Human reproduction最新文献

{"title":"Deep immune profiling of endometrial and peripheral blood cells in endometriosis.","authors":"A Kisovar, M Buttenschoen, Q Obrigewitch, K Powell, P Klenerman, K Zondervan, C M Becker, I E Granne, J H Southcombe","doi":"10.1093/humrep/deag090","DOIUrl":"10.1093/humrep/deag090","url":null,"abstract":"<p><strong>Study question: </strong>How is endometrial and systemic immunity modulated throughout the menstrual cycle and are there changes in women with endometriosis?</p><p><strong>Summary answer: </strong>Endometriosis is associated with reduced endometrial early natural killer (NK) cells and increased mucosal-associated invariant T (MAIT)-like CD8+ T cells, with cyclical variation.</p><p><strong>What is known already: </strong>The endometrial mucosa contains innate and adaptive immune cells that fluctuate across the menstrual cycle. Immune dysregulation is found in endometriosis, however few studies have broadly assessed endometrial immune single-cell proteome phenotypes.</p><p><strong>Study design, size, duration: </strong>This observational cross-sectional immune phenotyping study included 40 participants (28 with surgically confirmed endometriosis and 12 controls).</p><p><strong>Participants/materials, setting, methods: </strong>Endometrial and peripheral blood samples were analysed by spectral flow cytometry using a 36-parameter immune phenotyping panel and a 13-parameter MAIT-specific panel. Totals of 1 950 292 circulating and 1 023 215 endometrial immune cells were profiled. Full-thickness uterine biopsies (n = 3) underwent multiplex immunohistochemical imaging to assess spatial organization across the menstrual cycle.</p><p><strong>Main results and the role of chance: </strong>Compared with controls, patients with endometriosis exhibited decreased endometrial early NK cells (P.adj = 0.006, log2FC = -1.369) and increased MAIT-like CD8+ T cells (CD161+CD8+CD3+) (P.adj = 0.033, log2FC = 1.415). The MAIT cells (CD161+Va7.2+CD3+) peaked during ovulation and the implantation window (P.adj < 0.05). Peripheral immunity also showed cyclical variation with increased early NK cells (P.adj = 0.001, log2FC = 1.052) and decreased effector CD4 T (P.adj = 0.002/log2FC = -2.010) and effector CD8 T cells (P.adj = 0.002, log2FC = -1.180) in the endometriosis group.</p><p><strong>Limitations, reasons for caution: </strong>The cytometric panel design was biased towards acquired immunity, and the endometriosis patient sample size prevented subtype analysis.</p><p><strong>Wider implications of the findings: </strong>MAIT cell dysregulation represents a novel feature of endometriosis, potentially contributing to subfertility and providing new avenues for therapeutic development.</p><p><strong>Study funding/competing interest(s): </strong>This study was funded by the Nuffield Department of Women's and Reproductive Health, University of Oxford, and also supported from the University of Oxford Medical Sciences HIDI Internal Fund Award (0010398), Academy of Medical Science Award (SBF007100078) and, British Society for Immunology Career Enhancing Grant. C.M.B. has a consultancy role with ObsEva, Theramex, Roche Diagnostics, Sumitovant, Gedeon Richter, Gesyntha, and they have Research Grants from Bayer, Gesyntha, and Serac Life Services. K.Z. is a Board member (non","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1324-1337"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163011","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":"Natural versus artificial cycle for endometrial preparation in ovulatory women undergoing frozen-thawed embryo transfer: a randomised controlled trial.","authors":"B Geysenbergh, S Debrock, S Lie Fong, A Vanhie, C Tomassetti, C Bafort, L Meeuwis, S Neyens, S Pelckmans, A Laenen, J Vriens, P De Loecker, E Dancet, K Peeraer","doi":"10.1093/humrep/deag095","DOIUrl":"10.1093/humrep/deag095","url":null,"abstract":"<p><strong>Study question: </strong>Does a natural cycle result in higher clinical pregnancy rates (CPR) with foetal heartbeat compared to an artificial cycle for frozen-thawed embryo transfer (FET) preparation in ovulatory women?</p><p><strong>Summary answer: </strong>The CPR with foetal heartbeat did not differ between natural and artificial cycles in ovulatory women undergoing FET.</p><p><strong>What is known already: </strong>Several protocols for endometrial preparation have been developed for the increasing number of FET cycles in reproductive medicine. In natural cycle FET (NC-FET), spontaneous ovulation is used to time the embryo thawing and transfer, while in artificial cycle FET (AC-FET), endometrial preparation involves sequential oestrogen and progesterone administration. Current evidence on pregnancy rates does not favour one regimen over the other in women with regular ovulatory cycles.</p><p><strong>Study design, size, duration: </strong>We conducted a multicentre, open-label, randomised trial comparing NC-FET with AC-FET across five Belgian fertility centres. Between October 2018 and October 2024, 561 women were randomised (1:1) using a computer-generated allocation after written informed consent. The primary outcome was CPR with foetal heartbeat per cycle analysed on an intention-to-treat basis. Secondary outcomes included endometrial thickness, number of clinic visits for FET cycle monitoring and the rates of (biochemical) pregnancy, ongoing pregnancy, live birth, miscarriage, ectopic pregnancy, multiple pregnancy and cycle cancellation. Obstetric outcomes were recorded for all ongoing pregnancies.</p><p><strong>Participants/materials, setting, methods: </strong>Women aged 18-45 with regular ovulatory cycles and normal uterine cavities undergoing FET after vitrification and warming of one or two day-3 embryos or blastocysts were included. In NC-FET, spontaneous ovulation was detected by serial ultrasounds and serum LH and oestradiol measurements. In AC-FET, oestradiol valerate (6 mg/day) was administered from cycle day 2 (increased to 8 mg/day after 1 week if endometrial thickness was <7 mm) and micronized progesterone (600 mg/day) was initiated once endometrial thickness reached ≥7 mm.</p><p><strong>Main results and the role of chance: </strong>Clinical pregnancy rates with foetal heartbeat were similar between NC-FET and AC-FET in both intention-to-treat (33.1% [94/284] vs 28.9% [80/277]; RR 1.15, 95% CI 0.89, 1.47) and as-treated analyses (34.3% [97/283] vs 31.8% [77/242]; RR 1.08, 95% CI 0.85, 1.38). Cycle cancellations were less frequent in NC-FET (3.9% vs 9.4%; RR 0.41, 95% CI 0.21, 0.82), but NC-FET required more monitoring visits (mean 3.0 vs 2.4; P = 0.0002). Caesarean section was more common after AC-FET (42.7% vs 20.2%; P = 0.003). Other reproductive, obstetric, and perinatal outcomes did not differ significantly between groups.</p><p><strong>Limitations, reasons for caution: </strong>The sample size was powered to de","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1420-1429"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277325","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":"Characterizing endometriosis and adenomyosis symptom clusters and their impact on quality of life in the All of Us Research Program.","authors":"Oksana Goroshchuk, Noelia Pérez-Gómez, Francisco Carmona, Hugh S Taylor, Idhaliz Flores, Miriam Saiz-Rodríguez, Dora Koller","doi":"10.1093/humrep/deag101","DOIUrl":"10.1093/humrep/deag101","url":null,"abstract":"<p><strong>Study question: </strong>Are there distinct symptom clusters in women with endometriosis and adenomyosis, and how do these clusters predict quality of life?</p><p><strong>Summary answer: </strong>Latent class analyses of 22 438 women with endometriosis identified four symptom phenotypes, including high pain-gastrointestinal and psychological-neurological clusters; adenomyosis cases were concentrated in high‑pain classes without a minimal‑symptom group, and high‑burden phenotypes had poorer quality of life.</p><p><strong>What is known already: </strong>Endometriosis and adenomyosis are heterogeneous conditions with diagnostic delays of 4-11 years. The classification based on surgical findings and imaging fails to capture the complex, systemic symptom combinations that affect patients' quality of life (QoL).</p><p><strong>Study design, size, duration: </strong>Large-scale cross-sectional cohort study using data from the United States-based All of Us Research Program (Controlled Tier v8; May 2018-October 2023).</p><p><strong>Participants/materials, setting, methods: </strong>The dataset included 22 438 women with electronic health records (EHR) and/or self-reported endometriosis. Four Latent Class Analyses (LCA) were performed on different patient groups: (i) the full endometriosis cohort (n = 22 438); (ii) an age-corrected subset restricted to premenopausal women (aged 18-45; n = 5542) to minimize menopausal confounding; and two subgroups derived from the age-corrected cohort to test whether concomitant adenomyosis defines distinct symptomatic phenotypes: (iii) clinically confirmed endometriosis without adenomyosis (n = 1797) and (iv) adenomyosis with endometriosis (n = 643). LCA was performed using 19 self-reported and EHR-derived symptoms and comorbidities (e.g. chronic pelvic pain, migraine, depression, gastrointestinal symptoms) to identify patient subgroups. Multinomial logistic regression assessed sociodemographic (age, BMI, deprivation index) and clinical predictors (hormonal contraceptive use, surgical history) of class membership. The association between latent classes and QoL outcomes was evaluated using data from the 'Overall Health' and 'Health Care Access and Utilization' surveys. Data are available via the All of Us Researcher Workbench (https://workbench.allofus.org).</p><p><strong>Main results and the role of chance: </strong>Latent class analysis of clinically confirmed endometriosis identified four distinct symptom phenotypes, most notably a severe 'High Pain & Gastrointestinal with Mood Symptoms' (High) cluster and a unique 'Predominantly Psychological/Neurological' cluster that challenges traditional gynecological-focused diagnostic frameworks. Patients with adenomyosis exhibited a distinct profile with two high-pain symptom classes and the absence of a fully asymptomatic group, indicating a higher overall disease burden. Membership in the High class was significantly associated with lower general health scores, reduc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1310-1323"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360539","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":"Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice.","authors":"Aoran Zhi, Ming Li, Muhammad Zubair, Musavir Abbas, Wasim Shah, Abu Mansoor, Fazal Rahim, Imtiaz Ali, Yousaf Raza, Ghulam Murtaza, Nisar Ahmad, Zain Abideen, Hanwei Jiang, Baolu Shi, Huan Zhang, Qinghua Shi","doi":"10.1093/humrep/deag086","DOIUrl":"10.1093/humrep/deag086","url":null,"abstract":"<p><strong>Study question: </strong>Do variants in YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) cause male infertility in humans, and what is the underlying pathogenic mechanism?</p><p><strong>Summary answer: </strong>Biallelic pathogenic missense variants in YTHDC2 disrupt the mitotic-to-meiotic transition, causing meiotic arrest and non-obstructive azoospermia (NOA) or severe oligozoospermia in humans.</p><p><strong>What is known already: </strong>YTHDC2 is a male germ cell-specifically expressed RNA helicase essential for meiotic progression. In mice, loss of Ythdc2 leads to meiotic arrest at the early prophase. However, clinical evidence linking YTHDC2 variants to human male infertility and the underlying mechanisms involved remains to be established.</p><p><strong>Study design, size, duration: </strong>This study utilized a large cohort comprising 56 consanguineous families and 89 sporadic infertile men diagnosed with NOA or severe oligozoospermia. Through extensive genetic screening, we specifically identified five infertile men from three unrelated families who harbored candidate pathogenic variants in the YTHDC2 gene. The overall study design encompassed genetic screening followed by in vivo functional validation using a knock-in mouse model.</p><p><strong>Participants/materials, setting, methods: </strong>Whole-exome sequencing (WES) and bioinformatic analyses were performed on the patient cohort to screen for candidate pathogenic variants. Human meiotic defects were characterized via histological analyses and immunofluorescence staining of testicular sections. To validate the pathogenicity of the identified variant, a knock-in mouse model harboring the equivalent variant found in patients was generated by CRISPR/Cas9 technology, and analyzed for spermatogenesis and meiosis using spermatocyte spreading and immunofluorescence staining, quantitative real-time PCR, and western blotting.</p><p><strong>Main results and the role of chance: </strong>Two homozygous missense variants in YTHDC2 were identified in four NOA patients from two unrelated consanguineous families (MT1: c.3491A>T, p. E1164V; MT2: c.2639G>A, p. R880H), and compound-heterozygous missense variants were identified in a sporadic patient with severe oligozoospermia (MT3: c.1145A>G, p. D382G; MT4: c.292A>G, p. R98G). The MT1 variant (p.E1164V) is not located in any annotated domains, the other three variants reside within known functional domains of YTHDC2 protein. The knock-in mouse model carrying the MT1 variant recapitulated the patient's phenotype, with both exhibiting meiotic prophase arrest during spermatogenesis. Mechanistically, significantly decreased levels of MEIOC and RBM46, two YTHDC2-interacting proteins required for meiotic transcriptome reprogramming, were observed in the patient's testes. Concurrently, mitotic cell cycle regulators such as CCNA2, CCND1, and WEE1 were aberrantly upregulated in the patient's testicular cells expressing meiosis markers, i","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1277-1292"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175851","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":"A population-based study of the co-occurrence of hypospadias and congenital heart defects among boys conceived with in vitro fertilization†.","authors":"Melissa A Richard, Barbara Luke, Elwin Jaime, Sarah C Fisher, Dayana Betancourt, Mahsa M Yazdy, Sarah L Stone, Nina E Forestieri, Ethan Wantman, Valerie L Baker, Michael L Eisenberg, Carrie Williams, Alastair G Sutcliffe, Philip J Lupo","doi":"10.1093/humrep/deag093","DOIUrl":"10.1093/humrep/deag093","url":null,"abstract":"<p><strong>Study question: </strong>Is there an association of co-occurring hypospadias and congenital heart defects (CHD) with method of conception?</p><p><strong>Summary answer: </strong>There is a small excess risk for co-occurring hypospadias and CHD among boys conceived through in vitro fertilization (IVF) not fully explained by other risk factors.</p><p><strong>What is known already: </strong>We previously reported a higher prevalence of major CHDs among boys born with hypospadias. Our previous analyses leveraged 3.7 million pregnancies recorded through birth defect registries in 11 US states but could not evaluate the role of IVF in the risks for these pregnancy outcomes. Simultaneously, in registry data linked to fertility parameters, we observed excess risk for hypospadias and CHD with conception by IVF. The rarity of co-occurring birth defects requires large sample sizes with key information on both IVF treatment parameters and maternal characteristics to differentiate their roles in birth defects.</p><p><strong>Study design, size, duration: </strong>We conducted a population-based study of live births in four US states (Massachusetts, New York, North Carolina, and Texas) from 2004 to 2018 and linked to IVF cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS). Information on the treatment cycle included the use of autologous or donor oocytes, fresh or frozen embryos, male infertility diagnosis, and the use of ICSI. Non-IVF births were sampled 10:1 at the time of IVF births. For the purposes of evaluating isolated and co-occurring hypospadias and CHD, our study included 731 838 boys born over the study period.</p><p><strong>Participants/materials, setting, methods: </strong>State birth defect registries reporting British Pediatric Association codes were used to identify major birth defects. We formed four outcome groups: (i) boys with CHD alone, (ii) boys with hypospadias alone, (iii) boys with both (hypospadias-CHD), and (iv) boys without birth defects (comparison group). We used unadjusted and adjusted logistic regression to associate IVF conception with each outcome group relative to the common comparison group. Adjustments in each outcome model included backward elimination for birth year, plurality, maternal race/ethnicity, age, education, diabetes, hypertension, and parity. We additionally calculated the prevalence of CHD and hypospadias by IVF treatment parameters.</p><p><strong>Main results and the role of chance: </strong>Among 731 838 boys, we identified 267 who had both hypospadias and a major CHD, 65 conceived through IVF and 202 controls. We observed strong unadjusted associations of IVF with hypospadias (OR 1.49, 95% CI 1.37-1.62), CHD (OR 1.64, 95% CI 1.49-1.81), and hypospadias-CHD (OR 2.63, 95% CI 1.39-4.69). The associations of IVF with isolated hypospadias and isolated CHD were attenuated, but not fully explained, after adjustment for key covariates (hypospadia","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1440-1447"},"PeriodicalIF":6.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277266","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":"LRPPRC deficiency impairs trophoblast function through disrupted phosphatidylinositol metabolism in recurrent pregnancy loss.","authors":"Cancan Wang, Haoyu Yang, Mengyuan Li, Wenxuan Li, Xiafei Wu, Liping Jin, Xiang-Hong Xu","doi":"10.1093/humrep/deag123","DOIUrl":"https://doi.org/10.1093/humrep/deag123","url":null,"abstract":"<p><strong>Study question: </strong>Is leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) involved in the development of recurrent pregnancy loss (RPL) and, if so, what is the potential mechanism?</p><p><strong>Summary answer: </strong>LRPPRC deficiency impairs trophoblast viability and promotes apoptosis and oxidative stress through disruption of phosphatidylinositol (PI) metabolism, and low preconception serum PI (18:1/18:1) levels are associated with subsequent miscarriage in women with RPL.</p><p><strong>What is known already: </strong>RPL is commonly associated with impaired trophoblast function. LRPPRC works as a multifunctional protein that regulates a myriad of biological processes, including energy metabolism.</p><p><strong>Study design, size, duration: </strong>The investigation included re-analysis of a public transcriptomic dataset, functional experiments in trophoblast cell models, lipidomic profiling of first-trimester human villous tissues obtained from 11 clinically healthy pregnant women and 11 patients with RPL, and analysis of preconception serum lipids in a cohort of 63 women with a history of RPL, who were prospectively followed for subsequent pregnancy outcomes resulting in 32 normal deliveries and 31 cases of early pregnancy loss.</p><p><strong>Participants/materials, setting, methods: </strong>Bioinformatics screening of the public transcriptomic dataset GSE76862 was first conducted to identify candidate genes dysregulated in RPL villous tissues. Following the identification of LRPPRC, its functional role was investigated through siRNA-mediated knockdown in the human trophoblast cells, specifically assessing the resultant effects on cell viability, apoptosis, and oxidative stress levels. To elucidate the downstream molecular pathways, transcriptomic analysis of the LRPPRC-depleted cells was performed. Subsequent Gene Ontology analyses revealed a significant enrichment of candidate differentially expressed genes that are involved in the phospholipid biosynthetic process. In parallel, comprehensive lipidomic profiling of human villous tissue samples from both RPL patients and matched controls was carried out using mass spectrometry to validate bioinformatic predictions at the metabolite level. To explore translational potential, the preconception serum levels of lipids, including PI species, were measured in a cohort of women with a history of RPL and statistically correlated with their subsequent pregnancy outcomes. Finally, direct functional rescue experiments were executed by exogenously supplementing PI (18:1/18:1) to the culture medium of LRPPRC-deficient trophoblast cells to determine if this intervention could reverse the observed phenotypic impairments.</p><p><strong>Main results and the role of chance: </strong>LRPPRC was downregulated in RPL villous tissues. Functional validation in trophoblast cells demonstrated that knockdown of LRPPRC suppressed viability and increased apoptosis/oxidative stress. ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602339","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":"Methodological considerations in the ADAPT-1 ovarian stimulation study.","authors":"Susana Montenegro,Christoph Helwig","doi":"10.1093/humrep/deag120","DOIUrl":"https://doi.org/10.1093/humrep/deag120","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"17 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564951","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: Methodological considerations in the ADAPT-1 ovarian stimulation study.","authors":"Andrea Bernabeu,Philipp Zajc,Marta García Sánchez,Enrico Papaleo,Stefan Jirecek,Ida Engberg Jepsen,Rita Lobo","doi":"10.1093/humrep/deag121","DOIUrl":"https://doi.org/10.1093/humrep/deag121","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"13 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564959","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":"Can AI speak endo? A multi-platform evaluation of large language models against ESHRE endometriosis guidelines.","authors":"Gaetano Riemma,Florindo Mario Caniglia,Camilla Casolari,Antonio Maiorana,Mauro Cozzolino,Vittorio Agrifoglio,Pasquale De Franciscis,Luigi Cobellis,Raffaela Maria Carotenuto,Andrea Etrusco","doi":"10.1093/humrep/deag116","DOIUrl":"https://doi.org/10.1093/humrep/deag116","url":null,"abstract":"STUDY QUESTIONHow do the three most widely accessible large language models perform in terms of accuracy, consistency, and reliability when answering clinically relevant questions derived from the 2022 ESHRE guideline on endometriosis?SUMMARY ANSWERModel A achieved the highest accuracy scores, model C demonstrated significantly superior consistency across repeated queries, and all three models showed comparable but suboptimal reliability under free-tier access, while under official API access median accuracy converged across providers and reliability increased.WHAT IS KNOWN ALREADYLarge language models are increasingly consulted by both clinicians and patients as readily accessible sources of medical information. In reproductive medicine, preliminary evidence suggests that individual platforms may retrieve endometriosis-related content with mixed fidelity. However, no study has simultaneously benchmarked multiple models against a single, internationally recognized endometriosis guideline. The extent to which these tools can be trusted to faithfully reproduce evidence-based recommendations on endometriosis diagnosis and management remains largely unexplored.STUDY DESIGN, SIZE, DURATIONCross-sectional, multi-platform comparative study. Fifty clinically relevant questions covering the diagnostic and therapeutic domains of the 2022 ESHRE endometriosis guideline were simultaneously submitted to all three models during December 2025. Each question was entered in duplicate using independent sessions to assess response consistency and reliability. Subgroup analyses were carried out by submitting the questions to the API version and to the free-tier version of the platforms available in May 2026.PARTICIPANTS/MATERIALS, SETTING, METHODSThe three models were accessed through their respective free web interfaces using new accounts, without prompt engineering, prior training, or retrieval-augmented generation. A zero-shot prompting approach was adopted. Accuracy was evaluated by two independent experts using the Global Quality Score (GQS); consistency was defined as identical responses across the three iterations; reliability was defined as the alignment of each response with the ESHRE guideline. Discrepancies were settled by a third reviewer.MAIN RESULTS AND THE ROLE OF CHANCESignificant differences in accuracy were observed across models (Kruskal-Wallis H = 37.10, P < 0.001). Model A achieved the highest median GQS (5, interquartile range [IQR] 4-5), followed by model C (4, IQR 3-5) and model B (3, IQR 3-4). Post-hoc analysis confirmed that model A significantly outperformed model B (P < 0.001) but not model C (P = 0.123), while model C also scored significantly higher than model B (P < 0.001). For consistency, model C demonstrated a significantly higher rate of reproducible responses (92.0%) compared with model A (72.0%, P = 0.028) and model B (68.0%, P = 0.008). No significant between-model differences were found for reliability (χ2 = 1.029, P = 0.598), w","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"17 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148522395","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":"Incidence and factors associated with premature ovarian insufficiency: a population-based cohort study","authors":"J N Macintyre, J Pudwell, J Shellenberger, M P Velez","doi":"10.1093/humrep/deag111","DOIUrl":"https://doi.org/10.1093/humrep/deag111","url":null,"abstract":"STUDY QUESTION What is the incidence of premature ovarian insufficiency (POI) and its associated factors in Ontario, Canada, between 1995 and 2019? SUMMARY ANSWER The incidence of POI increased after 2011, driven primarily by non-iatrogenic POI, and was highest among women with a history of endometriosis. WHAT IS KNOWN ALREADY Recent estimates suggest a global POI prevalence of ∼3.7%, with increasing rates over time. POI has heterogeneous etiologies, including genetic, autoimmune, infectious, and iatrogenic causes; however, the cause remains unknown in ∼70% of non-iatrogenic cases. Existing incidence estimates are limited by recall bias, cross-sectional designs, small sample sizes, and limited assessment of associated factors. STUDY DESIGN, SIZE, DURATION This population-based cohort study included all women aged ≤ 39 years residing in Ontario between 1995 and 2019. Follow-up continued until POI diagnosis, age 40 years, death, loss of provincial health insurance, or end of the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS POI was defined using administrative health data as a diagnosis occurring before age 40 years identified by either (i) surgical menopause or (ii) ≥1 physician consultation coded as menopause (ICD-9 627). Annual incidence rates (IRs) were calculated using census data, with the Ontario female population aged ≤ 39 years as the denominator. POI was classified as non-iatrogenic, surgical, post-chemotherapy and/or radiotherapy, or combined surgical with chemotherapy and/or radiotherapy. Associations between clinical factors and POI were estimated using age-adjusted modified Poisson regression to derive incidence rate ratios (IRRs). MAIN RESULTS AND THE ROLE OF CHANCE Among 3 635 702 eligible women, 168 173 developed POI from any etiology (IR 389.4 per 100 000 person-years). Median follow-up was 11 years (IQR 6–18), and median age at POI diagnosis was 31 years (IQR 25–36). IRs were 351.4 per 100 000 person-years for non-iatrogenic POI, 30.2 for surgical POI, 5.5 for post-chemotherapy and/or radiotherapy POI, and 2.3 for combined surgical with chemotherapy and/or radiotherapy POI. Overall POI incidence declined between 2002 and 2008, followed by a sustained increase through 2019, largely attributable to non-iatrogenic POI. The incidence of surgically induced POI decreased from 60 per 100 000 person-years in 1995 to 20 in 2019, while combined surgical with chemotherapy and/or radiotherapy POI increased steadily over the study period. Factors associated with higher POI incidence included endometriosis (IRR 3.45, 95% CI 3.39, 3.52), cancer treated with chemotherapy or radiotherapy (IRR 2.01, 95% CI 1.89, 2.14), drug or tobacco use (IRR 1.59, 95% CI 1.51, 1.67), chromosomal disorders (IRR 1.50, 95% CI 1.42, 1.59), and autoimmune diseases (IRR 1.19, 95% CI 1.17, 1.22). LIMITATIONS, REASONS FOR CAUTION Use of administrative health data may result in outcome misclassification and limited availability of detailed clinical and demograph","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"32 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440854","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}