Human reproduction open最新文献

{"title":"Bridging the gap: meta-epidemiological analysis on the clinical translation of stem cell-based therapies in women's reproductive diseases.","authors":"Hankun Su, Yu Jian, Ronghui Tang, Hoksan Chau, Xinyu Cheng, Xiao Liu, Yuqian Tong, Jinyao Ning, Xinhua Zhang, Jiayi Chen, Yilin Zhang, Zixin Tong, Yuemeng Yang, Yunyang Zhao, Liye Sun, Jingjing Chen, Hui Li","doi":"10.1093/hropen/hoag024","DOIUrl":"10.1093/hropen/hoag024","url":null,"abstract":"<p><strong>Study question: </strong>What is the current landscape of randomized controlled trials (RCTs) evaluating stem cell-based therapies for women's reproductive diseases, and how effectively has preclinical research informed their clinical translation?</p><p><strong>Summary answer: </strong>The current clinical trial landscape for stem cell-based therapies in women's reproductive diseases is characterized by rapid growth in trial registration, particularly for premature ovarian failure (POF) and intrauterine adhesions (IUA), yet remains predominantly in early-phase, single-center, single-country studies with significant heterogeneity in design and outcome reporting.</p><p><strong>What is known already: </strong>Stem cell-based therapies show promise in preclinical models for conditions such as POF, IUA, and endometriosis. However, despite increasing clinical interest, the extent to which these therapies have been rigorously evaluated in RCTs and how well clinical trials reflect preclinical evidence remains unclear.</p><p><strong>Study design size duration: </strong>This translational analysis integrated a meta-epidemiological approach with bibliometric methods. We searched the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, EudraCT, and ChiCTR from inception to 1 December 2025, using terms related to 'stem cells', 'reproductive diseases', and 'randomized controlled trials'. Only English and Chinese registration records were included.</p><p><strong>Participants/materials setting methods: </strong>Two reviewers independently screened registration records for RCTs assessing stem cell or derivative therapies in women's reproductive diseases. Eligible criteria included RCTs that reported the use of stem cells or their derivatives in female patients with reproductive conditions. Data on trial design, disease focus, stem cell type, source, phase, sample size, outcomes, and results were extracted. A hybrid approach combined traditional systematic data extraction with machine learning-assisted screening (ASReview) for basic research. Bibliometric analysis using VoSviewer and CiteSpace mapped research trends, while Health Research Classification System (HRCS) scores assessed translational potential. Consistency in screening and extraction was evaluated using kappa and Cronbach's alpha.</p><p><strong>Main results and the role of chance: </strong>From 804 records, 38 RCTs met inclusion criteria. The majority were early-phase (Phase 1/2, 76.3%), single-center (81.6%), and conducted in one country (97.4%), with China (50.0%) and the USA (18.9%) leading. POF (34.2%), ovarian cancer (23.7%), and IUA (18.4%) were the most studied conditions. Umbilical cord-derived mesenchymal stem cells (28.9%) were the most commonly used. While preclinical research shows strong mechanistic support, especially for POF and IUA, there was minimal overlap in primary outcome measures across trials, limiting comparability. Only 36.8% of RCTs included","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag024"},"PeriodicalIF":8.6,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624989","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":"When drugs meet disease: disentangling diabetes, obesity, and periconceptional GLP-1 receptor agonist safety.","authors":"Yeyi Zhu, Monique M Hedderson","doi":"10.1093/hropen/hoag016","DOIUrl":"10.1093/hropen/hoag016","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag016"},"PeriodicalIF":8.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482545","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":"Periconceptional GLP-1 receptor agonist exposure and obstetric outcomes: a Danish nationwide cohort study.","authors":"Kathrine Vauvert R Hviid, Karina Banasik, Laust Hvas Mortensen, Sten Madsbad, Katrine Strandberg-Larsen, Nina Rica Wium Geiker, David Westergaard, Henriette Svarre Nielsen","doi":"10.1093/hropen/hoag015","DOIUrl":"10.1093/hropen/hoag015","url":null,"abstract":"<p><strong>Study question: </strong>What is the association between periconceptional GLP-1 receptor agonist exposure and risk of obstetric complications?</p><p><strong>Summary answer: </strong>Periconceptional GLP-1 receptor agonist exposure was associated with increased preterm birth risk when used for diabetes treatment (liraglutide aOR 1.70, 95% CI 1.17-2.48; semaglutide aOR 1.84, 95% CI 1.24-2.7) but not for weight management, suggesting the underlying diabetes rather than the medication may be the causal factor.</p><p><strong>What is known already: </strong>GLP-1 receptor agonists are rapidly expanding in use among reproductive-age women for diabetes and obesity treatment. While not approved for use in pregnancy, inadvertent periconceptional exposure occurs frequently. Limited safety data exist, with recent small studies suggesting no increased risk of major congenital malformations, but comprehensive obstetric outcome data remain lacking.</p><p><strong>Study design size duration: </strong>This nationwide observational cohort study used data from Danish health registries from October 2009 through December 2023. We analyzed 756 636 singleton pregnancies among 480 231 women, with 529 pregnancies having periconceptional GLP-1 receptor agonist exposure.</p><p><strong>Participants/materials setting methods: </strong>We identified periconceptional liraglutide or semaglutide exposure (prescription redemption within 8 weeks before/after last menstrual period) using the National Prescription Register. Exposed pregnancies were stratified by maternal pre-existing diabetes status and compared with propensity score-matched unexposed controls. Propensity score matching incorporated maternal age, BMI, smoking, geographic region, education, pre-existing diabetes, parity, and temporal factors.</p><p><strong>Main results and the role of chance: </strong>Before adjustment, exposed women had higher rates of multiple obstetric complications. After propensity score matching, only the risk of preterm birth remained elevated for exposed women. This increased risk was confined to women using GLP-1 receptor agonists for diabetes treatment (liraglutide aOR 1.70, 95% CI 1.17-2.48; semaglutide aOR 1.84, 95% CI 1.24-2.71). Among women without pre-existing diabetes using these medications for weight management, no association with preterm birth was observed (liraglutide aOR 1.01, 95% CI 0.58-1.76; semaglutide aOR 0.71, 95% CI 0.30-1.70).</p><p><strong>Limitations reasons for caution: </strong>Study limitations include the absence of data regarding medication compliance post prescription redemption, potential misclassification due to parallel importation, and the inability to control for unmeasured confounding factors. The observational design cannot establish causality. Most semaglutide weight-loss prescriptions occurred late in the study period, limiting long-term follow-up data.</p><p><strong>Wider implications of the findings: </strong>The results are compatible with t","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag015"},"PeriodicalIF":8.6,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12995393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482410","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 progesterone timing on live birth rates in day-6 blastocyst frozen-thawed embryo transfer cycles: a randomized controlled trial.","authors":"Ruiqiong Zhou, Zhaoyi Wang, Mei Dong, Li Huang, Nianjun Su, Quan Qi, Ju Huang, Fuxiang Wang, Xiqian Zhang, Fenghua Liu","doi":"10.1093/hropen/hoag023","DOIUrl":"10.1093/hropen/hoag023","url":null,"abstract":"<p><strong>Study question: </strong>What is the optimal timing of progesterone exposure to achieve live births for day-6 blastocysts in artificial frozen-thawed embryo transfer (FET) cycles?</p><p><strong>Summary answer: </strong>Live birth rates (LBRs) were comparable between day-6 and day-7 progesterone supplementation for day-6 blastocyst transfers in artificial FET cycles.</p><p><strong>What is known already: </strong>In artificial FET cycles, embryo-endometrium synchrony is primarily determined by the duration of progesterone exposure. Although blastocyst transfer is conventionally performed on day six of progesterone supplementation, the optimal duration of progesterone exposure remains uncertain. Available evidence suggests that the window of implantation may be relatively flexible for day-5 blastocysts, whereas day-6 blastocysts may have a distinct and potentially narrower window of implantation. However, prospective data evaluating different durations of progesterone exposure for blastocyst transfer-particularly for day-6 blastocysts-remain limited.</p><p><strong>Study design size duration: </strong>This open-label randomized controlled trial (RCT) included 338 women undergoing FET in artificial cycles who had exclusively day-6 blastocysts available for transfer at enrolment. These blastocysts originated either from IVF/ICSI cycles with exclusive day-6 blastocyst formation or from previous embryo transfer attempts in which only day-6 blastocysts remained cryopreserved. Participants were randomized prior to progesterone initiation to undergo blastocyst transfer on 6 or 7 days of progesterone supplementation. Recruitment occurred between September 2022 and May 2024, with final follow-up completed in March 2025.</p><p><strong>Participants/materials setting methods: </strong>A total of 338 participants were randomized equally to undergo blastocyst transfer on either Day 6 or Day 7 of progesterone supplementation. The primary outcome was LBR. Secondary outcomes included singleton and twin LBR, biochemical and clinical pregnancy, pregnancy loss, good birth outcome, and maternal and neonatal outcomes. The primary analysis followed the intention-to-treat (ITT) principle, with a per-protocol (PP) analysis also performed. Post hoc analyses included multivariable regression and subgroup analyses.</p><p><strong>Main results and the role of chance: </strong>In the ITT analysis, the LBR was 45.0% (76/169) in the day-6 progesterone group and 40.2% (68/169) in the day-7 group (absolute difference, -4.7% [95% CI, -15.3% to 5.8%]; adjusted relative ratio (RR), 0.90 [95% CI, 0.70-1.14], <i>P </i>= 0.367). Rates of biochemical pregnancy, clinical pregnancy, pregnancy loss, and good birth outcome were comparable between groups. No differences were observed in maternal and neonatal outcomes. PP analysis yielded results consistent with the ITT analysis. Exploratory post hoc subgroup analyses identified a significant interaction between blastocyst expansion sta","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag023"},"PeriodicalIF":8.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576808","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":"Clinical and genetic basis of congenital gonadotropin deficiency.","authors":"Yi Wang, Jing Zhai, Imen Habibi, Zofia Kolesińska, Fernanda de Azevedo Correa, Yassine Zouaghi, Adelina Ameti, Alexia Boizot, Cecilia Perdices-López, Tommaso Todisco, Nicolas J Niederländer, James S Acierno, Andrea Messina, Federico Santoni, Nelly Pitteloud","doi":"10.1093/hropen/hoag017","DOIUrl":"10.1093/hropen/hoag017","url":null,"abstract":"<p><strong>Study question: </strong>What is the clinical and genetic overlap across subtypes of congenital gonadotropin (Gn) deficiency?</p><p><strong>Summary answer: </strong>This study reveals substantial clinical and genetic overlap among Gn deficiency disorders, with shared genetic and developmental features across congenital hypogonadotropic hypogonadism (CHH), combined pituitary hormone deficiency (CPHD), and syndromic forms of Gn deficiency.</p><p><strong>What is known already: </strong>Congenital Gn deficiency includes a subset of hypogonadotropic hypogonadism (HH) and can result from defects at the level of the hypothalamus or the pituitary. It includes (i) CHH, further classified into normosmic CHH (nCHH) and Kallmann syndrome (KS); (ii) CPHD; and (iii) syndromic forms such as CHARGE syndrome and septo-optic dysplasia (SOD).</p><p><strong>Study design size duration: </strong>The study included all probands with Gn deficiency recruited at a tertiary care center between 2011 and 2024 (n = 568), including 276 KS, 247 nCHH, 29 CPHD, and 16 syndromic Gn deficiency cases. All individuals underwent detailed clinical phenotyping followed by DNA sequencing.</p><p><strong>Participants/materials setting methods: </strong>Genetic analysis focused on pathogenic (P) and likely pathogenic (LP) variants and variants of uncertain significance (VUS) within established CHH and CPHD genes. Oligogenicity was assessed in the CHH/syndromic HH cohort (n = 523) compared with controls from 1000 Genomes (n = 601). Genetic overlap among CHH, CPHD, and syndromic Gn deficiency was systematically investigated.</p><p><strong>Main results and the role of chance: </strong>Cleft lip/palate, dental agenesis, and ear abnormalities were recurrent across all Gn-deficient groups. Notably, some CPHD and SOD patients exhibited anosmia and a preserved Gn response to LH-releasing hormone (LHRH) stimulation, indicating a hypothalamic component to their HH. Rare variants in CHH genes were identified in 53% of KS probands (40% P/LP, 13% VUS) and 33% of nCHH probands (23% P/LP, 10% VUS). <i>FGFR1</i>, <i>ANOS1</i>, and <i>PROKR2</i> were most frequently mutated in KS, while <i>GNRHR</i>, <i>FGFR1</i>, and <i>KISS1R</i> predominated in nCHH. Oligogenic inheritance was detected in 15% of CHH cases, with variants in <i>FGFR1</i> being most commonly involved. Importantly, a substantial proportion (14%) of CHH patients without a molecular diagnosis carried rare variants predicted to be P or LP in genes typically associated with CPHD (e.g. <i>ROBO1</i>, <i>BRAF</i>, <i>FAT2</i>, and <i>DCHS2</i>). Conversely, several CHH-associated genes such as <i>FGFR1</i> and <i>FGF8</i>, already implicated in CPHD, were also identified in patients with CPHD and syndromic GN deficiency, further supporting a shared genetic architecture between CHH and CPHD.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations reasons for caution: </strong>Non-coding and copy number variants were not st","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag017"},"PeriodicalIF":8.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505672","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":"Menstrual fluid-derived small extracellular vesicles: a novel reservoir with distinct molecular signatures and implications for endometriosis etiopathology.","authors":"Vicente Peragallo-Papic, Paz Cerda-Castro, Aliosha I Figueroa-Valdés, Hugo E Tobar, Patricia Valdebenito, Manuel B Donoso, Benjamín Bustos, Javiera Yakcich, Reyna Peñailillo, Gino Nardocci, Stephanie Acuña-Gallardo, Sebastián E Illanes, Francisca Alcayaga-Miranda, Lara J Monteiro","doi":"10.1093/hropen/hoag020","DOIUrl":"10.1093/hropen/hoag020","url":null,"abstract":"<p><strong>Study question: </strong>Can the transcriptomic profile of small extracellular vesicles (sEVs) derived from menstrual fluid (MF) provide preliminary insights into their potential roles as biomarkers and mediators in endometriosis (EM) progression?</p><p><strong>Summary answer: </strong>MF-derived sEVs from EM patients display altered molecular signatures and enhanced proangiogenic activity <i>in vitro</i>, suggesting their potential involvement in EM pathophysiology.</p><p><strong>What is known already: </strong>EM is a chronic gynecological disorder affecting ∼10% of reproductive-age women, associated with pain, infertility, and delayed diagnosis. sEVs carry cargo that resembles their cellular origin, making them promising biomarkers for various diseases. While sEVs have previously been isolated from MF and their protein content has been analyzed, their transcriptomic content and biological function remain unexplored.</p><p><strong>Study design size duration: </strong>Two cross-sectional studies were conducted. The first compared MF-sEVs between nulliparous (n = 10) and multiparous (n = 12) women. The second compared MF-sEVs from EM patients (n = 10) and Controls (n = 11). Participants were recruited between 2021 and 2023 from a tertiary care center in Santiago, Chile.</p><p><strong>Participants/materials setting methods: </strong>MF from healthy (nulliparous and multiparous) and EM patients was self-collected using a menstrual cup on Day 2 of menstruation, and peripheral blood of a subset of healthy women was obtained by venipuncture. sEVs were isolated from the plasma fraction of MF and from peripheral blood plasma. Nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry were used to assess sEVs concentration, size, morphology, and tetraspanin expression. Next-generation sequencing was performed to analyze MF-derived sEVs' transcriptomic profiles, and endothelial tubulogenesis assays using human umbilical vein endothelial cells (HUVECs) assessed angiogenic function <i>in vitro</i>.</p><p><strong>Main results and the role of chance: </strong>MF-derived sEVs of healthy women were significantly more abundant than those isolated from their peripheral blood (<i>P </i>= 0.008), and they exhibited typical morphology and tetraspanin expression. Neither parity nor disease affected MF-sEVs' concentration or size; however, CD63 expression was significantly reduced in sEVs from nulliparous women and EM patients (<i>P </i>= 0.02). Transcriptomic analysis revealed unique mRNAs and long noncoding RNAs (lncRNAs) signatures that reflect their potential contribution to disease etiopathology. Functionally, MF-derived sEVs from EM patients (MF-EM-derived sEVs), significantly enhanced tubule formation <i>in vitro</i> (<i>P </i>< 0.05), indicating proangiogenic potential in EM.</p><p><strong>Large scale data: </strong>The raw sequencing data have been deposited in the NCBI GEO database under the accession number GSE310627.</p","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag020"},"PeriodicalIF":8.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13038252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596322","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":"Treatment of human oocytes with extracellular vesicles from follicular fluid during rescue <i>in vitro</i> maturation enhances maturation rates and modulates oocyte proteome and ultrastructure.","authors":"Sofia Makieva, Mara D Saenz-de-Juano, Carmen Almiñana, Stefan Bauersachs, Sandra Bernal-Ulloa, Min Xie, Ana G Velasco, Natalia Cervantes, Maike Sachs, Susanne E Ulbrich, Brigitte Leeners","doi":"10.1093/hropen/hoag021","DOIUrl":"10.1093/hropen/hoag021","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Could follicular fluid-derived extracellular vesicles (ffEVs) benefit human oocyte rescue &lt;i&gt;in vitro&lt;/i&gt; maturation (rIVM)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Supplementation of rIVM culture with ffEVs isolated from mature follicles enhanced oocyte maturation rates by &gt;20%, inducing changes in oocyte protein profile and organelle distribution.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;IVM involves the culture of immature germinal vesicle (GV) oocytes under set laboratory conditions to allow for their transition to mature metaphase II (MII) stage, which is confirmed by the extrusion of the first polar body. Efficient IVM could circumvent controlled ovarian stimulation (COS), reduce the cost and broaden the repertoire of infertility treatments. Animal studies suggest that extracellular vesicles (EVs), membranous nanosized vesicles containing different molecular content (e.g. nucleic acids, proteins) and present in the ovarian follicular fluid, could enhance oocyte maturation. The uptake of ffEVs by bovine, equine, and feline oocytes, but not human, has been demonstrated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Women undergoing transvaginal oocyte retrieval after COS (n = 83) were recruited to donate follicular fluid (n = 54 single follicles) and/or immature GV oocytes (n = 95). We aimed to: (i) define differences in the protein cargo of ffEVs derived from human follicles containing mature (MII-ffEVs, n = 10) versus immature (GV-ffEVs, n = 5; metaphase I MI-ffEVs, n = 5) oocytes, (ii) demonstrate the capacity of human GV oocytes to uptake MII-ffEVs and (iii) determine the effect of MII-ffEVs supplementation on oocyte maturation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;ffEVs were isolated by ultracentrifugation. The protein content of ffEVs was analysed by mass spectrometry. The uptake of fluorescently-labelled MII-ffEVs by GV oocytes (n = 15) was assessed by confocal microscopy. GVs were cultured for rIVM in a timelapse incubator with MII-ffEVs (n = 45 GVs) or without (n = 40 GVs), and extrusion of polar body denoted maturation. The impact of MII-ffEVs supplementation on IVM-matured oocytes was assessed through single-cell proteomics and the appearance of intracellular organelles upon transmission electron microscopy (TEM) analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;We identified 1340 proteins in ffEVs, with proteins such as F12, IGKV1-39, FREM2, and C1QC being significantly enriched in MII-ffEVs. GV oocytes internalized MII-ffEVs, and their supplementation for 48 h increased the oocyte maturation rate compared to control by 22.8 ± 9.4% (77.8% vs 55% maturation rate respectively; &lt;i&gt;P&lt;/i&gt;-value = 0.0372). Proteomic analysis of ffEV-supplemented mature oocytes (n = 5) revealed 56 differentially abundant proteins (DAPs) compared to non-supplemented mature oocytes (n = 5). Among them, 37 DAPs were in higher abundance in ffEVs-supplemented mature ooc","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag021"},"PeriodicalIF":8.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13037814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596407","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":"Evaluating the potential for sperm DNA fragmentation testing to guide the use of ICSI for couples with non-severe male infertility.","authors":"Yuanyuan Wang, Rui Wang, Ying Lian, Rui Yang, Jiangman Gao, Jianqiao Liu, Li Tang, Xiaoyan Liang, Yunxia Cao, Wen Li, Li Jin, Yimin Zhu, Junli Zhao, Guimin Hao, Huichun Wang, Ben W Mol, Rong Li, Jie Qiao","doi":"10.1093/hropen/hoag011","DOIUrl":"10.1093/hropen/hoag011","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;In couples with non-severe male infertility, can sperm DNA fragmentation index (DFI) testing serve as a biomarker to identify couples who would benefit from ICSI over conventional IVF, based on cumulative live birth rate?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our secondary analysis of a randomized clinical trial (RCT) indicated that sperm DFI testing has limited value in identifying couples who would benefit from use of ICSI over IVF, based on cumulative live birth rate.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;We recently demonstrated that in couples with non-severe male factor infertility, ICSI decreases cumulative live birth rates following the first transfer compared to IVF. However, it remains unclear whether sperm DFI testing can effectively guide treatment selection between ICSI and IVF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We used data of participants included in a randomized controlled trial comparing ICSI versus IVF in couples with non-severe male factor infertility. Participants had been recruited between April 2018 and November 2021 from seven centres in China, with follow-up outcomes collected as of 31 August 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;We included 953 of 2329 couples in whom the male partner had a baseline sperm DFI test from seven centres within the original RCT. The primary outcome was cumulative live birth, defined as a live birth following embryo transfers that occurred within 12 months after randomization within one oocyte retrieval cycle. The statistical analysis was performed based on an as-treated population, including 480 in the ICSI group and 473 in the IVF group. Multivariable fractional polynomial interaction analysis was performed to investigate non-linear interaction between DFI test and treatment effects of ICSI over IVF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The median values of sperm DFI were 18.8% (interquartile range [IQR]: 12.2%∼26.3%) in the ICSI group, and 18.4% (IQR: 12.6%∼25.1%) in the IVF group. In each quantile of sperm DFI (Q1: DFI &lt; 12.3%; Q2: 12.3≤DFI &lt; 18.6%; Q3: 18.6≤DFI &lt; 25.9%; Q4: DFI ≥ 25.9%), there were no significant differences of ICSI vs IVF on cumulative live birth (Q1: 36.7% vs 49.6%, adjusted odds ratio (aOR) = 0.61, 95% CI: 0.36 to 1.04; Q2: 51.8% vs 50.4%, aOR = 1.06, 95% CI: 0.60 to 1.84; Q3: 48.4% vs 56.3%, aOR = 0.78, 95% CI: 0.46 to 1.33; Q4: 45.2% vs 49.1%, aOR = 0.80, 95% CI: 0.47 to 1.37). Multivariable fractional polynomial interaction analysis showed no evidence of interaction between sperm DFI and the treatment effect of ICSI over IVF on cumulative live birth (&lt;i&gt;P&lt;/i&gt; = 0.298).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations and reasons for caution: &lt;/strong&gt;First, sperm DFI testing was not routinely performed across all trial sites. Second, this study may be underpowered to detect differences in some outcomes, especially total fertilization failure, due to the very small number of e","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag011"},"PeriodicalIF":8.6,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470175","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":"Vaginal microbial community state types fail to predict IVF outcomes, whereas <i>Ureaplasma parvum</i> and <i>Lactobacillus iners</i> are negative predictors of implantation, clinical pregnancy, and live birth.","authors":"Simon Graspeuntner, Mariia Lupatsii, Noemi Hamala, Antonia Masuch, Marion Depenbusch, Iris Pfeffer, Askan Schultze-Mosgau, Tanja K Eggersmann, Jan Rupp, Georg Griesinger","doi":"10.1093/hropen/hoag018","DOIUrl":"10.1093/hropen/hoag018","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are previously proposed vaginal microbial community state types (CSTs) valid predictors of IVF success, or do alternative microbial signatures provide stronger associations?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Previously proposed CSTs as predictors of implantation, clinical pregnancy, and live birth were not confirmed, while an interaction between &lt;i&gt;Ureaplasma parvum&lt;/i&gt; and &lt;i&gt;Lactobacillus iners&lt;/i&gt; emerged as a strong negative predictor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Infertility affects 17% of the global population. Only one-third of treatment cycles of assisted reproductive technologies result in embryo implantation, and even fewer lead to clinical pregnancy or live births. While early findings have spurred the development of microbiome-based tests for success prediction, evidence on supporting their reliability remains inconclusive.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This prospective, single-centre study aimed to validate existing, and identify better, microbial predictors of infertility treatment outcomes. A cohort of 266 infertile female patients (age 18-45 years) undergoing a frozen-thawed embryo transfer cycle in an anovulatory regimen (i.e. a cycle with transfer of an embryo following a previous oocyte retrieval, fertilization, and freezing of embryos) was recruited for the study within a timeframe from May 2017 to March 2019.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The female, infertile patients, aged 18-45 years, were undergoing routine care. Vaginal swabs were taken prior to embryo transfer and subjected to DNA isolation for 16S-based microbiota analysis. Extended demographic and treatment data were recorded. Clinical outcomes were defined as: (i) implantation, confirmed by a positive hCG test, (ii) clinical pregnancy, and (iii) live birth (defined as the birth of a viable infant). Sequencing data were processed in mothur following established pipelines, and microbial composition (taxonomy) as well as microbial diversity (dissimilarity analyses) were determined using the open-source software R. A prediction model for implantation success was built using binary logistic regression based on abundance of putatively predictive microbial taxa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;This study suggests that vaginal microbial CSTs, alpha-diversity, and the ratio of dominant &lt;i&gt;Lactobacillus&lt;/i&gt; species do not correlate in statistical terms or in a clinically meaningful manner with implantation and clinical pregnancy (as a surrogate for endometrial receptivity) or with live birth (as a surrogate for ongoing pregnancy viability). However, &lt;i&gt;Ureaplasma parvum&lt;/i&gt; and &lt;i&gt;Lactobacillus iners&lt;/i&gt; abundances were identified as negative predictors of embryo implantation, clinical pregnancy, and live birth. A subset of women colonized by these taxa experienced drastically reduced embryo implantation and completely failed to achieve cl","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag018"},"PeriodicalIF":8.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13037765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596536","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":"Comparative effect of different surgical treatments for ovarian endometrioma on anti-Müllerian hormone levels: a systematic review and network meta-analysis.","authors":"Konstantinos Nirgianakis, Dimitrios Rafail Kalaitzopoulos, Nikolaus Fadinger, Michael D Mueller, Chiara Gastaldon","doi":"10.1093/hropen/hoag019","DOIUrl":"10.1093/hropen/hoag019","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Which surgical technique for endometrioma has the least detrimental effect on ovarian reserves?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Drainage with hemostatic sealants and cystectomy with ovarian suturing were associated with relatively smaller anti-Müllerian hormone (AMH) declines 3-6 months postoperatively; however, further research assessing fertility and long-term outcomes is needed to clarify the safety and efficacy of these techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Ovarian endometriomas are common in women of reproductive age and can affect their ability to have a pregnancy. Surgical removal of the endometrioma is one of the strategies to favor pregnancy, with different possible surgical techniques. However, damage to the ovary can result in lower ovarian reserve. To date, it is uncertain what surgical technique provides the best balance between efficacy and safety.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We conducted a systematic review and network meta-analysis (NMA), searching PubMed, Embase, and Cochrane Register of Trials for randomized controlled trials (RCTs) that compared the impact of different surgical techniques for endometrioma on ovarian reserves (measured with the AMH level or antral follicle count (AFC)) from inception to June 2024. All relevant peer-reviewed studies were included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The primary outcome was ovarian reserve, measured by the change in AMH levels (ng/ml) at 3-6 months after the treatment. Secondary outcome was the change in AFC at 3-6 months after the surgery. We assessed the quality of included studies with the Cochrane risk of bias tool 2 and performed an NMA, comparing the head-to-head effect of different surgical strategies, calculating mean differences (MDs) and 95% CIs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;21 RCTs with 1519 participants, comparing 8 different surgical techniques (cystectomy with ovarian suturing, cystectomy with hemostatic sealants, cystectomy with tranexamic acid, cystectomy alone, drainage with hemostatic sealants, drainage alone, laser ablation, and transvaginal sclerotherapy) were included in the systematic review and 17 studies in the NMA. Regarding AMH at 3-6 months after surgery, drainage with hemostatic sealants (MD: 0.96; 95% CI: 0.60-1.33; high level of certainty), cystectomy with ovarian suturing (MD: 0.69; 95% CI: 0.39-0.98; moderate certainty), and cystectomy with hemostatic sealants (MD: 0.37; 95% CI: 0.12-0.61; low certainty) resulted in higher values of AMH compared with cystectomy alone. Regarding AFC at 3-6 months after surgery, laser ablation showed higher values of AFC (MD: 2.30; 95% CI: 0.20-4.40) compared with cystectomy alone at 3-6 months after surgery, followed by cystectomy with ovarian suturing (MD: 1.88; 95% CI: 0.98-2.79). The overall risk of bias of the included studies was low. The Confidence in Network Meta-Analy","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag019"},"PeriodicalIF":8.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984728","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}