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Excessive KLF2 impairs mesenchymal–epithelial transition efficiency and adhesion in endometrial stromal cells via AKT phosphorylation 过量的KLF2通过AKT磷酸化影响子宫内膜间质-上皮细胞的转化效率和粘附。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105123
S. Yin , X. Liu , H. Zhao , X. Zhang , H. Bao

Research question

What is the dynamic expression profile of Krüppel-like factor 2 (KLF2) during the progression of mesenchymal–epithelial transition (MET), and through which molecular mechanisms does KLF2 regulate transformation?

Design

This study examined changes in KLF2 expression during the in-vivo menstrual cycle using immunohistochemistry and an in-vitro decidualization cell model. KLF2 negative control (KLF2-NC) and KLF2 overexpression (KLF2-OE) models were constructed in primary and immortalized human endometrial stromal cells via lentiviral transfection. Mesenchymal and epithelial protein changes were detected in the KLF2-NC and KLF2-OE groups on different days of MET using immunofluorescent staining. Potential KLF2 binding sites were predicted through motif enrichment analysis, and the interaction between KLF2 expression and AKT phosphorylation during MET was analysed using co-immunoprecipitation (co-IP) and western blotting. Finally, the effects of excessive KLF2 expression on the expression of adhesion factor and the efficiency of adhesion of BeWo-spheroids were determined.

Results

The results showed that KLF2 demonstrated significantly higher expression during the proliferative phase compared with the decidual phase in normal human endometrial tissue (P = 0.0095). Furthermore, KLF2 expression showed a progressive decline during MET. KLF2 overexpression decreased epithelial gene expression. Further, co-IP and western blotting demonstrated that KLF2 affects the MET process by regulating AKT phosphorylation, affecting the expression of adhesion factor and the efficiency of adhesion.

Conclusions

This study found that KLF2 expression changes during the menstrual cycle, and excessive KLF2 is not conducive to AKT phosphorylation during MET in the decidual phase.
研究问题:kr ppel样因子2 (KLF2)在间充质-上皮转化(MET)过程中的动态表达谱是什么? KLF2通过哪些分子机制调控转化?设计:本研究使用免疫组织化学和体外脱胞细胞模型检测体内月经周期中KLF2表达的变化。通过慢病毒转染,在原代和永生化人子宫内膜基质细胞中构建KLF2阴性对照(KLF2- nc)和KLF2过表达(KLF2- oe)模型。免疫荧光染色法检测KLF2-NC组和KLF2-OE组在MET不同天数间充质和上皮蛋白的变化。通过基序富集分析预测潜在的KLF2结合位点,并使用共免疫沉淀(co-IP)和western blotting分析MET过程中KLF2表达与AKT磷酸化之间的相互作用。最后,测定KLF2过度表达对BeWo-spheroids粘附因子表达及粘附效率的影响。结果:正常人子宫内膜增殖期KLF2的表达明显高于蜕膜期(P = 0.0095)。此外,KLF2表达在MET期间呈进行性下降。KLF2过表达降低上皮基因表达。此外,co-IP和western blotting结果表明,KLF2通过调节AKT磷酸化影响MET过程,影响粘附因子的表达和粘附效率。结论:本研究发现KLF2在月经周期中表达发生变化,在蜕膜期MET时,KLF2过多不利于AKT磷酸化。
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引用次数: 0
Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts 抗逆转录病毒治疗中的雌二醇和生殖结果:当好事太多会造成伤害时。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105131
Mathilde Bourdon , Chloé Maignien , Marion Ouazana , Fleur Kefelian , Louis Marcellin , Catherine Patrat , Khaled Pocate-Cheriet , Charles Chapron , Pietro Santulli
Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.
雌二醇在生殖中起着至关重要的作用,特别是在辅助生殖技术(ART)中,它可以达到超生理浓度。这些波动发生在新鲜胚胎移植周期的卵巢刺激和冷冻胚胎移植的子宫内膜准备期间,可能影响着床和围产期结局。雌二醇影响子宫内膜增殖、接受性、着床和胎盘,子宫内膜对全身雌激素的敏感性是生殖成功的关键决定因素。在新鲜胚胎移植周期中,卵巢刺激引起子宫内膜的组织学、免疫学和遗传变化,与雌二醇浓度升高相关,并可能破坏着床。然而,这种不良反应似乎是有时间限制的,因为子宫内膜容受性在随后的周期中恢复。在FET周期中,雌二醇暴露的持续时间和强度都是至关重要的,因为过度或长时间暴露于外源性雌二醇可能会损害生殖结果。尽管有这些潜在的影响,在抗逆转录病毒治疗中调节雌二醇浓度的策略仍未得到充分探索。本文综述了雌二醇在自然周期和ART周期中的生理和病理作用,重点介绍了其对子宫内膜功能、着床和妊娠结局的影响。它强调需要进一步研究,以确定最佳雌二醇阈值,并制定个性化的ART方案,同时考虑雌二醇浓度和子宫内膜敏感性,以提高生殖成功率和产科结果。最后,它强调了旨在调节雌二醇暴露以优化生殖成功的策略。
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引用次数: 0
Impact of native language on the pursuit of fertility care 母语对生育护理追求的影响。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105055
R. Garland Almquist, Marisa R. Young, Maranatha Genet, Heather Hipp

Research question

Are there any differences in the demographics, diagnostic work-up, fertility treatments attempted, and clinical pregnancy rate between patients whose native language is English compared with those whose native language is not English at a reproductive endocrinology and infertility (REI) clinic within an urban safety-net hospital in the USA?

Design

This retrospective cohort study included 321 patients who presented at the REI clinic between 2016 and 2022 with concern of infertility. The exposure of interest was native language spoken: English versus non-English. The primary outcome measure was attempt at any type of fertility treatment. Secondary outcome measures included completion of infertility diagnostic work-up, clinical pregnancy, and discontinuation of care.

Results

Among patients evaluated for infertility, 106 (33%) reported a native language other than English. Of 266 patients who underwent fertility testing, 218 (82%) completed sufficient diagnostic work-up to determine the type of infertility. Types of infertility were similar between the two groups, except for tubal factor infertility which was more common in native-English-speaking patients [62 (29%) versus 15 (14%); P = 0.003]. Fifty-six percent (149/266) of patients who underwent diagnostic testing for infertility attempted fertility treatment. Patients whose native language is not English were significantly more likely to attempt fertility treatment (adjusted risk ratio 1.44, 95% CI 1.09–1.91; P = 0.011) and to achieve clinical pregnancy (adjusted risk ratio 1.72, 95% CI 1.07–2.76; P = 0.025) compared with native-English-speaking patients. In total, 141 (44%) patients discontinued care.

Conclusions

Patients whose native language is not English were more likely to attempt fertility treatment and achieve clinical pregnancy compared with native-English-speaking patients. This suggests that, in a setting in the USA which aimed to reduce disparities and improve access to care, patients can overcome language barriers to pursue fertility care and undergo treatment.
研究问题:在美国城市安全网医院的生殖内分泌和不孕症(REI)诊所,母语为英语的患者与母语为非英语的患者在人口统计学、诊断检查、生育治疗尝试和临床妊娠率方面是否存在差异?设计:本回顾性队列研究纳入了2016年至2022年期间在REI诊所就诊的321例不孕患者。兴趣的暴露是母语口语:英语和非英语。主要结局指标是尝试任何类型的生育治疗。次要结局指标包括完成不孕症诊断检查、临床妊娠和终止治疗。结果:在评估为不孕症的患者中,106例(33%)报告母语非英语。在266例接受生育测试的患者中,218例(82%)完成了充分的诊断检查以确定不孕症的类型。两组之间的不孕症类型相似,除了输卵管因素不孕症在母语为英语的患者中更为常见[62(29%)对15 (14%);P = 0.003]。56%(149/266)接受不孕症诊断测试的患者尝试过生育治疗。与母语为英语的患者相比,母语非英语的患者更有可能尝试生育治疗(调整风险比1.44,95% CI 1.09-1.91; P = 0.011)和实现临床妊娠(调整风险比1.72,95% CI 1.07-2.76; P = 0.025)。总共有141名(44%)患者停止了治疗。结论:与母语为英语的患者相比,母语为非英语的患者更有可能尝试生育治疗并实现临床妊娠。这表明,在旨在减少差异和改善护理机会的美国环境中,患者可以克服语言障碍,寻求生育护理并接受治疗。
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引用次数: 0
Towards a universal rapid warming protocol for cryopreserved human ovarian tissue 人类卵巢组织低温保存通用快速升温方案的研究。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.rbmo.2025.105151
Cara Maria Färber , Rebekka Einenkel , Norah LA Emrich , Emily Zia Kestermann , Lodovico Parmegiani , Andreas Schallmoser , Nicole Sänger

Research question

Is it feasible to apply a universal warming protocol to slow-frozen human ovarian tissue, using the rapid-warming protocols already established for vitrified tissue, so that a single protocol could be used for both methods?

Design

Slow-frozen ovarian tissue samples from 25 patients were thawed by conventional protocol (slow freezing–thawing) or by a rapid-warming protocol produced ‘in-house’ or by commercially available media. Anti-Müllerian hormone values and follicular viability were determined before cryopreservation. Twenty-four hours after thawing, follicular viability was determined. Hypoxic tissue culture was conducted for 48 h to determine VEGF-A levels to estimate the angiogenic potential. Tissue sections were analysed with TUNEL staining for apoptosis and with haematoxylin and eosin staining for primordial follicles.

Results

Follicular survival did not statistically differ: based on fresh tissue (67.5), viable follicle numbers after conventional thawing (44.5), rapid warming with ‘in-house’ produced (54.5) and commercially available media (58.5) revealed no statistically significant differences between the groups, but were the highest using the rapid warming protocols. After 48 h in culture, preservation of primordial follicles was highest in the rapid warming groups (52% and 57%) compared with the regular thawing group (33%). No significant differences in vascular endothelial growth factor-A were observed comparing conventional thawing protocol with the rapid warming protocol using ‘in-house’-produced media. Although VEGF-A secretion was significantly lower in tissues after using commercially available rapid-warming media (P ≤ 0.0001) compared with conventional thawing, apoptosis level was significantly lower (P = 0.014) indicating improved tissue preservation.

Conclusions

Rapid-warming protocols provide similar to superior results compared with the conventional thawing approach. A universal protocol would increase the efficiency of ovarian tissue thawing–warming, potentially optimizing costs and improving outcome.
研究问题:使用已经建立的用于玻璃化组织的快速升温方案,将通用升温方案应用于慢速冷冻的人类卵巢组织是否可行,以便两种方法都可以使用单一方案?设计:25例患者缓慢冷冻的卵巢组织样本通过常规方案(缓慢冻融)或通过“内部”生产的快速升温方案或通过市售介质进行解冻。冷冻保存前测定抗勒氏杆菌激素值和卵泡活力。解冻后24小时,测定卵泡活力。组织缺氧培养48小时,测定VEGF-A水平,评估血管生成潜能。组织切片用TUNEL染色检测细胞凋亡,用苏木精和伊红染色检测原始卵泡。结果:卵泡存活率没有统计学差异:基于新鲜组织(67.5),常规解冻后的活卵泡数(44.5),用“内部”生产的快速加热(54.5)和市售培养基(58.5)显示各组之间没有统计学差异,但使用快速加热方案时最高。培养48 h后,快速加热组的原始卵泡保存率最高(52%和57%),而常规解冻组的保存率最高(33%)。血管内皮生长因子- a在常规解冻方案和使用“内部”生产培养基的快速升温方案之间没有显著差异。虽然与常规解冻相比,使用市售快速加热培养基后组织中VEGF-A的分泌显著降低(P≤0.0001),但细胞凋亡水平显著降低(P = 0.014),表明组织保存得到改善。结论:与传统的解冻方法相比,快速升温方案提供了类似的优越结果。一个通用的协议将提高卵巢组织解冻-升温的效率,潜在地优化成本和改善结果。
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引用次数: 0
Serum progesterone monitoring after embryo transfer 胚胎移植后血清孕酮监测。
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-21 DOI: 10.1016/j.rbmo.2025.105412
Jan Tesarik
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引用次数: 0
Live Birth After Assisted Reproductive Techniques in a Patient with Unicornuate Uterus and Diminished Ovarian Reserve: A Case Report 单角子宫和卵巢储备减少患者辅助生殖技术后的活产一例报告
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105336
Esra Oncu , Shamama Behzad , Sinziana Petruta Mihai , Zeynep Ece Utkan Korun , Erkut Attar

INTRODUCTION

Unicornuate uterus is a rare Müllerian anomaly associated with infertility and adverse obstetric outcomes. The coexistence of advanced maternal age and diminished ovarian reserve further complicates reproductive management. Herein, we present the case of a 41-year-old woman with diminished ovarian reserve and unicornuate uterus who achieved a live birth following modified induction protocols and assisted reproductive techniques.

CASE PRESENTATION

A 41-year-old woman presented to our clinic in 2023 with primary infertility. Baseline ovarian reserve parameters were as follows: AMH 0.66 ng/mL, FSH 7.9 IU/L, and LH 5.6 IU/L. Semen analysis was within normal limits. The first stimulation cycle was cancelled due to lack of follicular response. In subsequent cycles, the induction protocol was modified, and different medication combinations were used.
During a stimulation in February 2024, an endometrial polyp was identified. In March 2024, hysteroscopic polypectomy was performed. At that time, hysterosalpingography suggested a unilateral fallopian tube, whereas hysteroscopic evaluation confirmed bilateral tubal patency. In May 2024, stimulation resulted in embryo cryopreservation. In January 2025, a single blastocyst transfer led to clinical pregnancy. During follow-up, gestational diabetes was diagnosed and successfully managed with dietary modification. At 36+6 weeks of gestation, an elective cesarean section was performed, delivering a healthy male infant weighing 2120 g.

CONCLUSION

This case demonstrates that in patients with diminished ovarian reserve and uterine anomalies such as unicornuate uterus, modified induction protocols combined with assisted reproductive techniques may lead to successful pregnancy outcomes. Moreover, the discrepancy between hysterosalpingography and hysteroscopic findings highlights the importance of a multidisciplinary approach in infertility evaluation.
简介:独角子宫是一种罕见的与不孕症和不良产科结局相关的子宫异常。高龄产妇和卵巢储备减少的共存进一步使生殖管理复杂化。在这里,我们提出的情况下,41岁的妇女卵巢储备减少和子宫独角兽谁实现了活产修改诱导方案和辅助生殖技术。病例介绍:一名41岁女性于2023年因原发性不孕症来到我们诊所。基线卵巢储备参数如下:AMH 0.66 ng/mL, FSH 7.9 IU/L, LH 5.6 IU/L。精液分析在正常范围内。由于缺乏卵泡反应,第一个刺激周期被取消。在随后的周期中,修改诱导方案,并使用不同的药物组合。在2024年2月的一次刺激中,发现子宫内膜息肉。2024年3月行宫腔镜息肉切除术。当时,子宫输卵管造影提示单侧输卵管,而宫腔镜评估证实双侧输卵管通畅。2024年5月,刺激导致胚胎冷冻保存。2025年1月,单个囊胚移植导致临床妊娠。在随访期间,诊断出妊娠期糖尿病并通过饮食调整成功管理。妊娠36+6周,择期剖宫产,生下体重2120克的健康男婴。结论本病例提示卵巢储备功能减退和子宫异常如独角子宫的患者,改良诱导方案结合辅助生殖技术可获得成功妊娠结局。此外,子宫输卵管造影和宫腔镜检查结果之间的差异突出了多学科方法在不孕症评估中的重要性。
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引用次数: 0
Is the Presence of Sexual Dysfunction Associated with IUI Success in Patients with Unexplained Infertility? 不明原因不孕症患者是否存在性功能障碍与IUI成功相关?
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105330
Emine Acar , Abdullah Acar , Serap Mutlu Ozcelik Otcu , Cigdem Kilinc

OBJECTIVE

To assess the association of sexual dysfunction and IUI success in unexplained infertile women

MATERIALS AND METHODS

The sexual functions of 265 patients presenting to our clinic with unexplained infertility were evaluated using Female Sexual Functioning Index (FSFI), and the association of the results and IUI success was assessed. 15 patients declined to complete the test. 13 patients were excluded from the evaluation because they partially answered the questions. FSFI scores were divided into two groups: <26.5 and >26.5, and IUI success in these groups was evaluated.

RESULTS

Of the 237 patients who completed the FSFI test, 143 (0.60) had a FSFI score <26.5. Of these patients, 23 (16%) were BHCG positive and 20 (13%) had a live birth. The remaining 94 patients had a FSFI score >26.5. Of these patients, 15 (15.9%) were BHCG positive and 13 (13.8%) had a live birth.

CONCLUSIONS

As a result, no difference was found in terms of IUI results (BHCG positivity, live birth, etc.) between patients with sexual dysfunction (FSFI <26.5) and patients with normal sexual function (FSFI>26.5).

IMPACT STATEMENT

The fact that recent studies have generally focused on how the IUI process affects the sexual functions of patients or what changes occur during the IUI process, and the lack of clear information in the literature about the association of sexual function on IUI success, makes our study effective.
目的探讨不明原因不孕症患者的性功能与宫内人工授精成功率的关系。材料与方法采用女性性功能指数(FSFI)对265例不明原因不孕症患者的性功能进行评价,并分析其与宫内人工授精成功率的关系。15名患者拒绝完成测试。13例患者因部分回答问题而被排除在评估之外。FSFI评分分为两组:<;26.5和>;26.5,评估两组IUI的成功程度。结果在完成FSFI测试的237例患者中,143例(0.60)的FSFI评分为26.5。在这些患者中,23例(16%)BHCG阳性,20例(13%)活产。其余94例患者FSFI评分为26.5。其中15例(15.9%)BHCG阳性,13例(13.8%)活产。结论性功能障碍患者(FSFI>26.5)与性功能正常患者(FSFI>26.5)的IUI结果(BHCG阳性、活产等)无差异。最近的研究主要集中在IUI过程如何影响患者的性功能或在IUI过程中发生了什么变化,而关于性功能与IUI成功的关系的文献缺乏明确的信息,这使得我们的研究是有效的。
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引用次数: 0
Unexpected Poor Ovarian Response in IVF: Does Systemic Inflammation Matter? 体外受精卵巢反应不佳:全身性炎症重要吗?
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105328
Caner Kose , Busra Korpe , Dicle Mutel Gurer , Inci Kahyaoglu , Caganay Soysal

OBJECTIVE

This study aimed to investigate the association between the Systemic Immune-Inflammation Index (SII) and ovarian response parameters in women undergoing IVF who exhibit unexpected poor ovarian response (POR).

MATERIALS AND METHODS

A retrospective analysis was conducted on women aged 20–40 years undergoing IVF treatment at Ankara Etlik City Hospital between May 2024 and June 2025. Participants with normal ovarian reserve (AFC ≥5 and AMH ≥1.2 ng/mL) were grouped according to their ovarian response: unexpected poor responders (n=26) and normal responders (n=53). SII was calculated using peripheral blood neutrophil, lymphocyte, and platelet counts. Ovarian response was evaluated by Follicular Output Rate (FORT), Follicle-Oocyte Index (FOI), and Ovarian Sensitivity Index (OSI). Correlations between SII and ovarian response parameters were analyzed, and logistic regression was used to identify predictors of unexpected POR.

RESULTS

There was no significant difference in SII levels between women with low and normal AMH (624.75 ± 536.80 vs. 808.05 ± 973.28, p=0.103). However, women with unexpected poor ovarian response had significantly lower SII levels compared to normal responders (376.19 ± 180.57 vs. 1010.99 ± 1148.57, p=0.008). No significant correlations were found between SII and individual ovarian response parameters such as FORT, FOI, and OSI. Multivariate logistic regression showed that lower SII values were independently associated with a unexpected poor ovarian response, with each unit decrease in SII linked to a 52.7% increase in the odds of being a poor responder (OR = 0.473; 95% CI: 0.313–0.723; p < 0.001).

CONCLUSIONS

Lower systemic immune-inflammation levels are linked to unexpected poor ovarian response in women with normal ovarian reserve. Assessing SII may help personalize IVF treatments by identifying patients at risk of suboptimal response. Further studies are needed to confirm these findings.

IMPACT STATEMENT

Contrary to the expectation that higher systemic inflammation impairs ovarian response, our findings reveal that lower SII levels are linked to suboptimal ovarian responsiveness in women with normal ovarian reserve. This may suggest that a balanced level of systemic immune activation is essential for effective folliculogenesis and optimal oocyte yield. These results underscore the importance of a finely tuned immune-inflammatory environment in ovarian function and highlight systemic inflammation as a potential contributor to unexpected poor ovarian response.
目的:本研究旨在探讨体外受精(IVF)中出现意外卵巢反应差(POR)的女性的全身免疫炎症指数(SII)与卵巢反应参数之间的关系。材料与方法回顾性分析2024年5月至2025年6月在安卡拉Etlik市医院接受体外受精治疗的20-40岁女性。卵巢储备正常(AFC≥5和AMH≥1.2 ng/mL)的参与者根据卵巢反应分为意外不良反应者(n=26)和正常反应者(n=53)。通过外周血中性粒细胞、淋巴细胞和血小板计数计算SII。通过卵泡输出率(FORT)、卵泡-卵母细胞指数(FOI)和卵巢敏感性指数(OSI)评估卵巢反应。分析SII与卵巢反应参数之间的相关性,并使用逻辑回归来确定意外POR的预测因素。结果低AMH组与正常AMH组SII水平差异无统计学意义(624.75±536.80∶808.05±973.28,p=0.103)。然而,与正常应答者相比,卵巢反应意外不良的女性SII水平显著降低(376.19±180.57比1010.99±1148.57,p=0.008)。SII与个体卵巢反应参数(如FORT、FOI和OSI)之间无显著相关性。多因素logistic回归显示,较低的SII值与意料之外的卵巢不良反应独立相关,SII每降低一个单位,不良反应的几率增加52.7% (OR = 0.473;95% CI: 0.313-0.723; p < 0.001)。结论在卵巢储备正常的女性中,较慢的全身免疫炎症水平与意料之外的较差的卵巢反应有关。评估SII可以通过识别有次优反应风险的患者来帮助个性化试管婴儿治疗。需要进一步的研究来证实这些发现。影响声明:与预期较高的全身性炎症会损害卵巢反应相反,我们的研究结果显示,在卵巢储备正常的女性中,较低的SII水平与卵巢反应不佳有关。这可能表明,平衡水平的全身免疫激活对于有效的卵泡生成和最佳的卵母细胞产量至关重要。这些结果强调了精细调节免疫炎症环境对卵巢功能的重要性,并强调了全身性炎症是卵巢意外不良反应的潜在因素。
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引用次数: 0
Effects of Sperm Preparation Protocols Using Cumulus Cell Extracellular Matrix on Semen Parameters 积云细胞细胞外基质精子制备工艺对精液参数的影响
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105301
Sabina Aghayeva , Duygu Gok-Yurtseven , Cihan Cakir , Isil Kasapoglu

OBJECTIVE

In this study, it was aimed to determine the effects of the addition of cumulus cell extracellular matrix (CCEMC) to the culture medium used during conventional sperm preparation techniques used in assisted reproductive treatment approaches on routine sperm parameters, fertilisation capacity and sperm DNA fragmentation and to perform comparative analyses of protocols used in sperm separation techniques.

MATERIALS AND METHODS

Ejaculate samples from 30 normozoospermic male patients and oocytes collected on the same day from their spouses were used in the study. The semen sample from each patient was divided into 5 equal volumes, and 5 different groups were formed as control, density gradient (DG), density gradient + cumulus cell extracellular matrix (DG+K), swim-up (SU), and swim-up + cumulus cell extracellular matrix (SU+K).

RESULTS

According to the results obtained, sperm concentration was significantly lower in all experimental groups compared to the control group, and there was a statistically significant difference, especially in the swim-up group. Motility rate was highest in the (SU+K) group, and it was also significantly increased in the (DG+K) and SU groups. TPMSS value decreased significantly in the SU and (SU+K) groups. There was no significant difference between the groups in terms of morphology. It was observed that the viability rate was significantly increased in the groups to which CCECM was added, and this significant increase continued in all experimental groups compared to the control group. ARIC scores indicating acrosomal reaction capacity were also significantly higher in the (DG+K) and (SU+K) groups. In addition, DFI values reflecting DNA damage were significantly lower in these two groups, indicating that CCECM contribution may protect DNA integrity.

CONCLUSIONS

As a result, it was determined that the addition of CCECM to the culture medium used during different sperm washing techniques, especially when used in combination with the swim-up method, had an effect on sperm quality and efficiency. We think that the applied method will be an applicable technique for male infertility treatment in the assisted reproductive treatment approach.

IMPACT STATEMENT

This study provides a novel sperm preparation approach using cumulus cell extracellular matrix, which may enhance fertilization potential and reduce sperm DNA damage in assisted reproductive technologies.
目的在本研究中,旨在确定在辅助生殖治疗方法中使用的传统精子制备技术中使用的培养基中添加积云细胞细胞外基质(CCEMC)对常规精子参数、受精能力和精子DNA片段化的影响,并对精子分离技术中使用的方案进行比较分析。材料与方法采用30例正常精子男性患者的精液样本及当日从其配偶处采集的卵母细胞。将每个患者的精液样本分成5个等体积,组成5个不同的组,分别为对照组、密度梯度组(DG)、密度梯度 + 积云细胞细胞外基质组(DG+K)、游动组(SU)、游动组( + 积云细胞外基质组)。结果结果显示,各实验组的精子浓度均显著低于对照组,且差异有统计学意义,特别是游泳组。运动率以(SU+K)组最高,(DG+K)组和SU组也显著升高。SU组和(SU+K)组TPMSS值明显降低。两组间在形态上无显著差异。结果显示,添加CCECM的各组细胞存活率均显著提高,且与对照组相比,各实验组的存活率均有显著提高。(DG+K)和(SU+K)组的ARIC评分显示顶体反应能力也显著提高。此外,反映DNA损伤的DFI值在这两组中显著降低,表明CCECM的贡献可能保护了DNA的完整性。结论在不同洗精工艺的培养基中添加CCECM对精子质量和效率有显著影响,特别是与浮液法结合使用时。我们认为该方法将成为辅助生殖治疗方法中男性不育症治疗的一种适用技术。影响声明本研究提供了一种利用积云细胞细胞外基质制备精子的新方法,可在辅助生殖技术中提高受精潜力,减少精子DNA损伤。
{"title":"Effects of Sperm Preparation Protocols Using Cumulus Cell Extracellular Matrix on Semen Parameters","authors":"Sabina Aghayeva ,&nbsp;Duygu Gok-Yurtseven ,&nbsp;Cihan Cakir ,&nbsp;Isil Kasapoglu","doi":"10.1016/j.rbmo.2025.105301","DOIUrl":"10.1016/j.rbmo.2025.105301","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>In this study, it was aimed to determine the effects of the addition of cumulus cell extracellular matrix (CCEMC) to the culture medium used during conventional sperm preparation techniques used in assisted reproductive treatment approaches on routine sperm parameters, fertilisation capacity and sperm DNA fragmentation and to perform comparative analyses of protocols used in sperm separation techniques.</div></div><div><h3>MATERIALS AND METHODS</h3><div>Ejaculate samples from 30 normozoospermic male patients and oocytes collected on the same day from their spouses were used in the study. The semen sample from each patient was divided into 5 equal volumes, and 5 different groups were formed as control, density gradient (DG), density gradient + cumulus cell extracellular matrix (DG+K), swim-up (SU), and swim-up + cumulus cell extracellular matrix (SU+K).</div></div><div><h3>RESULTS</h3><div>According to the results obtained, sperm concentration was significantly lower in all experimental groups compared to the control group, and there was a statistically significant difference, especially in the swim-up group. Motility rate was highest in the (SU+K) group, and it was also significantly increased in the (DG+K) and SU groups. TPMSS value decreased significantly in the SU and (SU+K) groups. There was no significant difference between the groups in terms of morphology. It was observed that the viability rate was significantly increased in the groups to which CCECM was added, and this significant increase continued in all experimental groups compared to the control group. ARIC scores indicating acrosomal reaction capacity were also significantly higher in the (DG+K) and (SU+K) groups. In addition, DFI values reflecting DNA damage were significantly lower in these two groups, indicating that CCECM contribution may protect DNA integrity.</div></div><div><h3>CONCLUSIONS</h3><div>As a result, it was determined that the addition of CCECM to the culture medium used during different sperm washing techniques, especially when used in combination with the swim-up method, had an effect on sperm quality and efficiency. We think that the applied method will be an applicable technique for male infertility treatment in the assisted reproductive treatment approach.</div></div><div><h3>IMPACT STATEMENT</h3><div>This study provides a novel sperm preparation approach using cumulus cell extracellular matrix, which may enhance fertilization potential and reduce sperm DNA damage in assisted reproductive technologies.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"51 ","pages":"Article 105301"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532939","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
Insulin Resistance in PCOS: Impact on Follicular Microenvironment, Adipokines, Embryo Development & Clinical Outcomes 多囊卵巢综合征胰岛素抵抗:对卵泡微环境、脂肪因子、胚胎发育和临床结果的影响
IF 3.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.rbmo.2025.105303
Selahattin Emiroğlu , Cihan Cakir , Isil Kasapoglu , Kiper Aslan , Gurkan Uncu

OBJECTIVE

Hyperinsulinemia as a result of IR is seen in 50-75% of patients with PCOS and is among the main etiologic mechanisms of ovulatory dysfunction and hyperandrogenism. Adipokines are polypeptide biological molecules involved in energy metabolism, fertilization, inflammatory processes and endocrine regulation. It is known that changes in adipokine secretion affect oocyte quality, ovulation, hormonal balance and general metabolic processes and are closely related to infertility. The aim of this study was to evaluate whether the presence of IR in women with PCOS is associated with adipokine imbalance and increased apoptosis in the follicular microenvironment and to investigate the possible effects of these biological changes on embryo quality and clinical outcomes.

MATERIALS AND METHODS

A total of 60 female patients were included in the study and the patients were divided into 3 groups as Control group (n=20), group with PCOS and IR (PCOS+IR, n=20) and group without PCOS and IR (PCOS-IR, n=20). Adipokine (CTRP3, adiponectin, leptin, visfatin) amounts, fasting insulin, fasting glucose levels, HOMA-IR values, FSHR/LHR (follicle stimulating hormone/ luteinizing hormone) ratios in serum, follicular fluid and cumulus cell samples obtained from the patients, caspase-3, IL-6 (interleukin-6), IGF-1 (insulin-like growth factor) values were statistically analyzed by ELISA and the results were evaluated in relation to embryology parameters and clinical outcomes

RESULTS

In the PCOS+IR group, CTRP3, adiponectin, IGF-1, FSHR, and LHR levels decreased, while leptin, visfatin, IL-6, and Caspase-3 increased. These alterations negatively affected embryo development, leading to reduced MII oocyte, fertilization, cleavage, and blastocyst rates, and significantly impaired blastocyst quality scores.

CONCLUSIONS

In conclusion, in PCOS women with IR (PCOS+IR) and PCOS women without IR (PCOS-IR), significant differences were found in adipokine levels in follicular fluid, serum and cumulus cells compared to the control group. It has also been scientifically shown that increased apoptotic activation negatively affects embryologic parameters and clinical outcomes.

IMPACT STATEMENT

Data demonstrate that IR is a direct determinant not only of metabolic but also of reproductive outcomes, highlighting the importance of considering the presence of IR in personalized treatment approaches. It is thought that controlling IR may improve fertility outcomes in women with PCOS.
IR导致的高胰岛素血症在50-75%的PCOS患者中可见,是排卵功能障碍和高雄激素症的主要病因机制之一。脂肪因子是一种多肽生物分子,参与能量代谢、受精、炎症过程和内分泌调节。已知脂肪因子分泌的变化影响卵母细胞质量、排卵、激素平衡和一般代谢过程,与不孕症密切相关。本研究的目的是评估PCOS女性中IR的存在是否与卵泡微环境中脂肪因子失衡和细胞凋亡增加有关,并探讨这些生物学变化对胚胎质量和临床结果的可能影响。材料与方法将60例女性患者分为对照组(n=20)、PCOS合并IR组(PCOS+IR, n=20)和无PCOS合并IR组(PCOS-IR, n=20)。采用ELISA法统计分析患者血清、卵泡液和积云细胞样本中脂肪因子(CTRP3、脂联素、瘦素、内脏脂肪素)含量、空腹胰岛素、空腹血糖水平、HOMA-IR值、促卵泡激素/促黄体生成素比值、caspase-3、IL-6、IGF-1(胰岛素样生长因子)值,并评价其与胚胎学参数和临床结局的关系。结果:PCOS+IR组,CTRP3、脂联素、瘦素、内脏脂肪素含量、促卵泡生成素含量、促卵泡生成素含量、促卵泡生成素含量、促卵泡生成素含量。脂联素、IGF-1、FSHR和LHR水平下降,而瘦素、visfatin、IL-6和Caspase-3水平升高。这些改变对胚胎发育产生负面影响,导致MII卵母细胞、受精、卵裂和囊胚率降低,并显著降低囊胚质量评分。结论PCOS合并IR组(PCOS+IR)和PCOS不合并IR组(PCOS-IR)卵泡液、血清和积云细胞中脂肪因子水平与对照组比较差异有统计学意义。科学研究也表明,凋亡激活的增加会对胚胎学参数和临床结果产生负面影响。影响声明数据表明,IR不仅是代谢结果的直接决定因素,也是生殖结果的直接决定因素,强调了在个性化治疗方法中考虑IR存在的重要性。人们认为控制IR可改善多囊卵巢综合征妇女的生育结果。
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引用次数: 0
期刊
Reproductive biomedicine online
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