Increased Uterine Contractility Research Articles

Evaluation of the Efficacy and Safety of Dienogest in the Treatment of Primary Dysmenorrhea: A Study in a District-Level Hospital in Bangladesh

Background: Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. Objectives: The aim of this study is to evaluate of the efficacy and safety of dienogest in the treatment of primary dysmenorrhea: a study in a district-level hospital in Bangladesh. Methods: The cross-sectional observational study was conducted in the Department of Gynae and Obs, Naogaon Sadar Hospital from July 2022 to June 2023. A total of 100 subjects who received DNG (1 mg/day, orally) were included in the study. Data were collected by face-to-face interview and analyzed by appropriate computer based programmed software Statistical Package for the Social Sciences (SPSS), version 24. Results: In this study, most of the patients 43% lies between 21 years to 25 years and body weight of 24% patients were between 51 to 55 kg. In this study, most of the patients 41% body mass index were 18.5 – 24.9 kg/m2. Most of the patients’ clinical symptoms were cramping pain in the lower abdomen (89%), low back pain (86%), pain spreading down to the leg (73%), fatigue (64%). About (56%) adverse effects were body weight gain and irregular uterine bleeding occurred in 35 of 100 cases (35%). Conclusion: Primary dysmenorrhea is one of the most common illnesses in women of childbearing age. When severe, it may interfere with the activities of daily living and may lead to school and work absenteeism. Primary dysmenorrhea is also one of the most underdiagnosed diseases, so clinicians should suspect the diagnosis in a timely manner and provide appropriate treatment.

Contemporary management of arrhythmias in pregnancy: efficacy and outcomes of catheter ablation without fluoroscopy

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart rhythm disorders are the most common cardiac complication occurring in pregnancy. Haemodynamically unstable and drug refractory arrhythmias warrant catheter ablation. However, there are little data of efficacy and outcomes of catheter ablation in pregnant women. Purpose To assess efficacy and outcomes of catheter ablation without of fluoroscopy in pregnant women. Methods This single center, prospective study included all cases of catheter ablation during gestation (n=48, study group) and pregnant women with antiarrhythmic drug therapy (n=50, control group). Complications, pregnancy course, obstetric and neonatal outcomes were determined and compared. Results The most common reported arrhythmias in both groups was supraventricular tachycardia (n=39; 81% vs n=31; 62%, p=0.045). Premature contractions was in 13% cases in study group and 32% in control group (p=0.029). Ventricular tachycardia was rare during pregnant (n=3; 6% vs n=3; 6%, p=1.0). All ablation procedures were performed without fluoroscopy (mean gestation age 24,21±3,32 weeks, mean procedural time of 71±15 minutes). In one women in study group occurred ileofemoral thrombosis, which was treated successfully. Pregnancy course was benign in all women in both group without termination. Uterine blood flow violation was in 12.5% in study group and in 8% - in control (p=0.520). Increased uterine contractility occurred only in women with catheter ablation (n=2; 4.2%, p=0.237). Type of delivery was vaginal in the majority in both groups (n=36; 75% vs n=40; 80%, p=0.553). Operative delivery was rare (n=12; 25% vs n=10; 20%, p=0.553), mainly due to obstetric indications. In 2 cases in study group were placental abraption (vs n=0, p=0.237) and preeclampsia (vs n=1; 2%, p=0.613). There were live births in all cases without maternal and fetal mortality. During 1 year follow-up there was no arrhythmia recurrence in study group. Conclusions Catheter ablation in pregnant women is safe and effective and can be performed without fluoroscopy. Majority of women with arrhythmias have benign course of pregnancy and perinatal outcomes

A single-cell atlas of the myometrium in human parturition.

Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type–specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.

Acupuncture Alleviates Menstrual Pain in Rat Model via Suppressing Eotaxin/CCR3 Axis to Weak EOS-MC Activation.

Introduction Emerging data show that chemokine-mediated inflammation is involved in the occurrence and maintenance of pain. Recent evidence suggests that eotaxin levels rise when dysmenorrhea happens. The purpose of this study is to investigate whether eotaxin/CC chemokine receptor 3 (CCR3) axis, a key regulatory pathway for eosinophils (EOS) recruitment, is involved in acupuncture analgesia for dysmenorrhea. Methods After the cold congealing dysmenorrhea (CCD) rat model prepared, animals received perpendicular needling (PN) and transverse needling (TN) at SP6, respectively, for 20 min. The CCR3 agonist CCL11 was administered 30 min prior to acupuncture. Pain behavior was assessed via a writhing response. The uterine contraction test was detected by an electrophysiological method. Eotaxin, histamine (HIS), and interleukin-6 (IL-6) levels were evaluated by ELISA. The expression of CCR3 and histamine H1 receptor (H1R) was analyzed by RT-qPCR and Western blot. The expression of EOS, mast cells (MCs), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP) was assessed by hematoxylin-eosin staining (HE), Toluidine Blue staining (TB), and immunohistochemistry, respectively. Results Acupuncture prominently attenuated the menstrual pain in CCD rats, particularly TN technique. Electrophysiological recording data showed that the increased uterine contractility was ameliorated by acupuncture. In addition, TN decreased the release of eotaxin, HIS, IL-6, and the expression of CCR3 and H1R. HE, TB staining, and immunohistochemistry experiments showed that the increased expression of EOS, MCs, EPO, and ECP in uterine tissues was reversed by TN. Furthermore, we found that the effects of TN against CCD-induced menstrual pain, increased ECP expression, and HIS level were abolished by CCL11. Conclusion TN alleviated menstrual pain by improving the uterine inflammatory environment via suppressing eotaxin/CCR3 axis to weak EOS-MC activation in CCD rats. The study findings support the acupuncture as a promising approach for dysmenorrhea, meanwhile, indicating the importance of performing appropriate needling technique.

Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility

Uterine contractile dysfunction leads to pregnancy complications such as preterm birth and labor dystocia. In humans, it is hypothesized that progesterone receptor isoform PGR-B promotes a relaxed state of the myometrium, and PGR-A facilitates uterine contraction. This hypothesis was tested in vivo using transgenic mouse models that overexpress PGR-A or PGR-B in smooth muscle cells. Elevated PGR-B abundance results in a marked increase in gestational length compared to control mice (21.1 versus 19.1 d respectively, P < 0.05). In both ex vivo and in vivo experiments, PGR-B overexpression leads to prolonged labor, a significant decrease in uterine contractility, and a high incidence of labor dystocia. Conversely, PGR-A overexpression leads to an increase in uterine contractility without a change in gestational length. Uterine RNA sequencing at midpregnancy identified 1,174 isoform-specific downstream targets and 424 genes that are commonly regulated by both PGR isoforms. Gene signature analyses further reveal PGR-B for muscle relaxation and PGR-A being proinflammatory. Elevated PGR-B abundance reduces Oxtr and Trpc3 and increases Plcl2 expression, which manifests a genetic profile of compromised oxytocin signaling. Functionally, both endogenous PLCL2 and its paralog PLCL1 can attenuate uterine muscle cell contraction in a CRISPRa-based assay system. These findings provide in vivo support that PGR isoform levels determine distinct transcriptomic landscapes and pathways in myometrial function and labor, which may help further the understanding of abnormal uterine function in the clinical setting.

Uterine contractility changes in a perfused swine uterus model induced by local anesthetics procaine, lidocaine, and ropivacaine.

BackgroundLocal anesthetics (LAs) are increasingly used as therapeutics due to their multiple molecular effects. They may be potential agents also in gynecology and reproductive medicine. The objective of this study was to investigate the contractility response of the perfused swine uterus to different concentrations of the LAs procaine, lidocaine, and ropivacaine.Methods and findingsIn an extracorporeal perfusion model with fresh swine uteri, effects of administered boli of these three LAs in concentrations of 0.1 mg/mL, 0.5 mg/mL and 1.0 mg/mL on uterine contractility and peristalsis were assessed using an intrauterine double-chip micro-catheter. A dose-dependent increase in intrauterine pressure (IUP) in the isthmus and corpus uteri was observed after the administration of the ester-LA procaine 0.1, 0.5, and 1.0%, which was not seen with lower concentrations, or buffer solution. An increase-decrease curve was found after increasing concentrations of the amide-LA lidocaine and ropivacaine, with an IUP plateau with 0.1 and 0.5%, and a decrease with 1% (p<0.01). All reactions were seen in both the isthmus and corpus uteri. The difference of the contractility pattern between ester- and amide-LA at 1% concentration was significant.ConclusionLAs dose-dependently modulate contractility in non-pregnant swine uteri. The amid-LAs lidocaine and ropivacaine reduce contractility in higher concentrations and may be used as therapeutics in disorders with increased uterine contractility, as dysmenorrhoea, endometriosis, and infertility. The multiple molecular effects of LAs may explain these effects. This in-vitro pilot study in vitro provides initial data for designing further studies to transfer the results onto humans.

Dysmenorrhea and related disorders.

Dysmenorrhea is a common symptom secondary to various gynecological disorders, but it is also represented in most women as a primary form of disease. Pain associated with dysmenorrhea is caused by hypersecretion of prostaglandins and an increased uterine contractility. The primary dysmenorrhea is quite frequent in young women and remains with a good prognosis, even though it is associated with low quality of life. The secondary forms of dysmenorrhea are associated with endometriosis and adenomyosis and may represent the key symptom. The diagnosis is suspected on the basis of the clinical history and the physical examination and can be confirmed by ultrasound, which is very useful to exclude some secondary causes of dysmenorrhea, such as endometriosis and adenomyosis. The treatment options include non-steroidal anti-inflammatory drugs alone or combined with oral contraceptives or progestins.

Molecular Regulation of Parturition: A Myometrial Perspective.

The molecular mechanisms that maintain quiescence of the myometrium throughout most of pregnancy and promote its transformation to a highly coordinated contractile unit culminating in labor are complex and intertwined. During pregnancy, progesterone (P4) produced by the placenta and/or ovary serves a dominant role in maintaining myometrial quiescence by blocking proinflammatory response pathways and expression of so-called "contractile" genes. In the majority of placental mammals, increased uterine contractility near term is heralded by an increase in circulating estradiol-17β (E2) and/or increased estrogen receptor α (ERα) activity and a sharp decline in circulating P4 levels. However, in women, circulating levels of P4 and progesterone receptors (PR) in myometrium remain elevated throughout pregnancy and into labor. This has led to the concept that increased uterine contractility leading to term and preterm labor is mediated, in part, by a decline in PR function. The biochemical mechanisms for this decrease in PR function are also multifaceted and interwoven. In this paper, we focus on the molecular mechanisms that mediate myometrial quiescence and contractility and their regulation by the two central hormones of pregnancy, P4 and estradiol-17β. The integrative roles of microRNAs also are considered.

Menstrual Disorders

Menstrual Disorders

Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis

To evaluate uterine contractility, oxytocin receptor (OTR) expression in myometrial smooth muscle cells (MSMCs) derived from uterine tissues from women with and without adenomyosis correlate OTR expression with uterine contractility and dysmenorrhea severity, and see whether trichostatin A (TSA) and andrographolide inhibit OTR expression. Laboratory study using human tissues. Academic hospital. Twenty patients (cases) with histologically confirmed adenomyosis and 10 (controls) with leiomyomas, cervical dysplasia, and cancer but no adenomyosis or endometriosis. Dysmenorrhea severity was scored by Visual Analog Scale. Uterine tissue samples were collected during hysterectomy. Myometrial smooth muscle cells derived from tissue samples were cultured and OTR protein levels were measured. The effect of TSA (0.5 or 1 μM) and andrographolide (15 or 30 μM) on OTR expression was evaluated. Visual Analog Scale scores, and contractile amplitude and frequency. The OTR protein levels in MSMCs were quantified by Western blot analysis. The contractile amplitude and OTR expression levels were significantly higher in cases than in controls. Dysmenorrhea Visual Analog Scale scores correlated positively with contractile amplitude and OTR expression level. Both TSA and andrographolide dose-dependently inhibit OTR expression in MSMC. Oxytocin receptor overexpression in MSMCs may be responsible for increased uterine contractility and adenomyosis-associated dysmenorrhea. Both histone deacetylase inhibitors and andrographolide are therapeutically promising.

In vitro Myometrial Contractility Profiles of Different Pharmacological Agents Used for Induction of Labor

To investigate the effects of different pharmacological induction agents on myometrial contractility. Myometrial biopsies were obtained from 13 term nonlaboring women undergoing scheduled cesarean delivery. Tissue strips were suspended in organ chambers for isometric tension recording. The effects of cumulative doses (10-10 mol/L to 10-5 mol/L) of prostaglandin E1 (PGE1), E2 (PGE2), and oxytocin on spontaneous uterine contractility were determined. Areas under the contraction curve were compared using one-way analysis of variance on ranks with Dunn post hoc test. Oxytocin-induced myometrial contractility was superior to PGE1, PGE2, and time controls (CTR) at all the concentrations tested. When only prostaglandins were compared with CTR, PGE1 10-5 mol/L increased myometrial contractility, and PGE2 had no effects. Oxytocin and prostaglandins have different effects on myometrial contractility accounting for different mechanisms of action and side effects. The increased uterine contractility observed with PGE1 as compared with PGE2 can contribute to explain the higher success of vaginal delivery.

The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?

Objective: The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. Methods: Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). Results: (1) Intra-amniotic inflammation was present in 12.1% (16/132); (2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and (3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < 0.05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. Conclusion: Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes.

Ultrasound Markers of Implantation

ABSTRACT Endometrial 3D power Doppler indices change significantly during the normal menstrual cycle. Vascularity indices of the endometrial and subendometrial vessels increase throughout the proliferative phase of the menstrual cycle, reaching a maximum value 2 to 3 days prior to ovulation. From this peak, vascularity indices decrease and reach a nadir 2 to 5 days after ovulation. Reduced endometrial perfusion assessed by 3D power Doppler ultrasound is most likely related to increased uterine contractility. If prolonged, it may cause endometrial hypoxia, leading to detrimental effect on implantation potential. In normal spontaneous menstrual cycles, endometrial vascular indices increase progressively during the course of the luteal phase. Endometrial and subendometrial perfusion is negatively affected by serum estradiol concentrations, which can explain why patients with hyperstimulation have lower endometrial and subendometrial blood flow during the early luteal phase. Our results indicate that 3D power Doppler implantation markers are crucial for planning a single embryo transfer in order to select the most suitable cycle for transfer of a single cryopreserved embryo. How to cite this article Mercé LT, Barco MJ, Kurjak A. Ultrasound Markers of Implantation. Donald School J Ultrasound Obstet Gynecol 2012;6(1):14-26.

The Retardation of Myometrial Infiltration, Reduction of Uterine Contractility, and Alleviation of Generalized Hyperalgesia in Mice With Induced Adenomyosis by Levo-Tetrahydropalmatine (l-THP) and Andrographolide

Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.

G-1-Activated Membrane Estrogen Receptors Mediate Increased Contractility of the Human Myometrium

Estrogens are key mediators of increased uterine contractility at labor. We sought to determine whether membrane-associated estrogen receptors, such as the recently described seven-transmembrane receptor G protein-coupled receptor 30 (GPR30), mediated some of this effect. Using human myometrium obtained at term cesarean section before or after the onset of labor, we demonstrated the presence of GPR30 mRNA and protein using quantitative RT-PCR and Western blotting. GPR30 receptor was localized to the cell membrane and often colocalized with calveolin-1. Using the specific estrogen membrane receptor agonist G-1 and myometrial explants, we showed that membrane receptor activation led to phosphorylation of MAPK and the actin-modifying small heat shock protein 27. Using myometrial strips incubated with G-1 or vehicle we demonstrated that estrogen membrane receptor activation increased the myometrial contractile response to oxytocin. These data suggest that activation of the plasma membrane estrogen receptor GPR30 likely participates in the physiology of the human myometrium during pregnancy and identifies it as a potential target to modify uterine activity.

Analysis of preterm deliveries below 35 weeks' gestation in a tertiary referral hospital in the UK. A case-control survey

BackgroundPreterm birth remains a major public health problem and its incidence worldwide is increasing. Epidemiological risk factors have been investigated in the past, but there is a need for a better understanding of the causes of preterm birth in well defined obstetric populations in tertiary referral centres; it is important to repeat surveillance and identify possible changes in clinical and socioeconomic factors associated with preterm delivery. The aim of this study was to identify current risk factors associated with preterm delivery and highlight areas for further research.FindingsWe studied women with singleton deliveries at St Michael's Hospital, Bristol during 2002 and 2003. 274 deliveries between 23-35 weeks' gestation (preterm group), were compared to 559 randomly selected control deliveries at term (37-42 weeks) using standard statistical procedures. Both groups were >80% Caucasian. Previous preterm deliveries, high maternal age (> 39 years), socioeconomic problems, smoking during pregnancy, hypertension, psychiatric disorders and uterine abnormalities were significantly associated with preterm deliveries. Both lean and obese mothers were more common in the preterm group. Women with depression/psychiatric disease were significantly more likely to have social problems, to have smoked during pregnancy and to have had previous preterm deliveries; when adjustments for these three factors were made the relationship between psychiatric disease and pregnancy outcome was no longer significant. 53% of preterm deliveries were spontaneous, and were strongly associated with episodes of threatened preterm labour. Medically indicated preterm deliveries were associated with hypertension and fetal growth restriction. Preterm premature rupture of the membranes, vaginal bleeding, anaemia and oligohydramnios were significantly increased in both spontaneous and indicated preterm deliveries compared to term controls.ConclusionsMore than 50% of preterm births are potentially preventable, but remain associated with risk factors such as increased uterine contractility, preterm premature rupture of the membranes and uterine bleeding whose aetiology is unknown. Despite remarkable advances in perinatal care, preterm birth continues to cause neonatal deaths and long-term morbidity. Significant breakthroughs in the management of preterm birth are likely to come from research into the mechanisms of human parturition and the pathophysiology of preterm labour using multidisciplinary clinical and laboratory approaches.

321: Cervical ripening with hyaluronidase: effect on myometrial contractility in vivo and in vitro

We have shown that intracervical injection of hyaluronidase can induce cervical ripening and accelerate parturition after induction of labor in rats. Hyaluronidase also affects the biophysical properties of the rat cervix consistent with augmented ripening. A common issue using cervical ripening agents is their concomitant effect on uterine activity. The objective of this study was to determine whether hyaluronidase causes an increase in uterine contractility. Timed pregnant Sprague-Dawley rats were injected intracervically with 100 I.U. of hyaluronidase or saline on day 18 of pregnancy (n=7 or 8 per group). All rats were euthanized at term. Uterine rings were isolated for isometric tension experiments. Cumulative dose response curves to oxytocin and hyaluronidase, as well as the maximum contractile response to KCl (60 mM) were obtained and compared between the two groups. There was no difference in the contractile response of rat myometrium to oxytocin between hyaluronidase treated animals and controls (figure). Similarly, exposure of the myometrium to increasing doses of hyaluronidase did not cause uterine contractions in either of the study groups (figure). There was no signifiacnt variation in the maximal myometrial response to KCl between groups. Despite its effect on cervical maturation, the use of hyaluronidase is not associated with an increase in uterine contractions or myometrial sensitivity to oxytocin. This makes hyaluronidase a potentially superior agent for pre-induction cervical ripening as compared to currently available agents. It may be a safer alternative in women with a history of a previous cesarean delivery, or a candidate for use in outpatient settings.

IgE-Independent Mast Cell Activation Augments Contractility of Nonpregnant and Pregnant Guinea Pig Myometrium

Background: We have previously shown that in sensitized guinea pigs premature labor can be induced by a type I hypersensitivity reaction. We further hypothesize that premature labor occurs due to increased uterine contractility caused by activation of mast cells and possibly eosinophils, and collective release of their mediators. The objective of this study was to test the hypothesis that IgE-independent mast cell degranulation could increase uterine contractility. Methods: Longitudinal uterine strips from nonpregnant and pregnant guinea pigs were incubated in organ chambers with vehicle, histamine H₁, serotonin 5-HT₂/5-HT_1C, thromboxane A₂, leukotriene D₄ receptor antagonists, mast cell stabilizer, and cyclooxygenase or lipoxygenase inhibitors. Then, supernatant, obtained after activation of a mast cell line (MC/9) with compound 48/80, culture medium, or compound 48/80 alone were added. Cumulative concentration-response curves to histamine and serotonin were also obtained. Results: The supernatant and compound 48/80 significantly increased contractility of uterine strips. A mast cell stabilizer considerably reduced the effect of compound 48/80. Other substances attenuated uterine contractile responses to supernatant and compound 48/80, and responses varied depending on the pregnancy period. Histamine and serotonin increased contractility of uterine strips, and uterine sensitivity to these agents were dependent on gestational age. Conclusions: In summary, mast cells increase uterine contractility through multiple mediators, and uterine responses to these mediators are dependent on gestational age. We postulate that the simultaneous release of these mast cell/eosinophil mediators in the uterus could be a stimulus to trigger and/or maintain myometrial contractions during preterm and term labor.

An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate

Patients with an episode of preterm labor that subsides in response to tocolysis and who, subsequently, deliver at term are considered to have false preterm labor. However, the episode of "preterm labor" may represent the uterine response (ie, uterine contractions) to an insult not severe enough to trigger preterm parturition, but which may put the fetus at risk for additional pregnancy complications, including growth restriction. The objective of this study was to compare the frequency of small-for-gestational-age (SGA) neonates among patients with an episode of increased uterine contractility who delivered at term and those who delivered preterm. This retrospective cohort study included 849 patients. Inclusion criteria were (1) regular uterine contractions that required hospitalization, (2) intact membranes, and (3) gestational age between 20 and 36 weeks. SGA was defined as a birth weight of <10th percentile for gestational age. Placental pathologic evidence was reviewed, and the results were used to classify patients into an inflammatory cluster, vascular cluster, or both. Contingency tables, Mann-Whitney U test, and multivariate logistic regression were used for statistical analyses. A probability value of <.05 was considered significant. The prevalence of SGA neonates in the study population was 16.1% (124/772). Patients who delivered at term had a significantly higher frequency of SGA neonates than those who delivered preterm (21.5% [64/298] vs 12.7% [60/474]; P = .001); the results of placental pathologic evidence were available in 63.7% (492/772) of the patients. Patients who delivered at term had a higher frequency of fetal or maternal vascular lesions without histologic evidence of inflammation than those who delivered preterm (29.1 % [43/148] vs 18.9% [65/344]; P = .01). Term delivery after an episode of regular preterm uterine contractions was associated with an odds ratio of 2.22 (95% CI, 1.28-3.85) to deliver an SGA neonate after the statistics were controlled for confounding variables. A subanalysis limited to patients who received tocolysis showed similar results. Patients with an episode of increased uterine contractility that subsided and who deliver at term are at risk for delivering an SGA neonate, which suggests that an episode of false preterm labor is not a benign condition. We propose that insults to the fetoplacental unit may be resolved by either irreversible preterm parturition or restriction of fetal growth.

Effects of slow release misoprostol on uterine contractility in early pregnancy

The effect of a novel slow release form of misoprostol (SR misoprostol) on uterine activity during early pregnancy was investigated in a pilot study. Thirty women with a pregnancy between 8 and 12 weeks requesting surgical abortion were allocated to treatment according to computerized randomization. SR misoprostol (400 and 800 microg) was compared to 400 microg of conventional misoprostol, all given orally. Intrauterine pressure was recorded using a pressure transducer inserted extra-amniotically and connected to a computer 30 min before treatment until 4 h thereafter when suction curettage was performed. Uterine tonus (mmHg) and contractility in Montevideo Units (MU) were calculated. An increase in uterine tonus occurred after a significantly shorter time interval and was significantly more pronounced following conventional misoprostol compared to SR misoprostol. Regular uterine contractions developed in only a few patients treated with 400 microg conventional misoprostol or 400 microg SR misoprostol. In contrast the increase in uterine contractility (MU) was significantly more pronounced following 800 microg SR misoprostol treatment and was still continuing at 4 h of recording. SR misoprostol acts less on uterine tonus than orally administered conventional misoprostol but leads to development of regular uterine contractions.