Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.

The Role of Nanomedicine in Benign Gynecologic Disorders.

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.

Patient Experiences With Obstetric Counseling on Fetal Malpresentation.

Introduction Fetal malpresentation is a complication of pregnancy in which the fetus does not present cephalically as required for vaginal birth. After a diagnosis is made, management options include cesarean section (CS) or external cephalic version (ECV). ECV is a procedure in which providers attempt to manually maneuver the fetus to cephalic position, allowing patients to attempt vaginal birth. Selecting between CS or ECV can be a complex and stressful decision, yet literature exploring patient perspectives on counseling of these options is limited. This study aims to describe patient perspectives on decision-making when diagnosed with fetal malpresentation. Methods We included English-speaking pregnant patients greater than 18 years of age diagnosed with malpresentation at 35-37 weeks' gestation. Patients who previously underwent CS or had maternal or fetal contraindications besides malpresentation to vaginal birth requiring CS were excluded. Semi-structured interviews were conducted with participants from four obstetric clinics in Baltimore, Maryland, at time of diagnosis. Themes were derived using data analysis in NVivo 11 (released 2015, Lumivero, USA). Results We recruited 10 participants (median age = 32 years, 90% Caucasian, 70% nulliparous, 50% chose ECV). We categorized our findings into the following themes: (1) facilitators and (2) barriers to deciding on malpresentation management, (3) participant priorities and values, and (4) other methods of malpresentation management. The participants identified incorporation of statistics and medical history into counseling as facilitators and the lack of information about ECV as a significant barrier. The participants prioritized fetal safety and, among those who chose ECV, a desire to avoid CS. Chiropractors, acupuncture, and moxibustion were identified as valuable additional methods of malpresentation management. Conclusion Overall, patients desire more information about ECV when diagnosed with fetal malpresentation. Uncertainty about ECV safety is a barrier to deciding between management options. Based on our findings, obstetric providers should provide comprehensive counseling on ECV and CS. Counseling should aim to demystify ECV and quantify risk in a patient-specific context. This will allow patients to make an informed decision on the management of fetal malpresentation that aligns with their goals for pregnancy.