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Objective: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation before breast cancer chemotherapy treatment., Design: Retrospective observational cohort., Subjects: Two hundred thirteen women aged 18 to 43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients, and 141 did not (controls)., Exposure: controlled ovarian stimulation for fertility preservation., Main Outcome Measures: Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first., Results: At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs. 38.5 years), were less likely to be partnered (44.4% vs. 90.1%) or parous (38.9% vs. 95%), and were more likely to harbor a BRCA germline mutation (36.5% vs. 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being >5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls. Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. Five-year invasive disease-free survival was 80% for fertility preservation recipients and 86% for controls. In a multivariate analysis adjusted for statistically significant covariates, invasive disease-free survival remained similar between the groups (hazards ratio [HR], 0.86; 95% confidence interval [CI], 0.4-1.87). Invasive disease-free survival rates were not statistically different in clinically relevant subgroups, including patients receiving neoadjuvant chemotherapy (HR, 1.57; 95% CI, 0.62-3.99) and those cotreated with tamoxifen during stimulation because of an estrogen receptor positive disease (HR, 1.66; 95% CI, 0.67-3.49)., Conclusion: Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emergent clinically relevant subgroups., Competing Interests: Declaration of Interests M. Shapira has nothing to disclose. T.S. has nothing to disclose. M. Safrai has nothing to disclose. E.V. has nothing to disclose. D.L. has nothing to disclose. R.O. has nothing to disclose. E.G.-Y. reports honoraria from Roche, Pfizer, Gilead, MSD, Novartis, Eli-Lilly, Astra-Zeneca, and Stemline. D.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Objective: Parents of girls with Turner syndrome (TS) are coping with various challenges associated with caring for a child with a genetic disorder. We aimed to explore the importance of group support for parents of girls with TS in a small pilot study., Methods: Group support sessions for parents of girls with TS were divided into meetings regarding psychological aspects, medical aspects, and social aspects. Questionnaires about how the families perceive TS and what obstacles they are facing were given before and after the group support through the Mentimeter application. Questionnaires were given at the end of the group sessions to assess efficacy and satisfaction., Results: Parents of 18 girls, with a median (interquartile range) age of 9 (5.5, 12) years old, participated in the group, 56% with 45X karyotype. On average 72% of the participants said that the sessions much/very much contributed, and 10% said that the sessions hardly contributed (P < .05). At the end of the sessions, parents shared that they felt more confident, less isolated, and gained more knowledge regarding TS, and a community-based sharing process was initiated. At the end of the support group, 15 (83%) versus 3 (17%) said they would like to continue the meetings of the support group (P = .0001)., Conclusion: A support group specifically designed for parents of girls diagnosed with TS enhanced cooperation and empathy through diminishing feelings of isolation, offering crucial information, and fostering a secure environment for sharing and support., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Safrai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

Background: The COVID-19 pandemic spreads worldwide, causing devastating consequences. BioNTech (BioNTech SE, Mainz, Germany) and Pfizer's (Pfizer Inc., Brooklyn, NY, USA) BNT162b2 vaccine was one of the first vaccines to receive emergency-use authorization. However, its impact on women's fertility has not been primarily assessed leading to spread of unfounded rumors, causing vaccine hesitancy. We investigate the possible impact of BNT162b2 COVID-19 vaccine on in-vitro fertilization (IVF) outcomes., Methods: We compared data from 42 women undergoing their first IVF following 2 doses of BNT162b2 vaccination to 42 unvaccinated women undergoing their first IVF. The first outcome consisted of the pregnancy based on first hCG value; secondary outcomes were IVF cycle outcomes. A second analysis was done on 29 paired patients from both groups based on age, FSH, and the indication for IVF., Results: We report different levels of the pregnancy formation; oocyte's development: numbers of oocytes retrieved (9.3±6.8 vs. 11.5±7.9, P=0.19) and matured (6.9±4.8 vs. 9.1±6.6, P=0.14), and embryonal stage: fertilization rates (64.1±26.6 vs. 66.3±23.3, P=0.14), the quantity (4.3±3.2 vs. 5.7±4.4, P=0.23) and qualities of embryos (good/fair/poor) at day 3 were comparable. The analysis showed no significant difference between the groups, and the odds for pregnancy were similar (OR=0.9, 95% CL [0.3-2.8] P value 0.833)., Conclusions: From our results, this vaccine does not affect IVF performance and outcomes from the early stage of oocyte development through to the early beginning of pregnancy; therefore, it seems that the BNT162b2 vaccine does not compromise women's fertility.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Safrai, Azaria. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Study Question: Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regard to cryopreservation of immature testicular tissue?, Summary Answer: Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding., What Is Known Already: For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established., Study Design Size Duration: A detailed survey was sent to 17 centres within the recently established ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1 July to 1 November 2022., Participants/materials Setting Methods: Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA. Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis., Main Results and the Role of Chance: Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm 3 with the remainder preserving fragments sized 6-20 mm 3 . Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres., Limitations Reasons for Caution: While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre., Wider Implications of the Findings: Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients., Study Funding/competing Interests: K.D. is supported by a CRUK grant (C157/A25193). R.T.M. is supported by an UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). C.L.M. is funded by Kika86 and ZonMW TAS 116003002. A.M.M.v.P. is supported by ZonMW TAS 116003002. E.G. was supported by the Research Program of the Research Foundation-Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB&#95;SRP89), and the Scientific Fund Willy Gepts. J.-B.S. is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). C.E is supported by the Health Department of the Basque Government (Grants 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). M.P.R. is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. A.F. and N.R. received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. K.E.O. is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. V.B-L is supported by the French National Institute of Cancer (Grant Seq21-026). Y.J. is supported by the Royal Children's Hospital Foundation and a Medical Research Future Fund MRFAR000308. E.G., N.N., S.S., C.L.M., A.M.M.v.P., C.E., R.T.M., K.D., M.P.R. are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (C.Y.A.). The authors declare no competing interests., Trial Registration Number: N/A., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Instant messaging applications for mobile phones have recently grown in popularity among medical personnel, including both physicians and medical students. During the COVID-19 pandemic, medical education was largely transferred to virtual platforms, making such applications an increasingly important tool for medical education. "Siilo" is a secure instant messaging application that was designed for medical professionals, and offers several advantages over other instant messaging services that are vital for its use in medical settings, including information security, data encryption, and a built-in blurring tool to maintain patient privacy. In addition, Siilo allows for the creation of individual folders for each case, enabling users to conduct separate discussions about multiple patients simultaneously., Objective: To evaluate student satisfaction in a case-based learning program using Siilo as a medical education tool in improving student learning outcomes and motivation., Methods: A case-based learning program was conducted with 24 fifth-year medical students using Siilo to evaluate its effectiveness as a medical education tool. The program was evaluated through the use of pre- and post-program questionnaires and focus group discussions to assess student satisfaction., Results: The majority of students (83.3%) were highly satisfied with the Siilo platform and felt that it enhanced their learning experience, and a majority of students (79.1%) reported that the program was highly effective. Students reported that the platform was easy to use and provided a clear and organized way to follow discussions about cases. The focus group discussions further revealed that students appreciated the real-time communication and felt that the use of Siilo helped to improve the quality of communication and collaboration during the learning process. The use of Siilo as a medical education tool was found to contribute to positive relationships between doctors and students and improve student motivation for learning and outcomes., Conclusion: These findings suggest that Siilo can be a valuable resource for medical education, particularly due to its secure and convenient features, which are well-suited for use in medical settings. The use of Siilo in a case-based learning program was found to be effective in improving student satisfaction and learning outcomes and contributed to positive relationships between doctors and students. These results highlight the potential for utilizing mobile instant messaging apps as a tool for enhancing clinical teaching in medical education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shahar, Tadmor, Dior, Porat, Safrai, Ezra and Kabiri.)

Background: Ovarian hyperstimulation syndrome (OHSS) is reduced when using antagonist cycle with gonadotrophin releasing hormone (GnRH) agonist trigger before ovum pick up. This trigger induces short luteinizing hormone (LH) and follicle stimulating hormone (FSH) peaks, resulting in an inadequate luteal phase and a reduced implantation rate. We assessed whether the luteal phase can be rescued by supplementing with oral dydrogesterone (duphaston) in antagonist cycles after a lone GnRH agonist trigger., Methods: A retrospective cohort study. The study group (N.=123) included women who underwent IVF. Patients received a GnRH-antagonist with a lone GnRH-agonist trigger due to imminent OHSS. The control group (N.=374) included patients who underwent a standard antagonist protocol with a dual trigger of a GnRH-agonist and human chorionic gonadotrophin (hCG). All the patients were treated with micronized progesterone (utrogestan) for luteal phase support. Study patients were given duphaston in addition., Results: The fertilization rate was comparable between the two groups. The mean number of embryos transferred, the clinical pregnancy rate and the take-home baby rate were comparable between groups (1.5±0.6 vs. 1.5±0.5 and 46.3% vs. 41.2%, and 66.7% vs. 87.7%, respectively). No OHSS event was reported in either group., Conclusions: This study was the first to evaluate outcomes of duphaston supplementation for luteal support in an antagonist cycle with lone GnRH agonist trigger. The functionality of the luteal phase of those cycles could be restored by adding duphaston. This approach was found to be safe and prevented the need to postpone embryo transfer in case of pending OHSS.

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 mm 3 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 mm 2 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]., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Objective: 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., Methods: 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., Results: 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., Conclusion: 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.

Research Question: Does the BNT162b2 COVID-19 vaccine affect sperm parameters of patients with a normal or an abnormal semen analysis?, Design: Data were collected from male patients undergoing IVF treatment after completing vaccination between February 2021 and June 2021 (post-vaccine). For comparison, records of the same patients were reviewed before the vaccination (pre-vaccine) back to January 2017. Patients with azoospermia were excluded. Sperm parameters were compared between pre- and post-vaccine groups. Each patient served as self-control., Results: Seventy-two patients were included in the study (median interquartile range [IQR] age 35.7 [33.0-43.0] years), of whom 57 had a normal semen analysis. The time between the first vaccine and the post-vaccine sperm analysis was 71.0 (40.5-104.8) days. The sperm parameters before and after the vaccination were as follows: sperm volume before 3.0 (2.0-4.0) and after 3.0 (1.6-3.9) ml, P = 0.02; sperm concentration before 26.5 (14.0-64.7) and after 31.0 (14.2-80.0) 10 6 /ml, P = 0.35; and total motile sperm count before 33.7 (9.0-66.0) and after 29 (6.0-97.5)10 6 , P = 0.96. Sub-group analyses were conducted for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes after vaccination., Conclusion: Sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine does not seem to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To develop an efficient, clinical-grade, freezing protocol toward experimental clinical cryopreservation of testicular tissues in prepubertal boys suffering from cancer., Design: Experimental cryopreservation of testicular tissue., Setting: University Medical Center., Patients: Adult patients undergoing orchiectomy for various tumors and prepubertal boys scheduled for gonadotoxic treatment., Interventions: None., Main Outcome Measures: Histopathological analysis of tissue architecture, structural integrity, and cellular morphology was performed for control and frozen-thawed cryopreserved tissues.The number of seminiferous tubules per testicular section was calculated. The survival of spermatogonial stem cells (SSCs) and Sertoli cells of the control and frozen-thawed cryopreserved tissues was analyzed by immunofluorescence staining., Results: Uncontrolled Slow Freezing, Controlled slow freezing, and vitrification similarly preserved the integrity of the adult testicular tissues and the survival of SSCs and Sertoli cells. Controlled slow freezing of prepubertal testicular tissues effectively preserved their architecture, the number of tubules, SSCs, and Sertoli cells. In addition, we observed SSC loss after chemotherapy in prepubertal boys, reemphasizing the importance of fertility preservation before gonadotoxic treatment ., Conclusions: Future fertility restoration for male survivors of pediatric cancers depends on the development of an optimal prepubertal testicular tissue cryopreservation method. Our findings demonstrate the effectiveness of controlled slow freezing for cryopreservation of human prepubertal testicular tissues and may contribute to more effective banking of these tissues and potential fertility restoration., Clinical Trial Registration Number: NIH research clinical trials number: NCT02529826., (© 2021 The Authors.)

Background: Retained products of conception following delivery or early pregnancy failure are often treated by operative hysteroscopy. We aimed to evaluate reproductive and obstetric outcomes following operative hysteroscopy for treatment of retained products of conception. We also investigated the effect of time interval between operative hysteroscopy and pregnancy on these outcomes., Methods: A retrospective cohort study conducted at the gynecology department of a tertiary teaching hospital between January 2012 and December 2016. Included were women who underwent operative hysteroscopy for treatment of retained products of conception and became pregnant following the procedure. Reproductive and obstetric data were retrieved from electronic medical records and by telephone questionnaire. The effect of time interval between operative hysteroscopy and pregnancy on reproductive outcomes was also evaluated by comparing women who conceived 6 months or less and women who conceived more than 6 months following surgery., Results: Seventy-nine women who underwent operative hysteroscopy for treatment of retained products of conception and who conceived later were included. Mean time from women's attempt to conceive to conception was 4.6 (SD=6.4) months. Conception rate was 84.8% at 6 months and reached 92.4% at 12 months postsurgery. Miscarriage rate for the consecutive pregnancy following hysteroscopy was 15.2% and delivery rate was 84.8%. Two cases of obstetric complications including one case of retained placenta and one case of post-partum hemorrhage were noted. Time interval between operative hysteroscopy and pregnancy did not affect reproductive or obstetric outcomes., Conclusions: Women treated by operative hysteroscopy for retained products of conception have no negative reproductive and obstetric outcomes. Time interval between the procedure and pregnancy has no effect on these outcomes.

Objective: The use of intraoperative ultrasound guidance for second-trimester elective dilation and curettage reduces the incidence of uterine perforation. However, the role of intraoperative ultrasound guidance during curettage following second-trimester delivery has not been evaluated. We aim to evaluate the effect of intraoperative ultrasound guidance during curettage following second-trimester delivery., Methods: We conducted a retrospective cohort study that included patients who had a second-trimester delivery at up to 23 6/7 weeks gestation and underwent uterine curettage after the fetus was delivered., Results: Overall, 273 patients were included. Of them, 194 (71%) underwent curettage without intraoperative ultrasound guidance, while 79 (29%) underwent the procedure utilizing intraoperative ultrasound guidance. The overall rate of a composite adverse outcome was higher among those undergoing curettage under intraoperative ultrasound guidance compared with no ultrasound guidance (31 [39.2%] vs. 40 [20.6%]; OR 2.4; 95% CI 1.4-4.4, P = 0.002). Placental morbidity (10 [12.6%] vs. 11 [5.6%]; OR 1.9; 95% CI 1.01-5.9, P = 0.04) and infectious complications (6 [7.5%] vs. 5 [2.5%]; OR 3.1; 95% CI 1.01-10.4, P = 0.05) were more frequent among those undergoing curettage with intraoperative ultrasound guidance. In a multivariate logistic regression analysis, intraoperative ultrasound guidance was the only independent factor positively associated with the occurrence of an adverse outcome (adjusted OR 1.93; 95% CI 1.1-3.4, P = 0.02). Procedure time was longer when ultrasound guidance was used (9:52 vs. 6:58 min:s; P < 0.001)., Conclusion: Intraoperative ultrasound guidance during curettage after second-trimester delivery is associated with a higher complication rate than no guidance., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

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.

Objective: Pelvic inflammatory disease (PID) is a common infection which can result in severe long term morbidity, such as chronic pelvic pain and infertility. The morbidity increases in correlation to the number of PID events. Our study aim to assess the risk factors for recurrence of pelvic inflammatory disease., Methods: A retrospective case control study was conducted using data for all women who were admitted to a tertiary medical center for a recurrent PID over a duration of 15 years. Women who had a recurrent PID were compared to women admitted for PID treatment without further recurrence. Forward stepwise multivariate logistic regression analysis was subsequently carried out., Results: The study included 133 women of whom 33 had recurrent PID. Women in the recurrent PID group had a higher rate of previous pelvic surgery (12 (36 %) vs. 20 (20 %), adjusted odds ratio [OR] 2.2 (95 % confidence interval CI 1.06-5.4, p = 0.05) and more had intrauterine devices (IUD) still in place if they had been previously present (5 (71.4 %) vs. 9(25.7 %), OR 7.2, (95 % CI 1.18-43.9), p = 0.02). The majority were treated with a combination of Ampicillin and Gentamycin, fewer received Augmentin or a cephalosporin base regimen (28 (84.8 %) vs 56 (56.0 %), OR 4.4, (95 % CI 1.5-12.3, p = 0.02), (1 (3.0 %) vs 27 (27.0 %), OR 0.08, (95 % CI 0.01-0.64), (4 (12.2 %) vs 17 (17.0 %)) respectively. In addition, invasive treatment had been required in more patients who later had a recurrent PID (6 (18.1 %) vs. 4(4.0 %), OR 5.3 (95 % CI 1.1.4-20.2), p = 0.007). Antibiotic regimens and invasive treatment were independently associated with recurrent PID (OR 2.69; 95 % CI 1.13-6.41, OR 2.10; 95 % CI 1.19-3.71, respectively)., Conclusion: Among women with PID, special awareness should be given to women with previous pelvic surgery, who required an additional interventional treatment and have an IUD inserted. Efforts should be made to achieve treatment success and optimal prevention to prevent recurrent PID., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Objective: To determine whether prophylactic antibiotics reduce the frequency of postpartum endometritis after manual removal of the placenta., Methods: A retrospective cohort study was conducted using data for all women who underwent manual removal of the placenta after vaginal delivery at a tertiary medical center in Jerusalem, Israel, between January 1, 2010, and December 31, 2015. The study group comprised women who had not received prophylactic antibiotic treatment, whereas the control group comprised women who had received prophylactic antibiotic treatment. The primary outcome measure was the frequency of postpartum endometritis., Results: Of the 407 women included in the analysis, 7 (1.7%) developed postpartum endometritis. Six of the women with postpartum endometritis had received prophylactic treatment with antibiotics, whereas one woman had not (odds ratio 0.555, 95% confidence interval 0.065-4.630)., Conclusion: Prophylactic antibiotics before manual removal of the placenta did not decrease the odds of postpartum endometritis., (© 2017 International Federation of Gynecology and Obstetrics.)

Uterine leiomyomas have drawn much attention since being described more than 200 years ago. These common benign uterine tumors often present with prolonged menstrual bleeding, pelvic pressure, and reproductive disorders and pose a true financial burden on health care systems all over the world. Over the past few decades, surgical treatment of uterine leiomyomas has received most of the focus compared with other treatment options. Choosing the appropriate surgical technique depends on many factors such as uterine leiomyoma location, patient's age, interest in future fertility, concomitant comorbidities, and the patient's preference. Pharmacologic treatments such as gonadotropin-releasing hormone agonists and antagonists have been used for the treatment of symptomatic uterine leiomyomas with only partial success. Myriad side effects and limited clinical results have rendered them less popular and have exposed a true need for new effective medical treatments. Recently, treatment with selective progesterone receptor modulators has shown promising results with shrinkage of uterine leiomyomas and a prolonged clinical effect. Selective progesterone receptor modulators provide hope for women with this challenging condition and are a promising new option in the armamentarium of medical treatments for uterine leiomyomas.

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.)

Cervical cancer is initiated by infection with high-risk human papillomavirus (HPV). The viral E6 and E7 oncogenes are required for the initiation of cervical epithelial cell immortalization, but do not suffice to cause cervical cancer. Human oncogenes and tumor suppressor genes with altered activity in cervical carcinoma have been recognized, but none of these appears to be an absolute precondition for the development of the cancer. To examine the contribution of chromosomal aberrations to the development of cervical carcinoma, we used an in vitro model system consisting of primary keratinocytes (K) and papillomavirus transformed keratinocytes from early (E) and late (L) passages and from benzo[a]pyrene treated L cells (BP). Using DIGMAP software we compared alterations in gene expression as a function of chromosomal location. SKY chromosomal painting confirmed that the alterations identified by DIGMAP include gross chromosomal aberrations. Nearly half of the transcripts that were significantly reduced or increased in BP cells mapped to chromosomal regions showing coordinate changes in expression. These included transcripts involved in previously characterized phenotypic changes involved in transformation, such as the switch from apoptosis to necrosis and the reduction in cap-dependent translation. The global chromosomal changes that occurred during transformation are highly correlated with the phenotypic changes in HPV transformed keratinocytes. Our data are consistent with the theory that global chromosomal change is a necessary step in the process of cervical transformation.