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Temporal and Spatial Variation of the Human Placental Microbiota During Pregnancy 妊娠期人类胎盘微生物群的时空变化。
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-12-05 DOI: 10.1111/aji.70023
Liping Liu, Tingting Yin, Xin Zhang, Lizhou Sun, Yin Yin

Problem

Previously believed sterile, the placenta hosts distinct microbial species across various locations. This study aims to elucidate the temporal and spatial variations of placental microbiota throughout gestation, addressing gaps in current understanding.

Method of Study

A case–control study at a single-center compared microbial profiles in pregnant women delivering preterm (<37 weeks) or at term (>37 weeks) across placental sites: basal plate, fetal membranes, and placental villous. Microbial abundance and diversity were evaluated using QIIME and the R package “Phyloseq,” while Q-PCR with specific primers validated absolute abundance in samples.

Results

We found no alteration in bacterial communities based on delivery mode across all samples. Q-PCR detected low-abundance bacteria, notably enriched in preterm samples, especially in early preterm cases. Throughout gestation, bacterial composition varied, with increasing levels of Proteobacteria and Firmicutes observed in the placenta. Significant differences in bacterial profiles were noted across locations and gestational stages, with Ralstonia insidiosa consistently present in the basal plate throughout gestation. Species-specific Q-PCR confirmed the presence of Ralstonia and revealed an inverse relationship between Streptococcus agalactiae and pregnancy progression.

Conclusions

The placenta hosts its own microbiome, with distinct profiles observed between term and preterm samples. Further research is needed to clarify the impact of bacterial dysbiosis on preterm birth and develop methods to distinguish pathological bacteria from the natural microbiome.

问题:以前被认为是无菌的,胎盘在不同的位置承载着不同的微生物物种。本研究旨在阐明胎盘微生物群在整个妊娠期的时空变化,解决目前认识的空白。研究方法:一项单中心病例对照研究比较了早产(37周)孕妇在胎盘部位(底板、胎膜和胎盘绒毛)的微生物特征。使用QIIME和R包“Phyloseq”评估微生物丰度和多样性,而使用特定引物的Q-PCR验证样品的绝对丰度。结果:我们发现所有样品中基于递送方式的细菌群落没有变化。Q-PCR检测到低丰度细菌,特别是在早产儿样本中富集,特别是在早期早产儿病例中。在整个妊娠期间,细菌组成变化,在胎盘中观察到变形菌门和厚壁菌门的水平增加。在不同的位置和妊娠阶段,细菌谱的显著差异被注意到,在整个妊娠期间,裂谷杆菌始终存在于底板。物种特异性Q-PCR证实了Ralstonia的存在,并显示无乳链球菌与妊娠进展呈负相关。结论:胎盘拥有自己的微生物群,在足月和早产儿样本中观察到不同的特征。需要进一步的研究来阐明细菌生态失调对早产的影响,并开发区分病理细菌和天然微生物组的方法。
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引用次数: 0
Cyclophosphamide-Induced Infertility and the Impact of Antioxidants 环磷酰胺致不孕症及抗氧化剂的影响
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-12-03 DOI: 10.1111/aji.70014
Morteza Abdi, Manouchehr Fadaee, Amirreza jourabchi, Hadi Karimzadeh, Tohid Kazemi

An important drawback of anticancer chemotherapy is the harm it causes to healthy cells. Cyclophosphamide (CP) is a widely used chemotherapeutic alkylating agent that is regularly used in cancer treatment. However, it can cause severe side effects, including genotoxicity, due to its ability to damage DNA. This toxicity is thought to be associated with oxidative stress induced by an excessive amount of reactive oxygen species (ROS). Therefore, there is a specific focus on the potential effects of anticancer treatments on fertility. Due to the increasing life expectancy of cancer patients, those desiring parenthood may face the negative impacts of therapies. Utilizing substances with antioxidant and cytoprotective characteristics to protect the reproductive system from harmful consequences during chemotherapy would be highly beneficial. This review introduces the physiological and pathological roles of ROS in the reproductive systems of both males and females, then we address the adverse effects of CP administration on infertility and discuss how antioxidants can reverse these effects.

抗癌化疗的一个重要缺点是它会对健康细胞造成伤害。环磷酰胺(Cyclophosphamide, CP)是一种广泛应用于肿瘤治疗的烷基化化疗药物。然而,由于其破坏DNA的能力,它会引起严重的副作用,包括遗传毒性。这种毒性被认为与过量活性氧(ROS)诱导的氧化应激有关。因此,人们特别关注抗癌治疗对生育能力的潜在影响。由于癌症患者的预期寿命越来越长,那些渴望成为父母的人可能会面临治疗的负面影响。利用具有抗氧化和细胞保护特性的物质来保护生殖系统免受化疗期间的有害后果将是非常有益的。本文介绍了活性氧在男性和女性生殖系统中的生理和病理作用,然后我们讨论了CP给药对不育的不良影响,并讨论了抗氧化剂如何逆转这些影响。
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引用次数: 0
Immunophenotyping and Activation Status of Maternal Lymphocytes to Predict Spontaneous Preterm Birth in Women With Threatened Preterm Labor: A Prospective Observational Study 免疫表型和母体淋巴细胞激活状态预测先兆早产妇女自发性早产:一项前瞻性观察研究
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-12-03 DOI: 10.1111/aji.70015
Maeva Wendremaire, Tarik Hadi, Tatiana E. Lopez, Julien Guy, Fabrice Neiers, Carmen Garrido, Emmanuel Simon, Zohra Jaffal, Virginie Bernigal, Marc Bardou, Frédéric Lirussi

Problem

Preterm birth (PTB) remains the leading cause of neonatal morbidity and mortality. Identifying women at high risk of spontaneous preterm labor (PTL) is challenging due to limited efficient diagnostic markers. Since human parturition involves inflammatory immune processes, we hypothesized that phenotyping of maternal peripheral lymphocytes might predict PTL. Therefore, we aimed to explore the relationship between maternal lymphocyte subpopulations and labor onset characterized by delivery within 7 days of admission in women hospitalized for PTL between 24 and 34 weeks of gestation.

Methods of Study

Lymphocyte subpopulations were obtained from peripheral blood samples and characterized by flow cytometry: activated and regulatory T cells, natural killer and B cells, and TH1/TH2/TH17 lymphocytes. Data analysis was conducted retrospectively based on the delivery within 7 days of admission.

Results

Among 167 women admitted for PTL, less than 10% delivered within 7 days post-admission. HLA-DR expression was significantly increased on CD4+CD8, CD4CD8+, and CD4+CD8+ lymphocytes in women who delivered within 7 days. Subset levels below 5% of CD4+CD8HLA-DR+ lymphocytes and 20% of CD4+CD8+HLA-DR+ lymphocytes were associated with no probability of delivering within 7 days.

Conclusion

Our study suggests that combining these two consecutive markers allowed us to identify 57% of women hospitalized for PTL with no probability of delivering within 7 days while retaining patients who delivered within 7 days. If prospectively validated, these markers may be able to identify patients at high risk of PTB and avoid a significant number of unnecessary admissions and healthcare costs.

Trial Registration

ANSM number: 2010-A00516-33; ClinicalTrials.gov identifier: NCT01340222

问题早产(PTB)仍然是新生儿发病率和死亡率的主要原因。由于有限的有效诊断标记,识别自然早产(PTL)高风险妇女具有挑战性。由于人类分娩涉及炎症免疫过程,我们假设母体外周淋巴细胞的表型可能预测PTL。因此,我们旨在探讨产妇淋巴细胞亚群与妊娠24 - 34周PTL住院妇女入院后7天内分娩的关系。研究方法外周血淋巴细胞亚群:活化T细胞、调节性T细胞、自然杀伤细胞、B细胞、TH1/TH2/TH17淋巴细胞。回顾性分析患者入院后7天内的分娩情况。结果167名因PTL入院的妇女中,不到10%的人在入院后7天内分娩。7天内分娩的妇女CD4+CD8−、CD4 - CD8+和CD4+CD8+淋巴细胞中HLA-DR表达显著升高。CD4+CD8+HLA-DR+淋巴细胞亚群水平低于5%和CD4+CD8+HLA-DR+淋巴细胞亚群水平低于20%与7天内无分娩概率相关。结论:我们的研究表明,结合这两个连续的指标,我们可以确定57%的因PTL住院的7天内不可能分娩的妇女,同时保留7天内分娩的患者。如果前瞻性验证,这些标记可能能够识别PTB高风险患者,并避免大量不必要的入院和医疗费用。试验注册ANSM号:2010-A00516-33;ClinicalTrials.gov识别码:NCT01340222
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引用次数: 0
Mechanism of Endometrial Receptivity Affected by Fibroids 子宫肌瘤影响子宫内膜容受性的机制
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-12-03 DOI: 10.1111/aji.70022
Ping Sun, Chunyan Zhang, Weisha Wang, Huagang Ma

Fibroids are the most common benign tumors of the female reproductive system. Most patients with fibroids are asymptomatic, but the presence of fibroids can still cause some abnormal clinical symptoms, such as increased menstrual volume, abnormal uterine bleeding, pelvic pain, urinary tract and gastrointestinal tract compression symptoms, etc. The impact of fibroids on pregnancy is worth discussing. At present, it is believed that submucosal myoma and intramural myoma affecting uterine cavity shape affect the pregnancy outcome of patients, while the impact of type III intramural myoma on pregnancy is still controversial. A number of studies have found that in addition to direct contact with the endometrial compression, uterine myoma also affects the endometrial flexibility through other ways. In this review, we summarized the effects of fibroids on endometrial receptivity and discussed in depth the mechanisms of such effects, including secretion of cytokines, changes in endometrial blood flow and angiogenesis, effects on endometrial peristalsis and mechanical stress conduction, changes in uterine microecological environment, and abnormal signal transduction pathways. Understanding the mechanism of endometrial receptivity affected by fibroids is significant for exploring the treatment of fibroids, improving the pregnancy outcome of patients with fibroids and increasing the clinical pregnancy rate.

肌瘤是女性生殖系统最常见的良性肿瘤。大多数肌瘤患者是无症状的,但肌瘤的存在仍可引起一些异常的临床症状,如月经量增加、子宫异常出血、盆腔疼痛、尿路和胃肠道受压症状等。肌瘤对妊娠的影响值得探讨。目前认为影响子宫腔形态的粘膜下肌瘤和壁内肌瘤影响患者妊娠结局,而III型壁内肌瘤对妊娠的影响仍存在争议。多项研究发现,子宫肌瘤除了直接接触压迫子宫内膜外,还通过其他途径影响子宫内膜柔韧性。本文综述了子宫肌瘤对子宫内膜容受性的影响,并从细胞因子的分泌、子宫内膜血流和血管生成的变化、对子宫内膜蠕动和机械应力传导的影响、子宫微生态环境的变化、异常信号转导途径等方面对其影响机制进行了深入探讨。了解肌瘤对子宫内膜容受性的影响机制,对于探索肌瘤的治疗方法,改善肌瘤患者的妊娠结局,提高临床妊娠率具有重要意义。
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引用次数: 0
Single and Joint Associations Between Blood Cell-Based Inflammatory Indicator in Early Pregnancy and Risk of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study 妊娠早期血细胞炎性指标与妊娠期糖尿病(GDM)风险之间的单一和联合关联:一项前瞻性队列研究
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-12-03 DOI: 10.1111/aji.70021
Yanling Xiao, Haonan Zhang, Songlin An, Rui Yu, Jing Yang, Xingting Zheng, Nian Wu, Lin Tao, Dengqing Liao, Mingyu Deng, Zhongmei Hu, Yijun Liu, Qing Chen, Yuanzhong Zhou

Problem

This study aims to introduce the Bayesian kernel machine regression (BKMR) model to explore the single and joint associations between exposure to blood cell-based inflammatory in early pregnant women and gestational diabetes mellitus (GDM).

Method of Study

The study included 536 singleton pregnant women from the Zunyi Birth Cohort. Logistic regression, restricted cubic spline regression, and BKMR were used to investigate single, nonlinear, and combined associations.

Results

In this study, the adjusted odds ratio (OR) of white blood cell (WBC), neutrophil (NEUT), monocyte (MONO), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were 2.20 (95% confidence interval [CI]: 1.43–3.37), 2.27 (95% CI: 1.48–3.48), 1.67 (95% CI: 1.09–2.57), 1.66 (95% CI: 1.07–2.58), 1.65 (95% CI: 1.08–2.54), and 1.89 (95% CI: 1.23–2.91), respectively. Nonlinear associations of WBC (cutoff level: 7.91 × 109/L) and NEUT (cutoff level: 5.52 × 109/L) with GDM were also observed. Furthermore, BKMR analysis showed that the risk of GDM was linked with increased levels of blood cell-based inflammatory indicators.

Conclusion

In early pregnancy, multiple blood cell-based inflammatory indicators are significantly positively correlated with the risk of GDM. Specifically, WBC and NEUT counts exhibit the most prominent association with GDM risk. Therefore, more attention should be paid to the inflammation levels of early pregnant women.

本研究旨在引入贝叶斯核机回归(BKMR)模型,探讨早期妊娠妇女暴露于血细胞性炎症与妊娠糖尿病(GDM)之间的单一和联合关联。研究对象为来自遵义出生队列的536名单胎孕妇。使用逻辑回归、受限三次样条回归和BKMR来研究单一、非线性和联合关联。结果本研究中,白细胞(WBC)、中性粒细胞(NEUT)、单核细胞(MONO)、血小板(PLT)、中性粒细胞与淋巴细胞比值(NLR)和全身免疫炎症指数(SII)的校正比值比(OR)分别为2.20(95%可信区间[CI]: 1.43 ~ 3.37)、2.27 (95% CI: 1.48 ~ 3.48)、1.67 (95% CI: 1.09 ~ 2.57)、1.66 (95% CI: 1.07 ~ 2.58)、1.65 (95% CI: 1.08 ~ 2.54)和1.89 (95% CI: 1.23 ~ 2.91)。WBC(临界值:7.91 × 109/L)和NEUT(临界值:5.52 × 109/L)与GDM也存在非线性关联。此外,BKMR分析显示,GDM的风险与血细胞炎症指标水平的增加有关。结论妊娠早期多项血细胞炎性指标与GDM发生风险显著正相关。具体而言,WBC和NEUT计数与GDM风险表现出最显著的相关性。因此,应更加关注孕早期妇女的炎症水平。
{"title":"Single and Joint Associations Between Blood Cell-Based Inflammatory Indicator in Early Pregnancy and Risk of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study","authors":"Yanling Xiao,&nbsp;Haonan Zhang,&nbsp;Songlin An,&nbsp;Rui Yu,&nbsp;Jing Yang,&nbsp;Xingting Zheng,&nbsp;Nian Wu,&nbsp;Lin Tao,&nbsp;Dengqing Liao,&nbsp;Mingyu Deng,&nbsp;Zhongmei Hu,&nbsp;Yijun Liu,&nbsp;Qing Chen,&nbsp;Yuanzhong Zhou","doi":"10.1111/aji.70021","DOIUrl":"https://doi.org/10.1111/aji.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>This study aims to introduce the Bayesian kernel machine regression (BKMR) model to explore the single and joint associations between exposure to blood cell-based inflammatory in early pregnant women and gestational diabetes mellitus (GDM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The study included 536 singleton pregnant women from the Zunyi Birth Cohort. Logistic regression, restricted cubic spline regression, and BKMR were used to investigate single, nonlinear, and combined associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, the adjusted odds ratio (OR) of white blood cell (WBC), neutrophil (NEUT), monocyte (MONO), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were 2.20 (95% confidence interval [CI]: 1.43–3.37), 2.27 (95% CI: 1.48–3.48), 1.67 (95% CI: 1.09–2.57), 1.66 (95% CI: 1.07–2.58), 1.65 (95% CI: 1.08–2.54), and 1.89 (95% CI: 1.23–2.91), respectively. Nonlinear associations of WBC (cutoff level: 7.91 × 10<sup>9</sup>/L) and NEUT (cutoff level: 5.52 × 10<sup>9</sup>/L) with GDM were also observed. Furthermore, BKMR analysis showed that the risk of GDM was linked with increased levels of blood cell-based inflammatory indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In early pregnancy, multiple blood cell-based inflammatory indicators are significantly positively correlated with the risk of GDM. Specifically, WBC and NEUT counts exhibit the most prominent association with GDM risk. Therefore, more attention should be paid to the inflammation levels of early pregnant women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
IL-17 Producing T to Foxp3+CD4+ Regulatory T Cell Ratio as a Diagnostic and Prognostic Marker in Women With Recurrent Pregnancy Loss and Its Implications for Intravenous Immunoglobulin Therapy 作为复发性妊娠失败妇女诊断和预后标志的 IL-17 产 T 与 Foxp3+CD4+ 调节性 T 细胞之比及其对静脉注射免疫球蛋白疗法的影响
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-25 DOI: 10.1111/aji.70020
Jin-Sol Park, Ah-Yun Song, Ju-Young Bae, Jae Won Han, Tae Hyun Kim, Chul-Jung Kim, Sung Ki Lee
<div> <section> <h3> Problem</h3> <p>The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut-off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut-off value.</p> </section> <section> <h3> Method of Study</h3> <p>This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL-17<sup>+</sup> T cell to Foxp3<sup>+</sup> T cell ratios in peripheral blood were measured using flow cytometry. The cut-off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high- and low-ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio.</p> </section> <section> <h3> Results</h3> <p>Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (sensitivity at 97%) and CD4<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was the most valuable prognostic marker. In RPL women with high CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, <i>p</i> = 0.026). On the other hand, RPL women with low CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, <i>p</i> = 0.219). In a correlation study, the CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio.</p> </section> <section> <h3> Conclusion</h3> <p>The CD3<sup>+</sup>IL-17<sup>+</sup> T/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demo
问题 Th17/调节性 T(Treg)细胞比率失衡与复发性妊娠失败(RPL)有关。本研究旨在确定Th17/Treg细胞比率的临界值,以预测RPL的妊娠结局,并根据该临界值评估静脉注射免疫球蛋白(IVIG)的效果。 研究方法 这项回顾性队列研究包括 49 例特发性 RPL 和 75 例对照组。使用流式细胞术测量了外周血中 IL-17+ T 细胞与 Foxp3+ T 细胞比率的亚组。通过 ROC 曲线确定 Th17/Treg 细胞比率的临界值,以区分 RPL 和对照组。比较了高比率组和低比率组的 IVIG 治疗对妊娠结局的影响。皮尔逊相关性评估了Th17/Treg细胞比率与NK细胞细胞毒性(NKC)、NK细胞百分比和Th1/Th2细胞比率的关系。 结果 利用 ROC 曲线,我们确定了 6 个具有诊断价值的 Th17/Treg 细胞比值标志物,其中 CD3+IL-17+ T 细胞/CD3+Foxp3高 T 细胞比值(敏感性为 97%)和 CD4+IL-17+ T 细胞/CD3+Foxp3高 T 细胞比值(特异性为 93.61%)在诊断特发性 RPL 中显示出最高的统计学意义。在六种诊断标志物中,CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值是预测 IVIG 治疗妊娠结局的最有价值的预后标志物。在 CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值较高(≥ 1.096)的 RPL 妇女中,IVIG 治疗可提高活产率(LBR)。(IVIG治疗,78.57%;无IVIG治疗,28.57%,P = 0.026)。另一方面,CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值较低的 RPL 妇女并没有显示出 IVIG 的有效性(接受 IVIG 治疗的活产率为 50.00%,不接受 IVIG 治疗的活产率为 84.62%,P = 0.219)。在一项相关性研究中,CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值是一个独立的预后指标,与 NKC、NK 细胞百分比和 Th1/Th2 细胞比值没有相关性。 结论 CD3+IL-17+ T/CD4+Foxp3+ T 细胞比值可作为了解 RPL 发病机制、预测妊娠结局和选择免疫疗法候选者的重要标志物。我们的研究表明,IVIG 治疗可显著改善 CD3+IL-17+ T/CD4+Foxp3+ T 比率高的妇女的 LBR,为这一具有挑战性的病症提供了一种有前景的治疗方法。
{"title":"IL-17 Producing T to Foxp3+CD4+ Regulatory T Cell Ratio as a Diagnostic and Prognostic Marker in Women With Recurrent Pregnancy Loss and Its Implications for Intravenous Immunoglobulin Therapy","authors":"Jin-Sol Park,&nbsp;Ah-Yun Song,&nbsp;Ju-Young Bae,&nbsp;Jae Won Han,&nbsp;Tae Hyun Kim,&nbsp;Chul-Jung Kim,&nbsp;Sung Ki Lee","doi":"10.1111/aji.70020","DOIUrl":"https://doi.org/10.1111/aji.70020","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Problem&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut-off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut-off value.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Method of Study&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL-17&lt;sup&gt;+&lt;/sup&gt; T cell to Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratios in peripheral blood were measured using flow cytometry. The cut-off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high- and low-ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD3&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;high&lt;/sup&gt; T cell ratio (sensitivity at 97%) and CD4&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD3&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;high&lt;/sup&gt; T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD4&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratio was the most valuable prognostic marker. In RPL women with high CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD4&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, &lt;i&gt;p&lt;/i&gt; = 0.026). On the other hand, RPL women with low CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD4&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, &lt;i&gt;p&lt;/i&gt; = 0.219). In a correlation study, the CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T cell/CD4&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The CD3&lt;sup&gt;+&lt;/sup&gt;IL-17&lt;sup&gt;+&lt;/sup&gt; T/CD4&lt;sup&gt;+&lt;/sup&gt;Foxp3&lt;sup&gt;+&lt;/sup&gt; T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demo","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Association of Systemic Inflammatory Indices and Last Trimester APRI Score With Perinatal Outcomes in Pregnant Women With Pregestational Diabetes–A Prospective Observational Study 妊娠期糖尿病孕妇全身炎症指数和最后三个月 APRI 评分与围产期结果的关系--前瞻性观察研究。
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1111/aji.70018
Gulcan Okutucu, Atakan Tanacan, Sengul Kara, Osman Onur Ozkavak, Aysegul Atalay, Ozgur Kara, Dilek Sahin

Aims

To investigate whether systemic inflammatory indices and the last trimester APRI score change in PGDM and to evaluate the relationship between these alterations and perinatal outcomes.

Methods

A total of 240 pregnant women, 120 of whom were pregestational diabetic (40 with T1DM and 80 with T2DM), were analyzed. In each trimester, WBC, NEU, LNF, PLT, NLR, dNLR, PLR, PNR, and SII values, and in the last trimester MON, PMR, SIRI, AST values, and APRI score were recorded and compared between PGDM and control cohorts.

Results

The first trimester WBC, NEU, and LNF values were higher and the PNR values were lower, the second trimester LNF value was higher and the NLR was lower, the third trimester APRI score was higher in the PGDM group. In diabetic pregnant women, the optimal cut-off value of NEU for predicting LBW in the first trimester was 6.965 × 10⁹/L (62.5% sensitivity and 61.6% specificity), while the optimal cut-off value of the last trimester APRI score for predicting preterm delivery was 0.072 (61.9% sensitivity and 61.6% specificity). In predicting NICU, the optimal cut-off value for second trimester NLR was found to be 3.973 (70% sensitivity and 70% specificity) in the T1DM group, while the optimal cut-off values for first and second trimester LNF were 2.395 × 10⁹/L (75% sensitivity and 71.1% specificity) and 2.23 × 10⁹/L (75% sensitivity and 68.4% specificity) in the T2DM group, respectively.

Conclusions

In routine clinical practice, the first trimester NLR and last trimester APRI score may be used as additional tools for predicting perinatal outcomes in pregnancies affected by PGDM.

目的:研究全身炎症指数和最后三个月的 APRI 评分在 PGDM 中是否会发生变化,并评估这些变化与围产期结局之间的关系:共对 240 名孕妇进行了分析,其中 120 名为妊娠期糖尿病孕妇(40 名 T1DM 孕妇和 80 名 T2DM 孕妇)。记录每个孕期的白细胞、NEU、LNF、PLT、NLR、dNLR、PLR、PNR 和 SII 值,以及最后三个孕期的 MON、PMR、SIRI、AST 值和 APRI 评分,并对 PGDM 和对照组进行比较:结果:PGDM 组孕妇前三个月白细胞、NEU 和 LNF 值较高,PNR 值较低,后三个月 LNF 值较高,NLR 值较低,第三个月 APRI 评分较高。在糖尿病孕妇中,预测前三个月低体重儿的 NEU 最佳临界值为 6.965 × 10⁹/L(灵敏度为 62.5%,特异度为 61.6%),而预测早产的最后三个月 APRI 评分最佳临界值为 0.072(灵敏度为 61.9%,特异度为 61.6%)。在预测新生儿重症监护室方面,T1DM 组中孕期后三个月 NLR 的最佳临界值为 3.973(灵敏度为 70%,特异度为 70%),而 T2DM 组中孕期前三个月和后三个月 LNF 的最佳临界值分别为 2.395 × 10↪No_2079/L(灵敏度为 75%,特异度为 71.1%)和 2.23 × 10↪No_2079/L(灵敏度为 75%,特异度为 68.4%):在常规临床实践中,前三个月的 NLR 和最后三个月的 APRI 评分可作为预测受 PGDM 影响的孕妇围产期结局的额外工具。
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引用次数: 0
Galectin-1 Elicits a Tissue-Specific Anti-Inflammatory and Anti-Degradative Effect Upon LPS-Induced Response in an Ex Vivo Model of Human Fetal Membranes Modeling an Intraamniotic Inflammation 在模拟羊膜腔内炎症的人胎膜体外模型中,Galectin-1 对 LPS 诱导的反应具有组织特异性抗炎和抗降解作用。
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1111/aji.70016
Jazmin Hernández-Rodríguez, Jesús Pérez-Hernández, Pilar Flores-Espinosa, Andrea Olmos-Ortiz, Pilar Velazquez, Rodrigo Zamora-Escudero, Marcela Islas-López, Addy Cecilia Helguera-Repetto, Karla Hernández-Bones, Samara Rodríguez-Flores, Rodrigo Jiménez-Escutia, Amaury Fortanel-Fonseca, Arturo Flores-Pliego, Rosario Lopez-Vancell, Veronica Zaga-Clavellina

Problem

Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal–fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu.

Method of Study

Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments.

Results

In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9.

Conclusion

Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal–fetal interface.

问题:宫内感染是与包括早产在内的不良预后相关的最危险情况之一;然而,母胎界面上有多种耐受机制在运作,以避免胎儿受到排斥。在维持子宫作为免疫优势部位的因素中,母胎单位分泌的一种免疫调节糖结合蛋白--Galectin-1(Gal-1)在促进免疫细胞稳态方面起着关键作用。这项研究旨在评估 Gal-1 在脂多糖(LPS)诱导的炎症环境中的作用:研究方法:利用具有两个独立隔室的体外培养,用 40 和 80 纳克/毫升 Gal-1 预处理足月的人类胎膜,然后用 500 纳克/毫升 LPS 刺激胎膜一侧 24 小时,以再现羊膜腔内炎症。测量了羊膜和绒毛膜中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、单核细胞趋化蛋白(MCP1)、巨噬细胞炎症蛋白(MIP1)α、正常T细胞表达和分泌激活调节因子(RANTES)和基质金属蛋白酶(MMP)-9的浓度:结果:从组织特异性角度看,使用生理浓度的 Gal-1 预处理可显著减少依赖于 LPS 的 TNF-α、IL-1β、Il-6、MCP1、MIP1α、RANTES 和 MMP-9 的分泌:结论:Gal-1能对受LPS刺激的人类胎膜产生抗炎作用,这支持了Gal-1是免疫调节机制的一部分,旨在阻止母胎界面炎症的有害影响的假设。
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引用次数: 0
Circ-ADAM9 Knockdown Reduces Insulin Resistance and Placental Injury in Diabetic Mice via MAPK Pathway Inactivation Circ-ADAM9 基因敲除通过 MAPK 通路失活减轻糖尿病小鼠的胰岛素抵抗和胎盘损伤
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1111/aji.70017
Ai Zhao, Yawen Yang, Yijun Yang, Zhenjing Chi, Yanlan Sun
<div> <section> <h3> Background</h3> <p>Gestational diabetes mellitus (GDM) significantly risks maternal and neonatal health. Circular RNAs (circRNAs) regulate various diseases but their role in GDM is unclear. We investigated the involvement of circ-ADAM9 in GDM.</p> </section> <section> <h3> Methods</h3> <p>We analyzed circ-ADAM9 expression in GDM-related microarray data (GSE182737) and measured its levels in the blood of GDM patients. In a high-fat diet-induced GDM mouse model, we inhibited circ-ADAM9 expression and tracked blood glucose levels, serum insulin, lipid levels, placental apoptosis, and reactive oxygen species (ROS) levels. Pathological changes in pancreatic tissues and fetal outcomes were also examined. Molecular interactions were explored using bioinformatics tools and validated through luciferase assays, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting in high glucose (HG)-induced human trophoblast cells (HTR-8/SVneo). We further investigated the involvement of circ-ADAM9/miR-375/FPR2 axis in HG-induced injury in HTR-8/SVneo cells by assessing cell viability, apoptosis, ROS production, and antioxidant levels.</p> </section> <section> <h3> Results</h3> <p>Both GDM patients and GDM-induced mice exhibited a substantial upregulation of circ-ADAM9. Knockdown of circ-ADAM9 lowered blood glucose, alleviated insulin resistance, improved lipid metabolism, decreased placental apoptosis and ROS levels, and reduced pancreatic lesions in GDM mice. Circ-ADAM9 downregulation also improved fetal viability, weight, and crown-rump length. In HG-induced HTR-8/SVneo cells, circ-ADAM9 overexpression and miR-375 downregulation were evident. Overexpression of miR-375 inhibited circ-ADAM9 activity, substantiating their binding interaction. In GDM mice, circ-ADAM9 deficiency restored miR-375 expression. TargetScanHuman predicted and luciferase assays confirmed the miR-375-FPR2 interaction and elevated FPR2 levels in GDM mice were reduced by circ-ADAM9 silencing. In HG-induced HTR-8/SVneo cells, circ-ADAM9 knockdown restored cell viability, suppressed apoptosis and ROS levels, and enhanced antioxidant enzyme levels. These effects were reversed by miR-375 inhibition or FPR2 overexpression, suggesting circ-ADAM9 upregulates FPR2 expression by sponging miR-375 and modulating the MAPK pathway.</p> </section> <section> <h3> Conclusion</h3> <p>This study is the first to demonstrate the expression and function of circ-ADAM9 in the progression of GDM. Circ-ADAM9 downregulation ameliorates insulin resistance and placental injury in GDM by modulating the miR-375/FPR2 axis and inactivating the MAPK pathway, which may
背景:妊娠糖尿病(GDM)严重危害孕产妇和新生儿的健康。环状 RNA(circRNA)可调控多种疾病,但在 GDM 中的作用尚不清楚。我们研究了 circ-ADAM9 在 GDM 中的作用:我们分析了 GDM 相关芯片数据(GSE182737)中 circ-ADAM9 的表达,并测量了 GDM 患者血液中的其水平。在高脂饮食诱导的 GDM 小鼠模型中,我们抑制了 circ-ADAM9 的表达,并跟踪了血糖水平、血清胰岛素、血脂水平、胎盘凋亡和活性氧(ROS)水平。我们还研究了胰腺组织的病理变化和胎儿的结局。我们使用生物信息学工具探索了分子相互作用,并通过荧光素酶测定、实时定量聚合酶链反应(RT-qPCR)和高葡萄糖(HG)诱导的人滋养层细胞(HTR-8/SVneo)的 Western 印迹进行了验证。我们通过评估细胞活力、凋亡、ROS生成和抗氧化剂水平,进一步研究了circ-ADAM9/miR-375/FPR2轴在HG诱导的HTR-8/SVneo细胞损伤中的参与情况:结果:GDM 患者和 GDM 诱导的小鼠都表现出 circ-ADAM9 的大量上调。敲除 circ-ADAM9 能降低 GDM 小鼠的血糖、缓解胰岛素抵抗、改善脂质代谢、减少胎盘凋亡和 ROS 水平并减少胰腺病变。下调 Circ-ADAM9 还能提高胎儿存活率、体重和头臀长。在 HG 诱导的 HTR-8/SVneo 细胞中,circ-ADAM9 的过表达和 miR-375 的下调是显而易见的。miR-375的过表达抑制了circ-ADAM9的活性,证实了它们之间的结合相互作用。在 GDM 小鼠中,circ-ADAM9 的缺乏可恢复 miR-375 的表达。TargetScanHuman 预测和荧光素酶测定证实了 miR-375-FPR2 的相互作用,并且通过沉默 circ-ADAM9 降低了 GDM 小鼠中升高的 FPR2 水平。在 HG 诱导的 HTR-8/SVneo 细胞中,circ-ADAM9 基因敲除可恢复细胞活力,抑制细胞凋亡和 ROS 水平,提高抗氧化酶水平。这些效应被miR-375抑制或FPR2过表达所逆转,表明circ-ADAM9通过疏导miR-375和调节MAPK通路上调FPR2的表达:本研究首次证明了 circ-ADAM9 在 GDM 进展过程中的表达和功能。通过调节miR-375/FPR2轴和失活MAPK通路,下调circ-ADAM9可改善GDM中的胰岛素抵抗和胎盘损伤,这可能为治疗GDM提供一个新的治疗靶点。
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引用次数: 0
Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study Omicron 变异感染对女性生育能力和实验室结果的影响:一项自我控制研究
IF 2.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-13 DOI: 10.1111/aji.70012
Yu-Ling Hu, Yong-Jia Zhang, Xing-Yu Lv, Rui-Ling Liu, Zhao-Hui Zhong, Li-Juan Fu, Mei-Hua Bao, Li-Hong Geng, Hai-Jiao Xu, Shao-Min Yu, Yu-Bin Ding

Problem

Investigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected.

Methods of the Study

This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection.

Results

The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E2], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14 mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (p > 0.05). When stratified by age, the ≤ 35 years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35 years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3 months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded three months.

Conclusion

Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory outcomes.

问题:调查严重急性呼吸系统综合征冠状病毒-2(SARS-CoV-2)感染对接受辅助生殖技术(ART)治疗的最初未感染但后来感染的患者的女性生育力和实验室结果的影响:这项自控研究纳入了 2021 年 3 月至 2023 年 4 月期间在感染 SARS-CoV-2 前后接受重复卵母细胞提取的 197 名患者,其中 117 人在一致的年龄范围内使用了相同的卵巢刺激方案。我们评估了 SARS-CoV-2 感染前后患者的卵巢储备、卵巢反应和实验室结果:结果:卵巢储备量(卵泡刺激素[FSH]、黄体生成素[LH]、雌激素[E2]、抗穆勒氏管激素[AMH]、前卵泡数[AFC])、卵巢反应(Gn总用量、Gn用药时间、触发日≥14 mm的卵泡数、取到的卵母细胞数在 117 例患者中,SARS-CoV-2 感染前后的卵巢反应(Gn 总用量、Gn 给药时间、触发日≥14 mm 的卵泡数、取到的卵母细胞数)和实验室结果(卵裂期优质胚胎率、囊胚形成率和周期冷冻率)无显著差异(P > 0.05).如果按年龄分层,感染后年龄小于 35 岁组的双前核(2PN)受精率较高,而年龄大于 35 岁组的成熟分裂期 II(MII)卵母细胞和囊胚期优质胚胎率较高。此外,根据感染 SARS-CoV-2 与抗逆转录病毒疗法之间的时间间隔进行分层,感染后 MII 卵母细胞率、2PN 受精率和囊胚期优质胚胎率在感染后≤ 3 个月组均有所增加。结论:我们的研究表明,IVF-IVF(体外受精-胚胎移植)术后的卵母细胞成熟度、2PN受精率和囊胚期优质胚胎率均有所提高:我们的研究表明,从 COVID-19 感染中恢复后接受 IVF/ICSI 治疗可能不会对女性的生育能力和实验室结果产生不利影响。
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引用次数: 0
期刊
American Journal of Reproductive Immunology
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