Search Results (7)

Background: Uterine contractility, also known as uterine peristalsis (UP), is a critical determinant of fertility, affecting sperm transport and embryo implantation. Increased uterine peristaltic activity has been associated with reduced pregnancy rates. However, data are heterogeneous and uterine contractility has not been widely translated into clinical practice. Cine-MRI, although limited by cost and heterogeneity in data reporting, has emerged as a promising tool to assess uterine dynamics and increase our knowledge of UP in physiological and pathological conditions. Objective: This systematic review and meta-analysis aimed to describe patterns of UP in physiological and pathological uterine conditions, including endometriosis and fibroids, using cine-MRI. Methods: A systematic literature search of the Medline, Embase, Cochrane and CENTRAL databases and Google Scholar was conducted up to May 2024, including studies evaluating UP by cine-MRI. Clinical studies evaluating uterine contractility were included, excluding those affected by therapeutic interventions or unrelated pathologies. This meta-analysis pooled data from studies comparing uterine contractility in patients with endometriosis. Results: In the 13 included studies (365 women), uterine contractility varied significantly according to menstrual cycle phases and pathological conditions. This meta-analysis showed that women with endometriosis had higher uterine contractility in the luteal phase (0.74; 95% CI: 0.27–1.21) but not in the periovulatory phase (SMD 0.8; 95% CI: −3.78–5.37). Conclusions: Cine-MRI is a promising diagnostic tool for the analysis of UP. Endometriosis is associated with impaired UP, which may be a cause of the decreased implantation rate and infertility in endometriosis. However, further research is needed to consolidate the effect of UP on implantation and fertility and to develop standardised and cost-effective tools to assess uterine contractility and tailor infertility treatment. Full article

Background: This prospective study aims to identify the effect of the dienogest 2 mg/day and aspirin 150 mg/day combined treatment for two months before frozen ET on the assisted reproduction outcome in women with adenomyosis and recurrent implantation failure (RIF). Methods: Patients were selected based on specific criteria and divided into two groups (with and without treatment). Preimplantation biochemical parameters and ultrasonographic features (endometrial thickness, uterine peristalsis, and junctional zone thickness) were compared with pregnancy rate in a non-natural cycle frozen embryo transfer technique. A comparison between the two study groups indicated an increased successful implantation rate and clinical pregnancy rate (25% vs. 7.4%). Results: These results were attributed to the reduced uterine peristalsis and the reduction in thickness of the junctional zone following treatment. Available data were limited due to the nature of the study though maximal effort was exerted for the selected patients between groups to be as demographically similar and free from other potential pathology that may affect the results. Conclusions: In conclusion, it appears that the above stated treatment improves outcomes in women with adenomyosis and RIF; the parameters used may provide an insight as to the reasons why this occurs, though an explanation of the molecular mechanisms is still elusive. Full article

(1) Background: Abnormal uterine contractility for nonpregnant women has been associated with gynecological pathologies and infertility. The objective of this study was to evaluate the ability of a novel monitoring technique to assess the contractility of the nongravid uterus using a simple, standardized, direct, in vivo methodology during the different phases of the menstrual cycle. (2) Methods: Twenty-six healthy women of reproductive age (28–48 years) were recruited. An ElectroUteroGraph (EUG) was used to measure the electrical activity from the contractility of the junctional zone endometrium (JZE) across the menstrual cycle. Derived recordings were separated into the early proliferative (EP) (n = 10), late proliferative (LP) (n = 31), early luteal (EL) (n = 27), and late luteal (LL) (n = 12) phases of the menstrual cycle. EUG recordings were performed by inserting a flexible electrode array into the endometrial cavity. (3) Results: Waveforms that were measured from the electrode closer to the fundus (1 cm distance) were processed. The Root-Mean-Square (RMS) Voltage Amplitude (VJZE-RMS) (in μV) and the Mean Frequency (fJZE-mean) (in cycles/min) of the JZE’s electrical activity, as direct indicators of the intensity and frequency changes in the JZE’s contractions, were extracted from the recorded waveforms. There was a trend in the median values of the VJZE-RMS decreasing from the EP to the LP phase (247–158 μV). During the EL phase, an upward trend was observed (158–374 μV, p < 0.05), reaching its highest value during the LL phase (374–477 μV, p < 0.05) when compared to the LP phase. The fJZE-mean showed the opposite trend, increasing from 2.5 cycles/min during the EP phase to 2.96 cycles/min during the LP phase. During the EL phase, a downward trend was observed (2.96–2.37 cycles/min), continuing to fall to 1.33 cycles/min, in the LL phase, with p < 0.05 when compared to the previous three phases. (4) Conclusions: The novel in vivo monitoring technique has shown clinically, for the first time, significant electrical activity differences in the different sub-phases of the menstrual cycle, recorded in a safe and painless way. Full article

The main function of interstitial cells of Cajal (ICCs) is to regulate gastrointestinal peristalsis by acting as a “pacemaker” cell by generating spontaneous slow electrical waves. In 2005, electron microscopy revealed a cell type similar to ICCs (ICC-like) outside the gastrointestinal tract, with contractile activity and c-Kit⁺ immunohistochemistry shared with ICCs. Among the locations where ICC-like cells have been observed, it is in the uterus where they have a significant functional and pathophysiological role. These cells are involved in obstetric phenomena of contractile action, such as ascending sperm transport, embryo implantation, pregnancy, delivery, and the expulsion of menstrual debris. Within the pathophysiology related to these cells, we find obstetric alterations such as recurrent miscarriages, premature deliveries, abolition of uterine contractions, and failures of embryo implantation, in addition to other common conditions in the fertile age, such as endometriosis and leiomyoma. Full article

As understanding their pathogenesis remains elusive, both endometriosis and adenomyosis are often referred to as “enigmatic diseases”. The uncertainty and heightened interest are reflected in the range of expressed views and opinions. There is a sense of urgency because of the entailed patient suffering. The plethora of opinions calls for a critical analysis of proposed theories, both old and new. A series of papers published since 2009 proposed that both endometriosis and adenomyosis originate from the same aberrations occurring within the uterus. This came to be recognized as the tissue injury and repair theory, and the newly coined term “archimetrosis” posits that the two diseases share the same origin. While the theory opens an interesting channel for exploration, its claim as a unifying theory necessitates a critical appraisal. We, thus, undertook this review of the theory and analyzed its underpinnings based on a comprehensive review of the literature. Our appraisal indicates that the theory is open to a range of criticisms. Chief among these is the need for confirmatory evidence of features of abnormal uterine contractility and the lack of data addressing the question of causality. In addition, the theory has, as yet, no supporting epidemiological evidence, which is a major weakness. The theory suffers as it is not open to the test of falsifiability, and it lacks the ability to make useful predictions. It has not addressed the questions, such as why only a small percentage of women develop adenomyosis or endometriosis, given the ubiquity of uterine peristalsis. On the other hand, the triggers and prevention of hyper- or dys-peristalsis become critical to a theory of causation. We conclude that additional supportive evidence is required for the theory to be accepted. Full article

Myometrium plays critical roles in multiple processes such as embryo spacing through peristalsis during mouse implantation, indicating vital roles of smooth muscle in the successful establishment and quality of implantation. Actin, a key element of cytoskeleton structure, plays an important role in the movement and contraction of smooth muscle cells (SMCs). However, the function of peri-implantation uterine smooth muscle and the regulation mechanism of muscle tension are still unclear. This study focused on the molecular mechanism of actin assembly regulation on implantation in smooth muscle. Phalloidin is a highly selective bicyclic peptide used for staining actin filaments (also known as F-actin). Phalloidin staining showed that F-actin gradually weakened in the CD-1 mouse myometrium from day 1 to day 4 of early pregnancy. More than 3 mice were studied for each group. Jasplakinolide (Jasp) used to inhibit F-actin depolymerization promotes F-actin polymerization in SMCs during implantation window and consequently compromises embryo implantation quality. Transcriptome analysis following Jasp treatment in mouse uterine SMCs reveals significant molecular changes associated with actin assembly. Tagln is involved in the regulation of the cell cytoskeleton and promotes the polymerization of G-actin to F-actin. Our results show that Tagln expression is gradually reduced in mouse uterine myometrium from day 1 to 4 of pregnancy. Furthermore, progesterone inhibits the expression of Tagln through the progesterone receptor. Using siRNA to knock down Tagln in day 3 SMCs, we found that phalloidin staining is decreased, which confirms the critical role of Tagln in F-actin polymerization. In conclusion, our data suggested that decreases in actin assembly in uterine smooth muscle during early pregnancy is critical to optimal embryo implantation. Tagln, a key molecule involved in actin assembly, regulates embryo implantation by controlling F-actin aggregation before implantation, suggesting moderate uterine contractility is conducive to embryo implantation. This study provides new insights into how the mouse uterus increases its flexibility to accommodate implanting embryos in the early stage of pregnancy. Full article

It is well-known that the physiological uterine peristalsis, related to several phases of reproductive functions, plays a pivotal role in fertility and female reproductive health. Here, we have addressed the role of hydrogen sulfide (H₂S) signaling in changes of uterine contractions driven by diabetes in non-obese diabetic (NOD) mice, a murine model of type-1 diabetes mellitus. The isolated uterus of NOD mice showed a significant reduction in spontaneous motility coupled to a generalized hypo-contractility to uterotonic agents. The levels of cyclic nucleotides, cAMP and cGMP, notoriously involved in the regulation of uterus homeostasis, were significantly elevated in NOD mouse uteri. This increase was well-correlated with the higher levels of H₂S, a non-specific endogenous inhibitor of phosphodiesterases. The exposure of isolated uterus to L-cysteine (L-Cys), but not to sodium hydrogen sulfide, the exogenous source of H₂S, showed a weak tocolytic effect in the uterus of NOD mice. Western blot analysis revealed a reorganization of the enzymatic expression with an upregulation of 3-mercaptopyruvate-sulfurtransferase (3-MST) coupled to a reduction in both cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) expression. In conclusion, the increased levels of cyclic nucleotides dysregulate the uterus peristalsis and contractility in diabetic mice through an increase in basal H₂S synthesis suggesting a role of 3-MST. Full article