Human reproduction open最新文献

{"title":"Cost-to-baby as a percentage of median household income predicts population-level access to ART: a global health economics analysis.","authors":"Giuseppe Silvestri, Steve Rooks, Alejandro Chavez-Badiola, Silvana Perez, Stephanie Kuku, Alan Murray, David Sable, G David Adamson","doi":"10.1093/hropen/hoag084","DOIUrl":"10.1093/hropen/hoag084","url":null,"abstract":"<p><strong>Study question: </strong>Does cost-to-baby, expressed as a percentage of median household income (HHI), predict population-level utilization of ART across countries?</p><p><strong>Summary answer: </strong>ART affordability follows a power-law relationship with population-level utilization (<i>R</i> <sup>2</sup> = 0.77-0.84), with highest-utilization countries consistently achieving gross cost-to-baby below 100% and net out-of-pocket cost-to-baby below 50% of median HHI.</p><p><strong>What is known already: </strong>Cost has been consistently identified as a dominant barrier to ART access worldwide, and earlier cross-national work has shown that per-cycle IVF cost as a proportion of disposable income is associated with national utilization. However, no prior analysis has used the cumulative cost of achieving a live birth, normalized it to median HHI, tested a non-linear functional form, or separated gross from net (out-of-pocket) cost as independent predictors.</p><p><strong>Study design size duration: </strong>Cross-national study using secondary aggregate data from ART registries and economic/demographic agencies for reporting years 2021-2023, covering 22 countries and regions that together represent more than 95% of estimated global ART cycle volume.</p><p><strong>Participants/materials setting methods: </strong>ART cycle volumes and live births were extracted from ICMART, ESHRE EIM, CDC NASS, CARTR, HFEA, REDLARA, ANZARD, and national registries. Median after-tax disposable HHI data were sourced from the Organisation for Economic Cooperation and Development (OECD) and World Bank, while female population aged 15-49 years and total live births were obtained from the United Nations Population Division. Gross cost-to-baby was calculated as the product of mean per-cycle cost (including embryo transfer, preimplantation genetic testing weighted by national usage, and medications) and the age-weighted number of cycles required to achieve a live birth. Net out-of-pocket cost-to-baby was derived after applying published reimbursement schedules, subsidies, and tax benefits, with structured estimates where authoritative published data were unavailable. Both metrics were expressed as a percentage of median HHI. Utilization was measured as the percentage of total national live births achieved via ART and as ART births per 1000 women aged 15-49 years. Power-law (log-log) regression was fitted by ordinary least squares; a subgroup analysis was performed for women aged 38-49 years. A Monte Carlo probabilistic sensitivity analysis (10 000 iterations; Program Evaluation and Review Technique (PERT) distributions with uncertainty bands of ±5%, ±7.5%, or ±10% calibrated to data-source quality) generated 90% simulation envelopes around each baseline regression.</p><p><strong>Main results and the role of chance: </strong>Gross cost-to-baby varied more than 12-fold across countries, ranging from 66% of median HHI in Israel to 833% in Africa (excluding Egypt","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag084"},"PeriodicalIF":8.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217428","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":"High sperm DNA fragmentation is associated with increased embryonic chromosomal abnormality: a retrospective study of 8 years involving 5637 couples undergoing ART.","authors":"Li Lou, Pengcheng Xu, Pingyuan Xie, Huan Zhang, Yifan Gu, Fei Gong, Ge Lin, Guangxiu Lu, Jing Dai, Shujuan Ma","doi":"10.1093/hropen/hoag082","DOIUrl":"https://doi.org/10.1093/hropen/hoag082","url":null,"abstract":"<p><strong>Study question: </strong>Does sperm DNA fragmentation impair blastocyst chromosomal integrity?</p><p><strong>Summary answer: </strong>A high sperm DNA fragmentation index (DFI) is associated with an increased risk of blastocyst aneuploidy, particularly when the man has poor semen quality or when the female partner is aged ≥35 years.</p><p><strong>What is known already: </strong>Evidence linking sperm DFI to embryo development and blastocyst chromosomal integrity remains inconsistent, and controversy persists regarding its association with blastocyst aneuploidy detected by preimplantation genetic testing for aneuploidy (PGT-A). Existing studies have often been limited by small sample sizes, inconsistent DFI assays, and insufficient controls of key confounders.</p><p><strong>Study design size duration: </strong>This retrospective cohort study was conducted at a tertiary reproductive center. A total of 5637 infertile couples undergoing assisted reproduction between January 2016 and March 2023 were screened, and 3948 couples with complete data were included after applying standardized exclusion criteria.</p><p><strong>Participants/materials setting methods: </strong>All male partners who underwent sperm DNA fragmentation assessment using the Sperm Chromatin Structure Assay were included. Infertile couples were stratified by treatment modality, age of both partners, and male semen quality parameters. The primary outcome was blastocyst aneuploidy rate. Beta-binomial regression and zero-inflated beta-binomial regression were used to analyze embryonic outcomes, with model selection guided by the Akaike Information Criterion. Generalized linear mixed models were applied to account for clustering of multiple embryos within the same ovarian stimulation cycle.</p><p><strong>Main results and the role of chance: </strong>Higher DFI was associated with a higher rate of blastocyst aneuploidy. Compared to the low DFI group, the high DFI group had a significantly higher adjusted odds ratio (aOR) of aneuploidy (38.19% vs 24.42%, aOR = 1.35, 95% CI: 1.10-1.81, <i>P </i>= 0.042), while there was no substantial difference between the medium and low DFI group (25.78% vs 24.42%, aOR = 0.93, 95% CI: 0.76-1.13, <i>P </i>= 0.465). Particularly, when women were aged ≥35 years, the embryonic aneuploidy rate in the high DFI group was significantly higher than low DFI subgroup (52.02% vs 38.75%, aOR = 1.61, 95% CI: 1.12-2.32, <i>P </i>= 0.010). Also, among men with severe oligoasthenoteratozoospermia, high DFI significantly increased aneuploidy risk (36.81% vs 18.03%, aOR = 1.99, 95% CI: 1.11-3.57, <i>P </i>= 0.022). For all men aged <40 years, high DFI was associated with a reduced likelihood of high-quality blastocyst formation (aOR = 0.79, 95% CI: 0.64-0.99, <i>P </i>= 0.044).</p><p><strong>Limitations reasons for caution: </strong>Given the single-center retrospective design, residual confounding cannot be excluded despite rigorous statistical adjustment.</p><p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag082"},"PeriodicalIF":8.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186629","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":"Comparing the euploidy rate between the progestin-primed and gonadotrophin-releasing hormone antagonist protocols in preimplantation genetic testing for aneuploidy: a randomized controlled trial.","authors":"He Li, Min Yu, Wenbi Zhang, Junling Chen, Hua Chen, Xiang Lu, Lu Li, Ernest Hung Yu Ng, Xiaoxi Sun","doi":"10.1093/hropen/hoag081","DOIUrl":"https://doi.org/10.1093/hropen/hoag081","url":null,"abstract":"<p><strong>Study question: </strong>In patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), does the progestin-primed ovarian stimulation (PPOS) protocol result in a euploidy rate of blastocysts per patient comparable to that of the GnRH antagonist protocol?</p><p><strong>Summary answer: </strong>The euploidy rate of blastocysts per patient is comparable for patients using PPOS and GnRH antagonist protocols.</p><p><strong>What is known already: </strong>Progestin is effective in blocking the pituitary LH surge during ovarian stimulation, and the PPOS protocol is simpler and cheaper. However, published studies comparing euploidy rates between the two protocols have yielded contradictory results.</p><p><strong>Study design size duration: </strong>This was an open-label, randomized controlled trial of 400 women recruited between June 2020 and August 2024. Eligible women were randomly assigned in a ratio of 1:1 to the PPOS or GnRH antagonist group using an online randomization programme and sealed opaque envelopes. The primary outcome was the euploidy rate of blastocysts per patient.</p><p><strong>Participants/materials setting methods: </strong>Women aged <43 years undergoing PGT-A cycles were randomly assigned to either the PPOS group (n = 200) or antagonist group (n = 200). PGT-A was indicated for advanced maternal age, recurrent pregnancy loss, repeated implantation failure, or history of foetal aneuploidy in previous pregnancies. PGT-A was performed using the next-generation sequencing technology.</p><p><strong>Main results and the role of chance: </strong>The PPOS and antagonist groups were similar in demographic characteristics and the numbers of oocytes obtained/fertilized, cleavage-stage embryos, and developed blastocysts. The PPOS group had a significantly lower total gonadotrophin doses and significantly higher serum oestradiol levels on the ovulation trigger day when compared to the GnRH antagonist group. No statistically significant difference was observed in the euploidy rate of blastocysts between the PPOS and antagonist groups (40.0 (0-66.7)% versus 44.4 (25.0-71.4)%, <i>P</i> = 0.192). The number of euploid blastocysts per patient was comparable for the PPOS and antagonist groups (1 (1-2) versus 1 (1-2.5), <i>P</i> = 0.47). There were 136 women in the PPOS group and 152 women in the antagonist group who had their first frozen embryo transfer after PGT-A. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, ectopic pregnancy, and live birth rates after the first frozen embryo transfer.</p><p><strong>Limitations reasons for caution: </strong>The participants and researchers were not blinded to the treatment allocation. The sample size was powered only to detect a 10% euploidy rate difference; smaller differences cannot be excluded. Not all women completed their first transfer cycle, and outcomes from a single cycle do not represent cumulative live birth rates. Results are based solely","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag081"},"PeriodicalIF":8.6,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119467","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":"Fetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study.","authors":"Margit B Fischer, Gylli Mola, Karin Sundberg, Lone Scheel, Katrine B Wraae, Ane L Rom, Hanne Frederiksen, Richard A Anderson, Maria Assens, Anna-Maria Andersson, Lærke Priskorn, Jørgen H Petersen, Hanne K Hegaard, Katharina M Main, David M Kristensen, Anders Juul, Casper P Hagen","doi":"10.1093/hropen/hoag073","DOIUrl":"10.1093/hropen/hoag073","url":null,"abstract":"<p><strong>Study question: </strong>Is fetal exposure to paracetamol associated with markers of ovarian function in infancy?</p><p><strong>Summary answer: </strong>Mild to moderate doses of prenatal paracetamol exposure, assessed by detailed maternal reports and urinary measurements, are associated with ovarian morphology and activity as well as reduced size of estrogen-responsive tissues in infant girls.</p><p><strong>What is known already: </strong>Maternal use of paracetamol is widespread. Across multiple independent animal studies, fetal exposure consistently impairs the formation of primordial ovarian follicles, causing subfertility and premature estropause in female offspring.</p><p><strong>Study design size duration: </strong>The Copenhagen Analgesic study (COPANA) is a single-center, prospective, observational cohort study conducted at a university hospital (March 2020 to November 2022). From 3425 eligible participants, 685 healthy singleton pregnant women of Caucasian origin, were enrolled in the first trimester of pregnancy, and 302 infant daughters were examined at follow-up. Exclusion criteria included maternal diabetes or thyroid disease, pre- or post-term delivery, or severe infant illness.</p><p><strong>Participants/materials setting methods: </strong>Pregnant women reported paracetamol use biweekly and provided first-trimester urinary samples which were analyzed for paracetamol levels (LC-MS/MS) and adjusted for urinary osmolarity (n = 299). Girls were classified by timing of initial exposure: early fetal life (<17 weeks, n = 92), mid-late fetal life (≥17 weeks, n = 67), or unexposed controls (n = 143). Of the 92 girls initially exposed in early fetal life, a subgroup was exposed exclusively in early fetal life (n = 22).In an independent confirmatory cohort, 1210 girls were followed from infancy to adolescence. Their exposure was maternal self-reported (any) use of paracetamol during pregnancy and reported early in the third trimester (yes/no).</p><p><strong>Main results and role of chance: </strong>Early fetal exposure was associated with reduced ovarian volume (-0.11 cm<sup>3</sup>, 95% CI -0.19 to -0.03) and reduced uterine volume (-0.18 cm<sup>3</sup>, -0.35 to -0.01), whereas mid-late fetal exposure was associated with fewer ovarian follicles (-1.05 follicles, -1.71 to -0.39) compared to unexposed girls. AMH levels were lower in girls exposed exclusively in early fetal life (-0.45 SDS, -0.87 to -0.03) compared to unexposed girls. Maternal urinary paracetamol concentrations were inversely associated with ovarian and uterine volume as well as breast tissue diameter. In the independent confirmatory cohort, fetal paracetamol exposure was associated with reduced uterine volume at puberty (-4.11 cm<sup>3</sup>, -7.29 to -0.92) and smaller ovarian volume during adolescence (-2.76 cm<sup>3</sup>, -4.82 to -0.70).</p><p><strong>Limitations reason for caution: </strong>The observational design of the study allows evaluation of exposure","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag073"},"PeriodicalIF":8.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914288","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":"A context-specific evaluation of polygenic embryo screening in best-prognosis preimplantation genetic testing cycles.","authors":"Qi Wang, SiCong Zeng, ZiXu Chen, Liang Hu, Xiao Hu, PingYuan Xie, Juan Du, XiLin Xu, GuangXiu Lu, YueQiu Tan, Ge Lin","doi":"10.1093/hropen/hoag078","DOIUrl":"https://doi.org/10.1093/hropen/hoag078","url":null,"abstract":"<p><strong>Study question: </strong>In best-prognosis preimplantation genetic testing (PGT) cycles-defined by the availability of multiple transferable embryos-can polygenic embryo screening (PES) provide meaningful, context-dependent stratification that may influence embryo prioritization?</p><p><strong>Summary answer: </strong>In a sister-pair breast cancer validation cohort, the polygenic risk score (PRS) showed modest predictive performance, and when applied retrospectively to embryos, differences in modelled susceptibility were context-dependent, primarily influenced by the number of available embryos, parental polygenic risk profile, the limited discriminative power of the PRS, and the presence of disease-related monogenic variants.</p><p><strong>What is known already: </strong>The use of PES as an embryo-ranking tool within PGT remains controversial. Its potential utility depends on embryo availability and clinical context, yet empirical evaluations in real-world PGT settings remain limited.</p><p><strong>Study design size duration: </strong>This retrospective study combined (i) family-based validation using 184 affected-unaffected sisters, and (ii) embryo-level analysis of 310 PGT for monogenic disorders (PGT-M) cycles comprising 1722 embryos. Simulation modelling estimated differences in modelled embryo-level PRS percentile ranking under varying clinical and genetic scenarios.</p><p><strong>Participants/materials setting methods: </strong>Family-based performance of a breast cancer PRS was evaluated using affected and unaffected sister pairs. Embryo genotype data from PGT-M cycles were used to model PES under varying conditions, including the number of transferable embryos, the presence of pathogenic monogenic variants, and parental PRS percentile strata.</p><p><strong>Main results and the role of chance: </strong>Within-family PRS discrimination was modest: sisters in the top 10% of the PRS distribution had 4.07-fold higher breast cancer odds than their siblings (95% CI: 1.55-6.33). In the PGT-M cohort, 55% of cycles produced ≥3 transferable embryos, with a median within-cycle spread of approximately 25 PRS percentiles. In <i>BRCA1/2</i>-related cycles, PRS did not introduce distinct risk strata but revealed dispersion in modelled susceptibility among embryos sharing the same monogenic background. Embryo PRS distributions were concordant with parental profiles: 71% of embryos from couples with parental PRS ≥80th percentile were classified as high-PRS, compared with 7% when at least one parent was ≤20th percentile. Simulation analyses indicated that PRS-based embryo prioritization was associated with a 12-point lower mean embryo PRS percentile compared with morphology-based embryo prioritization in PGT-M cycles, attenuating to 10 points when PGT-A was incorporated. These differences reflect a statistical surrogate outcome only and do not demonstrate reduction in lifetime disease incidence or other clinical benefits.</p><p><strong>Large s","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag078"},"PeriodicalIF":8.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119424","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":"Connecting prenatal exposure to paracetamol with postnatal reproductive development: a first of its kind study in reproductive toxicology.","authors":"Christian De Geyter","doi":"10.1093/hropen/hoag074","DOIUrl":"10.1093/hropen/hoag074","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag074"},"PeriodicalIF":8.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914214","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":"Multi-omics factor analysis v2 (MOFA+) reveals specific co-variation patterns in women with PMOS that are strongly influenced by obesity.","authors":"Edmond Géraud-Aguilar, M Ángeles Martínez-García, María Insenser, Susana Barceló-Cerdá, Manuel Luque-Ramírez, Francisco García-García, Héctor F Escobar-Morreale","doi":"10.1093/hropen/hoag080","DOIUrl":"10.1093/hropen/hoag080","url":null,"abstract":"<p><strong>Study question: </strong>What are the mechanisms underlying the complex interactions between polyendocrine metabolic ovarian syndrome (PMOS) and obesity as studied by a multi-omics integration approach?</p><p><strong>Summary answer: </strong>Multi-Omics Factor Analysis v2 (MOFA+) suggested that PMOS was characterized by an androgen-driven metabolic reprogramming in which sexual dimorphism was reshaped in an obesity- and omics-specific manner, consisting of strong associations of proinflammatory proteins and adipokines with gut microbiota genera and metabolomics variables that were amplified by obesity.</p><p><strong>What is known already: </strong>PMOS is a common metabolic-endocrine disorder in which androgen excess, weight excess, and obesity complex interactions define a particularly unfavorable cardiometabolic phenotype.</p><p><strong>Study design size duration: </strong>Cross-sectional study with 2 control groups involving 46 Caucasian young adults, conducted at an academic hospital in Madrid, Spain.</p><p><strong>Participants/materials setting methods: </strong>We recruited 15 women with PMOS, 16 healthy control women, and 15 control men of similar mean age and BMI. Participants were further grouped into non-obese (BMI < 30 kg/m²) or obese (BMI ≥ 30 kg/m²) subjects. We integrated serum metabolomics and circulating proteins with gut microbiota composition, using MOFA+.</p><p><strong>Main results and the role of chance: </strong>MOFA+ identified five latent factors explaining the main sources of variation across omics layers. Results showed sexual dimorphism in an omics- and obesity-specific manner: the metabolomics profile presented sexual dimorphism in non-obese individuals, whereas circulating proteins and gut microbiota differed between women with or without PMOS and men only in obese subjects. Correlation analyses revealed a global weakening of associations in men, particularly among metabolites, a reinforcement of protein-related associations with obesity, and a distinct PMOS-specific pattern characterized by strengthened correlations within and between gut microbiota and proteomic features. Women with PMOS exhibited the strongest metabolomics-proteomics correlations, further exacerbated by obesity.</p><p><strong>Limitations reasons for caution: </strong>The relatively small sample size of our study might have missed relevant associations that could have reached statistical significance in larger samples. Also, we only included women with hyperandrogenic phenotypes of PMOS. Hence, our results may not apply to non-hyperandrogenic phenotypes of the syndrome.</p><p><strong>Wider implications of the findings: </strong>PMOS showed a metabolic profile similar to that of obesity even in the absence of excess weight, supporting the concept that adipose tissue dysfunction, proinflammatory proteins, and adipokines, rather than fat mass excess <i>per se</i>, were a central driver of the metabolic disturbances of the syndrome. Altogether","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag080"},"PeriodicalIF":8.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066538","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":"Geographic patterns of ovarian tissue cryopreservation utilisation across age groups in a nationwide multicentre cohort.","authors":"Norah L A Emrich, Rebekka Einenkel, Cara M Färber, Andreas Schallmoser, Nicole Sänger","doi":"10.1093/hropen/hoag076","DOIUrl":"10.1093/hropen/hoag076","url":null,"abstract":"<p><strong>Study question: </strong>Does geographic proximity to a centralised cryobank reflect age-dependent differences in ovarian tissue cryopreservation (OTC) utilisation?</p><p><strong>Summary answer: </strong>Paediatric patients resided significantly closer to the cryobank than adolescents and adult women, suggesting age-dependent geographic differences in the utilisation of fertility preservation services.</p><p><strong>What is known already: </strong>OTC is an established fertility preservation option, and previous studies have primarily focused on return rates of cryopreserved ovarian tissue and subsequent pregnancy and live birth outcomes. However, less is known about utilisation patterns of fertility preservation, particularly for OTC in paediatric oncology, where utilisation may be influenced by factors such as clinician-initiated counselling and local referral pathways.</p><p><strong>Study design size duration: </strong>This retrospective nationwide multicentre cohort study included 2,426 patients referred from 124 centres who underwent OTC at a central cryobank between 2000 and 2021.</p><p><strong>Participants/materials setting methods: </strong>Patients were stratified into children (<15 years, n = 149), adolescents (15-19 years, n = 296), and adults (≥20 years, n = 1,981). Residential addresses were geocoded, and distances to the cryobank were calculated. Regional distribution was categorised by population size. Statistical analyses included Chi-square and non-parametric tests with Bonferroni correction.</p><p><strong>Main results and the role of chance: </strong>Median distance to the cryobank increased with age (children: 136 km; adolescents: 183 km; adults: 222 km), with children living significantly closer than adolescents (<i>p</i> = 0.03) and adults (<i>p</i> = 0.001). Overall, 44.8% of patients resided in large cities, with significant age-group differences (<i>p</i> < 0.001). Paediatric cases were concentrated in urban areas, whereas adults were more geographically dispersed. Among adults, distance varied by indication (<i>p</i> = 0.021), but not in younger groups. This pattern persisted despite the nationwide referral network.</p><p><strong>Limitations reasons for caution: </strong>The retrospective design precludes causal inference. Distances were calculated as straight-line measures instead of real travel time, and socioeconomic factors were not available. Furthermore, only patients who successfully underwent OTC were available for analysis. Consequently, the study cannot assess true access to fertility preservation, referral rates, counselling rates, or the number of eligible patients who did not proceed to treatment. Although patients were referred from centres across Germany, cryopreservation was centralized in Bonn. Regional referral relationships and the structure of the referral network may therefore have influenced the observed geographic distribution, particularly in paediatric patients, and may limit generalisa","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag076"},"PeriodicalIF":8.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148946199","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 cryopreservation duration on pregnancy outcomes in embryos: a systematic review and meta-analysis.","authors":"Bowen Wei, Yinni Chen, Jiayi Nie, Xiating Li, Kecheng Wei, Yuxiang Wan, Jingzhen Lai","doi":"10.1093/hropen/hoag077","DOIUrl":"10.1093/hropen/hoag077","url":null,"abstract":"<p><strong>Study question: </strong>Is prolonged cryopreservation associated with adverse clinical pregnancy and live birth after frozen-thawed embryo transfer?</p><p><strong>Summary answer: </strong>Prolonged embryo cryopreservation is associated with lower clinical pregnancy and live birth rates, particularly within the first 3-12 months of storage, but rates plateau after 2 years.</p><p><strong>What is known already: </strong>Evidence on the impact of cryopreservation duration on reproductive outcomes remains scarce and conflicting, with some studies reporting no adverse effects and others suggesting increased risks of pregnancy loss, preterm birth, and epigenetic alterations after prolonged storage.</p><p><strong>Study design size duration: </strong>Systematic review and meta-analysis of studies comparing pregnancy outcomes by cryopreservation duration. PubMed, Embase, and the Cochrane Library were searched from inception to 31 December 2025, for English-language articles. The search strategy combined terms for embryos (e.g. 'Embryo', 'Blastocyst'), cryopreservation techniques (e.g. 'vitrification', 'cryopreservation', 'freezing'), and pregnancy outcomes (e.g. 'pregnancy', 'live birth') using Boolean operators. A total of 5208 records were identified from PubMed, 9272 from Embase, and 331 from the Cochrane Library.</p><p><strong>Participants/materials setting methods: </strong>Two independent reviewers screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. Inclusion required reporting of clinical pregnancy rate (CPR) or live birth rate (LBR) stratified by cryopreservation duration. Studies on donated embryos, preimplantation genetic testing, or gamete cryopreservation were excluded. Pooled odds ratios (ORs) with 95% CIs were calculated using fixed- or random-effects models based on heterogeneity (<i>I</i>²). Subgroup analyses were performed for neonatal outcomes (singleton vs. multiple births). Publication bias was assessed via funnel plots.</p><p><strong>Main results and the role of chance: </strong>A total of 14 811 records were screened (5208 from PubMed, 9272 from Embase, 331 from Cochrane). After removal of duplicates, 11 077 records were screened by title and abstract, and 785 full-text articles were assessed for eligibility. Twenty-three studies (254 017 transfer cycles/patients) were included. Embryos cryopreserved >5 years had lower survival rates (OR = 0.84, 95% CI: 0.72-0.98, <i>P</i> = 0.03; <i>I</i> <sup>2</sup> = 0%, <i>P</i> = 0.99). Compared with ≤3 months storage, longer storage was associated with reduced CPR (>3 months: OR = 0.87, 95% CI: 0.78-0.96, <i>P</i> = 0.005; >6 months: OR = 0.70, 95% CI: 0.66-0.74, <i>P</i> < 0.00001; >12 months: OR = 0.71, 95% CI: 0.61-0.82, <i>P</i> < 0.00001; >2 years: OR = 0.77, 95% CI: 0.65-0.91, <i>P</i> = 0.003), reduced LBR (>3 months: OR = 0.90 95% CI: 0.84-0.95, <i>P</i> = 0.0008; >6 months: OR = 0.74, 95% CI: 0.69-0.80, <i>P</i> < 0.00001; >12 months: OR","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag077"},"PeriodicalIF":8.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009454","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":"Hyperestrogenic imprinting and developmental origins of endometriosis and adenomyosis.","authors":"Sun-Wei Guo, Paola Viganò","doi":"10.1093/hropen/hoag075","DOIUrl":"10.1093/hropen/hoag075","url":null,"abstract":"<p><p>The pathogenesis of endometriosis and adenomyosis remains incompletely understood, and a notable gap persists between the reported heritability and the disease variation explained by identified susceptibility loci. In this manuscript, we showcase key epidemiological and clinical observations-including associations with early menarche, shorter anogenital distance, specific childhood growth trajectories, hypospadias in males, and developmental exposure to endocrine-disrupting chemicals-that collectively point to the influence of early-life developmental programming. Recent evidence revealing a hyperestrogenic/hypoandrogenic hormonal imbalance in the umbilical cord blood of pregnant women with endometriosis provides a critical link between these seemingly disparate findings. We propose a novel hypothesis of hyperestrogenic imprinting: Female offspring of women with endometriosis and/or adenomyosis are exposed <i>in utero</i> to a distinct hormonal environment, which induces lasting epigenetic changes in the developing reproductive tract, thereby imprinting a lifelong susceptibility to these two diseases. This mechanism offers a cohesive explanation for the familial aggregation of endometriosis and possibly adenomyosis, addresses the issue of 'missing heritability', and integrates various risk factors rooted in early development. A limitation of this opinion piece is that its hypothesis is primarily informed by animal studies and conceptual synthesis, and would benefit from further validation through original human data. As a falsifiable hypothesis, it presents a clear pathway for future validation and, if proven, opens avenues for novel preventive strategies.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 4","pages":"hoag075"},"PeriodicalIF":8.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992707","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}