Reproductive Endocrinology And Infertility Clinical Training Program

生殖内分泌与不孕不育临床培训项目

• 批准号: 7734765
• 负责人: James H. Segars
• 金额: $ 201.84万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7734765
• 关键词: Accounting; Actins; Address; Affect; African American; Ants; Appearance; Basic Science; Biochemical; Biological Preservation; Biopsy; Cancer Survivor; Caring; Cells; Cesarean section; Characteristics; Clinical; Clinical Investigator; Clinical Management; Clinical Research; Collaborations; Color; Condition; Conduct Clinical Trials; Connective Tissue; Couples; Cytoskeleton; Development; Diagnosis; Diagnostic; Disease; Economics; Endometriomas; Ethnic group; Evaluation; Extracellular Matrix; Fertility; Fertility Rates; Fertilization in Vitro; Fibroid Tumor; Genes; Goals; Gonadotropin Hormone Releasing Hormone; Growth; Growth and Development function; Health; Hemorrhage; Hispanics; Histologic; Hormone Antagonists; Infertility; Investigation; Knowledge; Leiomyoma; Lesion; Logistic Models; Measures; Mechanical Stress; Mechanics; Medical; Modeling; Multicenter Trials; Operative Surgical Procedures; Outcome; Ovarian; Pain; Patients; Pelvic Pain; Pregnancy Outcome; Prevalence; Probability; Questionnaires; Randomized Controlled Clinical Trials; Rate; Reporting; Reproduction; Reproductive Endocrinology; Reproductive Health; Research; Research Design; Research Personnel; Severity of illness; Signal Transduction; Spontaneous abortion; Structure; Students; Surgeon; Surveys; Testing; Tissues; Training; Training Programs; Treatment Protocols; Uterine Fibroids; Uterine myomectomy; Visit; Weight-Bearing state; Woman; Women' s Health; cancer therapy; career; cell growth; chemotherapy; chronic pelvic pain; clinically relevant; design; desire; endometriosis; experience; girls; graduate medical education; health disparity; hypothalamic-pituitary-adrenal axis; insight; interest; mullerian-inhibiting hormone; protective effect; racial and ethnic; reproductive; reproductive function; solid state

Uterine leiomyoma Uterine leiomyoma, commonly called fibroids, disproportionately affect African American women and are associated with adverse pregnancy outcomes, such as pre-term delivery, miscarriage, and cesarean section. The condition adversely impacts the health of millions of women, leading to excessive menstrual bleeding and pelvic pain. Despite their prevalence, leiomyoma growth and development remain poorly understood, and there are few non-surgical, long-term treatment options for women with fibroids. In order to gain insight into strategies that may be developed for medical treatment of fibroids, our unit has used a gene profiling approach to uncover genes associated with leiomyoma development. This approach led to the realization that genes encoding the connective tissue between cells, the extracellular matrix (ECM), were altered in expression in uterine leiomyoma. Further studies showed that the structure of the ECM was altered in leiomyoma. Together, these findings raised the question whether the altered ECM might contribute to growth of the fibroids through mechanical signaling, since the ECM is a load-bearing structure and increases in loading can affect the growth rate of cells. To test that hypothesis, in the past year in collaboration with Drs. Tuan and Chen in NIAMS, we measured tissue stiffness and found that cells within fibroid tumors were exposed to increased mechanical stress. The increased mechanical stress was accompanied by cellular changes, such as alteration in the actin cytoskeleton and biochemical evidence of activation of solid state signaling. In brief, the studies support the conclusion that cells within a fibroid have fundamental alterations in mechanical signaling and that altered mechanical signaling may contribute to growth of uterine leiomyoma. In the coming year, we plan to characterize the altered mechanical signaling in fibroids in greater detail and characterize factors that might be responsible for the alterations in cell growth. The unit has also continued clinical studies related to leiomyoma. Information about the possible impact of myomectomy on ovarian function is important in the clinical management of patients with fibroids who desire fertility. This question has not been systematically investigated. Specifically, the estimates of subsequent fertility rates in fertile women (or at least in women not proved to be infertile) are not available. To address this gap in the current knowledge, in the past year we examined the impact of leiomyoma on fertility and ovarian reserve. We plan to expand this investigation to include evaluation of anti-mullerian hormone pre and post myomectomy. Endometriosis and Chronic Pelvic Pain Chronic pelvic pain significantly affects the health of up to 10 percent of women with endometriosis. The diagnosis of endometriosis is established at a surgical procedure. One persistent issue in surgical diagnosis is whether histologic confirmation of the disease should be obtained, given the variable appearance of lesions. In the past year, we have correlated biopsy results with lesion appearance in two different ways. In the first study, we reported on the histologic confirmation given varying lesion characteristics, illustrating that no single color was associated with endometriosis and that surgeons should biopsy any suspicious lesion. Subtle lesions were as likely to contain endometriosis as classic lesions (64%) and 40% of women who had only small, subtle lesions had biopsy-proven endometriosis. Mixed color lesions and endometriomas were the only two lesion types that were more commonly biopsy-proven (78%). In a second study, we created a logistic model to predict endometriosis. This model identified characteristics which indicated a high and low probability of biopsy-proven endometriosis. It was useful as a guide in choosing appropriate lesions for biopsy, but should not be used as a substitute for histologic confirmation. In collaboration with Drs. Greene and Sinaii, the group led by Dr. Stratton described the diagnostic experience of women with chronic pelvic pain and endometriosis responding to the Endometriosis Association Survey. The group examined the relationship between disease severity and patient characteristics in endometriosis by analyzing questionnaires from 1000 women in the Oxford Endometriosis Gene (OXYGENE) study. In the coming year, this group will continue examining aspects of the health of women with endometriosis by analyzing the Endometriosis Association Survey, continue efforts to define the pain outcomes in endometriosis clinical trials, and conduct analyses of the hypothalamic pituitary-adrenal-axis in women with chronic pelvic pain and endometriosis. Assessment and preservation of ovarian function in women and girls undergoing cancer treatment As a result of more successful cancer treatments, many young girls and women are now cancer survivors but find that their reproductive function is irreparably damaged by their treatment. Dr. Armstrong recently led an initiative to devise strategies to enable women who are cancer survivors to maximize and preserve reproductive function. In the past year, we have continued our study of treatment regimens designed to minimize the effect of cancer treatments on the later reproductive function of women. To move toward that goal we helped to initiate a large multicenter, randomized trial of gonadotropin-releasing hormone antagonists (GnRH-ant) in young women before cancer treatments. This study will test the hypothesis that medical treatment would benefit young girls undergoing chemotherapy. In addition we have begun basic science studies designed to elucidate the mechanism of the possible protective effect attributable to GnRH-ant treatment prior to chemotherapy. Infertility and reproductive health disparities Reproductive health disparities exist for many women. Our unit has been interested in examining the causes and consequences of these disparities in an effort to devise strategies to optimize reproductive outcome across racial and ethnic groups. In the past year we have continued our study of reproductive health disparities and the context of multicenter investigations. Specifically, Dr. Armstrong was an investigator in a study of racial disparities that examined over 130,000 IVF cycles. The results of this investigation confirmed the findings of disparate outcomes among African American women. In the past year we also evaluated ART utilization and outcome among Hispanic couples. That study suggested that contrary to claims of some that economic barriers accounted for lower rates of utilization, other factors may be responsible for reproductive health disparities. In the coming year we plan to continue to investigate racial disparities in reproductive health in multicenter trials of women in assisted reproduction and infertility care.

子宫肌瘤 子宫肌瘤，通常称为肌瘤，对非裔美国女性影响尤为严重，并与不良妊娠结局相关，例如早产、流产和剖腹产。这种情况对数百万女性的健康产生不利影响，导致月经出血过多和盆腔疼痛。尽管子宫肌瘤很常见，但人们对子宫肌瘤的生长和发育仍知之甚少，而且对于患有肌瘤的女性来说，几乎没有非手术的长期治疗选择。 为了深入了解可用于治疗肌瘤的策略，我们的单位使用基因分析方法来揭示与平滑肌瘤发展相关的基因。这种方法使人们认识到，编码细胞间结缔组织、细胞外基质（ECM）的基因在子宫肌瘤中的表达发生了改变。进一步的研究表明，平滑肌瘤中 ECM 的结构发生了改变。总之，这些发现提出了一个问题：改变的 ECM 是否可能通过机械信号传导促进肌瘤的生长，因为 ECM 是一种承载结构，负载的增加会影响细胞的生长速率。为了验证这一假设，去年与博士合作。在 NIAMS 的 Tuan 和 Chen 的带领下，我们测量了组织硬度，发现纤维瘤内的细胞暴露在增加的机械应力下。机械应力的增加伴随着细胞变化，例如肌动蛋白细胞骨架的改变和固态信号传导激活的生化证据。简而言之，这些研究支持这样的结论：肌瘤内的细胞在机械信号方面存在根本性改变，并且改变的机械信号可能有助于子宫肌瘤的生长。在来年，我们计划更详细地描述肌瘤中机械信号改变的特征，并描述可能导致细胞生长改变的因素。 该单位还继续进行与平滑肌瘤相关的临床研究。有关子宫肌瘤切除术对卵巢功能可能影响的信息对于希望生育的子宫肌瘤患者的临床管理非常重要。这个问题还没有被系统地研究过。具体而言，无法获得对生育妇女（或至少未证明不孕妇女）随后生育率的估计。为了解决当前知识的这一空白，去年我们研究了平滑肌瘤对生育力和卵巢储备的影响。 我们计划扩大这项研究，包括对子宫肌瘤切除术前后抗苗勒氏管激素的评估。 子宫内膜异位症和慢性盆腔疼痛 慢性盆腔疼痛严重影响高达 10% 的子宫内膜异位症女性的健康。 子宫内膜异位症的诊断是通过外科手术确定的。 外科诊断中的一个长期存在的问题是，考虑到病变外观的变化，是否应该获得疾病的组织学确认。 在过去的一年中，我们以两种不同的方式将活检结果与病变外观相关联。 在第一项研究中，我们报告了不同病变特征的组织学确认，表明没有单一颜色与子宫内膜异位症相关，外科医生应对任何可疑病变进行活检。 细微病变与典型病变 (64%) 一样可能含有子宫内膜异位症，并且只有小而细微病变的女性中有 40% 经活检证实患有子宫内膜异位症。 混合颜色病变和子宫内膜异位瘤是仅有的两种更常通过活检证实的病变类型（78%）。 在第二项研究中，我们创建了一个逻辑模型来预测子宫内膜异位症。 该模型确定了表明活检证实的子宫内膜异位症的高概率和低概率的特征。 它可作为选择适当活检病变的指南，但不应用作组织学确认的替代品。 与博士合作。斯特拉顿博士领导的格林和西奈小组描述了患有慢性盆腔疼痛和子宫内膜异位症的女性对子宫内膜异位症协会调查的诊断经验。该小组通过分析牛津子宫内膜异位症基因 (OXYGENE) 研究中 1000 名女性的问卷调查，研究了子宫内膜异位症疾病严重程度与患者特征之间的关系。 来年，该小组将通过分析子宫内膜异位症协会调查，继续研究子宫内膜异位症女性的健康状况，继续努力定义子宫内膜异位症临床试验中的疼痛结果，并对女性下丘脑垂体肾上腺轴进行分析患有慢性盆腔疼痛和子宫内膜异位症。 接受癌症治疗的妇女和女孩卵巢功能的评估和保存 由于癌症治疗更加成功，许多年轻女孩和妇女现在成为癌症幸存者，但发现她们的生殖功能因治疗而受到不可挽回的损害。阿姆斯特朗博士最近领导了一项倡议，旨在制定策略，使癌症幸存者女性能够最大限度地发挥和保​​留生殖功能。在过去的一年里，我们继续研究治疗方案，旨在最大限度地减少癌症治疗对女性后期生殖功能的影响。为了实现这一目标，我们帮助在年轻女性癌症治疗前启动了一项大型多中心随机试验，对促性腺激素释放激素拮抗剂 (GnRH-ant) 进行试验。这项研究将检验医学治疗对接受化疗的年轻女孩有益的假设。此外，我们已经开始基础科学研究，旨在阐明化疗前 GnRH-ant 治疗可能产生的保护作用的机制。 不孕不育和生殖健康差异 许多妇女都存在生殖健康方面的差异。我们的部门一直有兴趣研究这些差异的原因和后果，以制定优化不同种族和民族群体生殖结果的策略。在过去的一年中，我们继续研究生殖健康差异和多中心调查的背景。 具体来说，阿姆斯特朗博士是一项种族差异研究的调查员，该研究检查了超过 130,000 个 IVF 周期。这项调查的结果证实了非裔美国女性的不同结果的发现。去年，我们还评估了西班牙裔夫妇的 ART 利用率和结果。该研究表明，与一些人声称经济障碍导致利用率较低的说法相反，其他因素可能是造成生殖健康差异的原因。来年，我们计划继续在女性辅助生殖和不孕不育护理的多中心试验中调查生殖健康方面的种族差异。

项目成果

Assessment of resident competency in the performance of sonohysterography: does the level of training impact the accuracy?

住院医师进行宫腔超声造影的能力评估：培训水平是否会影响准确性？

• DOI: 10.1016/j.ajog.2004.03.011
• 发表时间: 2004
• 期刊: American journal of obstetrics and gynecology
• 影响因子: 9.8
• 作者: Parker,JasonD;Alvero,RubenJ;Luterzo,Julie;Segars,JamesH;Armstrong,AliciaY
• 通讯作者: Armstrong,AliciaY

History and challenges surrounding ovarian stimulation in the treatment of infertility.

• DOI: 10.1016/j.fertnstert.2012.02.030
• 发表时间: 2012-04
• 期刊: FERTILITY AND STERILITY
• 影响因子: 6.7
• 作者: Beall, Stephanie A.;DeCherney, Alan
• 通讯作者: DeCherney, Alan

Intracytoplasmic sperm injection increases embryo fragmentation without affecting clinical outcome.

胞浆内单精子注射会增加胚胎破碎，但不会影响临床结果。

• DOI: 10.1023/a:1009439800398
• 发表时间: 2000
• 期刊: Journal of assisted reproduction and genetics
• 影响因子: 3.1
• 作者: Frattarelli,JL;Leondires,MP;Miller,BT;Segars,JH
• 通讯作者: Segars,JH

The tangled web of reasons for the delay in diagnosis of endometriosis in women with chronic pelvic pain: will the suffering end?

慢性盆腔疼痛女性子宫内膜异位症诊断延迟的错综复杂的原因：痛苦会结束吗？

• DOI: 10.1016/j.fertnstert.2006.06.044
• 发表时间: 2006
• 期刊: Fertility and sterility
• 影响因子: 6.7
• 作者: Stratton,Pamela

New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2.

DNA 阵列中子宫肌瘤的新潜在调节因子：离子型谷氨酸受体 GluR2。

• DOI: 10.1016/j.bbrc.2003.09.189
• 发表时间: 2003
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Tsibris,JohnCM;Maas,Stefan;Segars,JamesH;Nicosia,SantoV;Enkemann,StevenA;O'Brien,WilliamF;Spellacy,WilliamN
• 通讯作者: Spellacy,WilliamN