Multicenter Retrospective Cohort Study Research Articles

Erectile dysfunction in patients treated with selpercatinib for RET altered thyroid cancer.

The highly selective RET inhibitor selpercatinib showed high efficacy and favorable toxicity profile in treating patients with RET-altered thyroid cancer (TC). Erectile dysfunction (ED) is a common adverse event observed in patients with advanced cancers. This study aims to evaluate the occurrence of ED in TC patients treated with selpercatinib. In a multi-center retrospective cohort study, we investigated the prevalence of ED in 25 male patients treated with selpercatinib for advanced TC. The management of ED was also examined. 18/25 (78.3%) patients presented ED after starting selpercatinib treatment. However, only 2/18 (11.1%) spontaneously reported ED, while 16/18 (88.9%) reported ED only after specific questioning. Ten patients started treatment with phosphodiesterase-5 inhibitors (PDE-5i) with a significant improvement of ED. In this study, we observed that ED was not infrequently reported among men treated with selpercatinib for RET-altered TC. We believe that clinicians should actively inquire about ED in such patients at it may be underreported but may be amenable to treatment.

Association between pre-gravid body mass index and clinical outcomes in in vitro fertilization: a multicentered retrospective cohort study

BackgroundWith the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity’s impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age.MethodsA retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI < 18.5; group 2: 18.5 ≤ BMI < 23.0; group 3: 23.0 ≤ BMI < 25.0; group 4: 25.0 ≤ BMI < 30.0; group 5: BMI ≥ 30.0). The primary outcome was cumulative live birth rate (CLBR), and other clinical and neonatal outcomes were weighed as secondary outcomes. Multivariate logistic regression analyses were carried to evaluate the association between BMI and the CLBR, or between BMI and some neonatal outcomes. Furthermore, we implemented a machine-learning algorithm to predict the CLBR based on age and BMI.ResultsA total of 115,287 women who underwent first IVF cycles with autologous oocytes from January 2013 to December 2017 were included in our study. The difference in the CLBR among the five groups was statistically significant (P < 0.001). The multivariate logistic regression analysis showed that BMI had no significant impact on the CLBR, while women’s age associated with the CLBR negatively. Further, the calculation of the CLBR in different age stratifications among the five groups revealed that the CLBR lowered with age increasing, quantitatively, it decreased by approximately 2% for each one-year increment after 35 years old, while little difference observed in the CLBR corresponding to the five groups at the same age stratification. The machine-learning algorithm derived model showed that BMI’s effect on the CLBR in each age stratification was negligible, but age’s impact on the CLBR was overwhelming. The multivariate logistic regression analysis showed that BMI did not affect preterm birth, low birth weight infant, small for gestational age (SGA) and large for gestational age (LGA), while BMI was an independent risk factor for fetal macrosomia, which was positively associated with BMI.ConclusionsMaternal pre-gravid BMI had no association with the CLBR and neonatal outcomes, except for fetal macrosomia. While the CLBR was lowered with age increasing. For the IVF-pursuing women with obesity plus advanced age, rather than losing weight first, the sooner the treatment starts, the better. A multicentered prospective study with a large size of samples is needed to confirm this conclusion in the future.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study

Most cutaneous squamous cell carcinoma recurrences occur in the first three years after diagnosis: A multicenter retrospective cohort study

Most cutaneous squamous cell carcinoma recurrences occur in the first three years after diagnosis: A multicenter retrospective cohort study

Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.

TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoJIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent OligoJIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). Younger age at onset, uveitis, duration of tapering, and not-persistent OligoJIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.

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 (&amp;gt;3 failed ET), recurrent miscarriages (&amp;gt;2 miscarriages) or had advanced maternal age (&amp;gt;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 &amp;lt; 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’

P-715 outcomes of in vitro fertilization and embryo transfer among ethnic Tibetan, Yi and Han Chinese women

Abstract Study question Does difference exist in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) among ethnic Tibetan, Yi and Han Chinese women? Summary answer We report that the outcomes of IVF-ET were poorer among ethnic Yi women compared with ethnic Han and Tibetan women. What is known already It has been reported that the outcomes of IVF-ET are correlated with ethnicity/race in Europe and the United States as an independent factor. Sichuan is the only province in China where all 56 ethnic groups reside, with ethnic Han, Yi and Tibetan Chinese having the highest proportions. In Chengdu city (the capital of Sichuan province, basin), the majority ethnic group is Han, whilst in Liangshan and Aba Prefectures (plateau), the major ethnic groups are Yis and Tibetans. The living environment, diet, custom, medical condition and genetic backgrounds are different among different ethnic groups. Study design, size, duration In this multi-center retrospective cohort study, a total of 58374 Chines women aged 20 ∼ 45 had undergoing the first IVF or intracytoplasmic sperm injection (ICSI) ET treatment cycle with non-donor gametes from January 2014 to December 2022 were enrolled. Participants/materials, setting, methods The patients were enrolled from two University Affiliated Hospitals and one Reproductive Hospital in Chengdu. The controlled ovarian stimulation protocols were gonadotropin releasing hormone (GnRH) agonist protocol or GnRH antagonist protocol. The patients were divided into three groups based on their ethnic origins: Tibetans (n = 1069), Yis (n = 2273) and Hans (n = 55032). The outcomes of IVF-ET were compared, with the primary outcome being the live birth rate. Main results and the role of chance The proportion of GnRH agonist protocol and IVF fertilization, the rates of moderate and severe ovarian hyper-stimulation syndrome (OHSS), and cleavage embryo formation in ethnic Han women were significantly higher than in the ethnic Yis and Tibetans (P &amp;lt; 0.05). The rates of implantation, clinical pregnancy and live birth (35.5% vs. 42.4%) were significantly lower, whereas the late abortion rate was significantly higher in Yi women than that in Han women (P &amp;lt; 0.05). The live birth rate was significantly lower in Yi women (35.5%) than in Tibetan (43.3%) and Han women (42.2%) (P &amp;lt; 0.05). Adjustment was made for age, duration, type and etiology of infertility, history of spontaneous abortion, smoking, alcohol, tuberculosis infection, body mass index, antral follicle count, antimüllerian hormone, and so on, by multivariate logistic regression analysis. Yi women had significantly lower rates of moderate and severe OHSS (OR = 0.69, 95% CI = 0.49-0.94, P = 0.024) and clinical pregnancy (OR 0.8, 95% CI 0.70-0.93, P = 0.002) compared with ethnic Hans. Yi women had significantly lower live birth rate compared with ethnic Hans (OR = 0.79, 95% CI = 0.68-0.92, P = 0.002) and Tibetans (OR 0.73, 95% CI 0.58-0.92, P = 0.007). Limitations, reasons for caution The limitations are related with the retrospective study and lack of some demographic characteristics of the patients which may influence the outcomes of IVF-ET, including diet habits, educational level, and economic status. Wider implications of the findings The ethnic group is an independent factor for the outcomes of IVF-ET among ethnic Tibetan, Yi and Han women. Among the three ethnic groups, the Yis had lower live birth rate and moderate and severe OHSS, whilst ethnic Han women had more moderate and severe OHSS. Trial registration number ChiCTR2300070269

Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.

P-277 Focal rather than diffuse nature of adenomyosis might be more detrimental to IVF outcomes after single euploid embryo transfer

Abstract Study question Is the nature of adenomyosis a factor to consider after a single euploid embryo transfer? Summary answer Focal adenomyosis was associated with lower live birth rate per transfer when compared to diffuse adenomyosis. What is known already Adenomyosis is widely described to hamper reproductive potential of women who suffer it. This uterine pathology has a detrimental impact on in vitro fertilization (IVF) clinical outcomes, as described by a series of recent metanalysis. Nevertheless, there is scarce evidence regarding clinical studies that address the impact of adenomyosis depending either on its diffuse or focal nature. Study design, size, duration A multicenter retrospective cohort study in which 229 patients undergoing IVF treatment were included. Patients with single embryo transfer (SET) in blastocyst stage after pregestational testing for aneuploidy (PGT-A) between years 2015 and May 2023 were divided into two groups: diffuse adenomyosis (n = 167) and focal adenomyosis (n = 62). Participants/materials, setting, methods Inclusion criteria consisted of patients in a PGT-A program who had a cryotransfer of a single euploid blastocyst-stage embryo. Patients were diagnosed within our facilities using transvaginal ultrasonography (TVUS) prior to their IVF cycle. Diffuse adenomyosis was diagnosed when irregular endometrial-myometrial junction, increased uterine volume, ill-defined myometrial heterogeneity, presence of anechoic round myometrial cysts, hyperechoic islands, fan-shaped shadows and/or echogenic subendometrial lines were detected. Focal adenomyosis was diagnosed when foci with adenomyotic characteristics were observed. Main results and the role of chance Clinical pregnancy rate per embryo transfer was 81/167 (48.5%) in those women diagnosed with diffuse adenomyosis versus 23/62 (37.1%) in the focal adenomyosis group (OR = 0.63 95% CI [0.33-1.18], NS). Differences found in clinical miscarriage rate were not statistically significant, being 33/81 (40.7%) for diffuse adenomyosis and 14/23 (60.1%) for the focal adenomyosis group (OR = 2.24 95% CI [0.79-6.63], NS). A lower live birth rate per euploid embryo transfer was observed in women diagnosed with focal adenomyosis, being 9/62 (14.5%) and 48/167 (28.7%) for women who presented diffuse adenomyosis (OR = 0.42 95% CI [0.17-0.95], p=0.027). There were no statistically significant differences between childbirth delivery method (vaginal versus caesarean section). Furthermore, means of gestational age at the time of delivery, newborn size and weight and incidences of low birth weight did not differ between the two groups. Limitations, reasons for caution The retrospective nature of this observational study implies that possible confounders cannot be completely excluded. Also, the accurate diagnostic of adenomyosis is not without complexity and although gynecologists were equally trained to identify direct and indirect markers, different criteria may have been used Wider implications of the findings To our knowledge this is the first study to use an euploid model to assess the impact of the focal versus diffuse nature of adenomyosis in IVF patients. This model permits to correct for numerous covariables attributed to patient’s age and embryo genetic constitution. Trial registration number Not applicable

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 &amp;gt; 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 &amp;gt;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 &amp;lt; 0.001), and a higher number of available blastocysts (2.82±2.21 vs 1.22±2.00, p &amp;lt; 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 &amp;lt; 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-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

O-252 Cumulative live birth rates (CLBR) in in vitro fertilization per oocyte used, embryo transferred, and embryo transfer impair with increasing female body mass index (BMI)

Abstract Study question Does the number of oocytes used, embryos transferred, or embryo transfers to achieve specific cumulative live birth rates differ according to female body mass index? Summary answer The greater the female BMI, the higher the number of oocytes, embryos and embryo transfers needed to achieve a liveborn, indicating a lower reproductive potential. What is known already The negative impact of high female BMI on in vitro fertilization (IVF) cycles has been extensively described in the medical literature, although there is no clear agreement on the potential role of oocytes, embryos, and endometrial receptivity on these results. However, the clinical outcome is commonly assessed per embryo transfer in isolated cycles and less frequently in cumulative cycles from the same cohort of oocytes. The number of oocytes or embryos needed to reach specific clinical goals has been never estimated in comparison to women with other BMIs, which gives a relevant multicycle overview of reproductive outcomes. Study design, size, duration This is a multicenter retrospective observational cohort study including a total of 31,289 women undergoing IVF with known BMI and 35,430 embryo transfers performed in 15 IVIRMA centers in Spain, from January 1, 2017, to October 1, 2023 with known outcome. Patients were grouped as Underweight (U, BMI&amp;lt;18.5 kg/m2), Normoweight (N, BMI 18.5-&amp;lt;25 kg/m2), Overweight (Ov, BMI 25-&amp;lt;30 kg/m2), and Obese (Ob, BMI≥30 kg/m2). Participants/materials, setting, methods IVF-ICSI cycles with autologous oocytes and partner’s sperm were analyzed according to female BMI. CLBR per oocyte used, embryos replaced, and embryo transfers in consecutive treatments until reaching live birth or abandon were calculated by survival curve analyses with Kaplan-Meier’s methods estimating hazard ratios (HR), and BMI groups compared by with Log-Rank test. Outcomes per embryo transfer/completed cycle and descriptives were compared by chi square tests, and ANOVA where appropriate. Main results and the role of chance Mean women’s age was 37.6years, 95%CI(37.5-37.6), 36.9 years95%CI(36.7-37.1), 37.7years95%CI(37.6-37.8), and 37.2years95%CI(37.0-37.4) for N, U, Ov, and OB respectively. Mean stimulation days and serum progesterone concentrations the day of hCG administration were comparable. Estradiol on triggering day was statistically higher(p &amp;lt; 0.05) on U group, 2073pg/ml95%CI(2008-2138), compared to the other groups, N 1942pg/ml95%CI(1926-1957), Ov 1840pg/ml95%CI(1808-1872), and Ob 1789pg/ml 95%CI(1742-1835). Number of aspirated oocytes was higher on Ob 9.47,95%CI(9.23-9.71), compared with N 9.1,95%CI(9.02-9.17),p&amp;lt;0.05. LBR per embryo transfer was 35.0%95%CI(32.9-37.3) for U, 33.3%95%CI(32.7-33.9) for N, 32.13%95%CI(30.9-33.4) for Ov ad 28.3%95%CI(26.6-30.1) for Ob, p &amp;lt; 0.001. LBR per completed IVF-ICSI cycle (until reaching live birth or using all embryos) was 41.8%95%CI(69.7-43.9) for U, 40.6%95%CI(40.0-41.18) for N, 39.50%95%CI(38.4-40.6) for Ov, and 39.6%95%CI(37.9-41.37) for Ob, being statistically comparable. Using N as a reference group, HR were 1.07,95%CI(0.98-1.17) for U, 0.98,95%CI(0.93-1.03) for Ov, and 0.90,95%CI(0.84-0.98) for Ob, p-value=0.011, being Ob significantly different compared to N. Regarding HR per embryo transfer, 0.96,95%CI(0.82-1.13) for U, 0.87,95%CI(0.79-0.96) for Ov and 0.76,95%CI(0.66-0.89) for Ob, being statistically different Ov (p = 0.0055) and OB (p &amp;lt; 0.001) from N. With the total number of embryos transferred, HR were better than N in U group, 1.11,95%CI(1.02-1.20), p = 0.0192 and significantly worse in Ov and Ob, 0.91,95%CI(0.87-0.96) and 0.85,95%CI(0.79-0.92), p &amp;lt; 0.001 on both. Limitations, reasons for caution Despite the huge sample of patients included and the statistical approach used, the retrospective design of the study represents its main limitation, thus needing to interpret the findings with caution. Wider implications of the findings IVF-ICSI cycles in women high BMI are less efficient than in normoweight women since a greater number of oocytes, embryos and embryo transfers are needed to reach similar CLBRs. This finding highlights again the advice of initiating IVF with an adequate female body weight. Trial registration number not applicable

O-089 Association of pituitary suppression method with euploid blastocyst yield in preimplantation genetic testing for aneuploidy (PGT-A) cycles

Abstract Study question Do progestin primed ovarian stimulation (PPOS) cycles have lower euploidy yield compared to pituitary suppression with gonadotropin releasing hormone (GnRH) antagonists? Summary answer The choice of pituitary suppression method has no bearing on euploid retrieval per blastocyst tested. What is known already Progestin primed ovarian stimulation cycles are an alternative to GnRH antagonists when fresh embryo transfer is not a priority. While the two approaches have been shown to be similar in terms of conventional stimulation outcomes such as mature oocyte retrieval, and blastulation rates, there is still some lingering controversy regarding cumulative pregnancy rates and the effects of progestins on embryo genetic constitution. Study design, size, duration This was a multicenter retrospective cohort study including data from two tertiary-level treatment centers. Participants/materials, setting, methods Infertile women undergoing ovarian stimulation with either progestin primed or GnRH antagonist pituitary suppression with the intention of transfer after PGT-A embryo testing with next-generation sequencing. The main outcome parameter was euploid embryo count per blastocyst tested and was modeled with mixed-effects log-binomial regression models. Results were adjusted for patient age and laboratory performing the PGT-A tests while they were not adjusted for embryo quality to avoid collider bias. Main results and the role of chance A total of 1425 PGT-A tested blastocysts from 383 cycles of 365 patients were included in the analysis. 243 cycles (63.4%) received GnRH antagonists for pituitary suppression while 140 (36.5%) received progestins. The overall euploidy rates per blastocyst tested in the GnRH antagonist and PPOS groups were 38.8% vs. 31.1%, 30.2% vs. 29.4%, 27.0% vs. 25.2%, and 13.8% vs. 14.5% for the age categories &amp;lt;35, 35-37, 38-40, and &amp;gt;40, respectively. After adjusting for the effect of female age at testing and the laboratory performing the PGT-A test, the type of pituitary suppression was not significantly associated with euploid retrieval per blastocyst tested (adjusted risk ratio: 0.94, 95% CI: 0.70 - 1.28, P = 0.701). After testing, 191 women received 233 embryo transfers. Human chorionic gonadotropin (hCG) positivity per transferred embryo was not significantly different between progestin primed and GnRH antagonist cycles (RR: 0.89, 95% CI: 0.71 – 1.08, P = 0.268). Limitations, reasons for caution This is a retrospective study with data from multiple centers with a non-standardized selection of blastocysts to be tested. In addition, the sample size and retrospective nature of the data may have biased the estimates. Wider implications of the findings The choice of pituitary suppression method does not appear to have a significant effect on euploid embryo retrieval rates or hCG positivity per transfer. The choice of medication can be based on the needs of the individual case without concern for suboptimal PGT-A outcomes. Trial registration number Not Applicable

P-603 Combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) in donors could negatively affect egg donation outcomes in recipients: a multicentre retrospective study

Abstract Study question Could COCP use before COH with a progestin primed ovarian stimulation protocol (PPOS) in donors also negatively influence the egg donation outcomes in recipients? Summary answer Synchronization with a combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) involving progestin for pituitary suppression shows worst outcomes in egg donation treatments. What is known already It is well known that COCP leads to a long-lasting pituitary suppression, a reversible reduction in AMH and antral follicle count with higher risk of inappropriate response to COH and GnRH-agonist trigger, potentially reducing number and quality of retrieved oocytes. This is supported by the latest international guidelines on COH that strongly discourage COCP use before GnRH antagonist protocols because of a reduced efficacy of such cycles, also, in terms of ongoing pregnancy rate (OPR). They also underlie that interactions between COCP pretreatment and PPOS protocols remain inadequately explored and more research are needed to clarify discrepancies persisting in literature. Study design, size, duration Multicentre retrospective cohort study evaluating egg donation outcomes, depending on the use or not of COCP pre-treatment in donors, in terms of OPR, Live Birth Rate (LBR), and secondly of fertilization rate (FR), blastulation rate (BR), implantation rate (IR) and miscarriage rate (MR). The treatments were realized in a Private Fertility Clinic (where donors also underwent COH with PPOS protocol) and a public hospital (transnational egg donation program) between January 2022 and September 2023. Participants/materials, setting, methods 216 egg donation cycles were studied. Excluding cases of fertilization and/or embryo development failure and cases for which embryo transfer outcomes were not available at the time of data collection, the study analysed the outcomes of 90 embryo transfers (ETs). After the first analysis on total cycles, a stratification was made to evaluate whether COCP could have a different influence depending on the oocytes type used: fresh or vitrified. Main results and the role of chance COCP-No and COCP-Yes groups show similar FR and BR, after donation of same oocytes number (6,4 ± 1,1 vs 6,5± 1). Interestingly, vitrified oocytes from COCP-Yes donors produced a statistically lower yield of viable blastocysts (22,2% versus 37,9%; p = 0,007). IR was higher in the COCP-No group, (46,4% vs. 28,6%), data confirmed also in the two subgroups (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). Higher MR was observed in the COCP-Yes group, achieving statistical significance both for total oocytes (66,7% vs. 9,4%; p = 0,006) and vitrified ones (60% vs. 5%; p = 0,016). Pregnancy rate was higher in the COCP-No group (46,4% vs. 28,6%), the same trend was found regardless of the type of oocytes used (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). The greatest discrepancies were observed in OPR and LBR subcategories. In fact, a statistically higher OPR was obtained in the COCP-No group (42% vs. 9,5%, p = 0,008), which leads to a statistically higher LBR (30,4% vs. 0%; p = 0,004). Notably, the LBR after using both fresh and vitrified oocytes was markedly higher in the COCP-No group (fresh: 28,6% vs. 0%, p = 0,385; vitrified: 31,7% vs. 0%, p = 0,041), presenting a significant difference when vitrified oocytes were used with potential clinical relevance. Limitations, reasons for caution The main limitation lies in the retrospective nature of the study and the small sample size, but the multicentre design gives greater reliability. Further research is needed to confirm these findings and better understand the specific circumstances in which COCP may or may not be beneficial. Wider implications of the findings COCP pretreatment in egg donors undergoing PPOS protocol may negatively impact embryo development and pregnancy outcomes in recipients, with increased MR, and reduced OPR, and LBR. Particularly, the worst outcomes involve vitrified oocytes, providing valuable insights to reconsider COCP use in transnational egg donation programs, but also fertility preservation ones. Trial registration number Not Applicable

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.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007–2021: a nationwide, multicentre, retrospective cohort study

It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p<0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p<0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p<0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p<0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p<0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p<0.0001). Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. The Korea Disease Control and Prevention Agency.

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML

AbstractAlthough intensive induction chemotherapy (IC) remains the standard of care for younger patients with acute myeloid leukemia (AML), data from older patients show that hypomethylating agents + venetoclax (HMA/VEN) can lead to durable remission among patients with nucleophosmin 1 (NPM1) mutations. Whether IC or HMA/VEN is superior in patients aged ≥60 years with NPM1-mutant AML is unknown. To compare IC and HMA/VEN, we performed an international, multicenter retrospective cohort study of patients with newly diagnosed, NPM1-mutant AML. We included 221 patients (147 IC and 74 HMA/VEN) with previously untreated NPM1-mutant AML. Composite complete remission (cCR) (defined as CR + CR with incomplete count recovery) rate was similar for IC and HMA/VEN (cCR, 85% vs 74%; P = .067). Although overall survival (OS) was favorable with IC in unselected patients compared with HMA/VEN (24-month OS, 59% [95% confidence interval (CI), 52-69] vs 38% [95% CI, 27-55]; P = .013), it was not statistically different among patients aged 60 to 75 years (60% [95% CI, 52-70] vs 44% [95% CI, 29-66]; P = .069) and patients who received an allogeneic stem cell transplant (70% [95% CI, 58-85] vs 66% [95% CI, 44-100]; P = .56). Subgroup analyses suggested that patients with normal cytogenetics (24-month OS, 65% [95% CI, 56-74] with IC vs 40% [95% CI, 26-60] with HMA/VEN; P = .009) and without FLT3 internal tandem duplication mutations might benefit from IC compared with HMA/VEN (24-month OS, 68% [95% CI, 59-79] vs 43% [95% CI, 29-63]; P = .008). In multivariable analysis, OS was not statistically different between patients treated with IC and HMA/VEN (hazard ratio for death with HMA/VEN vs IC, 0.71; 95% CI, 0.40-1.27; P = .25).

Trimethoprim-sulfamethoxazole dosing and outcomes of pulmonary nocardiosis.

Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens. We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10mg/kg/day), intermediate- (5-10mg/kg/day) or low-dose (< 5mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses. Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001). Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis.