This article in the Women’s Health series discusses uterine perforation occurring during gynecological procedures, including prevention, identification of risk factors, recognition, management, and long-term outcomes.
Uterine factor infertility (UFI) may affect up to 1 in 500 reproductive age women. The uterus is an essential component of achieving pregnancy and carrying a pregnancy to term successfully. There are many etiologies of UFI which may be categorized into either congenital or acquired causes. In this review, we discuss the different causes of UFI as well as the treatment options, which now includes uterine transplant.
Endometriosis is a leading cause of pelvic pain and infertility. It is defined by the presence of endometrial tissue in extrauterine locations. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Outside of primates, few mammals menstruate, and none develop spontaneous endometriosis. Rodent models are popular but require artificial induction of endometriosis, with many utilizing either immunocompromised mice or surgically induced disease. Recently, more attention has been given to models involving intraperitoneal injection. We present a murine model of endometriosis that integrates several features of existing endometriosis models into a novel, simplified system that relies on microscopic quantification in lieu of subjective grading. In this model, we perform hormonal stimulation of donor mice, intraperitoneal injection, systematic abdominal survey and tissue harvest, and histologic quantification that can be performed and verified at any time after necropsy. This model requires minimal resources and training; does not require expertise by lab technicians in murine survival surgery or in the identification of gross endometriotic lesions; can be used in immunocompromised, immunocompetent, and/or mutant mice; and reliably creates endometriotic lesions that are histologically consistent with human endometriotic disease.
<i>Background/Aims:</i> Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system activation are crucial in the pathogenesis of hypertension, cardiovascular and renal disease. NADPH oxidase-mediated increases in reactive oxygen species (ROS) are an important mediator for RAAS-induced cardiovascular and renal injury. Increased levels of ROS can diminish the bioactivity of nitric oxide (NO), a critical modulator of RAAS effects on the kidney. Thereby, we hypothesized that in vivo nebivolol therapy in a rodent model of activated RAAS would attenuate glomerular damage and proteinuria through its actions to reduce NADPH oxidase activity/ROS and increase bioavailable NO. <i>Methods:</i> We utilized the transgenic Ren2 rat which displays heightened tissue RAAS, hypertension, and proteinuria. Ren2 rats (6–9 weeks of age) and age-matched Sprague-Dawley littermates were treated with nebivolol 10 mg/kg/day (osmotic mini-pump) for 21 days. <i>Results:</i> Ren2 rats exhibited increases in systolic blood pressure, proteinuria, kidney cortical tissue total NADPH oxidase activity and subunits (Rac1, p67<sup>phox</sup>, and p47<sup>phox</sup>), ROS and 3-nitrotyrosine, as well as reductions in podocyte protein markers; each of these parameters improved with nebivolol treatment along with increases in renal endothelial NO synthase expression. <i>Conclusions:</i> Our data suggest that nebivolol improves proteinuria through reductions in renal RAAS-mediated increases in NADPH oxidase/ROS and increases in bioavailable NO.
Endometriomas are a unique and complex representation of the classic phenotypes of endometriosis. Associated symptoms, high recurrence rate, and multimodal approach represent ongoing challenges in the management of this chronic disease.To review current literature regarding medical and surgical management of endometriomas.An extensive literature search including PubMed and Cochrane Library was performed. Review was performed using the following key words: "endometrioma," "cystectomy," "chronic pain," "infertility," "IVF," "menopause," "recurrence." All pertinent articles were assessed. The references of those articles were then reviewed, and additional publications were evaluated. Eligibility of the studies was first assessed on titles and abstracts. Full articles were then reviewed for all selected studies, and decision for final inclusion was made at that time.Cystectomy of ovarian endometriomas has been the first-line treatment for management for many years because it provides improved pain relief, reduces recurrence rates, and was thought to be favorable in in vitro fertilization. However, a growing body of evidence is demonstrating benefit, or at least no harm, in expectant management for asymptomatic patients with small, stable endometriomas. Medical management is often very effective and appropriate first line. When surgical intervention is appropriate, careful ovarian cyst excision with goal of ovarian tissue preservation and treatment of additional endometriosis by a trained surgeon can provide the patient the best long-term outcome and preservation of ovarian tissue and function.
Emerging evidence indicates that mineralocorticoid receptor (MR) blockade reduces the risk of cardiovascular events beyond those predicted by its blood pressure–lowering actions; however, the underlying mechanisms remain unclear. To investigate whether protection elicited by MR blockade is through attenuation of vascular apoptosis and injury, independently of blood pressure lowering, we administered a low dose of the MR antagonist spironolactone or vehicle for 21 days to hypertensive transgenic Ren2 rats with elevated plasma aldosterone levels. Although Ren2 rats developed higher systolic blood pressures compared with Sprague-Dawley littermates, low-dose spironolactone treatment did not reduce systolic blood pressure compared with untreated Ren2 rats. Ren2 rats exhibited vascular injury as evidenced by increased apoptosis, hemidesmosome-like structure loss, mitochondrial abnormalities, and lipid accumulation compared with Sprague-Dawley rats, and these abnormalities were attenuated by MR antagonism. Protein kinase B activation is critical to vascular homeostasis via regulation of cell survival and expression of apoptotic genes. Protein kinase B serine 473 phosphorylation was impaired in Ren2 aortas and restored with MR antagonism. In vivo MR antagonist treatment promoted antiapoptotic effects by increasing phosphorylation of BAD serine 136 and expression of Bcl-2 and Bcl-xL, decreasing cytochrome c release and BAD expression, and suppressing caspase-3 activation. Furthermore, MR antagonism substantially reduced the elevated NADPH oxidase activity and lipid peroxidation, expression of angiotensin II, angiotensin type 1 receptor, and MR in Ren2 vasculature. These results demonstrate that MR antagonism protects the vasculature from aldosterone-induced vascular apoptosis and structural injury via rescuing protein kinase B activation, independent of blood pressure effects.
