Human reproduction最新文献

{"title":"Planned egg freezing over 15 years: return to treatment and success rates in Australia and New Zealand","authors":"Oisin Fitzgerald,Elena Keller,Devora Lieberman,Michelle Peate,Damian Kotevski,Repon Paul,Iolanda Rodino,Anna Parle,Karin Hammarberg,Tessa Copp,Georgina M Chambers","doi":"10.1093/humrep/deag155","DOIUrl":"https://doi.org/10.1093/humrep/deag155","url":null,"abstract":"Abstract STUDY QUESTION What are the characteristics and treatment outcomes of women who undertook planned egg freezing (PEF) in Australia and New Zealand between 2009 and 2023? SUMMARY ANSWER There has been an average year-on-year increase in the uptake of PEF of 35%, with most women undergoing a single PEF procedure in their mid-thirties and given 10 years follow-up, a little over one in four women return to thaw their eggs, with nearly half of those using donor sperm and one-third achieving a live birth. WHAT IS KNOWN ALREADY PEF, where women freeze their eggs as a strategy to preserve fertility, has increased dramatically in high-income countries in the last decade. Despite the rapid uptake of PEF, there remains limited information to guide women, clinicians, and policy-makers regarding the characteristics of women undertaking this procedure and treatment outcomes. STUDY DESIGN, SIZE, DURATION A retrospective population-based cohort study of all women who undertook PEF in Australia and New Zealand between 2009 and 2023, including their subsequent return to thaw their eggs and treatment outcomes. Where women returned to utilize their eggs, all subsequent embryo transfer procedures were linked enabling calculation of live birth rates per woman. PARTICIPANTS/MATERIALS, SETTING, METHODS Twenty thousand two hundred and nine women who undertook PEF in Australia and New Zealand between 2009 and 2023 including 1657 women who returned to thaw their eggs. Descriptive statistics were used to characterize the cohort at freeze and thaw, along with trends in PEF. Associations between the chance of a live birth upon egg thaw and patient and treatment characteristics were evaluated using a multivariable generalized additive model. MAIN RESULTS AND THE ROLE OF CHANCE There has been a huge increase in uptake of PEF, from 55 women in 2009 to 4919 in 2023. Women who freeze their eggs are typically aged 34–38 years (interquartile range) and nulliparous (98.6%). For women with at least 10 years follow-up (i.e. undertook PEF in 2009–2013; N = 514), 27.9% returned and thawed their frozen eggs (average time to return: 4.9 years). This reduced to 22.1% in those with at least 5 years follow-up (i.e. undertook PEF in 2009–2018; N = 4288). Of those who used their frozen eggs, 47% used donor sperm. After at least 2 years follow-up, 33.9% had a live birth, rising over time to 37.8% for eggs thawed between 2019 and 2021. Female age at egg freeze, number of eggs thawed, and year of egg thaw (but not length of freeze) were associated with the chance of a live birth following egg thaw. LIMITATIONS, REASONS FOR CAUTION In the timeframe 2009–2019, we did not have information on whether egg freezing occurred because of a cancer diagnosis, a cohort we wished to exclude from the study. As a result, for this timeframe, we weighted observations by the probability that egg freezing occurred due to cancer, with the prediction model developed on the years 2020–2023. Changes in laborator","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088276","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":"Publisher's Note: Addendum to Volume 41, Supplement 1, July 2026, Abstracts 42nd Annual Meeting of the European Society of Human Reproduction and Embryology Conference.","authors":"","doi":"10.1093/humrep/deag148","DOIUrl":"https://doi.org/10.1093/humrep/deag148","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108618","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":"Cell cycle regulators contribute to extravillous trophoblast cell differentiation and function.","authors":"Regan L Scott, Ayelen Moreno-Irusta, Kaela M Varberg, Marija Kuna, David K Johnson, Hiroaki Okae, Takahiro Arima, Michael J Soares","doi":"10.1093/humrep/deag132","DOIUrl":"10.1093/humrep/deag132","url":null,"abstract":"<p><strong>Study question: </strong>What is the contribution of cyclin-dependent kinase inhibitor 1C (CDKN1C) to the regulation of extravillous trophoblast (EVT) cell differentiation and function?</p><p><strong>Summary answer: </strong>Cell cycle regulators CDKN1C, cyclin-dependent kinase 7 (CDK7), and cyclin E1 (CCNE1) contribute to the development of a healthy placenta by promoting trophoblast stem (TS) cell differentiation to the invasive EVT cell lineage.</p><p><strong>What is known already: </strong>Early in gestation, cytotrophoblast cells expand and then differentiate into terminal cell lineages, including EVT cells, which invade into uterine tissue and facilitate redirection of maternal resources to the fetus. Cyclin-dependent kinase inhibitor 1C (CDKN1C) is a cell cycle regulator implicated in placental development.</p><p><strong>Study design, size, duration: </strong>In this study, we used control versus gene-silenced human trophoblast stem cells to assess mechanisms regulating human TS cell differentiation to the EVT cell lineage. An 8-day EVT cell differentiation protocol was utilized. RNA sequencing data include n = 3 for control EVT cells and n = 3 for gene-silenced cells. Assessment of cell counts, DNA content, qPCR, and migration assays were performed with between n = 3 and n = 6.</p><p><strong>Participants/materials, setting, methods: </strong>In situ hybridization was used to evaluate CDKN1C, CDK7, and CCNE1 transcript expression in human placental tissue sections. A human trophoblast stem cell model was utilized to assess the contributions of CDKN1C, CDK7, and CCNE1 to EVT cell development. Gene perturbation was achieved through lentiviral delivery of short-hairpin RNAs to XY (CT29) and XX (CT27) human TS cell lines. Characterization of cell models and effects of gene silencing were measured by assessing cell morphology and number, reverse transcriptase-quantitative polymerase chain reaction, western blotting, flow cytometry, and co-immunoprecipitation.</p><p><strong>Main results and the role of chance: </strong>CDKN1C was expressed in EVT cells of the placenta and in EVT cells derived from TS cells. Disruption of CDKN1C in TS cells affected cell proliferation, morphology, DNA content, migration, and transcript profiles. CDKN1C is a known modulator of CDK-CCN complexes. CDK7 and CCNE1 were prominently expressed in EVT cells of the placenta and in EVT cells derived from TS cells. CDKN1C was also shown to physically interact with CDK7 and CCNE1. Loss of CDK7 or CCNE1 impaired EVT cell differentiation.</p><p><strong>Large scale data: </strong>RNA-seq datasets are available at the Gene Expression Omnibus database under accession number GSE316875.</p><p><strong>Limitations, reasons for caution: </strong>In vitro experiments were used to evaluate contribution of cell cycle regulators to EVT cell development. Therefore, these methods do not completely recapitulate the in vivo cell environment.</p><p><strong>Wider implications of the f","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1672-1687"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792405","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}

{"title":"Ambient temperature reduces oocyte yield in assisted reproductive technology via a partially sex hormone-mediated pathway.","authors":"Yi-Yan Zeng, Yu-Ling Hu, Rui-Ling Liu, Li-Hong Geng, Zhao-Hui Zhong, Li-Juan Fu, Gong-Li Chen, Yu-Bin Ding","doi":"10.1093/humrep/deag128","DOIUrl":"10.1093/humrep/deag128","url":null,"abstract":"<p><strong>Study question: </strong>Are higher ambient temperatures before oocyte retrieval associated with adverse oocyte-related outcomes in women undergoing their first IVF or ICSI cycle?</p><p><strong>Summary answer: </strong>Higher pre-retrieval temperatures are associated with reduced oocyte yield, an effect partially mediated through LH and partially counteracted by compensatory increases in FSH and estradiol (E2).</p><p><strong>What is known already: </strong>Evidence on the impact of ambient temperature on IVF/ICSI outcomes is emerging but limited. A recent study reported weak negative associations between higher ambient temperatures during folliculogenesis and oocyte yield, though the effect was modest and findings across populations remain inconsistent. However, these findings are further limited by small sample sizes, specific clinical subpopulations or geographic regions, which prevents the establishment of a generalizable dose-response relationship and leaves the underlying biological mechanisms largely unexplored.</p><p><strong>Study design, size, duration: </strong>A retrospective cohort study of 58 468 women undergoing their first IVF/ICSI cycle with oocyte retrieval between 1 January 2018 and 31 May 2024.</p><p><strong>Participants/materials, setting, methods: </strong>Women undergoing their first IVF/ICSI cycle were included. The primary outcomes were total oocytes retrieved, mature oocytes retrieved, and 2PN (two pronuclei) fertilized oocytes. Secondary outcomes included rates of oocyte maturation, normal fertilization, and blastocyst formation. Basal sex hormone levels were measured during the early follicular phase (cycle days 2-4). Environmental exposure data, including both ambient temperature and apparent temperature (integrating air temperature and humidity), were assessed over biologically relevant exposure windows. Generalized linear mixed-effects models were used to estimate associations between temperature exposures and oocyte-related outcomes. Restricted cubic spline models assessed nonlinearity. A counterfactual causal mediation analysis examined the roles of basal sex hormones. Stratified analyses by age, BMI, antral follicle count, anti-Müllerian hormone, season, COVID-19 period, and the distance to ART center, along with sensitivity analyses, were performed to evaluate robustness.</p><p><strong>Main results and the role of chance: </strong>Each 1°C increase in apparent temperature was associated with significant decreases in total oocytes retrieved (-0.20%; 95% CI: -0.28%, -0.12%), mature oocytes retrieved (-0.17%; 95% CI: -0.26%, -0.09%), and 2PN fertilized oocytes (-0.19%; 95% CI: -0.28%, -0.09%); consistent associations were observed for ambient temperature (-0.25%, -0.22%, and -0.22% per 1°C, respectively). For rate-based outcomes, no significant associations were observed for the normal fertilization rate or blastocyst formation rate; the mature oocyte rate showed small positive associations in longer-term ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1725-1740"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653491","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":"Monitoring ovarian reserve dynamics via a high-sensitivity anti-Müllerian hormone assay in premenopausal breast cancer patients undergoing chemotherapy.","authors":"Xiaojun Kuang, Min Ji, Yongzhe Tang, Qian Wang, Shun Pan, Jialiang He, Richard A Anderson, Bing-Shun Wang, Hong Xu, Dongmei Lai","doi":"10.1093/humrep/deag136","DOIUrl":"10.1093/humrep/deag136","url":null,"abstract":"<p><strong>Study question: </strong>Does an ultra-sensitive anti-Müllerian hormone (UD-AMH) assay enhance the accuracy of ovarian dysfunction assessment in premenopausal women with breast cancer (PBC) during and after chemotherapy?</p><p><strong>Summary answer: </strong>Low AMH levels at pre-treatment and end-of-chemotherapy, measured by the UD-AMH assay, are strong predictors for the development of premature ovarian insufficiency (POI) at 12 months post-chemotherapy.</p><p><strong>What is known already: </strong>Anti-Müllerian hormone (AMH) is a recognized biomarker for assessing ovarian reserve and serves as an early indicator of ovarian dysfunction in female cancer patients. However, post-chemotherapy AMH levels frequently fall below detectable limits of conventional assays, hindering rapid and accurate evaluation of residual ovarian reserve.</p><p><strong>Study design, size, duration: </strong>Prospective cohort study; 145 total subjects enrolled; follow-up conducted from pre-treatment through 12 months post-chemotherapy.</p><p><strong>Participants/materials, setting, methods: </strong>Premenopausal women (aged 18-46 years) with breast cancer recruited at diagnosis; 83 scheduled to receive chemotherapy and 62 who did not. Serum samples were collected pre-treatment (T0), after each chemotherapy cycle, at end-of-chemotherapy (T1), 3 (T2), 6 (T3), and 12 (T4) months post-chemotherapy. AMH levels were quantified using the UD-AMH assay (detection limit 0.13 pg/ml, offering 100-fold higher sensitivity than conventional methods). POI was defined as oligo/amenorrhea with follicle-stimulating hormone (FSH) levels >25 mIU/ml.</p><p><strong>Main results and the role of chance: </strong>AMH was quantifiable in all samples by using the UD-AMH assay. At T4, 30% of PBC exhibited POI. AMH levels at T0 were significantly higher in the non-POI group compared to the POI group (median 5425 pg/ml vs 1103 pg/ml, P < 0.001), as were levels at T1 (median 127 pg/ml vs 10 pg/ml, P < 0.001). T0 AMH predicted POI with an AUC of 0.86 (sensitivity 67%, specificity 95%), while T1 AMH showed superior predictive value with an AUC of 0.89 (sensitivity 81%, specificity 93%).</p><p><strong>Limitations, reasons for caution: </strong>This trial was a single-center study with sample size attrition due to the COVID-19 pandemic. Additionally, the study focused on hormonal dynamics up to 1 months post-chemotherapy, lacking long-term data on clinical fertility outcomes in the identified risk groups.</p><p><strong>Wider implications of the findings: </strong>The application of the UD-AMH assay enables early prediction of POI and offers a valuable tool to guide personalized treatment decisions and fertility preservation strategies in young female cancer patients.</p><p><strong>Funding: </strong>This work was supported by the National Key Research and Development Program of China (2023YFB3210301), National Natural Science Foundation of China (82271664), Shanghai Municipal Council for Sci","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1800-1809"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850564","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 double-blind multi-centre randomised placebo-controlled trial of doxycycline in women with recurrent miscarriage and chronic endometritis defined by CD138 positive stromal cells.","authors":"J Odendaal, N Black, K Fishwick, J Thornton, K Makwana, L Ewington, K Larsen, A Hawkes, C Leeson, J Fisher, R Lall, J Guck, A Coomarasamy, I Granne, M Underwood, G Bouliotis, S Quenby","doi":"10.1093/humrep/deag133","DOIUrl":"10.1093/humrep/deag133","url":null,"abstract":"<p><strong>Study question: </strong>Does preconceptual doxycycline prevent miscarriage in women with recurrent miscarriage (RM) and chronic endometritis (CE) defined by CD138+ stromal cells?</p><p><strong>Summary answer: </strong>Preconceptual doxycycline was not associated with improved livebirth rates in women with CE and a history of RM.</p><p><strong>What is known already: </strong>CE is characterised by asymptomatic endometrial inflammation and has been associated with RM. Some national and international RM guidelines advise testing and treating for CE with antibiotics, most commonly doxycycline, whereas others do not.</p><p><strong>Study design, size, duration: </strong>Definitions of CE vary widely; in this study, all CD138+ cells, not only morphological plasma cells were included in the assessment. This was an adaptive, multi-centre, parallel-arm, double-blind, placebo-controlled, randomised trial. Recruitment started on January 2020, and follow-up finished on October 2023. Of 2178 women screened, 505 were positive for CD138 and 438 were randomised. A subgroup (202) had repeat endometrial biopsies in the luteal phase of their treatment cycle analysed. A screen negative group (208) were followed up in their first pregnancies. Screen positive women were randomised using an online web tool to preconceptual doxycycline 100 mg or an identical placebo from day 1 of the menstrual cycle, twice daily for 14 days. Patients, their clinicians and outcome assessors were blinded to treatment allocation.</p><p><strong>Participants/materials, setting, methods: </strong>Women, aged ≥18 to <42 years with ≥2 consecutive first trimester miscarriages were recruited in specialist RM clinics from 27 UK sites. Screening was by luteal phase endometrial biopsy with immunohistochemistry for CD138. The primary outcome was cumulative live birth and pregnancies ≥24 + 0 weeks gestation at cessation of the trial. Secondary outcomes included first pregnancy outcome, time to first conception and pregnancy complication rates. A prospective Bayesian analysis with no prior information was undertaken to estimate posterior probabilities.</p><p><strong>Main results and the role of chance: </strong>There were 113/219 (52%) cumulative livebirths or ongoing pregnancies in the doxycycline group and 109/219 (50%) in the placebo group (adjusted Relative Risk (aRR)1.02; Credible Interval (CrI) 0.85-1.21). Sensitivity analysis did not influence these results. In the CE negative group, there were 62/208 (30%) livebirths or ongoing first pregnancies compared to 89/219 (41%) in the placebo group (aRR 0.73; CrI 0.56-0.95). The amount and pattern of CD138 staining varied equally before and after placebo (98 paired biopsies) and doxycycline (104 paired biopsies) treatments.</p><p><strong>Limitations, reasons for caution: </strong>In keeping with the adaptive Bayesian design, the trial was stopped at interim analyses. Whilst a higher-than-expected prevalence of CD138+ CE occurred in this stud","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1661-1671"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792347","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}

{"title":"Impact of chemotherapy received prior to testicular tissue cryopreservation on somatic cells from prepubertal to postpubertal males.","authors":"V Rousseau, N Rives, M Basille-Dugay, C Neusius, F Fraissinet, E Chemin, M Dufour, H Dupuis, C Rondanino, A Feraille, L Dumont","doi":"10.1093/humrep/deag135","DOIUrl":"10.1093/humrep/deag135","url":null,"abstract":"<p><strong>Study question: </strong>Does exposure to first-line chemotherapies affect the density and maturity status of testicular somatic cells from prepubertal to postpubertal males at the time of cryopreservation?</p><p><strong>Summary answer: </strong>Chemotherapy exposures, particularly high doses of alkylating agents, are associated with alterations in immunohistochemical markers of testicular somatic cell density and maturation, including SOX9 for Sertoli cell density, COUP-TFII for peritubular myoid cell maturation, and CYP11A1 and INSL3 for Leydig cell maturation, with the related effects becoming more nuanced when age and underlying pathology are considered.</p><p><strong>What is known already: </strong>The increased survival rates following cancer treatment highlight the importance of integrating fertility preservation, whether through sperm cryopreservation in pubertal and postpubertal males or testicular tissue freezing (TTF), which is now established for prepubertal and peripubertal boys. Although induction chemotherapy is known to impair germ cells, its effects on somatic cells (Sertoli, peritubular myoid, and Leydig cells) within testicular tissue collected after exposure to chemotherapeutic drugs remain largely unexplored.</p><p><strong>Study design, size, duration: </strong>This retrospective study included testicular tissue samples from 51 patients from prepubertal to postpubertal males diagnosed with cancer, aged between 6 months and 33 years. Their medical diagnoses and previous chemotherapy exposures were recorded. We examined histological sections of testicular tissue to assess the impact of chemotherapy on somatic cell density and maturity status.</p><p><strong>Participants/materials, setting, methods: </strong>The density and maturity status of testicular somatic cells were assessed by immunofluorescent staining. The analyses were performed on fresh testicular tissue fragments from prepubertal and postpubertal males with cancer who had undergone TTF prior to conditioning for hematopoietic stem cell transplantation. All had received first-line chemotherapies. In addition, the functionality of somatic cells was assessed using hormone serum levels that reflect their endocrine activity, to provide a better understanding of the functional integrity of the testicular environment.</p><p><strong>Main results and the role of chance: </strong>This study investigated the impact of chemotherapy drug exposure and cancer type on testicular somatic cells in boys. Patients were categorized based on their exposure to specific chemotherapeutic drugs, including carboplatin, other alkylating agents, anthracyclines, vincristine, and cytarabine. High cumulative exposure to alkylating agents, defined as a cyclophosphamide equivalent dose (CED) ≥ 8000 mg/m², led to a decrease in COUP-TFII expression in peritubular myoid cells and CYP11A1 in Leydig cells (P = 0.038 and P = 0.013, respectively). Additionally, INSL3 expression in Leydig cells decl","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1643-1660"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808481","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":"Increased risk of congenital anomalies after fertility treatment is partially mediated by multiple birth: a population-based cohort study.","authors":"B M Milne, M P Velez, J Shellenberger, S B Brogly","doi":"10.1093/humrep/deag124","DOIUrl":"10.1093/humrep/deag124","url":null,"abstract":"<p><strong>Study question: </strong>To what extent does multiple birth mediate the association between fertility treatment and congenital anomalies?</p><p><strong>Summary answer: </strong>Multiple birth explained only a modest proportion of the increased risk of congenital anomalies associated with fertility treatment, suggesting that most of the excess risk is independent of multiple birth.</p><p><strong>What is known already: </strong>Fertility treatments have been associated with an increased risk of congenital anomalies. Because fertility treatment also increases the probability of multiple birth, it remains unclear whether the observed increase in congenital anomalies is attributable to treatment itself, multiple gestation, or underlying infertility.</p><p><strong>Study design, size, duration: </strong>Population-based cohort study of all live and stillbirths delivered ≥22 weeks' gestation from 2006 to 2021 among women with a history of infertility diagnosis in Ontario, Canada.</p><p><strong>Participants/materials, setting, methods: </strong>Data were obtained from administrative health records routinely collected within a universal healthcare system for epidemiological surveillance. Exposure was defined as (1) infertility without fertility treatment, (2) ovulation induction (OI) or IUI, and (3) IVF or ICSI. Congenital anomalies were categorized as (1) any anomaly, (2) organ system, and (3) specific anomalies. Modified Poisson regression models generated adjusted relative risks (aRR). For statistically significant aRR > 1, causal mediation was used to decompose the total effect into direct and mediated effects to estimate proportion mediated by multiple birth.</p><p><strong>Main results and the role of chance: </strong>There were 274 893 births included in the cohort, of which 229 932 (83.6%) occurred among women with infertility who did not receive fertility treatment, 20 525 (7.5%) after OI/IUI, and 24 536 (8.9%) after IVF/ICSI. Multiple birth rates were 2.3%, 7.2%, and 13.3%, respectively. Compared with infertility without treatment, the aRR of any anomaly was 1.11 (95% CI 1.05-1.17) after OI/IUI and 1.28 (95% CI 1.22-1.34) after IVF/ICSI. Mediation analyses demonstrated that multiple birth accounted for only a minority of the excess risk, although the proportion mediated varied by anomaly type. The greatest mediation was observed for pulmonary artery stenosis, where multiple birth explained 33.9% of the association after OI/IUI and 44.4% after IVF/ICSI.</p><p><strong>Limitations, reasons for caution: </strong>As with all studies using administrative health data, our findings are subject to potential misclassification of infertility status based on billing codes, particularly when consultations do not reflect a confirmed diagnosis, as well as residual confounding from unmeasured factors. .</p><p><strong>Wider implications of the findings: </strong>This study suggests that multiple birth explains only part of the increased risk of congenit","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1810-1819"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630241","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}

{"title":"The impact of menstrual cycle phase and BMI on mitochondrial dysfunction in PMOS endometrium.","authors":"L Luyckx, M Myllykangas, J Kinnunen, S Lukashevich, A Salumets, A Velthut-Meikas, I Rooda, V Izzi, R K Arffman, U Saarela, T T Piltonen","doi":"10.1093/humrep/deag127","DOIUrl":"10.1093/humrep/deag127","url":null,"abstract":"<p><strong>Study question: </strong>Does the endometrium of oligo-ovulatory women with polyendocrine metabolic ovarian syndrome (PMOS) exhibit menstrual cycle phase-specific transcriptomic alterations compared to women without PMOS?</p><p><strong>Summary answer: </strong>Compared to healthy controls, women with PMOS exhibit endometrial transcriptomic dysregulations which are menstrual cycle phase-specific and, most notably, related to mitochondrial function.</p><p><strong>What is known already: </strong>Infertility and gestational dysfunction in women with PMOS are increasingly attributed to endometrial abnormalities, yet the underlying mechanisms behind PMOS-related endometrial dysfunction remain unclear. Previous studies have focused on anovulatory phenotypes, resulting in a poor understanding of cycle phase-specific defects in the endometria of women with PMOS.</p><p><strong>Study design, size, duration: </strong>Endometrial biopsies were obtained from oligo-ovulatory women with PMOS and healthy controls at four distinct menstrual cycle phases (proliferative, early-, mid-, and late-secretory phases) and subjected to RNA sequencing. Parallel in vitro experiments were conducted using cultured endometrial stromal cells (ESCs) and epithelial organoids (EEOs) derived from an additional endometrial sample cohort.</p><p><strong>Participants/materials, setting, methods: </strong>RNA sequencing was performed on biopsies from 78 (oligo-)ovulatory women, age- and BMI-matched between PMOS (n = 39) and control (n = 39) groups. Phase-specific transcriptomic profiles and pathway enrichment analyses were performed. For functional assays, endometrial cells were isolated from four PMOS and four control donors per BMI group (lean: < 25 kg/m2; obese: ≥30 kg/m2). Mitochondrial function, including respiration, ATP and reactive oxygen species production, and membrane potential, was assessed in both cell types before and after hormonal exposure.</p><p><strong>Main results and the role of chance: </strong>Endometrial transcriptomes clustered primarily by cycle phase; however, PMOS-specific dysregulation was observed related to extracellular matrix organization, estrogen receptor (ESR) signaling, ion transport, and mitochondrial respiratory function. Gene trajectory analyses revealed phase-specific alterations in progesterone-, insulin signaling-, and mitochondria-related gene expression during the early-secretory phase, and epithelial function during the mid-secretory phase. Functionally, decidualized ESCs from obese PMOS women displayed reduced mitochondrial respiration, whereas EEOs from lean PMOS patients exhibited increased mitochondrial activity.</p><p><strong>Large scale data: </strong>Sequencing data are available from the corresponding author upon request.</p><p><strong>Limitations, reasons for caution: </strong>Women with PMOS were oligo-ovulatory while controls exhibited regular cycles. The sample size for in vitro studies was modest, warranting validation i","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1762-1779"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705716","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}

{"title":"Preconception 1-hour blood glucose as an early indicator of gestational diabetes mellitus risk in PMOS/PCOS women undergoing IVF treatment: a multi-centre cohort study.","authors":"Guiquan Wang, Lulu Xie, Yi Chen, Ziyin Ding, Haijie Gao, Haiyan Yang, Peiyu Wang, Xiaohua Gong, Xiaowei Ji, Lin Wang, Liying He, Wanyi Xie, Luping Xin, Haiping Dai, Xi Dong, Ping Li, Liming Zhou, Juanzi Shi, Xiaoling Liang, Zimiao Chen, Liangshan Mu","doi":"10.1093/humrep/deag119","DOIUrl":"10.1093/humrep/deag119","url":null,"abstract":"<p><strong>Study question: </strong>Is the preconception 1-h plasma glucose level during the oral glucose tolerance test (OGTT) more strongly associated with subsequent gestational diabetes mellitus than the fasting or 2-h glucose levels in women with PMOS/PCOS undergoing IVF treatment?</p><p><strong>Summary answer: </strong>Preconception 1-h plasma glucose showed a stronger and more consistent association with gestational diabetes mellitus than the fasting or 2-h glucose levels in women with PMOS/PCOS undergoing IVF treatment.</p><p><strong>What is known already: </strong>Women with PMOS/PCOS have an increased risk of gestational diabetes mellitus. International guidelines recommend a preconception OGTT in women with PMOS/PCOS without pre-existing diabetes because of the risk of hyperglycaemia and pregnancy complications. However, the comparative predictive value of different preconception OGTT time points, particularly 1-h glucose, remains unclear.</p><p><strong>Study design, size, duration: </strong>This was a multi-centre retrospective cohort study including 2571 women with PMOS/PCOS who underwent their first IVF treatment at three reproductive medicine centres in China and had a preconception 75-g OGTT between March 2018 and December 2023.</p><p><strong>Participants/materials, setting, methods: </strong>Women with PMOS/PCOS who completed a preconception 75-g OGTT before initiation of the IVF treatment were included. The primary outcome was GDM diagnosed at 24-28 weeks of gestation. Generalized linear mixed-effects models were used to assess associations between OGTT glucose levels and GDM, adjusting for age, BMI, infertility duration, hormonal profiles, and treatment protocols. Stratified analyses by BMI and PMOS/PCOS phenotype were conducted, and multiple imputation was applied for missing data.</p><p><strong>Main results and the role of chance: </strong>Preconception fasting (aOR 1.97 [1.49-2.61]), 1-h (aOR 1.23 [1.13-1.34]) and 2-h glucose (aOR 1.30 [1.17-1.45]) were all significantly associated with GDM (all P < 0.001). Within the diabetic range, only the 1-h glucose measurement of ≥11.6 mmol/l remained a significant indicator. The association of 1-h glucose with GDM was significant in normal-weight and obese women but not in overweight women. The associations were consistent across PMOS/PCOS phenotypes.</p><p><strong>Limitations, reasons for caution: </strong>The retrospective design may have introduced residual confounding and limits causal inference. Missing data required imputation, and subgroup analyses may have limited statistical power.</p><p><strong>Wider implications of the findings: </strong>These findings suggest that preconception 1-h glucose may provide additional value for identifying women who are a higher risk of GDM among normal-weight and obese women with PMOS/PCOS undergoing IVF treatment, and support its consideration in preconception metabolic assessments.</p><p><strong>Funding: </strong>This work was supported by th","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1790-1799"},"PeriodicalIF":6.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700446","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}