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Home > Unit on Reproductive Endocrinology and Infertility

Reproductive Endocrinology and Infertility

James Segars, MD
  • James Segars, MD, Head, Unit on Reproductive Endocrinology and Infertility
  • Alicia Armstrong, MD, Associate Fellowship Program Director, Reproductive Endocrinology and Infertility
  • Hyacinth Browne, MD, Clinical Fellow
  • William H. Catherino, MD, PhD, Special Volunteer
  • Xiaoxiao C. Guo, Student Fellow
  • Hisashi Koide, MD, PhD, Visiting Postdoctoral Fellow
  • John Norian, MD, Research Fellow
  • Carter M. Owen, BA, BS, Fellow, Clinical Research Training Program
  • Pamela Stratton, MD, Head, Gynecology Consult Service

The Unit on Reproductive Endocrinology and Infertility supports basic, translational, and clinical studies of clinically-relevant reproductive disorders. Current research focuses on uterine leiomyomas (fibroids), endometriosis, health disparities, and reproductive disorders leading to infertility in women. We also support the accredited, NICHD-supported Clinical Fellowship Program in Reproductive Endocrinology and Infertility.

Uterine leiomyomas

Uterine fibroids are a highly prevalent disease, but the fundamental causes of leiomyoma growth and development remain poorly understood. Our past studies suggested that the altered extra cellular matrix (ECM) in fibroids might affect fibroid growth and development. In the past year, we found that dysregulated expression of ATF-3 was a possible link between mechanical stress and fibroid development. In another study, we found that elevated levels of TGF-beta in fibroids led to increased expression of the ECM protein versican. Also during the past year, in a collaborative effort with Bradford Wood and Aradhana Venkatesan, the Unit began a trial of MRI-guided high frequency ultrasound (HIFU) treatment for fibroids. In addition, we completed analysis of a case series for the possible impairment of ovarian function by myomectomy (removal of fibroids). In the coming year, we plan to dissect the altered mechanical signaling in fibroids in greater detail and to expand studies of HIFU as a treatment modality for uterine fibroids.

Role of BRX (also known as AKAP13) in osmotic stress and inflammation

We continued to study the protooncogene BRX (also known as AKAP13), which we cloned, and the murine model of targeted deletion of the BRX gene. In collaboration with Tomoshige Kino, studies in the past year focused on the reduced size of the spleen in haplo-insufficient mice. Investigation of the phenotype led to the discovery that BRX was involved in the response of lymphocytes to osmotic stress. In fact, BRX was found to be an essential factor for activation of the nuclear factor of activated t-cells 5 (NFAT5) via a p38MAPK-dependent cascade with JIP4. This observation indicates that BRX is a link to integrate osmotic stress and inflammation. In the coming year, we plan to further characterize the role of BRX in development and cancer, using our murine model.

Assessment and preservation of ovarian function in women and girls undergoing cancer treatment

Many young girls and women who are cancer survivors find their reproductive function irreparably damaged by chemotherapy or radiation. In the past year, the Unit tested a murine model of medical treatment prior to chemotherapy. The model confirmed efficacy of pre-treatment with GnRH-therapy, which appeared to act by reducing apoptosis in ovaries of pre-treated mice. In the coming year, we plan to investigate the mechanism by which GnRH-antagonist functions in the murine model and launch a clinical study of GnRH-agonist treatment prior to chemotherapy in young women.

Infertility and reproductive health disparities

Our Unit has continued to conduct studies of infertility and reproductive health disparities. In the past year, Alicia Armstrong was an investigator in a study of racial disparities in reproductive health in over 130,000 IVF cycles. The study supported our prior work and revealed that the likelihood of live birth was reduced in women of African-American and Asian women. The reasons for this disparity remain unclear. To encourage research on reproductive health disparities, Armstrong chaired a meeting at NIH on Reproductive Problems in Women of Color. The meeting spawned new studies and collaborations. During the past year, we also continued clinical studies of infertility related to evidence-based and cost-effective infertility care. We modeled the effect of age and FSH levels on the cost of a live-born child at assisted reproduction. In another study, we examined the difference between age-related increases in FSH and increases in FSH prior to age 35. In the coming year, we plan to examine the pathophysiology underlying ovarian hyperstimulation syndrome (OHSS), a major risk factor for women pursuing assisted reproductive technologies.

Endometriosis and chronic pelvic pain

In the past year, in collaboration with Lynette Nieman, Pamela Stratton concluded a study of raloxifene for treatment of endometriosis-related pelvic pain. Contrary to expectations, raloxifene appeared to hasten, not prevent, the recurrence of pelvic pain. In collaboration with Rebecca Greene and Ninet Sinaii, the group led by Stratton also examined the relationship between disease severity and patient characteristics from 1,000 women with endometriosis. Using this approach, the group devised a model of the characteristics of endometriosis lesions that were associated with pain. In the coming year, the group will conclude a clinical study of the hypothalamic pituitary-adrenal-axis in women with chronic pelvic pain and endometriosis.

Additional Funding

  • ZO1 HD-008737-09

Publications

  • Rogers R, Norian J, Malik M, Christman G, Abu-Asab M, Chen F, Korecki C, Iatridis J, Catherino W, Tuan R, Dhillon N, Leppert P, Segars JH. Mechanical homeostasis is altered in uterine leiomyoma. Am J Obstet Gynecol 2008 198:474.e1-e11.
  • Stratton P, Sinaii N, Segars J, Koziol D, Wesley R, Zimmer C, Winkel C, Nieman LK. Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial. Obstet Gynecol 2008 111:88-96.
  • Kino T, Takatori H, Manoli I, Wang Y, Tiulpakov A, Blackman MR, Su YA, Chrousos GP, DeCherney AH, Segars JH. Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT. Sci Signal 2009 2:ra5.
  • Payson M, Malik M, Morris SSN, Segars JH, Chason R, Catherino WH. Activating transcription factor 3 gene expression in uterine leiomyoma: a molecular link between tissue stress and leiomyoma development. Fertil Steril 2009 92:748-755.
  • Henne MB, Stegmann BJ, Neithardt AB, Catherino WH, Armstrong AY, Kao T-C, Segars JH. The combined effect of age and basal FSH on the cost of a live birth at ART. Fertil Steril 2008 89:104-110.

Collaborators

  • Faye Chen, PhD, Cartilage Biology and Orthopaedics Branch, NIAMS, Bethesda, MD
  • Paul Driggers, PhD, Uterine Fibroid Tissue Bank, USUHS-NICHD, Bethesda, MD
  • Rebecca Greene, BA, Reproductive Biology and Medicine Branch, NICHD, Bethesda, MD
  • Tomoshige Kino, PhD, Program in Reproductive and Adult Endocrinology, NICHD, Bethesda, MD
  • Phyllis Leppert, MD, PhD, Duke University, Durham, NC
  • Lawrence Nelson, MD, Program in Reproductive and Adult Endocrinology, NICHD, Bethesda, MD
  • Lynnette Nieman, MD, Program in Reproductive and Adult Endocrinology, NICHD, Bethesda, MD
  • Steven Z. Pavletic, MD, Experimental Transplantation and Immunology Branch, NCI, Bethesda, MD
  • Mark Payson, MD, Uniformed Services University of the Health Sciences, Bethesda, MD
  • Ninet Sinaii, MPH, PhD, Office of the Deputy Director for Clinical Care, Clinical Center, NIH, Bethesda, MD
  • Rocky Tuan, PhD, Cartilage Biology and Orthopaedics Branch, NIAMS, Bethesda, MD
  • Aradhana Venkatesan, MD, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD
  • Heiner Westphal, MD, Program in Genomics of Differentiation, NICHD, Bethesda, MD
  • Bradford J. Wood, MD, Center for Interventional Oncology, NIH Clinical Center, Bethesda, MD

Contact

For more information, email segarsj@mail.nih.gov.

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