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STUDY QUESTION What is the involvement of ovarian stroma in the anti-Müllerian hormone (AMH) signaling pathway and which stromal cells are involved? SUMMARY ANSWER Mouse and human ovaries show high expression of AMH receptor II (AMHR2) in the stromal fibroblasts surrounding the follicles and activation of the post-AMHR2 pathway by recombinant AMH was evidenced by increased phosphorylation of SMAD1,5 and 9, increased expression AMHR2 and upregulation of αSMA, suggesting fibroblast activation to initiate myofibroblast differentiation. WHAT IS KNOWN ALREADY AMH secreted by small growing follicles, regulates ovarian activity. It suppresses initial primordial follicle (PMF) recruitment and FSH-dependent growth. AMH signal transduction is mediated by AMHR2, activating intracellular SMAD proteins and other signaling cascades to induce target-gene expression. Although AMHR2 expression has been reported within the follicle unit, there is evidence suggesting it may be identified in the stroma as well. STUDY DESIGN, SIZE, DURATION Fresh murine ovaries were extracted from BALB/c mice (6 weeks old; n = 12 and 21 days old; n = 56). Frozen-thawed ovarian fragments were obtained from 10 women, aged 18–35, who had undergone ovarian tissue cryopreservation and donated frozen ovarian tissue for research. PARTICIPANTS/MATERIALS, SETTING, METHODS Murine (6 weeks old) and human donor ovaries were immunostained for AMHR2 and Collagen 1α/αSMA/VCAM1, with additional vimentin staining in mice. Murine (21 days old) and human donor ovaries were used for fibroblast isolation and subsequent 7-day cultures. Prior to assessing AMH effects on isolated fibroblast culture, purity validation tests were implemented to ensure the absence of epithelial, immune, endothel, granulosa, and theca ovarian cell populations. The fibroblast culture's homogeneity was validated by RT-qPCR and western-blot assays, confirming negativity for E-cadherin, CD31, aromatase, CYP17A1, and positivity for αSMA and vimentin. Fibroblasts were then subjected to rAMH treatment in vitro (200 ng/ml) for 0–72 h, with an additional time point of 96 h for human samples, followed by RT-qPCR, western blot, and immunocytochemistry (ICC) for AMHR2 expression. AMHR2 post-receptor signaling was examined by pSMAD1,5,9 levels via western blot. Activated fibroblast marker, αSMA, was assessed via western blot and ICC. MAIN RESULTS AND THE ROLE OF CHANCE Immunostaining of mouse and human ovarian tissue showed that stromal cells around follicles at all developmental stages exhibit high AMHR2 expression, while granulosa cells of growing follicles show considerably lower levels. The majority of these AMHR2-positive stromal cells were identified as fibroblasts (Collagen1α in mice and human; vimentin in mice). RT-qPCR, western blot, and immunostaining were performed on cultured mouse and human fibroblasts, confirming that they consisted of a pure fibroblast population (αSMA/vimentin positive and negative for other cell-type markers). A total of 99.81% (average 28.94 ± 1.34 cells/field in mice) and 100% (average 19.20 ± 1.39 cells/field in human samples) of these fibroblasts expressed AMHR2 (ICC). rAMH treated cultured fibroblasts showed increased pSMAD1,5 and 9 levels, demonstrating the effects of AMH on its downstream signaling pathway. pSMAD1,5 and 9 expression increased, as detected by western blot: 1.92-fold in mice (48 h, P  = 0.026) and 2.37-fold in human samples (48 h, P  = 0.0002). In addition, rAMH treatment increased AMHR2 protein expression, as observed in ICC (human): a 2.57-fold upregulation of AMHR2 Mean Fluorescence Intensity (MFI) (96 h, P  = 0.00036), and western blot, showing a 4.2-fold time-dependent increase (48 h, P  = 0.026) in mice and 2.4-fold change (48 h, P  = 0.0003) in human donors. Exposure to rAMH affected AMHR2 transcription upregulation, with a 6.48-fold change (72 h, P  = 0.0137) in mice and a 7.87-fold change (72 h, P  < 0.0001) in humans. rAMH treatment induced fibroblast activation (αSMA positive), demonstrating the dynamic effects of AMH on fibroblast behavior. αSMA expression elevation was detected in ICC with a 2.28-fold MFI increase in humans (96 h, P  = 0.000067), and in western blot with a 5.12-fold increase in mice (48 h, P  = 0.0345) and a 2.69-fold increase in humans (48 h, P  ≤ 0.0001). Activated AMHR2-positive stained fibroblast fractions were solely located around growing follicles, in both human and mice. In addition, a small population of AMHR2-positive stained theca cells (VCAM1 positive) was observed. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Ex vivo , fibroblast gene expression might be changed by adhesion to the tissue-culture plate. Nevertheless, cultured fibroblasts (with and without rAMH) are subjected to the same conditions. Observations or significant differences can therefore be considered reliable. In addition, the presented effect of rAMH on fibroblasts is not directly linked to the known inhibitory effect of AMH on follicle activation. WIDER IMPLICATIONS OF THE FINDINGS Clarifying the populations of AMH-responsive cells in the ovary provides a foundation for further investigation of the complex AMH signaling across the ovary. The composition of AMH-releasing and -responsive cells can shed light on the communication network between follicles and their environment, which may elucidate the mechanisms behind the AMH inhibitory effect on PMF activation. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by grants from the Kahn Foundation. There are no competing interests in this study. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Oral contraceptives (OC) are the most used form of contraception among women in the U.S. and Europe. Like other medications, their packaging must include patient information leaflets. This study quantifies the environmental impact of paper waste generated by these leaflets. We conducted an observational analysis, measuring the weight of leaflets, pills, and packaging components across various OC brands. Significant variations in leaflet weights were observed. On average, leaflets accounted for 55% of the package weight, while pills and blister dispensers represented only 32%. The mean weight of OC leaflets was 12.3 ± 5.5 grams (4.7–21.9 grams), leading to an estimated annual paper waste of 6,118.4 tons, 5,763.5 tons of carbon dioxide equivalent emissions, and the use of approximately 146,841 trees for production. Standardizing leaflet weight to the lightest reported can reduce annual waste by 3780.5 tons of paper. This study highlights the substantial environmental cost of the waste generated from OC leaflets and proposes practical strategies to mitigate waste, including electronic leaflets and standardized packaging. Targeting these materials presents a significant opportunity to enhance sustainability, aligning with global efforts to reduce greenhouse gas emissions from the healthcare sector. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ability of ChatGPT-4 to generate a biomedical review article on fertility preservation. Methods: ChatGPT-4 was prompted to create an outline for a review on fertility preservation in men and prepubertal boys. The outline provided by ChatGPT-4 was subsequently used to prompt ChatGPT-4 to write the different parts of the review and provide five references for each section. The different parts of the article and the references provided were combined to create a single scientific review that was evaluated by the authors, who are experts in fertility preservation. The experts assessed the article and the references for accuracy and checked for plagiarism using online tools. In addition, both experts independently scored the relevance, depth, and currentness of the ChatGPT-4's article using a scoring matrix ranging from 0 to 5 where higher scores indicate higher quality. Results: ChatGPT-4 successfully generated a relevant scientific article with references. Among 27 statements needing citations, four were inaccurate. Of 25 references, 36% were accurate, 48% had correct titles but other errors, and 16% were completely fabricated. Plagiarism was minimal (mean = 3%). Experts rated the article's relevance highly (5/5) but gave lower scores for depth (2–3/5) and currentness (3/5). Conclusion: ChatGPT-4 can produce a scientific review on fertility preservation with minimal plagiarism. While precise in content, it showed factual and contextual inaccuracies and inconsistent reference reliability. These issues limit ChatGPT-4 as a sole tool for scientific writing but suggest its potential as an aid in the writing process. [ABSTRACT FROM AUTHOR]

Efforts are being made to improve the time effectiveness of healthcare providers. Artificial intelligence tools can help transcript and summarize physician-patient encounters and produce medical notes and medical recommendations. However, in addition to medical information, discussion between healthcare and patients includes small talk and other information irrelevant to medical concerns. As Large Language Models (LLMs) are predictive models building their response based on the words in the prompts, there is a risk that small talk and irrelevant information may alter the response and the suggestion given. Therefore, this study aims to investigate the impact of medical data mixed with small talk on the accuracy of medical advice provided by ChatGPT. USMLE step 3 questions were used as a model for relevant medical data. We use both multiple-choice and open-ended questions. First, we gathered small talk sentences from human participants using the Mechanical Turk platform. Second, both sets of USLME questions were arranged in a pattern where each sentence from the original questions was followed by a small talk sentence. ChatGPT 3.5 and 4 were asked to answer both sets of questions with and without the small talk sentences. Finally, a board-certified physician analyzed the answers by ChatGPT and compared them to the formal correct answer. The analysis results demonstrate that the ability of ChatGPT-3.5 to answer correctly was impaired when small talk was added to medical data (66.8% vs. 56.6%; p = 0.025). Specifically, for multiple-choice questions (72.1% vs. 68.9%; p = 0.67) and for the open questions (61.5% vs. 44.3%; p = 0.01), respectively. In contrast, small talk phrases did not impair ChatGPT-4 ability in both types of questions (83.6% and 66.2%, respectively). According to these results, ChatGPT-4 seems more accurate than the earlier 3.5 version, and it appears that small talk does not impair its capability to provide medical recommendations. Our results are an important first step in understanding the potential and limitations of utilizing ChatGPT and other LLMs for physician-patient interactions, which include casual conversations. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the influence of parental biometric factors on fetal birthweight (BW). Study design This prospective study was conducted between 2015 and 2017 in Hadassah University Hospital. Inclusion criteria included singletons that were born to healthy mothers at 37–41 weeks’ gestation and had no growth abnormality or congenital malformation. Maternal and paternal head circumference, weight, and height were measured. Other data including neonatal head circumference and neonatal birthweight were also collected. Neonatal head circumference and birthweight percentiles were converted to sex-specific ranks according to the neonatal Intergrowth 21 charts (rank = 1 for percentile <3, rank = 2 for percentile 3–10, etc.). Results One hundred and ninety-nine trios (mother, father, and neonate) were included in the final analysis. In univariate analysis, maternal head circumference (p = .006), maternal height (p = .001), maternal weight before pregnancy (p < .001), maternal weight at term (p < .001), gestational weight gain (p = .009), paternal height (p = .018), neonatal head circumference (p < .001), and neonatal head circumference percentile rank (p < .001) were significant predictors of neonatal birthweight percentile rank. In multivariate regression, the three factors that were significant independent predictors of neonatal birthweight percentile rank were maternal weight before pregnancy (p = .047), maternal weight at term (p = .01), and neonatal head circumference percentile rank (p < .001). No interaction was found between neonatal sex and any of the tested variables. Neonatal sex-specific multivariate analysis showed that maternal height (p = .013), gestational weight gain (p = .005), and neonatal head circumference percentile rank (p < .001) were predictors of birthweight percentile rank in males. Maternal weight at term (p < .001) and neonatal head circumference percentile rank (p < .001) were predictors of birthweight percentile rank in females. Conclusions Maternal height and weight parameters as well as neonatal head circumference percentile rank were found to be independent predictors of birthweight percentile rank. Paternal parameters did not show any significant association in multivariable analysis. The biological regulation of fetal size is assumed to be the result of strong evolutionary selection. As the fetus must pass through the mother's birth canal, there should be a natural match between maternal and fetal size to ensure the successful birth and survival of mother and offspring. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility, effectiveness, and reproductive outcomes of transplantation of tiny cryopreserved ovarian pieces through a pipelle cannula during laparoscopic surgery. Methods: A retrospective study of patients who underwent ovarian tissue transplantation for fertility restoration between 2004 and 2022. The "pipelle group" had their ovarian cortex cut into tiny pieces of ~ 1–2 mm3 before cryopreservation. The pieces were too small to be handled and transplanted via standard laparoscopic tools. Transplantation was performed using a pipelle cannula during laparoscopic surgery. The "control group" underwent transplants of ovarian cortex pieces 1–2 mm thick, measuring approximately 25–50 mm2 pieces, using standard procedures. Results: The pipelle group consisted of 4 patients aged 19, 21, 27, and 28 years old at ovarian tissue cryopreservation (OTC). The control group consisted of 14 patients aged 21–30 years old. All pipelle patients restored their endocrine activity, and all of them conceived. FSH levels dropped during the first 3 months following the pipelle transplant. IVF cycle outcomes were similar for both groups. All patients from the pipelle group conceived, resulting in 5 pregnancies and 4 live births (one patient had 2 deliveries, and one additional pregnancy is ongoing), compared to the control group, where 8 patients achieved a total of 20 pregnancies and 18 live births. Conclusion: Pipelle transplantation for tiny cryopreserved ovarian pieces is feasible and effective. This study opens a door for patients who had their ovaries cut into small pieces and may even simplify the procedure in some instances, making ovarian transplant more accessible. Trial registration : (#6531–19-SMC) [18/09/2019]. [ABSTRACT FROM AUTHOR]

Urinary tract injury during cesarean delivery is a rare but severe complication. Due to the high prevalence of cesarean delivery, this injury may pose a high burden of morbidity. We reviewed the cases of lower urinary tract injuries identified during cesarean delivery in a tertiary medical center and identified diagnosis and treatment methods, as well as short and long-term outcomes, to establish a protocol of care for such cases. We included women with urinary tract injury during cesarean delivery between 2004 and 2018. The cases were identified according to ICD-9 codes, as well as free text in the medical report and discharge letter. Data were collected retrospectively. Telephone interviews were conducted to obtain additional data regarding long-term outcomes. In14 years, a total of 17,794 cesarean deliveries were performed at our institution (17.5% of all deliveries), 14 cases of bladder injury, and 11 cases of ureteral injury were identified featuring an incidence of 0.08 and 0.06%, respectively. All bladder injuries were diagnosed and repaired intra-operatively. Six (55%) cases of ureteral injury were diagnosed in the post-operative period, and 3 of these patients required further surgery for definitive treatment. None of the patients suffered long-term adverse effects. Most bladder injuries occurred in women with previous cesarean delivery in the presence of abdominal adhesions. In contrast, most ureteral injuries occurred in women with emergency cesarean delivery during the second stage of labor, and were accompanied by an extension of the uterine incision. All women had normal kidney function in follow up and did not suffer from long term sequelae. Urinary tract injury is an uncommon complication of cesarean delivery. A high index of suspicion is recommended to avoid late diagnosis and complications. We propose a comprehensive protocol for the management of these injuries. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine whether a single episode of vaginal bleeding occurring between 24 and 34 weeks gestation is associated with preterm delivery and other adverse maternal and neonatal outcomes.Study design: We conducted a retrospective cohort study in the Maternal-Fetal unit of two campuses of a large tertiary, medical center with approximately 12,000 deliveries annually. The study group consisted of all women with a singleton pregnancy between 24 + 0/7 and 33 + 6/7 weeks of gestation, admitted to the high-risk antenatal ward due to a single episode of vaginal bleeding of unknown origin between May 2003 and December 2014. Maternal and neonatal parameters of the study group were compared to the maternal and neonatal parameters of the rest of the singleton deliveries occurring in our institution during the study period. The primary outcome was rate of preterm delivery while secondary outcomes were other adverse maternal and neonatal outcomes. Multivariate logistic regression was performed to identify risk factors for preterm delivery in the study group.Results: Two hundred thirty women met the inclusion criteria and 51,468 women were in the comparison group. Preterm delivery rates were 20% and 5.5% in the study and the comparison group, respectively OR = 3.55 [2.63-4.78] (p < .001). The aOR for preterm delivery among the study group for women with a previous preterm delivery was 4.62 [1.17-18.20] (p = .029) and for women with a short cervix was 9.35 [2.30-37.95] (p = .002).Conclusions: A single episode of third-trimester vaginal bleeding is an independent risk factor for spontaneous preterm delivery. The presence of a shortened cervix or a history of a prior spontaneous preterm delivery increases this risk significantly.Key messageThird trimester vaginal bleeding is strongly associated with preterm delivery. Knowledge of this relationship has valuable clinical implications for practicing obstetricians. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of obstetric, maternal, and fetal variables with successful membrane sweeping and to develop a calculator that can predict spontaneous delivery within 24 hours of membrane sweeping. Methods: This secondary analysis of the STRIP-G Study included all singleton term parturients who underwent membrane sweeping in a tertiary center in October 2011 to July 2013. Primary end point was a 24-hour time interval from sweeping to delivery. Women who delivered without formal induction within the 24-hour interval were included in the "successful sweeping group". Stepwise logistic regression was used to calculate the adjusted odds ratio (aOR) for successful membrane sweeping and to create the calculator. The predictive power of the calculator was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC) curve and by Nagelkerke R-square. The model was validated by the Hosmer-Lemeshow test and by these validation measures: sensitivity, specificity, and positive and negative predictive value. Results: We analyzed data from 542 women. Parity (aOR = 1.66, 95% confidence interval [CI] 1.1-2.54), cervical dilation (aOR = 3.33, 95%CI 2.04-5.44), and gestational age (aOR = 1.44, 95%CI 1.21-1.72) were independent predictors of spontaneous delivery during the first 24 hours. A cross validation procedure showed that the calculator had a good accuracy (68%). Conclusions: A simple calculator based on maternal age, parity, gestational age, cervical dilatation, effacement and station, can accurately predict the chances of delivery within 24 hours of membrane sweeping. This may assist physicians better counseling of women regarding the likelihood of successful membrane sweeping. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of obstetric, maternal, and fetal variables with successful membrane sweeping and to develop a calculator that can predict spontaneous delivery within 24 hours of membrane sweeping.Methods: This secondary analysis of the STRIP-G Study included all singleton term parturients who underwent membrane sweeping in a tertiary center in October 2011 to July 2013. Primary end point was a 24-hour time interval from sweeping to delivery. Women who delivered without formal induction within the 24-hour interval were included in the "successful sweeping group". Stepwise logistic regression was used to calculate the adjusted odds ratio (aOR) for successful membrane sweeping and to create the calculator. The predictive power of the calculator was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC) curve and by Nagelkerke R-square. The model was validated by the Hosmer-Lemeshow test and by these validation measures: sensitivity, specificity, and positive and negative predictive value.Results: We analyzed data from 542 women. Parity (aOR = 1.66, 95% confidence interval [CI] 1.1-2.54), cervical dilation (aOR = 3.33, 95%CI 2.04-5.44), and gestational age (aOR = 1.44, 95%CI 1.21-1.72) were independent predictors of spontaneous delivery during the first 24 hours. A cross validation procedure showed that the calculator had a good accuracy (68%).Conclusions: A simple calculator based on maternal age, parity, gestational age, cervical dilatation, effacement and station, can accurately predict the chances of delivery within 24 hours of membrane sweeping. This may assist physicians better counseling of women regarding the likelihood of successful membrane sweeping. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia is a disease with unfavourable prognosis. The significance of various prognostic parameters is not fully understood. We studied 293 patients to examine the influence of ethnicity and molecular markers. The median survival for all patients was correlated with age, white blood cell count and karyotype, and marginally with FLT3 internal tandem duplication. Arab patients were younger than Jewish patients; however, their survival was poorer albeit being treated with the same protocols and having more favourable cytogenetics. Survival rates improved over time but only for patients undergoing allogeneic bone marrow transplantation (alloBMT). We conclude that in our young patient cohort, recent improvement in survival is attributed to alloBMT therapy and that ethnicity affected treatment outcome. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]