Noncancerous Uterine Diseases Research Program
The uterus is a critical and dynamic organ that is understudied. Mayo Clinic's Noncancerous Uterine Diseases Research Program, led by Ebbie A. Stewart, M.D., studies healthy uterine function and uterine conditions, including uterine fibroids — leiomyomas or myomas — adenomyosis, and uterine-factor infertility. These common conditions cause significant symptoms and, in many people, result in health disparities, particularly for Black and African American individuals. The Noncancerous Uterine Diseases Research Program studies new therapies for these disorders. Researchers also aim to better understand the long-term consequences of the removal of the uterus, also called hysterectomy, which is one of the most widely practiced surgeries worldwide.
Focus areas
Fibroids
Fibroids are noncancerous tumors of the uterus that commonly cause heavy menstrual bleeding, pelvic pain and pressure, and bowel and bladder problems. Fibroids also sometimes cause infertility and pregnancy complications. These tumors also are the leading reason for hysterectomy. For people of African descent, fibroids develop earlier and are more frequent and severe. This makes fibroids a significant cause of health disparities.
Dr. Stewart's team does both basic science research and clinical and translational research on fibroids. The team studies the epidemiology of fibroids, the economics of fibroids and fibroid treatments, and the genetics of fibroids. Dr. Stewart and her team also are developing new methods of fibroid diagnosis and treatment and studying the long-term sequelae of hysterectomy.
Adenomyosis
Adenomyosis is a disease in which tissue that looks like the uterine lining is trapped inside the uterus muscle. Until recently, adenomyosis was thought to occur primarily in women approaching menopause, causing painful and heavy menstrual periods. But new developments suggest it also can play a role in painful menstrual periods and infertility in young women.
Infertility
Infertility is a disease that prevents 1 in 6 people from creating the family that's desired. There are many causes of infertility, including problems with eggs and sperm, but infertility caused by problems in the uterus — referred to as uterine-factor infertility — is less well understood. While fibroids, adenomyosis or both can cause uterine-factor infertility in some people, in other people the uterus can seem healthy but the body has difficulty establishing a pregnancy.
Research activities
Ascertaining Long-Term Outcomes of Fibroid Treatments (ALOFT) study
The ALOFT study attempts to define the long-term outcomes for people who previously participated in one of two earlier studies, the Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) trial or the Uterine Leiomyoma Treatment With Radiofrequency Ablation (ULTRA) trial. ALOFT study participants had one of these four uterine-sparing fibroid treatments as part of the earlier trials:
- Endometrial ablation.
- Laparoscopic radiofrequency ablation.
- Myomectomy.
- Uterine artery embolization.
Researchers are comparing changes in participants' fibroid symptoms and quality of life from before their procedures until up to 10 years after their procedures. The study team also looks at participants whose earlier treatments failed. The team compares the rate of and time until treatment failure for up to 10 years after the initial treatment. Finally, the team aims to identify baseline factors that predict clinical effectiveness of these fibroid treatments.
ALOFT was launched in late 2023 and has three major collaborating institutions:
- Henry Ford Health
- University of California, San Francisco
- University of North Carolina
Funding: R01 HD109127, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Collaboration for Equity in Uterine Leiomyomas (COEQUaL) specialized center for uterine fibroids and health disparities
The COEQUaL specialized center is designated and funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health. Its research goals are to improve outcomes for all people with uterine fibroids and to eliminate health disparities for Black and African American people with these conditions. COEQUaL uses a patient-centric behavioral and social science research approach within the National Institute on Minority Health and Health Disparities Research Framework.
COEQUaL supports three research projects. One project, which focuses on articulating and eliminating individual barriers to fibroid care, provides targeted awareness and education on fibroid symptoms and management options. The goal is to empower patients to collaboratively design values-congruent and culturally appropriate care plans.
Another project examines healthcare system factors that influence health disparities in uterine fibroid treatment. The project team aims to delineate external barriers to getting treatment for fibroids — including insurance barriers and healthcare professional limitations — and identify targeted solutions to these barriers.
A third project focuses on developing innovative tools for the early diagnosis of uterine fibroids, with the goal of overcoming factors that limit positive outcomes for all patients and heighten disparities for Black and African American patients. This project uses technology embedded within the electronic health record to improve risk prediction models and identify patients with fibroids sooner.
The COEQUaL specialized center also has two cores: an Administrative Core and a Community Partnership, Education and Outreach (CPEO) Core. The Administrative Core provides research infrastructure. It also provides the framework for training the next generation of diverse fibroid leaders by funding a pilot project for an early-stage investigator every year. The CPEO core disseminates COEQUaL research findings and serves as the authoritative source of fibroid information on ethical, psychological, scientific, legislative and advocacy issues.
COEQUaL was launched in 2024 and has three collaborating institutions:
- The Fibroid Foundation
- University of Florida College of Medicine — Jacksonville
- University of Mississippi Medical Center
Faculty members are:
- Joyce E. (Joy) Balls-Berry, Ph.D.
- Washington University School of Medicine, St. Louis
- Lori A. Bilello Ph.D., M.B.A., M.H.S.
- University of Florida College of Medicine — Jacksonville
- Andrew M. Kaunitz, M.D., FACOG
- University of Florida College of Medicine — Jacksonville
- Gregory K. Lewis, M.B.B.S.
- University of Florida College of Medicine — Jacksonville
- Sateria Venable
- The Fibroid Foundation
- Kedra M. Wallace, Ph.D.
- University of Mississippi Medical Center
- Fern J. Webb, Ph.D.
- University of Florida College of Medicine — Jacksonville
Funding: P50 HD115283, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Comparing Options for Management: Patient-Centered Results for Uterine Fibroids (COMPARE-UF) registry
COMPARE-UF was a collaborative, prospective registry designed to answer key questions regarding procedural outcomes for patients who received treatment for symptomatic uterine fibroids. It included nine clinical sites across the United States with expertise in treating uterine fibroids and followed participants for three years after treatment. The COMPARE-UF team published significant evidence regarding the efficacy of treatments.
Related publications:
Funding: P50 HS023418, Agency for Healthcare Research and Quality in collaboration with the Patient-Centered Outcomes Research Institute
Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT) study — Comparing uterine artery embolization and MRI-guided focused ultrasound
The FIRSTT study was a randomized controlled trial of uterine artery embolization versus magnetic resonance imaging. The research goal was to determine symptom relief and ovarian function after each treatment. Participants had not completed menopause and had symptomatic uterine fibroids. Volunteers who declined randomization were enrolled in a parallel observational cohort.
The study found that both groups had significant symptom reduction, but individuals undergoing uterine artery embolization experienced normalization of their symptoms, albeit with a more significant decline in ovarian reserve. Participants with lower ovarian function at baseline were less likely to have a second fibroid intervention.
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Funding: RC1 HD063312 and R01 HD060503, Eunice Kennedy Shriver National Institute of Child Health and Human Development
New concepts in the biology and epidemiology of adenomyosis
Adenomyosis is typically characterized as a disease that primarily impacts women in their 40s with heavy menstrual bleeding, often resulting in hysterectomy. However, as image-based diagnosis has become more widespread, it is clear that adenomyosis also affects younger women, including those who have menstrual pain or infertility.
Investigators in the Noncancerous Uterine Diseases Research Program are conducting clinical projects and basic science projects to better define this understudied disease. These include a collaboration with researchers at University of Kansas to understand the role of the RE1-silencing transcription factor (REST) system. Dr. Stewart's team also is working with collaborators at the Karolinska Institute to understand the prolactin system in the uterus.
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Funding: R01 HD105714, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Targeting mechanobiological feedback in uterine fibroids
Uterine fibroids are rich in the extracellular matrix that binds cells together, and this matrix plays an active role in the biology of fibroids. Dr. Stewart's team designed in vitro studies to test the hypothesis that the Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding domain (TAZ) are mechanobiological drivers of uterine fibroid growth and thickening. The team aims to generate new mechanistic insight and open the door to novel therapeutic approaches.
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Understanding the health disparities of uterine fibroids for individuals of African descent
Uterine fibroids occur in approximately 75% of all uteri, and about 25% of fibroids cause heavy menstrual bleeding and symptoms due to their size. However, fibroids are more common and more severe and occur at an earlier age in Black and African American people. This prevalence interacts with personal, system and societal issues in which the people who are most likely to have fibroids also are more likely to have difficulty accessing care and finding the appropriate care. Dr. Stewart's research team considers this issue a public health priority and a key area of study.
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Understanding the economics of uterine fibroid treatments
Recognizing and analyzing the costs and cost effectiveness of fibroid treatments is critically important to understand practice patterns and healthcare costs. The Noncancerous Uterine Diseases Research Program studies economic issues for people with uterine fibroids.
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Understanding the long-term risks of gynecologic surgery for noncancerous conditions
The surgical removal of the uterus, also called hysterectomy, and the surgical removal of the ovary or ovaries, also called oophorectomy, are frequently performed even when there are other options that could spare these organs. Dr. Stewart and colleagues have shown that only 8% of hysterectomies are performed due to cancerous conditions.
In partnership with the Rochester Epidemiology Project medical records linkage system, Dr. Stewart's team examines the long-term consequences of these procedures. Because patients ages 25 to 50 typically undergo these surgeries, it is critical to examine the results in midlife and late life. To date, most of this work is focused on ovary removal.
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The Mayo Clinic Study of Uterine Disease and Health extends this work, focusing on the uterus. The study investigates the hypothesis that the uterus is more than a reproductive organ and aims to delineate the long-term sequela of hysterectomy, even when patients keep both of their ovaries. This ongoing project has already highlighted the increased risk of cardiovascular conditions and mental health concerns after hysterectomy.
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Funding: The Rochester Epidemiology Project is supported by National Institute on Aging grant AG 058738 to Dr. Rocca.
Using artificial intelligence (AI) to improve pregnancy outcomes in frozen embryo transfer
Even with good-quality embryos, approximately half the people who undergo frozen embryo transfer do not achieve a birth. This project uses AI analysis of ultrasounds taken before transfers to enhance the pregnancy rate.
Faculty members are:
- Daniel J. Quest, Ph.D., M.S.
- Mayo Clinic