The association of inflammatory changes of the uterus and chorioamniotic membranes with different types of labor activity anomalies.

OBJECTIVE: Aim: To clarify the association between different types of uterine contractility dysfunction and the inflammation of the uterus and chorioamniotic membranes. PATIENTS AND METHODS: Materials and Methods: The association between the inflammation of the uterine layers, chorioamniotic membranes, umbilical cord, and different types of labor activity abnormalities was examined in 382 patients with singleton pregnancies at 28-42 weeks' gestation who underwent Caesarean section (CS) for abnormal uterine contractions and other complications. Statistical analyses included the Mann-Whitney U, Chi-squared test, and logistic regression. RESULTS: Results: In the control group, slight infiltration with polymorphonuclear leukocytes (PMNs) and macrophages of the myometrium and decidua of the lower uterine segment at term pregnancy was found in 59.7% and 73.6% of cases. The main clinical risk factors for placental and decidual membrane inflammation in patients with excessive uterine activity (EUA) were prematurity, multiparity, group B streptococcus (GBS) colonization, and duration of ruptured fetal membranes before the CS. Moderate or marked myometrial inflammation of both uterine segments in the EUA group was diagnosed only in patients with cervical dilation of >6 cm and duration of labor of >8h. In women with hypotonic uterine activity (HUA), decidual and myometrial inflammation was significantly associated with nulliparity and intrapartum factors, such as protracted active first stage of labor, advanced cervical dilation, and number of vaginal examinations. In all cases, inflammation of the myometrium was accompanied by deciduitis. CONCLUSION: Conclusions: Mild inflammation of the decidual membrane and myometrium of the lower segment at term pregnancy is a common physiological phenomenon contributing to labor initiation. Uterine hyperfunction comes as the response of the unaffected myometrium to the release of high concentrations of proinflammatory cytokines produced by the inflamed decidual and chorioamniotic membranes into the bloodstream. Marked myometrial inflammation that occurs in prolonged labor is an additional factor aggravating the hypotonic uterine activity.

Modeling normal mouse uterine contraction and placental perfusion with non-invasive longitudinal dynamic contrast enhancement MRI.

BACKGROUND: The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual's entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities. OBJECTIVE: Our goal is to create a non-invasive preclinical imaging pipeline that can longitudinally probe murine placental health in vivo. We use advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development. METHODOLOGY: We implement dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and analysis pipeline to quantify uterine contraction and placental perfusion dynamics. We use optic flow and time-frequency analysis to quantify and characterize contraction-related placental motion. Our novel imaging and analysis pipeline uses subcutaneous administration of gadolinium for steepest slope-based perfusion evaluation, enabling non-invasive longitudinal monitoring. RESULTS: We demonstrate that the placenta exhibits spatially asymmetric contractile motion that develops from E14.5 to E17.5. Additionally, we see that placental perfusion, perfusion delivery rate, and substrate delivery all increase from E14.5 to E17.5, with the High Perfusion Chamber (HPC) leading the placental changes that occur from E14.5 to E17.5. DISCUSSION: We advance the placental perfusion chamber paradigm with a novel, physiologically based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and remodeling throughout gestation. CONCLUSION: Our pipeline enables the non-invasive, longitudinal assessment of multiple placenta functions from a single imaging session. Our pipeline serves as a key toolbox for advancing research in mouse models of placental disease and disorder.

A new effect of intravenous iron treatment in pregnancy: contraction in nonstress test and timing of labor.

OBJECTIVE: The aim of this study was to elucidate the cause and results of contractions occurring in term pregnant women receiving intravenous iron therapy. METHODS: During 2019-2020, 136 pregnant women beyond 35 weeks of gestation, who received intravenous iron treatment due to iron deficiency anemia, were included through retrospective screening. Iron deficiency anemia was defined as having hemoglobin levels <10 g/dL and ferritin levels <15 ng/mL, and the pregnant women underwent nonstress test before and after treatment. RESULTS: The average treatment week for the pregnant women was 36.82±0.74, and the presence of regular contractions in post-treatment follow-up nonstress tests was 72.1% (n=98). The average week of birth was 38.48±1.60. Pregnant women with contractions who had previous cesarean were found to have a mean delivery week of 36.82±0.67, which was statistically significant earlier than for nulliparous and multiparous women (p<0.001). CONCLUSION: In pregnant women with iron deficiency anemia who were beyond 35 weeks, temporary regular contractions may be observed in the nonstress test following intravenous iron replacement. We think that this effect may lead to early term birth in pregnant women with a history of cesarean section. It needs to be confirmed by further prospective studies and animal studies.

Therapeutic Potential of Thunbergia laurifolia L. Extract in Gestational Diabetes Mellitus: Insights from a Rat Model.

OBJECTIVE: To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model. METHODS: Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement. RESULTS: In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05). CONCLUSIONS: TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.

Rac1 promotes the lipopolysaccharide-induced inflammatory response and contraction-associated proteins (CAPs) expression in mouse uterine smooth muscle cells.

Activation of the maternal immune system leads to a downstream cascade of proinflammatory events that culminate in the activation of spontaneous uterine contractions, which is associated with preterm birth. Ras-related C3 botulinum toxin substrate 1 (Rac1) is a crucial protein related to cell contraction and inflammation. The main purpose of this study was to explore the role and function of Rac1's regulation of inflammation through in- vivo and in-vitro experiments. Rac1 inhibitor was used in animal model of preterm birth and cells isolated from the uterine tissues of pregnant mice on gestational day 16 were transfected with adenovirus to knockdown or overexpress Rac1 and treated with the Calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. The expression of Rac1, uterine contraction-associated proteins (CAPs) (COX-2 and Connexin43), and inflammatory cytokines, were assessed by Western blotting and RTPCR. LPS upregulated Rac1, COX-2 and Connexin43 expression in uterine smooth muscle cells (USMCs). The expression of inflammatory cytokines, COX-2, and Connexin43 was significantly decreased in shRac1-transfected cells compared with cells stimulated with LPS only. Rac1 overexpression led to an increase in the expression of inflammatory cytokines, COX-2, and Connexin43. Furthermore, after Rac1 overexpression, KN93 reduced the expression of uterine contraction-associated proteins and inflammatory cytokines. It is thought that the effect of Rac1 on inflammatory cytokine and contraction-associated protein expression in USMCs is mediated by CaMKII. Rac1 can modulate the expression of contraction-associated proteins and inflammatory cytokines through the CaMKII pathway. Rac1 could be an effective therapeutic target for improving the outcome of preterm birth.

Decline in corepressor CNOT1 in the pregnant myometrium near term impairs progesterone receptor function and increases contractile gene expression.

Progesterone (P4), acting via its nuclear receptor (PR), is critical for pregnancy maintenance by suppressing proinflammatory and contraction-associated protein (CAP)/contractile genes in the myometrium. P4/PR partially exerts these effects by tethering to NF-κB bound to their promot-ers, thereby decreasing NF-κB transcriptional activity. However, the underlying mechanisms whereby P4/PR interaction blocks proinflammatory and CAP gene expression are not fully understood. Herein, we characterized CCR-NOT transcription complex subunit 1 (CNOT1) as a corepressor that also interacts within the same chromatin complex as PR-B. In mouse myome-trium increased expression of CAP genes Oxtr and Cx43 at term coincided with a marked decline in expression and binding of CNOT1 to NF-κB-response elements within the Oxtr and Cx43 promoters. Increased CAP gene expression was accompanied by a pronounced decrease in enrichment of repressive histone marks and increase in enrichment of active histone marks to this genomic region. These changes in histone modification were associated with changes in expression of corresponding histone modifying enzymes. Myometrial tissues from P4-treated 18.5 dpc pregnant mice manifested increased Cnot1 expression at 18.5 dpc, compared to vehicle-treated controls. P4 treatment of PR-expressing hTERT-HM cells enhanced CNOT1 expression and its recruitment to PR bound NF-κB-response elements within the CX43 and OXTR promoters. Furthermore, knockdown of CNOT1 significantly increased expression of contractile genes. These novel findings suggest that decreased expression and DNA-binding of the P4/PR-regulated transcriptional corepressor CNOT1 near term and associated changes in histone modifications at the OXTR and CX43 promoters contribute to the induction of myometrial contractility leading to parturition.

Effects of Liquid Fructose Supplementation and Chronic Unpredictable Stress on Uterine Contractile Activity in Nonpregnant Rats.

Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.

Imaging the dynamics of murine uterine contractions in early pregnancy†.

Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent. Even still, uterine contractions have primarily been studied in the context of preterm labor. This is partly due to a lack of methods for studying the uterine muscle contractility in the intact organ. Here, we describe an imaging-based method to evaluate mouse uterine contractility of both the longitudinal and circular muscles in the cycling stages and in early pregnancy. By transforming the image-based data into three-dimensional spatiotemporal contractility maps, we calculate waveform characteristics of muscle contractions, including amplitude, frequency, wavelength, and velocity. We report that the native organ is highly contractile during the progesterone-dominant diestrus stage of the cycle when compared to the estrogen-dominant proestrus and estrus stages. We also observed that during the first phase of uterine embryo movement when clustered embryos move toward the middle of the uterine horn, contractions are dynamic and non-uniform between different segments of the uterine horn. In the second phase of embryo movement, contractions are more uniform and rhythmic throughout the uterine horn. Finally, in Lpar3-/- uteri, which display faster embryo movement, we observe global and regional increases in contractility. Our method provides a means to understand the wave characteristics of uterine smooth muscle in response to modulators and in genetic mutants. Better understanding uterine contractility in the early pregnancy stages is critical for the advancement of artificial reproductive technologies and a possibility of modulating embryo movement during clinical embryo transfers.

Histological Features of Uterine Myometrial Dysfunction: Possible Involvement of Localized Inflammation.

OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Uterine contractile activity and neonatal outcome - A blind analysis of a randomized controlled trial cohort.

INTRODUCTION: Sufficient contractions are necessary for a successful delivery but each contraction temporarily constricts the oxygenated blood flow to the fetus. Individual fetal or placental characteristics determine how the fetus can withstand this temporary low oxygen saturation. However, only a few studies have examined the impact of uterine activity on neonatal outcome and even less attention has been paid to parturients' individual characteristics. Our objective was therefore to find out whether fetuses compromised by maternal or intrapartum risk factors are more vulnerable to excessive uterine activity. MATERIAL AND METHODS: Uterine contractile activity was assessed by intrauterine pressure catheters. Women (n = 625) with term singleton pregnancies and fetus in cephalic presentation were included in this secondary, blind analysis of a randomized controlled trial cohort. Intrauterine pressure as Montevideo units (MVU), contraction frequency/10 min and uterine baseline tone were calculated for 4 h prior to birth or the decision to perform cesarean section. Uterine activity in relation to umbilical artery pH linearly or ≤7.10 was used as the primary outcome. Need for operative delivery (either cesarean section or vacuum-assisted delivery) due to fetal distress was analyzed as a secondary outcome. In addition, belonging to vulnerable subgroups with, for example, chorioamnionitis, hypertensive or diabetic disorders, maternal smoking or neonatal birthweight <10th percentile were investigated as additional risk factors. RESULTS: A linear decline in umbilical artery pH was seen with increasing intrauterine pressure in all deliveries (p < 0.001). Among parturients with suspected chorioamnionitis, every increasing 10 MVUs increased the likelihood of umbilical artery pH ≤7.10 (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.02-1.34, p = 0.023). The need for operative delivery due to fetal distress was increased among all laboring women by every increasing 10 MVUs (OR 1.05, 95% CI 1.01-1.09, p = 0.015). This association with operative deliveries was further increased among parturients with hypertensive disorders (OR 1.23, 95% CI 1.05-1.43, p = 0.009) and among those with diabetic disorders (OR 1.13, 95% CI 1.04-1.28, p = 0.003). CONCLUSIONS: Increasing intrauterine pressure impairs umbilical artery pH especially among parturients with suspected chorioamnionitis. Fetuses in pregnancies affected by chorioamnionitis, hypertensive or diabetic disorders are more vulnerable to high intrauterine pressure.

Simulation of Uterus Active Contraction and Fetus Delivery in ls-dyna.

Vaginal childbirth is the final phase of pregnancy when one or more fetuses pass through the birth canal from the uterus, and it is a biomechanical process. The uterine active contraction, causing the pushing force on the fetus, plays a vital role in regulating the fetus delivery process. In this project, the active contraction behaviors of muscle tissue were first modeled and investigated. After that, a finite element method (FEM) model to simulate the uterine cyclic active contraction and delivery of a fetus was developed in ls-dyna. The active contraction was driven through contractile fibers modeled as one-dimensional truss elements, with the Hill material model governing their response. Fibers were assembled in the longitudinal, circumferential, and normal (transverse) directions to correspond to tissue microstructure, and they were divided into seven regions to represent the strong anisotropy of the fiber distribution and activity within the uterus. The passive portion of the uterine tissue was modeled with a Neo Hookean hyperelastic material model. Three active contraction cycles were modeled. The cyclic uterine active contraction behaviors were analyzed. Finally, the fetus delivery through the uterus was simulated. The model of the uterine active contraction presented in this paper modeled the contractile fibers in three-dimensions, considered the anisotropy of the fiber distribution, provided the uterine cyclic active contraction and propagation of the contraction waves, performed a large deformation, and caused the pushing effect on the fetus. This model will be combined with a model of pelvic structures so that a complete system simulating the second stage of the delivery process of a fetus can be established.

Extracellular acidification increases uterine contraction in pregnant mouse by increasing intracellular calcium.

AIMS: As uterine extracellular pH decreases during the ischemic conditions of labor, but its effects on myometrial contraction are largely unknown, there is a need to elucidate its physiological effects and mechanisms of action. Furthermore, it is not known if any of the effects of extracellular acidification are affected by pregnancy, thus we also determined how gestation affects the response to acidification. METHODS: Nonpregnant, mid-, and term-pregnant myometrial strips were obtained from humanely killed mice. Contractions were recorded under spontaneous, depolarized, and oxytocin-stimulated conditions. The extracellular pH of the perfusate was changed from 7.4 to 6.9 or 7.9 in HEPES-buffered physiological saline. Intracellular pH was measured using SNARF, and intracellular calcium was measured using Indo-1. Statistical differences were tested using the appropriate t-test. RESULTS: Extracellular acidification significantly increased the frequency and amplitude of spontaneous contractions in pregnant, but not nonpregnant, myometrium, whereas alkalinization decreased contractions. Intracellular acidification, via Na-butyrate, transiently increased force in pregnant tissue. Intracellular pH was gradually acidified when extracellular pH was acidified, but extracellular acidification increased contractility before any significant change in intracellular pH. If myometrial force was driven by oxytocin or high-K depolarization, then extracellular pH did not further increase force. Intracellular calcium changes mirrored those of force in the spontaneously contracting pregnant myometrium, and if calcium entry was prevented by nifedipine, extracellular acidification could not induce a rise in force. CONCLUSION: Extracellular acidification increases excitability, calcium entry, and thus force in pregnant mouse myometrium, and this may contribute to increasing contractions during labor when ischemic conditions and acidemia occur.

Effect of low-intensity focused ultrasound therapy on postpartum uterine involution in puerperal women: A randomized controlled trial.

BACKGROUND: Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. METHODS: A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. RESULTS: Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. CONCLUSIONS: This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

Multicentric intelligent cardiotocography signal interpretation using deep semi-supervised domain adaptation via minimax entropy and domain invariance.

BACKGROUND AND OBJECTIVE: Obstetricians use Cardiotocography (CTG), which is the continuous recording of fetal heart rate and uterine contraction, to assess fetal health status. Deep learning models for intelligent fetal monitoring trained on extensively labeled and identically distributed CTG records have achieved excellent performance. However, creation of these training sets requires excessive time and specialist labor for the collection and annotation of CTG signals. Previous research has demonstrated that multicenter studies can improve model performance. However, models trained on cross-domain data may not generalize well to target domains due to variance in distribution among datasets. Hence, this paper conducted a multicenter study with Deep Semi-Supervised Domain Adaptation (DSSDA) for intelligent interpretation of antenatal CTG signals. This approach helps to align cross-domain distribution and transfer knowledge from a label-rich source domain to a label-scarce target domain. METHODS: We proposed a DSSDA framework that integrated Minimax Entropy and Domain Invariance (DSSDA-MMEDI) to reduce inter-domain gaps and thus achieve domain invariance. The networks were developed using GoogLeNet to extract features from CTG signals, with fully connected, softmax layers for classification. We designed a Dynamic Gradient-driven strategy based on Mutual Information (DGMI) to unify the losses from Minimax Entropy (MME), Domain Invariance (DI), and supervised cross-entropy during iterative learning. RESULTS: We validated our DSSDA model on two datasets collected from collaborating healthcare institutions and mobile terminals as the source and target domains, which contained 16,355 and 3,351 CTG signals, respectively. Compared to the results achieved with deep learning networks without DSSDA, DSSDA-MMEDI significantly improved sensitivity and F1-score by over 6%. DSSDA-MMEDI also outperformed other state-of-the-art DSSDA approaches for CTG signal interpretation. Ablation studies were performed to determine the unique contribution of each component in our DSSDA mechanism. CONCLUSIONS: The proposed DSSDA-MMEDI is feasible and effective for alignment of cross-domain data and automated interpretation of multicentric antenatal CTG signals with minimal annotation cost.

On the uncertainty quantification of the active uterine contraction during the second stage of labor simulation.

Uterine contractions in the myometrium occur at multiple scales, spanning both organ and cellular levels. This complex biological process plays an essential role in the fetus delivery during the second stage of labor. Several finite element models of active uterine contractions have already been developed to simulate the descent of the fetus through the birth canal. However, the developed models suffer severe reliability issues due to the uncertain parameters. In this context, the present study aimed to perform the uncertainty quantification (UQ) of the active uterine contraction simulation to advance our understanding of pregnancy mechanisms with more reliable indicators. A uterus model with and without fetus was developed integrating a transversely isotropic Mooney-Rivlin material with two distinct fiber orientation architectures. Different contraction patterns with complex boundary conditions were designed and applied. A global sensitivity study was performed to select the most valuable parameters for the uncertainty quantification (UQ) process using a copula-based Monte Carlo method. As results, four critical material parameters ( C 1 , C 2 , K , Ca 0 ) of the active uterine contraction model were identified and used for the UQ process. The stress distribution on the uterus during the fetus descent, considering first and second fiber orientation families, ranged from 0.144 to 1.234 MPa and 0.044 to 1.619 MPa, respectively. The simulation outcomes revealed also the segment-specific contraction pattern of the uterus tissue. The present study quantified, for the first time, the effect of uncertain parameters of the complex constitutive model of the active uterine contraction on the fetus descent process. As perspectives, a full maternal pelvis model will be coupled with reinforcement learning to automatically identify the delivery mechanism behind the cardinal movements of the fetus during the active expulsion process.

The utility of combined utero-cervical index in predicting preterm delivery in pregnant women with preterm uterine contractions.

PURPOSE: To evaluate the utility of a novel ultrasound index "combined utero-cervical index (CUCI)" in the prediction of preterm delivery. METHODS: The present prospective cohort study was conducted in Ankara Bilkent City Hospital Perinatology Clinic between January 1, 2023, and March 31, 2023. Pregnant women with uterine contractions between 24 and 36th gestational weeks but did not have dilatation or effacement were included. CUCI was calculated as: (utero-cervical angle)/(anterior cervical lip thickness + fundal thickness + lower uterine segment thickness + cervical length). In the presence of cervical funneling, one point was added to the final result. A ROC analysis was conducted to determine the potential of CUCI in predicting delivery <37 weeks of gestation, <34 weeks of gestation, and <4 weeks after the first admission to the hospital for uterine contractions, respectively. RESULTS: Optimal cut-off values of CUCI were found to be 1.4 (67.1% sensitivity, 67.2% specificity) for predicting delivery at <37th weeks, 1.7 (72.7% sensitivity, 65.7% specificity) for predicting delivery at <34th weeks, and 1.4 (62.5% sensitivity, 61.7% specificity) for predicting delivery at <4 weeks. CONCLUSION: CUCI may be used in the prediction of preterm delivery for pregnant women admitted to hospital with preterm uterine contractions.