Human reproduction open最新文献

{"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":"https://doi.org/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":11.1,"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":"Thank you to our reviewers - 2025.","authors":"","doi":"10.1093/hropen/hoag022","DOIUrl":"https://doi.org/10.1093/hropen/hoag022","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag022"},"PeriodicalIF":11.1,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724734","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":"Improving governance of IVF and oncofertility practice in the USA: a call to action.","authors":"Mahmoud Salama, Teresa K Woodruff","doi":"10.1093/hropen/hoag033","DOIUrl":"https://doi.org/10.1093/hropen/hoag033","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag033"},"PeriodicalIF":11.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870774","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":"Effectiveness of 12-month GnRH antagonist treatment for endometriosis-associated pain: driven by reduction in uterine bleeding?","authors":"Thomas M D'Hooghe","doi":"10.1093/hropen/hoag031","DOIUrl":"https://doi.org/10.1093/hropen/hoag031","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag031"},"PeriodicalIF":11.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824369","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":"Linzagolix, with and without add-back therapy, in women with endometriosis-associated pain: results from EDELWEISS 6, a double-blind randomized extension and withdrawal study.","authors":"Jacques Donnez, Christian M Becker, Felice Petraglia, Andrew W Horne, Sven Becker, Stefan P Renner, Francisco Carmona Herrera, Hugh S Taylor, Maciej Paszkowski, Elke Bestel, Satoshi Hori, Marie-Madeleine Dolmans","doi":"10.1093/hropen/hoag030","DOIUrl":"https://doi.org/10.1093/hropen/hoag030","url":null,"abstract":"<p><strong>Study question: </strong>Was the efficacy of linzagolix, observed at 6 months in women with endometriosis-associated pain, maintained when administered for an additional 6 months?</p><p><strong>Summary answer: </strong>Efficacy from this extension study complements the results of the main trial, by showing that linzagolix is effective at reducing endometriosis-associated pain for a majority of women.</p><p><strong>What is known already: </strong>In the pivotal EDELWEISS 3 randomized controlled trial, the efficacy and safety of 24 weeks of once-daily oral linzagolix (a GnRH antagonist) were reported in women with endometriosis-related pain. Risks of bone mineral density (BMD) loss and vasomotor symptoms were minimized in both groups.</p><p><strong>Study design size duration: </strong>EDELWEISS 3 was a prospective, randomized, double-blind study. Subjects completing the 6-month treatment period in EDELWEISS 3 were invited to participate in the present extension study: EDELWEISS 6. Only subjects who had completed the full 6-month treatment course in the main study and who met the inclusion criteria were eligible for entry into the extension study. Among 486 patients who completed the 6-month study, 353 participated in the extension study from March 2020 to February 2023. The current extension study started at Month 6 of the main EDELWEISS 3 phase-3 trial. Upon the end of treatment in the extension study (6-month treatment period from Month 6 to Month 12), subjects entered a post-treatment follow-up period of 6 months. The current report describes outcomes from the extension treatment period (up to 12 months) and subsequent follow-up of 6 months with no investigational medicinal product. The co-primary endpoints were the reduction in dysmenorrhea and non-menstrual pelvic pain at Month 12.</p><p><strong>Participants/materials setting methods: </strong>Premenopausal women with moderate-to-severe endometriosis who previously completed the full 6-month treatment period in the main study and met the inclusion criteria were eligible for the extension study. All subjects (n = 353), whether given placebo or not in the main study, received either 75 mg linzagolix alone or 200 mg combined with hormonal add-back therapy (ABT) once daily for the additional 6 months, i.e. those who were given a placebo during the main study were randomized to either group and those who had received active treatment continued with the same treatment (placebo/75 mg linzagolix [n = 57], placebo/200 mg linzagolix plus ABT [n = 57], 75 mg linzagolix [n = 118], and 200 mg linzagolix plus ABT [n = 121]). Pain was measured daily on a verbal rating scale and recorded in an electronic diary. The trial was performed in clinics and university hospitals in the USA and Europe.</p><p><strong>Main results and the role of chance: </strong>By Month 12, of the 353 women who were treated and analyzed, the proportion of subjects with a significant reduction in dysmenorrhea and stable or de","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag030"},"PeriodicalIF":11.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824407","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":"Perfluorooctane sulfonate (PFOS) in follicular fluid and human granulosa cell dysfunction: a physiologically based toxicokinetic model translation of long-term low-level <i>in vitro</i> exposure data.","authors":"Tamara Tomanic, Dragana Samardzija Nenadov, Sava Radovic Pletikosic, Bojana Stanic, Darija Obradovic, Sasa Lazovic, Nebojsa Andric","doi":"10.1093/hropen/hoag029","DOIUrl":"https://doi.org/10.1093/hropen/hoag029","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are bioactive human-equivalent doses (HEDs) of perfluorooctane sulfonate (PFOS), derived from long-term low-level &lt;i&gt;in vitro&lt;/i&gt; exposure of human granulosa cells comparable to HEDs inferred from follicular fluid PFOS concentrations in women undergoing ART and in occupationally exposed women?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The bioactive HEDs overlapped with and, in some cases, were lower than the median HEDs inferred from follicular fluid PFOS concentrations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;PFOS exposure is a growing public health concern, with evidence suggesting adverse female reproductive effects. However, the relevance of current human exposure levels to granulosa cell function remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Four independent vials of human granulosa cells (HGrC1 cells) were thawed and expanded into separate flasks (biological replicates). Cells were allocated to four experimental groups and exposed to PFOS (0.01, 0.1, or 1 µM) or vehicle control (0.05% DMSO) for up to 12 weeks, with re-dosing at each passage. Different apical endpoints, along with transcriptomic changes, were evaluated at designated time points. Clinical relevance of PFOS risk to human granulosa cells was assessed by integrating experimental data with physiologically based toxicokinetic (PBTK) modeling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Viability of HGrC1 cells was assessed using the Alamar Blue assay. Estradiol and progesterone secretion were quantified by enzyme-linked immunosorbent assay. Flow cytometry was used to determine the proportions of live, apoptotic and necrotic cells, as well as cell cycle distribution. Global mRNA expression was assessed by DNA nanoball sequencing technology (DNBSEQ), whereas pathway-level molecular functions were derived using bioinformatic tools. Benchmark concentrations (BMCs) were calculated from key endpoints with concentration-dependent responses and used to estimate HEDs via PBTK modeling. These HEDs were compared with HEDs inferred from follicular fluid PFOS levels reported in the literature to derive bioactivity exposure ratios (BERs) and assess relevance to human exposure.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;In HGrC1 cells, long-term PFOS exposure altered steroidogenesis, apoptosis/necrosis, cell cycle distribution (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), and gene expression (at least 2-fold change, &lt;i&gt;Q&lt;/i&gt;-value ≤ 0.05). Median transcriptomic HEDs were 18.1 (95% CI: 1.1-35.1) and 17.5 ng/kg bw/day (95% CI: 8-27.1) for 6- and 12-week exposures, respectively, with corresponding 5th percentile HEDs of 3.7 ng/kg bw/day (95% CI: 0.4-9.3) and 1.4 ng/kg bw/day (95% CI: 0.5-3.5). Pathway-level HEDs ranged from 2.8 to 24.1 ng/kg bw/day, with eicosanoid synthesis showing the greatest sensitivity. HEDs for apical endpoints ranged from 0.4 to 203 ng/kg bw/day, with the sub-G&lt;sub&gt;1&lt;/sub&gt; cell cycle phase being most sensi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag029"},"PeriodicalIF":11.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791245","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":"Reproductive fluids, commercial media, and organoids: bridging the gap in IVF culture systems.","authors":"Nathaly Hernández-Díaz, Sergio Navarro-Serna, Pilar Coy, Vicente Pérez-García","doi":"10.1093/hropen/hoag028","DOIUrl":"https://doi.org/10.1093/hropen/hoag028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Although assisted reproductive technologies have enabled millions of births worldwide, &lt;i&gt;in vitro&lt;/i&gt; embryo culture systems remain a simplified and static approximation of the highly dynamic environment of the female reproductive tract. Commercial culture media lack many of the biochemical, biophysical, and temporal features of oviductal and uterine fluids, including hormonally regulated secretions, extracellular vesicles, and epithelial-derived signaling cues. These limitations are increasingly linked to altered embryonic programming, suboptimal implantation, and subtle but persistent effects on perinatal and long-term health outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;This review critically examines how reproductive tract-derived factors and advanced three-dimensional (3D) &lt;i&gt;in vitro&lt;/i&gt; models can improve the physiological relevance of embryo culture systems in human ART. We focus on the biological roles of native reproductive fluids and extracellular vesicles and the emerging contribution of reproductive tract organoids and assembloids as sources of defined, stage-specific secretomes capable of bridging the gap between artificial and &lt;i&gt;in vivo&lt;/i&gt;-like conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science for studies published up to March 2026 using terms related to embryo culture media, reproductive fluids, extracellular vesicles, organoids, implantation, and human IVF. Evidence from human studies and relevant animal models was included to provide mechanistic insight and translational context, with emphasis on experimental approaches directly informing ART practice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;Reproductive tract fluids contain complex mixtures of proteins, metabolites, lipids, and extracellular vesicles that regulate fertilization, early embryonic development, epigenetic programming, and maternal-embryo communication. While supplementation of embryo culture media with native fluids improves embryo quality and developmental competence in multiple species, clinical translation is constrained by donor variability, biosafety concerns, and limited standardization. Reproductive tract 3D cell cultures represent a promising complementary approach, as they can recapitulate key aspects of epithelial architecture, hormonal responsiveness, and secretory activity under controlled conditions. Organoid-derived secretomes, including extracellular vesicle cargo, have been shown to support reproductive processes such as sperm viability, trophoblast function, immune modulation, and endometrial receptivity. Moreover, advances in epithelial-stromal assembloids and microengineered platforms further enhance physiological fidelity by partially restoring multicellular interactions relevant to implantation-related signaling. However, these systems also present important limitations, including variability between lines, incomplete c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag028"},"PeriodicalIF":11.1,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791186","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":"IVF in endometriosis: emerging evidence of exacerbation of pelvic pain and potential predictors.","authors":"Jonas Vibert, Eliane Maalouf, Jean-Marie Wenger, Antonio Mercorio, Giuseppe Benagiano, Nicola Pluchino","doi":"10.1093/hropen/hoag027","DOIUrl":"https://doi.org/10.1093/hropen/hoag027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does IVF worsen pelvic pain in women with endometriosis?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Nearly half of women with endometriosis reported perceived worsening of pelvic pain after IVF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Prior studies generally suggested no IVF-related pain worsening, but few assessed delayed flares or longer-term trajectories.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;International cross-sectional study based on an online survey conducted between September 2024 and April 2025 including 546 respondents.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Women aged ≥18 years with surgically or imaging-confirmed endometriosis and at least one completed IVF cycle. A 25-item questionnaire captured demographics, reproductive history, comorbidities, and patient-reported pain trajectories before, during, and after IVF. The primary outcome was perceived worsening of pelvic pain after IVF (patient-reported outcome measure; PROM). Secondary outcomes were worsening of dysmenorrhoea and dyspareunia. Group comparisons and exploratory multivariable logistic regressions were performed. Predictor analyses were exploratory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Among 546 respondents, 48.9% reported worsening pelvic pain after IVF, 49.1% reported worsening dysmenorrhoea, and 35.5% worsening dyspareunia. Current pain scores were significantly higher in women reporting worsening versus no worsening (all &lt;i&gt;P&lt;/i&gt; &lt; 0.001). In multivariable analyses, immediate post-cycle pain flare emerged as the strongest and most consistent predictor across all pain outcomes, independently associated with worsening of pelvic pain (adjusted odds ratio [aOR] 5.91, 95% CI 3.88-9.14), dysmenorrhoea (aOR 4.03, 95% CI 2.08-8.05), and dyspareunia (aOR 3.17, 95% CI 2.07-4.90) (all &lt;i&gt;P&lt;/i&gt; &lt; 0.001). For the primary outcome, reporting oocyte retrieval as the most painful IVF step (aOR 0.53, 95% CI 0.31-0.88; &lt;i&gt;P&lt;/i&gt; = 0.016) and achieving a live birth after IVF (aOR 0.63, 95% CI 0.42-0.92; &lt;i&gt;P&lt;/i&gt; = 0.020) were independently associated with lower odds of pelvic pain worsening. In secondary outcome models, live birth was associated with lower odds of dysmenorrhoea worsening, while bladder pain syndrome/interstitial cystitis independently predicted worsening of dyspareunia. A formal response rate could not be calculated due to open online dissemination without a known denominator.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Self-reported, retrospective data are prone to recall and selection bias, and the cross-sectional design precludes causal inference. Recruitment via associations and social media without a denominator limits generalizability, absence of baseline pain scores impedes assessment of change, and incomplete capture of peri-IVF hormonal regimens may confound results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;IVF may not be pain-neutral in e","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag027"},"PeriodicalIF":11.1,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724749","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":"Reclaiming 'abnormal' embryos after preimplantation genetic testing for aneuploidy: patients' perspectives on transferring embryos against prior institutional advice.","authors":"Shizuko Takahashi, Sonia Gayete-Lafuente, Elizabeth Choong, Lara Guijarro-Baude, David H Barad, Pasquale Patrizio, Michael Dunn, Julian Savulescu, Norbert Gleicher","doi":"10.1093/hropen/hoag025","DOIUrl":"https://doi.org/10.1093/hropen/hoag025","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How do patients make sense of and justify the transfer of embryos labelled 'abnormal' by preimplantation genetic testing for aneuploidy (PGT-A)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Patients described a process of unlearning the authority of genetic testing and reframing their decisions as morally reasoned acts of reproductive agency-a reclaiming of possibility amid biomedical exclusion.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;PGT-A is widely used in IVF, although its clinical utility and interpretation remain debated, and its claimed benefit on cumulative live birth rates unproven. Many clinics refuse transfer of embryos labelled 'abnormal', despite reports of healthy live births following transfer of selected embryos labelled 'mosaic' or 'aneuploid'.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Qualitative retrospective study of 21 participants (15 women and 6 men) conducted between 2019 and 2025 at a private fertility clinic associated with a research university in New York City, NY, USA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Participants had previously been denied transfer of embryos labelled 'abnormal' by PGT-A at multiple clinics and sought care at the study site. Semi-structured interviews were conducted, audio-recorded, transcribed verbatim, and analysed using inductive, reflexive thematic analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Among 21 participants, transfer outcomes included 6 healthy births following transfers of embryos labelled 'abnormal', 1 ongoing, 4 first-trimester miscarriages, 1 chemical pregnancy, and 12 failed implantations. One overarching theme 'reclaiming possibility', spanning four interrelated phases, was identified: (i) reassessing scientific authority of PGT-A; (ii) navigating institutional and relational constraints; (iii) embracing moral responsibility to give, or withhold, embryos a chance; and (iv) retrospective/anticipatory validation through a no-regrets stance. Participants resisted exclusionary classifications, pursued transfer despite refusals, and made sense of known, unknown, or adverse outcomes without equating results with the test's predictive accuracy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Participants were self-selected from a single clinic that was willing to consider such embryo transfers; therefore, the findings may have limited transferability to other settings or to patients who accepted an original institutional transfer refusal.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;Patients' narratives challenge assumptions that PGT-A results are determinative of embryo viability and highlight the ethical complexity of categorical transfer refusals by clinics. These findings support the need for transparent pre-test counselling, explicit institutional policies on embryo transfer, and patient-led pathways under robust informed consent. Integrating uncertainty-aware counse","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag025"},"PeriodicalIF":11.1,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678983","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":"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":"https://doi.org/10.1093/hropen/hoag024","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;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?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;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":11.1,"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}