Human reproduction最新文献

{"title":"Association between weight loss and reproductive outcomes among women with overweight or obesity: a cohort study using UK real-world data","authors":"Maximiliane Lara Verfürden, Volker Schnecke, Eva Winning Lehmann, Adriana Rendón Guillén, Adam H Balen","doi":"10.1093/humrep/deaf122","DOIUrl":"https://doi.org/10.1093/humrep/deaf122","url":null,"abstract":"STUDY QUESTION In women with BMI ≥25 kg/m2, does a 10–25% weight loss versus stable weight increase the chance of pregnancy? SUMMARY ANSWER In women with overweight or obesity, weight loss was associated with an increase in the chance of pregnancy. WHAT IS KNOWN ALREADY Weight loss has been shown to improve conception rates among women with overweight or obesity and concomitant polycystic ovary syndrome (PCOS). However, evidence on the effect of weight loss on conception rates among the general population of women with overweight or obesity, irrespective of PCOS status, is lacking. STUDY DESIGN, SIZE, DURATION A large cohort study of patient data collected from primary-care practices linked to hospital records in England between January 2000 and May 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were included if they were aged 18–40 years with BMI ≥25 kg/m2. Patient data were extracted from the UK Clinical Practice Research Datalink Aurum database of electronic medical records. The primary outcome was the first pregnancy recorded during a 3-year follow-up period. Key secondary outcomes were the occurrence of miscarriage, gestational diabetes, and pregnancy-induced hypertension, as well as emergency caesarean section, and risk of babies being born large for gestational age (LGA). MAIN RESULTS AND THE ROLE OF CHANCE The final cohort of 246 670 women comprised 195 666 who kept a stable weight and 51 004 who lost weight. Pregnancy occurred in 22 756/246 670 (9.2%) women. On average, a 10–25% weight loss (median 14%) was associated with a 5.2% increase in the chance of pregnancy over the following 3 years (hazard ratio 1.05; 95% CI 1.02, 1.09; P = 0.003) compared with stable weight. Gestational diabetes was reported for 950/11 825 (8.0%) women, and weight loss reduced the risk of gestational diabetes by 42% (odds ratio [OR] 0.58; 95% CI 0.48, 0.70; P < 0.001). Emergency caesarean section was performed in 1453/11 558 (12.6%) pregnancies. This intervention was significantly reduced in the weight-loss cohort (OR 0.82; 95% CI 0.71, 0.95; P = 0.008). Pregnancy-induced hypertension was reported in a few women (244/11 740 [2.1%]) and one-tenth of women (791/7988 [9.9%]) gave birth to babies who were LGA. Weight loss prior to pregnancy resulted in non-significant reductions in pregnancy-induced hypertension (OR 0.77; 95% CI 0.55, 1.07; P = 0.121) and risk of babies being born LGA (OR 0.86; 95% CI 0.72, 1.04; P = 0.117). Rates of miscarriages, preterm births, live births, or babies born small for gestational age were not impacted by weight loss. LIMITATIONS, REASONS FOR CAUTION In our study, the intention of pregnancy was unknown. Women who intend to conceive are more likely to attempt weight loss. The inclusion of women who do not intend to conceive may therefore underestimate the true relationship between weight loss and chance of pregnancy. Also, we assessed women aged between 18 and 40 years, but due to the requirement of having two BMI record","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565798","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":"Association between markers of female adiposity and live birth among patients undergoing fertility treatment or attempting unassisted conception","authors":"Iris T Lee, Kurt T Barnhart, Wei-Ting Hwang, Stefanie N Hinkle, Erica Johnstone, James L Mills, Ellen C Caniglia, Enrique F Schisterman, Pauline Mendola, Ginny L Ryan, Jim Hotaling, C Matthew Peterson, Bradley J Van Voorhis, Sunni L Mumford","doi":"10.1093/humrep/deaf124","DOIUrl":"https://doi.org/10.1093/humrep/deaf124","url":null,"abstract":"STUDY QUESTION Beyond BMI, are there better predictors of the impact of high female adiposity on reproductive outcomes in patients undergoing fertility treatment or attempting unassisted conception? SUMMARY ANSWER Though BMI remains a predictor of fertility outcomes, alternative markers of adiposity, such as percent body fat, provide distinct information and may be more strongly associated with outcomes than BMI. WHAT IS KNOWN ALREADY Elevated BMI is associated with a lower probability of live birth, though randomized trials have not consistently demonstrated the efficacy of weight loss for increasing live birth among patients utilizing infertility treatment. STUDY DESIGN, SIZE, DURATION This was a secondary analysis of data gathered from 2013 to 2017 during the Folic Acid and Zinc Supplementation Trial (FAZST). Participants in FAZST included 2370 heterosexual couples seeking infertility care at four US fertility centers. Couples were followed for 9 months while undergoing fertility treatments or attempting unassisted conception, with up to 9 additional months of follow-up if pregnancy occurred. PARTICIPANTS/MATERIALS, SETTING, METHODS For inclusion in the present study, female participants must have had at least one marker of adiposity measured at their baseline visit for FAZST. The primary exposure was high adiposity (defined by commonly used cutoffs in the literature) by each of five markers: BMI, percent body fat measured by dual-energy X-ray absorptiometry (DXA), serum leptin, serum adiponectin/leptin ratio, and waist circumference. Of the participants in FAZST, BMI was available for 99.6%, percent body fat for 7.3% (DXA only offered to 218 participants at two study sites between 2016 and 2017), leptin for 89.7%, adiponectin/leptin ratio for 89.7%, and waist circumference for 90.9%. Generalized linear models including age, race, parity, education, physical activity, male partner BMI ≥30 kg/m2, and Healthy Eating Index were used to estimate the relative risk of live birth. MAIN RESULTS AND THE ROLE OF CHANCE High adiposity by BMI was associated with decreased probability of live birth (adjusted relative risk [aRR] 0.85, 95% CI 0.74–0.98). The other markers demonstrated similar associations, though a stronger effect size was seen with percent body fat (aRR 0.34, 95% CI 0.22–0.55). In an analysis by tertile, even moderately elevated percent body fat was associated with a decrease in live birth. When stratifying by infertility treatment status, associations were attenuated for most markers in the group utilizing infertility treatment, though percent body fat remained significantly associated with live birth. However, this marker was only available in a subset of participants. LIMITATIONS, REASONS FOR CAUTION Only a subset of participants underwent DXA scans and had data on percent body fat, limiting the generalizability of the finding that this marker was most strongly associated with live birth. There were few participants with low BMIs, limiti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547224","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":"Stem cell-derived gametes: what to expect when expecting their clinical introduction.","authors":"Ilse J de Bruin,Merel M Spaander,Simone Harmsen,Rosanne Edelenbosch,M Corrette Ploem,Nina Dartée,Madalena Cardoso Vaz Santos,Mathangi Lakshmipathi,Callista L Mulder,Ans M M van Pelt,Willy M Baarends,Susana M Chuva de Sousa Lopes,Guido M W R de Wert,Seppe Segers,Geert Hamer,Ana M Pereira Daoud","doi":"10.1093/humrep/deaf123","DOIUrl":"https://doi.org/10.1093/humrep/deaf123","url":null,"abstract":"Stem cell-derived (SCD)-gametes derived from induced or autologous (i.e. patient-specific) cells may help mitigate human fertility problems caused by physiological or social factors in the (near) future. While this technology is still in its infancy, recent advancements with SCD-gametes generated from mouse pluripotent stem cells have led some researchers to expect-and investors to anticipate-the clinical introduction of human gametes derived from induced pluripotent stem cells (iPSCD-gametes) within two decades. However, it remains to be investigated how realistic these expectations are, and how they would balance against careful consideration of technical, ethical, legal, and societal aspects, including-but not limited to-safety and effectiveness. This mini-review aims to encourage that investigation by providing a brief overview of the state-of-the-art and highlighting the breadth of issues involved in the potential clinical introduction of human iPSCD-gametes. These issues emerge before (Stage 1), during (Stage 2), and after (Stage 3) clinical trials, and are discussed in that order. Issues discussed in the context of Stage 1 suggest that gathering the evidence required to preclinically assess the safety of human iPSCD-gametes will be time-consuming and require parallel experiments with sensitive research materials. Issues discussed in the context of Stage 2 suggest that it might take several years for human iPSCD-gametes to transition through distinct clinical trial phases, and that inevitable (and unforeseeable) variations in the quality of human iPSCD-gametes are likely to further slow this down. Finally, issues discussed in the context of Stage 3 suggest that offering human iPSCD-gametes clinically will require addressing questions of accountability and monitoring, some of which might be difficult to formalize by law. Combined, these findings suggest that a responsible clinical introduction of human iPSCD-gametes may take considerably longer than expected, underscoring the importance of transdisciplinary collaborations with a broad range of stakeholders to make well-informed and well-considered choices about their development and application.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"50 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547873","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":"O-250 Infertility and endometriosis: a 30-yearlong national population-based study of prevalence, association and pregnancy outcomes","authors":"L Saraswat, D Ayansina, M Nath, D Rytter, P Saunders, A Horne","doi":"10.1093/humrep/deaf097.250","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.250","url":null,"abstract":"Study question What is the population prevalence of endometriosis in those with infertility (and vice-versa) and likelihood of pregnancy in women with endometriosis with and without infertility? Summary answer Women with endometriosis associated infertility are 2.5 times more likely to have a pregnancy compared with other causes of female infertility. What is known already While the link between endometriosis and infertility is well recognised, the true prevalence of endometriosis in women with infertility (and vice versa) is not clearly known. Most of the available data has been derived from hospital-based studies with relatively small sample size. Similarly, there is limited data on likelihood of pregnancy and their outcomes (such as live birth, miscarriage, ectopic) in individuals with endometriosis-associated infertility compared with other causes of infertility as well as overall chances of pregnancy in those with endometriosis – a key concern for women when they first receive the diagnosis of endometriosis. Study design, size, duration A population-based national cohort study using routinely collected linked data from primary and secondary care and maternity database. The study comprised of > 4million women with infertility and other symptoms of endometriosis (pelvic pain, dysmenorrhoea) in England over a period of 30 years (1991-2020). Participants/materials, setting, methods Routinely collected primary care data on 4,041,770 women aged 13-50 years with infertility and other endometriosis symptoms was linked with secondary care data (hospital data and maternity records) to identify those with surgically confirmed diagnosis of endometriosis to estimate prevalence. Data was collected on age, social class and year of diagnosis. Logistic regression was used to evaluate odds of pregnancy in women with endometriosis compared to other causes of infertility and in those without endometriosis. Main results and the role of chance Between 1991 and 2020, there were 4,041,770 women aged 13-50 years, who attended primary care with infertility (n = 245,994) or other symptoms of endometriosis (e.g. pelvic pain, dysmenorrhoea and dyspareunia). 111,197 women had a surgically confirmed diagnosis of endometriosis via laparoscopy or laparotomy during this period. The overall population prevalence (95% CI) of female infertility (per 1000 women) over a 30-year period was 48.9 (48.6, 49.0). with highest prevalence between 30-39 years. Amongst those with infertility, 6.1% (14,904) had surgically confirmed endometriosis, of which 57.4% (8,556) had infertility before their diagnosis of endometriosis. The chances of having endometriosis in women with infertility was 2.5 times higher compared to those without infertility with Odds ratio (OR) and 95% CI of 2.48 (2.43,2.52). Among women with infertility, 12.9% (31,821) had at least one pregnancy during the study period. The chances of having a pregnancy in those with endometriosis associated infertility was 2.5 t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547230","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":"O-280 Unveiling the hidden danger: detection and characterisation of microplastics in human follicular and seminal fluids","authors":"E Gomez-Sanchez, R M Peñalver-Soler, N Almunia, M C Pérez-Álvarez, M D Luque, N Campillo, A Flores Monreal, N Arroyo-Manzanares, Y Ruiz-Moreno, R Jiménez, A M Villaquirán, J Mendiola, P Viñas","doi":"10.1093/humrep/deaf097.280","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.280","url":null,"abstract":"Study question Can we detect and characterise the presence and composition of microplastics (MPs) in human follicular (FF) and seminal fluids (SF)? Summary answer Various types of MPs were identified in both male and female reproductive systems, providing essential evidence to evaluate their potential risks to human reproductive health. What is known already Microplastics (MPs), defined as plastic particles smaller than 5 mm, have emerged as a pervasive form of pollution in consumer products and the environment. They represent a critical global environmental challenge with significant public health implications. Concerns regarding their impact on the human reproductive system have grown. However, limited data exist on the presence of MPs in human reproductive tissues and their potential effects on oocyte and sperm quality. Study design, size, duration This study evaluated the presence of MPs in the reproductive systems of donors and patients at our centre by analysing their FF and SF. FF samples were obtained from 25 women undergoing follicular aspiration, stored in sterile glass containers, and subsequently frozen. SF samples were collected from 18 men undergoing semen analysis and were similarly stored frozen in glass tubes. Participants/materials, setting, methods The detection of MPs in FF and SF was performed using direct laser infrared microscopy (LDIR). Prior to analysis, the samples were subjected to a mineralisation process with 10% (w/v) potassium hydroxide (KOH) and incubated at 40 °C for 48 hours. As a control, the containers used for sample collection and storage were analysed to confirm the absence of MP contamination. Main results and the role of chance A range of MPs was detected in both FF and SF, including polyamide (PA), polytetrafluoroethylene (PTFE), polyethylene (PE), polyurethane (PU), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS), polyvinyl chloride (PVC), and polylactic acid (PLA). The overall concentration of MPs was relatively low compared to non-plastic particles but was notably higher in FF than in SF. Specifically, over 50% of FF samples contained PA, PU, and PE, while PTFE and PET were detected in more than 30% of samples. PP, PVC, and PLA were identified in over 20%, with PS observed less frequently. In SF samples, MPs were detected in less than 30% of cases, except for PTFE, which was identified in 56% of samples. Limitations, reasons for caution The limited number of samples analysed, due to the challenges associated with obtaining them, is a key limitation. Expanding the sample size in future studies would strengthen the findings. Additionally, incorporating detailed information on the participants’ lifestyles and consumption habits would provide valuable context. Wider implications of the findings This study demonstrates the presence of MPs in both male and female reproductive systems, likely attributable to their easy entry into the body through ingestion, inhalation, and skin contact.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"71 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547231","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":"O-089 Maternal plasma cell-free RNA as a liquid biopsy for first-trimester screening of early and late-onset preeclampsia","authors":"N Castillo Marco, T Cordero, M Igual, I Muñoz-Blat, C Gómez-Álvarez, N Bernat-González, Á Gaspar-Doménech, É Ortiz-Domingo, A Vives, S Ortega-Sanchís, R Monfort-Ortiz, P Volkov, P Consortium, C Simón, T Garrido-Gómez","doi":"10.1093/humrep/deaf097.089","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.089","url":null,"abstract":"Study question Could liquid biopsy using maternal plasma cell-free RNA (cfRNA) serve as early screening for early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE)? Summary answer Distinct cfRNA profiles identified early in pregnancy allow the accurate risk-prediction of both EOPE and LOPE months before their clinical diagnosis. What is known already Screening efforts to predict preeclampsia have traditionally focused on placental biomarkers, such as sFLT1 and PlGF, which are effective for short-term prediction when preeclampsia is clinically suspected, but have significant limitations in accuracy and broad application. Liquid biopsy-based cfRNA studies offer valuable insights for early prediction, though these findings remain unimplemented clinically. Recently, we conducted a multi-omic analysis of decidualization resistance (DR)—a defect in endometrial cell differentiation—in patients with prior severe preeclampsia, identifying biomarkers that could enable earlier diagnosis1. 1Nat Med (2025). https://doi.org/10.1038/s41591-024-03407-7 Study design, size, duration This prospective longitudinal study involves 9,586 pregnant women recruited from 14 hospitals across Spain between September 2021 and June 2024 (ClinicalTrials.gov: NCT04990141). Participants provided 20 mL of peripheral blood at three time points: T1: 9–14 weeks, T2: 18–28 weeks, T3: >28 weeks or at the time of preeclampsia diagnosis using ACOG/FIGO guidelines. Plasma cfRNA was analyzed in EOPE (n = 42) and LOPE (n = 43) cases compared to normotensive controls that had uncomplicated pregnancies (n = 75). Participants/materials, setting, methods cfRNA was isolated using the MiRNeasy Serum/Plasma Advanced Kit from plasma samples (n = 457) collected throughout pregnancy from the selected participants (n = 160) and sequenced using Illumina technology. Participants were divided into discovery (70%) and validation (30%) sets to develop and validate the predictive models. Lasso regression was used to select the relevant cfRNAs and algorithms were evaluated using leave-one-out cross-validation. The algorithm with the best F1-score was selected and validated in the hold-out set. Main results and the role of chance We developed a first-trimester predictive model for EOPE using 36 transcripts, achieving 83% sensitivity, 88% specificity and an AUC of 0.85 in the validation sample set, and detecting risk 18.0 weeks before onset. Of these, 47.2% were associated with DR signature (e.g. PAEP, MMP7). For the second trimester, the most effective EOPE model used 87 cfRNA transcripts achieving 87% sensitivity, 84% specificity, and an AUC of 0.85 in the validation set, approximately 8.5 weeks before onset. The 36.8% of transcripts included in the model were associated with the DR signature (e.g. IGF1, WNT5A). For LOPE, the best model included 92 cfRNAs, achieving 86% sensitivity, 89% specificity and an AUC of 0.88 in the hold-out set, detecting risk 14.9 weeks before onset and just inclu","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"92 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547225","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":"O-015 Advanced paternal age affects miscarriage and live birth outcomes following the first transfer in oocyte donation cycles","authors":"M C Guglielmo, J J Fraire-Zamora, E Bartoli, M Valerio, E De Ponti, A Rodriguez, M Popovic, J Buratini, M R Mignini Renzini, M Dal Canto","doi":"10.1093/humrep/deaf097.015","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.015","url":null,"abstract":"Study question Does advanced paternal age affect miscarriage and/or live birth outcomes following the first transfer in oocyte donation cycles? Summary answer Advanced paternal age (>45 years old) increases miscarriage rates and decreases live birth rates following the first transfer in oocyte donation cycles. What is known already 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 Multi-center, retrospective study of 1,712 first oocyte donation cycles performed between January 2019 and December 2023, across six IVF centers. Only ICSI cycles with fresh donor oocytes, inseminated with frozen 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 ages were categorized in two groups: ≤45 years old and >45 years old (advanced paternal age, APA). We assessed fertilization rates, the number of usable blastocysts and blastocyst utilization rate. Clinical outcomes included clinical pregnancy, miscarriage and live birth rates. P < 0.05 was considered statistically significant after Fisher’s exact test and a multivariate logistic analysis adjusting for recipient and oocyte age, number of mature (MII) oocytes injected and fresh/frozen embryo transfer. Main results and the role of chance Within the cohort of 1,712 patients who underwent a first oocyte donation cycle, the mean recipient age (±SD) was 43.3 (±4.1) years, the mean oocyte donor age (±SD) was 26.1 (±4.1) years, and the mean paternal age (±SD) was 43.5 (±6.3). In the ≤45 paternal age group (n = 1066), the mean paternal age (±SD) was 39.8 (±4,0) years, while in the APA group (n = 646), it was 49.6 (±4.1). No differences were observed in recipient age, oocyte donor age, number of oocytes fertilized or number of blastocysts obtained among paternal age groups. Interestingly, miscarriage rate was 23.8% (71/298) in the APA group and 16.3% (85/522) in the ≤45 years old group. The differences were significantly different (p = 0.006). Consequently, the live birth rate was also reduced 35.1% APA vs 41.0%, ≤45 years old (227/646 vs 437/1066; p = 0,009). These results were further confirmed in the adjusted analysis, where AP","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"48 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547227","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":"O-014 Unraveling the interplay of gut microbiota, metabolic alterations, and endometrial senescence in polycystic ovary syndrome and its implications for adverse pregnancy outcomes","authors":"M Jing, A Liu","doi":"10.1093/humrep/deaf097.014","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.014","url":null,"abstract":"Study question What gut microbiota and metabolic alterations are associated with Polycystic ovary syndrome (PCOS) and linked to adverse pregnancy outcomes (APOs)? Summary answer In PCOS, P. merdae decreases, BCAAs increase, raising the risk of APOs. Meanwhile, endometrial senescence and decidualization impairment are found, worsening with higher Ile concentration. What is known already PCOS, a prevalent and complex endocrine disorder, stands as the primary cause of anovulatory infertility. The rising prevalence of PCOS in China over the past decade has led to a substantial increase in disease burden. Our previous ten-year retrospective analysis revealed that PCOS patients undergoing their first fresh embryo transfer faced a heightened risk of APOs, such as miscarriage. However, the factors influencing disease progression and future obstetric outcomes in PCOS remain elusive. Study design, size, duration This prospective cohort study encompassed a diverse cohort of 220 women (110 with PCOS and 110 controls) from 44 cities across China, with a median follow-up duration of 16.6 months. Participants/materials, setting, methods Women aged < 35 years with PCOS (Rotterdam criteria) and age-/BMI-matched controls were recruited. Fecal microbiomes were analyzed using 16S rRNA sequencing and metagenomics, while serum metabolites were assessed through both untargeted and targeted metabolomics. Endometrial stromal cell senescence was evaluated based on a constellation of markers, including cell proliferation, senescence-associated secretory phenotype factors, cell cycle, ROS levels, and SA-β-Gal activity. Endometrial decidualization was gauged by measuring prolactin and IGFBP-1 levels using ELISA. Main results and the role of chance Our study revealed significant gut microbiota alterations, including reduced α-diversity and a notable decline in Parabacteroides merdae (P. merdae), a key species differentiating PCOS from controls. Serum metabolomics identified 45 differential metabolites, with branched-chain amino acids (BCAAs), especially isoleucine (Ile), exhibiting strong diagnostic potential. Targeted metabolomics further validated BCAAs’ (Valine, Leucine, and Ile) upregulation and short-chain fatty acids’ downregulation in PCOS. During follow - up, PCOS patients had a higher cumulative incidence of APOs despite similar pregnancy rates. And the adjustment for potential confounders did not substantially change the estimates. Intriguingly, individuals who experienced APOs showed a reduction in gut P. merdae levels and an elevation in serum BCAAs, suggesting their potential association with APOs occurrence. Further analysis revealed increased Ile levels in the endometrial tissue of PCOS (P < 0.05) and higher proportions of cells positive for senescence markers (P21, P16, IL6, and IL1β), indicating aggravated cellular senescence, particularly in endometrial stromal cells (ESCs). ESCs from PCOS patients displayed classical senescence features, inclu","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547229","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":"O-130 Dysregulated Epigenetic Reprogramming during Pre-Implantation Development of Embryos from Patients with Polycystic Ovary Syndrome","authors":"Q Zhu, X Ruimin, G Shaorong, L Xiaoyu, J Cizhong","doi":"10.1093/humrep/deaf097.130","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.130","url":null,"abstract":"Study question How Abnormal Epigenetic Reprogramming Prior to Embryo Implantation Contributes to the Onset and Intergenerational Inheritance of Polycystic Ovary Syndrome (PCOS)? Summary answer PCOS embryos exhibit dysregulated epigenetic reprogramming, including H3K4me3, H3K27me3, H3K9me3, and DNA methylation, which are associated with abnormal gene expression and inherited anomalies from oocytes. What is known already PCOS is a leading cause of infertility, with familial aggregation and unclear intergenerational inheritance mechanisms. Abnormal epigenetic regulation in early embryonic development has been linked to disease inheritance. Study design, size, duration This was a comparative study analyzing the transcriptome and epigenome of oocytes and preimplantation embryos collected from 133 PCOS patients and 95 non-PCOS infertile women. Participants/materials, setting, methods Oocytes and embryos from PCOS and non-PCOS infertile women were analyzed using ultra-low-input sequencing techniques, including Smart-seq2, CUT&RUN, and WGBS, to identify transcriptomic and epigenomic abnormalities. Main results and the role of chance PCOS embryos demonstrated significant dysregulation of zygotic genome activation genes, epigenetic regulators, PCOS-linked genes, and retrotransposons during preimplantation development. These anomalies were linked to abnormal epigenetic reprogramming, particularly in histone modifications (H3K4me3, H3K27me3, H3K9me3) and DNA methylation, with a substantial portion inherited from PCOS oocytes. Treatment with PRC2 complex inhibitors effectively rescued abnormal gene expression, indicating a critical role of these epigenetic modifications in driving the observed abnormalities. Key regulatory factors associated with these epigenetic disruptions were identified. Statistical analyses confirmed the robustness of the findings, minimizing the role of chance. Limitations, reasons for caution The study’s findings are based on in vitro analyses of oocytes and preimplantation embryos, which may not fully capture in vivo processes. Further research is needed to validate the long-term effects of these epigenetic abnormalities on post-implantation development and the health of offspring. Wider implications of the findings This study highlights a direct link between aberrant epigenetic reprogramming in early embryos and the intergenerational inheritance of PCOS. These findings provide a foundation for developing targeted therapeutic interventions and risk assessment strategies for PCOS in offspring, offering new avenues for prevention and treatment. Trial registration number No","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"154 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547228","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 to: Intra-individual variability of serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.","authors":"","doi":"10.1093/humrep/deaf108","DOIUrl":"10.1093/humrep/deaf108","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"1390"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173722","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}