Fiskani J M Kondowe, Matthew Gittins, Peter Clayton, Daniel R Brison, Stephen A Roberts
{"title":"Birthweight trends for babies born using Assisted Reproductive Treatments between 1991 and 2018: a national cohort study.","authors":"Fiskani J M Kondowe, Matthew Gittins, Peter Clayton, Daniel R Brison, Stephen A Roberts","doi":"10.1093/humrep/deag140","DOIUrl":"https://doi.org/10.1093/humrep/deag140","url":null,"abstract":"<p><strong>Study question: </strong>Has the average birthweight (BW) for singletons born in the UK through ART changed between 1991 and 2018 relative to the general population?</p><p><strong>Summary answer: </strong>The average gestation-adjusted BW for ART singletons increased steadily between 1991 and 2012 before becoming almost static until 2018; these changes were not observed in the general UK population.</p><p><strong>What is known already: </strong>Many older studies have shown that ART babies are low BW (LBW) compared to naturally conceived babies. Some subsequent evidence suggests that the average BW for fresh and frozen transfer ART babies has increased over recent years.</p><p><strong>Study design, size, duration: </strong>This cohort study utilized the UK Human Fertilisation and Embryology Authority (HFEA) dataset of 140 859 singleton ART babies born between 1991 and 2018 in the UK following both fresh and frozen embryo transfer (FET). Comparative aggregated data of 11 790 372 singleton babies born in the UK general population during the same period were obtained from NHS Digital.</p><p><strong>Participants/materials, setting, methods: </strong>The HFEA dataset was used to explore ART BW (raw or gestation-adjusted) and gestational age trends between 1991 and 2018. Appropriate regression models assessed the outcomes and adjusted for child sex, available treatment factors (fresh/frozen ET, embryo transfer stage (cleavage or blastocyst transfer), number of embryos transferred, ovarian stimulation, ICSI, treatment centre/clinic, and pre-implantation genetic screening of embryos) and patient factors (maternal age, previous IVF attempts, previous live births, previous pregnancies, ethnicity, country of treatment within the UK (England, Northern Ireland, Scotland, and Wales), funding source, total number of oocytes retrieved, and infertility causes (endometriosis, idiopathic, ovulatory, tubal diagnosis, and male factor)). BW, LBW, and macrosomia models were additionally adjusted for gestational age. Segmented trend analysis using linear splines was used to capture non-linear time effects for BW and gestation outcomes. For the general population data, mean BW and gestation outcomes were assessed as raw, unadjusted yearly averages.</p><p><strong>Main results and the role of chance: </strong>Unadjusted raw BW trends show that ART babies were initially smaller than the general population, but over time, are becoming closer to it. Fully adjusted mean ART BW increased by ∼75 g between 1991 and 2012, and after that, it was almost static. A drop in ART raw BW starting in 2013 was concurrent with a drop in average gestation by an overall average of 2.5 days between 2012 and 2018. The mean raw BW in the general population remained almost static over the study period and consistently higher than the ART BW average, with a notable drop beginning in 2013, concurrent with a decline in average gestation. Between 1991 and 2000, and 2012 and 2018, average ge","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038332","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}
Karolina Nowak, Carrie J Nobles, Oladele A Oluwayiose, Ricardo P Bertolla, Alexander Suvorov, J Richard Pilsner
{"title":"Interindividual variability of sperm DNA methylation is associated with reduced fecundability in couples attempting natural conception.","authors":"Karolina Nowak, Carrie J Nobles, Oladele A Oluwayiose, Ricardo P Bertolla, Alexander Suvorov, J Richard Pilsner","doi":"10.1093/humrep/deag145","DOIUrl":"https://doi.org/10.1093/humrep/deag145","url":null,"abstract":"<p><strong>Study question: </strong>Is sperm DNA methylation variability, referred here as sperm Epigenetic Variability Outliers and Stochasticity (EVOS), associated with time-to-pregnancy (TTP) and pregnancy outcomes in couples attempting to conceive naturally?</p><p><strong>Summary answer: </strong>Higher sperm EVOS is linked to reduced fecundability in couples attempting to conceive naturally.</p><p><strong>What is known already: </strong>Sperm methylation variability in promoter regions has been linked to poor reproductive outcomes in the clinical population.</p><p><strong>Study design, size, duration: </strong>The study was conducted among couples from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (n = 372), which comprised couples attempting natural conception.</p><p><strong>Participants/materials, setting, methods: </strong>Sperm EVOS was calculated as the sum of sperm DNA methylation CpG outliers on the Illumina EPIC (v1) array. The association of log-transformed sperm EVOS and TTP was examined using Cox proportional hazards model (CoxPH) and Kaplan-Meier survival analysis (KM), and by comparing pregnancy rates at 3, 6, and 12 months of follow-up. Associations between sperm EVOS and pregnancy outcomes (gestational age, live birth, and newborn metrics) were also investigated using multivariable linear or logistic regression. Models were performed with and without adjustments for potential confounders, including male and female age, BMI, smoking status, and average methylation at the DLK1 region as an indicator for potential somatic cell contamination. Sensitivity analysis was restricted to couples with normospermic men based on 5th percentile values from the World Health Organization (WHO) 2010. The functional and biological relevance of CpGs identified with EVOS were evaluated using Metascape.</p><p><strong>Main results and the role of chance: </strong>Sperm EVOS displayed a right-skewed distribution, with median numbers of EVOS CpGs of 673. Men from non-pregnant couples had higher median sperm EVOS than men from pregnant couples at 3, 6, and 12 months (P < 0.05). In both crude and adjusted CoxPH, sperm EVOS was associated with reduced fecundability of couples attempting natural conception (adjusted fecundability odds ratio (FOR) = 0.79; 95% CI: 0.67, 0.94; P = 0.01), indicating a longer TTP. KM analysis revealed that couples in the highest quartile (Q4) of EVOS had longer times to pregnancy compared to those in the middle (Q2+Q3) and lowest (Q1) quartiles (P = 0.001), with respective 66% (95% CI: 53%, 75%), 81% (95% CI: 73%, 87%), and 86% (95% CI: 76%, 91%) predicted probabilities of conceiving within 12 months for each group. No association was found between sperm EVOS and live birth, gestational age or newborn metrics. Functional enrichment analysis revealed that most variable EVOS-associated sites were enriched in genes involved in glycolysis, carbohydrate metabolism, DNA damage checkpoint signaling, and","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038269","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":"Semen, stigma, and spectacle: reclaiming the narrative around male reproductive health.","authors":"Rafael Trinchant, Felicitas Azpiroz","doi":"10.1093/humrep/deag151","DOIUrl":"https://doi.org/10.1093/humrep/deag151","url":null,"abstract":"<p><p>Male infertility contributes to nearly half of all cases of infertility worldwide, yet male reproductive health remains under-recognized in research, clinical practice, and public health. Paradoxically, male fertility has recently gained cultural visibility-not through medical initiatives but through spectacle. In 2025, staged 'sperm races' in Los Angeles presented motile spermatozoa as competitors in a sporting contest; online masculinity movements recast declining sperm counts as a symptom of civilizational decline; and, at a recent international reproductive-medicine congress, a sculpture displayed human semen as a multimillion-euro commodity. We argue that these framings, whether fertility as a virile contest or a marketable asset, detach the reproductive body from its clinical, emotional, and relational meaning, entrench stigma, and sit uneasily with the principle that the human body and its parts should not, as such, give rise to financial gain. They also obscure robust evidence. Sperm concentration has declined by roughly 50% since the 1970s, alongside consistent associations between poorer semen parameters and higher all-cause mortality. Together, this evidence positions semen quality as a barometer of men's general health. Meanwhile, men affected by infertility experience shame, delayed help-seeking, and scarce psychosocial support, while services and education remain oriented towards women. Reproductive medicine should reclaim this narrative through male-focused education, the deconstruction of stigma, and early engagement in care, resisting both silence and spectacle while reaffirming the scientific and ethical foundations of reproductive health.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038310","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}
Chenglin Zhan, Jing Guo, Chengkun Zhong, Feiwu Long, Caiyu Wang, Xiang-Shun Cui, Richard M Schultz, Wenfa Lyu, Xin Ma
{"title":"Maternal TRIM28 safeguards bovine embryonic genome activation by regulating SAM-dependent methylation via lipid metabolism.","authors":"Chenglin Zhan, Jing Guo, Chengkun Zhong, Feiwu Long, Caiyu Wang, Xiang-Shun Cui, Richard M Schultz, Wenfa Lyu, Xin Ma","doi":"10.1093/humrep/deag152","DOIUrl":"https://doi.org/10.1093/humrep/deag152","url":null,"abstract":"<p><strong>Study question: </strong>Does maternal TRIM28 coordinate lipid metabolism and epigenetic regulation during bovine preimplantation development?</p><p><strong>Summary answer: </strong>Maternal TRIM28 preserves phospholipid homeostasis and S-adenosylmethionine (SAM) availability to maintain H3K9me3-dependent transcriptional repression during embryonic genome activation (EGA).</p><p><strong>What is known already: </strong>Successful preimplantation development requires tight coordination between metabolic remodeling and epigenetic reprogramming. TRIM28 is a conserved transcriptional co-repressor essential for chromatin silencing and embryonic development, but whether it integrates metabolic and epigenetic regulation during mammalian EGA remains unclear. Bovine embryos share several developmental features with human embryos, including the timing of major EGA and aspects of metabolic and epigenetic remodeling, making them a useful comparative model for investigating preimplantation development.</p><p><strong>Study design, size, duration: </strong>A mechanistic study was performed using bovine embryos generated by IVF after siRNA-mediated TRIM28 knockdown (KD) in oocytes. Embryonic development, transcriptional activity, lipid metabolism, SAM homeostasis, and epigenetic remodeling were evaluated across at least three independent biological replicates using RNA sequencing, lipidomics, immunofluorescence, ELISA assays, and metabolic rescue experiments.</p><p><strong>Participants/materials, setting, methods: </strong>TRIM28 KD embryos were generated by microinjection of siRNAs into bovine oocytes prior to IVF. Embryonic development was evaluated through the blastocyst stage. RNA sequencing, lipidomic profiling, ATP measurement, immunofluorescence staining, and ELISA assays were used to assess transcriptional regulation, lipid metabolism, SAM availability, and epigenetic modifications. Choline and betaine supplementation experiments were performed to evaluate rescue of developmental and epigenetic defects.</p><p><strong>Main results and the role of chance: </strong>TRIM28 KD embryos showed impaired developmental progression around the 8-cell-to-morula transition, coinciding with major bovine EGA, and exhibited significantly reduced blastocyst formation. KD embryos exhibited widespread transcriptional dysregulation, increased global RNA synthesis, DNA damage, apoptosis, and ATP depletion. Lipidomic analyses revealed marked accumulation of triacylglycerols together with depletion of phosphatidylethanolamine (PE) and phosphatidylcholine (PC), indicating disrupted phospholipid homeostasis. TRIM28-deficient embryos also showed reduced H3K9me3 and DNA methylation levels accompanied by aberrant activation of EGA-associated genes. Mechanistically, altered phospholipid metabolism was associated with reduced intracellular SAM levels, raising the possibility that phospholipid remodeling affects the allocation of methyl donors between metabolic and chromatin ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030510","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":"Reproductive outcomes among Canadian-born and immigrant women with infertility in Ontario: a population-based cohort study","authors":"A Mishra, M Velez, S Yang, N Dayan","doi":"10.1093/humrep/deag144","DOIUrl":"https://doi.org/10.1093/humrep/deag144","url":null,"abstract":"STUDY QUESTION Do reproductive outcomes, including live birth rates, differ between Canadian-born women and immigrant women with infertility in Ontario, Canada? SUMMARY ANSWER Immigrant women with infertility, particularly refugees, had lower probabilities of live birth within 2 years of diagnosis compared with Canadian-born counterparts. WHAT IS KNOWN ALREADY Immigrant populations experience barriers to fertility care, yet population-level data on reproductive outcomes among immigrant women diagnosed with infertility are limited. STUDY DESIGN, SIZE, DURATION This population-based retrospective cohort study used linked administrative and registry data from ICES (formerly the Institute for Clinical Evaluative Sciences) Ontario between 2010 and 2019, with follow-up through 2021. The cohort comprised 254 463 women aged 18–55 years with a new physician-diagnosed infertility visit (OHIP 628), including 177 289 Canadian-born (69.7%) women, 66 131 non-refugee immigrants (26.0%), and 11 043 refugee immigrants (4.3%). PARTICIPANTS/MATERIALS, SETTING, METHODS Immigration status (Canadian-born, non-refugee immigrant, refugee immigrant) was derived from Immigration, Refugees and Citizenship Canada (IRCC-PR) data. The primary outcome was live birth within 2 years of infertility diagnosis. Secondary outcomes included time-to-pregnancy and birth by assisted conception. Relative risks were estimated using log-binomial regression and fecundability odds ratios (FORs) using discrete-time Cox models, adjusting for age, parity, income quintile, rurality, chronic conditions, and index year. Analyses followed the STROBE reporting guidelines. MAIN RESULTS AND THE ROLE OF CHANCE Among 177 289 Canadian-born, 66 131 non-refugee immigrant, and 11 043 refugee immigrant women, live birth within 2 years occurred in 68 394 (38.5%) Canadian-born women, 22 363 (33.8%) non-refugees, and 3525 (31.9%) refugees, with aRRs of 0.96 (95% CI 0.94–0.97) and 0.90 (95% CI 0.87–0.94), respectively, compared to the Canadian-born cohort. The median time-to-pregnancy was 10 months (IQR 4–23) for Canadian-born women and 11 months (IQR 4–24) for immigrants, with reduced fecundability among both non-refugee (aFOR 0.97, 95% CI 0.96–0.99) and refugee immigrants (aFOR 0.89, 95% CI 0.86–0.91). Among those who achieved pregnancy, births by assisted conception occurred in 21 449 (24.5%) Canadian-born women, 5174 (17.6%) non-refugees, and 666 (14.4%) refugees, with adjusted RRs of 0.73 (95% CI 0.70–0.75) and 0.64 (95% CI 0.60–0.69), respectively, compared to the Canadian-born cohort. LIMITATIONS, REASONS FOR CAUTION Administrative data capture physician-diagnosed infertility, which may under-represent immigrants who are less likely to receive a diagnosis, leading to potential selection bias and underestimation of disparities. Residual confounding and incomplete ascertainment of conception type or social determinants remain possible. WIDER IMPLICATIONS OF THE FINDINGS Despite universal health coverage and","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"51 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027555","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}
J da Silva, A P Satie, L Houzet, M J Lista Brotos, R Mathieu, A Goepp, F Aubry, N Dejucq-Rainsford
{"title":"Novel ex vivo models reveal segment-specific infection of the human efferent ducts and epididymis: implications for Zika virus persistence and shedding in semen.","authors":"J da Silva, A P Satie, L Houzet, M J Lista Brotos, R Mathieu, A Goepp, F Aubry, N Dejucq-Rainsford","doi":"10.1093/humrep/deag141","DOIUrl":"https://doi.org/10.1093/humrep/deag141","url":null,"abstract":"<p><strong>Study question: </strong>Can human epididymis and efferent ducts (ED) support Zika virus (ZIKV) replication ex vivo and act as a source of prolonged viral shedding in semen of infected men?</p><p><strong>Summary answer: </strong>Our novel ex vivo models demonstrate that ZIKV exhibits segment-specific tropism, with sustained replication in the ED epithelium and restricted infection of epididymal stromal macrophages, identifying these organs as distinct reservoirs for viral persistence in semen.</p><p><strong>What is known already: </strong>The 2015-2017 ZIKV outbreak revealed that the virus persists in semen and can be sexually transmitted by men long after the acute phase of infection. While the human testis is an established reservoir, animal studies and longitudinal semen analyses suggest that additional organs within the male genital tract contribute to the prolonged excretion of infectious ZIKV. However, the specific roles of the human EDs and epididymis have remained unexplored due to the lack of physiologically relevant human models.</p><p><strong>Study design, size, duration: </strong>Organotypic cultures of human EDs and epididymis corpus (EC) were developed and characterized using post-mortem tissues obtained from 11 uninfected organ donors (age range 29-79 years, median age: 58 years). Using this innovative ex vivo platform, we investigated ZIKV replication kinetics, cellular tropism, and the resulting impact on tissue viability and innate immune responses over a 9-day culture period.</p><p><strong>Participants/materials, setting, methods: </strong>ED and EC tissues were dissected and cultured on PET inserts at the air/medium interface. Tissue integrity was validated via histology, lactate dehydrogenase (LDH) viability assays, and transcriptomic/protein marker expression, assessed by RT-qPCR and immunohistochemistry. Explants were exposed to ZIKV, with replication monitored via viral RNA (vRNA) quantification, as assessed by RT-qPCR, and plaque assays for infectious virion release. Cellular targets were identified using RNAscope combined with immunohistochemistry. To determine the impact of the infection, we analyzed the innate immune response by RT-qPCR and ELISA and cell viability by LDH assays and cleaved caspase 3 expression, as well as the transcriptional and protein expression of a selected panel of cell markers, assessed by RT-qPCR and immunohistochemistry.</p><p><strong>Main results and the role of chance: </strong>The ex vivo models preserved global tissue architecture, viability, and the expression of epithelial, macrophage and smooth muscle markers throughout the study. ZIKV infected the ED epithelium, with replicative vRNA persisting from 3 days post-infection (dpi) until the end of culture (P = 0.01). Conversely, in the EC, infection was limited to stromal macrophages and smooth muscle cells, peaking at 3 dpi before diminishing (P = 0.002). Both segments exhibited robustly repeatable results across donors. Notabl","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989784","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}
G Sydsjö, M Bladh, C Lampic, E Nedstrand, A Skoog Svanberg, S Liffner
{"title":"Oocyte donors' health before and after their donation-a national Swedish register study.","authors":"G Sydsjö, M Bladh, C Lampic, E Nedstrand, A Skoog Svanberg, S Liffner","doi":"10.1093/humrep/deag139","DOIUrl":"https://doi.org/10.1093/humrep/deag139","url":null,"abstract":"<p><strong>Study question: </strong>Are Swedish oocyte donors comparable to an age-matched control group of women with regard to medical conditions, drug prescription, and hospitalization both before and up to 15 years after their donation?</p><p><strong>Summary answer: </strong>Compared with age-matched controls, Swedish oocyte donors exhibited higher outpatient healthcare utilization and medication use, were more frequently diagnosed with genitourinary disorders, and, among donors born in 1973 or later, had mental and nervous disorders.</p><p><strong>What is known already: </strong>During the donation process, oocyte donors self-assess their health as good, but longitudinal studies based on objective data are scarce.</p><p><strong>Study design, size, duration: </strong>Longitudinal study initiated in 2005 following identity-release oocyte donors' health from 1995 until 2023.</p><p><strong>Participants/materials, setting, methods: </strong>In total, 170 women recruited and accepted as identity-release oocyte donors in a non-commercial setting between 2005 and 2008 were included in this national register study. Of these, 21 women were directed donors, donating to a known recipient couple. For each donor, four age-matched controls from the general population were identified to form a control group of 680 women. Data from the National Patient Register, the Prescribed Drug Register, and Cause of Death register were used to obtain information on diagnoses using the ICD classification, medications, and hospitalizations from 1995 until 2018.</p><p><strong>Main results and the role of chance: </strong>Before donation, ∼10% of donors had received specialized healthcare for neoplasms, mental disorders, respiratory disorders, digestive disorders, or skin disorders. Genitourinary disorders were common, with 50% of donors diagnosed prior to donation. With post-donation period included, this proportion increased to almost 80%, which is markedly higher than among controls (58%, P < 0.001). The younger oocyte donors, born from 1973 onwards, were more often than the matched controls diagnosed with mental disorders due to psychoactive substance use, neurotic and stress-related disorders, and behavioural syndromes associated with physiological disturbances (all P < 0.05). Oocyte donors had approximately twice as many outpatient visits compared to the controls, even after excluding visits related to genitourinary disorders (mean number of visits/SD 17.9/20.6 versus 10.1/17.1, P < 0.001). The oocyte donors had also more often received prescribed medications, including systemic hormonal preparations, excluding sex hormones and insulins (73.5% vs 34.7%, P < 0.001) and drugs related to the nervous system (75.9% vs 65.0%, P < 0.012). More than 40% of the oocyte donors had used antidepressants, and 37% had used sedatives. Hospitalization rates did not differ between donors and controls. Directed donors had more outpatient visits than non-directed donors and were also mor","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976160","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}
N H Z Clasen, M E M van der Perk, S L Broer, J van Leeuwen, C H E Weimar, I M IJgosse, J Rascon, A J Klijn, A L F van der Kooi, A F W van der Steeg, S J C M M Neggers, M A Veening, A M E Bos, M D van de Wetering, M M van den Heuvel-Eibrink
{"title":"Oncofertility care evaluation of 599 children and adolescents with cancer and a high risk of treatment-induced gonadal damage: a national paediatric oncology cohort study.","authors":"N H Z Clasen, M E M van der Perk, S L Broer, J van Leeuwen, C H E Weimar, I M IJgosse, J Rascon, A J Klijn, A L F van der Kooi, A F W van der Steeg, S J C M M Neggers, M A Veening, A M E Bos, M D van de Wetering, M M van den Heuvel-Eibrink","doi":"10.1093/humrep/deag138","DOIUrl":"https://doi.org/10.1093/humrep/deag138","url":null,"abstract":"<p><strong>Study question: </strong>What is the quality of our standard oncofertility care, with a focus on fertility counselling and preservation rates, in children and adolescents with cancer and a high risk of treatment-induced gonadal damage (HRgd) at our national centralised paediatric oncology centre?</p><p><strong>Summary answer: </strong>Standardised personalised oncofertility care was achieved in 66.1% of identified HRgd children and adolescents with cancer, of whom 60.1% of patients underwent fertility preservation methods.</p><p><strong>What is known already: </strong>Increasing survival rates among childhood cancer patients have heightened awareness of long-term treatment-related toxicities, including gonadal damage and subsequent risk of infertility. The American Society for Reproductive Medicine and the International Guideline Harmonization Group recommend that fertility preservation counselling should be offered to paediatric and adolescent cancer patients at high risk of gonadal damage, including consideration of gonadal tissue preservation when appropriate. However, evidence on the implementation of oncofertility care programmes in HRgd paediatric and adolescent cancer patients remains limited.</p><p><strong>Study design, size, duration: </strong>This descriptive cohort study reports on standard oncofertility care in a national prospective cohort of HRgd childhood cancer patients, between January 2020 and December 2023, in our national paediatric oncology centre.</p><p><strong>Participants/materials, setting, methods: </strong>In all HRgd childhood cancer patients, who were diagnosed or relapsed between January 2020 and December 2023 in the Princess Máxima Center, our standard oncofertility care strategy was evaluated. Prospective collection of demographics, tumours, treatment, and oncofertility care details, as well as retrospective collection and analysis of reasons why HRgd patients and their families were not counselled or did not undergo fertility preservation, was performed.</p><p><strong>Main results and the role of chance: </strong>Between January 2020 and December 2023, 599 patients (age range 0-23 years; 345 males, 254 females) were triaged as HRgd (459 children newly diagnosed and 140 relapsed patients), including 396 (66.1%) who were counselled with 238 of these (60.1%) undergoing fertility preservation. Reasons why HRgd patients did not receive fertility counselling (n = 203/599, 34%) included their clinical status at diagnosis, young age of the patient, and anticipated poor prognosis. Uncertainties regarding future reproductive outcomes after autotransplantation of preserved tissue and concerns about potential risks of preservation procedures, were reasons for HRgd patients (n = 158/396, 40%) to refrain from fertility preservation.</p><p><strong>Limitations, reasons for caution: </strong>Triage information of HRgd patients who were diagnosed and/or relapsed during the establishment of oncofertility care in our centr","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900486","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}
N Brix, A Ernst, A Gaml-Sørensen, L H Arendt, G Toft, S S Tøttenborg, K S Hougaard, J P E Bonde, C H Ramlau-Hansen
{"title":"Body fat percentage in relation to semen characteristics, testicular volume, and reproductive hormones: a cross-sectional study.","authors":"N Brix, A Ernst, A Gaml-Sørensen, L H Arendt, G Toft, S S Tøttenborg, K S Hougaard, J P E Bonde, C H Ramlau-Hansen","doi":"10.1093/humrep/deag104","DOIUrl":"10.1093/humrep/deag104","url":null,"abstract":"<p><strong>Study question: </strong>Is body fat percentage associated with semen characteristics, testicular volume, and reproductive hormone levels?</p><p><strong>Summary answer: </strong>Higher body fat percentage was associated with poor semen characteristics and impaired reproductive hormone levels but not with testicular volume.</p><p><strong>What is known already: </strong>High BMI is associated with poor semen characteristics and impaired reproductive hormone levels. However, it remains unsettled whether body fat percentage is related to semen characteristics, testicular volume, and hormone levels; whether body fat percentage is a better measure of adiposity than BMI and waist-to-height ratio and hence stronger associated with semen characteristics, testicular volume, and reproductive hormones; and whether a high body fat percentage is associated with semen characteristics, testicular volume, and reproductive hormones, even among men considered normal weight according to BMI.</p><p><strong>Study design, size, duration: </strong>In this cross-sectional study, we used data from the Fetal Programming of Semen Quality (FEPOS) Cohort nested within the Danish National Birth Cohort. During 2017-2019, 1058 (19%) of 5697 invited men participated in FEPOS at the age of 18 years and 9 months.</p><p><strong>Participants/materials, setting, methods: </strong>The participants had their body fat percentage measured by bioelectrical impedance and had measured their BMI and waist-to-height ratio. They provided a semen and a blood sample, self-measured their testicular volume, and filled in a questionnaire on health behavior. Body fat percentage was analyzed as categories (<8%[low], 8-19% [normal, reference], 20-24% [high], ≥25% [very high]) and as a linear variable (in SDs). Relative differences in the outcomes in percent (with 95% confidence intervals) were estimated using negative binomial regression models. We further explored whether body fat percentage was stronger associated with impaired male fecundity than BMI and waist-to-height ratio, and whether an association for body fat percentage was present even among men considered normal weight according to BMI (BMI 18.5-24.9 kg/m2).</p><p><strong>Main results and the role of chance: </strong>Compared to normal body fat percentage (8-19%), high (20-24%) and very high (≥25%) body fat percentages were associated with lower total sperm count (high: -23% [-35%, -9%]; very high: -15% [-35%, 13%]; continuous, per SD-increase in BMI: -8% [-13%, -2%]), and tendencies toward lower semen volume and concentration were observed. No associations were observed for the remaining semen characteristics and testicular volume. A higher body fat percentage was associated with lower sex hormone-binding globulin and testosterone levels, and higher free androgen index, LH, and estradiol levels. The results for low body fat (<8%) were generally in the opposite direction but less consistent. The associations with total sperm coun","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1602-1611"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619582","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}
Jonas Vibert, Milos Stojanov, Tatiana Da Silva, David Baud, Nicola Pluchino
{"title":"Microbiome and chronic pelvic pain in women: a mini-review.","authors":"Jonas Vibert, Milos Stojanov, Tatiana Da Silva, David Baud, Nicola Pluchino","doi":"10.1093/humrep/deag110","DOIUrl":"10.1093/humrep/deag110","url":null,"abstract":"<p><p>Chronic pelvic pain (CPP) is a prevalent, disabling syndrome encompassing overlapping disorders such as endometriosis/adenomyosis, bladder pain syndrome/interstitial cystitis, irritable bowel syndrome, vulvodynia, and myofascial pain syndrome. Despite distinct clinical phenotypes, these conditions converge on shared biological axes-immune dysregulation, endocrine imbalance, and central sensitization-that sustain chronic pain. Increasing evidence implicates the human microbiome as a potential upstream regulator of these pathways. Dysbiosis across the gut, vaginal, urinary, and endometrial microbial ecosystems may promote local and systemic inflammation, compromise epithelial barrier integrity, alter estrogen recirculation through the estrobolome, and engage aberrant neuroimmune signalling along gut-brain and hypothalamic-pituitary-ovarian circuits. Recent multi-site profiling suggests that microbial alterations often co-occur across pelvic compartments but remain anatomically distinct, with shifts in anaerobic taxa and paired cervicovaginal immune signatures supporting microbiome-immune interactions in CPP pathophysiology. This narrative review synthesizes observational, multi-omics, and mechanistic evidence linking microbial dysbiosis to CPP, highlights microbial metabolites as key functional mediators, and evaluates causal data from experimental models. Finally, it discusses translational opportunities and limitations, including microbiome-targeted interventions (dietary modulation, probiotics/psychobiotics, postbiotics, and microbiota transfer approaches) and the need for harmonized, longitudinal and biomarker-embedded trials to enable mechanism-based stratification and rational therapeutic development.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1482-1496"},"PeriodicalIF":6.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584243","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}