Human reproduction最新文献

{"title":"Loss-of-function variants in CFAP57 , SEPTIN4 , SPEM2 , and CFAP46 cause asthenoteratozoospermia","authors":"Shoaib Nawaz, Hiroaki Kitakaze, Maha A Abdulla, Nida Khan, Haruhiko Miyata, Mohamed Nadhir Djekidel, Manar Ata, Yuki Kaneda, Hammal Khan, Ihsan Khan, Maria Esteves, Geethanjali Devadoss Gandhi, Fadi Choucair, Shabir Hussain, Elbay Aliyev, Yuki Hatanaka, Yuma Kujime, Go Tsujimura, Takahiro Imanaka, Sohei Kuribayashi, Norichika Ueda, Mohamed M Arafa, Haitham T Elbardisi, Kentaro Takezawa, Shinichiro Fukuhara, Norio Nonomura, Abbirami Sathappan, Abdul Rahman Salhab, Johnny Awwad, Imran Ullah, Khalid Fakhro, Masahito Ikawa, Matteo A Avella","doi":"10.1093/humrep/deag154","DOIUrl":"https://doi.org/10.1093/humrep/deag154","url":null,"abstract":"STUDY QUESTION What are the genetic causes of asthenoteratozoospermia in consanguineous families, and what is the specific role of cilia- and flagella-associated proteins (CFAP) 46 in mammalian spermiogenesis? SUMMARY ANSWER CFAP46 is a central apparatus protein essential for sperm flagellar assembly and head remodeling. WHAT IS KNOWN ALREADY Asthenoteratozoospermia is a genetically heterogeneous condition characterized by reduced sperm motility and abnormal morphology. While several CFAPs are known to support axonemal organization, the functional role of CFAP46 in mammals remained uncharacterized prior to this study. STUDY DESIGN, SIZE, DURATION We performed whole-genome or whole-exome sequencing on 13 consanguineous families affected by primary male infertility. Functional validation was conducted using three CRISPR/Cas9-engineered mouse models: a null allele, a FLAG-tagged knock-in, and a humanized patient-specific nonsense allele. PARTICIPANTS/MATERIALS, SETTING, METHODS Genomic DNA from affected individuals and fertile relatives was analyzed by NGS and validated via Sanger sequencing. Mouse phenotypes were characterized through sperm analysis, immunofluorescence, and electron microscopy. Protein interactions were identified via immunoprecipitation and mass spectrometry. Additionally, a gene-level burden analysis was applied to unresolved cases across 345 spermiogenesis-associated genes. MAIN RESULTS AND THE ROLE OF CHANCE We identified homozygous loss-of-function variants in CFAP46, CFAP57, SEPTIN4, and SPEM2 segregating with infertility. Cfap46-deficient males were infertile due to significantly decreased sperm count, motility, and severe axonemal disruptions. CFAP46 was found to form an in vivo complex with CFAP54, CFAP74, and CFAP221. In families without a monogenic cause, affected individuals harbored a significantly higher burden of rare deleterious variants (4–16 genes) compared to fertile controls. LARGE SCALE DATA Large-scale datasets and scripts are available via GitHub (https://github.com/sirusb/Nawaz_et_al_scripts). LIMITATIONS, REASONS FOR CAUTION While functional mouse data strongly supports the identified variants, the rare-variant burden analysis identifies associations that require further functional validation to confirm specific oligogenic interactions. WIDER IMPLICATIONS OF THE FINDINGS This study establishes CFAP46 as a regulator of mammalian spermiogenesis and suggests that, beyond monogenic defects, aggregated rare-variant burden may also contribute to male infertility. These findings refine the genetic basis of asthenoteratozoospermia, supporting precise molecular diagnosis, individualized prognostic counseling, and informed use of assisted reproduction (e.g. ICSI) in affected couples. FUNDING This work was supported by Sidra Medicine grant SDR400185 (to M.A.A.), the FERTILITY-IQ Study and Qatar National Research Fund (QNRF) grant NPRP12S-0318-190394 (to M.A.A. and K.F.), the Qatar Research, Development and Innovation ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"15 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229910","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":"Releasing the syndrome from captivity: why renaming PCOS to PMOS widens reproductive care beyond the anovulatory frame","authors":"Terhi T Piltonen, Helena J Teede, Mahnaz Bahri Khomami","doi":"10.1093/humrep/deag150","DOIUrl":"https://doi.org/10.1093/humrep/deag150","url":null,"abstract":"Polycystic ovary syndrome (PCOS) has long been focused on the ovary and infertility aspects, rooted in the early observations by Stein and Leventhal (1935). The aggregated data, however, show that the syndrome has a wide comorbidity risk beyond fertility aspects involving several endocrine and metabolic derangements, yet without a true risk of ovarian cysts, benign or pathological, as expected with the old name. Moreover, with modern fertility care, women with the condition can reach cumulative childbirth rates comparable to those of unaffected women. The women may have spontaneous ovulations and pregnancies across the reproductive life course and, having high ovarian reserve, enter the menopause later. The endometrium and pregnancy complications have, however, been the blind spots in fertility care. Taking all this into account, in May 2026, a multi-step global consensus process culminating in a Lancet statement renamed the condition polyendocrine metabolic ovarian syndrome (PMOS), with transitional adoption already underway in current international guidance and consolidation into the next major international evidence-based guideline update scheduled for 2028. This opinion argues that the rename is not a cosmetic relabelling but a clinical mandate to widen fertility and pregnancy care, address fragmented care across primary, fertility, obstetric, and endocrine services, and acknowledge the endocrine, metabolic, psychological, and oncological burden. For Human Reproduction’s readership, the 2028 guideline update is the concrete deadline around which language, registry coding, trial protocols, education, and clinical practice can align.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229912","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":"Correction: L26/O-169 Association between endometrial pattern and reproductive outcomes in donor oocyte cycles: a multicentric retrospective analysis on 14,039 single embryo transfers.","authors":"","doi":"10.1093/humrep/deag158","DOIUrl":"https://doi.org/10.1093/humrep/deag158","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181445","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":"Structured reporting of diagnostic hysteroscopy findings in women with reproductive disorders: an ESGE-ESHRE-IFFS international consensus†ǂ.","authors":"U Catena, G Grimbizis, A Arena, R Campo, C De Angelis, A Di Spiezio Sardo, A Feki, H Fernandez, M Horton, E Mocanu, L A Pacheco, G Pados, A Vereczkey, S Saravelos, A Vitagliano, M Acién, L Gianaroli","doi":"10.1093/humrep/deag143","DOIUrl":"https://doi.org/10.1093/humrep/deag143","url":null,"abstract":"<p><strong>Study question: </strong>How should the findings of diagnostic hysteroscopy in women with reproductive disorders be reported?</p><p><strong>Summary answer: </strong>This collaborative document by the European Society for Gynaecological Endoscopy (ESGE), the ESHRE, and the International Federation of Fertility Societies (IFFS) provides the first detailed structured reporting template for diagnostic hysteroscopy findings in women with reproductive disorders.</p><p><strong>What is known already: </strong>Despite its widespread use in women with reproductive disorders, no standardized framework currently exists for reporting of hysteroscopic findings. This lack of uniformity may limit the utility of the procedure and contribute to substantial heterogeneity among operators and centers. As a result, the reproducibility of hysteroscopy is limited, making it difficult to conduct robust studies that define its prognostic value in specific patient subgroups.</p><p><strong>Study design, size, duration: </strong>A dedicated working group from ESGE, ESHRE, and IFFS collaborated to develop a consensus for comprehensive structured reporting of diagnostic hysteroscopy findings in women with reproductive problems.</p><p><strong>Participants/materials, setting, methods: </strong>This consensus paper focuses on grouping diagnostic hysteroscopic findings, structuring their reporting, and adopting standardized terminology for women with reproductive disorders. The virtual Nominal Group Technique, a structured consensus-building method, was adopted to ensure equal contribution from all members in the development of the final consensus.</p><p><strong>Main results and the role of chance: </strong>The document provides a structured reporting of hysteroscopic findings into five sections, each systematically capturing patient characteristics, procedural findings, and pathological observations as follows: patient's characteristics, and findings from the vagina, cervix, uterine cavity, endometrium, and tubal ostia.</p><p><strong>Limitations, reasons for caution: </strong>The inclusion of a finding in this structured report is not a proof of its clinical significance, but it could be used as a validation tool for further research.</p><p><strong>Wider implications of the findings: </strong>The standardized reporting of hysteroscopic findings promotes consistent data collection across centers and could help inform research and exchange of clinical experience, enhancing the value of hysteroscopy in fertility evaluation.</p><p><strong>Funding: </strong>No external funding was received for the development of the consensus process or manuscript preparation.</p><p><strong>Disclosures: </strong>All authors declare that they have no competing interests.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165353","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":"FSP1+ stromal cell-associated macrophage efferocytosis contributes to impaired decidualization in adenomyosis","authors":"Xiaoying Wang,Jie Mei,Rong Li,Yang Zhang,Guangfeng Zhao,Yali Hu,Guijun Yan,Haixiang Sun,Haining Lv","doi":"10.1093/humrep/deag160","DOIUrl":"https://doi.org/10.1093/humrep/deag160","url":null,"abstract":"Abstract STUDY QUESTION Does disrupted cell crosstalk contribute to embryo implantation failure in adenomyosis, and what is the underlying molecular mechanism? SUMMARY ANSWER Expanded Fibroblast-Specific Protein 1 (FSP1)+ stromal cell populations in adenomyosis may promote GAS6-associated macrophage efferocytosis, which correlates with increased macrophage TNF-α secretion and senescence of adjacent stromal cells. WHAT IS KNOWN ALREADY Adenomyosis impairs endometrial receptivity and decidual transformation, contributing to implantation failure and pregnancy loss. Women with this condition exhibit increased endometrial macrophage abundance. STUDY DESIGN, SIZE, DURATION Three mid-secretory phase eutopic endometrial samples from patients with adenomyosis were subjected to single-cell RNA sequencing (scRNA-seq) and integrated with publicly available normal endometrial scRNA-seq data (GSE183837) to characterize cellular alterations and intercellular interactions. Primary human endometrial stromal cells and endometrial macrophages were isolated for in vitro mechanistic studies, including genetic manipulation and functional co-culture assays to investigate stromal–macrophage crosstalk. Peripheral blood mononuclear cells-derived macrophages were generated by M-CSF induction to further validate efferocytosis-related mechanisms, and a mechanical injury-induced C57BL/6 mouse model of adenomyosis was employed to validate key molecular changes in vivo. PARTICIPANTS/MATERIALS, SETTING, METHODS ScRNA-seq data were processed with Cell Ranger and Seurat for clustering and differential expression analysis, while cell–cell communication was analyzed using CellPhoneDB and CellChat. Macrophage efferocytosis was assessed by TUNEL/CD68 staining and in vitro co-culture assays. Senescence was evaluated by senescence-associated β-galactosidase staining and senescence-associated markers/senescence-associated secretory phenotype profiling, while decidualization was assessed by mRNA or protein levels of PRL and IGFBP1. Methods for mechanistic studies included adenovirus transduction, quantitative real-time PCR, western blotting, ELISA, chromatin immunoprecipitation-quantitative PCR, immunohistochemistry, immunofluorescence, and EdU staining. MAIN RESULTS AND THE ROLE OF CHANCE Our findings revealed a significant elevation in the abundance of FSP1+ stromal cells within the eutopic endometrium of adenomyosis patients during the mid-secretory phase. These FSP1+ stromal cells orchestrated GAS6 secretion via the transcription factor ZBTB7A, and GAS6 could potentially interact with MERTK receptors on macrophages to facilitate efferocytosis. Notably, activated macrophages secreted TNF-α, which contributed to senescence in stromal cells and could promote decidualization defects that may further compromise fertility. LARGE SCALE DATA The raw scRNA-seq data have been deposited in the NCBI Sequence under accession number PRJNA1270747. LIMITATIONS, REASONS FOR CAUTION The integration of ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"11 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150367","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":"Conception methods and perinatal outcomes among women with kidney disorders: an Australian population-based cohort study","authors":"Erandi Hewawasam,Shilpanjali Jesudason,Amanda Sluiter,M Louise Hull,Kaushalya Arulpragasam,Louisa Jorm,Wentao Li,Georgina M Chambers","doi":"10.1093/humrep/deag161","DOIUrl":"https://doi.org/10.1093/humrep/deag161","url":null,"abstract":"Abstract STUDY QUESTION Do conception methods and related pregnancy outcomes differ between women with and without kidney disease? SUMMARY ANSWER In this cohort, 3.3% of births among women with kidney disorders were conceived using ART, 1.9% were conceived following IUI and ovulation induction (OI), and 94.8% were conceived spontaneously; however, women with kidney disorders consistently experienced higher risks of adverse pregnancy outcomes than those without, regardless of conception method. WHAT IS KNOWN ALREADY Kidney disorders can impair fertility and pregnancy outcomes, but population‑level data on the use of medically assisted reproduction (MAR), including ART, IUI, and OI, in this group are limited. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included all live births and stillbirths in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia, between 2009 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS We used linked state perinatal records to identify births. Kidney disorder diagnoses before delivery were identified using hospital dataset diagnostic coding. Conception mode was classified as (i) spontaneous conception, (ii) IUI/OI, or (iii) ART (including IVF or ICSI or other procedures [e.g. gamete intra-fallopian transfer, surrogacy]) using the Australia and New Zealand Assisted Reproduction Database and the national claims databases for medical services and pharmaceutical dispensing. MAIN RESULTS AND THE ROLE OF CHANCE During the study period, 911 229 babies were born from 898 084 pregnancies among 606 488 mothers in NSW/ACT. Among these, 10 858 babies (1.2%) were born to 7634 mothers with kidney disorders. Of the babies born to mothers with kidney disorders, 563 babies (5.2%), born to 470 mothers, were MAR-conceived. Women who conceived via MAR were older than those who conceived spontaneously in both groups (kidney disorders: MAR median age 33 (IQR: 30–37) years vs spontaneous median age 29 (24–33), standardized difference (sdiff) = 0.80; non-kidney disorders: MAR median age 34 (31–38) years vs spontaneous median age 31 (27–35), sdiff = 0.71). The most common kidney disorders were renal tubulo-interstitial diseases (MAR: 62.1% vs spontaneous: 72.7%) and urolithiasis (MAR: 36.8% vs spontaneous: 27.2%). The proportion of births conceived using ART was 3.3% among births to women with kidney disorders. The most common MAR treatments were fresh embryo transfers (33.6% kidney disorders vs 37.4% non-kidney disorders), frozen embryo transfers (28.7% vs 29.5%), any OI/IUI (36.0% vs 31.8%), and OI using clomiphene citrate alone (27.0% vs 23.5%). After adjusting for maternal age, parity, Index of Relative Socio-economic Disadvantage, multiple births and pre-existing diabetes, hypertension, and cardiovascular disease, women with kidney disorders had higher odds of caesarean section (MAR: OR 1.49, 95% CI 1.22–1.81; spontaneous: 1.36, 1.29–1.44), preterm birth (MAR: 2.09, 1.62–2.70; spontaneous: 1.76, 1.64–1.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"8 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150368","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":"Ovarian reserve after chemotherapy in premenopausal women with breast cancer undergoing fertility preservation counselling with and without unilateral ovarian tissue cryopreservation.","authors":"Anna Mathilde Yde, Lotte Berdiin Colmorn, Anja Pinborg, Julie Lyng Forman, Ida-Marie Højgaard Prietzel, Catharyn Stern, Stine Gry Kristensen, Lene Hee Christensen, Elisabeth Clare Larsen, Anette Tønnes Pedersen, Kirsten Tryde Macklon","doi":"10.1093/humrep/deag156","DOIUrl":"https://doi.org/10.1093/humrep/deag156","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the impact of chemotherapy on the ovarian reserve in premenopausal women diagnosed with breast cancer, and how is this impacted by fertility preservation (FP) strategy and age at diagnosis?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Chemotherapy reduces ovarian reserve in women with breast cancer, with the greatest reductions observed among women who underwent ovarian tissue cryopreservation (OTC) and those of advanced reproductive age (≥35 years).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Breast cancer is the most prevalent cancer among women of reproductive age, and in recent decades increasing emphasis has been placed on FP, including ovarian tissue, embryo, and oocyte cryopreservation. However, few large prospective studies have evaluated the effect of chemotherapy on ovarian reserve in patients with breast cancer using both anti-Müllerian hormone (AMH) and antral follicle count (AFC), and no large studies have assessed the impact by choice of FP.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;In this combined retro and prospective cohort study, we included 152 premenopausal women diagnosed with breast cancer who received FP counselling at Rigshospitalet, Copenhagen University Hospital, between 1 January 2018 and 31 August 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Women aged 18-42 years scheduled for FP counselling before chemotherapy were included. Exclusion criteria were previous chemotherapy, oophorectomy, and death or emigration within 2 years of inclusion. Medical and gynecological history, and oncological treatment plans were recorded. Ovarian reserve was assessed using AMH and AFC at baseline and at 6, 12, and 24 months after chemotherapy. Changes over time were analyzed using linear mixed models adjusted for age at baseline and hormonal contraceptive use.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Of 152 women, 57 underwent OTC, while 41 underwent oocyte/embryo cryopreservation and 54 had no FP. Baseline median AMH was 13.9 [95% CI: 10.7, 18.1] pmol/l among women who did not undergo OTC and 13.3 [10.9, 16.3] pmol/l among those who did. A marked reduction in both AMH and AFC was observed after chemotherapy, with partial recovery within 2 years after treatment. The reduction was more pronounced, and recovery more limited, in women with OTC and in those of advanced reproductive age (≥35 years). Compared to baseline, the adjusted reduction in median AMH was 90% [95% CI: 85%, 93%] at 6 months and 75% [95% CI: 63%, 83%] at 24 months in women without OTC and 93% [95% CI: 85%, 95%] and 85% [95% CI: 78%, 90%] in women with OTC, respectively. Similar patterns, however, not as profound, were seen for AFC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;Not all women completed assessments at all three follow-up visits, likely reflecting emotional exhaustion, hospital fatigue, reluctance to attend additional appointments, or changes in reproduc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147325","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":"Advanced paternal age affects miscarriages and live birth outcomes in oocyte donation cycles","authors":"Juan J Fraire-Zamora,Maria Cristina Guglielmo,Elena Bartoli,Marzia Valerio,Serena Maruccia,Mario Romano Mignini Renzini,Elena De Ponti,Maria José Zamora,Rafael Lafuente,Juan José Guillen,Amelia Rodriguez-Aranda,Mariabeatrice Dal Canto","doi":"10.1093/humrep/deag159","DOIUrl":"https://doi.org/10.1093/humrep/deag159","url":null,"abstract":"Abstract STUDY QUESTION Does advanced paternal age affect miscarriage and/or live birth outcomes following the first transfer attempt in oocyte donation cycles? SUMMARY ANSWER Paternal age has a gradual but cumulative effect that becomes apparent above 45 years of age, where it evidently increases miscarriage rates and decreases live birth rates following the first transfer in oocyte donation cycles. WHAT IS ALREADY KNOWN Donor oocyte cycles are becoming a common strategy for addressing female age-related infertility, offering high success rates (∼60% ongoing pregnancies) attributed to superior oocyte quality. However, male age-related effects on the success of ART have received less attention. In autologous cycles, advanced paternal age has been associated with poor clinical outcomes. However, disentangling its effects from female factors remains challenging. Oocyte donation cycles offer a useful model for studying the impact of male factors on ART outcomes, eliminating biases related to female age and underlying diagnoses. STUDY DESIGN, SIZE, DURATION Multicentric, retrospective study of 1606 first oocyte donation cycles performed between January 2019 and December 2023, across seven IVF centers. Only ICSI cycles with fresh donor oocytes, inseminated with partner sperm were included. Only the first single blastocyst transfers (fresh or frozen) were considered. Cycles with abnormal male karyotypes, sperm obtained from testicular biopsy, donor sperm, frozen oocytes, in vitro matured oocytes or preimplantation genetic testing (PGT) were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS Paternal age was assessed as a continuous variable, in multiple age strata (&amp;lt;35, 35–40, 40–45, and &amp;gt;45 years) and dichotomized into ≤45 and &amp;gt;45 years. Fertilization rates, the number of usable blastocysts and blastocyst utilization rates were assessed. Clinical outcomes included clinical pregnancy, miscarriage, and live birth rates. P &amp;lt; 0.05 was considered statistically significant after univariate tests and a multivariable logistic analysis adjusting for recipient and oocyte age, male and recipient BMI, fresh/frozen semen for insemination, number of mature (MII) oocytes injected, embryo morphology grade, and fresh/frozen embryo transfer. An exploratory analysis comparing Kaplan–Meier curves for subsequent embryo transfers was performed. MAIN RESULTS AND THE ROLE OF CHANCE Within the cohort of 1606 patients who underwent a first oocyte donation cycle, the mean female recipient age (±SD) was 43.2 (±4.1) years, the mean oocyte donor age (±SD) was 26.2 (±4.2) years, and the mean paternal age (±SD) was 43.1 (±6.0). Paternal age as a continuous variable showed a modest but gradual reduction in live birth without a discrete transition at any specific age. Stratifying paternal age (&amp;lt;35, 35–40, 40–45, and &amp;gt;45 years) showed a trend to reduced odds of live birth when comparing the &amp;gt;45 years group to the &amp;lt;35 years group (","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088277","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":"Infertility and inequality: a plea for action","authors":"Letizia Li Piani,Edgardo Somigliana","doi":"10.1093/humrep/deag157","DOIUrl":"https://doi.org/10.1093/humrep/deag157","url":null,"abstract":"Abstract The recent global guidelines from the World Health Organization on diagnosis, prevention, and treatment of infertility invites us to consider infertility beyond the traditional framing as a clinical condition, recognizing it as a profound issue of equity. The guideline explicitly states that fertility care should be founded on equity, evidence-based information, and respect for human rights while rejecting stigma or discrimination. In this contribution, we propose a conceptual framework that interprets infertility as a system of layered inequalities operating across global, structural, social, temporal, narrative, and individual dimensions. At the global and system levels, geographical differences, legislative fragmentation, disparities in access, and public–private services imbalances define reproductive opportunities. Social and cultural factors, including unequal access to education, limited fertility awareness, biased representations, and potential stigmatization, further contribute to the marginalization of affected individuals, disproportionately impacting vulnerable and minority groups. Time represents a crucial yet often overlooked determinant of injustice. Its manifestations differ across settings, sparing from delayed access to infertility treatment in resource-limited countries to the growing mismatch between biological reproductive constraints and societal trends toward delayed parenthood in many high-income settings. In this context, technological solutions such as assisted reproduction and elective egg freezing may inadvertently reinforce disparities by shifting responsability to individuals rather than addressing broader barriers, partly sustained by misleading narratives in social media. These dynamics often weigh more on women and ultimately interact to shape the individual experience of infertility. Infertility care requires coordinated action beyond a clinical one. Embracing a public health perspective and ameliorating access to fertility services must become the priority, sustained by investment in fertility education, inclusive narratives, and family-friendly policies, alongside greater harmonization of legislation. Considering infertility as an issue of equity means addressing upstream determinants that influence reproductive opportunities long before individuals seek care. The key question is not only who can access fertility treatment, but who reaches it with a meaningful chance of success. Only through such efforts can the opportunity to pursue one’s reproductive goals and build a family, if wished, becomes a reality for many, rather than a privilege for a few.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"50 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088275","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":"L26/O-014  Inositol supplementation in polycystic ovary syndrome (PCOS): a systematic review of randomised controlled trial focusing on data integrity","authors":"J Sung,M Flanagan,N Brown,G Meyerowitz-Katz,B Mol","doi":"10.1093/humrep/deag147","DOIUrl":"https://doi.org/10.1093/humrep/deag147","url":null,"abstract":"Abstract Study question Are randomised controlled trials (RCTs) evaluating inositol for polycystic ovary syndrome (PCOS) methodologically trustworthy, and does excluding untrustworthy studies alter reported treatment effects? Summary answer Three of 28 RCTs met predefined trustworthiness criteria, which was insufficient to allow quantitative comparison of treatment effects between trustworthy and non-trustworthy studies. What is known already Inositol supplementation has been widely studied for the treatment of PCOS, with reported benefits on metabolic, hormonal, and reproductive outcomes. However, the quality of supporting evidence remains variable. While some meta-analyses suggest positive effects, others cite low-certainty findings. Nevertheless, inositol is frequently recommended and widely adopted by patients, often influenced by commercial and social media promotion. A 2024 systematic review formally assessed the trustworthiness of trials in this field. A 2024 systematic review was among the first to assess trial trustworthiness. Since then, tools such as the TRACT checklist have been developed to enable more rigorous integrity evaluation. Study design, size, duration We conducted a systematic review and integrity assessment of 30 RCTs evaluating inositol for PCOS, building on a prior review and updating the search to December 2025. Trial registration: PROSPERO CRD420251129602. Participants/materials, setting, methods We included RCTs reporting on metabolic, hormonal, or fertility outcomes in women with PCOS. Each trial was assessed using the Trustworthiness in RAndomised Controlled Trials (TRACT) checklist. We attempted to reproduce univariable statistical analyses and evaluated baseline randomisation using Monte Carlo simulations. Based on these criteria, studies were classified as meeting or not meeting trustworthiness standards. Treatment effects were then estimated separately for trustworthy and non-trustworthy trials to examine the impact of methodological quality. Main results and the role of chance From 30 RCTs, one had been retracted and one was labelled with an expression of concern. The remaining 28 RCTs were conducted predominantly in Europe and South Asia with 13 studies (46%) originating from Italy and 6 (21%) from India. The median sample size was 60 (range 20 to 526). Twenty-four trials (86%) began recruiting after 2010. From these 24, eight (33%) were prospectively registered, three (13%) were retrospectively registered, while 13 (52%) lacked any trial registration. After applying the TRACT checklist, 16 (57%) RCTs were identified as low risk, four as moderate risk (14%), and eight (26%) as high risk for trustworthiness issues. Overall, we could not reproduce 45% of reported p-values. In 12 papers (43%), more than 50% of p-values were non-reproducible. Simulation-derived baseline p-values deviated from the expected uniform distribution. Notably, five trials (18%) exhibited &amp;gt;40% of baseline p-values that were statisti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"8 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088274","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}