Human reproduction open最新文献

{"title":"Bone mineralization in children aged 7-10 years born after ART with frozen and fresh embryo transfer.","authors":"Elisabeth Waldemar Grønlund, Anna Sophie Lebech Kjaer, Louise Laub Asserhøj, Ikram Mizrak, Tine Dahlsgaard Clausen, Per Laub Madsen, Anja Pinborg, Rikke Beck Jensen","doi":"10.1093/hropen/hoaf055","DOIUrl":"10.1093/hropen/hoaf055","url":null,"abstract":"<p><strong>Study question: </strong>Does height-adjusted bone mineral content (BMC) at 7-10 years of age differ between children conceived after ART with frozen embryo transfer (FET) compared to children conceived after ART with fresh embryo transfer (fresh-ET) or naturally conceived (NC) children?</p><p><strong>Summary answer: </strong>Children conceived after FET had an increased BMC corrected for height compared with fresh-ET and NC when adjusted for confounders, a difference primarily mediated by the higher birthweight (BW) found in children conceived after FET compared with fresh-ET and NC.</p><p><strong>What is known already: </strong>Children conceived after ART with FET have a higher BW compared to NC children, while the opposite association is known for fresh-ET. In NC children, BW is positively associated with BMC and bone mineral density (BMD), but bone health in children born after ART is scarcely explored with inconsistent results.</p><p><strong>Study design size duration: </strong>This study was a retrospective cohort study as part of the 'Health in Childhood following Assisted Reproductive Technology' (HiCART) cohort, consisting of 606 singletons (292 boys), conceived after FET (n = 200), fresh-ET (n = 203), and NC (n = 203) born from November 2009 to December 2013. The children were 7-10 years old when clinically examined, and the study was conducted from January 2019 to September 2021.</p><p><strong>Participants/materials setting methods: </strong>Children were identified through the Danish Medical Birth Registry and Danish IVF Registry. These registries were also used to collect information regarding ART treatment, pregnancy, and delivery. The clinical examination involved anthropometric measurements, pubertal staging, fasting blood samples, and a whole-body dual-energy x-ray absorptiometry (DXA) scan. Both parents completed a questionnaire on background information regarding themselves and their child. The three groups were compared pairwise using univariate linear regression, and possible confounders and mediators were adjusted for using multiple linear regression analysis.</p><p><strong>Main results and the role of chance: </strong>Crude values of BMC corrected for height did not differ between children born after FET, fresh-ET, or NC. When adjusted for relevant confounders, children born after FET had a statistically significant higher BMC corrected for height compared with both fresh-ET and NC. After further adjustment for BW SD score, the differences in BMC corrected for height disappeared, and no statistically significant differences in BMC corrected for height between any of the three groups were found. Factors potentially affecting bone mineralization, such as calcium, parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), lean mass, and physical activity in childhood, did not differ between the three groups.</p><p><strong>Limitations reasons for caution: </strong>All relevant confounders were adjusted for, al","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf055"},"PeriodicalIF":11.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levothyroxine supplementation and pregnancy outcomes in women with thyroid disorders: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.","authors":"Jing Wang, Jiashu Li, Jing Zhang, Aihua Liu, Wanyu Yang, Xiaodan Zhai, Weiping Teng, Yongze Li, Zhongyan Shan","doi":"10.1093/hropen/hoaf036","DOIUrl":"10.1093/hropen/hoaf036","url":null,"abstract":"<p><strong>Study question: </strong>Does levothyroxine (LT4) treatment reduce adverse pregnancy outcomes in pregnant women with thyroid dysfunction?</p><p><strong>Summary answer: </strong>LT4 treatment significantly reduces the risks of pregnancy loss, preterm delivery, and gestational hypertension, with no significant impacts on rates of live birth, placental abruption, or gestational diabetes.</p><p><strong>What is known already: </strong>Multiple meta-analyses have examined the impact of LT4 on pregnancy outcomes, but quantitative confidence assessments are still lacking. Thus, an umbrella review is needed to systematically synthesize and assess the quality of this evidence.</p><p><strong>Study design size duration: </strong>This umbrella review of systematic reviews and meta-analyses used PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Searches included studies published in English or Chinese up to 20 March 2025.</p><p><strong>Participants/materials setting methods: </strong>Included studies were systematic reviews or meta-analyses of randomized controlled trials assessing the effects of LT4 on pregnancy outcomes in women with subclinical hypothyroidism (SCH) or thyroid peroxidase antibody (TPOAb) positivity. A set of 24 associations across six pregnancy outcomes were analyzed: pregnancy loss, preterm delivery, live birth, placental abruption, gestational hypertension, and gestational diabetes. Methodological quality was assessed using AMSTAR 1, and evidence quality was graded using GRADE. Sensitivity analyses were conducted to confirm robustness.</p><p><strong>Main results and the role of chance: </strong>Eleven meta-analyses were included. High-quality evidence showed that LT4 treatment reduced the risks of pregnancy loss (RR = 0.43; class III evidence), preterm delivery (RR = 0.56; class III evidence), and gestational hypertension (RR = 0.63; class IV evidence). Moderate-to-low-quality evidence indicated no significant impact on rates of live birth, placental abruption, or gestational diabetes. Of the 24 associations, 22 were rated as high confidence and two as medium confidence based on AMSTAR 1. Sensitivity analyses confirmed the robustness of the findings, but treatment effects varied according to the study population, treatment timing, and method. For pregnancy loss and preterm delivery outcomes, the risk was significantly reduced only when LT4 treatment was initiated in early pregnancy (pregnancy loss: RR = 0.60, <i>P</i> = 0.03; RR = 0.59, <i>P</i> = 0.003; preterm labor: RR = 0.58, <i>P </i>< 0.0001; RR = 0.46, <i>P</i> < 0.00001). Additionally, women with TSH levels greater than 4.0 mU/l derived greater benefits from LT4 treatment compared to those with TSH levels between 2.5 and 4.0 mU/l.</p><p><strong>Limitations reasons for caution: </strong>Limitations include small sample sizes, potential biases (selection and reporting), and language restrictions to English and Chinese studies, which may affec","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf036"},"PeriodicalIF":11.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generating human primordial germ cell-like cells from pluripotent stem cells: a scoping review of <i>in vitro</i> methods.","authors":"Madalena Vaz Santos, Ilse J de Bruin, Nina Dartée, Mathangi Lakshmipathi, Geert Hamer, Callista L Mulder, Willy M Baarends, Ans M M Van Pelt, Susana M Chuva De Sousa Lopes","doi":"10.1093/hropen/hoaf056","DOIUrl":"10.1093/hropen/hoaf056","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How do the methods and outcomes of established protocols to specify human primordial germ cell-like cells (hPGCLCs) &lt;i&gt;in vitro&lt;/i&gt; compare to each other?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;All analyzed protocols were successful in generating hPGCLCs, and a few were able to induce further germ cell maturation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;There are a variety of protocols for generating hPGCLCs &lt;i&gt;in vitro&lt;/i&gt;, each with its own advantages and disadvantages. To date no comparison has been made, hindering the practical application of &lt;i&gt;in vitro&lt;/i&gt;-derived hPGCLCs in research and the advancement toward generating mature germ cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;For this scoping review, a systematic search for protocols was conducted in the databases Scopus and Web of Science, including publications since 2010. Search terms included human, differentiation/specification/induction, germ cell/oogonia/spermatogonia, and primordial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Two separate authors performed the database search according to the inclusion/exclusion criteria. The data regarding the materials and methods as well as results of the included articles were extracted and organized based on protocol (cell type and culture system) and outcome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;A systematic search revealed 32 articles describing the generation of hPGCLCs. Of these, 24 articles contained an original hPGCLC differentiation protocol and 8 articles provided an extension of a previously published protocol. The extension protocols focused either on extending hPGCLC culture or maturing hPGCLCs further. The articles were compared regarding protocol methods and differentiation outcomes. The data showed that differentiation in 2D or 3D, in the presence of bone morphogenetic protein 4 (BMP4) (or retinoic acid), activated the WNT and NODAL signaling pathways to induce hPGCLCs. Further maturation (based on gene expression) was also achieved, depending on the inclusion of subsequent differentiation steps. The 2D culture systems showed high efficiency and scalability, while the 3D culture systems were more suitable for germ cell maturation purposes. Further improvements would include a deeper assessment of epigenetic and gene expression, functional analyses, and use of multiple cell lines to reflect protocol versatility.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Only literature has been compared; no extensive experimental comparison or a meta-analysis was performed due to the heterogeneity in outcome measurements.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;This review offers a comparison of hPGCLC differentiation protocols and aims to aid researchers in selecting appropriate protocols and making informed modifications to the culture conditions to achieve efficient germ cell differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study fun","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf056"},"PeriodicalIF":11.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate identification of abnormal ploidy using an artificial intelligence model in preimplantation genetic testing.","authors":"Pingyuan Xie, Rijing Pang, Luyao Zeng, Shuoping Zhang, Lei Sun, Kaisen Yang, Xiaoyi Yang, Shuang Zhou, Senlin Zhang, Guangjian Liu, Yueqiu Tan, Liang Hu, Fei Gong, Jia Fei, Ge Lin","doi":"10.1093/hropen/hoaf054","DOIUrl":"10.1093/hropen/hoaf054","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can ultra-low-coverage whole-genome sequencing (ulc-WGS) accurately identify abnormal ploidy during preimplantation genetic testing (PGT)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The artificial intelligence (AI)-based PGT-Plus model demonstrates high accuracy in ploidy detection, offering a cost-effective solution that enhances clinical utility of PGT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The predominant PGT for aneuploidy can identify chromosomal aneuploidies but cannot determine ploidy status. Transferring embryos with ploidy abnormalities can result in miscarriage and molar pregnancy. On the other hand, in ART, fertilization is assessed by morphological pronuclear assessment at the zygote stage. However, it has a low specificity in the prediction of abnormal ploidy status and embryos deemed abnormally fertilized can yield healthy pregnancies. Accurately identified abnormal ploidy in PGT-A can resolve current limitations and expand the utility range of PGT-A. Several studies have identified ploidy abnormalities; however, they were mainly based on single-nucleotide polymorphism (SNP) arrays or needed to combine additional targeted-next-generation sequencing (NGS) information. Studies based on ulc-WGS remain scarce.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;The study consisted of two stages: methodology establishment and validation. An AI model, named PGT-Plus, was developed using 653 samples with known ploidy status, which was further validated using 792 different ploidy status samples. In the clinical application stage, the approach was used to analyse the ploidy status of 19 103 normally fertilized PGT blastocysts and 140 single pronucleus (1PN)-derived blastocysts collected between May 2022 and December 2023. All blastocysts were tested using trophectoderm biopsy and NGS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The methodology is based on the ulc-WGS data. First, based on samples with known ploidy status: the heterozygosity rate of high-frequency biallelic SNPs, the likelihood ratio (LLR) of alleles was calculated under different assumptions ('both parental homologs' [BPH] from a single parent, 'single parental homolog' [SPH] from each parent, disomy, and monosomy) by leveraging allele frequencies and linkage disequilibrium (LD) measured in the 1000 genomes project database. Twenty-three continuous candidate features derived from heterozygosity rates and LLRs of chromosomes or selected windows were included to establish the ploidy prediction AI model. Gini importance analysis and multicollinearity mitigation was performed for feature selection, then the performance of Random Forest (RF), Support Vector Machine (SVM), and Logistic Regression for modelling was compared. Subsequently, the parameter optimization was performed based on the RF model. Ploidy constitution concordance was evaluated in known ploidy status samples. The frequency of abnormal ploidy in normal fert","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf054"},"PeriodicalIF":11.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Paternal age and neonatal health: unraveling epigenetic pathways.","authors":"Wenxue Xiong, Xijia Tang, Lu Han, Li Ling","doi":"10.1093/hropen/hoaf053","DOIUrl":"10.1093/hropen/hoaf053","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf053"},"PeriodicalIF":11.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paternal age and neonatal health: unraveling epigenetic pathways.","authors":"Yuquan Yuan, Chengzhi Zhao","doi":"10.1093/hropen/hoaf052","DOIUrl":"10.1093/hropen/hoaf052","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf052"},"PeriodicalIF":11.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic determinants of testicular sperm extraction outcomes: insights from a large multicentre study of men with non-obstructive azoospermia.","authors":"Antoni Riera-Escamilla, Mohamed M Arafa, Ginevra Farnetani, Miguel J Xavier, Manon S Oud, Ahmad A Majzoub, Liliana Ramos, Chiara Abrardo, Matilde Spinelli, Daniel Moreno-Mendoza, Giuseppe Defazio, Elisabet Ars, Marc Pybus, Josvany R Sánchez Curbelo, Haitham T Elbardisi, Shoaib Nawaz, Najeeb Syed, Eduard Ruiz-Castané, Godfried W van der Heijden, Khalid A Fakhro, Joris A Veltman, Csilla Krausz","doi":"10.1093/hropen/hoaf049","DOIUrl":"10.1093/hropen/hoaf049","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the diagnostic yield and the pre-testicular sperm extraction (TESE) prognostic value of a non-obstructive azoospermia (NOA)-specific virtual gene panel?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The diagnostic yield in our cohort was 6.1%, and by combining our data with published literature, we identified 11 genes compatible with testicular sperm production and 19 genes associated with no sperm retrieval in carriers of pathogenic (P) or likely pathogenic (LP) mutations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Azoospermia, the most severe form of male infertility, affects ∼1% of the male population, with TESE being the primary treatment option. However, in NOA, TESE fails in nearly 50% of cases and existing clinical parameters are unable to predict TESE failure. Over the past decade, next-generation sequencing (NGS) has identified several candidate NOA genes, but their diagnostic utility and impact on TESE outcomes have not been fully explored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size and duration: &lt;/strong&gt;A literature search was addressed to identify well-established NOA genes for designing a specific virtual gene panel for NOA. Our retrospective study analysed the diagnostic yield of the NGS-based virtual gene panel, comprising 145 genes, in 571 men affected by idiopathic NOA with known TESE outcomes. Subsequently, a second literature search was performed to identify carriers of LP/P variants in the genes where we identified mutations, focusing on individuals with known TESE outcomes. This approach allowed us to integrate the published data with our findings and predict a genotype-phenotype correlation between the affected genes and TESE success.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials settings methods: &lt;/strong&gt;571 NOA patients with known TESE outcomes were recruited in two European and one Middle East centres. Variants were obtained from a whole-exome sequencing dataset and crossed with the 145 genes of the virtual gene panel. After a filtering process, variants were manually assessed and classified according to ACMG guidelines by using two methods: (i) In order to compare our data with previously published studies, we applied ACMG-AMP guidelines along with ClinGen recommendations used by other similar studies. (ii) A new approach was used to optimize ACMG-AMP guidelines with all ClinGen recommendations and incorporated NOA-specific rules addressing phenotypic, locus, and allelic heterogeneity. LP and P variants were confirmed by Sanger sequencing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;By using the new variant classification approach adapted for NOA, we identified LP/P variants in 6.1% of patients, with a higher yield (9.4%) in cases with negative TESE outcomes and maturation arrest (11.7%). By integrating our findings with the literature, we highlight 19 genes recurrently associated with negative TESE outcomes and 11 genes associated with positive sperm retrieval either in the testis o","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf049"},"PeriodicalIF":11.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new human <i>in vitro</i> model of cytotypic and testosterone-producing organoids derived from testicular tissue of transgender women.","authors":"Samuel Madureira Silva, Frédéric Chalmel, Andrea Errico, Katerina Papageorgiou, Guillaume Richer, Edith Chan Sock Peng, Antoine D Rolland, Kelly Tilleman, Guy T'Sjoen, Ilaria Dando, Tamara Vanhaecke, Ellen Goossens, Yoni Baert","doi":"10.1093/hropen/hoaf043","DOIUrl":"10.1093/hropen/hoaf043","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can testicular tissue from trans women (trans tissue) be used to create human testicular organoids?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Testosterone-producing and cytotypic human testicular organoids with bicompartmental architecture can be successfully generated from trans tissue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Testicular organoids are a promising tool for studying testicular function and the effects of toxicants. Immature testicular cells are currently the most efficient at forming organoids that closely recapitulate seminiferous tubule-like architecture and functions. However, the scarcity of immature human testicular tissue limits its use in high-throughput applications. Conversely, trans tissue is abundantly available and characterized by an immature phenotype.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Trans tissue-derived organoids (trans organoids) were histologically and androgenically compared to reference organoids derived from immature (prepubertal and pubertal) and adult cisgender testicular tissues. Additionally, long-term testosterone production and gonadotrophic stimulation were assessed in trans organoids. To evaluate their cytotypic and transcriptomic resemblance to reference testicular tissue stages, trans organoids were compared at the gene expression level to prepubertal, pubertal, and adult cisgender tissues, along with their tissue of origin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Testicular tissue samples from transgender women, as well as from prepubertal, pubertal, and adult cisgender donors, were used to generate testicular organoids and to compare organoid formation efficiency and testosterone production according to tissue origin. These samples also served as references for transcriptomic comparisons with organoids derived from transgender women's testicular tissue at Day 14 of culture. Testicular organoids were generated and cultured using 3D Petri Dish&lt;sup&gt;®&lt;/sup&gt; platforms. Histochemistry and immunofluorescence staining were employed to characterize cellular composition and spatial organization. Testosterone production in culture media was assessed using electrochemiluminescence immunoassays. RNA was extracted and sequenced from organoids derived from transgender women, as well as from tissue samples of all donor groups. Deconvolution and differential gene expression analyses were performed to compare the organoids with testicular tissues across all groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Trans organoids form compartmentalized, cytotypic &lt;i&gt;de novo&lt;/i&gt; tissues similar to those from pubertal testicular tissue. Additionally, trans organoids exhibit significant testosterone production, sustain this function over extended culture periods, and respond to gonadotrophic stimulation. Deconvolved bulk RNAseq data indicate that cell population proportions within these organoids are close to those in prepubertal a","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf043"},"PeriodicalIF":11.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood plasma trimethylamine N-oxide and related metabolites and asthenozoospermia odds: a hospital-based matched case-control study in China.","authors":"Ze Xing, Meng-Meng Xie, Hui-Han Wang, Qi Cui, Xiao-Bin Wang","doi":"10.1093/hropen/hoaf045","DOIUrl":"10.1093/hropen/hoaf045","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are blood plasma trimethylamine N-oxide (TMAO) and related metabolites linked to the odds of asthenozoospermia?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Increased blood plasma TMAO levels were positively associated with the odds of asthenozoospermia, while elevated levels of choline and L-carnitine were related to reduced asthenozoospermia odds, implying that TMAO and its related metabolites might play an important role in the development of asthenozoospermia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Sperm motility and concentration are profoundly impaired by excessive reactive oxygen species (ROS). A positive correlation has been established between ROS levels and TMAO, which is regarded as a key regulatory factor for initiating mitochondrial ROS production. However, the precise interplay between TMAO and its metabolites and sperm quality remains inconclusive and insufficient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This case-control study was conducted from June 2020 to December 2020. A total of 314 pairs of asthenozoospermia cases and normozoospermia controls, matched based on age, BMI, and smoking status, were included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Blood plasma levels of TMAO and five related metabolites, such as choline, betaine, L-carnitine, methionine, and dimethylglycine, were measured using a liquid chromatography system coupled with tandem mass spectrometry. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) and corresponding 95% CIs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Compared with the lowest quartile, a significant association was observed between blood plasma TMAO level (OR = 1.80, 95% CI = 1.16-2.81) and the odds of asthenozoospermia for the highest quartile. In contrast, choline (OR = 0.59, 95% CI = 0.37-0.92) and L-carnitine (OR = 0.58, 95% CI = 0.37-0.90) levels were significant inversely associated with the odds of asthenozoospermia. Additionally, for each per SD change, significant dose-response relationships were noted with increased odds of asthenozoospermia linked to elevated TMAO (OR = 1.31, 95% CI = 1.12-1.55), as well as L-carnitine (OR = 0.79, 95% CI = 0.67-0.93) and total methyl donors exposure (OR = 0.82, 95% CI = 0.70-0.96) levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;We cannot infer causality from this study due to the case-control study. Since the current study was conducted on a population of Chinese men, the extrapolated results may not accurately reflect other regions or populations. As blood plasma TMAO and its metabolites were measured at a single time point and may not accurately represent long-term concentrations, the enduring effects on sperm quality may not be fully captured. Another limitation of the current study lies in its relatively modest sample size, which may have been insufficient to reach statistical power in subgroup analyses","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf045"},"PeriodicalIF":11.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of social determinants of health and age at menopause: NHANES 1999-2018 observational study.","authors":"Yu Guan, Qian Liu, Zhimin Deng, Sirui Liu, Jia Liang, Yujie Zou, Tailang Yin, Dongdong Tang, Jue Liu, Yan Zhang","doi":"10.1093/hropen/hoaf050","DOIUrl":"10.1093/hropen/hoaf050","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do social determinants of health (SDoH) influence the age at menopause among women?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In our study, adverse SDoH, particularly family low income-to-poverty ratio (PIR), low education level, and the marital status of being widowed, are associated with earlier age at menopause.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Some prior studies have considered certain SDoH variables (such as educational attainment and marital status) as potential factors influencing age at menopause, but systematic evidence clearly defining the relationship between multidimensional SDoH and menopausal age remains lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This cross-sectional analysis included 6083 naturally menopausal women from 10 cycles (1999-2018) of the United States National Health and Nutrition Examination Survey (NHANES) and excluded cases of surgical menopause.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The participants were derived from a nationally representative sample of the NHANES 1999-2018 in the USA. Eight SDoH variables were assessed: employment, PIR, food security, education, healthcare access, health insurance, housing stability, and marital status. Age at menopause was determined by self-reported last menstrual period among women with natural menopause. This study constructed weighted multivariate linear regression models and weighted quantile sum (WQS) analyses and calculated regression coefficients (β) and their 95% CIs. Subgroup analyses and sensitivity analyses were used to verify the robustness of our findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;After adjusting for relevant confounding factors, adverse PIR, education level, and marital status (such as being widowed) were significantly associated with earlier age at menopause. Specifically, compared to women with a PIR ≥500%, women with a PIR between 100% and 300% or PIR ≤100% had an earlier age at menopause by 0.877 years (95% CI: -1.526, -0.229, &lt;i&gt;P&lt;/i&gt; = 0.008) and 1.296 years (95% CI: -2.105, -0.487, &lt;i&gt;P&lt;/i&gt; = 0.002), respectively. Additionally, compared to women with an educational level of college or above, women with a high school education or less than a high school education had earlier age at menopause by 1.262 years (High school: 95% CI = -1.914, -0.609, &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and 1.403 years (Less than high school: 95% CI = -2.062, -0.743, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), respectively. Compared to women who were married or living with a partner, widowed women had earlier age at menopause by 1.363 years (95% CI = -1.887, -0.839, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). Analysis using a WQS regression model based on decile categorization demonstrated that each 1-unit increase in the composite exposure index of adverse SDoH factors was associated with 3.302 years earlier age at menopause in women (95% CI = -4.129, -2.476, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). The PIR contributed most substantially to the inver","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf050"},"PeriodicalIF":11.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}