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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。
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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。
{"title":"The Predictive Role of AMH In Letrozole Resistance Among PCOS Patients Undergoing Ovulation Induction","authors":"Elif Aylin Taskin ,&nbsp;Batuhan Aslan ,&nbsp;Yaprak Engin-Ustun","doi":"10.1016/j.rbmo.2025.105306","DOIUrl":"10.1016/j.rbmo.2025.105306","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>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.</div></div><div><h3>MATERIALS AND METHODS</h3><div>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).</div></div><div><h3>RESULTS</h3><div>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.</div><div>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.</div></div><div><h3>CONCLUSIONS</h3><div>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.</div></div><div><h3>IMPACT STATEMENT</h3><div>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.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105306"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532952","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
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
{"title":"Retraction notice to .ÇÿEffect of N-acetyl-cysteine after ovarian drilling in clomiphene citrate-resistant PCOS women: a pilot study.ÇÖ","authors":"A. Nasr","doi":"10.1016/j.rbmo.2025.105286","DOIUrl":"10.1016/j.rbmo.2025.105286","url":null,"abstract":"","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 5","pages":"Article 105286"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465394","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
Accuracy of Non-Invasive Preimplantation Genetic Testing For Aneuploidy (NiPGT-A) In Confirmed Aneuploid Embryos 确认非整倍体胚胎非整倍体(NiPGT-A)无创植入前基因检测的准确性
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105293
Engin Turkgeldi , Gozde Akcaoglu , Arife Kunt , Hasan Gursoy , Aylin Mutlu , Ali Osman Koyuncuoglu

OBJECTIVE

To assess the diagnostic concordance between non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and standard PGT-A with trophectoderm biopsy in embryos previously diagnosed as aneuploid.

MATERIALS AND METHODS

Nineteen embryos from four patients previously diagnosed as aneuploid via PGT-A were re-evaluated using niPGT-A upon patient request. Embryos were thawed using the Ultrafast-Kitazato method and incubated in an Esco MIRI incubator. Laboratory preparation included particle reduction, disinfection, and use of DNA/RNA-free single-use materials. Embryologists wore sterile attire. Embryos were washed in four 30 μL drops and transferred to 12 μL culture dishes. Each dish contained three embryo-specific drops and one negative control drop. Incubation was 24 hours for D5 and 8 hours for D6/D7 embryos. Post-incubation, embryos were re-cryopreserved. Eight microliters of medium were collected per embryo into separate PCR tubes. Negative controls were similarly processed. Samples were stored at −20°C and sent to Igenomix TR via cold chain for analysis. Statistical analysis was conducted with a 2 × 2 contingency table.

RESULTS

Of the 19 embryos diagnosed as aneuploid by PGT-A, 18 were also found aneuploid by niPGT-A, 13 with perfect chromosomal match and 5 with minor differences. One embryo was classified as euploid by niPGT-A. This yielded an accuracy of 94.7% (95% CI: 73.9%–99.8%), specificity of 94.7% (95% CI: 73.9%–99.8%), and NPV of 100% (95% CI: 81.5%–100%) for euploidy. Sensitivity, PPV, Cohen’s Kappa, and McNemar’s test could not be calculated due to the absence of PGT-confirmed euploid embryos.

CONCLUSIONS

Our results show that NiPGT-A has very high NPV and specificity compared to the gold standard, PGT-A in aneuploid embryos. However, the small sample size and lack of euploid embryos by PGT limit the generalizability of findings. The euploid outcome may be associated of cumulus cell (CC) contamination, as morphological evaluation of the embryo revealed a greater abundance of CC compared to the others. Notably, 68.4% of embryos showed perfect qualitative agreement between methods. Although minor discrepancies were observed in 26.3% of embryos, all were still reported as aneuploid, suggesting limited clinical impact. Still, further validation with a larger, balanced dataset is necessary to establish the clinical reliability of the NiPGT-A.

IMPACT STATEMENT

niPGT-A offers high specificity and NPV relative to PGT-A in aneuploid embryos, supporting its potential as a non-invasive alternative.
目的评价非整倍体胚胎的无创着床前基因检测(niPGT-A)和标准PGT-A与之前诊断为非整倍体胚胎的滋养外胚层活检的一致性。材料与方法应患者要求,使用niPGT-A对4例既往通过PGT-A诊断为非整倍体的患者的19个胚胎进行重新评估。使用ultraffast - kitazato方法解冻胚胎,并在Esco MIRI培养箱中孵育。实验室准备包括颗粒还原、消毒和使用无DNA/ rna的一次性材料。胚胎学家穿着无菌服装。胚胎在4滴30 μL的培养液中洗涤,转移到12 μL的培养皿中。每个培养皿含有3个胚胎特异性滴液和1个阴性对照滴液。D5胚胎孵育24小时,D6/D7胚胎孵育8小时。孵育后,胚胎再次冷冻保存。每个胚胎收集8微升培养基到单独的PCR管中。阴性对照同样处理。样品保存在- 20°C,通过冷链送到Igenomix TR进行分析。采用2 × 2列联表进行统计分析。结果19例经PGT-A诊断为非整倍体的胚胎中,18例为非整倍体,13例染色体完全匹配,5例差异较小。1个胚胎经niPGT-A分类为整倍体。结果显示,整倍体的准确度为94.7% (95% CI: 73.9%-99.8%),特异性为94.7% (95% CI: 73.9%-99.8%), NPV为100% (95% CI: 81.5%-100%)。敏感性、PPV、Cohen的Kappa和McNemar的测试无法计算,因为没有pgt证实的整倍体胚胎。结论与金标准PGT-A相比,NiPGT-A在非整倍体胚胎中具有很高的NPV和特异性。然而,PGT的小样本量和缺乏整倍体胚胎限制了研究结果的普遍性。整倍体的结果可能与积云细胞(CC)污染有关,因为胚胎的形态学评估显示,与其他细胞相比,积云细胞的丰度更高。值得注意的是,68.4%的胚胎在两种方法之间表现出完全的定性一致。尽管在26.3%的胚胎中观察到微小的差异,但所有的胚胎仍被报道为非整倍体,这表明临床影响有限。然而,为了建立NiPGT-A的临床可靠性,需要更大、更平衡的数据集进行进一步验证。影响声明:相对于PGT-A, nipgt - a在非整倍体胚胎中具有高特异性和NPV,支持其作为非侵入性替代品的潜力。
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引用次数: 0
Single-Cell RNA-Seq Profiling Reveals PCOS-Associated Alterations in Oocytes from Small Antral Follicles for IVM Optimization 单细胞RNA-Seq分析揭示小窦卵泡卵母细胞pcos相关改变,用于IVM优化
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105305
Nazli Akin , Laura Saucedo Cuevas , Antonio Galvao , Berta Cava Cami , Heidi Van Ranst , Michel De Vos , Gavin Kelsey , Ellen Anckaert

OBJECTIVE

Recommended by international guidelines, in vitro maturation (IVM) is a low treatment burden alternative for subfertile patients with polycystic ovary syndrome (PCOS) due to abolished risk of ovarian hyperstimulation syndrome. While IVM systems have been greatly optimized, lower cumulative live birth rates compared to IVF warrants further optimization. IVM targets maturation of GV oocytes collected from 2-9 mm antral follicles (AF) collected with minimal stimulation. Yet, previous studies that characterized PCOS oocyte molecular alterations focused on MII oocytes collected after conventional ovarian stimulation. Here, we provide a comprehensive molecular comparison of GV oocytes from PCOS and non-PCOS women to uncover targets for future IVM optimization.

MATERIALS AND METHODS

11 PCOS (phenotype A) and 7 non-PCOS (normo-ovulatory) donors were recruited for this study. Single-cell libraries were prepared with 81 GV oocytes (52 PCOS, 29 non-PCOS), aspirated from small-AF <10 mm, following minimal HP-hMG priming (PCOS 600 IU, non-PCOS 450 IU). RNA-seq reads were aligned to GRCh38 with HISAT2 (v2.0.5) and quantified via SeqMonk. Differential gene expression was analyzed in R using DESeq2 (FDR <0.05, |log2FC|>0.58), followed by gene ontology term enrichment.

RESULTS

267 differentially expressed genes (114 down-, 153 up-regulated) were identified between PCOS vs non-PCOS oocytes. Three main biological processes being affected included (i) energy metabolism (e.g. respiration, lipid metabolism), (ii) cytoskeletal dynamics (e.g. microtubules) and (iii) intracellular signalling pathways. These alterations occur in key cellular compartments such as mitochondria, cytoskeleton, and ribosomes and affect molecular functions like structural support, enzyme regulation, and ion transport.

CONCLUSIONS

This is the first study analyzing transcriptomic differences between PCOS and non-PCOS oocytes collected from small AF after minimal hormonal stimulation and to be cultured using IVM. Our data indicate that PCOS leads to distinct changes in processes essential for cellular energy balance, structural dynamics, and intracellular communication. Utilizing mitochondrial and cytoskeletal modulators, or targeted growth factor supplementation may boost IVM outcomes to potentially match the clinical efficacy observed in conventional IVF.

IMPACT STATEMENT

This pioneer study identifies the alterations associated with PCOS pathology in the GV oocytes from small antral follicles and provides insights for future IVM optimization studies.
目的体外成熟(IVM)是国际指南推荐的低负担治疗多囊卵巢综合征(PCOS)患者的替代方法,因为它消除了卵巢过度刺激综合征的风险。虽然IVM系统已经大大优化,但与IVF相比,较低的累计活产率值得进一步优化。IVM的目标是在最小刺激下从2- 9mm的腔卵泡(AF)中收集的GV卵母细胞成熟。然而,先前关于PCOS卵母细胞分子改变的研究主要集中在常规卵巢刺激后收集的MII卵母细胞上。在这里,我们提供了来自PCOS和非PCOS女性的GV卵母细胞的全面分子比较,以发现未来IVM优化的靶点。材料与方法本研究招募了11例PCOS(表型A型)和7例非PCOS(排卵正常)供体。用81个GV卵母细胞(52个PCOS, 29个非PCOS)制备单细胞文库,从10 mm的小af和lt中抽吸,最小HP-hMG启动(PCOS 600 IU,非PCOS 450 IU)。使用HISAT2 (v2.0.5)将RNA-seq reads与GRCh38对齐,并通过SeqMonk进行定量。使用DESeq2分析R中的差异基因表达(FDR <0.05, |log2FC|>0.58),然后进行基因本体项富集。结果在多囊卵巢综合征与非多囊卵巢综合征卵母细胞间共鉴定到267个差异表达基因(114个下调,153个上调)。受影响的三个主要生物过程包括(i)能量代谢(如呼吸,脂质代谢),(ii)细胞骨架动力学(如微管)和(iii)细胞内信号传导途径。这些改变发生在关键的细胞区室,如线粒体、细胞骨架和核糖体,并影响分子功能,如结构支持、酶调节和离子运输。结论本研究首次分析了从小房颤中收集的PCOS和非PCOS卵母细胞在最小激素刺激后的转录组学差异,并使用IVM进行培养。我们的数据表明,多囊卵巢综合征导致细胞能量平衡、结构动力学和细胞内通信所必需的过程发生明显变化。利用线粒体和细胞骨架调节剂,或靶向生长因子补充可能会提高IVM结果,潜在地达到传统试管婴儿中观察到的临床疗效。影响声明:这项开创性的研究确定了来自小窦卵泡的GV卵母细胞与PCOS病理相关的改变,并为未来的IVM优化研究提供了见解。
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引用次数: 0
Sibling Monozygotic Couples with Divergent Female Fertility: A Case Report Highlighting the Impact of BPA Exposure on OR 具有不同女性生育能力的同胞同卵夫妇:一个突出BPA暴露对OR影响的病例报告
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105311
Hande Nalan Tore , Hasan Bulut , Rovshan Jabbarov , Murat Berkkanoglu , Kevin Coetzee , Kemal Ozgur , Muhittin Serdar

OBJECTIVE

To present a rare case of monozygotic twin sisters with discordant ovarian reserve and fertility outcomes, highlighting the significant role of environmental exposure—particularly to bisphenol A (BPA)—and lifestyle factors in influencing reproductive health, despite identical genetic backgrounds. This case aims to underscore the necessity of incorporating environmental and epigenetic assessments in fertility evaluations.

MATERIALS AND METHODS

Sister B demonstrated normal ovarian reserve (AFC: 18; AMH: 2.4 ng/mL) and a reproductive history of two term pregnancies with live births. In contrast, Sister A had a seven-year history of infertility, with diminished ovarian reserve (AFC: 8; AMH: 0.8 ng/mL). Further evaluation revealed that Sister A had poor dietary habits—frequent fast-food consumption and minimal water intake, replaced by carbonated beverages. Occupational exposure to epoxy resins in a marble processing plant and pesticides in an agricultural setting was also noted. Semen analyses of both sisters' husbands were within normal parameters.

RESULTS

Toxicological screening revealed Sister A had a significantly elevated urinary BPA level (629.1 µg/L), over 50 times higher than her sister and their husbands (normal: 0–15.9 µg/L). After a diagnosis of diminished ovarian reserve, she adopted a healthier lifestyle to reduce environmental risks. Controlled ovarian stimulation yielded eight oocytes (three mature), resulting in three blastocysts. Two were transferred via ICSI and FET, leading to the term birth of a healthy 2750 g male infant. BPA levels normalized by 33 weeks of gestation.

CONCLUSIONS

This rare case demonstrates how even genetically identical individuals, living in the same environment, may exhibit striking differences in ovarian function, driven by differential exposure to environmental toxins such as BPA. This case report underscores the importance of investigating genetic (including epigenetics) as well as modifiable factors such as lifestyle habits, diet, and occupation in fertility workups and when encountering DOR and infertility.

IMPACT STATEMENT

This is the first reported case of significantly discordant ovarian reserve in monozygotic twins linked to differential BPA exposure. It underscores the critical impact of modifiable environmental and lifestyle factors on fertility and highlights the need to incorporate environmental and epigenetic assessments into routine reproductive evaluations. These findings offer novel insights with clinical and public health relevance.
目的报告一例罕见的单卵双胞胎姐妹卵巢储备和生育结果不一致的病例,强调环境暴露(特别是双酚a (BPA))和生活方式因素在影响生殖健康方面的重要作用,尽管遗传背景相同。本案例旨在强调在生育评价中纳入环境和表观遗传评价的必要性。材料与方法B姐妹卵巢储备正常(AFC: 18; AMH: 2.4 ng/mL),有两次足月妊娠和活产的生殖史。相比之下,A姐妹有7年的不孕症史,卵巢储备减少(AFC: 8; AMH: 0.8 ng/mL)。进一步的评估显示,A姐姐的饮食习惯很差,经常吃快餐,很少喝水,而是喝碳酸饮料。还注意到大理石加工厂的职业接触环氧树脂和农业环境中的农药。两姐妹丈夫的精液分析结果都在正常范围内。结果毒理学检查结果显示,A姐姐尿中BPA水平明显升高(629.1µg/L),是其姐姐和丈夫(正常值:0 ~ 15.9µg/L)的50多倍。在被诊断为卵巢储备功能减退后,她采取了更健康的生活方式来减少环境风险。控制卵巢刺激产生8个卵母细胞(其中3个成熟),形成3个囊胚。其中两个通过ICSI和FET转移,导致一个健康的2750克男婴足月出生。BPA水平在怀孕33周时恢复正常。结论:这个罕见的病例表明,即使是基因相同的个体,生活在相同的环境中,由于暴露于不同的环境毒素(如BPA),卵巢功能也可能表现出显著的差异。本病例报告强调了在生育检查和遇到DOR和不孕症时调查遗传(包括表观遗传学)以及生活习惯、饮食和职业等可改变因素的重要性。影响声明:这是首次报道的与不同BPA暴露有关的同卵双胞胎卵巢储备显著不一致的病例。它强调了可改变的环境和生活方式因素对生育率的重大影响,并强调需要将环境和表观遗传评估纳入常规生殖评估。这些发现提供了具有临床和公共卫生相关性的新见解。
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引用次数: 0
The Effect of Antagonist Initiation Day on IVF Outcomes in Patients with Unexplained Infertility: A Retrospective Analysis 拮抗剂起始日对不明原因不孕症患者体外受精结果的影响:回顾性分析
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105331
Dogukan Halis Ozkan , Merve Ayas Ozkan , Yaprak Engin Ustun

OBJECTIVE

This study aimed to investigate the effect of antagonist treatment initiation day on IVF outcomes in women with unexplained infertility undergoing controlled ovarian stimulation.

MATERIALS AND METHODS

This retrospective observational study included a total of 14 patients who were diagnosed with unexplained infertility and underwent antagonist protocol at our clinic between July 2024 and July 2025. Patients were divided into two groups based on the day antagonist treatment was initiated: fixed protocol group (Day 5, n=7) and flexible initiation group (≥Day 6, n=7).The groups were comparable in terms of age, body mass index (BMI), gravida, parity, and duration of infertility. The primary outcomes were the total number of oocytes retrieved, the number of mature oocytes, endometrial thickness on embryo transfer (ET) day, β-hCG positivity, and clinical pregnancy rate. Numerical data were analyzed using the Mann-Whitney U test, and categorical data were analyzed using Fisher's exact test.

RESULTS

The total number of oocytes was 11.57±2.37 in the fixed group and 8.71±3.64 in the flexible group (p=0.140). The number of mature oocytes was 8.71±2.56 and 7.29±3.77, respectively (p=0.561). Endometrial thickness on ET day was similar (10.53±3.15 vs. 10.74±2.97, p=0.798). β-hCG positivity was 57.1% in both groups (4/7 patients, p=1.000). The clinical pregnancy rate was 42.9% (3/7) in group 1 and 57.1% (4/7) in group 2 (p=1.000).

CONCLUSIONS

Starting the antagonist protocol later may allow for longer support of follicular development, thereby affecting oocyte response. Although clinical pregnancy rates were numerically higher in the later-starting group, statistical significance was not achieved. This may be related to the small sample size.Initiating the antagonist protocol on or after day 6 in patients with unexplained infertility may result in a clinically significant increase in oocyte response. This parameter, which influences IVF success, should be considered in individualized treatment planning. Further prospective studies with larger sample sizes are needed to validate these findings.

IMPACT STATEMENT

This study suggests that delaying antagonist initiation in IVF cycles for women with unexplained infertility may improve oocyte response and clinical pregnancy trends. These findings support individualized stimulation timing and warrant further validation in larger, prospective studies.
目的本研究旨在探讨拮抗剂起始日对不明原因不孕症患者接受控制性卵巢刺激的体外受精结果的影响。材料与方法本回顾性观察性研究共纳入14例诊断为不明原因不孕症的患者,于2024年7月至2025年7月在我诊所接受拮抗剂治疗。根据开始拮抗剂治疗的天数将患者分为两组:固定方案组(第5天,n=7)和灵活启动组(≥第6天,n=7)。两组在年龄、体重指数(BMI)、妊娠、胎次和不孕持续时间方面具有可比性。主要观察指标为卵母细胞总数、成熟卵母细胞数量、胚胎移植(ET)日子宫内膜厚度、β-hCG阳性、临床妊娠率。数值数据采用Mann-Whitney U检验,分类数据采用Fisher精确检验。结果固定组卵母细胞总数为11.57±2.37个,弹性组为8.71±3.64个(p=0.140)。成熟卵母细胞数分别为8.71±2.56个和7.29±3.77个(p=0.561)。ET当天子宫内膜厚度相似(10.53±3.15 vs 10.74±2.97,p=0.798)。两组患者β-hCG阳性率为57.1%(4/7例,p=1.000)。1组临床妊娠率为42.9%(3/7),2组为57.1% (4/7)(p=1.000)。结论较晚使用拮抗剂可延长卵泡发育的支持时间,从而影响卵母细胞的反应。虽然较晚开始组的临床妊娠率在数字上较高,但没有达到统计学意义。这可能与样本量小有关。不明原因不孕症患者在第6天或之后开始使用拮抗剂可能导致卵母细胞反应在临床上显著增加。在制定个体化治疗计划时,应考虑到这一影响IVF成功的参数。需要更大样本量的进一步前瞻性研究来验证这些发现。影响声明:本研究提示,对于不明原因不孕症的女性,延迟在IVF周期中使用拮抗剂可能改善卵母细胞反应和临床妊娠趋势。这些发现支持个性化刺激时机,并需要在更大规模的前瞻性研究中进一步验证。
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引用次数: 0
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Reproductive biomedicine online
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