Multicenter Retrospective Study Research Articles

O-152 Pre-implantation genetic testing for aneuploidies (PGT-A) improves reproductive outcomes in advanced maternal age patients undergoing IVF/ICSI: a multicentre retrospective cohort study with propensity score matching

Abstract Study question In patients > 37 years undergoing IVF/ICSI, does PGT-A improve live birth rates (LBR) and cumulative live birth rates (CLBR)? Summary answer In advanced maternal age women with ≥1 embryo to transfer, PGT-A improves the live birth and cumulative live birth rates. What is known already The age-related rate of aneuploidy remains a major cause of IVF failure. Therefore, PGT-A has been proposed as a method to select embryos with the highest implantation potential. Previous studies have shown that women younger than 37 years old do not benefit from PGT-A given the comparable outcomes in terms of implantation, clinical pregnancy, and live-birth rates. Moreover, PGT-A may also be inherently ineffective given the risk of mitotic mosaicism, sampling errors and misinterpretation of results. However, we are currently lacking solid scientific evidence to support whether this approach benefits advanced maternal age women. Study design, size, duration A multicenter retrospective cohort study was conducted including 9328 patients >37y undergoing their first IVF/ICSI cycle with an oocyte retrieval performed between 1/01/2013-31/07/2021 in a multinational private fertility clinic. The study group (n = 4664) included patients who performed PGT-A. The control group included patients without PGT-A (n = 4664) and was selected by propensity score matching adjusted for age at oocyte retrieval, number of oocytes retrieved and year of oocyte retrieval. Participants/materials, setting, methods The primary outcome was CLBR (delivery of at least one live birth per started cycle, including the fresh and subsequent frozen embryo transfer cycles). The secondary outcomes were LBR and time to pregnancy. The analysis was conducted including all patients with an initiated cycle of ovarian stimulation and also per embryo transfer. Comparisons are presented as adjusted odd-ratios (adjOR) and 95% confidence intervals (95%CI) following multivariable logistic regression (LBR) or cox regression (CLBR) analysis. Main results and the role of chance Patients in the PGT-A group had more oocytes retrieved (11.03±6.82 vs 9.24±6.15, p < 0.001), and a higher number of available blastocysts (2.82±2.21 vs 1.22±2.00, p < 0.001). In the PGT-A group, 13.153 embryos were analysed, with an euploidy rate of 29.30% (n = 3854). In total, 49.83% (n = 2324) patients did not undergo embryo transfer due to unavailable euploid embryos. Considering all patients that initiated ovarian stimulation, the PGT-A group presented a higher unadjusted CLBR per started cycle (27.38% vs 21.81%, p < 0.001). Considering only patients who underwent embryo transfer, a total of 5934 embryo transfers were analysed (n = 3166 in the control group and n = 2768 in the PGT-A group). Following multivariable logistic regression analysis, LBR and CLBR were significantly higher in the PGT-A group (respectively, adjOR 1.56 [95% CI 1.38-1.77], adjOR 1.53 [95% CI 1.39-1.68]). Following the transfer of 5 embryos, the CLBR was approximately 100% in the PGT-A group and 74.51% in the control group. Survival analysis was also perfomed to assess the impact of PGT-A on time to pregnancy. Despite the fact that from 6 months onwards the CLBR was higher in the PGT-A group, the median time to pregnancy was higher in the PGT-A group (3.27 (95%CI 3.16-3.40) vs 2.74 months (95%CI 2.57-3.03). Limitations, reasons for caution This study is limited by its retrospective design and low number of women with more than 3 embryos transferred. Also, the fact that only the first IVF/ICSI cycle was analysed provides a proper patient counselling in this specific context but does not provide data on repeated cycle outcomes. Wider implications of the findings Our findings suggest that, in women older than 37 years with at least one available embryo to biopsy, performing PGT-A may improve the reproductive outcomes in terms of LBR and CLBR, providing a useful clinical tool for embryo selection. Trial registration number not applicable

P-559 Pregnancy rates in conventional and non-invasive pre-implantation genetic testing – a multicentric retrospective cohort study

Abstract Study question To determine the pregnancy rates with embryo diagnosed as euploid by non-invasive preimplantation genetic testing (niPGT-A) and trophectoderm based pre-implantation genetic testing (cPGT-A) Summary answer Biochemical pregnancy rates are comparable in couples undergoing transfer with embryos diagnosed as euploid as judged by niPGT-A or cPGT-A What is known already NiPGT-A utilizes cell-free DNA in culture media to assess the chromosomal status of embryos. Several studies have shown that the niPGT-A and cPGT-A have a reasonable concordance rate and niPGT-A can be considered as an alternative in predicting the ploidy status of the embryos. However, limited information exist on the clinical outcomes of embryos deemed euploid by niPGT-A. Study design, size, duration Data of 1209 participants between June 2022 and Dec 2022 was collected from 46 centers of Indira IVF Hospital. These were couples who had experienced recurrent implantation failures (>3 failed ET), recurrent miscarriages (>2 miscarriages) or had advanced maternal age (>35 years) and opting either for niPGT-A or cPGT-A at our centres for euploid embryo transfers. Women with anatomical uterine defects and Asherman syndrome were excluded. Participants/materials, setting, methods Trophectoderm biopsy was done in 1383 Day 5 grade A embryos and PGT-A was done using NGS. Culture media of 3083 Grade A embryos were collected on D5 or D6 and frozen. NGS was done at an external facility. Embryos deemed euploid in either of the groups were transferred. Biochemical pregnancy was determined by measurements of beta hCG. Main results and the role of chance There were 906 patients in the niPGT-A group and 303 in the cPGT-A group. The clinical characteristics of the participants were comparable in both groups. Biochemical pregnancy rates were 60% and 69%, respectively. This difference was not statistically significant (p < 0.6). The euploidy rates were comparable in the niPGT-A and cPGT-A groups (40% and 46%) respectively. The aneuploidy rates were lower in the niPGT-A group as compared to the cPGT-A group (15% vs 26%). The mosaicism rates were higher in the niPGT-A group as compared to the cPGT-A group. Limitations, reasons for caution This is a preliminary data analysis of only the biochemical pregnancy rates. Clinical pregnancy, miscarriage, and live birth outcomes are subject to further investigation. Wider implications of the findings The study will aid IVF specialist to consider niPGT-A as a possible alternative to cPGT-A in clinical practice. Trial registration number ’not applicable’

Diagnostic MRI for deep pelvic endometriosis: towards a standardized protocol?

To assess the diagnostic efficacy of an MRI protocol and patient preparation in detecting deep pelvic endometriosis (DPE). The cohort is from the ENDOVALIRM database, a multicentric national retrospective study involving women who underwent MRI followed by pelvic surgery for endometriosis (reference standard). Two senior radiologists independently analyzed MRI findings using the deep pelvic endometriosis index (dPEI) to determine lesion locations. The study evaluated the impact of bowel preparation, vaginal and rectal opacification, MRI unit type (1.5-T or 3-T), additional sequences (thin slice T2W or 3DT2W), and gadolinium injection on reader performance for diagnosing DPE locations. Fisher's exact test assessed differences in diagnostic accuracy based on patient preparation and MRI parameters. The final cohort comprised 571 women with a mean age of 33.3 years (± 6.6 SD). MRI with bowel preparation outperformed MRI without bowel preparation in identifying torus/uterosacral ligament (USL) locations (p < 0.0001) and rectosigmoid nodules (p = 0.01). MRI without vaginal opacification diagnosed 94.1% (301/320) of torus/USL locations, surpassing MR with vaginal opacification, which diagnosed 85% (221/260) (p < 0.001). No significant differences related to bowel preparation or vaginal opacification were observed for other DPE locations. Rectal opacification did not affect diagnostic accuracy in the overall population, except in patients without bowel preparation, where performance improved (p = 0.04). There were no differences in diagnostic accuracy regarding MRI unit type (1.5-T/3-T), presence of additional sequences, or gadolinium injection for any endometriotic locations. Bowel preparation prior to MRI examination is preferable to rectal or vaginal opacification for diagnosing deep endometriosis pelvic lesions. Accurate diagnosis and staging of DPE are essential for effective treatment planning. Bowel preparation should be prioritized over rectal or vaginal opacification in MRI protocols. Optimizing MRI protocols for diagnostic performance with appropriate opacification techniques will help diagnose deep endometriosis more accurately. Evaluating deep endometriosis in collapsible organs such as the vagina and rectum is difficult. Bowel preparation and an absence of vaginal opacification were found to be diagnostically beneficial. Bowel preparation should be prioritized over rectal or vaginal opacification in MRI protocols.

P-714 Prevalence of chromosomal abnormalities in oocyte donor candidates: a French survey of over 8200 karyotypes

Abstract Study question Is karyotyping worth considering for fertile and childless oocyte donor candidates? Summary answer Karyotyping reduces the genetic risk of utilizing oocytes with balanced structural chromosomal rearrangements for recipient couples. What is known already While some countries including France consistently advocate for karyotype to be routinely performed, others suggest it as optional, specifically advising it for donors with a medical history indicating chromosomal rearrangements. Ravel et al. have demonstrated a higher incidence of balanced structural chromosomal rearrangements among 1196 french fertile oocyte donor candidates (FODC) compared to unselected newborns, raising the question whether oocyte donor recruitment could be biased towards chromosomally at-risk women. In 2016, France authorized childless oocyte donor candidates (CODC) to enhance recruitment, yet as of now, there is no reported study on their genetic status. Study design, size, duration A retrospective observational multicentric study conducted from January 2005 to October 2021. Participants/materials, setting, methods ODC were recruited within the French CECOS (Centre d’Etude et de Conservation des Œufs et du Sperme humain) network. Both FODC and CODC were compared to a control group composed of female newborns from literature. Quantitative and qualitative data were expressed as the median [25%–75%] or n (‰), respectively. Non-parametric Mann-Whitney tests were employed for quantitative parameters, while Chi-square tests or Fisher’s exact tests were used, as appropriate, to compare frequencies between groups. Main results and the role of chance A total of 8229 ODC from 22 CECOS centers were included in this study. FODC (n = 6339) and CODC (n = 1890) were compared to 8102 control female newborns. In total, 65 chromosomal abnormalities (7.9‰) were identified, leading to the exclusion of the ODC. This outcome was comparable to the 53 abnormalities observed in the control group (6.54‰, p = 0.3059). The occurrence of balanced structural chromosomal rearrangements was increased in ODC population (4.8‰) compared to controls (2.34‰, p = 0.0086). The occurance of reciprocal translocations was increased 5-fold in CODC (3.70‰) compared to the control group (0.74‰, p = 0.013). The number of gonosomal mosaics was notably increased in FOCD, with 17 cases (2.68‰) compared to the control group with six cases (0.74‰, p = 0.0052). Among chromosomal aberration carriers only two childless women (one reciprocal translocation and one gonosomal mosaïc) had fertility issues in their medical history with a diagnosis of premature ovarian failure. Limitations, reasons for caution This retrospective study was designed to examine ODC within the framework of French bioethics laws. ODC should adhered to specific criteria: being volunteers, anonymous, aged 18 to 38, and without any financial compensation. Since 2016, donors were permitted to retain around 50% of their gametes for personal oocyte cryopreservation. Wider implications of the findings Karyotyping is a straightforward and cost-effective approach to identify structurally balanced chromosomal abnormalities. Thus, chromosomal analysis limits genetic risks whithout resorting to the ethically debated expanded genetic screening in the ODC population. Nevertheless, it is crucial to communicate to gamete recipients the inherent genetic risks associated with any conception. Trial registration number not applicable

P-087 Obstetrical and perinatal outcomes from intracytoplasmic sperm injection couples with oocyte donation are not affected by advanced paternal age measured as a continuous variable

Abstract Study question Does paternal age (PA), considered a continuous variable, have any effect on obstetrical and perinatal outcomes in intracytoplasmic sperm injection (ICSI) with donated oocytes? Summary answer PA does not affect clinically relevant obstetrical and perinatal outcomes, but it significantly increases the pregnancy’s duration in ICSI with autologous sperm and donated oocytes. What is known already Currently there has been an evident delay in childbearing, therefore studies relating advanced PA with reproductive risks are increasing and results are controversial. These studies frequently study PA by dividing it in groups arbitrarily constructed, but probably a more precise evaluation is obtained using PA as a continuous variable. Furthermore, oocyte donation standardizes female factor, to some extent, allowing a more realistic male factor evaluation. In this regard, we aimed to evaluate the effect of PA at conception (continuous variable) on obstetrical and perinatal outcomes in ICSI couples with autologous sperm and donated oocytes in a large population of patients. Study design, size, duration This retrospective observational multicentric cohort study evaluated data from couples that performed an ICSI between January 2008 and March 2020 using autologous sperm and donated oocytes. We included only singleton deliveries and the first delivery of each couple. PA was analysed as a continuous variable, considered more informative in comparison to its analysis as categorical. Data available and included consisted of 15,696 patients who had a delivery with or without a live birth. Participants/materials, setting, methods PA ranged from 21-54 years. Clinical database was constructed with reproductive outcomes from electronic medical records. Erroneous or incomplete data were removed. Statistical analysis included a descriptive analysis, followed by univariate and multivariate models using binary logistic regression or linear regression. We adjusted for maternal age and body mass index, PA, fresh sperm concentration and progressive motility, cycle type, gestational age, transfer on day 5 and delivery type (when appropriate). P &amp;lt; 0.05 was considered statistically significant. Main results and the role of chance Mean PA was 41.45 (41.38-41.51). We included a total of 15,696 deliveries and 15,673 live births. Results from multivariate models are presented as adjusted odd ratio or regression coefficient with 95% confidence intervals and adjusted p. In terms of obstetrical outcomes, PA results were 1.086 (0.959-1.229) p = 0.194 for gestational diabetes, 0.963 (0.849-1.093) p = 0.561 for anemia, 0.947 (0.837-1.072) p = 0.388 for hypertension, 0.959 (0.878-1.048) p = 0.356 for preterm birth and 0.986 (0.929-1.046) p = 0.641 for caesarean delivery. Regarding perinatal outcomes, PA results were 0.442 (0.005-0.879) p = 0.047 for gestational age, -0.216 (-15.559-15.126) p = 0.978 for infant weight, 1.101 (0.941-1.288) p = 0.231 for low birth weight (&amp;lt;2,500 g), 0.710 (0.463-1.088) p = 0.116 for very low birth weight (&amp;lt;1,500g), 0.988 (0.933-1.047) p = 0.684 for female sex, 0.002 (-0.076-0.08) p = 0.96 for length, -0.012 (-0.088-0.064) p = 0.763 for cranial perimeter, 0.991 (0.876-1.12) p = 0.88 for NICU admission, and 0.027 (-0.028-0.083) p = 0.337, 0.025 (-0.012-0.061) p = 0.18 and -0.045 (-0.096-0.007) p = 0.089 for Apgar 1, 5 and 10 minutes, respectively. According to our results, PA does not affect clinically relevant outcomes for the health during pregnancy and of the infant. However, PA significantly increases the duration of the pregnancy in ICSI with autologous sperm and donated oocytes. Limitations, reasons for caution The study’s major strengths are the consideration of PA as a continuous variable, the use of oocyte donation (controlling female factors) and the inclusion of a huge sample size. However, due to its retrospective nature there are some biases derived from the clinical practice and the presence of missing data. Wider implications of the findings Current evident delay in childbearing merits further research on the effect of PA on reproductive outcomes, addressed in this study. Our study suggests that PA is not associated with obstetrical and perinatal outcomes, except for gestational age, which sends a hopeful message to fathers of advanced paternal age. Trial registration number not applicable

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

Abstract Study question Does personalized embryo transfer (pET) guided by Endometrial Receptivity Analysis (ERA) increase reproductive outcome in patients with &amp;gt;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 &amp;gt;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 &lt; 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.

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.