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Imatinib Inhibits Proliferation and Migration While Inducing Apoptosis in Endometriotic Cells via c-Abl Pathway Modulation 伊马替尼通过调节c-Abl通路抑制子宫内膜异位症细胞增殖和迁移,同时诱导细胞凋亡
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105316
Isil Yenigun , Nazlı Ece Huner , Erkut Attar , Basak Aru , Beyza Gaye Edepli , Elif Kilic , Aylin Yaba

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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<0.01). Early apoptosis was increased in all treatment groups (p<0.05), while late apoptosis was elevated in the 25 µM and 50 µM (p<0.05). Necrotic population was increased in the 12.5 µM and 25 µM groups at 48 hours (p<0.05), and in the 50 µM group at 72 hours (p<0.05). Cell cycle analysis at 48 hours showed G0/G1 arrest with 12.5 μM imatinib (p<0.001), while 50 μM caused cell cycle arrest in S (p<0.05) and G2/M phases (p<0.0001) and promoted aneuploidy. In 72 hours, 12.5 μM imatinib led to G0/G1 arrest (p<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<0.0001). Cell migration is decreased in all treatment groups(p<0.001). Immunofluorescence in 72 hours showed increased c-Abl at 50µM (p<0.05). In contrast, p-c-Abl levels decreased in all treatment groups (p<0.05).

CONCLUSIONS

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.

IMPACT STATEMENT

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.
目的子宫内膜异位症的特点是子宫内膜组织异位生长,与增殖和凋亡中断有关。参与这些过程的c-Abl (Abelson酪氨酸激酶)被伊马替尼抑制。然而,其在子宫内膜异位症中的作用尚不清楚。我们假设伊马替尼可以作为子宫内膜异位症的治疗靶点。材料与方法在叶迪特佩大学医院收集6例患者的异位组织(n=6,年龄23-45岁)。基质细胞在DMEM/F12(10%胎牛血清)中培养,然后用0(对照)、12.5、25和50µM伊马替尼处理48和72小时。用自动细胞计数器测量增殖。Annexin V/PI染色检测细胞凋亡/细胞活力,DNA含量分析细胞周期。通过伤口愈合试验评估迁移。免疫荧光法测定c-Abl和磷酸c-Abl (p-c-Abl)水平。结果25µM和50µM伊马替尼治疗后48小时和72小时子宫内膜异位症细胞增殖均显著降低(p < 0.01)。各处理组早期细胞凋亡增加(p < 0.05),晚期细胞凋亡在25µM和50µM时升高(p < 0.05)。12.5µM和25µM组48小时坏死细胞数量增加(p < 0.05), 50µM组72小时坏死细胞数量增加(p < 0.05)。48 h细胞周期分析显示,12.5 μM的伊马替尼阻滞G0/G1期(p<0.001), 50 μM的伊马替尼阻滞S期(p<0.05)和G2/M期(p<0.0001)细胞周期,促进非整倍体。在72小时内,12.5 μM伊马替尼导致G0/G1停止(p<0.05),在25和50µM的伊马替尼下观察到非整倍体,但仅在50µM时发生细胞周期停止,G2/M停止(p<0.0001)。所有治疗组的细胞迁移均减少(p<0.001)。72小时免疫荧光显示50µM时c-Abl升高(p<0.05)。p-c-Abl水平在各治疗组均下降(p < 0.05)。结论西马替尼抑制细胞增殖和迁移,促进细胞凋亡和坏死,具有剂量依赖性和时间依赖性。它通过引起阻滞改变细胞周期,并可能诱发非整倍体。这些发现提示抑制c-Abl活性可能在子宫内膜异位症细胞行为中起重要作用。影响声明对c-Abl抑制在子宫内膜异位症中的作用的进一步了解可以为子宫内膜异位症的潜在机制提供有价值的见解。我们相信我们的结果可以指导未来子宫内膜异位症的研究,并有助于开发新的治疗方法。
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引用次数: 0
Is Piezo-Icsi or Calcium Ionofor Superior for Oocyte Activation Compared to Standard Icsi 与标准Icsi相比,压电Icsi或钙离子在卵母细胞激活方面是否更好
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105295
Gokalp Oner , Enes Karaman , Ferhan Elmali , Suat Altmisyedioglu , Fatma Ozdemir

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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 < 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 < 0.001). No significant differences were observed between PIEZO-ICSI and calcium ionophore groups.

CONCLUSIONS

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.

IMPACT STATEMENT

PIEZO-ICSI or calcium ionophore may be preferred for oocyte activation in patients with a history of cleavage arrest.
目的:在辅助生殖技术中,卵母细胞激活失败是导致胚胎停滞、卵裂异常和囊胚发育受损的主要原因。在胞浆内单精子注射(ICSI)周期中,卵母细胞的激活可以通过化学、机械或物理刺激来诱导。钙离子载体是人工活化最常用的化学试剂。压电- icsi是一种机械技术,它使用压电致动器来促进微注射移液管精确穿透透明带。然而,直接比较piezoo - icsi和钙离子载体在胚胎卵裂停止患者中的前瞻性研究尚缺乏。材料与方法本前瞻性研究纳入240例因胚胎卵裂停止而取消胚胎移植的患者。严重男性因素不孕、子宫内膜异位症或绝对输卵管因素的患者被排除在外。已获得Nigde Omer Halisdemir大学伦理委员会的伦理批准(批准号:2025/04-39)。根据使用的卵母细胞激活方法,将患者分为三组:piezoo -ICSI,钙离子载体或常规ICSI。主要结果是囊胚数量、胚胎质量和临床妊娠率。结果两组在年龄、BMI、窦卵泡计数、AMH和基线激素水平(FSH、LH、雌二醇)方面相似。所有组的平均卵母细胞数量具有可比性(p = 0.911)。与传统ICSI(0.93±0.22;p = 0.045)相比,PIEZO-ICSI的受精率(1.69±0.22)显著高于传统ICSI(0.93±0.22;p < 0.001),妊娠率也更高(47% vs. 15%; p < 0.001)。钙离子载体的受精率与对照组相似(1.51±0.21∶0.93±0.22;p = 0.051),但妊娠率明显高于对照组(40%∶15%;p < 0.001)。压电- icsi组与钙离子载体组间无显著差异。结论PIEZO-ICSI和钙离子载体均能显著改善乳沟停育史患者的受精和妊娠结局。这是比较这两种方法的首次前瞻性研究。PIEZO-ICSI可以作为一个可行的机械替代卵母细胞激活在选定的试管婴儿患者。影响声明:对于有卵裂停止病史的患者,压电- icsi或钙离子载体可能优先用于卵母细胞激活。
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引用次数: 0
Comparison of Clinical and Artificial Intelligence (AI)-Based Interpretation: Agreement and Diagnostic Consistency 临床与人工智能(AI)解释的比较:一致性和诊断一致性
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105302
Simge Berrak Beyoglu Oruc , Rozerin Balci , Berfin Baybas , Busra Toper

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.
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.

CONCLUSIONS

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.

IMPACT STATEMENT

This study introduces an AI-based approach for clinical interpreting, such as NST categorization, aiming to enhance diagnostic clarity and support clinical education.
目的基于人工智能(AI)的模型在大型数据集和高级算法上进行训练,采用信号处理和模式识别技术来减少非压力测试(NST)评估中的主观性和人为错误。本研究考察了临床医生和基于人工智能的NST评估之间的一致性,强调了人工智能在临床决策支持方面的潜力。材料与方法在一组100例患者中,通过临床解释和ChatGPT对NST参数进行评估,将其分为7个子部分,并使用Cohen 's Kappa系数评估评分者间一致性。结果临床与ChatGPT评价结果吻合较好(Kappa 0.655,准确率77%)。亚组分析显示,由于胎儿窘迫而进行剖宫产手术的病例有中等程度的一致性(Kappa 0.47,准确率76%),ChatGPT将87%的病例分类为3类。值得注意的是,该亚组中没有患者被ChatGPT分类为1类,提示在高危情况下采用保守方法。在非反应性NST亚组中,也观察到中度一致性(0.42)。在所有9例胎儿心动过速中,ChatGPT正确识别了病情(100%准确),并将其中8例分类为2类。当评估单个NST参数时,观察到加速度存在的一致性非常强(0.84)。在NST分类(0.64),存在减速(0.79)和可变性存在(0.67)方面发现了良好的一致性。相比之下,在减速类型的分类(0.53)和变异性的分级(0.47)方面,只有中等程度的一致性(表1)。减速类型的详细比较显示弱至中度一致性(0.29)。“深度延长”减速被两位评估者一致认可,而在识别“复发性晚期”、“深度晚期”和“可变”模式时,发现了显著的差异。这些结果表明,虽然人工智能在一般模式识别中表现出可接受的性能,但其区分特定和复杂模式的能力仍然有限。结论本研究显示人工智能与临床评价有一定程度的一致性。对于减速类型和可变性等细微参数,该协议较低;但人工智能仍然可以支持早期诊断和基于证据的决策。影响声明本研究引入了一种基于人工智能的临床解释方法,如NST分类,旨在提高诊断清晰度和支持临床教育。
{"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}
引用次数: 0
Management of Tuba-ovarian Abscess After Incomplete Surgery and Drainage in an Endometrioma: A Case Report 子宫内膜异位瘤不完全手术引流后输卵管卵巢脓肿的处理:1例报告
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105332
Simge Berrak Beyoglu Oruc

OBJECTIVE

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.

MATERIALS AND METHODS

Case Report
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.
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.

RESULTS

Discussion
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.

CONCLUSIONS

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.

IMPACT STATEMENT

Treatment options and complication management in surgical or medical treatments for deep infiltrative endometriosis need to be individualized.
目的薄弱的囊肿壁和为出血内容物创造的培养基理论上可能有利于细菌着床和感染。我们的目的是讨论术前评估在预防深度浸润性子宫内膜异位症手术不完全的重要性,以及卵巢钻孔后脓肿的处理。材料与方法病例报告一例31岁高龄产妇因高热及盆腔疼痛入院。病史中了解到,20天前于外中心行腹腔镜下4厘米(cm)右卵巢子宫内膜瘤囊肿切除、左卵巢钻孔及子宫内膜异位症结节烧灼术。在她的术前申请中,她报告盆腔疼痛和痛经,妇科检查显示盆腔MRI显示一个8厘米的子宫内膜瘤囊肿。患者在腹腔镜下切除右侧卵巢子宫内膜瘤,左侧卵巢钻孔,烧灼结节,随后给予单剂量GnRH激动剂进行抑制治疗。患者入院诊断为输卵管卵巢脓肿,CRP: 223 mg/L,盆腔MRI观察左侧附件区5 cm异质收集区。经临床和实验室抗生素治疗改善后,骨盆MRI显示持续5厘米的左侧附件肿块(图1)。术前AMH为5.6 ng/mL,术后AMH为1.98 ng/mL,提示卵巢储备功能丧失。子宫输卵管造影(HSG)显示右侧输卵管通道正常,左侧输卵管无通道,明显输卵管积液。结果讨论我们认为使用卵巢钻孔是一种过时的方法,不完全手术后观察到的脓肿并发症可归因于这种方法。考虑到与盆腔炎继发的脓毒性输卵管积水相比,子宫内膜异位瘤相关的无菌输卵管积水对植入成功的负面影响相对较小,因此在计划继发手术干预之前,为患者提供了一个自然受孕的机会。新的治疗方案,如硬化疗法,也被报道在症状改善和妊娠结局方面有积极的结果。选择医疗管理,由于第二次手术卵巢储备减少的风险,对自然受孕进行随访。影响声明深浸润性子宫内膜异位症的手术或药物治疗方案和并发症管理需要个体化。
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引用次数: 0
Does Oocyte Morphology Differ in Polycystic Ovary Syndrome Patients During IVF Cycles?: A Preliminary Study 在IVF周期中多囊卵巢综合征患者的卵母细胞形态不同吗?:初步研究
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105310
Sebnem Alanya Tosun , Sedanur Yilmaz Dogan , Ayse Firuze Biyik , Emine Aksoy , Tugba Zengin , Recep Erin , Omur Erden , Kubra Baki Erin

OBJECTIVE

The purpose of this study was to determine the impact of polycystic ovary syndrome on oocyte morphology and fertility outcome in invitro fertilisation (IVF) cycles undergoing ovarian stimulation with a gonadotropin antagonist protocol.

MATERIALS AND METHODS

This retrospective study was conducted between June-2024 and June-2025 in a tertiary university hospital's IVF clinic with totally 67 IVF cycles of infertile women aged between 20 and 38 years who were applied antagonist gonadotropin stimulation procedure due to the unexplained infertility or polycystic ovary syndrome. All oocytes were individually classified and checked blindly by two different experienced senior embryologists. The oocyte morphology were recorded with the use of inverted microscope at 3200 magnification (Nikon Tokyo, Japan) and oocytes classified for morphological features as follows: empty zona, elliptical shape, vacuole, flat polar body, fragmented polar body, perivitelline septa, perivitelline debris, central granulation, dense central granulation, inclusion body, thick zona pellucida, smooth endoplasmic reticulum, resistance by oolemma. Fertilization was defined in oocytes when two pronuclei and two polar bodies were observed. The ratio of oocytes with specific morphological abnormalities was calculated and compared between groups.

RESULTS

Groups with and without polycystic ovary syndrome had similar baseline demographic and clinical characteristics including age, number of previous cycles, thyroid stimulating hormone, prolactin and follicle stimulating hormone tests (p >.05, Table 1). Although, average duration of ovarian stimulation day was slightly higher in PCOS group, mean total gonadotropin dose used was similar between groups (Table 1). Peak estradiol level on the day of trigger, mean numbers of total and mature oocytes (MII) were significantly higher in the PCOS group (p <.05, Table 1). Majority of specific oocyte morphological abnormalities were significantly higher in PCOS group (Table 1).

CONCLUSIONS

In conclusion, although PCOS patients had higher numbers of MII oocytes, PCOS was associated with a higher rate of abnormal oocytes morphologies.

IMPACT STATEMENT

Future studies using further oocyte quality assessment methods and prospective observational studies including live-birth rate should be designed.
目的本研究的目的是确定多囊卵巢综合征对体外受精(IVF)周期中接受促性腺激素拮抗剂方案卵巢刺激的卵母细胞形态和生育结果的影响。材料与方法本回顾性研究于2024年6月至2025年6月在某三级大学附属医院体外受精门诊进行,对年龄在20 ~ 38岁、因不明原因不孕或多囊卵巢综合征而应用促性腺激素拮抗剂刺激治疗的67例体外受精周期的不孕妇女进行研究。所有卵母细胞单独分类,并由两位经验丰富的资深胚胎学家进行盲检。用3200倍倒置显微镜(Nikon Tokyo,日本)记录卵母细胞形态,并将卵母细胞的形态特征分类为:空带、椭圆形、液泡、扁平极体、破碎极体、卵泡周围间隔、卵泡周围碎片、中心肉芽、密集的中心肉芽、包涵体、厚的透明带、光滑的内质网、有膜抵抗。当观察到两个原核和两个极体时,就可以确定卵母细胞受精。计算并比较各组特定形态异常卵母细胞的比例。结果多囊卵巢综合征组和非多囊卵巢综合征组具有相似的基线人口统计学和临床特征,包括年龄、既往周期次数、促甲状腺激素、催乳素和促卵泡激素测试(p > 0.05,表1)。虽然PCOS组平均卵巢刺激日持续时间稍长,但两组间平均总促性腺激素剂量相似(表1)。PCOS组触发当天雌二醇峰值水平、平均总卵母细胞数和成熟卵母细胞数(MII)均显著高于PCOS组(p < 0.05,表1)。PCOS组多数特异性卵母细胞形态异常明显高于PCOS组(表1)。结论尽管PCOS患者MII卵母细胞数量较高,但PCOS患者的卵母细胞形态异常率较高。影响声明应设计使用进一步卵母细胞质量评估方法的未来研究和包括活产率在内的前瞻性观察研究。
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引用次数: 0
Comparative Molecular Profiling of Exosomes from First-Trimester Human Placental Organoids and Explants 孕早期人类胎盘类器官和外植体外泌体的比较分子谱分析
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105294
Kerem Dalgic , Melike Ucak , Arda Inanc , Gizem Melis Kargin , Mert Turgal , Ozgur Oktem , Bora Akgun , Ciler Celik-Ozenci

OBJECTIVE

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.

MATERIALS AND METHODS

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< 0.001) and Kruskal-Wallis test for non-parametric NTA results (p< 0.05).

RESULTS

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< 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< 0.001) at 1080, 1445, and 1508 cm⁻¹, indicating differences in lipid and protein composition.

CONCLUSIONS

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.

IMPACT STATEMENT

This study introduces HPOs as a scalable source for placenta exosome research, enabling investigation of maternal–fetal signaling and pregnancy-related disorders.
目的外泌体是细胞外囊泡,对细胞间通讯至关重要,特别是在母胎信号传导中。本研究旨在分离和表征人胎盘类器官(HPOs)的外泌体,并将其与妊娠早期胎盘外植体的外泌体进行比较。材料与方法收集妊娠早期胎盘组织(6-9周;n = 9),并征得知情同意(伦理号:2025.107.IRB2.052)。绒毛外植体在DMEM/F12+10%不含外泌体的FBS+1%青霉素-链霉素培养基中培养24/48h, HPOs由细胞滋养层细胞包埋在Matrigel中形成,并在滋养层类器官培养基(TOM)中维持。对外植体进行CK7、Ki67、β-hCG和vimentin的免疫染色;免疫荧光法检测HPOs (CK7、TP63、β-hCG、Ki67、E-cadherin), ELISA法检测β-hCG分泌。从外植体和HPOs中收集条件培养基(第3/8天),通过超离心(100,000 × g, 2h, 4°C)分离外泌体。外泌体采用NTA、TEM、Western blot [CD63(一般)、PLAP(胎盘特异性)、β-肌动蛋白(阴性)外泌体标记物]和RT-qPCR (miR-517a-3p、miR-519d-3p)分析。PLAP在外植体中的表达作为阳性对照。采用表面增强拉曼光谱(SERS)评价分子指纹图谱。统计分析采用Mann-Whitney U检验对SERS数据进行Bonferroni校正(p< 0.001),对非参数NTA结果进行Kruskal-Wallis检验(p< 0.05)。结果两组的染色体形态、标记表达和大小范围(30-150 nm)均具有特异性。Explant-derived液有显著较高的粒子浓度(9.33 ×10 ¹⁰ ±8.71×10 ⁹24小时;9.04 ×10 ¹⁰ ±6.72×10 ⁹48 h)比HPO-derived液(3.19 ×10 ¹⁰ ±1.60×10 ⁹第三天,3.71 ×10 ¹⁰ ±2.64×10 ⁹第8天)(术中; 0.05)。两组外泌体均检测到CD63;PLAP和β-肌动蛋白缺失。透射电镜证实了典型的外泌体形态。两组均表达胎盘特异性mirna。SERS在1080、1445和1508 cm( - 1)处显示了显著的光谱差异(p<; 0.001),表明了脂质和蛋白质组成的差异。结论shpo衍生的外泌体与来自匹配的妊娠早期胎盘外植体的外泌体具有相同的关键特征,支持hpo作为研究胎盘细胞外囊泡的相关体外模型的实用性。影响声明:本研究将HPOs作为胎盘外泌体研究的可扩展来源,使母胎信号传导和妊娠相关疾病的研究成为可能。
{"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.2025.105294","DOIUrl":"10.1016/j.rbmo.2025.105294","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 105294"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532863","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}
引用次数: 0
The Predictive Role of AMH In Letrozole Resistance Among PCOS Patients Undergoing Ovulation Induction AMH在促排卵PCOS患者来曲唑耐药中的预测作用
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105306
Elif Aylin Taskin , Batuhan Aslan , Yaprak Engin-Ustun

OBJECTIVE

To investigate the predictive value of Anti-Müllerian Hormone (AMH) levels and define a threshold for the resistance to ovulation induction (OI) with Letrozole 5 mg/mL 5-day regimen in Polycystic Ovary Syndrome (PCOS) patients.

MATERIALS AND METHODS

A total of 195 PCOS patients undergoing 365 cycles of OI with Letrozole followed by IUI were enrolled to this retrospective cohort study. Patients with AMH levels lower than predefined age specific cut-offs were also excluded to increase diagnostic accuracy for PCOS and overcome interobserver bias for PCOM. OI with Letrozole (5 mg/day for 5 days) was initiated in all cycles, with dose escalation to 7.5 mg/day in resistant cases. Resistance to Letrozole, defined as failure to develop at least one pre-ovulatory follicle is the main outcome. Secondary outcomes include potential factors for resistance, predictive performance of AMH and clinical pregnancy rate (CPR).

RESULTS

Out of 195 patients 172 (88.2%) developed at least 1 dominant follicle in response to 5 mg/day letrozole for 5 days in at least one cycle constituting the Letrozole responsive group and 23 patients (11.8%) did not, constituting the letrozole resistant group. BMI, AMH, basal LH and LH/FSH ratio were higher in the resistant group (P˂0.05). Resistant group was characterized with a significantly high AMH when compared to responsive group (medians 8.5 vs 6.8 ng/mL, respectively, P=0.03) and probability of response was declining with increasing percentile of AMH, especially after the 75th percentile. In uni- and multivariant regression analyses, AMH and BMI are significant and independent predictors of resistance.
The ROC curve for prediction of resistance based on the serum AMH levels indicated moderate discrimination with AUC 0.64. Age-adjusted AMH thresholds for resistance are searched and above age of 30, AMH threshold of 6.5 ng/mL had 100% sensitivity and 86,4% specificity to predict resistance. CPR per cycle was 16.1% In responsive group and 9% in resistant group.

CONCLUSIONS

Our study demonstrates that high AMH levels and BMI are independent risk factors for letrozole resistance in PCOS patients. We propose an AMH threshold of 6.5 ng/mL as a sensitive and specific predictor of resistance in PCOS patients over 30 years of age.

IMPACT STATEMENT

High number of cycles with the same stimulation protocol in a large cohort with reliable diagnosis of PCOS enabled analysis of a very uniform data. We proposed an AMH threshold level to predict resistance to Letrozole in PCOS patients above 30.
目的探讨抗勒氏激素(AMH)水平对多囊卵巢综合征(PCOS)患者抗排卵诱导(OI)的预测价值,并确定来曲唑5mg /mL 5天治疗方案的阈值。材料与方法本回顾性队列研究共纳入195例PCOS患者,这些患者接受365个周期的来曲唑伴IUI治疗。AMH水平低于预定年龄特定临界值的患者也被排除在外,以提高PCOS的诊断准确性并克服PCOM的观察者间偏倚。在所有周期中开始使用来曲唑(5mg /天,连续5天),在耐药病例中剂量增加到7.5 mg/天。对来曲唑的耐药,定义为不能发育至少一个排卵前卵泡是主要的结果。次要结局包括潜在的耐药因素、AMH的预测表现和临床妊娠率(CPR)。结果195例患者中,172例(88.2%)患者在5 mg/d来曲唑治疗5天内至少出现1个显性卵泡,构成来曲唑反应组,23例(11.8%)患者未出现显性卵泡,构成来曲唑耐药组。耐药组BMI、AMH、基础LH和LH/FSH比值较高(P小于0.05)。耐药组AMH明显高于应答组(中位数分别为8.5 ng/mL和6.8 ng/mL, P=0.03),且随着AMH的增加,特别是在第75个百分位之后,应答概率下降。在单变量和多变量回归分析中,AMH和BMI是耐药性的重要和独立预测因子。基于血清AMH水平预测耐药的ROC曲线显示中度判别,AUC为0.64。寻找年龄调整的AMH耐药阈值,30岁以上,6.5 ng/mL AMH阈值预测耐药的敏感性为100%,特异性为86.4%。应答组每周期心肺复苏率为16.1%,耐药组为9%。结论高AMH水平和BMI是PCOS患者来曲唑耐药的独立危险因素。我们提出6.5 ng/mL的AMH阈值作为30岁以上PCOS患者耐药的敏感和特异性预测因子。影响声明:在一个具有可靠PCOS诊断的大队列中,使用相同刺激方案的高周期可以分析非常统一的数据。我们提出了一个AMH阈值水平来预测30岁以上PCOS患者对来曲唑的耐药性。
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引用次数: 0
Fertility knowledge as a tool for informed reproductive decision-making 生育知识作为知情生殖决策的工具。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105126
Shalini Singh
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引用次数: 0
Minimizing waste in medically assisted reproduction: a study on sustainability initiatives for oocyte retrieval and embryo transfer 尽量减少医疗辅助生殖中的浪费:关于卵母细胞回收和胚胎移植的可持续性倡议的研究。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105081
Roos A. Sluimer, Theodora C. van Tilborg, Ralph J.A. Oude Ophuis, Willem M.J. Verpoest, Taghride Dahhan

Research question

How can waste be reduced during medically assisted reproduction (MAR) procedures, including oocyte retrieval and embryo transfer, through sustainable interventions without compromising safety?

Design

A quality management initiative was conducted over 12 months (October 2023 to October 2024). Through a multidisciplinary approach, sustainability initiatives were developed aimed at reducing material and medication waste generated during oocyte retrieval and embryo transfer procedures. Sustainability interventions were implemented during a 3-month pilot phase. Waste generation was measured before and after implementation of these interventions. Infection rates were evaluated at baseline and after completing the pilot.

Results

During the study, 234 oocyte retrievals and 291 embryo transfers were carried out. The proposed interventions resulted in a material waste reduction of about 60% for oocyte retrieval and 8% for embryo transfer, with no clinical or laboratory infections recorded.

Conclusions

This study revealed the possibility for significant waste reduction in MAR procedures through targeted sustainability interventions. These findings underscore the feasibility of integrating sustainability practices in MAR procedures.
研究问题:如何在不影响安全性的情况下,通过可持续的干预措施,减少医学辅助生殖(MAR)程序(包括取卵和胚胎移植)中的浪费?设计:在12个月内(2023年10月至2024年10月)进行了质量管理计划。通过多学科方法,可持续发展倡议旨在减少在卵母细胞提取和胚胎移植过程中产生的材料和药物浪费。可持续性干预措施在3个月的试点阶段实施。在实施这些干预措施之前和之后测量了产生的废物。在基线和完成试点后评估感染率。结果:共进行卵母细胞提取234例,胚胎移植291例。建议的干预措施使卵母细胞回收的材料浪费减少了约60%,胚胎移植的材料浪费减少了8%,没有临床或实验室感染的记录。结论:本研究揭示了通过有针对性的可持续性干预措施显著减少MAR程序浪费的可能性。这些发现强调了将可持续性做法纳入MAR程序的可行性。
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引用次数: 0
Retraction notice to .ÇÿEffect of N-acetyl-cysteine after ovarian drilling in clomiphene citrate-resistant PCOS women: a pilot study.ÇÖ 撤回通知。ÇÿEffect耐氯米芬柠檬酸盐多囊卵巢综合征妇女卵巢钻孔后n -乙酰半胱氨酸的变化:一项试点study.ÇÖ
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105286
A. Nasr
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引用次数: 0
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Reproductive biomedicine online
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