Human reproduction open最新文献

{"title":"Reply: Reconsidering the interpretation of sperm DNA fragmentation testing in ART decision-making.","authors":"Yuanyuan Wang, Rui Wang, Ying Lian, Ben W Mol, Rong Li, Jie Qiao","doi":"10.1093/hropen/hoag046","DOIUrl":"10.1093/hropen/hoag046","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag046"},"PeriodicalIF":8.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201264","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":"The impact of vasectomy on the seminal microbiome: possible implications and source of microbes.","authors":"Nerea M Molina, Inmaculada Pérez-Prieto, Celia M Tenorio, Miriam Gámiz-Aguilera, Alberto Sola-Leyva, Eduardo Salas-Espejo, Eduardo Andrés-León, Eva Vargas, Analuce Canha-Gouveia, Irene Leonés-Baños, María C Gonzalvo, Juan Fontes, José Antonio Castilla, Signe Altmäe","doi":"10.1093/hropen/hoag043","DOIUrl":"10.1093/hropen/hoag043","url":null,"abstract":"<p><strong>Study question: </strong>Does vasectomy alter the seminal microbiome, and what proportions of seminal microorganisms originate from the urinary and upper reproductive tract?</p><p><strong>Summary answer: </strong>Vasectomy is associated with modest shifts in the seminal microbial community structure, where inter-individual variability prevails, and the semen shares over 60% of bacterial communities with urine, suggesting an influence of the urinary tract and upstream genitourinary compartments on the seminal microenvironment.</p><p><strong>What is known already: </strong>The semen harbours a polymicrobial community whose origin is not fully understood. Also, the effect of vasectomy, a common sterilization procedure, on seminal microenvironment is not clear. Recent studies with a limited sample size suggest that part of the seminal microbiome may derive from the upper genital tract, and that vasectomy may alter seminal microbial composition, potentially revealing testicular or epididymal microbial contributions.</p><p><strong>Study design size duration: </strong>This prospective cohort study including 82 men undergoing vasectomy, with paired semen and urine samples collected before and 3 months after the procedure.</p><p><strong>Participants/materials setting methods: </strong>Paired semen and urine samples were collected pre- and post-vasectomy. The seminal and urine microbiome was analysed by sequencing the V4 hypervariable region of the 16S rRNA gene. Amplicon sequence variants were decontaminated using rigorous negative-control-based methods. Microbial diversity, taxonomic composition, and differential abundance were assessed, and functional profiles were predicted using PICRUSt2.</p><p><strong>Main results and the role of chance: </strong>More than 60% of seminal bacterial genera were also present in urine, indicating substantial overlap. Vasectomy significantly altered β-diversity; however, the effect was small, and several predicted functional pathways were detected, including lipid metabolism. Although some genera differed between pre- and post-vasectomy samples, these did not remain significant after false discovery rate (FDR) correction. These findings should be interpreted considering the prevailing inter-individual variability and shared urinary-seminal taxa.</p><p><strong>Large scale data: </strong>The 16S rRNA gene sequencing data have been uploaded to the SRA database under BioProject ID PRJNA1355064.</p><p><strong>Limitations reasons for caution: </strong>The main limitations of the study are the use of 16S rRNA gene sequencing, which limits species-level resolution, the lack of repetitive sampling, and the absence of absolute bacterial load quantification. Also, the functional pathway analyses present predictive estimates from the sequencing data rather than from direct measurements of the microbial metabolic activity.</p><p><strong>Wider implications of the findings: </strong>Vasectomy may induce subtle changes in the ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag043"},"PeriodicalIF":8.6,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13278845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148297534","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":"Effect of vaginal estrogen supplementation for luteal phase support in the GnRH antagonist protocol on pregnancy outcomes for IVF/ICSI cycles: a randomized controlled trial.","authors":"Xinyun Yang, Linling Zhu, Ruizhe Chen, Tongtong Lin, Fang Le, Qitao Zhan, Huijuan Gao, Fen Wang, Yimin Zhu, Hangying Lou","doi":"10.1093/hropen/hoag042","DOIUrl":"10.1093/hropen/hoag042","url":null,"abstract":"<p><strong>Study question: </strong>Does adding vaginal estradiol to standard progesterone luteal phase support improve ongoing pregnancy rates in normal-responder IVF/ICSI patients undergoing GnRH antagonist cycles?</p><p><strong>Summary answer: </strong>The addition of vaginal estradiol to progesterone luteal support in GnRH antagonist cycles, compared to progesterone alone, enhances embryo implantation and clinical pregnancy rates in normal-responder IVF/ICSI patients, yet fails to significantly improve ongoing pregnancy or live birth outcomes.</p><p><strong>What is known already: </strong>The GnRH antagonist protocol for IVF, while advantageous in some aspects, may negatively impact estrogen levels and endometrial receptivity, potentially lowering fresh embryo transfer pregnancy rates compared to agonist protocols. The role of adding estrogen to standard progesterone luteal phase support in antagonist cycles remains controversial, with existing studies yielding conflicting results and a lack of robust randomized controlled trials (RCTs) specifically investigating vaginal estrogen administration.</p><p><strong>Study design size duration: </strong>In this single-centre RCT, participants were randomized 1:1 on the ovulation trigger day to receive either progesterone alone (P group) or progesterone plus vaginal 17β-estradiol (E + P group) for luteal phase support, starting on Day 1 post-oocyte retrieval. The sample size calculation, based on detecting a clinically significant 13% difference in ongoing pregnancy rate (43% vs 30%; α = 0.05, power = 80%) with an anticipated 10% attrition, determined a target of 236 women per group. A total of 518 women (P group: n = 259; E + P group: n = 259) were enrolled between April 2019 and June 2022. Allocation used computerized randomization by an independent data manager. Blinding of participants and physicians was not feasible; however, statisticians were blinded until analysis completion. The analysis was performed using intention-to-treat (ITT) and per-protocol (PP), followed by a sensitivity analysis using multivariable logistic regression.</p><p><strong>Participants/materials setting methods: </strong>This single-centre trial enrolled 518 infertile women (20-39 years) undergoing fresh IVF/ICSI cycles as normal responders at a tertiary care centre. Participants were allocated to either the P group or E + P group. Luteal support initiated on Day 1 post-oocyte retrieval comprised: vaginal progesterone 90 mg/day + oral dydrogesterone 10 mg twice daily for both groups, with the E + P group additionally receiving vaginal 17β-estradiol 2 mg nightly. The primary outcome was ongoing pregnancy rate, with secondary outcomes including the rates of implantation, clinical pregnancy, live birth, and maternal complications.</p><p><strong>Main results and the role of chance: </strong>The ITT analysis showed no significant differences in ongoing pregnancy rates of 46.33% (120/259) in the E + P group versus 39.00% (101/25","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag042"},"PeriodicalIF":8.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213549","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":"Altered miRNA cargo of endometrial extracellular vesicles in patients with endometriosis: potential implications for pregnancy outcomes.","authors":"Alba Bas-Rivas, Adrián Villalba, Aitana Merino-Pérez, Amparo Faus, Irene Juárez, Carmen Vidal, Pilar Alamá, Antonio Pellicer, Ana Corachán, Irene Cervelló, Hortensia Ferrero","doi":"10.1093/hropen/hoag040","DOIUrl":"10.1093/hropen/hoag040","url":null,"abstract":"<p><strong>Study question: </strong>Could the miRNA cargo of extracellular vesicles (EVs) secreted by eutopic endometrium from women with endometriosis be involved in the pregnancy complications related to endometriosis?</p><p><strong>Summary answer: </strong>EVs secreted by eutopic endometrium from women with endometriosis present altered miRNA that modulates biological processes related to pregnancy disorders.</p><p><strong>What is known already: </strong>Communication between endometrial cells, immune cells, endothelial cells, and the embryo is essential for the correct establishment and development of pregnancy, and EVs have been proposed as key mediators of this dialogue. This study aimed to elucidate whether EV-mediated communication is altered in endometriosis, by analysing the miRNA cargo of EVs secreted by eutopic endometrium from women with endometriosis, after differentiation to the gestational phase, compared with the miRNA cargo of EVs secreted by eutopic endometrium from healthy women, also after differentiation to the gestational phase.</p><p><strong>Study design size duration: </strong>This was a prospective experimental comparative study in which endometrial organoids were derived from eutopic endometrium of patients with endometriosis (n = 16) and healthy women (n = 15).</p><p><strong>Participants/materials setting methods: </strong>Organoids were differentiated to mimic the gestational phase through supplementation with pregnancy hormones. EVs were then isolated from the culture medium, characterized, and their miRNA cargo was profiled by sequencing. Target genes of the significantly differentially expressed miRNAs were identified, and functional enrichment analysis was subsequently performed. Finally, the organoids were co-cultured with human endometrial stromal cells (hESCs) and human placental choriocarcinoma JAR cells, and the effects of EV-derived miRNAs were assessed by qPCR using representative target genes selected based on their roles in endometrium-embryo communication and epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT-MET) in organoids, EMT in stromal (hESC) cells, and endometrium-embryo communication in JAR cells.</p><p><strong>Main results and the role of chance: </strong>EVs were successfully isolated. miRNA-seq showed eight significantly differentially expressed miRNAs (false discovery rate [FDR] < 0.05); six were downregulated: miR-1290, miR-1246, miR-320d, miR-4516, miR-12136, and miR-3065-5p; and two were upregulated: miR-191-5p, and miR-335-5p. These miRNAs target 3964 genes and GO enrichment analysis identified 789 biological processes (FDR < 0.05), mainly involved in embryo development and developmental growth, immune system function, angiogenesis, and epithelial-mesenchymal transition. KEGG pathway analysis revealed 32 deregulated pathways (FDR < 0.05), including the PI3K-Akt pathway commonly related to the pathogenesis of preeclampsia. Validation in gestational epithelial endometriosis","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag040"},"PeriodicalIF":8.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229560","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":"Meiotic gene variants contribute to recurrent blastulation failure.","authors":"Xueqin Chen, Lizhi Leng, Wenbin He, Weina Li, Lianyue Li, Xing Zhang, Xilin Xu, Jing Dai, Yifan Gu, Pingyuan Xie, Fei Meng, Huiling Hu, Miao Jin, Shujuan Ma, Fei Gong, Guangxiu Lu, Gang Liu, Yueqiu Tan, Ge Lin, Wei Zheng","doi":"10.1093/hropen/hoag039","DOIUrl":"10.1093/hropen/hoag039","url":null,"abstract":"<p><strong>Study question: </strong>What is the genetic etiology of recurrent blastulation failure, particularly in morphologically good-quality cleavage-stage embryos?</p><p><strong>Summary answer: </strong>Variants in meiotic genes may contribute to gamete-derived complex aneuploidy and impaired embryonic genome activation, which are strongly associated with recurrent blastulation failure in good-quality cleavage-stage embryos (R-GQBF).</p><p><strong>What is known already: </strong>Successful blastocyst formation is critical for implantation. Embryonic development undergoes a major transition around the 8‑cell stage, shifting from reliance on maternal transcripts to embryonic genome activation. While pathogenic variants in maternal-effect genes have been linked to developmental arrest before the 8-cell stage, the genetic basis of failure occurring between the 8-cell stage and blastulation remains unclear.</p><p><strong>Study design size duration: </strong>From 2018 to 2023, 707 couples who met the R-GQBF criteria were recruited. After rigorous exclusion, 204 couples remained, of whom 97 were ultimately included for genetic etiology analysis.</p><p><strong>Participants/materials setting methods: </strong>A total of 109 individuals from 97 selected couples (93 females and 16 males, including 13 couples with both partners) underwent whole-exome sequencing (WES). Genetic variants were compared with those from 1000 fertile controls (500 females and 500 males). The chromosomal constitutions of 103 blastulation-failure embryos from 50 R-GQBF couples were analyzed via WES. Copy number variation (CNV) parental origin analysis was performed on 13 aneuploid embryos. Paternally derived chromosomal anomalies were further investigated using single-sperm chromosome analysis. Additionally, single-cell RNA sequencing was carried out on 15 arrested embryos.</p><p><strong>Main results and the role of chance: </strong>Twenty-five variants in 10 meiotic genes were identified in 20 patients (18.3%). Female carriers predominantly harbored prophase I variants (<i>SPO11</i>, <i>MEI1</i>, <i>REC114</i>, <i>ANKRD31</i>, <i>DMC1</i>, <i>CNTD1</i>, <i>MLH3</i>, <i>SYCE1</i>, and <i>SYCP2</i>), while three male patients carried <i>MEIKIN</i> variants. Female carriers generally had preserved ovarian reserve, whereas male carriers showed severe oligoasthenoteratozoospermia. Chromosomal analysis revealed a high prevalence of complex aneuploidy in blastulation-failure embryos (63.1%). CNV tracing confirmed the parental origin of abnormalities from the meiotic variant carrier in analyzed case, and sperm from all <i>MEIKIN</i> carriers also exhibited severe chromosomal abnormalities. Single-cell transcriptomics revealed defective embryonic genome activation, impaired lineage specification, and activation of stress pathways. These consistent findings minimize the likelihood of chance associations.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag039"},"PeriodicalIF":8.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140004","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":"Intercornual distance and postoperative reproductive outcomes in moderate-to-severe intrauterine adhesions: a retrospective cohort study.","authors":"Yifu He, Xingping Zhao, Huan Huang, Changfa Shu, Xiaoming Guan, Jia Guo, Dabao Xu","doi":"10.1093/hropen/hoag038","DOIUrl":"10.1093/hropen/hoag038","url":null,"abstract":"<p><strong>Study question: </strong>Does intercornual distance (ICD), as reflected by intrauterine stent size during hysteroscopic adhesiolysis, have an association with reproductive outcomes and provide information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions?</p><p><strong>Summary answer: </strong>A smaller ICD was independently associated with a lower likelihood of clinical pregnancy within 1 year of the final hysteroscopy and may offer additional information for postoperative risk stratification in women with moderate-to-severe intrauterine adhesions.</p><p><strong>What is known already: </strong>Reproductive outcomes following treatment for moderate-to-severe intrauterine adhesions vary considerably. Existing severity classifications offer limited discrimination within this group. The potential association between ICD and postoperative reproductive outcomes has not been systematically evaluated.</p><p><strong>Study design size duration: </strong>Retrospective cohort study conducted at a tertiary academic center from November 2022 to October 2023. A total of 560 women were included, with up to 2 years of follow-up.</p><p><strong>Participants/materials setting methods: </strong>Retrospective single-center cohort of women aged 18-44 years with moderate-to-severe intrauterine adhesions (American Fertility Society [AFS] score ≥ 5) undergoing standardized hysteroscopic management with adhesiolysis, intrauterine stent placement, and scheduled second-look hysteroscopy. ICD was reflected by intraoperatively selected stent size, categorized into ordered levels (XXXS-XXXL) and dichotomized using an XS threshold (∼20-22 mm). Postoperative ultrasound-derived ICD was analyzed for supportive evaluation. The primary outcome was clinical pregnancy within 1 year of the final hysteroscopy. Associations were examined using multivariable logistic regression with sensitivity analyses. The incremental predictive value and clinical utility of stent-size classification (≤XS vs >XS) beyond established clinical variables were evaluated using discrimination, calibration, and decision-curve analyses.</p><p><strong>Main results and the role of chance: </strong>Women in the ≤XS group had lower odds of clinical pregnancy within 1 year of the final hysteroscopy compared with those in the >XS group (adjusted odds ratio [aOR] = 0.447, 95% CI 0.255-0.786; <i>P</i> = 0.005). The association was consistent in sensitivity analyses and when postoperative ultrasound-derived ICD was analyzed as a continuous variable. Although improvements in model discrimination were modest, the difference in the probability of clinical pregnancy between the ≤XS and >XS groups was 21.2% (absolute risk difference [ARD] = 21.2%, 95% CI 9.6-32.2; <i>P</i> < 0.001), corresponding to a number needed to benefit (NNB) of 4.7, indicating potential clinical utility for postoperative risk stratification.</p><p><strong>Limitations reasons for caution: </strong>T","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag038"},"PeriodicalIF":8.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13226053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148159372","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":"Paracetamol exposure during pregnancy, the risk of major congenital malformations, and perinatal and postnatal outcomes: a population-based cohort study.","authors":"Daphna Idan, Ariel Avraham Hasidim, Itamar Ben Shitrit, Tal Michael, Amalia Levy, Gali Pariente, Eitan Lunenfeld, Sharon Daniel","doi":"10.1093/hropen/hoag037","DOIUrl":"10.1093/hropen/hoag037","url":null,"abstract":"<p><strong>Study question: </strong>Is maternal paracetamol exposure during the first and third trimesters of pregnancy associated with major congenital malformations and adverse perinatal and postnatal outcomes?</p><p><strong>Summary answer: </strong>Maternal paracetamol use during the first or third trimester was not associated with major congenital malformations or adverse perinatal and postnatal outcomes.</p><p><strong>What is known already: </strong>Paracetamol is the most commonly used analgesic and antipyretic during pregnancy and has long been considered safe. However, recent concerns have been raised regarding potential fetal and perinatal risks, with inconsistent findings across studies.</p><p><strong>Study design size duration: </strong>In this population-based retrospective study, the cohort included 265 143 singleton pregnancies resulting in delivery or elective termination at a single tertiary medical center between 1998 and 2018. Separate analytic cohorts comprised 264 858 pregnancies for first-trimester analyses and 257 285 pregnancies for third-trimester analyses. Follow-up extended through delivery and the first year of life for congenital malformation ascertainment. There was no loss to follow-up for primary outcomes due to complete registry linkage.</p><p><strong>Participants/materials setting methods: </strong>All singleton pregnancies among women aged 15-45 years, insured by a regional health maintenance organization and managed at a tertiary university medical center, were included. Pregnancies with chromosomal or genetic abnormalities, teratogenic drug exposure, or multiple gestations were excluded. Paracetamol exposure (prescription and over-the-counter dispensations) was assessed separately for the first trimester (≤13 weeks) and third trimester (≥27 weeks) and categorized by total defined daily doses. Exposed and unexposed pregnancies were compared using multivariable Poisson regression and propensity score-based generalized full matching. Matching incorporated maternal demographics, comorbidities, pregnancy characteristics, and indications for paracetamol use. After matching, covariate balance was achieved (standardized mean differences <0.1 for all variables).</p><p><strong>Main results and the role of chance: </strong>During the first trimester, paracetamol exposure was recorded in 41 011 pregnancies (15.5%); major congenital malformations occurred in 7.9% of exposed versus 6.9% of unexposed pregnancies (crude RR 1.14; 95% CI, 1.1-1.18), with no association after matching (adjusted RR 1.04; 95% CI, 0.98-1.10) and no associations with organ-specific malformations. Third-trimester exposure was recorded in 36 375 pregnancies (14.1%) and was not associated, in the matched analyses, with preterm birth, low or very low birth weight, perinatal death, low Apgar scores, or markers of premature ductus arteriosus closure or neonatal renal impairment. Dose-response and sensitivity analyses showed no evidence of increased risk, a","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag037"},"PeriodicalIF":8.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019141","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":"Associations of prenatal exposure to maternal autoimmune disorders with a wide spectrum of psychiatric and neurodevelopmental disorders in offspring-a nationwide cohort study.","authors":"Elin Skott, Wenjie Cai, Miranda Stiernborg, Anna Fogdell-Hahn, Maibritt Giacobini, Mika Gissler, Samson Nivins, Catharina Lavebratt","doi":"10.1093/hropen/hoag026","DOIUrl":"10.1093/hropen/hoag026","url":null,"abstract":"<p><strong>Study question: </strong>Are children exposed <i>in utero</i> to various maternal autoimmune disorders (ADs) and autoinflammatory disorders (AIDs) at greater risk for developing any of a wide range of psychiatric or neurodevelopmental disorders?</p><p><strong>Summary answer: </strong>Prenatal exposure to maternal ADs and AIDs, but for those of the nervous system, was at modest effect sizes associated with a number of primarily early onset neurodevelopmental disorders.</p><p><strong>What is known already: </strong>Prenatal exposure to maternal immune activation and certain ADs or AIDs has been associated with psychiatric and neurodevelopmental disorders in offspring. However, most studies examined only one specific maternal exposure, such as rheumatoid arthritis, in relation to one specific outcome, such as autism spectrum disorder (ASD). The potential impact of a broader range of maternal AD/AIDs on various mental outcomes remains largely unexplored.</p><p><strong>Study design size duration: </strong>A nationwide, population-based cohort study of all live births in Finland from 1996 to 2014, with follow-up to 2021 (N = 1 107 802). Analyses were conducted from October 2023 to December 2025.</p><p><strong>Participants/materials setting methods: </strong>Maternal diagnoses of AD/AIDs, recorded prior to and/or during pregnancy, were identified through Finnish National Health Registers (N = 34 033). Cox regression was used to estimate the hazard ratios (HRs) with 99% and 95% CIs of psychiatric and neurodevelopmental disorder diagnoses in offspring to AD/AIDs mothers.</p><p><strong>Main results and the role of chance: </strong>Of the 1 107 802 births, 3.2% were to mothers with an AD/AID. Offspring exposed to maternal AD/AIDs had a 15% higher risk of a major psychiatric disorder (HR, 1.15 [99% CI, 1.09-1.21]) and an 18% higher risk of a neurodevelopmental disorder (HR, 1.18 [99% CI, 1.14-1.22]).Combining AD/AIDs according to the main body system affected, associations with offspring's mental diagnoses were detected mainly for connective tissue AD/AIDs and endocrine AD/AIDs. Although most effect sizes were modest (HRs below 2), there were two notable exceptions with more than 2-fold risk: (i) ASD in autoimmune thyroiditis, and (ii) other behavioral or emotional disorders (F98) in pernicious anemia. A 70-99% higher risk for certain neurodevelopmental disorders or milder regulatory disturbances was observed in offspring exposed to systemic vasculitis, type 1 diabetes mellitus (T1DM), acute thyroiditis, Crohn's disease, and SIC (being polymyalgia rheumatica, Sjögren's syndrome, and hypermobility syndrome). The T1DM associations were not completely mediated by adverse birth factors.</p><p><strong>Limitations reasons for caution: </strong>The number of exposure-discordant siblings was insufficient to fully adjust for shared unmeasured familial confounding, and paternal information and breastfeeding data were unavailable. Second, some AD/AIDs were r","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag026"},"PeriodicalIF":8.6,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13133672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824334","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":"Testicular tissue transplantation: from animal models to clinical application.","authors":"Ellen De Beer, Ellen Goossens","doi":"10.1093/hropen/hoag035","DOIUrl":"10.1093/hropen/hoag035","url":null,"abstract":"<p><strong>Background: </strong>Every year, approximately 14,000 new cases of childhood cancer are diagnosed in Europe. Chemo- and radiotherapy have improved significantly, leading to survival rates of up to 81% in children. The growing number of childhood cancer survivors has brought increased attention to the long-term gonadotoxic effects of these treatments, with lifelong infertility being one of the most frequent side effects. Consequently, fertility preservation and restoration strategies are actively under investigation. Since spermatogenesis starts only at puberty, pre-pubertal boys cannot benefit from sperm banking. However, as spermatogonial stem cells are present from birth, the surgical retrieval and cryopreservation of pre-pubertal testicular tissue represent a promising strategy to preserve fertility in boys before undergoing gonadotoxic treatment. Pre-pubertal testicular tissue has been cryopreserved for more than 3,000 boys worldwide. At adulthood, the cryopreserved testicular tissue may be used to restore fertility, either through testicular tissue transplantation or spermatogonial stem cell transplantation (SSCT), or through <i>in vitro</i> spermatogenesis (IVS). Reviews are already available for SSCT and IVS, but an updated cross-species comparative overview of testicular tissue transplantation with emphasis on recent clinical translation is needed.</p><p><strong>Objective and rationale: </strong>The aim of this review is to provide an overview of pre-clinical research on testicular tissue transplantation in animal models, and to highlight the initial steps of the clinical application of autologous testicular tissue transplantation.</p><p><strong>Search methods: </strong>A comprehensive review of peer-reviewed publications on testicular tissue transplantation was performed using PubMed and Google Scholar databases. The literature search was limited to English-language studies published between 2002 (the first study on testicular tissue transplantation) and December 2025. The search was conducted using the following search terms: testicular tissue grafting, allotransplantation of testicular tissue, xenotransplantation of testicular tissue, and autotransplantation of testicular tissue. Titles and abstracts were screened for relevance. Articles not subjected to peer review were excluded. Studies were included if they involved testicular tissue grafting and reported graft outcomes, such as the most advanced germ cell stage.</p><p><strong>Outcomes: </strong>Animal studies have demonstrated that donor age and graft site play a crucial role in the outcome of testicular tissue transplantation. For instance, transplantation of adult testicular tissue usually led to degeneration of the seminiferous tubules, while allo-, xeno-, and autotransplantation of pre-pubertal testicular tissue successfully restores complete spermatogenesis in most of the species. In addition, homotopic engraftment generally provides the best support to restore sper","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag035"},"PeriodicalIF":8.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13191325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019127","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":"Cost-effectiveness of time-lapse monitoring with or without the use of embryo selection software compared to routine incubation and selection.","authors":"Dorit C Kieslinger, Carlijn G Vergouw, Liliana Ramos, Brigitte Arends, Max H J M Curfs, Els Slappendel, E Hanna Kostelijk, Math H E C Pieters, Dimitri Consten, Marieke O Verhoeven, Dagmar E Besselink, Frank Broekmans, Ben J Cohlen, Jesper M J Smeenk, Sebastiaan Mastenbroek, Corry H de Koning, Yvonne M van Kasteren, Etelka Moll, Jeroen van Disseldorp, Egbert A Brinkhuis, Esther A M Kuijper, W Marchien van Baal, Hans G I van Weering, Paul J Q van der Linden, Marie H Gerards, Patrick M Bossuyt, Cornelis B Lambalk, Madelon van Wely","doi":"10.1093/hropen/hoag034","DOIUrl":"10.1093/hropen/hoag034","url":null,"abstract":"<p><strong>Study question: </strong>Is time-lapse monitoring (TLM) with or without a machine learning selection algorithm for embryo selection cost-effective when compared with conventional culture and selection?</p><p><strong>Summary answer: </strong>Neither TLM with or without the use of machine learning for embryo selection is likely to be cost-effective when compared with the conventional approach. TLM adds cost to IVF treatments without improving clinical results.</p><p><strong>What is known already: </strong>Recent randomized controlled trials (RCTs) provide evidence that TLM is unlikely to increase pregnancy or live birth rates (LBRs) relative to conventional embryo culture and selection. To date no cost-effectiveness analysis of TLM has been published.</p><p><strong>Study design size duration: </strong>A cost-effectiveness analysis (CEA) from a healthcare perspective was performed based on data from our multicentre RCT on TLM, which was conducted from 2017 to 2020. Women scheduled for Day 3 single embryo transfer during their first, second, or third oocyte retrieval were included. The trial included three strategies: (i) TLE: embryo selection based on a machine learning algorithm and uninterrupted culture; (ii) TLR: routine morphological embryo selection and uninterrupted culture; and (iii) CON (Control): routine morphological embryo selection and interrupted culture.</p><p><strong>Participants/materials setting methods: </strong>In total, 1731 couples were included. The difference in mean costs between treatment groups was calculated with the following cost items: laboratory procedures, laboratory facilities (incubator, disposables, service), embryo transfers, pregnancies, miscarriages, and deliveries. We did not consider costs of stimulation, oocyte retrieval, and IVF/ICSI procedures as these were identical in each group. The effectiveness measure for the CEA was the cumulative LBR. Incremental cost-effectiveness ratios were calculated for direct comparisons between strategies.</p><p><strong>Main results and the role of chance: </strong>The 12-month cumulative LBR rate was similar in the three treatment groups: TLE 48.7%, TLR 48.4%, CON 48.2%. The mean difference in costs was €237 (95% CI: -35 to 508) between TLE and CON, and €55 (95% CI: -203 to 313) between TLR and CON. The incremental cost-effectiveness ratio between TLE and CON for one additional live born was €45 950; for TLR versus CON, it was €26 905. The probability that TLE or TLR are cost-effective was low for all willingness-to-pay level, with several scenarios resulting in comparable findings.</p><p><strong>Limitations reasons for caution: </strong>This study reports the cost-effectiveness for one time-lapse incubator; however, more systems are currently available.</p><p><strong>Wider implications of the findings: </strong>While our cost-effectiveness analysis provides evidence that TLM is unlikely to be cost-effective, its use is not inferior to conventional methods in term","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag034"},"PeriodicalIF":8.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13167187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935900","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}