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PAPSS2-mediated BMPR1A sulfation in stromal cells regulating endometrial decidualization via autophagy. 间质细胞中papss2介导的BMPR1A巯基化通过自噬调节子宫内膜去细胞化。
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-09 DOI: 10.1093/humrep/deag103
Duo Zi,Wanying Deng,Xiaoli Zhang,Yunfei Li,Junzhi Liang,Jia Hu,Ruizhe Cao,Wenhui Gao,Na Zuo,Hao Chen,Da Li
{"title":"PAPSS2-mediated BMPR1A sulfation in stromal cells regulating endometrial decidualization via autophagy.","authors":"Duo Zi,Wanying Deng,Xiaoli Zhang,Yunfei Li,Junzhi Liang,Jia Hu,Ruizhe Cao,Wenhui Gao,Na Zuo,Hao Chen,Da Li","doi":"10.1093/humrep/deag103","DOIUrl":"https://doi.org/10.1093/humrep/deag103","url":null,"abstract":"STUDY QUESTIONDoes 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2)-mediated sulfation contribute to defective decidualization in patients with recurrent implantation failure (RIF), and what are the underlying mechanisms?SUMMARY ANSWERDownregulation of PAPSS2 enhances the interaction between bone morphogenetic protein receptor type 1A (BMPR1A) and bone morphogenetic protein 2 (BMP2), as well as SMAD family member 1/5/9 (SMAD1/5/9)-dependent autophagic flux, thereby promoting decidualization and increasing the receptivity of endometrial stromal cells to trophoblast invasion.WHAT IS KNOWN ALREADYDecidualization is essential for embryo implantation and pregnancy maintenance, and impaired decidualization is considered a key pathological mechanism underlying RIF. Although protein tyrosine sulfation is a critical post-translational modification, its role in endometrial decidualization remains unclear.STUDY DESIGN, SIZE, DURATIONWe integrated transcriptomic datasets, performed in vitro decidualization assays in immortalized human endometrial stromal cells (T-HESCs) and primary human endometrial stromal cells (hEnSCs), and established an artificial decidualization mouse model. Functional assays and molecular analyses were conducted between 2023 and 2026.PARTICIPANTS/MATERIALS, SETTING, METHODSMid-secretory endometrial tissues were collected from patients with RIF and fertile controls. Decidualization was induced in T-HESCs and primary hEnSCs using dibutyryl-cAMP and progesterone. The effects of PAPSS2 knockdown or overexpression were assessed by RT-qPCR, Western blotting, immunoprecipitation, immunofluorescence, and in vitro implantation assays with BeWo spheroids. In vivo, an ovariectomized mouse model was used to evaluate decidualization under pharmacological modulation of BMP-SMAD signaling and autophagy.MAIN RESULTS AND THE ROLE OF CHANCEWe found that sulfation levels were elevated in endometrial stromal cells from RIF patients. Transcriptomic analysis revealed that PAPSS2, a known sulfation-related gene, was consistently downregulated during decidualization. Mechanistically, PAPSS2 knockdown in endometrial stromal cells decreased BMPR1A sulfation, enhanced its binding affinity for BMP2, and activated the downstream SMAD1/5/9 signaling pathway. Functionally, the activation of this pathway promoted autophagy, thereby enhancing decidualization and increasing stromal cell receptivity to trophoblast invasion.LARGE SCALE DATAPublicly available bulk transcriptomic datasets GSE75425 and GSE17504, together with the single-cell RNA-seq dataset GSE183837, were obtained from the Gene Expression Omnibus (GEO) database.LIMITATIONS, REASONS FOR CAUTIONAlthough our data support dysregulated sulfotyrosine levels and implicate the PAPSS2-BMPR1A sulfation axis in stromal decidualization in RIF, further studies with larger sample sizes are required to confirm their in vivo relevance.WIDER IMPLICATIONS OF THE FINDINGSOur findings reveal a previously unrecognize","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408373","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}
引用次数: 0
L26/P-693 Laboratory–Clinical KPI alignment in POSEIDON 3 and 4 patients: Implications for counselling, predictability, and time to pregnancy L26/P-693 POSEIDON 3和4患者的实验室-临床KPI一致性:对咨询、可预测性和怀孕时间的影响
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.1023
K.C. Mantravadi, D. Rao, V. Syakasiri
{"title":"L26/P-693 Laboratory–Clinical KPI alignment in POSEIDON 3 and 4 patients: Implications for counselling, predictability, and time to pregnancy","authors":"K.C. Mantravadi, D. Rao, V. Syakasiri","doi":"10.1093/humrep/deag083.1023","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1023","url":null,"abstract":"Study question Do laboratory performance indicators align with pregnancy outcomes in POSEIDON 3 and 4 patients, and can they reliably guide counselling? Summary answer Laboratory indicators demonstrate clear differences between POSEIDON 3 and 4 patients, but do not consistently predict pregnancy and live birth outcomes. What is known already POSEIDON Groups 3 and 4 represent poor-prognosis IVF patients primarily limited by low oocyte numbers. Laboratory key performance indicators (KPIs) such as cycle cancellation, blastocyst formation, and embryo utilisation are commonly used to assess prognosis and guide counselling regarding expected success, number of cycles, and embryo pooling strategies. However, whether favourable laboratory performance translates predictably into pregnancy, miscarriage, and live birth outcomes remains unclear. The relationship between laboratory KPIs and reproductive outcomes in poor-prognosis patients has not been well characterised. Study design, size, duration This retrospective cohort study analysed IVF cycles performed between 2014–2024 at a tertiary fertility centre. A total of 1,250 women classified as POSEIDON Groups 3 and 4 were included. POSEIDON Group-3 comprised women aged <35 years with AMH <1.2 ng/mL (n = 547), and Group-4 comprised women aged ≥35 years with AMH <1.2 ng/mL (n = 703). All comparative analyses and outcome assessments were performed exclusively between POSEIDON Groups 3 and 4. Participants/materials, setting, methods All autologous IVF cycles in POSEIDON Groups 3 and 4 with extended embryo culture and without PGT were included. Laboratory KPIs—including cycle cancellation, blastulation rate, and embryo utilisation—were analysed to assess progression to embryo transfer. Pregnancy and live birth outcomes were evaluated only in cycles reaching transfer. All women underwent frozen embryo transfer of two good-quality blastocysts. Comparative assessments between Groups 3 and 4 used unadjusted odds ratios. Main results and the role of chance POSEIDON Group-3 demonstrated consistently more favourable laboratory performance and reproductive efficiency compared with Group-4. Cycle-cancellation prior to embryo transfer was significantly lower in Group-3 than Group-4(6%vs10%), corresponding to a reduced likelihood of cycle-cancellation before transfer in Group-3 (unadjusted OR 0.57, 95% CI 0.40–0.81). Blastocyst-conversion was significantly higher in Group-3(63%) compared with Group-4(43%), translating into more than a two-fold higher likelihood of blastocyst formation (unadjusted OR 2.24, 95%-CI 2.01–2.49), indicating superior upstream laboratory progression despite similarly reduced ovarian reserve. This laboratory advantage increased the probability of reaching embryo transfer; however, its translation into reproductive outcomes was incomplete. Implantation rates per embryo transferred were higher in Group-3 than Group-4 (49% vs 32%), corresponding to a modest but statistically signi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"273 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400933","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}
引用次数: 0
L26/P-399 A selective JAK1/JAK2 inhibitor, ruxolitinib, increases follicle retention, including primordial follicle, after exposure to cyclophosphamide in xenografted human ovarian tissue L26/P-399选择性JAK1/JAK2抑制剂ruxolitinib在暴露于异种移植卵巢组织环磷酰胺后增加卵泡保留,包括原始卵泡
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.733
L. Man, G. Montes de Oca, Z. Rosenwaks, D. James
{"title":"L26/P-399 A selective JAK1/JAK2 inhibitor, ruxolitinib, increases follicle retention, including primordial follicle, after exposure to cyclophosphamide in xenografted human ovarian tissue","authors":"L. Man, G. Montes de Oca, Z. Rosenwaks, D. James","doi":"10.1093/humrep/deag083.733","DOIUrl":"https://doi.org/10.1093/humrep/deag083.733","url":null,"abstract":"Study question Can systemic Ruxolitinib (Ruxo) treatment increase the retention of primordial follicles (PrFs) after cyclophosphamide (Cp) exposure in a human ovarian tissue xenograft model? Summary answer Administration of Ruxo before Cp exposure increases follicle viability and retention of PrFs in xenografted human ovarian tissue. What is known already Gonadotoxicity, manifesting as a reduction in PrFs, is a well-known side effect of Cp treatment. Current fertility preservation efforts focus primarily on banking oocytes, embryos, or ovarian tissue, as effective strategies to safeguard ovarian reserve in situ remain elusive. We have previously linked inflammatory signaling within the mouse ovary to Cp exposure and shown that pretreatment with Ruxo before Cp administration increased retention of PrFs. Building on these results, we utilized this treatment protocol to test the fertoprotective effect of Ruxo in human ovarian cortical fragments from four different organ donors xenografted into immunocompromised mice. Study design, size, duration We thawed four fragments (∼24x4x1 mm) of human ovarian tissue, each from an organ donor aged 21-28 years. Each strip was divided into six equal pieces, and tissue was evenly distributed among the experimental groups. Mice underwent ovariectomy and co-transplantation of ovarian tissue with endothelial cells (n = 24 grafts bilaterally in 12 NSG mice). Two weeks transplant, mice harboring xenografts representing an equal distribution of donors were treated for 15 days before graft recovery. Participants/materials, setting, methods Mice were divided into three groups for daily intraperitoneal injections. Control (DMSO 14%, daily); Cp (60 mg/kg once a week, with daily DMSO 14%); and Ruxo (100 mg/kg daily) -Cp (60 mg/kg once a week). Two weeks following the first Cp injection, grafts were harvested, fixed in 4% paraformaldehyde, and underwent histologic evaluation with H&E staining and light microscopy imaging. Serum from xenograft-bearing mice was tested for estradiol, progesterone, and AMH levels. Main results and the role of chance In a histological analysis, follicle counts showed a significantly higher (p = 0.03) ratio of PrFs to growing (primary + secondary) follicles in Ruxo-Cp (0.18) versus Cp (0.00) groups. To account for interpatient variability, we calculated the percentage of viable follicles derived from each condition relative to the entire count from each patient tissue fragment; this calculation was performed for all four donors for each follicle type. When comparing PrF percentage, the Ruxo-Cp group exhibited a significantly higher (p = 0.03) median retention rate (14.29%) compared to Cp (0.00%). The retention rate in the Ruxo-Cp group was not significantly different from the CTRL group. Comparing the percentage of total (PrF + growing) follicles, the Ruxo-Cp group (16.35%) had a higher (p = 0.007) median percentage than the Cp group (4.17%). The CTRL group median percentage (16.00%) was also ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"25 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400940","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}
引用次数: 0
L26/P-026 Single-cell profiling reveals aberrant germ-cell expression as predictor of TESE failure and identifies targets for regenerative interventions in NOA testes L26/P-026单细胞分析揭示了异常生殖细胞表达作为TESE失败的预测因子,并确定了NOA睾丸再生干预的目标
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.362
A. Guzmán-Jiménez, S. González-Muñóz, I. Higueras-Serrano, A. Robles-Fernández, M. Cerván-Martín, M. Molina, M.C. Gonzalvo, M.L. García-Peña, V. Maldonado, A. Espuch, J.A. Castilla, A. Clavero, C. Domínguez-Conde, F.D. Carmona, L. Bossini-Castillo
{"title":"L26/P-026 Single-cell profiling reveals aberrant germ-cell expression as predictor of TESE failure and identifies targets for regenerative interventions in NOA testes","authors":"A. Guzmán-Jiménez, S. González-Muñóz, I. Higueras-Serrano, A. Robles-Fernández, M. Cerván-Martín, M. Molina, M.C. Gonzalvo, M.L. García-Peña, V. Maldonado, A. Espuch, J.A. Castilla, A. Clavero, C. Domínguez-Conde, F.D. Carmona, L. Bossini-Castillo","doi":"10.1093/humrep/deag083.362","DOIUrl":"https://doi.org/10.1093/humrep/deag083.362","url":null,"abstract":"Study question Can comprehensive single-cell characterisation of germ cells identify molecular predictors of testicular sperm extraction (TESE) outcome and therapeutic targets in patients with non-obstructive azoospermia (NOA)? Summary answer Late-stage germ-cell maturation defects distinguish TESE outcomes, while spermatogonial heterogeneity highlights germ-cell niche restoration as therapeutic strategy. What is known already TESE success varies markedly across NOA histological subtypes, yet molecular predictors distinguishing successful from failed sperm retrieval remain elusive. Previous single-cell studies have characterised germ-cell populations in healthy testes but were limited by small sample sizes and insufficient representation of NOA phenotypes. Spermatogonial stem cell (SSC) heterogeneity and stage-specific markers predictive of sperm retrieval success have not been comprehensively mapped. Emerging evidence suggests growth factor-based therapies may support germ-cell viability and differentiation in vitro; however, their clinical translation requires an improved understanding which germ-cell states are the finest targets to regenerative interventions in NOA patients. Study design, size, duration Single-cell RNA sequencing (scRNA-seq) was performed on testicular biopsies from fourteen NOA patients stratified according to TESE outcome. All samples were collected and cryopreserved as single-cell suspensions at the time of testicular biopsy for assisted reproductive technologies. Germ-cell proportions and transcriptional profiles were compared between patient with successful (TESE+) and unsuccessful (TESE-) sperm retrieval to identify specific cell clusters and differentially expressed genes in each condition and germ-cell stages. Participants/materials, setting, methods Patients were comprehensively classified with embryologist support into TESE + (n = 3) or TESE- (n = 11). scRNA-seq libraries were generated using 10x Genomics Next GEM technology, followed by stringent quality control filtering. Over 20,000 germ-cell transcriptomes were retained and annotated using automated and manual approaches based on established markers such as UTF1, MAGEA4, HORMAD1 or PRM1. Trajectory inference and differential expression analyses were performed using Scanpy. Main results and the role of chance We initially defined 20 subclusters encompassing all germ-cell types. High-resolution single-cell profiling revealed previously unappreciated SSC heterogeneity, resolving four transcriptionally distinct populations arranged along a differentiation continuum. A primitive SSC subset characterised by high expression of GFRA1, FGFR2, and ICA1L was positioned at the root of the spermatogenic lineage by trajectory analysis, likely representing an early stem-cell pool. Additionally, late-stage germ cells exhibited TESE outcome-associated molecular signatures. Elongated spermatids from TESE- samples showed significantly increased mitochondrial gene expression, where","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400981","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}
引用次数: 0
L26/P-171 Associations between artificial intelligence (AI)-based oocyte imaging scores and subsequent embryo AI scores assessed using KIDScore D5, iDAScore and CHLOE-EQ: a retrospective study 基于人工智能(AI)的卵母细胞成像评分与随后使用KIDScore D5、iDAScore和CHLOE-EQ评估的胚胎AI评分之间的相关性:一项回顾性研究
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.507
Z. Yarkiner, Z. Atayurt, G. Raad, G. Liperis, Y. Yilancilar, O. Ammar, B. Yuksel, M. Serdarogullari
{"title":"L26/P-171 Associations between artificial intelligence (AI)-based oocyte imaging scores and subsequent embryo AI scores assessed using KIDScore D5, iDAScore and CHLOE-EQ: a retrospective study","authors":"Z. Yarkiner, Z. Atayurt, G. Raad, G. Liperis, Y. Yilancilar, O. Ammar, B. Yuksel, M. Serdarogullari","doi":"10.1093/humrep/deag083.507","DOIUrl":"https://doi.org/10.1093/humrep/deag083.507","url":null,"abstract":"Study question Is an AI-based oocyte imaging score associated with embryo AI scores following fertilisation generated by multiple AI platforms? Summary answer Higher AI-based oocyte scores were associated with significantly higher downstream embryo AI scores across multiple platforms. What is known already Several AI systems are integrated into early embryo assessment. KIDScore assesses implantation potential based on morphokinetics, CHLOE-EQ analyses time-lapse imaging to generate an AI-based embryo viability score, and iDAScore produces a score associated with implantation likelihood. However, these models are applied at the embryo stage, limiting their utility for expectation management in oocyte cryopreservation patients and early counselling on cycle prognosis. MAGENTA is a non-invasive AI tool that assigns a 0–10 score to metaphase II oocytes, with higher scores indicating greater blastocyst potential. Whether MAGENTA scores are associated with downstream embryo AI scores across platforms remains unknown. Study design, size, duration This retrospective, single-centre study analysed 2,341 fresh metaphase II oocytes from intracytoplasmic sperm injection (ICSI) cycles performed between March 2024 and December 2025. Only fresh semen samples were included; samples with concentration <5 million/ml and motility <10% were excluded. The primary variable was the AI-based oocyte imaging score (MAGENTA), compared with embryo AI scores generated by iDAScore, KIDScore D5 and CHLOE-EQ. Participants/materials, setting, methods Oocyte images were captured prior to ICSI and scored using MAGENTA, with oocytes categorised as A (7.6–10.0; high), B (5.1–7.5; medium–high), C (2.6–5.0; low–medium), or D (0.0–2.5; low). Injected oocytes were cultured until Day 5 in an EmbryoScope+. Embryo AI scores were generated using iDAScore (v1.2.0), KIDScore D5 (v.3) based on morphokinetic annotation, and CHLOE-EQ derived from time-lapse recordings. Main results and the role of chance The mean age of women was 28.54±5.73 years. For KIDScore D5, embryos from low-quality oocytes (MAGENTA group D) had a 22% lower score than those from high-quality oocytes (group A) (Exp(B)=0.78, 95% CI 0.70–0.86; p < 0.001). Embryos from medium–high-quality oocytes (group C) had a 9% lower KIDScore D5 than group A (Exp(B)=0.91, 95% CI 0.84–0.99; p = 0.026). For iDAScore, embryos from group D had a 27% lower score than group A (Exp(B)=0.73, 95% CI 0.65–0.82; p < 0.001), while embryos from group C had a 10% lower score (Exp(B)=0.90, 95% CI 0.81–0.99; p = 0.032). For CHLOE-EQ, embryos from group D showed a 27% lower score than group A (Exp(B)=0.73, 95% CI 0.63–0.86; p < 0.001), while embryos from group C had a 12% lower score (Exp(B)=0.88, 95% CI 0.77–0.99; p = 0.036). Oocytes in MAGENTA group B did not differ from group A for any embryo AI score (all p > 0.40). Limitations, reasons for caution This was a retrospective, single-centre study, limiting causal i","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400988","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}
引用次数: 0
L26/P-678 Optimal Timing of NIPT in IVF Vanishing Twin Pregnancies: A Retrospective Analysis of Fetal Heartbeat vs. Gestational Sac Only Groups IVF消失双胎妊娠NIPT的最佳时机:胎儿心跳与仅孕囊组的回顾性分析
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.1008
J.W. Moon, C.H. Kim
{"title":"L26/P-678 Optimal Timing of NIPT in IVF Vanishing Twin Pregnancies: A Retrospective Analysis of Fetal Heartbeat vs. Gestational Sac Only Groups","authors":"J.W. Moon, C.H. Kim","doi":"10.1093/humrep/deag083.1008","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1008","url":null,"abstract":"Study question In IVF pregnancies with a vanishing twin, what is the optimal timing for performing NIPT to ensure diagnostic accuracy? Summary answer NIPT should be performed at least 4 weeks after fetal loss to minimize false-positive results in IVF vanishing twin pregnancies What is known already In Vanishing Twin Syndrome (VTS), residual cfDNA from the demised twin often leads to discordant-positive NIPT results, complicating clinical management in IVF pregnancies. While previous studies suggest testing after 15 weeks, the precise timing based on the stage of loss remains poorly defined. Notably, false-positive NIPT results are reported to be higher in cases where a fetal heartbeat was previously observed compared to gestational sac-only losses. This ambiguity regarding the optimal testing interval increases unnecessary patient anxiety and the risk of invasive diagnostic procedures, highlighting the need for stage-specific clinical guidelines Study design, size, duration This retrospective study analyzed clinical data from pregnancies achieved through in vitro fertilization (IVF) between August 2016 and August 2025. A total of 53 patients with Vanishing Twin Syndrome (VTS) were included to evaluate the correlation between the developmental stage at fetal loss and the accuracy of subsequent NIPT results. Participants/materials, setting, methods 53 IVF-VTS patients were categorized into two groups: fetal loss after FHB observation (n = 29) and loss with only a G-sac (n = 24). Following weekly ultrasound monitoring, NIPT for trisomies 21, 18, 13, and sex chromosomes was performed at 11–12 weeks. Abnormal findings were validated through repeat NIPT at 14–15 weeks or amniocentesis for definitive chromosomal status. Main results and the role of chance The discordant (false-positive) rate was significantly higher in the FHB group than the G-sac group (4/29 [13.8%] vs. 1/24 [4.2%], p < 0.05). In the FHB group, false positives (T21, T18, and SCA) occurred at an average interval of 28.04 days post-loss (range: 14–25 days). In contrast, the G-sac group had a longer average interval of 40.63 days, with one T10 false-positive (p < 0.01). Importantly, all discordant cases were subsequently confirmed as euploid through amniocentesis or follow-up NIPT at 14–15 weeks, resulting in a 100% negative predictive value for follow-up testing. These results statistically demonstrate that a shorter testing interval, particularly in cases with prior FHB, significantly increases the risk of residual cfDNA interference. Limitations, reasons for caution A key limitation is the retrospective design and small sample size from a single center. Importantly, as PGT was not performed, the genetic status of the demised twins remained unknown, which may confound NIPT interpretation. Caution is warranted until validated by larger prospective multi-center studies. Wider implications of the findings Rather than a uniform recommendation of testing after 15 weeks’ gestati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"171 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400990","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}
引用次数: 0
L26/P-726 Targeted lipidomics in serum for risk prediction of premature ovarian insufficiency 血清L26/P-726靶向脂质组学用于卵巢早衰风险预测
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.1053
Q. Zhu, L. Sun, G. Huang, J. Li
{"title":"L26/P-726 Targeted lipidomics in serum for risk prediction of premature ovarian insufficiency","authors":"Q. Zhu, L. Sun, G. Huang, J. Li","doi":"10.1093/humrep/deag083.1053","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1053","url":null,"abstract":"Study question Can the serum lipidomics serve as potential predictive markers for premature ovarian insufficiency (POI)? What are the roles and mechanisms of key lipid metabolic markers? Summary answer Multiple serum lipid metabolites in patients can serve as predictive markers, and changes in their metabolic levels effectively indicate the risk of POI. What is known already POI poses a major threat to female reproductive health, with its pathogenesis closely linked to endocrine disorders and oxidative stress. Lipid metabolism is involved in regulating the homeostasis of the reproductive system; existing studies suggest that abnormal lipid profiles may be associated with ovarian dysfunction, but research on predicting this condition via targeted serum lipid metabolome remains limited. Study design, size, duration A case-control study was conducted, enrolling 71 patients with POI and 55 healthy controls (in two batches, with more samples planned). Serum samples were collected for targeted lipid metabolome detection to analyze differential metabolites and establish a prediction model, with a study duration of 10 months. Participants/materials, setting, methods Study subjects were reproductive-aged women meeting diagnostic criteria. Targeted lipidomics detected serum lipid components, and bioinformatics analysis screened differential metabolites. Machine learning (LASSO regression/random forest) was applied to construct a POI. Main results and the role of chance A total of 67 differential lipid metabolites were identified, among which phospholipids and triglycerides showed the most significant differences. The prediction model constructed with 10 core metabolites had an AUC of 0.82, with both sensitivity and specificity exceeding 80%. Experimental data were validated twice, demonstrating good repeatability; random errors had little impact on the results, and the expression levels of core metabolites were significantly correlated with ovarian function indices. Limitations, reasons for caution This is a single-center study with a limited sample size, lacking refined analysis across different age strata. Future studies need to expand the sample size and conduct multi-center research to verify the stability of the results. Wider implications of the findings It provides a non-invasive and efficient predictive method for POI, facilitating early screening and intervention, and offers a new direction for exploring the mechanism by which lipid metabolism regulates ovarian function. Trial registration number No","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"37 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401084","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}
引用次数: 0
L26/P-578 Shared-decision making and decisional conflict as important factors in anxiety and depressive symptoms among women planning to undergo fertility treatments 共同决策和决策冲突是计划接受生育治疗的妇女出现焦虑和抑郁症状的重要因素
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.911
S. Ribeiro, A. Fonseca, M. Moura-Ramos
{"title":"L26/P-578 Shared-decision making and decisional conflict as important factors in anxiety and depressive symptoms among women planning to undergo fertility treatments","authors":"S. Ribeiro, A. Fonseca, M. Moura-Ramos","doi":"10.1093/humrep/deag083.911","DOIUrl":"https://doi.org/10.1093/humrep/deag083.911","url":null,"abstract":"Study question What is the role of shared decision-making (SDM) and decisional conflict (DC) in the relationship between doctor-patient interaction quality and women’s anxiety and depressive symptoms? Summary answer Doctor-patient interaction quality (DPIQ) was indirectly associated with women’s anxiety and depressive symptoms, by affecting SDM and DC. What is known already Infertile patients have reported experiencing DC regarding family-building options, which could contribute to emotional distress. While evidence remains scarce in infertility contexts, DC is negatively associated with SDM in other health conditions. In fertility healthcare, patient-centred care (PCC) is recommended, with evidence showing that doctor’s attitude and patient’s involvement in the decisions are highly valued by patients. Furthermore, PCC is also associated with patients’ lower anxiety and depressive symptoms. Although SDM is a key aspect in fertility decisions, few studies have addressed how SDM and DC may have a role in the relationship between doctor-patient interaction and patients’ emotional distress. Study design, size, duration Data of this cross-sectional study was collected between April 2025 and January 2026 in a public IVF centre. Women were consecutively recruited after a clinical appointment with their doctor to decide the course of treatment. Data was collected through an online questionnaire. Inclusion criteria were having an indication to undergo a first autologous IVF/ICSI cycle, and being fluent in Portuguese. Participants/materials, setting, methods A total of 65 women completed the Questionnaire on the Quality of Physician-Patient Interaction, the 9-item Shared Decision Making Questionnaire, the Decisional Conflict Scale, and the Hospital Anxiety and Depression Scale. Path models’ analyses were performed to assess the indirect effects between DPIQ and anxiety (Model 1) and depressive symptoms (Model 2). Model fit and significance of indirect effects were evaluated. Main results and the role of chance Women were 34.34 (± 3.74) years old and were trying to conceive for 42.6 (± 27.92) months. Both model 1 (χ(2) = 6.22, p = .045; CFI = .97; SRMR = .08) and model 2 (χ(2) = 4.05, p =.132; CFI = .99; SRMR = .06) presented a very good fit to the data. Significant indirect effects were found for both models, that is, between the relationship of doctor-patient interaction quality and anxiety (Estimate: -.95; 90% BCCI -1.49, -.36), and between the relationship of doctor-patient interaction quality and depression (Estimate: -.89; 90% BCCI -1.31, -.49), indicating that doctor-patient interaction quality is negatively associated with anxiety and depression through the impact on SDM and DC. These models explained 11.4% of women’s anxiety and 17.2% of depressive symptoms, respectively. Limitations, reasons for caution This study has a cross-sectional design and included a small and convenient sample from a single fertility centre. A longitudinal design with a la","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401128","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}
引用次数: 0
L26/P-647 Trigger choice for final oocyte maturation does not affect the euploidy rate. A retrospective comparison of dual trigger, human Chorionic Gonadotropin and Gonadotropin-Releasing Hormone Agonist L26/P-647最终卵母细胞成熟的触发选择不影响整倍体率。双触发,人绒毛膜促性腺激素和促性腺激素释放激素激动剂的回顾性比较
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.977
G. Gaeta, V. Donno, S. Garcia-Martinez, N.P. Polyzos
{"title":"L26/P-647 Trigger choice for final oocyte maturation does not affect the euploidy rate. A retrospective comparison of dual trigger, human Chorionic Gonadotropin and Gonadotropin-Releasing Hormone Agonist","authors":"G. Gaeta, V. Donno, S. Garcia-Martinez, N.P. Polyzos","doi":"10.1093/humrep/deag083.977","DOIUrl":"https://doi.org/10.1093/humrep/deag083.977","url":null,"abstract":"Study question Could the final oocyte maturation trigger strategy (human chorionic gonadotropin-hCG vs. gonadotropin-releasing hormone agonist-GnRHa vs. dual trigger) affect the euploidy rate? Summary answer No significant differences in euploidy rates were observed according to the final oocyte maturation trigger, whether hCG, GnRHa, or a dual trigger was used. What is known already Final oocyte maturation is a key step in IVF(in vitro fertilization) and has traditionally been triggered with hCG. The adoption of GnRH-antagonist protocols has enabled the use of GnRH-agonist triggers, while dual-trigger strategies combining GnRH-agonist and hCG are increasingly applied across different responder profiles. Although these approaches are widely used and associated with comparable reproductive outcomes, evidence on their impact on embryo euploidy remains limited. Few studies have reported similar euploidy rates between dual trigger and hCG alone, and comparisons between GnRH agonist and dual trigger are lacking. Study design, size, duration A retrospective single-centre study was conducted at a university-affiliated fertility centre, including IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A) performed between January 2021 and December 2024. Cycles were compared according to the oocyte-trigger strategy: hCG (r-hCG 250µg or u-hCG 5,000IU), GnRH agonist (triptorelin 0.2 mg), or dual trigger (triptorelin 0.2 mg + r-hCG 250µg or u-hCG 5,000IU). Cycles with abnormal maternal or paternal karyotypes were excluded. Participants/materials, setting, methods A total of 2,677 IVF–PGT-A cycles were analyzed. Embryonic euploidy rates were compared among three trigger strategies (hCG vs. GnRH-a vs. dual trigger) and stratified by female age (<35, 35–37, 38–40, 41–42, >42 years). Descriptive statistics and ANOVA were used for bivariate analyses. Euploidy rates were estimated using a multivariable mixed-effects Poisson regression adjusted for clinical covariates, and results were reported as incidence rate ratios (IRR) with 95% confidence intervals. Main results and the role of chance Overall, a total of 2677 cycles were included: 728 with GnRH-agonist trigger; 1747 with dual-trigger, and 202 with hCG alone. Patients receiving a GnRH-agonist trigger were younger than those receiving dual or hCG-trigger (39.4±3.1vs.40.6±2.7vs.40.7±2.6 years; P<0.001), with higher AMH levels (2.9±2.2vs.1.3±1.2vs.1.4±1.3 ng/mL; P<0.001), while BMI did not differ (24.6±5.1vs.24.2±4.5vs.23.6±5.1 kg/m²; P=0.307). Regarding the stimulation outcomes, according to the higher ovarian reserve, the GnRH-agonist group showed higher number of oocytes retrieved as compared to the dual and hCG alone, respectively (13.7±7.5vs.7.8±4.8vs.7.4±5.1;p< 0.001), as well as higher number of MII oocytes (9.8±5.5vs.5.9±3.7vs.5.2±3.8, p < 0.001), fertilized oocytes (7.5±4.6vs.4.5±3.1vs.3.6±3.1; p < 0.001), and number of blastocysts (3.2±2.7vs.1","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"17 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401129","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}
引用次数: 0
L26/P-880 Gestational, obstetric, and neonatal outcomes in women aged over 50 undergoing donor in vitro fertilization (d-IVF): A prospective observational study 50岁以上妇女接受体外受精(d-IVF)的妊娠、产科和新生儿结局:一项前瞻性观察研究
IF 6.1 1区 医学
Human reproduction Pub Date : 2026-07-08 DOI: 10.1093/humrep/deag083.1204
K. Pantos, K. Sfakianoudis, A. Trypidi, E. Maziotis, A. Pantou, S. Grigoriadis, G. Kokkali, C. Markomichali, T. Griva, E. Baxevani, V.D. Koufonikola, K. Dafopoulos, M. Simopoulou
{"title":"L26/P-880 Gestational, obstetric, and neonatal outcomes in women aged over 50 undergoing donor in vitro fertilization (d-IVF): A prospective observational study","authors":"K. Pantos, K. Sfakianoudis, A. Trypidi, E. Maziotis, A. Pantou, S. Grigoriadis, G. Kokkali, C. Markomichali, T. Griva, E. Baxevani, V.D. Koufonikola, K. Dafopoulos, M. Simopoulou","doi":"10.1093/humrep/deag083.1204","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1204","url":null,"abstract":"Study question Does advancement of chronological age per year increase the risk of gestational, obstetric, and perinatal complications in women aged 50-years and older undergoing donor-IVF? Summary answer Among women aged 50-years and older undergoing donor-IVF, age advancement per year does not associate with higher risk of severe gestational, obstetric, or perinatal complications. What is known already A critical question in medically assisted reproduction (MAR) concerns the maternal age at which the risk of obstetric and perinatal complications becomes clinically significant, potentially rendering d-IVF unsafe. Evidence for addressing this issue remains limited, primarily deriving from small retrospective studies, case series and case reports. As a result, the overall quality of evidence is low, hindering robust clinical decision-making and the formulation of standardized management strategies for women aged 50 years and older. Addressing this knowledge gap is essential for informing practitioners, guiding patient counseling, and optimizing outcomes in this increasingly prevalent population undergoing d-IVF. Study design, size, duration This double-center, prospective, uncontrolled observational study was conducted from 2022 to 2025, enrolling 236 women aged 50 to 69 years undergoing d-IVF. All participants were recruited in accordance with the Declaration of Helsinki, following standard ethical and consent procedures. Participants underwent comprehensive monitoring throughout pregnancy, delivery, and the neonatal period to systematically document complications and adverse events, ensuring rigorous ethical compliance and methodological integrity. Participants/materials, setting, methods The study population consisted of perimenopausal/menopausal women aged 50 years or older. Menopause was defined by the diagnosis of amenorrhea for at least 12 consecutive months. Participants underwent d-IVF using either fresh or cryopreserved donor oocytes and were managed with conventional endometrial preparation protocols. Pregnancy monitoring was conducted in accordance with international clinical guidelines. Neonatal assessment included comprehensive pediatric monitoring up to 12 months. Statistical analysis was performed using R Language for Statistical Purposes. Main results and the role of chance Gestational diabetes mellitus (GDM) was the most frequently observed complication, occurring in 40% of cases (92/236). Hypertensive disorders in pregnancy (HDP) were identified in 20.3% (48/236), preeclampsia in 9.32% (22/236), and fetal growth restriction (FGR) in 3.81% (9/236). Eclampsia was documented in a single case (0.42%). Regarding pediatric follow-up, abnormal neonatal growth was observed in one case at 2, 4, and 6 months, and in two cases at 9 and 12 months. In one case, abnormal growth was accompanied by autism spectrum disorder at 12 months of follow-up. Logistic regression analysis was performed to assess whether the risk of complications increased","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"368 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401218","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}
引用次数: 0
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