Reproductive biomedicine online最新文献

{"title":"Comparative Molecular Profiling of Exosomes from First-Trimester Human Placental Organoids and Explants","authors":"Kerem Dalgic ,&nbsp;Melike Ucak ,&nbsp;Arda Inanc ,&nbsp;Gizem Melis Kargin ,&nbsp;Mert Turgal ,&nbsp;Ozgur Oktem ,&nbsp;Bora Akgun ,&nbsp;Ciler Celik Ozenci","doi":"10.1016/j.rbmo.2025.105318","DOIUrl":"10.1016/j.rbmo.2025.105318","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Exosomes are extracellular vesicles critical for intercellular communication, particularly in maternal–fetal signaling. This study aimed to isolate and characterize exosomes from human placenta organoids (HPOs) and compare their molecular profiles to those of exosomes from first-trimester placental explants.</div></div><div><h3>MATERIALS AND METHODS</h3><div>First-trimester placenta tissues (6–9 weeks; n = 9) were collected with informed consent (Ethics No:2025.107.IRB2.052). Villous explants were cultured at 24/48h in DMEM/F12+10% exosome-free FBS+1% penicillin-streptomycin, while HPOs were formed via cytotrophoblast cells embedded in Matrigel and maintained in trophoblast organoid medium (TOM). Explants were immunostained for CK7, Ki67, β-hCG, and vimentin; HPOs were evaluated via immunofluorescence (CK7, TP63, β-hCG, Ki67, E-cadherin), and β-hCG secretion was measured by ELISA. Conditioned media from explants and HPOs (day 3/8) were collected for exosome isolation by ultracentrifugation (100,000 × g, 2h, 4°C). Exosomes were analyzed by NTA, TEM, Western blot [CD63 (general), PLAP (placenta-specific), β-actin (negative) exosome markers], and RT-qPCR (miR-517a-3p, miR-519d-3p). PLAP expression in exosomes from term explants served as a positive control. Molecular fingerprints were assessed by surface-enhanced Raman spectroscopy (SERS). Statistical analysis included Mann-Whitney U test with Bonferroni correction for SERS data (p&lt; 0.001) and Kruskal-Wallis test for non-parametric NTA results (p&lt; 0.05).</div></div><div><h3>RESULTS</h3><div>Exosomes from both groups displayed characteristic morphology, marker expression, and size range (30–150 nm). Explant-derived exosomes had significantly higher particle concentrations (9.33 × 10¹⁰±8.71 × 10⁹ at 24h; 9.04 × 10¹⁰±6.72 × 10⁹ at 48h) than HPO-derived exosomes (3.19 × 10¹⁰±1.60 × 10⁹ at day 3; 3.71 × 10¹⁰±2.64 × 10⁹ at day 8) (p&lt; 0.05). CD63 was detected in exosomes for both groups; PLAP and β-actin were absent. TEM confirmed typical exosome morphology. Placenta-specific miRNAs were expressed in both groups. SERS revealed significant spectral differences (p&lt; 0.001) at 1080, 1445, and 1508 cm⁻¹, indicating differences in lipid and protein composition.</div></div><div><h3>CONCLUSIONS</h3><div>HPO-derived exosomes share key features with exosomes from matched first-trimester placenta explants, supporting the utility of HPOs as a relevant in vitro model to study placental extracellular vesicles.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study introduces HPOs as a scalable source for placenta exosome research, enabling investigation of maternal–fetal signaling and pregnancy-related disorders.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105318"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Per1 and Per2 Leads to Postnatal Growth Impairment Mimicking Fetal Growth Restriction","authors":"Begum Durkut Kuzu ,&nbsp;Yaren Sevval Yilmaz ,&nbsp;Cagla Faki ,&nbsp;Hana Asghari ,&nbsp;Derya Deniz Ozdemir ,&nbsp;Ciler Celik Ozenci","doi":"10.1016/j.rbmo.2025.105319","DOIUrl":"10.1016/j.rbmo.2025.105319","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Circadian disruption during pregnancy is clinically associated with an increased risk of fetal growth restriction; however, the underlying mechanisms remain largely unknown. To investigate the role of core circadian genes Per1 and Per2 in developmental growth, we analyzed early postnatal outcomes in a double knockout (dKO) mouse model.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Per1/Per2 dKO mouse lines were generated on a CB6F1 background using CRISPR/Cas9 genome editing, with ethical approval obtained from the institutional committee (2023.HADYEK.005). Genotyping was performed by agarose gel electrophoresis and validated through Sanger sequencing. Two experimental groups were established based on genotype: heterozygous Per1+/–/Per2+/– (dKO-het) and homozygous Per1–/–/Per2–/– (dKO-hom) breeding pairs. Gestational duration, pup number, pup body weight, and crown–rump length were recorded on postnatal days 7, 14, and 21. Data were shown as mean ± SD at each time point.</div></div><div><h3>RESULTS</h3><div>Mutant lines carried a nucleotide substitution and deletion in exon 2 of Per1, and a 19-bp deletion in exon 4 of Per2. Gestational duration was consistently 19 days across groups, and litter size was comparable between heterozygous (n=4) and homozygous dKO (n=2) breeders (6.75 ± 0.96 vs. 5.00 ± 2.83 pups per litter). However, dKO-hom pups (n=8) exhibited lower body weights compared to dKO-het pups (n=10): day 7, 4.02 ± 0.57 g vs. 4.77 ± 0.56 g (16% decrease); day 14, 6.16 ± 0.72 g vs. 8.43 ± 0.23 g (27% decrease); and day 21, 8.31 ± 0.89 g vs. 9.77 ± 0.84 g (15% decrease). Similarly, crown–rump lengths were reduced in homozygous dKO pups: day 7, 4.26 ± 0.21 cm vs. 4.37 ± 0.23 cm (3% decrease); day 14, 5.33 ± 0.22 cm vs. 6.00 ± 0.19 cm (12% decrease); and day 21, 6.05 ± 0.29 cm vs. 6.13 ± 0.27 cm (2% decrease).</div></div><div><h3>CONCLUSIONS</h3><div>We demonstrate that Per1/Per2 deficiency leads to postnatal growth impairment, despite normal gestational duration and litter size, recapitulating features of fetal growth restriction. This model provides a valuable tool for investigating the molecular mechanisms linking circadian clock disruption to developmental growth deficits.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study establishes a novel genetic model linking core circadian clock gene disruption to postnatal growth impairment, providing key mechanistic insight into how parental circadian disruption may contribute to fetal growth restriction. The Per1/Per2 double knockout mouse offers a valuable platform for investigating circadian-regulated pathways in developmental biology.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105319"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Oxygen Promotes Energy-Efficient Metabolism in Cumulus-Oocyte Complexes During IVM","authors":"Ellen Anckaert ,&nbsp;Gamze Ates ,&nbsp;Heidi Van Ranst ,&nbsp;Linde Mostinckx ,&nbsp;Wilfried Cools ,&nbsp;Ann Massie ,&nbsp;Michel De Vos ,&nbsp;Nazli Akin","doi":"10.1016/j.rbmo.2025.105291","DOIUrl":"10.1016/j.rbmo.2025.105291","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>In vitro maturation (IVM) is a mild-approach assisted reproductive technology designed to obtain mature oocytes after culturing cumulus–oocyte complexes (COCs) from 2–10 mm antral follicles. Particularly recommended for women with polycystic ovarian syndrome, IVM eliminates the risk of ovarian hyperstimulation with minimal or no gonadotropin use and abandoned ovulation trigger. Biphasic IVM culture systems are the most effective protocols with a pre-IVM phase supporting cytoplasmic maturation and oocyte competence under meiotic arrest, followed by IVM for nuclear maturation. There is currently no consensus on IVM culture oxygen settings: while in vivo COCs are exposed to low oxygen (2–9%), IVM is typically performed at atmospheric oxygen. Here we assess the effects of environmental conditions on COC energy metabolism performing pre-IVM under physiological (5%) vs atmospheric (20%) O₂.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Hyperresponder (non-PCOS) research oocyte donors (n=21) received minimal stimulation (75-150 IU menopur/day) for 0-2 days to collect COCs (n = 221) from follicles &lt;10 mm. After oocyte pick-up, COCs were randomly allocated to both atmospheric and physiological O2, for pre-IVM culture (22h). At the end of the culture, the COCs were processed to assess real-time metabolism, measure ATP concentrations, evaluate mitochondrial and antioxidative functions (CellROX, JC-1, and mBCl staining). Spent medium was analyzed for glucose and lactate. Statistical analysis was completed with a t-test or linear mixed model test.</div></div><div><h3>RESULTS</h3><div>A greater proportion of ATP was produced via mitochondrial respiration at 20% O₂ compared to 5% O₂ (43±5% vs 27±10%, p&lt;0.05). Yet, overall ATP production was greater in COCs cultured under 5% O₂ (50.3 ± 17.9 nmol/μg vs. 75.2 ± 32.7 nmol/μg, p&lt;0.05). Glucose uptake was similar between conditions, while lactate production was elevated with 5% O₂ (0.04 ± 0.03 mmol/L/COC vs 0.06 ± 0.03 mmol/L/COC, p&lt;0.05). Mitochondrial and antioxidative functions between groups were comparable.</div></div><div><h3>CONCLUSIONS</h3><div>This exploratory study shows that culturing COCs under 5% O₂ during pre-IVM leads to lower mitochondrial activity. While lacking clinical outcomes, the results support the idea that physiological conditions might be favoring an efficient energy metabolism, compared to metabolic exhaustion, possibly through lipid utilization rather than glucose.</div></div><div><h3>IMPACT STATEMENT</h3><div>Our results highlight the potential of low O2 levels to improve metabolic efficiency during IVM, encouraging re-evaluation of standard culture conditions.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105291"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of ICSI-to-Biopsy Inte rval on Embryo Ploidy Status: An Analysis of More Than 9000 Embryos.","authors":"Meral Gultomruk ,&nbsp;Fazilet Kubra Boynukalin ,&nbsp;Neslihan Sonmez ,&nbsp;Sinan Ozkavukcu ,&nbsp;Mustafa Bahceci ,&nbsp;Gurkan Bozdag","doi":"10.1016/j.rbmo.2025.105292","DOIUrl":"10.1016/j.rbmo.2025.105292","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Fertilized oocytes have the potential to develop into viable blastocysts in vitro by day5(D5), day6(D6), or day7(D7). Blastocyst expansion is key to trophectoderm biopsy (TB) success; biopsy may be ideal when herniation has begun. Due to variability expansion, TB is often delayed until optimal expansion for technical easier. However, data remain inconclusive regarding whether blastocysts with an elongated duration until TB are associated with ploidy status.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective cohort study conducted at Bahceci Health Group between January 2020-2024. The study evaluated 9.427 blastocyst stage embryos obtained from 4.616 PGT-A cycle. The interval between ICSI-TB was calculated for each embryo from software records. Time was given as hour: in(h) and minute(min). The interval has been divided into four quartiles separately for D5, and D6 embryos to evaluate the euploidy rates. Aneuploidy rates were compared across the quartiles of time between ICSI-TB. Additionally, logistic regression analysis was performed, incorporating the quartiles separately for D5, and D6 embryos to assess their impact on aneuploidy rates.</div></div><div><h3>RESULTS</h3><div>A total of 9.427 embryos were evaluated, of which 5.530(58.7%) were D5, and 3.897(41.3%) were D6 blastocyst. Euploidy rates decreased across Q1-Q4 for both D5 embryos 51.1%, 49.9%, 47.4%, 43.4% (p&lt;0.001) and 41.5%, 43.1%, 40.2%, and 33.1% (p&lt;0.001), respectively. Generalize mixed model (GMM) was used to investigate which factors affected the ploidy status of the embryo. GMM revealed that the female age[OR:0.88 CI 95%(0.87-0.89)p&lt;0.001)], embryo quality[ref:good; for poor OR:0.42 CI 95%(0.26-0.67), for moderate OR:0.58 CI 95% (0.51-0.65)p&lt;0.001], and absence of male factor[OR:1.38 CI 95%(1.03-1.84)p=0.029] were the independent determinants for D5 embryos. Female age[OR:0.86 CI 95%(0.85-0.88)p&lt;0.001), embryo quality [ref:good for poor OR:0.33 CI 95%(0.25-0.45), for moderate OR:0.48 CI 95%(0.41-0.56)p&lt;0.001], and ICSI-TB interval Q[ref:Q1, for Q2 OR:1.09 CI 95%(0.89-1.32), for Q3 OR:0.96 CI 95%(0.7-1.17), for Q4 OR:0.75 CI 95%(0.61-0.92)p=0.006] were the independent determinants for D6 embryos.</div></div><div><h3>CONCLUSIONS</h3><div>The current results suggest that, in D5 blastocysts, a longer duration from ICSI-TB does not predict ploidy status. However, within the D6 blastocyst cohort, embryos in the latest quartile exhibit the worst performance.</div></div><div><h3>IMPACT STATEMENT</h3><div>A more objective evaluation necessitates precise timing of embryo hatching, which should be assessed using morphokinetic parameters.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105292"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Homozygous c.838T>C (p.Cys280Arg) Mutation in the ZP1 (Zona Pellucida Glycoprotein 1) Gene in a Patient with EFS","authors":"Hande Nalan Tore ,&nbsp;Hasan Bulut ,&nbsp;Rovshan Jabbarov ,&nbsp;Murat Berkkanoglu ,&nbsp;Kemal Ozgur ,&nbsp;Kevin Coetzee ,&nbsp;Tarkan Kalkan","doi":"10.1016/j.rbmo.2025.105300","DOIUrl":"10.1016/j.rbmo.2025.105300","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>To present a rare case of \"true\" Empty Follicle Syndrome (EFS) associated with a novel homozygous ZP1 gene mutation and to emphasize the importance of comprehensive genetic analysis in elucidating the aetiology and guiding individualized management in cases of unexplained EFS.</div></div><div><h3>MATERIALS AND METHODS</h3><div>The case is that of a 33-year-old Asian patient who presented with a 7-year history of primary infertility, with a karyotype of 46, XX,1qh+, which was considered a clinically insignificant variant. The patient’s partner presented with a normal semen analysis and a normal karyotype (46, XY). The patient’s hormone assessment on cycle day 2 of OS showed normal basal E2 (58 pg/m) and LH (0.33 IU/L) levels, and, therefore, she underwent a routine GnRH antagonist OS, starting with a daily 375 IU dose of FSH (225 IU recombinant FSH + 150 IU HMG). When leading follicles reached ∼14 mm, the antagonist was added, with FSH stimulation continuing for 11 days. A Dual trigger (0.2mg GnRH agonist plus 250 ug hCG) was administered on day 12 when leading follicles were &gt;17 mm. Follicles were collected 36 hours after trigger injection. A comprehensive genetic evaluation (LHCGR, ZP1, ZP2, ZP3, FSHR, GDF9, BMP15, PANX1) was performed using whole-exome sequencing (WES) and targeted next-generation sequencing (NGS).</div></div><div><h3>RESULTS</h3><div>At oocyte pickup (OPU), approximately 35 intact follicles were aspirated; however, no oocytes or cumulus complexes were identified despite thorough microscopic examination. Genetic analysis revealed a homozygous ZP1 c.838T&gt;C (p.Cys280Arg) mutation, classified as likely pathogenic by ACMG. This variant is predicted to impair disulfide bond formation in the zona pellucida, potentially disrupting oocyte release.</div></div><div><h3>CONCLUSIONS</h3><div>The early use of comprehensive genetic techniques is critical in encountering \"true\" EFS to guide appropriate treatment planning and set realistic expectations, thereby, enabling a personalized and rational approach to patient management.</div></div><div><h3>IMPACT STATEMENT</h3><div>This case highlights the critical role of advanced genetic testing in uncovering the underlying aetiology of true Empty Follicle Syndrome (EFS). The identification of a novel homozygous ZP1 mutation not only expands the known genetic spectrum of EFS but also underscores the importance of personalized diagnostic strategies in reproductive medicine. Early genetic evaluation can prevent repeated failed IVF attempts, guide clinical decision-making, and provide meaningful prognostic information for affected patients.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105300"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Too Many Cycles, Limited Capacity: The Impact of Daily Laboratory Workload on Embryological and Clinical Outcomes in ICSI Cycle","authors":"Havva Yesilleme ,&nbsp;Zekiye Gulfem Yurtgezen ,&nbsp;Kiper Aslan ,&nbsp;Isil Kasapoglu ,&nbsp;Gurkan Uncu ,&nbsp;Cihan Cakir","doi":"10.1016/j.rbmo.2025.105296","DOIUrl":"10.1016/j.rbmo.2025.105296","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>With the rising number of patients and increasing procedural complexity in infertility treatment, maintaining an optimal workload balance in embryology laboratories has become essential for achieving successful clinical outcomes. This study aimed to assess whether daily workload, quantified by the number of OPU procedures performed per day, affects embryological and clinical outcomes in ICSI cycles.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This retrospective study was conducted at the Bursa Uludag University ART Center between 2011 and 2025 and included 4651 ICSI cycles. Cycles involving PGD, fertility preservation, or failed oocyte retrieval were excluded. Based on the number of daily OPU procedures, cycles were categorized into three groups to reflect laboratory workload: Group 1 (1–2 OPUs/day) (n=1870) Group 2 (3–4 OPUs/day) (n=1643), and Group 3 (≥5 OPUs/day) (n=1138). Baseline patient characteristics, hormonal profiles, and ovarian stimulation parameters were compared among groups. Semen parameters and oocyte quality scores were also evaluated. Embryological and clinical outcomes were then analyzed to determine potential associations with workload intensity.</div></div><div><h3>RESULTS</h3><div>Baseline patient characteristics, hormonal profiles, ovarian stimulation data, sperm parameters, and oocyte quality scores were statistically comparable among the three groups (p &gt; 0.05). While the number of retrieved oocytes and oocyte maturation rates did not differ significantly, both fertilization (p=0.004) and blastulation rates (p=0.046) were negatively correlated with increasing laboratory workload, reaching statistical significance. However, implantation rates following fresh embryo transfers remained similar across all groups (p=0.248).</div></div><div><h3>CONCLUSIONS</h3><div>The observed decline in fertilization and blastulation rates in association with increased daily laboratory workload highlights a potential vulnerability in embryology practice under high-volume conditions. Nevertheless, the lack of significant difference in implantation rates among fresh transfers suggests that the quality of the resulting blastocyst cohort was sufficient to maintain clinical outcomes in the first transfer.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study demonstrates that elevated embryology laboratory workload is associated with reduced fertilization and blastulation efficiency, despite stable clinical and laboratory baseline conditions. Optimizing daily case volume and implementing workload management strategies may be essential for sustaining high embryological performance and ensuring consistent ART outcomes.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105296"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imatinib Inhibits Proliferation and Migration While Inducing Apoptosis in Endometriotic Cells via c-Abl Pathway Modulation","authors":"Isil Yenigun ,&nbsp;Nazlı Ece Huner ,&nbsp;Erkut Attar ,&nbsp;Basak Aru ,&nbsp;Beyza Gaye Edepli ,&nbsp;Elif Kilic ,&nbsp;Aylin Yaba","doi":"10.1016/j.rbmo.2025.105316","DOIUrl":"10.1016/j.rbmo.2025.105316","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Endometriosis is characterized by the ectopic growth of endometrial tissue, linked to disrupted proliferation and apoptosis. c-Abl (Abelson tyrosine kinase), implicated in these processes, is inhibited by imatinib. However, its role in endometriosis remains unclear. We hypothesized that imatinib may be used as a therapeutic target for endometriosis.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Endometriotic tissues were collected from patients (n=6, aged 23-45) at Yeditepe University Hospital. Stromal cells were cultured in DMEM/F12 (10% FBS), then treated with 0 (control), 12.5, 25, and 50 µM imatinib for 48 and 72 hours. Proliferation was measured with an automatic cell counter. Apoptosis/viability was assessed via Annexin V/PI staining, and the cell cycle by DNA content analysis. Migration was evaluated by a wound-healing assay. c-Abl and phospho-c-Abl (p-c-Abl) levels were assessed by immunofluorescence.</div></div><div><h3>RESULTS</h3><div>Proliferation of endometriotic cells significantly decreased at 48 hours with 25 µM and 50 µM imatinib, and at 72 hours in all treatment groups (p&lt;0.01). Early apoptosis was increased in all treatment groups (p&lt;0.05), while late apoptosis was elevated in the 25 µM and 50 µM (p&lt;0.05). Necrotic population was increased in the 12.5 µM and 25 µM groups at 48 hours (p&lt;0.05), and in the 50 µM group at 72 hours (p&lt;0.05). Cell cycle analysis at 48 hours showed G0/G1 arrest with 12.5 μM imatinib (p&lt;0.001), while 50 μM caused cell cycle arrest in S (p&lt;0.05) and G2/M phases (p&lt;0.0001) and promoted aneuploidy. In 72 hours, 12.5 μM imatinib led to G0/G1 arrest (p&lt;0.05), and aneuploidy was observed at 25 and 50 µM imatinib, but cell cycle arrest occurred only at 50 µM, with G2/M arrest (p&lt;0.0001). Cell migration is decreased in all treatment groups(p&lt;0.001). Immunofluorescence in 72 hours showed increased c-Abl at 50µM (p&lt;0.05). In contrast, p-c-Abl levels decreased in all treatment groups (p&lt;0.05).</div></div><div><h3>CONCLUSIONS</h3><div>Imatinib inhibited proliferation and migration while promoting apoptosis and necrosis in a dose- and time-dependent manner. It alters the cell cycle by causing arrest and may induce aneuploidy. These findings suggest that inhibition of c-Abl activity may play a significant role in endometriotic cell behavior.</div></div><div><h3>IMPACT STATEMENT</h3><div>The expanding understanding of c-Abl inhibition in endometriosis could provide valuable insights into the underlying mechanisms of endometriosis. We believe that our results may guide future studies on endometriosis and contribute to the development of new therapeutic approaches.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105316"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Piezo-Icsi or Calcium Ionofor Superior for Oocyte Activation Compared to Standard Icsi","authors":"Gokalp Oner ,&nbsp;Enes Karaman ,&nbsp;Ferhan Elmali ,&nbsp;Suat Altmisyedioglu ,&nbsp;Fatma Ozdemir","doi":"10.1016/j.rbmo.2025.105295","DOIUrl":"10.1016/j.rbmo.2025.105295","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Oocyte activation failure is a major cause of embryo arrest, cleavage anomalies, and impaired blastocyst development in assisted reproductive techniques. In intracytoplasmic sperm injection (ICSI) cycles, oocyte activation can be induced using chemical, mechanical, or physical stimuli. Calcium ionophore is the most commonly used chemical agent for artificial activation. PIEZO-ICSI is a mechanical technique that uses a piezoelectric actuator to facilitate precise penetration of the zona pellucida with a microinjection pipette. However, prospective studies directly comparing PIEZO-ICSI and calcium ionophore in patients with prior embryo cleavage arrest are lacking.</div></div><div><h3>MATERIALS AND METHODS</h3><div>This prospective study included 240 patients with a history of embryo transfer cancellation due to embryo cleavage arrest. Patients with severe male factor infertility, endometriosis, or absolute tubal factor were excluded. Ethical approval was obtained from the Ethics Committee of Nigde Omer Halisdemir University (Approval No: 2025/04-39). Patients were allocated into three groups according to the oocyte activation method used: PIEZO-ICSI, calcium ionophore, or conventional ICSI. The primary outcomes were number of blastocysts, embryo quality, and clinical pregnancy rates.</div></div><div><h3>RESULTS</h3><div>The groups were similar in age, BMI, antral follicle count, AMH, and baseline hormone levels (FSH, LH, Estradiol). The mean number of retrieved oocytes was comparable across all groups (p = 0.911). PIEZO-ICSI achieved significantly higher fertilization rates (1.69±0.22) compared to conventional ICSI (0.93±0.22; p = 0.045), and also higher pregnancy rates (47% vs. 15%; p &lt; 0.001). Calcium ionophore showed similar fertilization to control (1.51±0.21 vs. 0.93±0.22; p = 0.051), but significantly higher pregnancy rates (40% vs. 15%; p &lt; 0.001). No significant differences were observed between PIEZO-ICSI and calcium ionophore groups.</div></div><div><h3>CONCLUSIONS</h3><div>Both PIEZO-ICSI and calcium ionophore significantly improved fertilization and pregnancy outcomes in patients with a history of cleavage arrest. This is the first prospective study comparing these two methods. PIEZO-ICSI may serve as a viable mechanical alternative for oocyte activation in selected IVF patients.</div></div><div><h3>IMPACT STATEMENT</h3><div>PIEZO-ICSI or calcium ionophore may be preferred for oocyte activation in patients with a history of cleavage arrest.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105295"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Clinical and Artificial Intelligence (AI)-Based Interpretation: Agreement and Diagnostic Consistency","authors":"Simge Berrak Beyoglu Oruc ,&nbsp;Rozerin Balci ,&nbsp;Berfin Baybas ,&nbsp;Busra Toper","doi":"10.1016/j.rbmo.2025.105302","DOIUrl":"10.1016/j.rbmo.2025.105302","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>Artificial intelligence (AI)-based models trained on large datasets and advanced algorithms employ signal processing and pattern recognition techniques to reduce subjectivity and human error in the evaluation of Non-Stress Tests (NST). This study examined the agreement between clinician and AI-based NST evaluations, highlighting AI’s potential in clinical decision support.</div></div><div><h3>MATERIALS AND METHODS</h3><div>In a cohort of 100 patients, NST parameters were assessed by both clinical interpretation and ChatGPT, categorized into seven subcomponents, and Inter-rater agreement was assessed using Cohen’s Kappa coefficient.</div></div><div><h3>RESULTS</h3><div>Good agreement was observed between clinician and ChatGPT evaluations (Kappa 0.655, accuracy 77%). Subgroup analyses showed moderate agreement in cases undergoing cesarean section due to fetal distress (Kappa 0.47, accuracy 76%), with ChatGPT classifying 87% of these cases as Category 3. Notably, no patients in this subgroup were classified as Category 1 by ChatGPT, suggesting a conservative approach in high-risk scenarios. In the non-reactive NST subgroup, moderate agreement (0.42) was also observed. In all 9 cases of fetal tachycardia, ChatGPT correctly identified the condition (100% accuracy) and classified 8 of them as Category 2.</div><div>When evaluating individual NST parameters, a very strong agreement was observed for the presence of accelerations (0.84). Good agreement was found in NST categorization (0.64), presence of decelerations (0.79),and variability presence (0.67). In contrast, only moderate agreement was observed in the classification of deceleration types (0.53) and grading of variability (0.47) (Table 1). Detailed comparison of deceleration type revealed weak-to-moderate agreement (0.29). “Deep prolonged” decelerations were consistently recognized by both evaluators, whereas significant discrepancies were noted in identifying “recurrent late,” “deep late,” and “variable” patterns. These results indicate that while AI shows acceptable performance in general pattern recognition, its ability to distinguish specific and complex patterns remains limited.</div></div><div><h3>CONCLUSIONS</h3><div>This study demonstrated moderate agreement between AI and clinical evaluations. The agreement was lower for nuanced parameters, such as deceleration type and variability; yet AI could still support early diagnosis and evidence-based decision-making.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study introduces an AI-based approach for clinical interpreting, such as NST categorization, aiming to enhance diagnostic clarity and support clinical education.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105302"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Tuba-ovarian Abscess After Incomplete Surgery and Drainage in an Endometrioma: A Case Report","authors":"Simge Berrak Beyoglu Oruc","doi":"10.1016/j.rbmo.2025.105332","DOIUrl":"10.1016/j.rbmo.2025.105332","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>The weak cyst wall and the creation of a culture medium for hemorrhagic content may theoretically facilitate bacterial implantation and infection. We aimed to discuss the importance of preoperative evaluation in preventing incomplete surgeries in deep infiltrative endometriosis, the management of abscess after ovarian drilling.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Case Report</div><div>A 31-year-old G0P0A0 nulliparous was admitted with high fever and pelvic pain. In the patient's history, it was learned that laparoscopic 4-centimeter(cm) right ovary endometrioma cyst excision, left ovary drilling and endometriotic noduls cauterization were performed at an external center 20 days ago. In her preoperative application, she reported pelvic pain and dysmenorrhea, and a gynecological evaluation revealed an 8-cm endometrioma cyst on a pelvic MRI. The patient had laparoscopic excision of a right ovarian endometrioma, left ovarian drilling, and cauterization of nodules, followed by a single dose of GnRH agonist for suppression therapy. The patient was hospitalized with the diagnosis of tubo-ovarian abscess with CRP: 223 mg/L and observation of a 5-cm heterogeneous collection area in the left adnexal area on the pelvic MRI.</div><div>After clinical and laboratory improvement with antibiotherapy, pelvic MRI showed a persistent 5-cm left adnexal mass (Figure 1). Preoperative AMH was 5.6 ng/mL and postoperative AMH 1.98 ng/mL, indicating a postoperative loss of ovarian reserve. Hysterosalpingography (HSG) showed normal right tubal passage and significant hydrosalpinx with no passage in the left tube.</div></div><div><h3>RESULTS</h3><div>Discussion</div><div>We believe that the use of ovarian drilling is an outdated approach, and that the abscess complication observed following incomplete surgery was attributable to this procedure. Considering the relatively lower negative impact of sterile hydrosalpinx, associated with endometrioma, on implantation success compared to septic hydrosalpinx secondary to pelvic inflammatory disease, the patient was offered an opportunity for spontaneous conception before planning secondary surgical intervention.</div></div><div><h3>CONCLUSIONS</h3><div>New treatment options, such as sclerotherapy, are also reported to have positive results in symptomatic improvement and pregnancy outcomes. Medical management was chosen, with follow-up for spontaneous conception due to the risk of diminished ovarian reserve from a second surgery.</div></div><div><h3>IMPACT STATEMENT</h3><div>Treatment options and complication management in surgical or medical treatments for deep infiltrative endometriosis need to be individualized.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105332"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}