Multicenter Retrospective Study Research Articles

P-446 Personalization of the euploid embryo transfer guided by the endometrial receptivity analysis in patients with >1 previous failed transfer

Abstract Study question Does personalized embryo transfer (pET) guided by Endometrial Receptivity Analysis (ERA) increase reproductive outcome in patients with >1 previous failed transfer of an euploid embryo? Summary answer pET guided by ERA resulted in a significantly higher Pregnancy Rate (PR), Ongoing Pregnancy Rate (OGPR) and Live Birth Rate (LBR) versus standard embryo transfer. What is known already pET consists of synchronizing embryo transfer with the optimal endometrial receptivity status by the transcriptomics identification of the personalized window of implantation (WOI). Euploid transfers improve reproductive outcome controlling the embryo contribution in the implantation. Controversial results have been published regarding the clinical usefulness of pET in a range of clinical indications. Here we present data from patients with >1 previous failed embryo transfer (ET) in a subsequent euploid ET. Study design, size, duration Multicenter retrospective study involving 270 patients with at least one previous implantation failure between 2017 and 2021. These patients were divided into two groups according to their subsequent transfer: study group (pET guided by ERA) (n = 200), and control group (standard transfer) (n = 70). All the ET were done in Hormone Replacement Therapy cycles (HRT). PR, OGPR and LBR were compared between the two groups. Participants/materials, setting, methods Age, body mass index, previous failed attempts, inner cell mass (ICM) and trophectoderm (TE) quality of the transferred embryos were compared between the groups. Study group had an ERA result as standard WOI or displaced WOI and pET of an euploid embryo was carried out in a subsequent HRT cycle (following the same conditions and recommendations provided by ERA). Wilcoxon rank sum test was applied to quantitative comparations. Chi-square test was done for categorical variables. Main results and the role of chance Clinical results in terms of PR, OGPR and LBR were significantly higher when pET guided by ERA was performed when compared to the non-ERA group. PR was 65% (130/200) in pET versus 37.14% (26/70) in control group (P = 0.000088); OGPR was 49% (98/200) in pET versus 27.14% (19/70) in control group (P = 0.0024); and LBR was 48.20% (95/197) in pET versus 26.09% (18/69) in control group (P = 0.0022). Control and demographics variables did not show differences between the two groups: Age: 35.27 ± 3.86 versus 35.77 ± 3.35 (P = 0.31); BMI: 22.99 ± 3.02 versus 23.25 ± 3.72 (P = 0.52); Previous failed attempts: 2.42 ±1.78 versus 2.17 ±1.81 (P = 0.32); P values where 0.1 and 0.36 for comparisons of optimal quality of ICM and TE, respectively. Limitations, reasons for caution This is a retrospective study, having the limitations of its nature. Wider implications of the findings These results show that pET guided by the ERA test of an euploid embryo significantly increases the reproductive outcomes (PR, OGPR and LBR) in patients with ≥1 previous failed transfer compared to the standard frozen ET. Trial registration number Hospital Clínico de Valencia Ethic Committee approval nº. 2021/018.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32weeks. The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32weeks and admission age within 72h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. (1) Gestational age, 5min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

P-327 A multicenter retrospective study of the investigation of detailed immunological inflammatory grading for chronic endometritis and their correlation with the endometrial microbiome

Abstract Study question There exists refractory chronic endometritis which does not respond to antibiotic treatment. This study aims to elucidate its pathogenesis and develop detection methods. Summary answer Through treatment intervention for chronic endometritis (CE), the inflammatory grade decreased overall and the bacteria most associated with endometritis were Lactobacillus iners. What is known already CE and endometrial dysbiosis have been reported to be associated with recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), but there is insufficient data confirming the interrelation between them. Moreover, the diagnosis of CE typically involves single immunohistochemical staining with CD138, but the diagnostic criteria vary across reports (e.g., McQueen’s method, Liu’s method, etc.) and moreover, use of this classical inflammatory assessment methods raises concerns about their sufficiency in evaluating the pathogenesis of endometritis in cases of RPL and RIF. Study design, size, duration A retrospective analysis was conducted on 206 samples of endometrial specimens collected from infertile patients at seven participating assisted reproductive healthcare facilities from 2021 to 2023. Among these, 73 samples (from 48 cases) had undergone both histological examination and simultaneous endometrial microbiome testing, and data on pregnancy outcomes (including implantation success and ongoing pregnancy rate) were collected until December 2023 for these cases. Participants/materials, setting, methods The endometrial specimens from cases with RIF or RPL were obtained through intrauterine aspiration in luteal phase. Immunohistochemical staining using CD138, CD56, and CD8 antibodies was performed. A composite grading for endometritis, based on histological findings and immunohistochemistry intensity, was established (INF grading; grade 0 to 5). Furthermore, a portion of the specimens underwent microbiome analysis using next-generation sequencing targeting the 16SrRNA, exploring correlations between bacterial taxa, abundance, histological findings, and pregnancy outcomes. Main results and the role of chance Among analyzed 48 cases, 11 cases underwent repeated endometrial microbiome analysis post-treatment again, while 7 cases had additional testing without improvement in chronic endometritis (CE) or endometrial dysbiosis. The McQueen’s method diagnosed 27 cases with CE, while the Liu method identified 4 cases. According to our INF grading, 11 cases were classified as endometritis grade 3 or above. Successful embryo implantation was achieved in 18 cases (37.5%), with ongoing pregnancy in 13 cases (27.1%). CE treatment involved broad-spectrum oral antibiotics, mainly doxycycline and metronidazole, resulting in improvement to grade 2 or below in 9 out of 11 cases with INF grade 3 or above. However, clear associations between pregnancy outcomes and INF grades were not apparent, with the most significant correlation found in CE diagnosis using Liu’s method. Analyzing biomarkers for CE through LEfSe (Linear discriminant analysis effect size), both McQueen’s method and INF grading 2 or above were associated with the intrauterine presence of Lactobacillus iners. Estimating endometrial inflammation based on intrauterine Lactobacillus iners presence yielded an AUC of 0.733 for McQueen’s CE and 0.723 for INF grade 2 or above. Limitations, reasons for caution This study is a retrospective analysis, and the treatment protocols and intervention criteria for chronic endometritis vary among different facilities. The number of cases is also limited, and it is desirable to conduct a unified prospective multicenter cohort study with consistent protocols. Wider implications of the findings The combination of the endometrial microbiome testing and detailed inflammatory grading suggests the potential for establishing appropriate treatment intervention strategies and predicting the success rate of infertile treatment. Since Lactobacillus iners tends to colonize extensively in the vaginal environment of East Asian women, it is necessary to explore region-specific measures. Trial registration number not appicable

P-428 Identifying key factors for achieving biochemical pregnancy in first autologous IVF cycles: an artificial intelligence-assisted approach

Abstract Study question What key factors determine a positive biochemical pregnancy outcome in first autologous IVF cycles, as identified by machine learning (ML) algorithms? Summary answer Maternal age, AMH, BMI, number of day 3 embryos and total embryos transferred emerged as top predictors for biochemical pregnancy across several ML methods. What is known already ML methods are powerful tools that discern patterns from multiple features to predict outcomes. Beyond their clear predictive capabilities, ML algorithms also offer valuable clinical insights by uncovering underlying data trends. These insights come from understanding the algorithms’ decision-making processes, revealing the rationale behind their predictions. While maternal age is known to influence IVF success, other pre-treatment and in-cycle factors also play a significant role. Understanding these factors can enhance patient management and guide clinical advice and interventions. Study design, size, duration This multicenter retrospective study included data from 9,945 cycles performed between January 2010 and July 2021. Only first autologous cycles using fresh oocytes and donor or patient sperm (fresh or frozen) were included. Preimplantation genetic testing (PGT) cycles were excluded. Both pre-treatment and in-cycle variables were considered, with treatment outcome expressed as cumulative biochemical pregnancy. Cases and variables deemed to have poor data quality were excluded. The final dataset comprised 80 variables and 7350 cycles. Participants/materials, setting, methods Five ML classifier algorithms were applied to predict cumulative biochemical pregnancy using pre-treatment and in-cycle variables. The models tested included logistic regression, support vector machine, random forests, gradient boosting and multilayer perceptron. Shapley values analysis was performed to explain the decision-making structures of all the algorithms tested, quantifying the impact of each included feature on outcome prediction. Main results and the role of chance Within our cohort, mean maternal age was 37.3±4.7 years, mean serum AMH was 2.4±2.1 ng/ml, mean BMI was 23.7±4.0 and mean antral follicle count (AFC) was 11.6± 7.6. Notably, 40.1% of cycles used donor sperm, while 33.8% of male patients were normozoospermic. The majority of cycles (90.8%) used antagonist stimulation protocols, yielding an average of 7.8±5.5 oocytes per patient. Fertilization rate was 70.6%, with a mean of 2.7±1.8 usable embryos obtained per cycle. Fresh embryo transfers accounted for 73% of cases, with an average of 1.5±0.9 transfers performed per cycle. The embryo utilization rate was 64.6% and 48.1% of cycles resulted in a biochemical pregnancy. Among the evaluated algorithms, the gradient boosting model demonstrated superior performance, with an accuracy of 70.6±1.4% and AUC of 77.3±1.7%. Shapley values across all five algorithms consistently revealed the negative correlation between maternal age and biochemical pregnancy rates. Among pre-treatment variables, AMH levels had a positive influence on outcomes, followed by BMI, AFC, and parity status. Regarding in-cycle variables, the number of embryos available at day 3 and the total number of embryos transferred, positively affected the chances of pregnancy. The number of mature oocytes was also an important in-cycle predictive feature. Limitations, reasons for caution his retrospective study spans an extended timeframe, suggesting potential variations in clinical and laboratory practices over the years. Therefore, caution is advised in generalizing the results to other patient populations or to contemporary data gathered using newer and enhanced clinical protocols. Wider implications of the findings The consistent identification of maternal age, ovarian reserve markers, and embryo quantity as primary predictors of pregnancy by the five AI models corroborates existing clinical understanding. This consistency emphasizes the strength and dependability of AI to reinforce and complement clinical knowledge with data-driven evidence. Trial registration number not applicable

O-309 Safety and fertility potential of residual ovarian cortex surrounding borderline tumors in women of reproductive age

Abstract Study question How do borderline ovarian tumors (BOTs) at different oncological stages affect safety (presence of occult lesions) and quality of the ovarian reserve? Summary answer The ovarian follicle pool is decreased in women with BOTS, especially at younger age, and oncological safety is compromised in more advanced oncological stages. What is known already The clinical decision-making balancing the type of surgical treatment (radical or fertility-sparing) with the the risk of recurrence is still controversial for women diagnosed with BOTs at different oncological stages. The same is for the use of adjuvant techniques like oocyte or ovarian tissue cryopreservation to optimize the likelihood of fertility recovery. The prevalence of occult lesions in healthy-looking ovarian cortex, which may be managed by surgery or cryopreservation, has not been analyzed in all tumor types. Moreover, the status of the ovarian follicle pool may be affected by tumoral masses, making fertility preservation even more challenging in these patients. Study design, size, duration Multicentric retrospective study involving Cliniques Universitaires Saint Luc in Brussels (Belgium) and Macedonio Melloni hospital in Milan (Italy). Forty-two women at reproductive age (15-45 years) diagnosed with borderline ovarian tumors (BOTs), including 24 serous, 14 mucinous and 4 endometrioid BOTs were included. Participants/materials, setting, methods Histological samples of ovarian cortex surrounding tumors were analyzed to characterize the follicle pool (follicle density, classification and atresia rates) and results were compared with an aged-matched population of 45 subjects with non-ovarian pathologies. Any occult malignant lesions in healthy-looking cortex were investigated using tumor-specific markers (cytokeratin 7 and mucin 1), while immune system infiltration was quantified by CD3 for tumor-infiltrating lymphocytes (TILs) and CD68 for tumor associated macrophages (TAMs). Main results and the role of chance Occult ovarian lesions were observed in 5 out of 39 cases (12.8%). These included one mucinous stage-I BOT (1/13), one serous stage-I BOT (1/13), and 3 advanced-stage serous BOTs (3/11). Three 3 cases were excluded from the analysis because no cortex was available. Notably, follicle density was significantly lower in subjects diagnosed with ovarian tumors than in controls (p &amp;lt; 0.001) at a younger age, while no difference was detected in older patients. Significantly greater follicle atresia was encountered in the ovarian tumor group than in controls (20.1 ± 8.8% vs 9.2 ± 9.4%, p &amp;lt; 0.001) at all ages, but no difference was detected in follicle classification parameters (primordial and growing follicle rates). Mucinous BOTs exhibited lower follicle density than serous BOTs (98.8 ± 152.8 vs 225.8 ± 220.7, p &amp;lt; 0.01), although no age difference was evidenced. Although mucinous BOTS had also significantly bigger volume than serous BOTs, no significant correlation between follicle density and tumoral volume was found. Other factors like tumor microenvironment may play a role in ovarian follicle pool damage. Both TILs and TAMs were found in ovarian tumors irrespective of histotype, but no link was established with the status of the ovarian reserve. Limitations, reasons for caution Although this study helped to elucidate the risk profile of different types of epithelial ovarian tumors, observing that late-stage BOTs ran a 27% (3/11) risk of occult ovarian lesions, further research is needed to identify predictive markers. Wider implications of the findings Personalized counseling for fertility preservation is required in case of BOTs. Fertility-sparing surgery and adjuvant gamete preservation should be considered, balancing any oncological risks against tumor stage and histotype and fertility potential, especially at a younger age. Trial registration number NA

O-298 Embryo long-term storage does not affect ART outcome: analysis of 58,001 vitrified blastocysts

Abstract Study question Does duration of storage affect clinical outcome in frozen embryo transfer (FET) cycles? Summary answer Long-term storage does not affect live birth rate (LBR) in elective and non-elective FET cycles. What is known already Despite the success rates provided by the embryo vitrification programs, some studies found an association between the duration of cryo-storage and decreased clinical outcome, raising concern about the potential negative effect that prolonged storage may have on embryos. Study design, size, duration This was a retrospective multicenter study including a total of 58001 vitrified/warmed day-5 blastocysts from two different populations according to the reason for FET: elective FET which involved patients undergoing freeze all cycles (N = 16,615 blastocysts and 16,615 patients); and non-elective FET including 41,386 embryos from 25,571 patients. FETs were performed in the period between January 2010 and December 2020. Participants/materials, setting, methods Main outcome was live birth rate (LBR) and secondary outcomes were embryo survival, miscarriage, clinical and ongoing pregnancy rates. The impact of storage time and the potential confounding variables was assessed by univariate analyses. Those covariables found to significantly modify the LBR were included in a multivariable logistic regression. GEE (generalized estimated equation) was performed to allow the analysis of repeated measurements. Odds ratios (OR) and 95% confidence intervals (CI) were provided. Main results and the role of chance The blastocysts sample was clustered into deciles which provided specific storage duration categories that ranked from ≤0.67 to ≥ 4.34 and ≤1.8 to ≥ 34.81 months in freeze-all and non-elective FET, respectively. In the freeze-all group, maximum storage time was 34.8 months (2.9 years), while it was 121.2 months (10.1 years) in the non-elective FET group. Embryo survival did not show statistical differences across the categories of storage time in freeze-all and non-elective FET groups. In the freeze-all group, statistical differences were found for LBR across some, but not all the subgroups of storage duration. Similarly, in the non-elective FET group, LBR among the deciles showed statistical differences in some comparisons but not in all. However, after adjusting for confounding variables, the multivariate analysis showed no association between storage time and LBR in both groups. Blastocyst quality, body mass index (BMI), number of retrieved oocytes, endometrial preparation, male factor and uterine factor were related to the drop in the LBR in the freeze-all group (p &amp;lt; 0.05). In the non-elective FET group, the variables that showed significant association with the LBR were age at retrieval and at FET, number of embryos transferred, number of retrieved oocytes, BMI, endometrial preparation, sperm origin and female factor. Limitations, reasons for caution The retrospective design of the study represents its main limitation. Wider implications of the findings Our results demonstrate the safety of long-term cryo-storage. This is reassuring for both IVF practitioners and patients especially considering the exponential increase in FET cycles observed in the last decades. Trial registration number Not applicable

P-567 Is mosaic embryo transfer a valid alternative for patients lacking euploid embryos? a multicentric study from Argentina

Abstract Study question How does low-level mosaicism embryo transfer affect reproductive outcomes, including pregnancy rates and live birth success, compared to transfers involving euploid embryos? Summary answer Most mosaic embryo transfers do not affect reproductive outcomes, as live birth rates appear to be similar to those observed with euploid embryos. What is known already Preimplantation genetic testing (PGT) is used to identify embryonic genetic abnormalities and, ideally, select euploid embryos for intrauterine transfer, to improve clinical IVF outcomes. Chromosomal mosaicism is defined as the presence of two or more different chromosomal cell lines within an embryo. Numerous sources describe the proportion of mosaic embryos ranging from 4 to 22%. Several publications report that mosaic embryo transfer can lead to successful pregnancies and healthy deliveries, albeit at a lower frequency and with higher rates of pregnancy loss compared to euploid embryos. However, the impact of mosaicism on IVF outcomes remains a matter of controversy. Study design, size, duration Observational and retrospective multi-center study analyzed 6241 embryos from 1218 patients, across 4 IVF centers, who underwent PGT between 2016 and 2023 in a single genetics laboratory. Embryos were categorized as euploid, aneuploid, or mosaic. Patients in group A (n = 894) were transferred an euploid embryo, while in group B (n = 55), a low-grade mosaic embryo, defined as those having less than 40% (2016-2021) or 50% (2021-2023) aneuploid cells, was transferred. Participants/materials, setting, methods The embryos were biopsied and vitrified for later transfer. Blastocyst biopsy DNA was amplified using the SurePlex kit, processed with the VeriSeq kit (Vitrolife), and sequenced on a MiSeq platform. The results were analyzed using BlueFuse-Multi software. Mosaic embryo transfers were conducted only in the absence of a euploid embryo, following genetic counseling. beta-hCG levels &amp;gt;25 IU were considered positive, and clinical pregnancy was confirmed through ultrasound visualization of the gestational sac with heartbeat. Main results and the role of chance Among the analyzed embryos, the proportion of euploid was 46.2% (n = 2883), while mosaic embryos accounted for 19.3% (n = 1207), with 69.5% classified as low-grade and 30.5% as high-grade. Aneuploid embryos comprised 31.3% (n = 1954), and results could not be obtained for 3.2% (n = 197). Fifty-five low-grade mosaic embryos were transferred, including 19 with complete chromosomal mosaicism, 34 with segmental mosaicism, and 2 cases with 2 chromosomes involved in the mosaicism. The positive beta-hCG rate post-transfer was 50.3% for Group A, compared to 49.1% for Group B. Clinical pregnancy rates were 36.9% and 36.4%, respectively. Regarding live births, in Group A 328 (36.7%) children were born, and in Group B, 16 (29.1%), with 2 ongoing pregnancies. Conversely, pregnancy losses in Group B (9.1%) were higher compared to the euploid group (2.9%). Regarding pregnancy losses, in 3 cases no fetal heartbeats were identified, there was one miscarriage &amp;lt;20 weeks, and one twin gestation was lost after a normal non-invasive prenatal testing. In all cases the newborns were apparently healthy after mosaic embryo transfer, with an average gestational week at birth of 39 (37-41), and an average weight of 3197 (2900-4390) grams. Cesarean section was performed for 15/16 births, and one was born by vaginal delivery. Limitations, reasons for caution The study is limited by its retrospective nature and the small number of samples and mosaics transferred. Prenatal and postnatal tests were not conducted. Furthermore, the health of newborns was evaluated only in the initial months of life. Wider implications of the findings Mosaic embryo transfer is a valid alternative for couples lacking euploid embryos. This multicenter study adds evidence that mosaic embryo transfer does not have a clinically relevant impact on pregnancy and live birth rates, similar to what has been reported by other authors. Trial registration number ‘not applicable’

Real Implication of Fertility-Sparing Surgery for Ovarian Cancer: Reproductive Outcomes.

to prove the effectivity of fertility-sparing procedures in early-stage ovarian cancer by assessing pregnancy rates and obstetrical outcomes. we performed a retrospective multicenter study among 55 Spanish hospitals, collecting patients from 18 to 40 years old with diagnosis of early-stage ovarian cancer, epithelial (EOC) or non-epithelial (non-EOC), from January 2010 to December 2019. Data on the use of assisted reproductive techniques, pregnancy attempts and obstetrical outcomes were collected. a total of 150 patients met inclusion criteria, 70 (46.6%) EOC and 80 (53.4%) non-EOC. Pregnancy attempts were reported in 51 (34%) patients, with 42 (28%) patients carrying the pregnancy to term. Among them, 30 (71.4%) underwent surgery alone and 12 (28.6%) had additional postoperative chemotherapy. A total of 32 (76.1% patients) had spontaneous pregnancies and 10 (23.9%) required in vitro fertilization. There was only one (2.4%) complication reported. Vaginal delivery was reported in twenty-nine (69%) patients and cesarean section in five (11.9%) patients. fertility-sparing management for ovarian cancer seems to be an option with proven good pregnancy rates and low complications. The selection of patients must consider strict criteria in order to maintain a good prognosis.

Does Antrum Size Matter in Sleeve Gastrectomy? Volume II-A Retrospective Multicentric Study with Long-Term Follow-Up.

Background: Laparoscopic sleeve gastrectomy (LSG) is the most widespread bariatric procedure due to its safety and efficacy. Despite continuous refinement, achieving a globally standardized procedure remains challenging. Moreover, due to its wide adoption, numerous studies have focused on complications associated with the technique, such as gastroesophageal reflux disease (GERD). This study evaluates the impact of antrum size (wide antrectomy versus small antrectomy) in LSG on long-term anthropometric outcomes and complications in patients with morbid obesity. Methods: Body mass index (BMI), percentage of excess weight loss (%EWL) at a 5-year follow-up, GERD Health-Related Quality-of-Life (GERD-HRQL) scores, and obesity-related diseases of patients undergoing LSG with gastric resections starting 2 cm and 6 cm from the pylorus were retrospectively evaluated. Results: Between January 2015 and November 2019, 597 patients who met the criteria for LSG were included in the study. Group A (241 patients) underwent wide antrectomy, while Group B (356 patients) underwent small antrectomy. Weight, BMI, %EWL, and %TWL significantly improved at 6 and 12 months in the wide-antrectomy group. However, these differences diminished by 24 months, with no significant long-term differences in weight loss outcomes between the two groups at 5 years. Conversely, GERD-HRQL scores were significantly better in the small-antrectomy group until 24 months; thereafter, results were comparable between groups over the long term. Conclusions: Therefore, while wide antrectomy may offer superior short-term anthropometric outcomes, both techniques yield similar long-term results regarding weight management and GERD incidence. Larger prospective studies are needed to further address this issue.

O-006 Oocyte factors as predictors of abnormal, mononucleated and trinucleated, zygotes and assessment of their morphokinetic differences

Abstract Study question Are there oocyte factors associated with the occurrence of mononucleated and trinucleated zygotes after ICSI? Does morphokinetics differ in embryos from normal and abnormal zygotes? Summary answer Formation of 1PN zygotes relates to vitrificated and donor oocytes. 3PN links to age and own oocytes. 1PN embryo morphokinetics are slower than 2PN, 3PN. What is known already In assisted reproduction, after monitoring fertilization, it is common to observe zygotes with one or more than 2 pronuclei. These abnormal zygotes are often discarded due to potential chromosomal abnormalities. The formation of these anomalous zygotes can be attributed to various causes, such as non-activation of the male pronucleus, non-extrusion of the second polar body, etc. Simultaneously, limited data exist on the morphokinetics of abnormal zygotes, explored in a few studies. The embryonic kinetics of 1PN zygotes seem slower than those of 2PN and 3PN zygotes, but further research is needed to confirm this aspect. Study design, size, duration Retrospective multicentre study involved time-lapse monitoring of 28,218 ICSI zygotes (26,252 2PN, 1,190 1PN, and 776 &amp;gt;3PN) generated between January 2019 and December 2023. The study includes donor and patient oocytes with various infertility diagnoses, whether fresh or vitrified. The comparison of embryonic morphokinetics from abnormal/normal zygotes was conducted on 254 embryos from a single centre, with 45 originating from 1PN zygotes, 198 from 2PN zygotes, and 11 from zygotes with 3 or more pronuclei. Participants/materials, setting, methods The study involved 1,053 couples treated in four different centres. Uniform culture media were used, and oocytes were cultivated in time-lapse technology-equipped incubators across all centres. A logistic regression analysis aimed to identify oocyte factors linked to an abnormal pronuclei count. Embryonic morphokinetics were analysed using the CHLOE artificial intelligence system (Fairtility, Israel). Evaluated parameters included: tPNa, tPNf, t2, t3, t4, t5, t6, t7, t8, t9+, tM, tSB, tB, and tEB. Main results and the role of chance Donor oocytes exhibited a 1.32 times higher risk of producing 1PN zygotes than 2PN or 3PN zygotes (p &amp;lt; 0.001). Similarly, vitrified oocytes had a 1.63-fold higher risk of generating 1PN zygotes than 2PN or 3PN zygotes (p &amp;lt; 0.001). Additionally, we found that both the use of own oocytes and advanced age were significantly associated with 3PN zygotes (p &amp;lt; 0.001). Regarding age, the risk increases by 10% for each additional year. The average durations for all morphokinetic parameters of 2PN and 3PN embryos were similar. In contrast, all events, except t3 (p = 0.2), occurred more slowly in embryos derived from 1PN zygotes compared to embryos from 2PN zygotes. Thus, the disappearance of pronuclei had a p-value &amp;lt;0.005, and from t4 to tEB, the p-value was &amp;lt;0.001. When comparing embryos from 1PN and 3PN zygotes, only tPNa, t4, t8, t9+, and tM were significantly different. If only zygotes that reached the blastocyst stage were used for analysis, the results were less conclusive due to a significantly reduced number of cases. Limitations, reasons for caution Embryos were cultured in an EmbryoScope incubator at three centres, while Geri was used in the fourth. Wider implications of the findings Using donor or vitrified oocytes may lead to an increased occurrence of zygotes with 1PN, as will occur with 3PN when patient or aged oocytes are used. The kinetics of embryos from 3PN oocytes resemble those from 2PN, while those from 1PN zygotes exhibit slower kinetics. Trial registration number not applicable

P-138 Effect of biofeedback from the blastocysts on the cumulative pregnancy rate

Abstract Study question The study is to compare cumulative pregnancy rates of embryos transferred with and without spent culture media to confront biofeedback’s role in clinical outcomes Summary answer Transferring the blastocysts with spent culture media improved the pregnancy rates. Biofeedback was observed from the blastocyst stage. The blastocyst freezing and transfer approach improved. What is known already Biofeedback is often encountered in regulating menstrual cycles and other events in continuing gestations with estrogen, progesterone, beta hCG..etc. A similar biofeedback is possible with growing blastocyst for implantation. Since the in-vitro culture of embryos is devoid of its occurrence, it may lead to asynchrony of subsequent events and implantation. There is no scientific evidence from metabolomics on the characterization of these substances or secretions from spent culture medium that includes cell-free DNA giving feedback and its role in improving clinical outcomes. Study design, size, duration This retrospective multi-centric study included the 3591 frozen embryo transfers from 1st Apr 2022 to 31st Nov 2023 out of 4623 women who underwent oocyte retrieval from 1st Jan 2022. Patients were divided into study (group A) and control (group B). In group A, 1035 women received the transfers from spent culture media; in group B, 2556 women received transfers after shifting the blastocysts to fresh culture media before loading into the ET catheter. Participants/materials, setting, methods All the transfers considered in this study were day-5 blastocysts, irrespective of their frozen state. Day-5 frozen-thawed were incubated short-time (∼1 hour) before the transfer. Whereas, the frozen embryos and morulas were cultured till day 5. In the study group, all cultures were conducted in 100ul of culture media under oil per embryo to maintain consistency amongst the group. The rest of the laboratory and clinical procedures were consistent between the two groups. Main results and the role of chance The cumulative pregnancy rate was significantly higher in group A than in group B (60.9% Vs 55.6%; OR = 1.23; 95% CI, 1.07 -1.44, Z-score 2.901, P &amp;lt; 0.003). The effect of spent culture media was further observed by regrouping the day-3 or 4 frozen (group A1) and day-5 frozen patients (group A2). Day-5 thawed blastocysts transferred after short incubation to allow the secretions to directly deposit on the endometrium. Group A1 might have a high concentration of secretions due to its accumulation from the embryo or morula stages. Pregnancy rates in group A1 were higher than A2 but not statistically significant (61.7% Vs 59.7%; OR = 1.08, 95% CI, 0.84-1.4, Z-score 0.654, P = 0.51). The less impact indicates that the feedback came from blastocysts rather than embryos. Limitations, reasons for caution It is not evident how these secretions contribute to biofeedback. Quantification, identifying their time of release and recovery from the qualitative tests for their therapeutic use are the limitations. Nevertheless, spent media can be employed if found beneficial. Wider implications of the findings We have taken a large possible data set for control against the test group and took cumulative pregnancy rate as the primary outcome indicator to prove biofeedback from blastocysts can improve the clinical outcomes irrespective of the age and other factors of infertility. Trial registration number Not applicable

Effects of differences in dose and frequency of teriparatide on bone structure in Proximal Femur. - Analysis by DXA-based 3D-modeling (3D-SHAPER Software) -TRIPLE-BONE study (The effects of TeRIParatide preparation on bone mineraL density increase and BONE structure).

To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n= 60) or 1/D TPTD (n= 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Efficacy and Safety of Ceftazidime-Avibactam Alone versus Ceftazidime-Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort.

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07-1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14-0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Hepatectomy versus systemic therapy for liver-limited BRAF V600E-mutated colorectal liver metastases: multicentre retrospective study.

To date, only two studies have compared the outcomes of patients with liver-limited BRAF V600E-mutated colorectal liver metastases (CRLMs) managed with resection versus systemic therapy alone, and these have reported contradictory findings. In this observational, international, multicentre study, patients with liver-limited BRAF V600E-mutated CRLMs treated with resection or systemic therapy alone were identified from institutional databases. Patterns of recurrence/progression and overall survival were compared using multivariable analyses of the entire cohort and a propensity score-matched cohort. Of 170 patients included, 119 underwent hepatectomy and 51 received systemic treatment. Surgically treated patients had a more favourable pattern of recurrence with most recurrences limited to a single site, whereas diffuse progression was more common among patients who received systemic treatment (19 versus 44%; P = 0.002). Surgically treated patients had longer median overall survival (35 versus 20 months; P < 0.001). Hepatectomy was independently associated with better OS than systemic treatment alone (HR 0.37, 95% c.i. 0.21 to 0.65). In the propensity score-matched cohort, surgically treated patients had longer median overall survival (28 versus 20 months; P < 0.001); hepatectomy was independently associated with better overall survival (HR 0.47, 0.25 to 0.88). BRAF V600E mutation should not be considered a contraindication to surgery for patients with resectable, liver-only CRLMs.

A comparative cohort study of surgical approaches for adult spinal deformity at a minimum 2-year follow-up.

This study was a retrospective multi-center comparative cohort study. A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

Real-world outcomes of combined lenvatinib and anti-PD-1 in advanced melanoma: the Lenvamel study, a multicenter retrospective study of the French Group of Skin Cancers (Groupe de Cancérologie Cutanée).

Currently, treatment options for patients with advanced melanoma who experience failed immunotherapy or targeted therapy are lacking. Recent studies suggest the antitumor activity of combined pembrolizumab and lenvatinib in patients with advanced melanoma progressing on immunotherapy. Herein, we report the clinical outcomes of combined lenvatinib and a programmed cell death protein-1 inhibitor (PD-1) in this population. This French multicenter real-world study was conducted between September 2020 and July 2023. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (version 1.1). Secondary variables were treatment-related adverse events (TRAEs), progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Of the 67 patients included (median age, 69 years; median follow-up, 5.0 months), 85% had stage IV-M1c or M1d disease. The overall ORR was 28.4% (95% CI, 18%-41%), including 3 complete (4.5%) and 16 partial (23.9%) responses. Median DOR was 3.1 (interquartile range, 1.3-4.3) months. Median PFS and OS were 3.1 (95% CI, 2.5-3.7) and 9.8 (95% CI, 5.6-13.9) months, respectively. Grades 3-5 TRAEs occurred in 16 (24%) patients; common TRAEs were fatigue (43.3%), nausea/vomiting (26.8%), diarrhea (20.9%), and hypertension (20.9%). No treatment-related deaths occurred. Our real-world study demonstrates an interesting response rate and acceptable safety profile in a population with poor prognostic factors. Our data support this treatment option for refractory melanoma, as it is not approved by the Food and Drug Administration or European Medicines Agency, and highlight the need for new strategies.

Safety and Performance of a Cell-Impermeable Endoprosthesis for Hemodialysis Vascular Access Outflow Stenosis: A Brazilian Multicenter Retrospective Study.

To evaluate the safety and performance of Wrapsody™, a cell-impermeable endoprosthesis (CIE), for treating hemodialysis vascular access outflow stenosis. Investigators retrospectively analyzed 113 hemodialysis patients treated with a CIE (11/2021-12/2022) across four centers in Brazil. Denovo or restenotic lesions were treated. The primary efficacy outcome measure was target lesion primary patency (TLPP) at 1, 3, 6, and 12months; the primary safety outcome measure was the absence of serious local or systemic adverse events within the first 30days post-procedure. Secondary outcome measures included technical and procedural success, access circuit primary patency (ACPP), and secondary patency at 1, 3, 6, and 12months post-procedure. Thirty-nine patients (34.5%) had thrombosed access at the initial presentation, and 38 patients (33.6%) presented with recurrent stenosis. TLPP rates at 1, 3, 6, and 12months were 100%, 96.4%, 86.4%, and 69.7%, respectively. ACPP rates were 100% at 1month, 89.2% at 3months, 70.9% at 6months, and 56.0% at 12months. The target lesion secondary patency rates at 1, 3, 6, and 12months were 100%, 97.3%, 93.6%, and 91.7%, respectively. In the adjusted multivariate Cox regression analysis, male sex and endoprosthesis with diameters of 10, 12, 14, and 16mm were associated with improved primary patency rates. No localized or systemic serious adverse event was observed through the first 30days post-procedure. The CIE evaluated in this study is safe and effective for treating peripheral and central outflow stenoses in hemodialysis vascular access. Level 2b, cohort study.

Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.

The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge. This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023. Propensity score matching was used to match these two cohorts with similar baseline characteristics. Among 5,326 patients receiving ICPis, 51 patients developed severe irH. irH occurred after a median duration of 36days and a median of two doses after the first ICPi administration. Patients receiving PD-L1 inhibitors faced a lower risk of developing severe irH. A higher dose of glucocorticoids (GCS) was administered to grade 4 irH than grade 3 irH. For steroid-sensitive patients, grade 4 irH individuals received a higher dosage of GCS than those with grade 3 irH, with no difference in time to resolution. Meanwhile, a significantly higher dose of GCS plus immunosuppression was needed in the steroid-refractory group. Liver biopsy of the steroid-refractory patients exhibited heterogeneous histological features. Twelve patients were retreated with ICPi. No irH reoccurred after a median follow-up of 9.3months. irH requires multidimensional evaluation. PD-L1 inhibitors correlated with a lower risk of severe irH. Grade 4 irH demands a higher dose of GCS than recommended. Pathology may guide the salvage treatment for steroid-refractory irH. ICPi rechallenge in severe irH is feasible and safe.

A Comparative Study of Human Leptospirosis between Mayotte and Reunion Islands Highlights Distinct Clinical and Microbial Features Arising from Distinct Inter-Island Bacterial Ecology.

Leptospirosis is a neglected zoonosis for which investigations assessing host-pathogen interaction are scarce. The aim of this study was to compare the severity and bacterial species involved in human cases of leptospirosis on Reunion and Mayotte islands, territories located in the southwest Indian Ocean that have recorded high human leptospirosis incidence but display fairly distinct epidemiological situations. A retrospective multicentric study including all patients over 18 years of age from Mayotte or Reunion with proven leptospirosis was conducted from January 2018 to April 2020. This study collected demographic, geographical, clinical, and biological data. Overall, 490 patients were included, 222 on Mayotte and 268 on Reunion. More patients were hospitalized on Reunion (n = 215, 80%) compared with Mayotte (n = 102, 46%). Severe disease was more common on Reunion (n = 75, 28%) than on Mayotte (n = 22, 10%). The dominant Leptospira species on Reunion was Leptospira interrogans (79%) followed by Leptospira borgpetersenii (21%), contrasting with the epidemiological situation on Mayotte where L. interrogans was found in only a minority of patients (10%). The high frequency of severe cases on Reunion could be explained not only by higher comorbidities but also by the higher occurrence of L. interrogans infections compared with Mayotte. Finally, the distribution of cases linked to L. borgpetersenii was found almost exclusively on the west coast of Reunion, raising the potential role of a ruminant reservoir.

A commentary on 'Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study'.

A commentary on 'Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study'.