Human reproduction最新文献

{"title":"Immature oocyte proportion may or may not compromise ICSI outcomes, but methods do: a critical appraisal.","authors":"Fatih Aktoz, Yucel Sahin","doi":"10.1093/humrep/deag012","DOIUrl":"10.1093/humrep/deag012","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"638-639"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of chromosomal aberrations in couples seeking assisted reproductive treatment.","authors":"Shimin Yuan, Dehua Cheng, Qing Zhang, Qing Zheng, Hua Zhang, Jun Zhang, Lanxiang Mo, Yufen Di, Xin Liu, Dun Xiao, Qiaoyuan Xiong, Yinhui Wang, Duo Yi, Yongteng Guo, Xueni She, Qiang Yang, Shuangshuang Nie, Qin Tan, Chunbo Xie, Qi Wang, Xuan Song, Danjun Zhang, Xiaoyu Hu, Lanlan Meng, Yangqin Peng, Juan Du, Liang Hu, Changgao Zhong, Hao Hu, Xiurong Li, Kailin Zhang, Lingzhi Feng, Fei Gong, Guangxiu Lu, Ge Lin, Yue-Qiu Tan","doi":"10.1093/humrep/deag008","DOIUrl":"10.1093/humrep/deag008","url":null,"abstract":"<p><strong>Study question: </strong>What are the prevalence, type, and stratified risks (reproductive failure subtype, sex, age, semen quality, and prior adverse pregnancy events) of chromosomal aberrations in couples seeking ART treatment in a large-scale cohort study?</p><p><strong>Summary answer: </strong>The prevalence of chromosomal aberrations in couples with reproductive failure was 3.42%, with a higher prevalence in younger individuals, men with poorer semen quality, and those experiencing multiple adverse pregnancy outcomes.</p><p><strong>What is known already: </strong>Reproductive failure is a global health issue, with chromosomal aberrations playing an important role. ART is widely used for the treatment of reproductive failure; however, large-scale, comprehensive studies characterizing the stratified risks of chromosomal aberrations in couples seeking ART remain scarce.</p><p><strong>Study design, size, duration: </strong>This retrospective study analysed chromosomal data from 227 818 couples seeking ART at our hospital between January 1993 and March 2024.</p><p><strong>Participants/materials, setting, methods: </strong>This study included 227 818 couples with reproductive failure, including 130 213 couples with primary infertility, 58 161 with secondary infertility, and 39 444 with adverse pregnancy outcomes. All participants underwent routine cytogenetic analysis using GTG-banding prior to ART. Statistical analysis was performed using R software (v4.4.0), with significance set at P < 0.05.</p><p><strong>Main results and the role of chance: </strong>Chromosomal aberrations were detected in 7785 couples (3.42%), with the highest prevalence in those with adverse pregnancy outcomes (4.83%), followed by those with primary infertility (3.54%) or secondary infertility (2.18%) (all P < 0.001). Significant sex differences were observed in infertile couples (men: 1.91% vs women: 1.52%) and couples with adverse pregnancy outcomes (men: 2.04% vs women: 2.81%), (P < 0.001). The prevalence of chromosomal aberrations was inversely correlated with age (2.36% in <25 years to 1.29% in ≥35 years) and increased significantly with poorer semen quality (0.89% in normozoospermia to 12.54% in azoospermia) and more adverse pregnancy events (3.07% in 1 event to 9.38% in ≥3 events, P < 0.001). Common structural aberrations included reciprocal and Robertsonian translocations and inversions, with frequent breakpoints at 11q23, 22q11, and 7q22. The percentage of haploid length of each autosome and the corresponding percentage of breakpoints showed a strong Pearson's correlation (R = 0.933, P < 0.001, two-tailed test). Robertsonian translocations and t(11;22)(q23;q11) were recurrent. The most frequent aneuploidies identified were 47,XXY (Klinefelter) and 45, X (Turner) syndromes, in both mosaic and non-mosaic forms.</p><p><strong>Limitations, reasons for caution: </strong>The lack of detailed clinical characteristics limited patient stratification and hindered t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"629-637"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNAH14 deficiency disrupts sperm annulus positioning and compromises offspring postnatal development.","authors":"Xiang Wang, Gan Shen, Jinhui Li, Tiechao Ruan, Xiaohui Jiang, Ying Ge, Jun Ma, Shikun Zhao, Chuan Jiang, Liangchai Zhuo, Yunchuan Tian, Guicheng Zhao, Xinyao Tang, Yihong Yang, Ying Shen","doi":"10.1093/humrep/deag014","DOIUrl":"10.1093/humrep/deag014","url":null,"abstract":"<p><strong>Study question: </strong>Does DNAH14 deficiency impair sperm flagellar integrity and contribute to male infertility?</p><p><strong>Summary answer: </strong>Loss of DNAH14 leads to disrupted sperm annulus positioning, defective mitochondrial assembly, reduced sperm motility, and impaired male fertility in both humans and mice.</p><p><strong>What is known already: </strong>Pathogenic variants in several axonemal dynein heavy chain (DNAH) genes have been implicated in male infertility and primary ciliary dyskinesia. DNAH14 remains the only member whose roles are undefined.</p><p><strong>Study design, size, duration: </strong>Genetic analysis was performed on two unrelated Han Chinese infertile men. Functional studies were carried out in a CRISPR-Cas9 Dnah14 knockout (KO) mouse model, with phenotyping of males and their offspring.</p><p><strong>Participants/materials, setting, methods: </strong>Whole-exome sequencing was applied to patient samples. Dnah14 KO mice were generated to assess reproductive phenotypes. Sperm morphology and motility were analyzed using Papanicolaou staining, scanning electron microscopy (SEM), transmission electron microscopy (TEM), immunofluorescence staining, and computer-assisted sperm analysis (CASA). Intracytoplasmic sperm injection (ICSI) was performed in both patients and KO mice, and offspring survival and growth were monitored.</p><p><strong>Main results and the role of chance: </strong>Biallelic DNAH14 variants were identified in two men with asthenoteratozoospermia. Patient HX-042 carried compound heterozygous variants c.1055T>C and c.9788T>C, whereas Patient HX-137 harbored compound heterozygous variants c.10434G>T and c.12512A>G. In both cases, sperm exhibited markedly reduced motility, disrupted annulus positioning and mitochondrial disorganization. DNAH14 was specifically localized to the midpiece of both human and mouse sperm. Dnah14 KO mice exhibited subfertility, characterized by reduced sperm motility, sperm mitochondrial sheath anomaly, annulus mislocalization, and midpiece bending, whereas ciliogenesis in non-reproductive tissues remained unaffected. ICSI achieved normal fertilization and embryonic development in both patients and KO mice. Offspring of KO males exhibited reduced survival and growth retardation.</p><p><strong>Large scale data: </strong>Not available.</p><p><strong>Limitations, reasons for caution: </strong>We have, for the first time, established genotype and phenotype associations of DNAH14/Dnah14 in humans and mice; however, mechanistic studies remain limited. Further in vivo investigations using animal models are necessary to elucidate the molecular mechanisms by which DNAH14 regulates the structural integrity of sperm flagella. In addition, potential epigenetic mechanisms underlying the role of DNAH14 in postnatal growth also warrant further clarification.</p><p><strong>Wider implications of the findings: </strong>These findings identify DNAH14 as a novel contributor to spe","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"515-530"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: immature oocyte proportion may or may not compromise ICSI outcomes, but methods do: a critical appraisal.","authors":"Veda Sripada, Denny Sakkas, Denis Vaughan, Brittany Morse, Yuval Fouks","doi":"10.1093/humrep/deag013","DOIUrl":"10.1093/humrep/deag013","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"640-641"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free apical surface hetero-cellular CDH1 homophilic binding is a major mediator of blastocyst-endometrium interaction in humans.","authors":"Hanzhang Ruan, Andy Chun Hang Chen, Yuxuan Xue, Kai Chuen Lee, Sze Wan Fong, Qi Qiu, Yongqi Tan, Ying Feng, Cheuk Lun Lee, Renwu Hua, Junrong Huang, Tianren Wang, Yanwen Xu, Kai-Fai Lee, Ning Xi, Raymond Hang Wun Li, Ernest Hung Yu Ng, William Shu Biu Yeung, Yin Lau Lee","doi":"10.1093/humrep/deag009","DOIUrl":"10.1093/humrep/deag009","url":null,"abstract":"<p><strong>Study question: </strong>Is E-cadherin (CDH1) expressed on the free apical surface of endometrial epithelial cells (EECs) involved in embryo attachment?</p><p><strong>Summary answer: </strong>Embryonic signals induced apical expression of endometrial CDH1, which facilitated attachment via hetero-cellular CDH1 homophilic binding.</p><p><strong>What is known already: </strong>Understanding human blastocyst-endometrium interaction helps fertility treatment by facilitating the evaluation of endometrial receptivity and blastocyst quality. CDH1 is an adhesion molecule commonly known for the maintenance of epithelial integrity through adherens junction formation on the lateral membranes of adjacent epithelial cells. The apical region of some epithelia also expressed CDH1 of unknown function.</p><p><strong>Study design, size, duration: </strong>Laboratory experimental study.</p><p><strong>Participants/materials, setting, methods: </strong>The potential apical cell plasma membrane proteins participating in adhesion between blastocysts and EEC were identified by comparing the surface proteomes of polar trophectoderm-like trophoblastic spheroids (BAP-EB) and receptive EEC. The apical surface expression of CDH1 in human blastocysts and primary EEC was confirmed by live-cell immunofluorescent staining. Antibody blocking and gene knockdown approaches were used to study the functional roles of hetero-cellular homophilic binding of CDH1. The adhesiveness of EEC and polar trophectoderm-like cells was confirmed by atomic force microscopy upon gene knockdown. The embryonic signals induced endometrial apical surface relocations of CDH1 and its stabilizer delta-1 catenin (CTNND1) were studied by treatments with conditioned media of BAP-EB and human blastocysts, as well as with HCG. The correlations of endometrial CDH1 and CTNND1 with pregnancy outcomes were confirmed by western blotting analysis of their protein expressions in EEC and immunofluorescent staining of endometrium collected from women who gave live birth, those who failed to become pregnant after IVF, and those with repeated implantation failure.</p><p><strong>Main results and the role of chance: </strong>We identified 27 pairs of potential interactive cell plasma membrane transmembrane proteins between BAP-EB and EEC, and CDH1 homophilic binding was one of them. CDH1 was localized to the apical surface of receptive EEC and the polar trophectoderm of human blastocysts. The CDH1 expression in EEC was higher during the window of implantation than those at the pre-receptive phase. With the use of atomic force microscopy, we revealed that the adhesiveness of the apical surface of polar trophectoderm-like cells and EEC decreased when CDH1 was silenced. The attachment rates of BAP-EB onto EEC were decreased when the surface CDH1 of BAP-EB and/or the EEC was blocked by an anti-CDH1 antibody, indicating that homophilic binding of trophectodermal CDH1 with endometrial CDH1 mediated the attachment of BAP","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"563-582"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal exposure to parental smoking and infertility in sons and daughters: a cohort study.","authors":"M V Stokholm, A Ernst, S E Håberg, C L Kjersgaard, A H Thomsen, C H Ramlau-Hansen","doi":"10.1093/humrep/deag011","DOIUrl":"10.1093/humrep/deag011","url":null,"abstract":"<p><strong>Study question: </strong>Is prenatal exposure to parental smoking associated with infertility in sons and daughters?</p><p><strong>Summary answer: </strong>The study does not provide robust evidence that prenatal smoking exposure increases the risk of infertility, defined as clinically diagnosed infertility or ART use, in adult sons and daughters.</p><p><strong>What is known already: </strong>Reproductive function is established early in fetal life and may be adversely affected by prenatal exposure to parental smoking.</p><p><strong>Study design, size, duration: </strong>In this cohort study, we used data from the Danish birth cohort, Health Habits for Two, established in 1984-1987. In total, 11 980 (87% of eligible) women participated and gave birth to 11 144 liveborn, singleton sons and daughters.</p><p><strong>Participants/materials, setting, methods: </strong>Adult sons and daughters born to mothers enrolled in the birth cohort constituted the study population and were aged 35-38 years at follow-up. Around gestational week 36, mothers provided information on parental smoking. The primary exposure of interest was maternal smoking. Paternal smoking and combined parental smoking were also assessed to explore individual and potential synergistic effects. Infertility among offspring was defined as either an ICD-10 infertility diagnoses or use of ART, identified within two nationwide registers and considering their partners' records. Associations were examined using Cox regression models estimating crude and adjusted hazard ratios (HRs) for categories of prenatal smoking, with non-smoking as the reference, accounting for competing risks of infertility. Dose-response associations were explored across categories of maternal and paternal smoking. The proportional hazards assumption was met only when stratifying analyses by age, using cutoffs of ≤26 and >26 years for sons, and ≤27 and >27 years for daughters. In a sensitivity analysis, follow-up was restricted to periods of registered partnership under the assumption that individuals in a relationship are more likely to be identified as infertile and vice versa. In a sub-analysis, analyses were stratified by offspring educational level to explore potential social gradients in being identified as infertile in medical records.</p><p><strong>Main results and the role of chance: </strong>Maternal smoking of >9 cigarettes/day tended to be associated with higher risk of infertility among sons ≤26 years (HR 1.7 (95% CI: 0.8-3.5)) and daughters ≤27 years (HR 1.2 (95% CI: 0.7-1.9)), both indicating suggestive dose-response patterns with higher risk of infertility with increasing maternal smoking levels. No associations for sons >26 years or daughters >27 years were observed. Paternal smoking of >10 cigarettes/day tended to be associated with higher risk of infertility among sons >26 years (HR 1.3 (95% CI: 0.9-1.8)), indicating suggestive dose-response patterns. No higher risk of infertility following","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"595-605"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide analysis highlights epigenetic link to age at menarche.","authors":"Z Ye, R Xu, G L Malone, P A Dugué, T L Nguyen, G G Giles, M C Southey, R L Milne, S Li","doi":"10.1093/humrep/deag019","DOIUrl":"10.1093/humrep/deag019","url":null,"abstract":"<p><strong>Study question: </strong>Do genome-wide DNA methylation patterns influence age at menarche?</p><p><strong>Summary answer: </strong>An epigenome-wide association study identified 63 differentially methylated regions (DMRs), with replication and Mendelian randomization supporting suggestive causal effects of TRIM61 methylation on age at menarche.</p><p><strong>What is known already: </strong>Age at menarche is a key reproductive milestone, associated with cancer and metabolic outcomes. Genome-wide studies have suggested genetic influences, but the epigenetic mechanisms regulating pubertal timing remain largely unexplored.</p><p><strong>Study design, size, duration: </strong>Cross-sectional epigenome-wide association study of blood DNA methylation in 3429 adult women (mean age 56 years) across discovery and replication cohorts. Discovery included 479 participants from the Australian Mammographic Density Twins and Sisters Study and 2614 from the Melbourne Collaborative Cohort Study. Replication was performed in 336 women from the European Prospective Investigation into Cancer and Nutrition-Italy.</p><p><strong>Participants/materials, setting, methods: </strong>Peripheral blood samples from adult women were profiled using the Illumina HumanMethylation450 BeadChip. Differentially methylated sites were identified using linear mixed-effect models, followed by identifying DMRs through DMRcate and combp methods and region-based effect analysis. Mendelian randomization assessed the causal effects of individual cytosine-phosphate-guanine (CpGs) within the identified DMR on age at menarche and nearby gene expression. Functional annotation integrated chromatin accessibility, transcription factor binding sites, and regulatory element mapping from public epigenomic databases.</p><p><strong>Main results and the role of chance: </strong>Sixty-three DMRs were identified in the discovery cohort. The TRIM61 region was replicated (P < 0.05) with consistent positive effects across CpGs and the region. Mendelian randomization indicated that TRIM61 methylation causally influenced age at menarche and regulated the expression of nearby genes at a suggestive level. Functional annotation revealed overlap with active regulatory elements, supporting a mechanistic role in modulating chromatin accessibility and transcriptional regulation.</p><p><strong>Large scale data: </strong>European Prospective Investigation into Cancer and Nutrition-Italy data can be accessed through the Gene Expression Omnibus (GSE51032). The methylation quantitative trait locus (mQTL) data can be downloaded from https://data.bris.ac.uk/data/dataset/r9bxayo5mmk510dczq6golkmb. The expression quantitative trait locus (eQTL) data can be downloaded from the eQTLGen Consortium (https://www.eqtlgen.org/cis-eqtls.html). The genome-wide association studies summary statistics of age at menarche can be available from the IEU OPENGWAS (https://gwas.mrcieu.ac.uk/); dataset ID: ieu-a-1095.</p><p><strong>Lim","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"616-628"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular features of ovarian stimulation in peripubertal girls with mosaic Turner's syndrome.","authors":"Ozgur Oktem, Hesam Ghafouri Kalajahi, Yashar Esmaeilian, Can Benlioglu, Francesko Hela, Sevgi Yusufoglu, Uzeyir Kalkan, Volkan Turan, Baris Ata","doi":"10.1093/humrep/deag016","DOIUrl":"10.1093/humrep/deag016","url":null,"abstract":"<p><strong>Study question: </strong>Do peripubertal girls with mosaic Turner's syndrome (TS) respond to ovarian stimulation (OS) for oocyte freezing as adult women with normal ovarian reserve?</p><p><strong>Summary answer: </strong>Clinical and molecular reproductive/endocrine features of OS in these patients are similar to those of adult females.</p><p><strong>What is known already: </strong>OS for oocyte freezing is quite a new concept in peripubertal and young adolescent girls with TS because ovarian tissue cryopreservation (OTC) does not have proven efficacy, likely due to already diminished ovarian reserve and accelerated follicle atresia. No data are available in the literature regarding the molecular IVF characteristics of these cycles in this group of patients. We aimed to address this issue in the current study by analyzing gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level in four peripubertal patients aged 9, 12, 13, and 15 in comparison to control adult females with normal ovarian reserve undergoing OS for male factor infertility.</p><p><strong>Study design, size, duration: </strong>This is a clinical and research study that simultaneously analyzes the clinical and molecular characteristics of OS in peripubertal young girls with TS between 2021 and 2023 at a university hospital and translational research center.</p><p><strong>Participants/materials, setting, methods: </strong>All participants underwent OS using a progestin-primed protocol with recombinant forms of FSH and LH, and final maturation was induced with recombinant hCG. Control patients who had normal ovarian reserve and underwent OS for male factor infertility were randomly recruited during the study period to simultaneously compare and analyze the clinical and molecular OS characteristics of the peripubertal TS cases. Luteinized mural granulosa cells obtained during oocyte retrieval procedures were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live-cell imaging, and hormone assays were used.</p><p><strong>Main results and the role of chance: </strong>All TS cases responded to gonadotropin stimulation. Nine mature oocytes were retrieved and vitrified in the 9-year-old prepubertal mosaic TS case after four cycles of OS with r-FSH (300 IU) and r-LH (150 IU)/day after a mean stimulation period of 9.72 ± 2.1 days. Eight mature oocytes were retrieved in the case aged 13 after three rounds of OS. The other cases, aged 12 and 15, underwent only one cycle of OS, and two mature oocytes from each were retrieved. The expression of FSH/LH receptors and steroidogenic enzymes, basal and gonadotropin-induced up-regulation in the expression of the steroidogenic enzymes, and estradiol and progesterone productions of the GCs of the TS patients were similar to those of adult control patients. Confocal immunofluorescence microscopy and live imaging revealed no differences in ch","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"583-594"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second report of registry of the International Society of Uterus Transplantation (ISUTx): international activities 2000-2024.","authors":"Mats Brännström, Catherine Racowsky, Johanna Wiik, Stefan G Tullius, Rebecca Deans, Paige M Porrett, Wellington Andraus, Tan Hak Koon, Francisco Carmona, Randa Akouri, Paolo Scollo, Smit Solanki, Padmapriya Vivek, J Richard Smith, Shailesh P Puntambekar, Sung Eun Kim, Ömer Özkan, Jean-Marc Ayoubi, Jiri Fronek, Sara Y Brucker","doi":"10.1093/humrep/deag017","DOIUrl":"10.1093/humrep/deag017","url":null,"abstract":"<p><strong>Study question: </strong>What have been the activities, characteristics, and outcomes of uterus transplantation (UTx) performed worldwide from 2000 through 2024?</p><p><strong>Summary answer: </strong>In 91 UTx cases, 67 involved live donors and 80 of the recipients had Mayer-Rokitansky-Küster-Hauser syndrome, with 12-month graft survival of 74%, enabling pregnancy attempts that yielded 44 healthy singleton deliveries with a live birth rate per embryo transfer of 30.3%.</p><p><strong>What is known already: </strong>UTx is the only treatment for women with absolute uterine factor infertility who wish to carry a pregnancy. According to a comprehensive report including data up to 2020 on 45 UTx cases, 19 live births occurred (35.8% per embryo transfer) at a mean of 35.3 weeks gestation.</p><p><strong>Study design, size, duration: </strong>Data were extracted from the web-based registry of the International Society of Uterus Transplantation (ISUTx). This registry captures information on donor and recipient characteristics, transplantation procedures, postoperative complications, immunosuppression, complications including rejections, and reproductive outcome. Analyses were undertaken of the 91 transplants performed between 6 April 2000 and 31 December 2024, that were recorded in the registry.</p><p><strong>Participants/materials, setting, methods: </strong>Twenty-four medical centers in five continents registered their uterus transplants by entering data from the day of transplantation until 3 months after graft removal. The following variables were assessed: the demographic and laboratory characteristics of donors and recipients, the source of graft (live versus deceased donor), surgical specifics including technique, duration, ischemic times, and post-op complications, immunosuppression, rejection data, pregnancy with live birth(s), and hysterectomy.</p><p><strong>Main results and the role of chance: </strong>In 91 uterus transplantations (67 from live donors, 24 from deceased donors), the overall surgical success rate, defined as graft viability by 12 months, was 75%. Most recipients (88%) had Mayer-Rokitansky-Küster-Hauser syndrome, with mothers being the most frequent (64%) live donors. Live donor hysterectomies were performed by laparotomy (54%), robotics (28%), or laparoscopy (18%). Total ischemic time was shorter in live- versus deceased-donor UTx procedures. Rejection episodes that were treated with escalations of immunosuppression were more frequent during months 1-5 (44%) than during months 6-10 (28%) post-UTx. Graft survival during the first 12 months was superior when grafts from premenopausal donors were used as compared to from postmenopausal donors. Forty-four singleton live births (mean gestational length of 34.5 weeks), including eight second births, were reported, with a live birth rate per embryo transfer of 30%. Preeclampsia was the most common pregnancy complication, occurring in 23% of live-birth pregnancies. Major po","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"541-551"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microsimulation reveals that medically assisted reproduction is unlikely to compensate for cohort fertility decline due to increasing maternal ages.","authors":"R Granholm, A E P Cantineau, A Hoek, G Stulp","doi":"10.1093/humrep/deag006","DOIUrl":"10.1093/humrep/deag006","url":null,"abstract":"<p><strong>Study question: </strong>Can medically assisted reproduction (MAR) compensate for completed cohort fertility (CCF) decline within coresidential unions due to increasing maternal ages among Dutch women born during 1974-1984?</p><p><strong>Summary answer: </strong>MAR is unlikely to compensate for cohort fertility decline within coresidential unions due to continued increase in maternal ages in our sample cohort of Dutch women born during 1974-1984, even under ideal conditions.</p><p><strong>What is known already: </strong>The pregnancy- and live birth rates for both expectant management and MAR decline at older reproductive ages. Some infertile couples can conceive naturally without undergoing treatment by trying to conceive for a longer period of time, which complicates estimating the contribution of MAR to cohort fertility.</p><p><strong>Study design, size, duration: </strong>We developed a microsimulation model, which includes MAR, that simulates the reproductive life courses of women. We simulate a sample of 1 000 000 women representing the 1974-1984 Dutch birth cohort. Sample sizes for the input parameters varied from hundreds to thousands to hundreds of thousands depending on the parameter and source (surveys, clinical studies, panel data, population registers).</p><p><strong>Participants/materials, setting, method: </strong>Our Monte Carlo microsimulation model uses probability distributions and parameters based on representative data sources to determine a woman's transitions through union and reproductive events across her reproductive life course. We assess the contribution of various components of the MAR process to CCF within coresidential unions and estimate the net contributions of MAR to CCF with counterfactual simulations.</p><p><strong>Main results and the role of chance: </strong>Increases in the maximum female age at MAR treatment, the time to starting IUI treatment, and the number of IUI cycles did not noticeably increase CCF. Out of the hypothetical policy levers that were adjusted, increasing the share of eligible women who took up MAR from 0% to 100% increased CCF linearly by 0.06 children. Increasing the waiting time to ART treatment after infertility diagnosis from 1 to 12 months reduced CCF by 0.01. Increasing the number of reimbursed IVF/ICSI cycles from 0 to 6 increased CCF by 0.05. The increase tapered off after cycle number 2, and levelled off after cycle number 4. Minimum ages at which MAR treatment was started that were between 20 and 30 resulted in near-identical patterns of change in CCF from the adjustment in the potential policy levers, whereas both the CCF levels and rate of increase or decline were reduced at age 35 years, and further at age 40 years. The main influences on the lower CCF levels and slower rate or increase or decline were the reduction in MAR pregnancy rates at advanced reproductive ages, the increasing probability of intrauterine mortality with age, and time spent trying to conceive","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"552-562"},"PeriodicalIF":6.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}