Search

Background: The association between greenness exposure and semen quality and the underlying mechanism are unclear., Objectives: To assess the association between greenness exposure and semen quality and whether the association is mediated by air pollutant exposure., Methods: We collected data from 10,273 men in Zhejiang, China, whose wives received assisted reproductive technology from 2015 to 2021. The mean exposure concentrations of air pollutants and greenness indices (normalized difference vegetation index (NDVI) and the soil-adjusted vegetation index (SAVI)) in the 300 m, 400 m, 800 m, and 1000 m buffer zones were assessed from 0-90 days prior to semen testing on the basis of the patient's residential address. A multivariate linear mixed-effects model was used to evaluate the associations, and mediation analysis was used to investigate the influences of air pollutant exposure and body mass index (BMI) on the associations., Results: The average (standard deviation) age of the participants was 33.1 (5.2) years. After adjusting for confounders, progressive motility was positively associated with the NDVI 400m (β (95 % CI): 1.744 (0.834, 2.655)) and SAVI 400m (β (95 % CI): 1.484 (0.591, 2.377)). Furthermore, we found that NO 2 and CO exposure significantly mediated part of the association between greenness exposure and progressive motility. Similar results are observed in the sensitivity analysis., Conclusions: Our results suggest that greater greenness exposure is associated with higher semen quality and can be partially mediated by lower NO 2 and CO exposure levels., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research Question: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring?, Design: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors., Results: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544)., Conclusion: This study suggests that children born through FET have increased risk of developing food allergy in early childhood., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Rationale: Spontaneous subcapsular hepatic hematoma (SSHH) is a rare yet severe complication of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome that can lead to life-threatening situations for both the mother and fetus. Determining an appropriate therapeutic strategy remains challenging, as it involves choosing between surgery, microinvasive percutaneous transhepatic drainage, or conservative treatment alone. Further successful cases are needed to support the optimal option. We retrospectively collected a patient's clinical record and imaging data to elucidate the natural progression, response to noninvasive treatment, and outcome of SSHH associated with HELLP syndrome., Patient Concerns: A 34-year-old woman, who underwent a cesarean section due to suspected fetal distress, developed SSHH accompanied by the potential risk of rupture and deteriorated serology within the first 24 hours after delivery., Diagnoses: Emergency blood routine examination, serum biochemistry analysis, and computed tomography of the abdomen revealed a SSHH associated with HELLP syndrome., Interventions: The main rescue measures included the use of corticosteroids, antihypertensive drugs, and platelet transfusion., Outcomes: A positive effect on the patient's condition was exhibited within 24 to 48 hours. The majority of the subcapsular hepatic hematoma could be absorbed without any sequelae over a period of 7 months., Lessons: For patients with pregnancy-induced hypertension, there is a heightened risk of HELLP syndrome occurrence in subsequent pregnancies. The assessment and treatment of SSHH should be conducted by an experienced multidisciplinary team. In addition to timely delivery, the administration of corticosteroids, usage of antihypertensive medication, and platelet transfusion are necessary, particularly within the first 48 hours if the patient's condition permits. This approach would provide valuable insights for further therapeutic decisions and facilitate a preliminary prognosis assessment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We analyze the characteristics and related factors of human chorionic gonadotropin (hCG) of pituitary origin to establish the reference interval to resolve clinical confusion and avoid harmful therapy to Chinese postmenopausal women with "positive" hCG., Materials and Methods: This retrospective cohort study identified individuals who underwent hCG measurements at an academic hospital. Three gonadotropins (hCG, follicle stimulating hormone (FSH), and luteinizing hormone (LH)) was drawn from medical records. The age-stratified analyses were performed first. Then the correlations of hCG and FSH, LH as well as age were analysed. Finally, characteristics and associations of hCG, LH, and FSH were evaluated to identify pituitary hCG in postmenopausal women in clinical settings., Results: In total, 9796 cases from 11172 records met inclusion criteria and contributed 9796 hCG, 7541 FSH, and 7536 LH values. The upper reference interval for our cohorts was 5.3 IU/L. HCG, FSH, and LH concentration had no significant correlations with age. HCG moderately correlated with FSH (r = 0.47) and LH level (r = 0.53). However, it was FSH but not LH that manifested good clinical applicability., Conclusion: The prevalence of hCG≥5.0 IU/L and 5.3 IU/L in women ≥55 years is 2.8% and 2.3% in the study population from China. The level of hCG 5.3 IU/L was suggested to be the positive threshold for postmenopausal women. FSH≥40IU/L helps to distinguish the pituitary source of hCG in postmenopausal women whose serum hCG concentrations were between 5.3 and 16 IU/L., Competing Interests: Conflicts of interest None reported., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study aimed to determine the alteration of endometrial expression levels of HOXA9/HOXA10/ HOXA11/HOXD10 genes and HOX transcript antisense intergenic RNA (HOTAIR) in mid-luteal phase endometrium in patients with hydrosalpinx before and after salpingectomy., Materials and Methods: In this prospective study, 14 infertile women with unilateral hydrosalpinx who were scheduled for laparoscopic salpingectomy were evaluated. The presence of hydrosalpinx was confirmed by hysterosalpingography or transvaginal 2D-ultrasonography. All patients had normal hormonal profiles, body mass index, and regular menstrual cycles identified by mid-luteal serum progesterone. Fourteen healthy fertile age-matched women with a successful pregnancy history were considered the control group. Mid-luteal-phase endometrial biopsies were performed at the time of surgery and during the mid-luteal phase of the fourth treatment cycle by Pipelle. After tissue collection, RNA extraction and cDNA synthesis were performed. Real-time polymerase chain reaction (PCR) technique was used for quantitative gene expression of HOXA9/HOXA10/ HOXA11/ HOXD10 and lnc HOTAIR ., Results: The endometrial expression of HOXA9 (P<0.001), HOXA10 (P=0.001), HOXA11 (P=0.003), and HOXD10 (P=0.004) were significantly lower in the patients with hydrosalpinx compared to the controls. After salpingectomy, we observed a significant increase in the endometrial HOXA9 (P=0.006) and HOXA10 (P=0.023) mRNA expression levels compared to before salpingectomy samples. Similarly, a significant upregulation in endometrial HOXA11 (P= 0.013) and HOXA10 mRNA expression levels (P=0.012) were detected in postoperative samples compared to preoperative tissue. Moreover, the lnc HOTAIR was significantly higher in the endometrium-induced hydrosalpinx fluid than in controls (P=0.020), which had a 2.89-fold decrease following salpingectomy (P=0.010)., Conclusion: Elevated endometrial lncRNA HOTAIR may disrupt the expression of endometrial receptivity HOX genes in women with hydrosalpinx. However, our results failed to show a significant inverse correlation between HOTAIR and HOX genes due to limited sample size. Further studies with larger sample sizes are required to investigate HOTAIR inverse co-expression with HOX genes in these subjects.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1st January 2024 and 1st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Autoimmune diseases (ADs) are among the most significant health complications, with their incidence rising in recent years. Type 1 diabetes (T1D), an AD, targets the insulin-producing β cells in the pancreas, leading to chronic insulin deficiency in genetically susceptible individuals. Regulatory immune cells, particularly T-cells (Tregs), have been shown to play a crucial role in the pathogenesis of diabetes by modulating immune responses. In diabetic patients, Tregs often exhibit diminished effectiveness due to various factors, such as instability in forkhead box P3 (Foxp3) expression or abnormal production of the proinflammatory cytokine interferon-gamma (IFN-γ) by autoreactive T-cells. Consequently, Tregs represent a potential therapeutic target for diabetes treatment. Building on the successful clinical outcomes of chimeric antigen receptor (CAR) T-cell therapy in cancer treatment, particularly in leukemias, the concept of designing and utilizing CAR Tregs for ADs has emerged. This review summarizes the findings on Treg targeting in T1D and discusses the benefits and limitations of this treatment approach for patients suffering from T1D., 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 © 2024 Elsevier B.V. All rights reserved.)

Pericytes (PCs) contribute to brain capillary/BBB integrity and PC migration is a hallmark for brain capillary leakage following pro-inflammatory insults. Estradiol promotes endothelial barrier integrity by inhibiting tumor necrosis factor-alpha (TNF-α)-induced PC migration. However, the underlying mechanisms remain unclear. Since micro-RNAs (miRs) regulate BBB integrity and increases in miR638 and TNF-α occur in pathological events associated with capillary leakage, we hypothesize that TNF-α mediates its capillary disruptive actions via miR638 and that estradiol blocks these actions. Using quantitative reverse transcription PCR, we first assessed the modulatory effects of TNF-α on miR638. The treatment of PCs with TNF-α significantly induced miR638. Moreover, transfection with miR638 mimic induced PC migration, whereas inhibitory miR638 (anti-miR) abrogated the pro-migratory actions of TNF-α, suggesting that TNF-α stimulates PC migration via miR638. At a molecular level, the pro-migratory effects of miR638 involved the phosphorylation of ERK1/2 but not Akt. Interestingly, estradiol downregulated the constitutive and TNF-α-stimulated expression of miR638 and inhibited the TNF-α-induced migration of PCs. In PCs treated with estrogen receptor (ER) ER-α, ER-β, and GPR30 agonists, a significant downregulation in miR638 expression was solely observed in response to DPN, an ER-β agonist. DPN inhibited the pro-migratory effects of TNF-α but not miR638. Additionally, the ectopic expression of miR638 prevented the inhibitory effects of DPN on TNF-α-induced PC migration, suggesting that interference in miR638 formation plays a key role in mediating the inhibitory actions of estradiol/DPN. In conclusion, these findings provide the first evidence that estradiol inhibits TNF-α-induced PC migration by specifically downregulating miR638 via ER-β and may protect the neurovascular unit during injury/stroke via this mechanism.

Background: In vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8-16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%)., Methods: Bovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7-8. Expanded blastocysts on days 7-8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing., Results: Under 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P < 0.05), with no difference according to the co-culture time. Under 5% oxygen, the presence of OES did not affect blastocyst rates but increased the number of cells per blastocyst after 7 days of co-culture (P < 0.05). Both oxygen level and OES co-culture had a significant impact on the embryonic transcriptome. The highest number of differentially expressed genes (DEGs) was identified after 7 days of co-culture under 20% oxygen. DEGs were involved in a wide range of functions, including lipid metabolism, membrane organization, response to external signals, early embryo development, and transport of small molecules among the most significantly impacted., Conclusion: OES had beneficial effects on embryo development and quality under both 5% and 20% oxygen, mitigating oxidative stress. Stronger effects on embryo quality and transcriptome were obtained after 7 than 4 days of co-culture. This study shows the impact of OES on embryo development and reveals potential molecular targets of OES-embryo dialog involved in response to stress and early embryonic development., (© 2024. The Author(s).)

The placenta, a temporary but essential organ for gestational support, undergoes intricate morphological and functional transformations throughout gestation. However, the spatiotemporal patterns of gene expression underlying placentation remain poorly understood. Utilizing Stereo-seq, we constructed a Mouse Placentation Spatiotemporal Transcriptomic Atlas (MPSTA) spanning from embryonic day (E) 7.5 to E14.5, which includes the transcriptomes of large trophoblast cells that were not captured in previous single-cell atlases. We defined four distinct strata of the ectoplacental cone, an early heterogeneous trophectoderm structure, and elucidated the spatial trajectory of trophoblast differentiation during early postimplantation stages before E9.5. Focusing on the labyrinth region, the interface of nutrient exchange in the mouse placenta, our spatiotemporal ligand-receptor interaction analysis unveiled pivotal modulators essential for trophoblast development and placental angiogenesis. We also found that paternally expressed genes are exclusively enriched in the placenta rather than in the decidual regions, including a cluster of genes enriched in endothelial cells that may function in placental angiogenesis. At the invasion front, we identified interface-specific transcription factor regulons, such as Atf3, Jun, Junb, Stat6, Mxd1, Maff, Fos, and Irf7, involved in gestational maintenance. Additionally, we revealed that maternal high-fat diet exposure preferentially affects this interface, exacerbating inflammatory responses and disrupting angiogenic homeostasis. Collectively, our findings furnish a comprehensive, spatially resolved atlas that offers valuable insights and benchmarks for future explorations into placental morphogenesis and pathology., (© 2024. The Author(s).)

Background: Geriatric depression results in additional difficulties for older people and their residing society. The case-control study intended to assess the association between cognitive social capital and depression in rural older people., Methods: We conducted this study from January to December 2020 among 420 rural tenants aged ≥60 years in Bangladesh. We enrolled 210 older persons with depression as cases and another 210 without depression as controls. We used a semi-structured questionnaire, the Geriatric Depression Scale (GDS-15), and a cluster sampling technique to collect data through face-to-face interviews. We performed quality control checks and followed all ethics guidelines., Findings: Geriatric depression had a significant association with gender ( p  = 0.006), marital status ( p  < 0.001), education ( p  < 0.001), occupation ( p  = 0.001), family type ( p  < 0.001), family size ( p  < 0.001), number of family members ( p  < 0.001), and monthly family income ( p  < 0.001) of the rural older adults. Both interpersonal trust ( p  < 0.001) and reciprocity ( p  < 0.001) were significantly associated with geriatric depression. The older adults who didn't believe in interpersonal trust (OR = 6.8, p  = 0.002) and who disagreed with reciprocity (OR = 31.1, p  < 0.001) were more likely to have depression., Implications: The study findings can contribute to formulating cognitive social capital policy and interventions to promote the psychological well-being of rural older people by alleviating geriatric depression., Competing Interests: The authors have no relevant conflicts of interest to declare. The funders had no role in designing and conducting the study., (© The Author(s) 2024.)

Research Question: To what extent do legislative measures impact standard reproductive outcome parameters?, Design: Retrospective cohort study using data from the Swiss national IVF registry analysing the outcomes of 13,908 women undergoing embryo transfers resulting from their first lifetime oocyte retrieval before (2014-2016) or after (2020-2022) revision of the legislation, allowing extended culture for 12 zygotes. Live birth rates (LBR) and cumulative LBR (cLBR) were compared in fresh and frozen embryo transfer strategies in both periods. Adjusted multivariable mixed model analyses were performed to determine OR and incidence rate ratios (IRR)., Results: Before revision of the legislation, LBR was higher for fresh embryo transfers compared with frozen embryo transfers (27.2% versus 22.7%; P = 0.006). After revision of the legislation, LBR was lower for fresh embryo transfers (29.3% versus 36.3%; P < 0.001), and cLBR was higher for the freeze-all embryo transfer strategy (59.0% versus 39.8%; P < 0.001). However, in a multivariable analysis, no difference in the odds of live birth was found between fresh and frozen embryo transfers (OR = 1.08, 95% CI 0.95-1.22), and the freeze-all embryo transfer strategy was not found to be more effective than the fresh embryo transfer strategy (IRR = 1.12, 95% CI 0.98-1.27). In a subgroup analysis, fresh blastocyst embryo transfers showed higher LBR than cleavage stage embryo transfers (OR = 2.01, 95% CI 1.62-2.49)., Conclusion: The change in national legislation provided the unique opportunity to evaluate the legal impact on reproductive outcomes. Besides a reduction in the number of multiple births, LBR in frozen embryo transfers improved, resulting in comparable success of fresh and frozen embryo transfer strategies. In addition to technological improvement, the legal framework influences the evolution of clinical practice, thereby contributing to enhanced reproductive outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In April 2023, the World Health Organization (WHO) reported that 17.5% of the global adult population experience infertility. What may be the contribution of per-and polyfluoroalkyl (PFAS) to this global public health problem? This study explored the associations between in vitro fertilization (IVF) outcomes and plasma concentrations of individual PFAS and PFAS mixtures in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and how these exposures might affect IVF outcomes. We analyzed 8 PFASs in plasma samples from women (N = 259) who underwent IVF treatment. In multivariable generalized linear mixed models, there were statistically significant associations of higher plasma concentrations of PFNA with reduced numbers of total retrieved oocytes [12.486 (95%CI: 0.446,25.418), p trend = 0.017], 2 PN zygotes [6.467(95%CI: 2.034,14.968), p trend = 0.007], and cleavage embryos [6.039(95%CI: 2.162,14.240), p trend = 0.008]. Similarly, there was a continuous decline in the numbers of retrieved 2 PN zygotes and cleavage embryos with increasing concentration of PFOS [6.467(95%CI: 2.034,14.968), p trend = 0.009 and 6.039(95%CI: 2.162,14.240), p trend = 0.031,respectively] and a negative association between PFHxS concentrations and clinical pregnancy during the initial cycles of frozen ET [0.525(95%CI:0.410,0.640), p trend = 0.021]. To investigate the joint effect of PFAS mixtures, a confounder-adjusted BKMR model analysis showed inverse relationship between PFAS mixtures and the number of high-quality embryos, 2 PN zygotes and cleavage embryos, to which the greatest contributors to the mixture effect are PFDeA and PFBS, respectively. It demonstrated that PFAS exposure might exert negative effects on oocyte yield, fertilization and high-quality embryo in women undergoing IVF. These findings suggest that exposure to PFAS may increase the risk of female infertility and further studies are needed to uncover the potential mechanisms underlying the reproductive effects associated with PFAS., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Partnership is an important resource in dealing with endometriosis related chronic pain. Hence, our objective was to assess partnership in the context of endometriosis and its symptoms, considering the perspectives of both individuals involved., Methods: The study was designed as a multi-center matched case-control study in Switzerland, Germany and Austria. Altogether 381 women with surgically/histologically confirmed endometriosis and 381 control women, 250 male partners of endometriosis-affected women and 229 of control women were evaluated. Partnership quality, partnership happiness, separation thoughts, and areas of conflict were evaluated through the Partnership Questionnaire and a validated list of conflict areas., Results: Quality of partnership was rated as high by 60.1% of the women with endometriosis and 66.7% of the control women, as well as by 45.8 and 50.2% of their respective partners. Women with endometriosis mentioned separation thoughts, mostly related to sexual satisfaction, more often (34.9%/28.3%) and experienced more partnership-related conflicts than control women. Chronic pain, dyspareunia, dissatisfaction with sexuality, fatigue, and infertility were significantly associated with partnership conflicts. Fatigue and infertility but not pain experiences were related to lower partnership quality. Male partners in both groups reported separation thoughts equally often. In men, a high intensity of pain experienced by their partner was associated with reduced partnership happiness., Conclusion: Given the significance of partnership in dealing with chronic diseases and the connection between symptoms of endometriosis and a decrease in partnership quality, it is essential to incorporate strategies that alleviate the negative impacts on relationships for both partners into medical support., Clinical Trial Registration: identifier NCT02511626., 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 © 2024 el Hadad, Schwartz, Gassner, Haeberlin, von Orelli, Imesch and Leeners.)

Background: Frozen embryo transfer (FET) is usually recommended for women with polycystic ovary syndrome (PCOS) undergoing In vitro fertilization (IVF). While there is no consensus as to the optimal protocol of endometrial preparation for FET. The effect of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment for FET among women with PCOS remains controversial., Purpose: We intend to explore whether GnRH-a pretreatment could improve clinical outcomes for women with PCOS undergoing FET., Methods: PubMed, Embase, ClinicalTrials.gov, Cochrane Library, and Web of Science were searched up to May 16, 2024. Eligible studies involved patients with PCOS undergoing FET and receiving GnRH-a pretreatment for endometrial preparation, with artificial cycle (AC) as the control therapy. Only randomized controlled trials (RCTs) published in Chinese and English were included. Data extraction was performed independently by two authors. Effect was quantified using odd ratios (ORs) with 95% confidence intervals (CIs) using random-effect models with the Mantel-Hansel (M-H) method in Revman software. Quality of outcomes was evaluated using the GRADEpro system. Primary outcomes contained the clinical pregnancy rate, miscarriage rate, and live birth rate. Secondary outcomes included the incidence of preterm labor and gestational diabetes mellitus (GDM)., Results: Ninety-seven records were initially retrieved, with 21 duplicates and 65 articles excluded after title and abstract screening. Seven studies were excluded due to retrospective design, leaving three RCTs with 709 participants. Among them, 353 received GnRH-a pretreatment as the intervention group and 356 received AC as the control group. No significant differences were observed in the clinical pregnancy rate (OR 1.09, 95% CI 0.75 to 1.56, P = 0.66), miscarriage rate (OR 0.73, 95% CI 0.28 to 1.90, P = 0.52), live birth rate (OR 0.87, 95% CI 0.61 to 1.25, P = 0.46), and the risk of preterm labor (OR 1.45, 95% CI 0.79 to 2.65, P = 0.23) and GDM (OR 0.73, 95% CI 0.37 to 1.48, P = 0.39) between the two groups., Conclusions: In this meta-analysis, GnRH-a pretreatment does not confer any advantages and appears unnecessary for women with PCOS undergoing FET. Additional RCTs should focus on maternal complications and the health of offspring., (© 2024. The Author(s).)

Background: The trend of postponing childbearing age is prevalent worldwide. Advanced paternal age (APA) is associated with adverse pregnancy outcomes and offspring health. However, the underlying mechanism by which paternal aging affects the risk of offspring neuropsychiatric disorders is unclear. Our study aims to explore the behavioral phenotypes and the pathologic epigenetic alterations of APA offspring inherited from aging sperm., Methods: Behavioral tests, ELISA assay, immunofluorescence and western blotting were performed on offspring mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA immunoprecipitation sequencing (RIP-seq) were used to investigate the modified N6-methyladenosine (m6A) profiles of paternal sperm and offspring hippocampus. Intervention of gene expression by lentivirus and adeno-associated virus in both vivo and vitro examined the potential therapeutic targets of intergenerational inherited neuroinflammation., Results: In our study, APA offspring exhibit cognitive impairment and autism-like behavior. An increase in neuroinflammation in APA offspring is associated with microglial overactivation, which manifests as abnormal morphology and augmented engulfment. MeRIP-seq of F0 sperm and F1 hippocampus reveal that Nr4a2 is hypermethylated with decreased expression in APA offspring involving in synaptic plasticity and microglial function. In addition, Ythdc1, an m6A reader protein, is markedly elevated in aging sperm and remains elevated in adult hippocampus of APA group. Enhanced Ythdc1 recognizes and suppresses the hypermethylated Nr4a2, thereby contributing to the abnormal phenotype in offspring. The overexpression of Ythdc1 triggers microglial activation in vitro and its suppression in the hippocampus of APA progeny alleviates behavioral aberrations and attenuates neuroinflammation., Conclusion: Our study provides additional evidence of the abnormal behavioral phenotypes of APA offspring and reveals potential epigenetic inheritance signatures and targeted genes for future research., (© 2024. The Author(s).)

Background: The impacts of maternal depression during mid-to-late pregnancy on fetal growth have been extensively investigated. However, the association between maternal depression during early pregnancy and fetal intrauterine growth are less clear., Methods: A prospective study comprised 23,465 eligible pregnant women and their offspring was conducted at a hospital-based center in Shanghai. Prenatal depression was assessed used using Patient Health Questionnaire (PHQ-9) before 14 gestational weeks. Differences in fetal growth trajectory of different maternal depressive statuses during three periods (16-23, 24-31, and 32-41 gestational weeks) were compared using a multilevel model with fractional polynomials., Results: Women with depressive symptoms during early pregnancy had higher longitudinal fetal trajectories, with an estimated increase in fetal weight (β = 0.33; 95 % CI, 0.06-0.61), compared to those without depressive symptoms. Increases in fetal abdominal circumference among women with depressive symptoms were observed before 23 gestational weeks. Offspring born to mothers with early pregnancy depression had a significantly higher birth weight of 14.13 g (95 % CI, 1.33-27.81 g) and an increased risk of severe large size for gestational age (adjusted odds ratio [aOR], 1.64; 95 % CI, 1.32-2.04) and macrosomia (aOR, 1.21; 95 % CI, 1.02-1.43)., Limitations: Self-rated scale was used to assess depressive symptoms rather than clinical diagnosis. And Long-term effects of early pregnancy depression on offspring were not explored., Conclusions: The study revealed an association between maternal depression during early pregnancy and increased fetal biometrics, higher birth weight, and an elevated risk of severe large size for gestational age and macrosomia., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To conduct the first-ever systematic review and meta-analysis evaluating calcium infusion versus cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) among high-risk women undergoing assisted reproductive technology., Methods: Six databases were screened from inception until April 1, 2024. The included randomized and non-randomized controlled studies were assessed for quality. The endpoints included the severity of OHSS and selected pregnancy-related outcomes. Endpoints were summarized as risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model., Results: Six studies were analyzed, including 1687 patients (828 in the calcium group and 859 in the cabergoline group). The quality of the studies varied and reflected low risk and high risk of bias in two and four studies, respectively, according to the revised Cochrane risk of bias tool. No significant differences were noted between both groups regarding the rates of overall (n = 5, RR = 0.65, 95 % CI [0.39, 1.07], p = 0.09), mild (n = 4, RR = 1.05, 95 % CI [0.59, 1.89], p = 0.86), moderate (n = 5, RR = 0.41, 95 % CI [0.15, 1.08], p = 0.07), and severe (n = 6, RR = 0.36, 95 % CI [0.11, 1.22], p = 0.1) cases of OHSS. Leave-one-out sensitivity analysis of an outlier study revealed that calcium significantly reduced the occurrence of severe OHSS compared with cabergoline (n = 5, RR = 0.16, 95 % CI [0.09, 0.43], p < 0.001, Higgins I 2  = 0 %). No significant differences were observed between both groups regarding the rates of clinical pregnancy (n = 4, RR = 0.97, 95 % CI [0.88, 1.07], p = 0.57), ongoing pregnancy, live birth, and spontaneous abortion (Higgins I 2  < 50 % for all)., Conclusion: Both agents yielded similar pregnancy-related outcomes. However, calcium infusion could potentially be more effective than cabergoline in reducing the rate of severe OHSS. Additional high-quality and well-controlled trials are essential to draw firm conclusions., 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 © 2024 Elsevier B.V. All rights reserved.)

Despite advancements in assisted reproductive technology, recurrent implantation failure (RIF) remains a challenge. Endometrial factors, including ferroptosis and immunity, may contribute to this issue. This study integrated bioinformatics analysis and Mendelian randomization (MR) to investigate the expression and significance of DEFRGs in RIF. We intersected 484 ferroptosis-associated genes with 515 differentially expressed genes (DEGs) to identify key DEFRGs. Subsequent analyses included enrichment analysis, molecular subtype identification, machine learning model development for biomarker discovery, immune cell infiltration assessment, single-cell RNA sequencing, and MR to explore the causal relationships of selected genes with RIF. In this study, we identified 11 differentially expressed ferroptosis-related genes (DEFRGs) between RIF and healthy individuals. Cluster analysis revealed two distinct molecular subtypes with different immune profiles and DEFRG expressions. Machine learning models highlighted MUC1, GJA1 and FANCD2 as potential diagnostic biomarkers, with high accuracy in RIF prediction. Single-cell analysis further revealed the cellular localization and interactions of DEFRGs. MR suggested a protective effect of FANCD2 against RIF. Validation in RIF patients confirmed the differential expression of key DEFRGs, consistent with bioinformatics findings. This comprehensive study emphasize the significant role of DEFRGs in the pathogenesis of RIF, suggesting that modulating these genes could offer new avenues for treatment. The FANCD2 is a potential gene contributing to RIF pathogenesis through a non-classical ferroptosis-dependent pathway, providing a foundation for personalized therapeutic strategies in RIF management., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China., Methods: We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect eight types of microplastics: polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites., Findings: Microplastics were detected in all semen and urine samples, with participants typically exposed to 3-5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [β = -15.4 (95% CI: -25.6, -5.2)], sperm concentration [β = -7.2 (95% CI: -12.4, -2.0)], and progressive motility [β = -8.3 (95% CI: -13.5, -3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p < 0.001). The nomogram can be used to assess the risk of sperm damage by combining the type of microplastic exposure in urine with age and BMI., Interpretation: Our findings highlight the potential reproductive health risks posed by microplastic contamination, particularly PTFE, a non-stick pan coating material, and raise concerns about the potential of urine testing as an indicator of male reproductive microplastic exposure. Future research is warranted to further elucidate the mechanisms underlying the adverse effects of microplastics on male fertility and cross-generational effects., Funding: This study was funded by the Clinical Research Project of Shanghai Municipal Commission of Health and Family planning (20224Y0085), Open Fund Project of Guangdong Academy of Medical Sciences (YKY-KF202202), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-064), Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200), Shanghai Urogenital System Diseases Research Centre (2022ZZ01012), Key Discipline Construction Project (2023-2025) of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (GWVI-11.1-35, GWVI-11.2-YQ29) and Shanghai Frontiers Science Research Base of Reproduction and Development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Preterm birth (PTB), recognized as delivery before 37 weeks of gestation, is a multifactorial syndrome characterizing as the main cause of neonatal mortality. Reactive oxygen species (ROS) have been identified as proinflammatory factors to cause placental inflammation, thereby resulting in several pregnancy outcomes. To date, limited knowledge regarding the underlying mechanisms of ROS-induced PTB has been reported. In this study, we aimed to investigate the role of oxidative stress in PTB and the protective effects of mitochondria-targeted antioxidant MitoTEMPO (MT) on preterm labor and offspring mice. Results: In this study, we found that preterm placentas had abnormal mitochondrial function, oxidative stress, and inflammatory response. In the lipopolysaccharide (LPS)-induced PTB mouse model, MT inhibited PTB by ameliorating maternal oxidative stress and inflammation, especially in placentas, thus improving placental function to maintain pregnancy. Antenatal administration of MT prevented LPS-induced fetal brain damage in acute phase and improved long-term neurodevelopmental impairments. Furthermore, our in vitro investigations validated that MT retarded the ROS accumulation and inflammatory response in LPS-stimulated trophoblast cells by promoting Kelch-like ECH-associated protein 1 (Keap1) degradation and subsequently activating nuclear factor erythroid 2-related factor 2 (Nrf2). By inhibiting Nrf2 activation, we discovered that the anti-inflammation and protective characteristics of MT were Nrf2/ARE pathway dependent. Innovation and Conclusion: MT inhibited PTB and fetal brain injury by inhibiting maternal inflammation and improving placental function through Keap1/Nrf2/antioxidant response element signaling pathway. Our findings provide a novel therapeutic strategy for PTB. Antioxid. Redox Signal. 41, 597-615.

Background: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester., Methods: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses., Results: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted β=0.026, 95 % CI: 0.003-0.050)., Conclusion: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester., Competing Interests: Declaration of Competing Interest The authors of this article declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Guidelines for the investigation and management of recurrent pregnancy loss (RPL) have been developed in Europe, USA and UK, but there is currently no Australasian guideline. The Australasian Certificate of Reproductive Endocrinology and Infertility Consensus Expert Panel on Trial Evidence group has prepared a two-part guideline to provide guidance on the management of RPL. In Part I chromosomal, anatomical, and endocrine factors are outlined along with relevant recommendations for clinical management, levels of evidence and grades of consensus. In Part II thrombophilia, autoimmune factors, infective, inflammatory, and endometrial causes, environmental and lifestyle factors, male factor and unexplained causes will be outlined., (© 2024 The Author(s). Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Exposure to certain heavy metals has been demonstrated to be associated with a higher risk of preterm birth (PTB). However, studies focused on the effects of other metal mixtures were limited. A nested case‒control study enrolling 94 PTB cases and 282 controls was conducted. Metallic elements were detected in maternal plasma collected in the first trimester using inductively coupled plasma‒mass spectrometry. The effect of maternal exposure on the risk of PTB was investigated using logistic regression, least absolute shrinkage and selection operator, restricted cubic spline (RCS), quantile g computation (QGC) and Bayesian kernel machine regression (BKMR). Vanadium (V) and arsenic (As) were positively associated with PTB risk in the logistic model, and V remains positively associated in the multi-exposure logistic model. QGC analysis determined V (69.42%) and nickel (Ni) (70.30%) as the maximum positive and negative contributors to the PTB risk, respectively. BKMR models further demonstrated a positive relationship between the exposure levels of the mixtures and PTB risk, and V was identified as the most important independent variable among the elements. RCS analysis showed an inverted U-shape effect of V and gestational age, and plasma V more than 2.18 μg/L was considered a risk factor for shortened gestation length. Exposure to metallic elements mixtures consisting of V, As, cobalt, Ni, chromium and manganese in the first trimester was associated with an increased risk of PTB, and V was considered the most important factor in the mixtures in promoting the incidence of PTB., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Insulin resistance (IR) is a well-recognized covariate of Polycystic Ovarian Syndrome (PCOS) with varying burden and risk factors among populations. The relationship of insulin secretory defect or ISD with PCOS is less understood. The presence of IR and ISD as well as their covariates have been explored in the present case-control study among young adult to early middle-aged, normal weight to obese, Bangalee women with PCOS. A number of 158 PCOS [age 23 (15-34) years, Median (Range)] and 126 Non-PCOS [24 (19-34) years] females were recruited purposively with PCOS diagnosed following Modified Rotterdam Criteria 2003. Hormones were measured by CLIA method and lower abdominal ultrasonography was done by trained personnel. IR and ISD were assessed by homeostasis model assessment with 75th percentile values of HOMA-IR (2.4) and HOMA%B (143) in Non-PCOS group considered as the cut-off values. Hyperandrogenism (HA) was measured by calculating Fasting Androgen Index (FAI). HOMA-IR was high among 52% of PCOS and 28% of Non-PCOS women. Body Mass Index (BMI) and HA were independently associated covariates of IR (p < 0.001). HOMA%B was compromised among 48% of PCOS subjects and the deficiency showed independent association (p < 0.001) with 2 h glycemia on OGTT in Non-PCOS and HA in PCOS groups. The data suggest insulin resistance as a major risk factor for PCOS among Bangalee women with obesity and hyperandrogenemia as its major covariates. The findings also indicate that presence of impaired insulin secretion is a major determinant of hyperglycemia and, consequently, of higher T2DM risk among young women in this population., (© 2024. The Author(s).)

Purpose: In vitro maturation (IVM) of oocytes is a promising technique among assisted reproductive technologies. Although IVM has been used for many years, its efficiency is still relatively low compared to that of traditional in vitro fertilization (IVF) procedures. Therefore, we aimed to explore the hotspots and frontiers of IVM research over the past two decades and provide direction for IVM advancement., Methods: The articles and reviews related to IVM in the Web of Science Core Collection (WoSCC) were retrieved on June 03, 2024. Three bibliometric tools, VOSviewer 1.6.18 (2010), CiteSpace 6.1. R6 (2006), and Bibliometrix R package 4.1.0 (2017), were used to generate network maps and explore knowledge frontiers and trends. To uncover the latest research advancements and frontiers in the IVM field, we conducted an analysis of the entire IVM field, including all species. Given our focus on human IVM developments, we identified the leading countries, institutions, authors, and journals driving progress in human IVM., Results: A total of 5150 publications about IVM and 1534 publications in the specific context of human IVM were retrieved from the WoSCC. The number of publications on both overall IVM and human IVM fields has increased steadily. In human IVM, the United States (USA) and McGill University were the most prolific country and institution, respectively. Human Reproduction was both the most published in and the most cited journal in human IVM. Seang Lin, Tan was the most productive author, and Ri-Cheng, Chian's papers were the most cited in human IVM. Furthermore, five hotspot topics were summarized, namely, culture system, supplementation, cooperation in the ovarian follicle, gene expression, and oocyte cryopreservation., Conclusions: Further studies could concentrate on the following topics: (1) the mechanisms involved in oocyte maturation in vivo and in vitro, especially in energy metabolism and intercellular communications; (2) the establishment of IVM culture systems, including standardization of the biphasic IVM culture system and supplementation; (3) the genetic differences between oocytes matured in vivo and in vitro; and (4) the mechanism of cryopreservation-inflicted damage and solutions to this challenge. For human IVM, it is necessary to precisely assess the developmental stages of oocytes and adjust the IVM process accordingly to develop tailored culture media. Concurrently, clinical trials are essential for evaluating the effectiveness and safety of IVM., (© 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.)

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders., 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 © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association., Methods: Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected., Results: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50)., Limitations: Absence of male evidence and control of socioeconomic status and environmental exposure., Conclusions: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: By regulating the functions of multiple RNAs, 5-methylcytosine (m 5 C) RNA methylation, particularly mediated by NOP2, is involved in tumorigenesis and developments. However, the specific functions and potential mechanisms of m 5 C, especially involving NOP2, in clear-cell renal cell carcinoma (ccRCC), remain unclear. Methods: NOP2 expression in cell lines and patient tissues was detected using western blotting, quantitative real-time polymerase chain reaction (RT-qPCR), and immunohistochemistry. The biological effects of NOP2 on ccRCC cells were investigated through a series of in vitro and in vivo experiments. To explore the potential regulatory mechanisms by which NOP2 affects ccRCC progression, m 5 C bisulfite sequencing, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation (RIP/MeRIP) RT-qPCR assay, luciferase reporter assay, RNA stability assay, and bioinformatic analysis were performed. Results: NOP2 expression was significantly upregulated in ccRCC tissues and was associated with poor prognosis. Moreover, loss-of-function and gain-of-function assays demonstrated that NOP2 altered ccRCC cell proliferation, migration, and invasion. Mechanistically, NOP2 stimulated m 5 C modification of apolipoprotein L1 (APOL1) mRNA, and m 5 C reader YBX1 stabilized APOL1 mRNA through recognizing and binding to m 5 C site in the 3'-untranslated regions. Silencing APOL1 expression inhibited ccRCC cell proliferation in vitro and tumor formation in vivo . Furthermore, NOP2/APOL1 affected ccRCC progression via the PI3K-Akt signaling pathway. Conclusion: NOP2 functions as an oncogene in ccRCC by promoting tumor progression through the m 5 C-dependent stabilization of APOL1, which in turn regulates the PI3K-Akt signaling pathway, suggesting a potential therapeutic target for ccRCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In the meiotic prophase, programmed SPO11-linked DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11-RAD50-NBS1 (MRN) complex is essential for initiating DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons. Here, we show that DNA end resection is completely abolished in Mre11 KO spermatocytes. In addition, Mre11 KO, but not Nbs1 KO, undifferentiated spermatogonia are rapidly exhausted due to DSB accumulation, proliferation defects, and elevated apoptosis. Cellular studies reveal that a small amount of MRE11 retained in the nucleus of Nbs1 KO cells likely underlies the differences between Mre11 and Nbs1 KO cells. Taken together, our study not only demonstrates an irreplaceable role of the MRE11 in DNA end resection at SPO11-linked DSBs but also unveils a unique function of MRE11 in maintaining the long-term viability of undifferentiated spermatogonia., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2 %-8 %), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO 2 , 20 %) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO 2 on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO 2 exposure on human embryonic development. We found that exposure to AtmO 2 can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50 % of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO 2 .Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO 2 during the early preimplantation stage negatively affects hESCs., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ectopic pregnancies are one of the most common causes of obstetric mortality worldwide. Interstitial ectopic pregnancies, defined as an extracavitary pregnancy within the portion of the Fallopian tube that transverses the myometrium, have reported mortality rates approximately seven times higher than all types of ectopic pregnancy combined. In contrast, intracavitary eccentric gestations, often labeled as "cornual" or "angular" pregnancies, have reportedly high rates of live birth. Unfortunately, the terms "interstitial," "cornual," and "angular" have long been used with varying diagnostic criteria and often interchangeably to describe a pregnancy near the uterotubal junction. The inconsistency in nomenclature and lack of clear diagnostic criteria to distinguish among these pregnancies has resulted in a paucity of data to provide accurate prognostic information and guide appropriate management. This review article aims to provide historical context for the terms "interstitial," "cornual," and "angular;" discuss previous and more recent innovations of diagnostic methods; and provide recommendations for concise terminology and inform management., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene., Methods: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father., Results: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful., Conclusion: This research identified a novel intronic pathogenic FBN1: c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M)., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: With improving prognosis in upper-tract urothelial carcinoma (UTUC), an increasing number of second primary malignancies (SPMs) are being identified. However, there is limited research on SPMs following UTUC. This study aims to evaluate the risk of SPMs in UTUC patients and create a nomogram to predict their survival rates., Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the risk of SPMs among UTUC patients. Additionally, we developed and validated an overall survival (OS) nomogram for SPM patients post-UTUC diagnosis., Results: The prevalence of SPMs among UTUC patients was 30.23%, with solid tumors being the most prevalent type of second malignancy, constituting 95.30% of all SPMs. The overall risk of SPMs was significantly elevated across all subgroups. Univariate and multivariate Cox regression analyses identified age, race, gender, UTUC SEER historic stage, surgery, SPM site, histologic type, grade, and SEER historic stage as independent prognostic factors for SPM OS. Subsequently, we developed a nomogram for predicting SPM OS. The C-index for the training and validation sets were 0.72 [95% confidence interval (CI): 0.70-0.74] and 0.71 (95% CI: 0.67-0.75), respectively. The area under the curve (AUC) demonstrated good performance of our model in predicting the 3-year (0.73 and 0.737) and 5-year (0.723 and 0.733) OS of SPMs in both sets., Conclusions: This study represents the first comprehensive analysis of SPM incidence in UTUC patients and introduces a nomogram for predicting SPM prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-515/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mild hypothyroidism, including subclinical hypothyroidism and isolated maternal hypothyroxinemia, is fairly common in pregnant women, but its impact on pregnancy outcomes is less clear, especially mild hypothyroidism in late pregnancy., Objective: To evaluate the impact of subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first and third trimesters, respectively, on obstetric and perinatal outcomes., Study Design: This large prospective study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai; 52,027 pregnant women who underwent the first-trimester antenatal screening at International Peace Maternity and Child Health Hospital were consecutively enrolled from January 2013 to December 2016. To evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the first trimester on pregnancy outcomes, participants were divided into 3 groups according to thyroid function in the first trimester: first-trimester euthyroidism group (n=33,130), first-trimester subclinical hypothyroidism group (n=884), and first-trimester isolated maternal hypothyroxinemia group (n=846). Then, to evaluate the impact of maternal subclinical hypothyroidism and isolated maternal hypothyroxinemia in the third trimester on pregnancy outcomes, the first-trimester euthyroidism group was subdivided into 3 groups according to thyroid function in the third trimester: third-trimester euthyroidism group (n=30,776), third-trimester subclinical hypothyroidism group (n=562), and third-trimester isolated maternal hypothyroxinemia group (n=578). Obstetric and perinatal outcomes, including preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus, large for gestational age, small for gestational age, macrosomia, cesarean delivery, and fetal demise were measured and compared between those in either subclinical hypothyroidism/isolated maternal hypothyroxinemia group and euthyroid group. Binary logistic regression was used to assess the association of subclinical hypothyroidism or isolated maternal hypothyroxinemia with these outcomes., Results: Thirty-four thousand eight hundred sixty pregnant women who had first (weeks 8-14) and third trimester (weeks 30-35) thyrotropin and free thyroxine concentrations available were included in the final analysis. Maternal subclinical hypothyroidism in the first trimester was linked to a lower risk of gestational diabetes mellitus (adjusted odds ratio 0.64, 95% confidence interval 0.50-0.82) compared with the euthyroid group. However, third-trimester subclinical hypothyroidism is associated with heightened rates of preterm birth (adjusted odds ratio 1.56, 95% confidence interval 1.10-2.20), preeclampsia (adjusted odds ratio 2.23, 95% confidence interval 1.44-3.45), and fetal demise (adjusted odds ratio 7.00, 95% confidence interval 2.07-23.66) compared with the euthyroid group. Isolated maternal hypothyroxinemia in the first trimester increased risks of preeclampsia (adjusted odds ratio 2.14, 95% confidence interval 1.53-3.02), gestational diabetes mellitus (adjusted odds ratio 1.45, 95% confidence interval 1.21-1.73), large for gestational age (adjusted odds ratio 1.64, 95% confidence interval 1.41-1.91), macrosomia (adjusted odds ratio 1.85, 95% confidence interval 1.49-2.31), and cesarean delivery (adjusted odds ratio 1.35, 95% confidence interval 1.06-1.74), while isolated maternal hypothyroxinemia in the third trimester increased risks of preeclampsia (adjusted odds ratio 2.85, 95% confidence interval 1.97-4.12), large for gestational age (adjusted odds ratio 1.49, 95% confidence interval 1.23-1.81), and macrosomia (adjusted odds ratio 1.60, 95% confidence interval 1.20-2.13) compared with the euthyroid group., Conclusion: This study indicates that while first-trimester subclinical hypothyroidism did not elevate the risk for adverse pregnancy outcomes, third-trimester subclinical hypothyroidism was linked to several adverse pregnancy outcomes. Isolated maternal hypothyroxinemia in the first and third trimesters was associated with adverse pregnancy outcomes, yet the impact varied by trimester. These results suggest the timing of mild hypothyroidism in pregnancy may be pivotal in determining its effects on adverse pregnancy outcomes and underscore the importance of trimester-specific evaluations of thyroid function., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/Objective: Fertility preservation is an important part of oncologic care for newly diagnosed gynecologic cancers for reproductive-age women, as many treatment options negatively impact fertility. The goal of this study is to examine factors that influence access to fertility specialists for women with newly diagnosed gynecologic cancer. Methods: This institutional review board approved a retrospective cohort study investigating the impacting factors on the referral rate from gynecologic oncologists (GO) to reproductive endocrinologists and infertility (REI) specialists at a single academic institution between 2010-2022 for patients age 18-41 at diagnosis. Electronic medical records were used to identify demographics and referral patterns. Mixed logistic models were utilized to control cluster effects of the physicians. Results: Of 816 patients reviewed, 410 met the criteria for inclusion. The referral rate for newly diagnosed gynecologic malignancies was 14.6%. Younger patients were more likely to have an REI referral ( p < 0.001). The median time from first GO visit to treatment was 18.5 days, and there was no significant difference in those who had REI referrals ( p = 0.44). Only 45.6% of patients had fertility desire documented. A total of 42.7% had fertility-sparing treatment offered by a GO. REI referral did not significantly change the time to treatment ( p = 0.44). An REI referral was more likely to be placed if that patient had no living children, no past medical history, or if the referring GO was female (OR = 11.46, 6.69, and 3.8, respectively). Conclusions: Fertility preservation counseling is a critical part of comprehensive cancer care; yet, the referral to fertility services remains underutilized in patients with newly diagnosed gynecologic cancer. By demonstrating these biases in REI referral patterns, we can optimize provider education to enhance fertility care coordination.

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings.

Polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder among women in their reproductive years, is linked to a higher occurrence and severity of atherosclerosis (AS). Nevertheless, the precise manner in which PCOS impacts the cardiovascular well-being of women remains ambiguous. The Gene Expression Omnibus database provided four PCOS datasets and two AS datasets for this study. Through the examination of genes originating from differentially expressed (DEGs) and critical modules utilizing functional enrichment analyses, weighted gene co-expression network (WGCNA), and machine learning algorithm, the research attempted to discover potential diagnostic genes. Additionally, the study investigated immune infiltration and conducted gene set enrichment analysis (GSEA) to examine the potential mechanism of the simultaneous occurrence of PCOS and AS. Two verification datasets and cell experiments were performed to assess biomarkers' reliability. The PCOS group identified 53 genes and AS group identified 175 genes by intersecting DEGs and key modules of WGCNA. Then, 18 genes from two groups were analyzed by machine learning algorithm. Death Associated Protein Kinase 1 (DAPK1) was recognized as an essential gene. Immune infiltration and single-gene GSEA results suggest that DAPK1 is associated with T cell-mediated immune responses. The mRNA expression of DAPK1 was upregulated in ox-LDL stimulated RAW264.7 cells and in granulosa cells. Our research discovered the close association between AS and PCOS, and identified DAPK1 as a crucial diagnostic biomarker for AS in PCOS., (© 2024. The Author(s).)

Objective, Design, and Methods: Although 17-hydroxyprogesterone (17OHP) has historically been the steroid assayed in the diagnosis of congenital adrenal 21-hydroxylase deficiency (CAH-21D), its C11-hydroxylated metabolite, 21-deoxycortisol (21DF), which is strictly of adrenal origin, is assayed in parallel in this pathology. This steroid (21DF) is oxidized by 11beta-hydroxysteroid dehydrogenase type 2 into 21-deoxycortisone (21DE). In the context of CAH-21D confirmation testing, confounding factors (such as intensive care unit admission, stress, prematurity, early sampling, and variations of sex development) can interfere with the interpretation of the gold-standard biomarkers (17OHP and 21DF). Since its tissue concentrations are especially high in the placenta, we hypothesized that 21DE quantification in the neonatal periods could be an interesting biomarker in addition to 17OHP and 21DF. To verify this hypothesis, we developed a new mass spectrometry-based assay for 21DE in serum and applied it to newborns screened for CAH-21D., Results: In newborns with CAH-21D, the mean serum levels of 21DE reached 17.56 ng/mL (ranging from 8.58 ng/mL to 23.20 ng/mL), and the mean 21DE:21DF ratio was 4.99. In contrast, in newborns without CAH-21D, the 21DE serum levels were low and not statistically different from the analytical 21DE limit of quantification (0.01 ng/mL)., Conclusion: Basal serum 21DE appears to be a novel sensitive and specific biomarker of CAH-21D in newborns., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The epididymis is important for sperm transport, maturation, and storage. Methods: The head and tail of the epididymis of 5-week-old and 10-week-old C57 BL/6J male mice were used for single-cell sequencing. Results: 10 cell types including main, basal, and narrow/clear cells are identified. Next, we performed cell subgroup analysis, functional enrichment analysis, and differentiation potential prediction on principal cells, clear cells, and basal cells. Our study indicates that the principal cells are significantly involved in sperm maturation, as well as in antiviral and anti-tumor immune responses. Clear cells are likely to play a crucial role in safeguarding sperm and maintaining epididymal pH levels. Basal cells are implicated in the regulation of inflammatory and stress responses. The composition and functions of the various cell types within the epididymis undergo significant changes before and after sexual maturity. Furthermore, pseudo-temporal analysis elucidates the protective and supportive roles of epididymal cells in sperm maturation during sexual maturation. Discussion: This study offers a theoretical framework and forecasts for the investigation of epididymal sperm maturation and epididymal immunity., 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 © 2024 Zhang, Xie, Wang, Kang, Wang, Xie, Dong, Tian and Huang.)

Background: Genital pain treatment regimens range from local or systemic pharmacological to non-pharmacological, manual and psychosexual therapies with poor to moderate evidence for their efficiency. The aim of this study was to evaluate the subjective therapeutic response (genital pain relief) of different treatment modalities for vulvodynia and the most prevalent other vulvar pathologies, chronic vulvar eczema and lichen sclerosus by means of a cross-sectional survey., Material and Methods: A questionnaire-based cohort study that included 128 vulvodynia, 116 eczema and 79 lichen sclerosus patients was used. All patients attended the vulvar clinic at the University Hospital of Zurich. The patients who had been treated were surveyed from January to October 2022, using a customized online questionnaire consisting of 37 questions on symptoms and treatment outcomes for guideline-recommended treatment modalities. The study was approved by the Cantonal Ethics Review Board of Zurich., Results: Altogether, 41 patients with vulvodynia, 37 with vulvar eczema and 23 with lichen sclerosus returned the questionnaire. The three groups were similar regarding pain characteristics and comorbidities. All three patient groups reported having benefited from non-pharmacological treatment (improvement rate vulvodynia 54%; eczema 51%; lichen sclerosus 58%), from topical (55%; 55%; 75%) and from locally invasive (46%; 66%; 50%) treatments. Overall, there was no significant difference in subjective treatment outcome between non-pharmacological, locally invasive, and topical treatments for vulvodynia, eczema, and lichen sclerosus. However, the use of oral medication was reported to be significantly less effective (p-value 0.050)., Conclusion: In conclusion, we found that in the patients' perception, topical, invasive and non-pharmacological treatments, but not oral medications, are helpful for genital pain relief in women with vulvodynia, vulvar eczema, and lichen sclerosus. Therefore, we recommend an escalating therapy approach with first-line non-pharmacological treatments together with topical therapies., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Berger et al.)

A questionnaire-based study was jointly organised by European Board and College of Obstetrics and Gynaecology and European Society of Contraception to evaluate the current status as regards access and quality of care regarding contraception, abortion care, and pre-conceptional counselling and care among the 26 European countries. There are considerable variations among these countries as regards the provision of contraceptive services and abortion care. There is ample room for improvement through European training and education programs. However, the most important difference is the absence of a comprehensive network of healthcare providers in various countries to deliver these services at different points of access. There is notable absence of educational programs and instructional materials tailored specifically for nurses and midwives in several countries. This deficiency impedes the professional development and skills enhancement of these healthcare professionals, potentially compromising the quality of healthcare services provided to women in these countries., 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 © 2024. Published by Elsevier B.V.)

Purpose: Although fertility preservation for patients with childhood and adolescent cancer is considered standard of care in the high-resource settings, it is rarely offered in low-resource settings. This study explores the experiences and perspectives of oncology health care professionals in Uganda to identify contextual barriers and facilitators to addressing oncofertility in low-resource settings. Methods: Using ground theory, we conducted in-depth face-to-face interviews of health care professionals managing pediatric patients at the Uganda Cancer Institute (UCI). Using a systematic, semi-structured interview guide, participants were asked open-ended questions about their understanding of fertility preservation and their perspectives on implementing this care at their institution. Although all the eligible health care providers were interviewed, interview transcripts were uploaded into NVivo version 12 and openly coded as per theoretical requirements. Codes were refined into categories and later into structured themes. Results: Twelve health care professionals were interviewed. Most participants identified as female ( n = 9). Their role in the medical team varied from nurses ( n = 6), medical officers ( n = 3), pediatric oncologists ( n = 2), and pediatric oncology fellow ( n = 1). Six themes were noted as follows: (1) importance of information, (2) importance of future fertility, (3) inadequate consideration to future fertility, (4) communication barriers, (5) inadequate knowledge, and (6) resource barriers. Conclusion: Although health care providers at the UCI face contextual barriers to addressing future fertility among patients with pediatric cancer, they value preserving fertility in this population. Future initiatives that aim to introduce oncofertility care in low-resource settings should prioritize educating providers and building capacity to meet the oncofertility needs in this setting.