Human reproduction open最新文献

{"title":"Association of social determinants of health and age at menopause: NHANES 1999-2018 observational study.","authors":"Yu Guan, Qian Liu, Zhimin Deng, Sirui Liu, Jia Liang, Yujie Zou, Tailang Yin, Dongdong Tang, Jue Liu, Yan Zhang","doi":"10.1093/hropen/hoaf050","DOIUrl":"10.1093/hropen/hoaf050","url":null,"abstract":"<p><strong>Study question: </strong>Do social determinants of health (SDoH) influence the age at menopause among women?</p><p><strong>Summary answer: </strong>In our study, adverse SDoH, particularly family low income-to-poverty ratio (PIR), low education level, and the marital status of being widowed, are associated with earlier age at menopause.</p><p><strong>What is known already: </strong>Some prior studies have considered certain SDoH variables (such as educational attainment and marital status) as potential factors influencing age at menopause, but systematic evidence clearly defining the relationship between multidimensional SDoH and menopausal age remains lacking.</p><p><strong>Study design size duration: </strong>This cross-sectional analysis included 6083 naturally menopausal women from 10 cycles (1999-2018) of the United States National Health and Nutrition Examination Survey (NHANES) and excluded cases of surgical menopause.</p><p><strong>Participants/materials setting methods: </strong>The participants were derived from a nationally representative sample of the NHANES 1999-2018 in the USA. Eight SDoH variables were assessed: employment, PIR, food security, education, healthcare access, health insurance, housing stability, and marital status. Age at menopause was determined by self-reported last menstrual period among women with natural menopause. This study constructed weighted multivariate linear regression models and weighted quantile sum (WQS) analyses and calculated regression coefficients (β) and their 95% CIs. Subgroup analyses and sensitivity analyses were used to verify the robustness of our findings.</p><p><strong>Main results and the role of chance: </strong>After adjusting for relevant confounding factors, adverse PIR, education level, and marital status (such as being widowed) were significantly associated with earlier age at menopause. Specifically, compared to women with a PIR ≥500%, women with a PIR between 100% and 300% or PIR ≤100% had an earlier age at menopause by 0.877 years (95% CI: -1.526, -0.229, <i>P</i> = 0.008) and 1.296 years (95% CI: -2.105, -0.487, <i>P</i> = 0.002), respectively. Additionally, compared to women with an educational level of college or above, women with a high school education or less than a high school education had earlier age at menopause by 1.262 years (High school: 95% CI = -1.914, -0.609, <i>P</i> < 0.001) and 1.403 years (Less than high school: 95% CI = -2.062, -0.743, <i>P</i> < 0.001), respectively. Compared to women who were married or living with a partner, widowed women had earlier age at menopause by 1.363 years (95% CI = -1.887, -0.839, <i>P</i> < 0.001). Analysis using a WQS regression model based on decile categorization demonstrated that each 1-unit increase in the composite exposure index of adverse SDoH factors was associated with 3.302 years earlier age at menopause in women (95% CI = -4.129, -2.476, <i>P</i> < 0.001). The PIR contributed most substantially to the inver","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf050"},"PeriodicalIF":11.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating endometrial response to human chorionic gonadotropin: alterations in epigenetic regulation and extracellular vesicle cargo of endometrial stromal cells.","authors":"Deimantė Žukauskaitė, Erika Girniūtė, Rūta Navakauskienė","doi":"10.1093/hropen/hoaf051","DOIUrl":"10.1093/hropen/hoaf051","url":null,"abstract":"<p><strong>Study question: </strong>What is the effect of hCG on the epigenetic profile and the expression of other molecular factors in endometrial stromal cells (ESCs)?</p><p><strong>Summary answer: </strong>Our findings suggest that hCG treatment alters the molecular environment of decidualized ESCs, potentially influencing implantation and immune regulation through epigenetic modifications and changes in the levels of secreted proteins and micro-ribonucleic acids (miRNAs).</p><p><strong>What is known already: </strong>Embryo implantation depends not only on the quality of the embryo but also on the receptivity of the endometrium, the specialized lining of the uterus that undergoes dynamic changes to support pregnancy. Effective communication between the maternal and fetal compartments, facilitated by molecular signals and cellular interactions, is essential for successful implantation.</p><p><strong>Study design size duration: </strong>Cross-sectional study of patient-derived ESCs comparing untreated cells with cells treated with hCG and/or decidualization induction. The number of samples depends on the method and varies from 2 to 8. Results were analyzed after 6-, 24-, 48-, and 72-h time-points.</p><p><strong>Participants/materials setting methods: </strong>ESCs were isolated from patients undergoing assisted reproductive technologies. In the study, we analyzed changes in the epigenetic profile and other molecular factors of ESCs during decidualization and in <i>in vitro</i> response to the embryo-secreted factor, hCG. ESCs were induced for decidualization for 3 days (medroxyprogesterone acetate+cAMP), or treated with hCG for 24 h, or given combined treatment: 2 days of decidualization followed by 24 h of hCG. Furthermore, we compared decidualized ESCs with decidualized ESCs that were also treated with hCG. We examined various cellular properties, including morphology, metabolic activity, and cell viability of ESCs after induction of decidualization and hCG treatment. Additionally, we assessed changes in the expression of genes associated with decidualization, inflammatory response, apoptosis regulation, and epigenetic factors using RT-qPCR. The levels of histone modifications and the factors regulating these modifications were explored by performing western blot assays. Additionally, we performed a chromatin immunoprecipitation assay to extract gene regions enriched with the epigenetic modification H3K27Ac. Finally, we analyzed the protein and miRNA level changes in ESC extracellular vesicles (ESC-EVs) after the indicated treatments, using mass spectrometry and small RNA sequencing.</p><p><strong>Main results and the role of chance: </strong>Our study found that hCG treatment increased prolactin gene (<i>PRL)</i> expression (<i>P</i> < 0.05), while the expression of <i>IL6</i> and <i>BAK1</i> was inhibited in ESCs (<i>P</i> < 0.05). We also revealed that hCG affects epigenetic regulation, leading to changes in the expression of <i>EED</i>, ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf051"},"PeriodicalIF":11.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016792","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":"The impact of <i>in utero</i> exposure to cancer treatments on foetal reproductive development and future fertility: a systematic review.","authors":"Elinor Sebire, Norah Spears, Rod T Mitchell, Agnes Stefansdottir","doi":"10.1093/hropen/hoaf046","DOIUrl":"10.1093/hropen/hoaf046","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does cancer treatment during pregnancy affect gonadal development in the exposed foetus?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our systematic review revealed that exposure &lt;i&gt;in utero&lt;/i&gt; to many cancer therapies does negatively impact gonadal development.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;It is well known that many cancer therapies can have a detrimental impact on the fertility of children and young people who have been treated for cancer. However, it is not yet known how much these agents impact the gonadal development and subsequent fertility of an &lt;i&gt;in utero-&lt;/i&gt;exposed foetus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We conducted a systematic review, following PRISMA guidelines, to investigate the evidence for associations between &lt;i&gt;in utero&lt;/i&gt; cancer therapy exposure and gonadal development in human tissues and animal models. A systematic search was conducted across PubMed, Web of Science, and Google Scholar for titles or abstracts containing terms relating to chemotherapy or hormonal therapy agents, &lt;i&gt;in utero&lt;/i&gt; exposure, and reproductive outcomes. We searched all available published articles up to July 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Two independent reviewers performed title and abstract, then full-text screening, using inclusion/exclusion criteria decided &lt;i&gt;a priori&lt;/i&gt;. We included clinical and laboratory studies on human foetal gonads and animal studies, &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;, where gonadal exposure occurred during the window that corresponded with human prenatal gonadal development. Data from the included studies were independently extracted and analysed by chemotherapy and hormonal drug class, focusing on reproductive outcome measures and results. Bias and quality assessments were performed with SciRAP &lt;i&gt;in vivo&lt;/i&gt; or &lt;i&gt;in vitro&lt;/i&gt; tool version 2.3.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;3360 titles and abstracts were screened for inclusion, following the removal of duplicates, with 57 undergoing full text review and 26 eligible studies identified for inclusion (human = 4, animal-model = 22). The collated results show clear evidence of significant germ cell loss and disruption to other gonadal cell types in male and female animal-model gonadal tissues exposed both &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt; to various chemotherapy and hormone therapies, and human male foetal tissue exposed to chemotherapy &lt;i&gt;in vitro&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The evidence provided was limited by the small number of studies available reporting on reproductive outcomes following &lt;i&gt;in utero&lt;/i&gt; exposure to cancer therapies, a lack of comparable outcome measures, and the use of single-drug exposures compared to the more clinically relevant multi-drug combinations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;This review provides evidence for the vulnerability of foetal gonads","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf046"},"PeriodicalIF":11.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981215","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":"Pregnancy and perinatal outcomes after modified natural cycle-frozen embryo transfers according to size of the dominant follicle on the hCG trigger day.","authors":"Jie Zhang, Shuwen Qiu, Hongyuan Gao, Xiaoyan Mao, Yi Guo, Ling Wu","doi":"10.1093/hropen/hoaf047","DOIUrl":"10.1093/hropen/hoaf047","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there an association between the dominant follicle size on the day of the hCG ovulation trigger and reproductive, obstetric, and perinatal outcomes in modified natural cycle-frozen embryo transfer (NC-FET) cycles in which intensive luteal phase support (LPS) was utilized?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The dominant follicle size on the day of triggering, ranging from above 10 to 18 mm or larger, was not associated with negative live birth or perinatal outcomes in modified NC-FETs when an intensive LPS was provided.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;There is growing evidence concerning the optimal timing for triggering final oocyte maturation during IVF ovarian stimulation cycles to obtain mature oocytes. However, a consensus on the ideal follicle size for administering hCG in modified NC-FETs has yet to be established. Interestingly, it has been suggested that the presence of a mature oocyte may not be necessary for FET.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A retrospective cohort study was conducted at a university-affiliated reproductive medicine center. The study included women with regular menstrual cycles who underwent autologous modified NC-FETs between 2013 and 2023 for potential analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Patients were categorized into eight groups based on the size of the dominant follicle at the time of hCG administration: &lt;12, 12-12.9, 13-13.9, 14-14.9, 15-15.9, 16-16.9, 17-17.9, and ≥18 mm. The primary outcome measured was the live birth rate (LBR), while secondary outcomes included the rates of positive pregnancy tests, implantation, clinical pregnancy, and pregnancy loss, as well as perinatal and obstetric complications. A generalized estimating equation logistic regression model was employed to account for the clustered nature of the data and to adjust for potential confounding factors. The group with a follicle size ≥18 mm was designated as the reference group in the logistic regression analyses. An intensive LPS, consisting of 400 mg dydrogesterone plus 400 mg vaginal progesterone, was adopted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;A total of 14 431 cycles that met the inclusion criteria were analyzed. The LBRs were similar across the eight groups. Furthermore, there were no significant differences in LBRs when the reference group was compared to the other follicle-size categories in the unadjusted models. Even after adjusting for several key confounders, the LBRs remained comparable between the study cohorts and the reference controls. Additionally, other reproductive parameters, such as rates of positive pregnancy tests, implantation, clinical pregnancy, and pregnancy loss, showed similar results between the control group and all other groups in both the unadjusted and confounder-adjusted analyses. Finally, pregnancies derived from the other follicle-size groups did not show increased risks","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf047"},"PeriodicalIF":11.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838767","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":"Androgen excess disorders remain undiagnosed in one of every four premenopausal women with Type 1 diabetes.","authors":"Ane Bayona Cebada, Lía Nattero-Chávez, Esther De la Calle De la Villa, Alejandra Quintero Tobar, Sara de Lope Quiñones, Beatriz Dorado Avendaño, Tom Fiers, Jean-Marc Kaufman, Manuel Luque-Ramírez, Héctor F Escobar-Morreale","doi":"10.1093/hropen/hoaf048","DOIUrl":"10.1093/hropen/hoaf048","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How frequent are androgen excess disorders, including polycystic ovary syndrome (PCOS), among women with Type 1 diabetes mellitus (T1D)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;One in every four women with T1D suffer from undiagnosed androgen disorders, with the classic phenotype of PCOS being the most frequent.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Systemic iatrogenic hyperinsulinism is unavoidable in patients with T1D because insulin is administered subcutaneously instead of being secreted directly into the portal circulation. Since insulin acts as a co-gonadotrophin at the ovary, iatrogenic hyperinsulinism might trigger androgen secretion in predisposed women. Most studies conducted to date have reported increased prevalences of androgen excess disorders in premenopausal women with T1D, yet these studies were hampered by methodological limitations that preclude reaching a definite conclusion on the issue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size and duration: &lt;/strong&gt;From January 2020 to March 2024, we conducted a cross-sectional study including women with T1D.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants setting methods: &lt;/strong&gt;We recruited 149 consecutive premenopausal women with T1D who attended the diabetes clinics of an Academic Hospital at Madrid, Spain. We compared them with 295 typical patients with PCOS who did not have T1D. We used state-of-the-art mass spectrometry techniques to measure serum androgens and equilibrium dialysis to measure free testosterone and followed the latest guidelines to phenotype patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Hyperandrogenic disorders (considering PCOS, idiopathic hyperandrogenism, and idiopathic hirsutism as a whole) were present in 39 (of 149) women with T1D (26%, 95% CI: 20-34%), including 30 women who fulfilled the PCOS diagnostic criteria, indicating a prevalence of 20% (95% CI: 15-27%). The most common PCOS phenotype was the classic combination of hyperandrogenism and ovulatory dysfunction. Women with T1D and PCOS were younger (mean age 25 ± 7 vs 31 ± 9 years-old, &lt;i&gt;P &lt;/i&gt;= 0.003) and their onset of T1D was more frequently premenarcheal (73% vs 46%, &lt;i&gt;P &lt;/i&gt;= 0.008) compared to those without PCOS. Compared to 295 typical patients with PCOS without T1D, the 30 women with T1D and PCOS showed milder hyperandrogenic signs and lower free testosterone concentrations [13 (9, 25) vs 21 (15, 29) pM, &lt;i&gt;P &lt;/i&gt;&lt; 0.001] regardless of the glucose tolerance of the former.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;We acknowledge the possibility of selection bias: having excluded T1D women already diagnosed with PCOS, we may have underestimated actual prevalence rates. Also, the cross-sectional design of the study precluded us from obtaining any causality insights about the associations found here.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;One in every four women with T1D suffer androgen excess disorders, with the classic combina","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf048"},"PeriodicalIF":11.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762493","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":"Association between novel per- and poly-fluoroalkyl substances and premature ovarian insufficiency: a case-control study.","authors":"Rui Qiao, Fanghao Guo, Haixia Ding, Di Sun, Qianhui Hu, Yanquan Li, Meiling Zhang, Qing Zhang, Wen Li","doi":"10.1093/hropen/hoaf044","DOIUrl":"10.1093/hropen/hoaf044","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do novel per- and poly-fluoroalkyl substances (Novel PFAS) have associations with premature ovarian insufficiency (POI)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Hexafluoropropylene oxide dimer acid (HFPO-DA), perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluoropentanesulfonic acid (PFPeS) are associated with an increased risk of POI, and the effect is worse with exposure to mixtures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;As public health concerns following Novel PFAS exposure are rising globally, there is a need to understand the exact association between Novel PFAS and various diseases. Epidemiologic studies suggest traditional PFAS exposures adversely affect women's reproductive health, but the association between exposure to Novel PFAS and POI remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A retrospective research study, including 371 women, with (case group, n = 151) and without POI (control group, n = 220), was conducted between June 2023 and May 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Thirteen types of Novel PFAS and basal concentrations of FSH, LH, estradiol (E2), and anti-Müllerian hormone (AMH) in plasma samples were measured in plasma samples collected during the early follicular phase (Days 2-5) of a natural menstrual cycle. In addition, characteristics of participants were collected. Both adjusted logistic regression and Bayesian kernel machine regression (BKMR) were used to evaluate associations between Novel PFAS (alone or as a mixture) and POI. Effect modification by age was also investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The concentrations of HFPO-DA, PFBA, PFPeA, and PFPeS in the case group were significantly higher than in the reference group. The adjusted logistic regression models demonstrated positive associations between plasma concentrations of HFPO-DA, PFBA, PFPeA, and PFPeS with the risk of POI [OR&lt;sub&gt;adj&lt;/sub&gt; = 2.89 (95% CI: 1.84-4.53), 1.54 (95% CI: 1.17-2.02), 3.12 (95% CI: 2.20-4.43), and 2.07 (95% CI: 1.31-3.27), respectively, per 2.7-fold increase in Novel PFAS concentrations]. High concentrations of Novel PFAS showed a negative correlation with AMH and antral follicle count (AFC), but a positive correlation with FSH. After controlling for other covariates, HFPO-DA, PFBA, PFBS, PFPeA, and PFPeS were the major contributors based on the BKMR models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;False positives cannot be ruled out. Therefore, experiments on PFBA, PFPeA, PFPeS, and HFPO-DA &lt;i&gt;in vivo&lt;/i&gt; also need to be conducted in animal models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;Our study is the first to discover the impact of Novel PFAS on the incidence of POI, with an investigation of indicators such as AMH, FSH, and AFC. Considering increasingly severe environmental pollution, our research results provide a broader understanding of ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf044"},"PeriodicalIF":11.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755272","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":"Silk-Ovarioids: establishment and characterization of a human ovarian primary cell 3D-model system.","authors":"Valentina Di Nisio, Tianyi Li, Zhijie Xiao, Kiriaki Papaikonomou, Anastasios Damdimopoulos, Ákos Végvári, Filipa Lebre, Ernesto Alfaro-Moreno, Mikael Pedersen, Terje Svingen, Roman Zubarev, Ganesh Acharya, Pauliina Damdimopoulou, Andres Salumets","doi":"10.1093/hropen/hoaf042","DOIUrl":"10.1093/hropen/hoaf042","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the best protocol to establish a long-term stable three-dimensional (3D) model for human primary ovarian cells?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;We developed and characterized long-term cultured 3D models of primary ovarian somatic cells isolated from adult tissues, using Biosilk as a scaffold.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; models that mimic ovaries are crucial for elucidating the biological mechanisms underlying follicle activation and growth, hormonal activity, ovarian angiogenesis, damage in response to toxic exposures, and other biological mechanisms that enable the functionality of this complex organ. Three-dimensional systems are particularly relevant because they replicate heterogeneity and cell-cell communication among different ovarian cell types. However, complex models using human ovarian primary cells are yet to be developed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Ovarian tissue samples were collected from five patients (age 26 ± 5 years) who underwent gender-affirming surgery. The cortex and medulla were separated and dissociated into single-cell suspensions using mechanical and enzymatic methods. Three approaches were tested to establish a 3D model culture system: matrix-free ovarian spheroids (MFOS), a Matrigel-based three-layer gradient system (3LGS), and Biosilk scaffolds (Silk-Ovarioid). In parallel, paired controls from each patient and ovarian area were cultured in a standard 2D system for the same duration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The 3D culture systems were monitored every second day to detect signs of aggregation and growth. Freshly fixed tissue, as well as 2D- and 3D-cultured samples were further processed for transcriptomic profiling after 42 days of culture using RNA sequencing. The culture of the 3D system was further characterized, regarding its protein profile and steroid and cytokine production, through proteomics and liquid chromatography-tandem mass spectrometry and the Luminex platform, respectively. The key findings from the high-throughput assays were finally validated through RNA fluorescent &lt;i&gt;in situ&lt;/i&gt; hybridization (RNA-FISH) and immunofluorescence staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The 3D model systems MFOS (n = 120) and 3LGS (n = 18) failed to form aggregates capable of long-term maintenance in culture (MFOS: maximum of 15 days for both cortex and medulla; 3LGS: maximum of 11 days for medulla only). In contrast, we successfully established ovarian cortex- and medulla-derived 3D systems using Biosilk, termed Silk-Ovarioids (n = 120). Silk-Ovarioids were maintained for up to 42 days as free-floating culture without any signs of cell death, as confirmed by the absence of TUNEL, γ-H2A.X, and cleaved caspase 3 fluorescent signals. The presence of key ovarian somatic cell types, including granulosa, stromal, endothelial, and perivascular cells, ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf042"},"PeriodicalIF":11.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838768","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":"Effects of different embryo culture media on birthweight following assisted reproductive technology.","authors":"Ming Li, Zhengyang Zhao, Qingqing Tao, Jin Huang, Ying Lian, Yue Li, Shengli Lin, Ping Liu, Qin Li, Rong Li, Jie Qiao","doi":"10.1093/hropen/hoaf041","DOIUrl":"10.1093/hropen/hoaf041","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does the type of embryo culture medium affect the birthweight of newborns conceived by ART?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;After fresh embryo transfers, singleton newborns in the G5 and HTF groups exhibited higher birthweight &lt;i&gt;z&lt;/i&gt;-scores and increased risks of being large for gestational age (LGA) compared to those in the Cook group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Current studies have not yet determined whether embryo culture medium affects birthweight and, if such an effect does exist, the significance of embryo culture medium among all the influencing factors is not yet clear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A retrospective cohort study including 23 403 fresh ET cycles between 1 January 2010 and 31 December 2022 at the reproductive medical center of a university-affiliated hospital was conducted.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;We performed a retrospective cohort study including 23 403 fresh ET cycles. Four embryo culture media were analyzed: Cook, G5-PLUS, G5, and HTF. Multiple linear regression analysis was used to evaluate potential associations between embryo culture medium and birthweight &lt;i&gt;z&lt;/i&gt;-score. Logistic regression analysis was used to evaluate potential associations between embryo culture medium and the risk of LGA and macrosomia. Random forest models were constructed to conduct significance analysis of all factors that may affect birthweight &lt;i&gt;z&lt;/i&gt;-score.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The cohort comprised 4453, 8460, 7463, and 3027 singletons in the Cook, G5-PLUS, G5, and HTF groups, respectively. Compared to the Cook group, newborns in the G5 and HTF groups had higher birthweight &lt;i&gt;z&lt;/i&gt;-scores (increased by 0.069 units, &lt;i&gt;P &lt;/i&gt;&lt; 0.001, and 0.073 units, &lt;i&gt;P = &lt;/i&gt;0.002, respectively) and higher risks of LGA (OR: 1.25, 95% CI: 1.12-1.39, &lt;i&gt;P &lt;/i&gt;&lt; 0.001; OR: 1.20, 95% CI: 1.05-1.37, &lt;i&gt;P &lt;/i&gt;= 0.009, respectively), while newborns in the G5 group also had a higher risk of macrosomia (OR: 1.21, 95% CI: 1.06-1.39, &lt;i&gt;P&lt;/i&gt; = 0.006). Of the main factors influencing birthweight, the embryo culture medium had a moderate significance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Due to commercial and regulatory reasons, various culture media were used for different periods, thus resulting in the different number of cases for the four culture media groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;Our analysis revealed that the type of embryo culture medium directly affected birthweight &lt;i&gt;z&lt;/i&gt;-scores and the risk of LGA and macrosomia in newborns conceived by ART. Consequently, the selection of embryo culture medium should be made cautiously. In addition, there's also a need for more post-market data on culture media for embryology labs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interests: &lt;/strong&gt;This study was supported by National Key Research and Development ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf041"},"PeriodicalIF":11.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735886","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":"Correction to: The interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.","authors":"","doi":"10.1093/hropen/hoaf037","DOIUrl":"https://doi.org/10.1093/hropen/hoaf037","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoae074.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf037"},"PeriodicalIF":8.3,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585690","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 sperm selection strategies for assisted reproduction through closing the knowledge gap in sperm maturation mechanics.","authors":"Hanah May Hart, Brett Nixon, Jacinta Hope Martin, Robert John Aitken, Geoffry Nunzio De Iuliis","doi":"10.1093/hropen/hoaf040","DOIUrl":"10.1093/hropen/hoaf040","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Male factors contribute to ∼50% of all infertility cases globally and are a major contributor to escalating use of ART. In most instances, sub-fertile men retain the ability to produce spermatozoa, albeit with reduced quality and function. By necessity, an important feature of ART is the use of technologies that bypass the natural selection barriers that prevent poor-quality spermatozoa from participating in fertilization. This means that ART carries a significant risk of facilitating fertilization with poor-quality gametes harbouring undetected DNA damage and/or altered epigenomes. Such a scenario may account for the epidemiological links between the use of 'high intervention' technologies [e.g. ICSI] and an increased risk of adverse offspring outcomes. Such data highlight a pressing need for improved sperm selection tools that better mimic natural selection barriers, to ensure only the highest-quality spermatozoa are used for ART.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;Current sperm selection techniques for ART and the processes underpinning sperm maturation have often been considered independently and therefore reviewed separately. Here we outline the requirement for connecting research paradigms towards advancing clinical outcomes. This review highlights the importance of combining our advancing knowledge of sperm maturation biology with the pursuit of rational sperm selection strategies for the clinic; specifically, this narrative review summarizes the current clinical technologies used for sperm selection with a focus on their physiological relevance and limitations. We have given consideration to the events associated with sperm maturation and the importance of zona pellucida (ZP) binding as inspiration to inform the development of the next generation of sperm selection strategies. The connections and information presented should provide utility and interest for both clinicians and reproductive biologists alike.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;The PubMed database was queried using the keywords: sperm selection/function/DNA quality/epigenome, ART, ICSI, male infertility, capacitation, zona pellucida, sperm-zona pellucida binding, DNA damage, and biofabrication. These keywords were combined with other relevant phrases. Literature was restricted to peer-reviewed articles in English (published between 1972 and 2024) with references within these articles also searched.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;During natural conception, high-quality sperm are 'selected', maximizing the chances of fertilization with healthy gametes carrying intact genomic/epigenetic cargo. This sub-population of spermatozoa possess the capacity to interact with the female reproductive tract and complete the suite of functional maturation processes required for successful fertilization and initiation of embryonic development. However, ART 'high intervention' strategies bypass these selective barriers leading to an increased ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 3","pages":"hoaf040"},"PeriodicalIF":8.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692668","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}