Human reproduction最新文献

{"title":"Studies of post-partum placentas provide insights into the origin of structural chromosomal aberrations.","authors":"S H Thomsen,A van Berkel,S van Veen,N van Koetsveld,M Joosten,K E M Diderich,M van den Born,M I Srebniak,D Van Opstal","doi":"10.1093/humrep/deaf235","DOIUrl":"https://doi.org/10.1093/humrep/deaf235","url":null,"abstract":"STUDY QUESTIONCan comprehensive cytogenetic follow-up of the placenta post-partum uncover possible explanations for discrepancies between non-invasive prenatal testing (NIPT) showing structural chromosomal aberrations and foetal follow-up showing normal results or other chromosomal aberrations?SUMMARY ANSWERIn 18/31 (58%) cases of structural chromosomal aberrations detected with NIPT, where foetal and maternal follow-up was normal or the foetus had another chromosomal aberration, genome-wide examination of term placental chorionic villi confirmed the discrepancy and in 7/18 (39%) confirmed cases complex foeto-placental mosaicism was found.WHAT IS KNOWN ALREADYComplex chromosomal rearrangements are often seen in single-cell studies of preimplantation embryos, but it is unknown if these persist into the mature placenta. Confined placental mosaicism explains most discordant NIPTs involving a trisomy, but little is known about structural chromosome aberrations.STUDY DESIGN, SIZE, DURATIONWe performed a retrospective diagnostic test study of cytogenetic follow-up data from post-partum placentas. We included data from pregnancies where (i) NIPT showed a structural aberration, (ii) follow-up of foetus (amniotic fluid and/or cord blood) and mother (genomic DNA and/or cfDNA after birth) was normal or the foetus showed another chromosomal aberration, (iii) follow-up was performed in the Erasmus MC, (iv) more than one sample from the post-partum placenta was analysed, and (v) samples were of good quality (not in formaldehyde, sufficient material).In the period from January 2014 to March 2022, 115 231 NIPTs were performed in the Erasmus MC; 217 of these showed structural chromosomal aberrations and 123 were followed up in the Erasmus MC (inclusion criteria 3). After exclusion of the foetal (same aberration as with NIPT) and maternal structural chromosome aberrations, 48 placentas were requested to elucidate the discrepancies seen between NIPT (abnormal) and foetal karyotype (normal or differently abnormal; inclusion criteria 1-2). Of these, 31 met criteria 4 and 5 and were included in this study.PARTICIPANTS/MATERIALS, SETTING, METHODSIn a diagnostic setting, we performed a cytogenetic analysis of postpartum placentas in order to confirm confined placental mosaicism in 31 cases in which NIPT showed a structural chromosome aberration. Two to four chorionic villus biopsies were taken per placenta, and separated enzymatically into cytotrophoblast (CTB) and mesenchymal core (MC) and analysed using SNP arrays. In our analysis, cases were assessed for copy number variants ≥0.5 Mb and regions of homozygosity ≥3 Mb.MAIN RESULTS AND THE ROLE OF CHANCEIn 18/31 cases (58%), we could confirm the structural chromosome aberration detected with NIPT in one or more placental biopsies. In 13/31 cases (42%), the structural chromosomal aberration detected with NIPT was not confirmed, but in one case an apparently unrelated aberration was found in the CTB of two biopsies. In 11","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"18 2 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664283","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":"Microdeletion and microduplication syndromes, including recurrent rearrangements at 16p11.2 and 22q11.21, are enriched in unexplained male infertility.","authors":"Triin Kikas,Avirup Dutta,Rain Inno,Kristjan Pomm,Stanislav Tjagur,Olev Poolamets,Hanno Roomere,Margus Punab,Maris Laan","doi":"10.1093/humrep/deaf231","DOIUrl":"https://doi.org/10.1093/humrep/deaf231","url":null,"abstract":"STUDY QUESTIONWhat is the impact of undiagnosed microdeletion and microduplication syndromes (MMS) for men with idiopathic low sperm count?SUMMARY ANSWERAmong idiopathic male infertility, ∼2% of cases harbour known disease-causing microdeletions and duplications linked to clinically well-established syndromes, representing ∼2.5-fold higher prevalence than in the general population.WHAT IS KNOWN ALREADYWhile infertility affects up to 10% of men, a substantial proportion of cases remain with no identifiable underlying cause. Recurrent submicroscopic losses or gains cause MMS, some of which also impact reproductive phenotypes, including cryptorchidism and reduced fertility.STUDY DESIGN, SIZE, DURATIONThis retrospective study investigated the proportion of undiagnosed MMS among idiopathic male infertility cases. Patients with unexplained low total sperm counts (TSC; defined as ≤39 million sperm per ejaculate) were recruited to the ESTonian ANDrology (ESTAND) cohort at the Andrology Clinic of Tartu University Hospital (AC-TUH) in Estonia. A total of 504 men were included in the analysis, and the study capitalized on available whole-exome sequencing (WES) data to explore large (>500 kb) chromosomal deletions and duplications.PARTICIPANTS/MATERIALS, SETTING, METHODSCopy number variant (CNV) calling was executed on the WES dataset, followed by a stringent, custom-developed filtering pipeline that retained only high-confidence CNVs larger than 500 kb. Candidate CNVs were validated by chromosomal microarray analysis (CMA) or whole-genome sequencing (WGS). Prevalence of identified MMS-linked deletions and duplications in the ESTAND cohort was compared to general population literature data.MAIN RESULTS AND THE ROLE OF CHANCEA total of nine patients (1.8%) carried losses and gains linked to clinically well-characterized MMS-recurrent microdeletions at 16p11.2 (two cases), 2q13-14.1, and 15q13.2-13.3, and microduplications at 22q11.21 (three cases), 16p11.2, and 8p23.1. The total burden of MMS among infertile men was ∼2.5-fold higher compared to the general population (P = 0.01, χ2 test). Cryptorchidism was a novel shared feature among all individuals with 16p11.2 rearrangements, suggesting a potential role in disrupting testicular development. Three subjects with MMS-linked microduplications, but none with a microdeletion, had achieved biological fatherhood. An oligozoospermia case (TSC 1.92 × 106/ej.) with 16p11.2 duplication had a naturally conceived child in youthhood. For two men carrying 22q11.21 duplication (TSC 0 and 4.2 × 106/ej., respectively), implementation of ARTs-ICSI with or without preceding testicular sperm aspiration-resulted in successful conception and childbirth. Evidence for a plausible link to male gonadal development and function has been reported for MAZ and KCTD13 at 16p11.2, and LZTR1 at 22q11.21. As an additional finding, a novel ∼3.8 Mb microduplication at 3p25.1 was identified in an oligozoospermia patient and his azoospermic son,","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"113 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A North American preconception study of sleep health and semen quality.","authors":"Chad M Coleman,Amelia K Wesselink,Jennifer J Yland,Greg J Sommer,Michael L Eisenberg,Suzanne M Bertisch,Kenneth J Rothman,Elizabeth E Hatch,Lauren A Wise","doi":"10.1093/humrep/deaf228","DOIUrl":"https://doi.org/10.1093/humrep/deaf228","url":null,"abstract":"STUDY QUESTIONTo what extent are self-reported sleep health measures associated with semen quality?SUMMARY ANSWERPoor sleep health-including short and long sleep durations, increased frequency of sleep trouble, and poor sleep quality-was associated with reduced sperm concentration, total sperm count, and total motile sperm count, and, in the case of short sleep duration and increased frequency of sleep trouble, reduced semen volume.WHAT IS KNOWN ALREADYSemen quality has declined over the past several decades. Sleep health may affect semen quality through multiple pathways, including endocrine dysfunction, and population-based prospective studies of the association are scarce.STUDY DESIGN, SIZE, DURATIONWe analyzed cross-sectional data from 690 male participants (1247 semen samples) aged ≥21 years at enrollment (2015-2023) in Pregnancy Study Online, a North American preconception cohort study.PARTICIPANTS/MATERIALS, SETTING, METHODSAt baseline, participants provided self-reported data on sleep duration in the past month and frequency of sleep trouble in the previous 2 weeks. A subset of participants completed the Pittsburgh Sleep Quality Index. We used generalized estimating equations (GEE) models to estimate mean percentage differences (%D) and 95% CIs for the associations of sleep health with semen parameters (semen volume, sperm concentration, percent motility), ascertained using a validated at-home semen testing kit. We also used GEE models to estimate prevalence ratios for poor semen quality (low vs normal) based on World Health Organization (WHO) standards.MAIN RESULTS AND THE ROLE OF CHANCEComparing sleep durations of <6 vs 7-8.9 h/day, %Ds (95% CIs) were -11.3% (-23.6%, 1.1%), -16.4% (-45.0%, 26.9%), -27.1% (-53.1%, 13.2%), and -20.0% (-50.3%, 28.8%) for semen volume, sperm concentration, total sperm count, and total motile sperm count, respectively. We observed similar associations for ≥9 vs 7-8.9 h/day and sperm concentration (-14.4% [-44.9%, 33.0%]), total sperm count (-13.9% [-44.1%, 32.7%]), and total motile sperm count (-6.8% [-42.1%, 49.9%]). Comparing sleep trouble >50% of the time vs never, %Ds (95% CIs) were -3.3% (-12.0%, 5.4%), -11.9% (-29.9%, 10.8%), -16.2% (-34.3%, 7.0%), and -16.9% (-37.3%, 9.9%) for semen volume, sperm concentration, total sperm count, and total motile sperm count, respectively. Comparing global Pittsburgh Sleep Quality Index scores of >5 (poor sleep quality) vs ≤5 (good sleep quality), %Ds (95% CIs) were -18.1% (-33.5%, 0.9%), -19.2% (-34.6%, -0.1%), and -16.3% (-33.5%, 5.4%) for sperm concentration, total sperm count, and total motile sperm count, respectively. Analyses based on WHO semen quality standards showed consistent results.LIMITATIONS, REASONS FOR CAUTIONNon-differential misclassification of sleep health was possible due to our reliance on self-reported data collected at a single point in time. Non-differential misclassification of semen quality was also possible, as participants used an at-home ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"39 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656839","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":"Safeguarding WHO guideline recommendations through strengthened scientific integrity to advance global health.","authors":"Gitau Mburu,Nancy Santesso,Romina Brignardello-Petersen,Cynthia Farquhar,Richard Kennedy,James Kiarie","doi":"10.1093/humrep/deaf217","DOIUrl":"https://doi.org/10.1093/humrep/deaf217","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"243 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613259","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":"WHO infertility guidelines 2025: a call for evidence-based practice.","authors":"Kirstine Kirkegaard,Chris Barratt","doi":"10.1093/humrep/deaf229","DOIUrl":"https://doi.org/10.1093/humrep/deaf229","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"23 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613261","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":"Patient-derived epithelial cell organoids mimic the phenotypic complexity of endometriosis subtypes.","authors":"K Gunther,D Liu,M Cortesi,E Powell,E Nesbitt-Hawes,J A Abbott,C E Ford","doi":"10.1093/humrep/deaf230","DOIUrl":"https://doi.org/10.1093/humrep/deaf230","url":null,"abstract":"STUDY QUESTIONCan patient-derived organoid models be reliably established from diverse surgical phenotypes of endometriosis, and how do clinical factors such as hormonal treatment affect their growth success and morphology?SUMMARY ANSWEREndometriosis organoids can be established across all major surgical phenotypes with variable efficiency, and hormonal treatment at the time of biospecimen collection significantly reduces organoid establishment success.WHAT IS KNOWN ALREADYOrganoid cultures have been developed from eutopic endometrium and select endometriosis tissue biospecimens previously, but their feasibility as pre-clinical models of endometriosis across diverse tissue types and clinical presentations remains unclear.STUDY DESIGN, SIZE, DURATIONTwenty-eight endometriosis tissue biospecimens were obtained from 23 patients undergoing surgery, with organoid cultures assessed through successive stages of establishment, passage, and cryopreservation.PARTICIPANTS/MATERIALS, SETTING, METHODSEndometriosis biospecimens, including deep infiltrating endometriosis (DIE), ovarian endometrioma (OMA), and superficial peritoneal (SUP) biospecimens, were processed into organoid cultures using a validated low-Wnt culture system. Organoid viability, morphology, hormone receptor expression, and cellular composition were evaluated by microscopy, immunohistochemistry, and quantitative morphometric analysis.MAIN RESULTS AND THE ROLE OF CHANCEOverall, 22/28 (78.6%) biospecimens established 3-dimensional structures, with 15/28 (53.6%) remaining viable after cryopreservation. Establishment success differed by phenotype (OMA 71.4%, DIE 63.6%, SUP 30%). Progesterone receptor expression was retained in SUP and DIE-derived organoids (7/7, 100%), while OMA-derived organoids showed substantial reductions (4/5 cases). Biospecimens from patients receiving hormonal treatment were smaller (P = 0.038) and had reduced organoid establishment success (3/13, 23.1% vs 12/15, 80.0%, P = 0.003). Organoids exhibited distinct morphological patterns correlating with disease phenotype.LIMITATIONS, REASONS FOR CAUTIONUniform culture conditions may limit growth of certain subtypes, and the in vitro organoid models may not fully represent in vivo tissue complexity. Sample sizes were modest, and pooling tissues from the same patient could mask intra-patient heterogeneity.WIDER IMPLICATIONS OF THE FINDINGSThese organoid models offer a promising platform for studying subtype-specific endometriosis biology, including hormone resistance mechanisms, and could inform personalized therapeutic development. The impact of hormonal treatment on organoid viability underscores the need to consider clinical context in pre-clinical models of endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the National Endometriosis Clinical and Scientific Trials (NECST) Network, funded by the Australian Government Department of Health and Aged Care (Grant 4-I66SNMA), and by a research grant from E","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"197 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609932","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":"Preimplantation genetic testing for neurofibromatosis type 1: molecular genetic aspects and impact on reproductive counseling.","authors":"V Vernimmen,M De Rycke,C Moutou,J Dreesen,M J Blok,R van Minkelen,J Lauer-Zillhardt,P Verdyck,K Keymolen,C van Uum,I Homminga,L Brandts,C T R M Stumpel,E Coonen,M Heijligers,W van Zelst-Stams,M Zamani Esteki,A van den Wijngaard,C E M de Die-Smulders,A D C Paulussen","doi":"10.1093/humrep/deaf224","DOIUrl":"https://doi.org/10.1093/humrep/deaf224","url":null,"abstract":"STUDY QUESTIONHow do the genetic complexities of neurofibromatosis type 1 (NF1) impact reproductive counseling, preimplantation genetic testing (PGT) design, and PGT treatment?SUMMARY ANSWERWe established association between both incidence and tissue mosaicism with multiple exon deletions and specific single-nucleotide variants (SNVs) in neurofibromin 1 (NF1), a clinical actionable finding that we structured as a flowchart outlining challenges in and an approach for reproductive counseling, PGT design, and PGT treatment for NF1.WHAT IS KNOWN ALREADYNF1 has a prevalence of 1 in 2500-3000 and is one of the most frequently requested autosomal dominant indications for PGT. NF1 is a large gene with a high mutation rate, resulting in a 50% de novo occurrence, many different reported variants scattered across the gene and relatively frequent mosaicism.STUDY DESIGN, SIZE, DURATIONWe conducted a retrospective, observational cohort study on PGT molecular design for NF1 in three large PGT centers (n = 281 couples), starting from the first assay for NF1 developed in 2004 until 2022.PARTICIPANTS/MATERIALS, SETTING, METHODSA PGT assay was developed for 281 couples with 218 different variants in NF1. Newly described variants (n = 76) were scored using the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) classification system and submitted prior to publication in the Leiden Open Variation Database (LOVD). The employed techniques were PCR-based PGT using short tandem repeat markers (n = 230), SNP-array-based PGT (n = 39), and next-generation sequencing (NGS)-based PGT (n = 12). Minisequencing (SNAPshot) or double amplification refractory mutation system (D-ARMS) was used to incorporate SNVs. Small deletions and insertions were incorporated using fragment length analysis. All PGT assays were designed and validated according to local protocols and ESHRE guidelines.MAIN RESULTS AND THE ROLE OF CHANCEMosaicism was present in 8% of the sporadic cases (n = 13/168), of which about half were unknown prior to PGT (n = 6/13). Mosaicism was significantly higher in patients with multiple exon deletions (n = 4/6) as compared to patients with SNVs (n = 9/162) (P < 0.001, Fisher's exact test). Additionally, two recurrent SNVs were significantly associated with mosaicism (P <0.0167, Fisher's exact test). Importantly, three unrelated families with different NF1 variants in close relatives were identified.LIMITATIONS, REASONS FOR CAUTIONDue to its retrospective design, not all details on the genetic test results and clinical phenotype could be retrieved for some cases (n = 6). The extent to which our findings are applicable to centers worldwide depends on their local procedures and legislation.WIDER IMPLICATIONS OF THE FINDINGSOur findings substantially impact reproductive counseling for couples with NF1, enabling informed reproductive decision-making. For couples affected with NF1 proceeding with PGT, our findings alert co","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"2 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599766","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":"Male infertility and risk of cardiometabolic conditions: a population-based cohort study","authors":"Jack Marozzi, Mark Hanly, Christos Venetis, Moira K O’Bryan, Robert McLachlan, Georgina M Chambers","doi":"10.1093/humrep/deaf218","DOIUrl":"https://doi.org/10.1093/humrep/deaf218","url":null,"abstract":"STUDY QUESTION Is male infertility independently associated with an increased risk of incident hypertension, ischemic and non-ischemic heart disease, diabetes, and/or cerebrovascular disease? SUMMARY ANSWER Fathers diagnosed with male infertility have a modestly increased risk of heart disease, diabetes, and hypertension compared with fertile fathers, after controlling for measured confounders; however, some important confounders remain inadequately measured. WHAT IS KNOWN ALREADY Cohort studies suggest that infertile men have an increased risk of incident cardiometabolic diseases, including diabetes, hypertension, heart disease, and cerebrovascular disease, although findings are mixed. The reasons for this association are unclear, but cardiometabolic conditions and male infertility share a wide range of shared etiological factors including age, chronic conditions such as obesity and obstructive sleep apnea, cancers and their treatments, environmental exposures such as pollution and pesticides, lifestyle factors such as smoking and cardiorespiratory fitness, autoimmune conditions such as lupus and Hashimoto’s thyroiditis, as well as congenital conditions such as cystic fibrosis and muscular dystrophy. STUDY DESIGN, SIZE, DURATION Our population-based cohort study included 445 909 men whose partner conceived a child between January 2009 and September 2016 in New South Wales (NSW), Australia. We excluded men with a diagnosis of infertility prior to 2009, men who were under the age of 14 at the time of the child’s conception, and men diagnosed with cardiometabolic conditions in the 6.5 years prior to their index date. The index date was the later of the date of the child’s conception or the date of the vasectomy for fertile men or the date of diagnosis of infertility for infertile men, i.e. the time when the exposure status was determined. From the index date, we followed participants for 5 years up until the latest available date of September 2021. PARTICIPANTS/MATERIALS, SETTINGS, METHODS The study was conducted in NSW, Australia. We determined infertility status by a diagnosis of male infertility in the Australian and New Zealand Assisted Reproduction Database, hospital records, or a record of fertility-related procedures. We assessed the following outcomes: incident hypertension, ischemic and non-ischemic heart disease, all heart disease, diabetes, and cerebrovascular disease. We calculated age-standardized prevalence rates at baseline. We mapped potential confounding pathways using directed acyclic graphs and controlled for measured confounders using inverse probability of treatment weighting and g-computation. We estimated adjusted marginal risk ratios (aRR) and adjusted marginal risk differences (aRD) using robust Poisson regression. MAIN RESULTS AND THE ROLE OF CHANCE The number of events and 5-year crude incidence rate for the outcomes were: hypertension (events: 17 433, fertile: 41.09 per 1000 population, infertile: 70.03 per 1000 populati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"55 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of progesterone via vaginal oil capsules versus pessaries for luteal phase support in assisted reproduction treatment: a multicentre cohort study of 42 291 cycles","authors":"R K Dhillon-Smith, M Khairy, T Bamford, V Sephton, A Richardson, A H Balen, A Coomarasamy","doi":"10.1093/humrep/deaf219","DOIUrl":"https://doi.org/10.1093/humrep/deaf219","url":null,"abstract":"STUDY QUESTION What is the effect of progesterone administered via vaginal oil capsules versus pessaries, on clinical outcomes, when used for luteal phase support (LPS) in ART? SUMMARY ANSWER Our study findings indicate a higher live birth rate with vaginal oil capsules compared with pessaries, in both fresh and frozen cycles. In the frozen cycles, a lower miscarriage rate was observed with vaginal oil capsules compared with pessaries. WHAT IS KNOWN ALREADY Sufficient LPS, with exogenous progesterone, is essential during ART to improve implantation and pregnancy rates. Micronized vaginal progesterone (MVP) is the most commonly used form of luteal support worldwide. There are no head-to-head comparisons of vaginal oil capsules versus pessaries, with a focus on clinical efficacy, for LPS. STUDY DESIGN, SIZE, DURATION Retrospective cohort study of patients who completed ART cycles with either only vaginal oil capsules 600–800 mg/day or only pessaries 800 mg/day for LPS. Primary outcomes were live birth and miscarriage. Data for fresh IVF/ICSI cycles and frozen embryo transfer cycles with hormone replacement therapy (HRT-FET) were analysed separately. Multivariable regression analyses were performed with adjustment for female age, BMI, ethnicity, ovarian reserve, duration and cause of subfertility, stimulation protocol, number of previous cycles, number of oocytes, number of embryos transferred, previous live births, and previous miscarriages. PARTICIPANTS/MATERIALS, SETTING, METHODS Our study population consisted of women undergoing treatment across 14 Care Fertility clinics in the UK, from January 2017 to December 2022. We included women with stimulated IVF/ICSI cycles with fresh embryo transfer and autologous HRT-FET cycles. A total of 42 291 cycles were analysed; vaginal oil capsules were exclusively used in 25 738 cycles and pessaries exclusively in 16 553 cycles. MAIN RESULTS AND THE ROLE OF CHANCE In the IVF/ICSI group, the live birth rate was higher in those taking vaginal oil capsules compared with pessaries: 34.3% vs 27.8%; adjusted risk ratio (aRR) 1.11 (95% CI 1.04–1.19; P < 0.001). In the HRT-FET group, the live birth rate was also higher in those taking vaginal oil capsules compared to pessaries: 36.7% vs 32.9% (aRR 1.09; 95% CI 1.04–1.14; P < 0.001). The miscarriage rate was lower in those taking vaginal oil capsules compared to pessaries for both IVF/ICSI (13.4% vs 14.5%, P < 0.05) and HRT-FET cycles (17.2% vs 19.7%, P < 0.001) in the crude analysis. The adjusted analysis for miscarriage found a statistically significant difference only for HRT-FET cycles (aRR 0.87; 95% CI 0.82–0.93). LIMITATIONS, REASONS FOR CAUTION This is a retrospective cohort study. Whilst we have extensively adjusted for confounding, there can still be residual confounding. WIDER IMPLICATIONS OF THE FINDINGS An appropriately powered randomized controlled trial directly comparing the two drugs, focusing on clinical efficacy, is require","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"14 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567205","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":"Serum miRNA-based diagnostic models for endometriosis: from discovery to validation","authors":"Antonella Ravaggi, Cosetta Bergamaschi, Jacopo Conforti, Giuseppe Ciravolo, Laura Zanotti, Aline S C Fabricio, Massimo Gion, Elia Cappelletto, Antonette E Leon, Diego Oreste Rossetti, Cesare Romagnolo, Stefano Calza, Eliana Bignotti, Franco Odicino","doi":"10.1093/humrep/deaf221","DOIUrl":"https://doi.org/10.1093/humrep/deaf221","url":null,"abstract":"STUDY QUESTION Can a serum miRNA signature serve as a potential diagnostic biomarker for endometriosis (END)? SUMMARY ANSWER A miRNA-based diagnostic model demonstrated an accuracy of 65.8% in distinguishing END patients from control subjects (CTR), demonstrating good sensitivity but limited specificity. WHAT IS KNOWN ALREADY Existing research has examined the potential utility of circulating miRNAs as biomarkers for END diagnosis, revealing their differential expression between women with END and CTR. Nevertheless, the findings remain conflicting, and at present, neither a single miRNA nor a panel of them has yet been established as a reliable diagnostic test in clinical practice for the management of END. STUDY DESIGN, SIZE, DURATION We previously reported different miRNA expression patterns in serum samples from 67 END patients and 60 CTR by high-throughput RT-qPCR. In this multicenter study, a total of 364 patients with pathology-confirmed diagnosis of END or a benign non-END gynecological condition were retrospectively selected from a biobank or prospectively enrolled. The aims of the present study were to analyze, in the entire cohort of patients, a set of 23 potential diagnostic miRNAs via RT-qPCR and to create models capable of diagnosing END through cross-validated machine learning algorithms. PARTICIPANTS/MATERIALS, SETTING, METHODS Total RNA was extracted from serum samples collected before surgical treatment and miRNAs were evaluated by RT-qPCR. Diagnostic models were developed using both the Random Forest and Logistic Regression algorithms. The performance assessment of the various models was derived from internal validation, using repeated cross-validation. MAIN RESULTS AND THE ROLE OF CHANCE The most effective diagnostic model was constructed with 11 miRNAs: miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p. The diagnostic efficacy of the model was defined by an AUC of 70.4%, a sensitivity of 75.6%, a specificity of 53.5%, and an accuracy of 65.8%. The model that used six miRNAs (miR-192-5p, miR-30b-5p, miR-335-5p, miR-338-3p, miR-486-5p, miR-652-3p) was the best at identifying deep infiltrating endometriosis compared to the control group, with an AUC of 80.4% and an accuracy of 75.9%. A lower accuracy was achieved by the model differentiating ovarian endometrioma (OMA) from CTR (AUC = 65.8%; accuracy = 62.4%). LARGE SCALE DATA miRNA expression profiles have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession numbers GSE279435. LIMITATIONS, REASONS FOR CAUTION Despite the internal cross-validation, the models still need to be tested on larger cohorts of prospectively enrolled patients across several centers to enhance their accuracy and robustness. This testing will also facilitate monitoring the model in a real-world setting, potentially integrating the miRNA-based model with other diagnostic tools, suc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"19 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567204","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}