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: 7594210
• 负责人: James H. Segars
• 金额: $ 64.31万
• 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/7594210
• 关键词: Accounting; African American; Appearance; Biopsy; Characteristics; Citric Acid Cycle; Clinical; Clinical Investigator; Clinical Research; Color; Couples; Depth; Diagnosis; Disease; Economics; Enzymes; Ethnic group; Event; Female; Fibroid Tumor; Fumarate Hydratase; Genes; Genetic; Glycolysis; Glycolysis Pathway; Gold; Hispanics; Incidence; Infertility; Inherited; Learning; Leiomyoma; Leiomyomatosis; Lesion; Mission; Multicenter Trials; Operative Surgical Procedures; Outcome; Patients; Phosphoglycerate Kinase; Pregnancy Outcome; Protein Overexpression; Provider; Rate; Renal Cell Carcinoma; Reproduction; Reproductive Endocrinology; Research; Reverse Transcriptase Polymerase Chain Reaction; Services; Specimen; Standards of Weights and Measures; Surgeon; Syndrome; Time; Training; Training Programs; Treatment Effectiveness; Uterine Fibroids; Visual; Width; Woman; career; endometriosis; experience; health disparity; interest; racial and ethnic; reproductive; research study; tumor

Uterine leiomyoma, commonly called fibroids, are one of the most common and prevalent diseases of the female reproductive tract.Some leiomyoma are associated with rare genetic syndromes, such as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). In order to learn whether the cellular events associated with HLRCC-associated leiomyoma resembled common or nonsyndromic leiomyoma, in the past year we used gene profiling experiments to compare the two types of leiomyoma. We found that while both types of leiomyoma had low levels of fumarate hydratase, there was a significant overexpression of glycolysis enzymes in the HLRCC-syndromic leiomyoma compared to common leiomyoma. We confirmed overexpression of these genes with real-time reverse-transcriptase PCR. Interestingly, overexpression of the glycolysis enzymes was consistent throughout the glycolysis pathway, with the exception of phosphoglycerate kinase in one HLRCC specimen. We interpret the findings to suggest that the glycolysis pathway is up-regulated in HLRCC leiomyoma, whereas the Krebs cycle function was diminished due to the low levels of fumarate hydratase. In short, these results indicate that while leiomyoma associated with rare syndromes may physically resemble common nonsyndromic leiomyoma, there are marked differences between the tumors. Diagnosis of endometriosis represents a problem for patients and providers since surgery is required, but one persistent question is the appearance of endometriosis lesions at surgery. In the past year Drs. Stratton and Stegmann correlated biopsy result with lesion appearance in order to determine the characteristics of lesions most likely to represent endometriosis. The results showed that, in contrast to prevailing opinion, no single colot had a high association with endometriosis and that surgeons operating on women with endometriosis should consider and biopsy any suspicious lesion. Specifically, subtle lesions were nearly as likely to contain endometriosis as were those that were black or of mixed colors. Overall, the lesions most likely to contain pathologically-confirmed disease were those that were >10mm in width and >5mm in depth. However, experienced surgeons were only able to correctly identify lesions 64% of the time. This study suggests that biopsy, not visual inspection, should remain the gold standard for disease diagnosis. 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. One health disparity idenfied was outcome of infertility treatments. Recently we found that the different incidence of leiomyoma in African-American women explained, at least in part, reduction in pregnancy outcome with assisted reproduction. In the past year we evaluated ART utilization and outcome among Hispanic couples. This study suggested that contrary to claims of some that economic barriers accounted for lower rates of utilization, other factors were responsible. In the coming year we plan to initiate a multicenter trial to assess disparities and utilization of infertility services.

子宫肌瘤，通常称为肌瘤，是女性生殖道最常见和流行的疾病之一。一些子宫肌瘤与罕见的遗传综合征有关，例如遗传性平滑肌瘤病和肾细胞癌（HLRCC）。为了了解与 HLRCC 相关平滑肌瘤相关的细胞事件是否类似于常见或非综合征性平滑肌瘤，在过去的一年中，我们使用基因分析实验来比较两种类型的平滑肌瘤。我们发现，虽然两种类型的平滑肌瘤的富马酸水合酶水平均较低，但与普通平滑肌瘤相比，HLRCC 综合征型平滑肌瘤中糖酵解酶显着过度表达。我们通过实时逆转录酶 PCR 证实了这些基因的过度表达。有趣的是，除了一份 HLRCC 样本中的磷酸甘油酸激酶外，糖酵解酶的过度表达在整个糖酵解途径中是一致的。我们对这些发现的解释是，HLRCC 平滑肌瘤中糖酵解途径上调，而三羧酸循环功能由于富马酸水合酶水平低而减弱。简而言之，这些结果表明，虽然与罕见综合征相关的平滑肌瘤可能在物理上类似于常见的非综合征性平滑肌瘤，但肿瘤之间存在显着差异。 子宫内膜异位症的诊断对患者和提供者来说是一个问题，因为需要进行手术，但一个持续存在的问题是手术时子宫内膜异位症病变的出现。在过去的一年里，博士。 Stratton 和 Stegmann 将活检结果与病变外观相关联，以确定最有可能代表子宫内膜异位症的病变特征。结果表明，与普遍观点相反，没有任何一个结肠与子宫内膜异位症具有高度相关性，对患有子宫内膜异位症的女性进行手术的外科医生应该考虑并活检任何可疑病变。具体来说，细微的病变几乎与黑色或混合颜色的病变一样可能含有子宫内膜异位症。总体而言，最有可能包含病理学确诊疾病的病变是宽度> 10毫米且深度> 5毫米的病变。然而，经验丰富的外科医生只能在 64% 的时间内正确识别病变。这项研究表明，活检，而不是目视检查，应该仍然是疾病诊断的金标准。 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。已确定的一项健康差异是不孕症治疗的结果。最近我们发现，非洲裔美国女性平滑肌瘤的不同发病率至少部分解释了辅助生殖妊娠结局的降低。去年，我们评估了西班牙裔夫妇的 ART 利用率和结果。这项研究表明，与一些人声称的经济障碍导致利用率较低的说法相反，其他因素也是原因之一。来年，我们计划启动一项多中心试验，以评估不孕不育服务的差异和利用情况。