Evaluating the intersection between sexually transmitted infections, inflammation and reproductive success

评估性传播感染、炎症和生殖成功之间的交叉点

• 批准号: 9887442
• 负责人: Brandie DePaoli Taylor
• 金额: $ 49.28万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9887442
• 关键词: Address; Adverse event; Age; Anti-Inflammatory Agents; Aspirin; Biological Assay; Birth; Birth Rate; Blood; Blood Platelets; C-reactive protein; Cells; Chlamydia; Chlamydia trachomatis; Chronic; Cicatrix; Clinical; Conceptions; Couples; Data; Decidual Cell Reactions; Defect; Diagnosis; Diagnostic; Disease; Dose; Endometrial; Epigenetic Process; Epithelial Cells; Event; Exposure to; Family; Fertility; Frequencies; Funding; Future; Goals; Growth; High Prevalence; IL6 gene; IL8 gene; Immune; Immune signaling; Immunologic Receptors; Infection; Infertility; Inflammation; Interleukin-15; Laboratories; Lead; Legal patent; Link; Live Birth; Measurement; Measures; Mediating; Menstrual cycle; Metadata; Methods; Mission; Morbidity - disease rate; Mycoplasma; Mycoplasma genitalium; Natural Immunity; Nature; Neisseria gonorrhoeae; Outcome; PGF gene; PTGS2 gene; Pathogenesis; Pathology; Pathway interactions; Phenotype; Placebos; Placentation; Plasma; Population; Pregnancy; Pregnancy Histories; Pregnancy loss; Prevalence; Prevention; Prostaglandins; Public Health; Randomized; Recording of previous events; Reproduction; Reproductive Health; Reproductive Medicine; Research; Research Support; Risk; Route; STI prevention; Serologic tests; Serological; Seroprevalences; Serum; Services; Sexually Transmitted Diseases; Sterility; Stimulus; Subfecundity; Surveys; Target Populations; Thromboxane A2; Time; Tissues; Training; Trichomonas vaginalis; Tube; United States National Institutes of Health; Variant; Vascular Endothelial Growth Factors; Woman; Women' s Group; Work; adverse event risk; adverse outcome; angiogenesis; cytokine; early pregnancy loss; fetal; high risk; high risk population; histone modification; human disease; improved; improved outcome; inflammatory marker; innovation; insight; interest; member; obstetric care; pathogen; reproductive; reproductive morbidity; reproductive success; reproductive tract; seropositive; subfertility; time-to-pregnancy; tissue repair; trying to conceive; tubal infertility; young adult

PROJECT SUMMARY ABSTRACT Pregnancy loss occurs in ~20% of women with a clinically recognized pregnancy. Couples with histories of pregnancy loss represent a large portion of those trying to conceive, but treatment is limited to widely inaccessible fertility services. Data from the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial has shown that preconception low-dose Aspirin therapy increases birth rates in women with histories of pregnancy loss when preconception chronic low-grade inflammation, determined by C-reactive protein, is present. There is a critical need to understand pathways that result in preconception chronic low-grade inflammation. This would help to identify a broader group of women whom would benefit from aspirin therapy and inform the use of aspirin in reproductive medicine. We hypothesize that prior exposure to common sexually transmitted infections (STIs) can lead to long-term immune dysregulation and defective tissue repair. Among women with histories of pregnancy loss, STI serology may indicate subsequent risk of adverse events or represent a group of women who would benefit from preconception anti-inflammatory therapy. Prevalent and mostly asymptomatic STIs such as Chlamydia trachomatis and Mycoplasma genitalium can ascend to the upper genital tract causing endometrial inflammation, tissue damage and scarring. Unfortunately, most women acquire these STIs as young adults, but do not know they were ever infected. The concept of “trained innate immunity” posits that innate immune cells can develop a long-term proinflammatory phenotype following infectious stimuli induced through epigenetic changes to immune and epithelial cells. Indeed, these STIs are linked to tubal infertility but associations with other measures of impaired fecundity are limited. The specific aims of this proposal will: 1) determine if seropositivity to Chlamydia trachomatis and Mycoplasma genitalium influences time-to-pregnancy, pregnancy loss and birth rates in women with histories of pregnancy loss while adjusting for other STIs known to infect the upper genital tract. 2) Determine if STI seropositive women have a unique blood immune and angiogenic profile compared to seronegative women. 3) Determine if STI seropositive women previously randomized to Aspirin therapy as part of the EAGeR trial (results described above) have improved birth outcomes. This study will include 1078 women from the EAGeR trial. All women have histories of pregnancy loss but no history of infertility. Access to preconception data from a study with extremely detailed reproductive outcomes is unique. Additionally, our team includes a world-leader in STI diagnostics, which allows for robust serological measurements. We will also leverage the expertise of our team members, currently funded to develop methods to address generalizability, to transport our results to our target population of US women with histories of pregnancy loss using the National Survey of Family Growth. Given the profound increase in STI prevalence in the U.S. and the frequency of pregnancy loss, this study and our future work could impact a large number of women.

项目摘要摘要 在临床公认的妊娠妇女中，约有20％发生妊娠丧失。有历史的夫妻 妊娠损失代表了试图受孕的人的很大一部分，但治疗仅限于广泛 无法访问的生育服务。来自阿司匹林在妊娠和繁殖（急切）试验中的影响的数据已有 表明先入为主的低剂量阿司匹林疗法会提高怀孕史的女性的出生率 当存在由C反应蛋白确定的先入慢性低度注射时损失。有 理解导致先入慢性低度炎症的途径的迫切需要。这会 帮助确定一群更广泛的妇女，这些妇女将从阿司匹林疗法中受益并告知使用阿司匹林 在生殖医学中。我们假设事先暴露于共同的性传播感染（STIS） 可能导致长期免疫失调和组织修复缺陷。在有历史的女性中 怀孕丧失，STI血清学可能表明随后发生不良事件的风险或代表一组妇女 谁将受益于先入为主的抗炎疗法。普遍，主要是不对称性传播感染 由于沙眼衣原体和支原体生殖器可以上升到上生殖道，从而引起子宫内膜 炎症，组织损伤和疤痕。不幸的是，大多数妇女都以年轻人的身份获得这些性传播感染 不知道他们曾经被感染。 “训练有素的先天免疫史”的概念认为先天性免疫史细胞 通过表观遗传学引起的传染性刺激，可以发展长期促炎表型 免疫细胞和上皮细胞的变化。确实，这些性传播感染与输管不育症有关，但与 繁殖受损的其他措施受到限制。该提案的具体目的是：1）确定是否是否 沙眼衣原体和支原体生殖器的血清管症影响怀孕时间，妊娠时间 在调整已知感染的其他性传播疾病的同时，患有怀孕病史的女性的损失和出生率 上生殖道。 2）确定STI血清阳性女性是否具有独特的血液免疫和血管生成特征 与血浆妇女相比。 3）确定STI血清女性是否以前是随机分配给阿司匹林的 作为急切试验的一部分（上述结果）的治疗改善了出生结果。这项研究会 包括来自急切审判的1078名妇女。所有妇女都有怀孕史，但没有不育病史。 从具有极为详细的生殖结果的研究中访问先选数据是独一无二的。此外， 我们的团队包括一个世界性STI诊断的世界领导者，该领导者可以进行良好的血清学测量。我们将 还利用我们的团队成员的专业知识，目前被资助用于开发解决方法来解决 可推广的能力，将我们的结果传达给我们有怀孕史的妇女的目标人群 使用全国性家庭增长调查。鉴于美国的性病患病率的大幅增加 怀孕损失的频率，这项研究和我们未来的工作可能会影响大量女性。