinics (mean±SD) were compared for models with/without calibration using KID embryos only, both overall and within subgroups of patient age (&lt;36,36-40,&gt;40 years). Main results and the role of chance The AUC across the three clinics was 0.675±0.041 (mean±SD) and unaffected by calibration. Without calibration, overall ECE was 0.223±0.057, indicating weak agreements between scores and actual implantation rates. With calibration on other clinics’ data, overall ECE was 0.040±0.013, indicating considerable improvements with moderate clinical variation. As implantation probabilities are both affected by clinical practice and patient demographics, subgroup analysis was conducted on patient age (&lt;36,36-40,&gt;40 years). With calibration on other clinics’ data, age-group ECEs were (0.129±0.055 vs. 0.078±0.033 vs. 0.072±0.015). These calibration errors were thus larger than the overall average ECE of 0.040, indicating poor generalisation across age. Including age as input to the calibration, age-group ECEs were (0.088±0.042 vs. 0.075±0.046 vs. 0.051±0.025), indicating improved agreements between scores and implantation rates across both clinics and age groups. With calibration including age on the clinic’s own data, however, the best calibrations were obtained with ECEs (0.060±0.017 vs. 0.040±0.010 vs. 0.039±0.009). The results indicate that both clinical practice and patient demographics influence calibration and thus ideally should be adjusted for. Testing lack of calibration using Hosmer-Lemeshow goodness-of-fit, only one age-group from one clinic appeared miscalibrated (P = 0.02), whereas all other age-groups from the three clinics were appropriately calibrated (P &gt; 0.10). Limitations, reasons for caution In this study, AI model calibration was conducted based on clinic and age. Other patient metadata such as BMI and patient diagnosis may be relevant to calibrate as well. However, for both calibration and evaluation on the clinic’s own data, a substantiate amount of data for each subgroup is needed. Wider implications of the findings With calibrated scores, AI models can predict actual implantation likelihood for each embryo. Probability estimates are a strong tool for patient communication and clinical decisions such as deciding when to discard/freeze embryos. Model calibration may thus be the next step in improving clinical outcome and shortening time to live birth. Trial registration number This work is partly funded by the Innovation Fund Denmark (IFD) under File No. 7039-00068B and partly funded by Vitrolife A/S

P–532 Embryo quality needs to be considered as a main criterion when selecting mosaic embryos for transfer

Study question Should we consider embryo quality as one of the most important criteria to follow when transferring a mosaic embryo? Summary answer Embryo quality is an implantation biomarker both for euploid and mosaic embryos, and also a determinant for selecting the most eligible mosaic for transfer. What is known already Several studies show the benefit of transferring mosaic embryos when there are no euploid embryos to transfer, and they still result in ongoing pregnancies and what is more important is that they result in healthy babies. Studies and guidelines suggest prioritizing mosaic embryos based on maternal age, chromosomes impacted, percentage of aneuploidy, number of chromosomes involved, type of mosaic (simple vs complex, segmental vs complete, monosomy vs trisomy) but embryo quality is never part of these criteria. Studies claim that mosaic implantation rate is lower than euploid embryos, but they never show if both populations are comparable in terms of quality. Study design, size, duration This is a retrospective observational study performed in a private centre between February 2018 and January 2020. The study includes the data analysis of 96 euploid blastocysts and 14 low risk mosaic blastocysts (defining low risk regarding chromosome syndromes and less than 50% level mosaicism). All transferred in single embryo transfer (SET) to 105 patients after PGT-A (mean maternal age 38,9 years). The SET factor enables us to track the implantation outcome of all embryos. Participants/materials, setting, methods PGT-A with NGS technology was offered to patients of advanced maternal age and/or with repeated IVF failures. Trophectoderm biopsies were performed on day 5 and/or day 6 embryos, with laser assistance. Blastocyst morphology was scored in 3 groups: A: excellent (AA, AB, BA), B: good (BB), C: average and poor-quality embryos (BC, CB, CC). (Gardner-Schoolcraft classification) Low risk mosaic embryo transfer was offered to patients with no euploid embryos to transfer. Main results and the role of chance We found no significant differences between both populations (euploid and mosaic embryos) in terms of embryo quality (Chi^2 p-value =0,0975) so we were able to compare the overall implantation of similar quality populations. Despite euploid implantation being higher as described in most studies, no statistical differences (Chi^2 p-value = 0,4344) were found in terms of implantation rates between mosaic (57,0%) and euploid (67,6%) blastocysts during the same period. There are no differences between the mean age of both groups (39,7 vs 38,8 years, respectively). The implantation rates for euploid blastocysts were 79,5% (n = 39), 62,7% (n = 51) and 33,3% (n = 6) in the A, B and C blastocyst quality groups, respectively, showing significative differences among the three groups. The implantation rates of low-risk mosaic blastocysts were 100% (n = 3), 62,5% (n = 8) and 0,0% (n = 3) in the A, B and C blastocyst morphology groups, respectively, showing also still significant differences among the three groups despite the small population. (Chi^2 p-values according to implantation: Euploid =0,0434; Mosaic=0,0419) We have also compared the three quality categories between both populations showing no significative differences (Chi^2 p-values according to quality: A = 0,4344; B = 0,9894; C = 0,2568), concluding that same quality embryos behave the same way despite being euploid or mosaic. Limitations, reasons for caution The study is limited by its retrospective nature and the low number of mosaic embryos transferred as they are the last option for transfer. Additionally, it is common to transfer more than one mosaic embryo to increase the chances of pregnancy, therefore losing implantation track. Wider implications of the findings: Embryo quality has always been a strong biomarker predictable for implantation and this is also true for mosaic embryos as well. It is a simple concept, but we cannot compare implantation potential of euploid embryos with mosaic embryos without describing both populations in terms of quality. Trial registration number Not applicable