Search

Background and Objectives: Previous studies have reported there were associations between ovarian function and dietary factors, metabolic factors and gut microbiota. However, it is unclear whether causal associations exist. We aimed to explore the causal relationship of these factors with risk of primary ovarian failure (POF)., Methods and Study Design: Two-sample Mendelian randomization (MR) analysis was performed to genetically predict the causal effects of dietary and metabolic factors and gut microbiota on POF. The inverse variance weighted (IVW) method was used as the primary statistical method. A series of sensitivity analyses, including weighted median, MR-Egger, simple mode, weighted mode methods, and leave-one-out analysis, were conducted to assess the robustness of the MR analysis results., Results: IVW analysis revealed that cigarettes smoked per day, coffee intake and cooked vegetable intake were not causally correlated with POF at the genetic level. However, POF were associated with fresh fruit intake, BMI, Eubacterium (hallii group), Eubacterium (ventriosum group), Adlercreutzia, Intestinibacter, Lachnospiraceae (UCG008), and Terrisporobacter. These findings were robust according to extensive sensitivity analyses., Conclusions: This study identified several dietary factors, metabolic factors and gut microbiota taxa that may be causally implicated in POF, potentially offering new therapeutic targets., Competing Interests: The authors report there are no competing interests to declare

Thanks to the progress of science and technology, human life expectancy has dramatically increased in the past few decades, but accompanied by rapid ageing of population, resulting in increased burden on society. At the same time, the living environment, especially the electromagnetic environment, has also greatly changed due to science and technology advances. The effect of artificial electromagnetic fields (EMFs) emitted from power lines, mobile phones, wireless equipment, and other devices on ageing and ageing-related diseases are receiving increasing attention. However, the information on the relationship between EMFs and ageing and ageing related susceptibility to EMFs is fragmentary, a review is needed. Only few studies directly investigate the effect of EMFs on ageing, and we reviewed the impact of EMFs on lifespan and cellular senescence to pry whether EMFs have an effect on ageing, and reviewed the age-dependent bioeffects and health impacts of EMFs to see whether ageing would affect biological susceptibility to EMFs. The results indicated that EMFs may have an effect on longevity and cellular senescence, but the results were inconsistent which may depend on EMF types (frequency, intensity, wave shape, etc.), species, and cell lines. Ageing has an impact on the biological or health effects of EMFs; however, the results differ depending on the EMF type and the endpoint or health outcome. Age-dependent changes in free radical metabolism, ion homeostasis, gene expression, enzyme activity, and tissue biophysical properties may be the reason; however, the underlying mechanisms are not fully elucidated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background: Individuals with normal weight obesity (NWO) often escape the attention of healthcare providers who may assume that a normal body mass index (BMI) correlates with low health risks. However, it remains unknown whether NWO increases the risk of breast cancer., Methods: This study included 22,257 and 52,506 pre- and postmenopausal females with normal BMI in the UK Biobank. NWO was defined as participants with a normal BMI (18.5-24.9 kg/m2) and an excess percent body fat (PBF > 33.3%). Cox proportional hazard models were used to investigate the associations of NWO and NWO-related biomarkers with incident breast cancer., Results: NWO was not associated with premenopausal breast cancer, whereas it was associated with a higher risk of postmenopausal breast cancer (hazard ratio = 1.19, 95% CI: 1.08-1.31). In our meta-analysis, per 5-unit increment in percent body fat level was linked to a 15% (95% CI: 10-19%) elevated risk of postmenopausal breast cancer in females with normal BMI. Stratified analyses showed a stronger positive association in females with higher genetic risk. In our NWO-biomarkers analyses, NWO was linked to 34 identified biomarkers, of which three inflammation markers (monocyte count, neutrophil count, and C-reactive protein), and one ketone body metabolite (β-Hydroxybutyrate) also indicated a positive association with postmenopausal breast cancer., Conclusions: NWO is associated with an increased risk of postmenopausal breast cancer, indicating that relying solely on BMI neglects the higher risk faced by non-obese postmenopausal women., Competing Interests: Competing interests: The author declares no competing interests. Ethics approval and consent to participate: The UK Biobank was approved by the North West Multi centre Research Ethics Committee (MREC) as a Research Tissue Bank (RTB) approval. All participants provided their informed written consent before participation. This study was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

Prenatal cell-free DNA (cfDNA) screening has advanced significantly, extending beyond detecting aneuploidies to sub-chromosomal copy number variations. However, its application for screening dominant single-gene conditions, often caused by de novo variants, remains underutilized in the general obstetric population. This study reviews recent data and experience on prenatal cfDNA screening for dominant monogenic conditions using multiple-gene panels, highlighting its potential to enhance early detection and management of genetic disorders. Integrating comprehensive cfDNA screening into routine prenatal care could complement current imaging techniques and standard prenatal cfDNA screening, which may overlook pre-symptomatic fetuses with dominant monogenic conditions in early gestation. Despite promising initial results, further research is needed to confirm the clinical validity and utility of cfDNA screening for these conditions. Larger and more diverse studies are necessary to assess the broader applicability of this technology. In addition, key challenges such as access, genetic counseling, ethical considerations, and policy development need to be addressed. A comprehensive approach, including rigorous test design, informed consent, and robust counseling, is essential for the successful adoption of expanded cfDNA screening, ultimately improving clinical outcomes., (© 2025 John Wiley & Sons Ltd.)

Purpose: Prior sperm DNA fragmentation index (DFI) thresholds for diagnosing male infertility and predicting assisted reproduction technology (ART) outcomes fluctuated between 15 and 30%, with no agreed standard. This study aimed to evaluate the impact of the sperm DFI on early embryonic development during ART treatments and establish appropriate DFI cut-off values., Methods: Retrospectively analyzed 913 couple's ART cycles from 2021 to 2022, encompassing 1,476 IVF and 295 ICSI cycles, following strict criteria. The WHO guidelines directed the semen analysis, while the acridine orange test (AOT) determined the DFI. Male factors (age, BMI, DFI, infertility duration, sperm parameters) and female parameters (age, BMI, AMH, retrieved oocytes) were evaluated. We also assessed embryological parameters like fertilization rate, cleavage rate, and blastocyst quality. Correlations between DFI and embryo quality were examined and DFI cut-off values were established using ROC analysis., Results: The Sperm DFI demonstrated a positive correlation with male age and a negative correlation with sperm motility, concentration, and normal morphology, while showing no relation to BMI. No connection between DFI and embryological parameters in only IVF and ICSI groups was found, but a negative correlation with fertilization rate was seen in all ART cycles. ROC curve analysis revealed a DFI cut-off value of 21.15% having 36.7% sensitivity and 28.9% specificity in predicting high fertilization rate (≥ 80%)., Conclusion: Sperm DFI had a negative correlation with fertilization rate, but limited predictive efficacy and no significant link to other embryological parameters. DFI assessments may improve early embryo development prediction during ART treatments, particularly in older males or those exhibiting poor sperm quality., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Zhuhai Maternal & Child Health Care (Approval No: [2018] ICE-22). Written informed consent from all enrolled patients was obtained prior to the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Despite increasing recognition that sex is a critical variable in appetite research, many studies fail to include participants of both sexes, fail to consider reproductive physiology in participant selection, or include both sexes but fail to test for sex differences in outcomes. To help remedy this situation, this article seeks to engender enthusiasm for including sex as a variable in appetite research. We first illustrate some sex differences in healthy and disordered eating, including both male-female differences and differences across the menstrual cycle. We next provide methodological guidance for studies involving male and female participants around puberty, during reproductive adulthood, and during reproductive senescence. Studies in children ≥5 y of age should consider adrenarche and gonadarche. Appetite studies in girls and women following menarche and similarly aged males should consider the influences of sex-specific aspects the hypothalamic-pituitary-gonadal (HPG) axis function. The cyclicity of HPG function (i.e., the menstrual cycle) in girls and women presents the challenge of identifying of menstrual-cycle subphases, which are highly variable within and between individuals. Reproductive senescence refers to changes in HPG axis function that occur in both men and women beginning in mid-life. Current best practices involve consideration of hormone-assay methodology, experimental design, and statistical analyses. On the horizon are options based on wearable-sensors and nanotechnology. Well informed consideration of sex as a variable will accelerate progress in appetite research by increasing rigor, replicability, and relevance., Competing Interests: Declaration of competing interest None of the authors has conflicts of interest to declare., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to examine the impact of laser-assisted hatching (LAH) on the physical, metabolic, cognitive and behavioural profiles of singletons conceived through frozen-thawed embryo transfer (FET) at the preschool age., Design: A matched cohort study., Setting: The reproductive centre of Women's Hospital, Zhejiang University School of Medicine., Population: Singletons born to couples with infertility who underwent FET cycles with or without LAH treatment from 2016 to 2019 and were followed up till age 4-6 years in 2023., Methods: Cognitive and behavioural development was evaluated at the preschool age using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) and the Adaptive Behavior Assessment System, Second Edition (ABAS-II). Statistical analysis was performed using moderated multiple linear regression., Main Outcome Measures: The full-scale intelligence quotient (FSIQ) and general adaptive composite (GAI)., Results: In total, 120 pairs of mother and child were included in the analysis. No significant differences in age, sex, height, weight, body mass index, blood pressure, thyroid function and metabolic indicators were observed between the two groups. After adjusting for demographics and socioeconomic status, LAH singletons showed FSIQ and GAI scores similar to those of non-LAH singletons., Conclusions: At 4-6 years of age, the cognitive, metabolic and physical developmental outcomes of preschool children born after LAH treatment were comparable with those of the non-LAH group, indicating that LAH may be considered a safe assisted reproductive technology method. However, further longer and regular follow-ups are needed to validate the findings of this study., (© 2025 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Competing Interests: Competing interests: The authors declare no competing interests.

This study aimed to identify shared gene expression related to circadian rhythm disruption in polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) to discover common diagnostic biomarkers. Visceral fat RNA samples were collected from 12 PCOS and 14 non-PCOS patients, a sample size representing the clinical situation and sufficient to capture PCOS gene expression profiles. Along with liver transcriptome profiles from NAFLD patients, these data were analyzed to identify crosstalk circadian rhythm-related genes (CRRGs) between the diseases. Single-sample and single-gene gene set enrichment analyses explored immune infiltration and pathways associated with CRRGs. Diagnostic biomarkers were identified using a random forest algorithm and validated through nomograms and a mouse model. Seven crosstalk CRRGs (FOS, ACHE, FOSB, EGR1, NR4A1, DUSP1, and EGR3) were associated with clinical features, immunoinflammatory microenvironment, and metabolic pathways in both diseases. EGR1, DUSP1, and NR4A1 were identified as diagnostic biomarkers, exhibiting robust diagnostic capacity (AUC = 0.7679 for PCOS, AUG = 0.9981 for NAFLD). Nomogram validation showed excellent calibration, and independent datasets confirmed their discriminatory ability (AUC = 0.6528 for PCOS, AUC = 0.8275 for NAFLD). Additionally, ceRNA networks and androgen receptor binding sites were identified, suggesting their regulatory roles. Mouse model validation confirmed significant downregulation of EGR1, DUSP1, and NR4A1 in liver tissues, consistent with sequencing data. This study identifies crosstalk CRRGs and diagnostic biomarkers shared between PCOS and NAFLD, highlighting their roles in immune and metabolic dysregulation. These biomarkers offer the potential for improving diagnosis and guiding targeted treatments for both diseases., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests. Ethics Approval and Consent to Participate: This study was approved by the Ethical Committee of Zhejiang Provincial Peoples' Hospital (Reference number: 2019KY040 for human studies and 20230525153354108592 for animal experiments). All participants provided informed consent before participating in the study. Consent for Publication: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The success of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in endometriosis patients varies widely, and predicting the likelihood of achieving a live birth remains a clinical challenge. This study aims to develop a predictive nomogram for assessing the cumulative live birth (CLB) rate following IVF/ICSI cycles among patients with endometriosis., Method: A retrospective cohort study was conducted to analyze the clinical data of 1457 patients with endometriosis after IVF/ICSI treatment from January 2017 to August 2022. The patients were divided into a training set (70%) and a validation set (30%) using a random number table. Univariate analysis and multifactorial logistic regression analysis were employed to identify relevant predictive factors affecting CLB rate. A predictive model was then established based on the identified factors., Results: Univariate analysis and multifactorial logistic regression analysis revealed that patients with concurrent adenomyosis had a decreased CLB rate (OR = 0.51, 95% CI: 0.31-0.82). As the duration of infertility increased, the CLB rate decreased (OR = 0.93, 95% CI: 0.88-0.99). Higher numbers of fertilized oocytes and high-quality embryos were associated with an increased likelihood of CLB. A nomogram predictive model for CLB rate, based on age, concurrent adenomyosis, duration of infertility, number of fertilization, and number of high-quality embryos, was developed. The area under the curve (AUC) for the training set and validation set was 0.823 (95% CI: 0.798-0.849) and 0.773 (95% CI: 0.729-0.818), respectively. The stratified analysis demonstrated the applicability of the model in the validation cohort., Conclusion: This predictive nomogram for CLB rate in patients with endometriosis provides valuable and precise information for personalized decision-making, which could be a visual and easily applied tool for IVF/ICSI counselling., Competing Interests: Declarations. Ethics approval and consent to participate: This study adhered to the principles outlined in the Declaration of Helsinki and received approval from the Medical Research Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (Ethics approval number: IRB-20230258-R). The requirement for informed consent was waived, due to the retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Both chronic endometritis and endometriosis are common entities in infertile patients. The association and the co-existence of these two entities are poorly evaluated. The aim of this systematic review and meta-analysis was to examine the association between chronic endometritis and endometriosis and to find the prevalence of chronic endometritis in women with endometriosis. A systematic electronic search was conducted using the MEDLINE, Scopus and Cochrane databases up to May 2022. Observational studies which examined the prevalence of chronic endometritis in women with endometriosis were included. Newcastle-Ottawa Scale was used for the quality assessment. Odds ratios (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and pooled prevalences with 95% CIs were calculated. 855 studies were identified, of which six studies were included in the systematic review and five in the meta-analysis. The prevalence of chronic endometritis in women with endometriosis was 28%, with higher frequency observed in women with endometriosis rASRM stage III-IV (43%) in comparison to women with endometriosis rASRM stage I-II (25%). The meta-analysis showed a significantly higher chronic endometritis in women with endometriosis in comparison to the control group (five studies, 264 endometriosis vs. 435 control, OR = 2.07; 95% CI 1.11-3.84, I 2 43%, p = 0.02). The present meta-analysis showed a significantly higher risk of chronic endometritis in women with endometriosis in comparison to the control group. These findings contribute to a better understanding of the causes and consequences of endometriosis and chronic endometritis and may help in the development of more efficient treatment strategies for women with associated infertility., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of Interest: DRK has nothing to disclose related to this study, UC has nothing to disclose related to this study, AKS has nothing to disclose related to this study, GS has nothing to disclose related to this study, BL has nothing to disclose related to this study, PD has nothing to disclose related to this study, NS has nothing to disclose related to this study., (© 2025. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The surgical management of cancer patients wishing fertility preservation is multidisciplinary, involving surgeon, anesthetist, hematologist, and nursing and laboratory staff. Many oncology patients have a multitude of medical or surgical conditions that require careful planning of all therapy including surgical removal of reproductive material, either oocytes or ovarian tissue. The significant risks related to either transvaginal or abdominal surgery should be discussed and documented and the final decision to proceed must be balanced against the risks, including death. Multidisciplinary communication for individual case management is the safeguard for patient safe return to cancer therapy., (© 2025 International Federation of Gynecology and Obstetrics.)

Fertility preservation services must offer information to patients, prior to their visit, so that they have time to read and digest the information, and also have the opportunity to write down any questions they wish to ask at the oncofertility consultation appointment. Appointments must be offered immediately, based on a specifically designed referral form. Each fertility service providing oncology cryopreservation should have a robust map of the patient's journey to include referral, counseling session, medical consultation, informed consent, treatment plan, and follow-up. Consent for fertility preservation should only be obtained after thorough assessment and discussion with the patient. It must contain basic aspects such as duration of storage, right to dispose or choose alternatives, wishes about stored material if death occurs, and need for patient contact on an annual basis. Appropriate legal advice should be sought in the process of establishing oncology cryopreservation services, most importantly related to patient consent. Ethical and legal aspects of fertility cryopreservation must be considered in the provision of care for cancer patients. Cancer patients attending for cryopreservation have significant concerns in relation to the success of the process, time frame to return for cancer treatment, and safety. Two major nonmedical aspects, coping ability and mortality, are best addressed by counselors and highlight the need to offer this type of psychological support to all cancer patients attending for fertility preservation. The role of genetic counseling is to discuss any potential risks of transmission of the disease to the resulting offspring and offer genetic testing when appropriate. A service based on availability of comprehensive information coupled with in-house implications counseling will have a positive impact and improve the overall care of patients attending for fertility cryopreservation and this should be standard care., (© 2025 International Federation of Gynecology and Obstetrics.)

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn., Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused., The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php, Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aims to investigate the association of serum iodine concentration (SIC) with thyroid function-associated parameters in pregnant women in mild iodine deficient area, and explore its potential to predict individual iodine nutrition status in pregnant women., Methods: A total of 741 pregnant women undergoing prenatal examinations in their second trimester at the Women's Hospital, Zhejiang University School of Medicine, from March 2021 to May 2022 were finally recruited into the study. Venous blood and morning urine were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyro-stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), UIC (urinary iodine concentration) and SIC were measured., Results: The median SIC was 54.44 μg/L. SIC was linearly and positively associated with concentrations of FT4 [ β = 0.10, 95 % CI: (0.07, 0.12), TT4 [ β = 0.29, 95 % CI: (0.26, 0.33), TT3 [ β = 0.14, 95 % CI: (0.09, 0.18). There was an inverted "U" shaped relationship between SIC and FT3. The associations between SIC and thyroid hormones remained robust when participants taking specific drug were excluded., Conclusions: SIC is associated with thyroid function-related parameters in pregnant women in their second trimester, indicating that the SIC may have the potential to predict individual iodine nutrition status in pregnant women., Competing Interests: Declaration of Competing Interest All authors have read and approved the final manuscript. The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2025 Elsevier GmbH. All rights reserved.)

Compared with long bone that arises from the mesoderm, the major portion of the maxillofacial bones and the front bone of the skull are derived from cranial neural crest cells and undergo intramembranous ossification. Human skeletal stem cells have been identified in embryonic and fetal long bones. Here, we describe a single-cell atlas of the human embryonic mandible and identify a population of cranio-maxillofacial skeletal stem cells (CMSSCs). These CMSSCs are marked by interferon-induced transmembrane protein 5 (IFITM5) and are specifically located around the periosteum of the jawbone and frontal bone. Additionally, these CMSSCs exhibit strong self-renewal and osteogenic differentiation capacities but lower chondrogenic differentiation potency, mediating intramembranous bone formation without cartilage formation. IFITM5 + cells are also observed in the adult jawbone and exhibit functions similar to those of embryonic CMSSCs. Thus, this study identifies CMSSCs that orchestrate the intramembranous ossification of cranio-maxillofacial bones, providing a deeper understanding of cranio-maxillofacial skeletal development and promising seed cells for bone repair.

Study Objective: The association between endometriosis and congenital uterine anomalies (CUAs) has been discussed for decades, but existing evidence about this association is scarce. The aim of our study is to evaluate the prevalence of CUAs in women with endometriosis and to identify specific characteristics in women with both CUAs and endometriosis in a large cohort of patients., Design: This is a retrospective single-center observational study conducted between January 2006 and June 2021., Setting: Swiss tertiary hospital PATIENTS: Women with histologically confirmed endometriosis at laparoscopy., Interventions: All women included in this study underwent a preoperative 2D ultrasound by an experienced sonographer. In cases of suspected intrauterine pathology, bleeding disorders, or infertility, an additional hysteroscopy was performed., Measurements and Main Results: Out of 1566 women with histologically confirmed endometriosis, 93 were diagnosed with CUAs (5.9%). The most frequent malformations were U1c (arcuate uterus) (41/93, 44.1%), U2a (partial septate uterus) (19/93, 20.4%), U3b (complete bicorporeal uterus) (17/93, 18.3%) and U3a (partial bicorporeal uterus) (10/93, 10.8%). Women with both CUAs and endometriosis were more frequently diagnosed with endometriosis rASRM stage IV (p=0.017) and presence of dysmenorrhea (p=0.019) in comparison to women with endometriosis and a morphologically normal uterus., Conclusions: To the best of our knowledge, this is the largest endometriosis population examined for the prevalence of CUAs. According to our findings, the prevalence of CUAs in women with endometriosis does not appear to be higher than in the general population. However, women with CUAs and endometriosis are more likely to suffer from severe endometriosis (rASRM stage IV) and dysmenorrhea compared to endometriosis patients without CUA., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest, (Copyright © 2025. Published by Elsevier Inc.)

Purpose: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists., Methods: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions"., Results: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91)., Conclusions: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines., Competing Interests: Declarations. Conflict of interest: LH, PP, EP, EVN and JCG received consultancy fees from Institut Biochimique SA. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed concent: For this type of study, formal consent is not required., (© 2024. The Author(s).)

Objective: This study aims to evaluate the reproductive outcomes after hysteroscopic adhesiolysis in patients experiencing recurrent pregnancy loss (RPL) combined with intrauterine adhesions (IUA)., Design: Single-center retrospective cohort study., Setting: International referral hospital for women with IUA and RPL., Patients: Between January 2018 and June 2022, a cohort of 64 women diagnosed with RPL and IUA were studied, with a follow-up period of at least one year after hysteroscopic adhesiolysis., Interventions: All patients had a diagnosis of IUA from the diagnostic hysteroscopy and were treated with hysteroscopic adhesiolysis, utilizing intraoperative ultrasound monitoring as required., Main Measurements: Live birth rate and menstrual pattern change (subjective assessment) after hysteroscopic adhesiolysis., Results: In our cohort, 59.38% (38/64) achieved pregnancy following hysteroscopic adhesiolysis, with 92.11% (35/38) conceiving within two years of the procedure. The miscarriage rate was recorded at 17.19% (11/64), and the live birth rate stood at 42.19% (27/64). Throughout the extended follow-up period, 64.06% (41/64) of the patients reported increased menstrual blood volume and improvements in menstrual patterns posthysteroscopic adhesiolysis. Univariate analysis indicated that being aged ≥35 years (p = .026), having a history of infertility (p = .003), the presence of moderate or severe IUA (p = .023), and experiencing menstrual improvements postsurgery (p = .001) were independent predictors of live birth. Multivariate analysis further identified that women with a history of infertility had a reduced chance of live birth following hysteroscopic adhesiolysis (p = .008), while those who reported menstrual pattern improvements postoperatively had an increased probability of achieving a live birth (p = .031)., Conclusions: Our findings indicate that RPL and IUA patients without prior infertility and showing menstrual pattern improvement after hysteroscopic adhesiolysis, are more likely to achieve live births. Standardized hysteroscopic treatment, postoperative anti-adhesion care, and early pregnancy planning are key to improving fertility outcomes in these patients., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Previous studies have suggested that metal/metalloid (hereafter referred to as metal) exposure may influence placental growth by affecting gene expression in the placenta. However, no epidemiological studies have been conducted to validate the relationships between metals exposure, placental gene expression, and placental growth at the population level. This study aims to investigate these relationships based on Hangzhou birth cohort study II (HBCS-II). Totally, 1025 participants were derived from HBCS-II. Thirteen metals levels in the placenta were measured using inductively coupled plasma mass spectrometry. Placental growth characteristics were assessed, including placental weight, chorionic disc area, placental eccentricity, and distance from cord insertion site to the nearest edge of placenta (DCIEP). The relationships between metals exposure and placental growth characteristics were examined using the elastic net model combined unpenalized linear regression model. Placental gene expression levels were analyzed through RNA sequencing and real-time polymerase chain reaction (RT-qPCR), and mediation analysis was conducted to investigate whether placental gene expression could mediate the relationship between metal exposure and placental growth. Notably, the results showed that a unite increase in Ln-transformed cadmium (Cd) levels was associated with a reduction of 16.4 g [95% confidence interval (CI): 31.2, -1.5] in placental weight, 13.9 cm 2 (95%CI: 20.0, -7.8) in chorionic disc area, and 0.3 cm (95%CI: 0.55, -0.06) in DCIEP. Through RNA sequencing followed by validation, significant associations were observed between placental Cd level and increased expression of placental genes, including TNFAIP2, OLAH, FLT4, SH3PXD2A, LIMCH1, BCL6, SLCO2A1, and CPSF1. Additionally, increased placental TNFAIP2, OLAH, FLT4, SH3PXD2A and LIMCH1 expression was linked to reduced placental weight. Moreover, SH3PXD2A was associated with decreased chorionic disc area. Mediation analysis showed that placental Cd level was associated with a 12.0 g (95%CI: 23.8, -2.7) decrease in placental weight mediated through the upregulation of FTL4 gene expression. The study provides evidence of the association between placental Cd exposure and decreased placental weight, and the FLT4 gene may play a mediating role in this relationship. Future experiment studies should be performed to validate the results., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: This study aimed to evaluate prophylactic uterotonics, antifibrinolytic medications, and vasoconstrictive agents in the prevention of hemorrhage during second-trimester abortions., Data Sources: PubMed, Embase (Elsevier platform), Evidence-Based Medicine Reviews (Ovid platform), and Web of Science were searched from database creation to October 30, 2023., Study Eligibility Criteria: Randomized controlled trials, cohort studies, case-control studies, and case series evaluating pregnant individuals (between 13 0/7 and 27 6/7 weeks of gestation) who underwent dilation and evacuation and received prophylactic uterotonics (methylergonovine, carboprost, oxytocin, or misoprostol), antifibrinolytic medications (tranexamic acid), or vasoconstrictive agents (vasopressin, lidocaine with epinephrine) were included in the study. The outcomes of interest included postprocedural bleeding, rate of medications to treat bleeding, blood transfusion, reoperation, and transfer to a higher level of care for hemorrhage., Methods: Of note, 2 authors independently screened the abstracts using the Systematic Review Data Repository. A third reviewer resolved discrepancies. The full text of accepted abstracts was retrieved and assessed for eligibility by 2 independent authors. Eligible studies were independently assessed for quality and bias by 3 authors. A consensus review resolved discrepancies., Results: Among 5834 abstracts screened, 11 studies met the inclusion criteria: 5 randomized controlled trials, 3 retrospective cohort studies, and 3 case series, totaling 3857 individuals. The paucity of studies combined with the heterogeneity of included trials precluded the performance of the meta-analysis. Of note, 4 studies evaluating misoprostol were of overall low-quality evidence and primarily assessed misoprostol's use for cervical dilation. Thus, its efficacy in bleeding prophylaxis remains unclear. Moreover, 2 high-quality trials evaluating oxytocin concluded that oxytocin use resulted in decreased blood loss, without a difference in interventions to control bleeding. Furthermore, 2 studies provided moderate-quality evidence that paracervical vasopressin use decreased blood loss, particularly at advanced gestational ages, but subsequent intervention outcomes were not assessed. High-quality evidence evaluating methylergonovine found that this medication increased blood loss at the time of the procedure., Conclusion: Current evidence on hemorrhage prophylaxis at the time of dilation and evacuation supports the use of intravenous oxytocin or paracervical vasopressin to decrease procedural blood loss, without an associated decrease in transfusion rate or use of other interventions. Future research on outcomes by gestational age can identify subgroups with the potential to derive the most benefit., (Published by Elsevier Inc.)

Background: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines., Purpose: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice., Methods: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries., Results: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak., Conclusions: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention., Competing Interests: Compliance with ethical standards. Conflict of interest: All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): during the period when data were collected from the Danish Endocrinologists, K.R.R. received her salary from a grant from the Danish Medicines Agency. Grants or contracts from any entity: D.F.S. from German Research Foundation (CRC/Transregio 296 LOCOTACT); MKrš from Czech grant agency as coinvestigator for research related to gestational diabetes. Consulting fees: E.V.N., L.H., and P.P. from IBSA; E.P. from IBSA and Terumo; T.B. from Merck KGaA; J.C.G. from IBSA and Abbott; L.H. from Horizon; MKre from Merck; MKrš from Recordati rare diseases; C.M. from Egetis Pharmaceuticals; P.K. from the Swiss National Foundation for Science. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: PP from IBSA; A.M.B. from Berlin-Chemie Menarini, and Merck; T.B. from Berlin-Chemie Menarini, Ipsen, Merck KGaA, Roche Diagnostics; J.C.G. from IBSA and Abbott; L.H. from IBSA, Berlin-Chemie, and Merck; MKre from Merck; MKrš from Recordati rare diseases and Merck; C.M. from Bahrain Diabetes & Endocrine Review Conference, Qatar Diabetes Endocrinology and Metabolic conference, Indiana University, Indonesian Society of Endocrinology meeting, 1st Annual Arab Thyroid Association Congress, European College of Veterinary Internal Medicine Annual Congress, and Thyroid Disease MSc Clinical Chemistry Trinity College Dublin; DAN from Merck Romania; ER from Merck, CTS Israel, Roche; MR from Merck, IBSA, Berlin-Chemie; PK from Merck, Ascendis. Support for attending meetings and/or travel: RA from IBSA; PP from IBSA; E.P. from IBSA; T.B. from Berlin-Chemie Menarini; H.D. from German Society for Endocrinology; J.C.G. from IBSA and Abbott; L.H. from IBSA, Berlin-Chemie, and Merck; MKre from Merck; MKrš from Novo Nordisk and Merck; F.M.P. from Lilly, Sanofi, Novo Nordisk; E.R. from Roche. Participation on a Data Safety Monitoring Board or Advisory Board: E.P., E.V.N., L.H., and P.P. were members of the IBSA scientific board; D.F.S. for IBSA; MKrš for Recordati rare diseases (osilodrostat and pasireotide); C.M. for Egetis Pharmaceuticals, Health products regulatory authority (HPRA) Ireland, LIONNS D2 Study; M.R. for IBSA and Merck. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: AMB from Bulgarian Society for Endocrinology (no payment); D.F.S. for AWMF-German Thyroid cancer guideline (including diagnosis and therapy of thyroid nodules); MKrš is the current President of the Czech Society of Endocrinology; C.M. is member of Executive Committee of European Thyroid Association (ETA), Chair of Study Review Committee on TRIAC withdrawal study (ReTRIACt, Egetis Pharmaceuticals), Programme Committee Member 2019–2023 for Society for Endocrinology, Secretary or Assistant Secretary 2017–2022 for British Thyroid Association, Lead of ETA Taskforce on Guidelines for Interference in Immunoassays of Hormones used in Thyroid Function Tests, Member of Committee of ETA Guideline on Diagnosis and Management of Syndromes of Resistance to Thyroid Hormone, previous invited Member expert working group on rare thyroid disorders for the European Reference Networks, National convenor Society for Endocrinology Thyroid Network. P.K. American Thyroid Association (no payment), Swiss Society for Endocrinology and Diabetology (no payment). Other financial or non-financial interests: C.M. received Publication Fees from IBSA for another publication., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases., Methods: The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT-PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT-PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined., Results: FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5' AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels ( P< 0.001) were elevated in ovariectomized mice with concurrent increases in cortisol ( P< 0.01), areal BMD (aBMD) ( P< 0.05), volumetric BMD (vBMD) ( P< 0.05), systolic BP (SBP) ( P< 0.05), diastolic BP (DBP) ( P< 0.05), and HR ( P< 0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels., Conclusion: The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Phospholipid and nucleotide syntheses are fundamental metabolic processes in eukaryotic organisms, with their dysregulation implicated in various disease states. Despite their importance, the interplay between these pathways remains poorly understood. Using genetic and metabolic analyses in Saccharomyces cerevisiae, we elucidate how cytidine triphosphate usage in the Kennedy pathway for phospholipid synthesis influences nucleotide metabolism and redox balance. We find that deficiencies in the Kennedy pathway limit nucleotide salvage, prompting compensatory activation of de novo nucleotide synthesis and the pentose phosphate pathway. This metabolic shift enhances the production of antioxidants such as NADPH and glutathione. Moreover, we observe that the Kennedy pathway for phospholipid synthesis is inhibited during replicative aging, indicating its role in antioxidative defense as an adaptive mechanism in aged cells. Our findings highlight the critical role of phospholipid synthesis pathway choice in the integrative regulation of nucleotide metabolism, redox balance and membrane properties for cellular defense., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)