Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

The aetiology of primary uterine inertia (PUI), which is the most common cause of canine dystocia, is still not elucidated. Prostaglandins (PGs) play a crucial role in parturition. We hypothesized that the expression of prostaglandin endoperoxidase synthase 2 (PTGS2), PGF2α synthase (PGFS), and corresponding receptor (PTGFR) is altered in PUI. We investigated PTGS2, PGFS, and PTGFR mRNA expression, and PTGS2 and PGFS protein expression in interplacental (IP) and uteroplacental sites (UP) in bitches with PUI, obstructive dystocia (OD), and prepartum (PC). PTGS2, PGFS, and PTGFR mRNA expression did not differ significantly between PUI and OD (IP/UP). PTGFR ratio in UP was higher in PC than in OD (p = 0.014). PTGS2 immunopositivity was noted in foetal trophoblasts, luminal and superficial glandular epithelial cells, smooth muscle cells of both myometrial layers, and weakly and sporadically in deep uterine glands. PGFS was localized in luminal epithelial cells and in the epithelium of superficial uterine glands. PTGS2 and PGFS staining was similar between PUI and OD, while PGFS protein expression differed between OD and PC (p = 0.0215). For PTGS2, the longitudinal myometrial layer of IP stained significantly stronger than the circular layer, independent of groups. These results do not support a role for PTGS2, PGFS, and PTGFR in PUI. Reduced PGFS expression in IP during parturition compared with PC and the overall lack of placental PGFS expression confirm that PGFS is not the main source of prepartal PGF2alpha increase. The difference in PTGS2 expression between IP myometrial layers warrants further investigation into its physiological relevance.

The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study.

BACKGROUND: Prophylactic administration of oxytocin as a part of active management of the third stage of labor reduces the risk of postpartum hemorrhage. Prophylactic oxytocin is often administered as an infusion rather than a bolus. The aim of the current up-down sequential allocation dose-response study was to test the hypothesis that parturients who receive intrapartum exogenous oxytocin therapy, and who subsequently undergo cesarean delivery for labor dystocia, will have a higher estimated effective dose in 90% of paturients (ED90) for oxytocin infusion in the third stage of labor compared with nonlaboring parturients. METHODS: The study design was a single-blinded, dual-arm, dose-response study using a 9:1 biased-coin sequential allocation method to estimate the ED90 of an infusion of prophylactic oxytocin in women undergoing cesarean delivery with neuraxial anesthesia. The experimental (laboring) group included women scheduled for intrapartum cesarean delivery after prior exposure to exogenous oxytocin, and the control (nonlaboring) group included women scheduled for elective cesarean delivery. The starting infusion rate was 18 IU/h, with an incremental dose of 2 IU/h. The outcome was satisfactory uterine tone 4 minutes after delivery as judged by the obstetrician. Secondary outcomes included requirement for additional uterotonic agents and maternal side effects (e.g., nausea and vomiting, ST-segment depression). Dose-response data for each group were evaluated by a log-logistic function and ED90 estimates derived from the fitted equations using the delta method. RESULTS: Thirty-eight and 32 subjects participated in the nonlaboring and laboring groups, respectively. The oxytocin ED90 was significantly greater for the laboring group (44.2 IU/h [95% confidence interval (CI), 33.8-55.6]) compared with that for the nonlaboring group (16.2 IU/h [95% CI, 13.1-19.3]; difference in dose 28 IU/h [95% CI of difference, 26-29, P < 0.001]). Significantly more women in the laboring group (34%) than in the nonlaboring group (8%) required supplemental uterotonic agents (difference 26% [95% CI of the difference, 7%-44%, P = 0.008]). The overall incidence of side effects was greater in the laboring group (69%) than in the nonlaboring group (34%; difference 25% [95% CI of the difference, 10%-59%, P = 0.004]). CONCLUSIONS: Women with prior exposure to exogenous oxytocin require a higher initial infusion rate of oxytocin to prevent uterine atony after cesarean delivery than women without prior exposure.

B-Lynch uterine compression sutures in the conservative surgical management of uterine atony.

AIM: To evaluate the success rate and possible complications of the B-Lynch uterine compression sutures in women who suffered from postpartum uterine atony unresponsive to medical treatment. MATERIALS AND METHODS: A total of 36 women who were managed with the B-Lynch suture, with or without additional surgical procedures following uterine atony unresponsive to medical treatment, were evaluated retrospectively. RESULTS: Sixteen women were primarily managed with the B-Lynch compression sutures, and 11 women had the B-Lynch compression sutures following failure of achievement of hemostasis by ligation of uterine artery alone (n = 4), or uterine artery plus uterine branch of ovarian artery (n = 7). Eight women had bilateral internal iliac artery ligation (BIIAL) following failure of achievement of hemostasis by the B-Lynch compression sutures. Two women (5.5%) underwent post-cesarean hysterectomy. The overall success rate of B-Lynch was 75% (27/36), and the overall success rate of B-Lynch plus BIIAL was 94.4% (34/36). Three women were admitted to the intensive care unit. There was no death related to the hemorrhage in our series. No short-term complications such as uterine necrosis, hematometra, pyometra, or uterine erosion related to the uterine compression suture were observed. CONCLUSION: Overall success rate of the B-Lynch sutures and B-Lynch sutures plus BIIAL was 75 and 94.4%, respectively. The B-Lynch technique does not necessarily require specific suture material. Uterine devascularization or BIIAL did not increase the risk of the possible short-term complications such as uterine necrosis. In case of failure of the B-Lynch uterine compression sutures, BIIAL may be beneficial to save the uterus.

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

OBJECTIVE: to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. MATERIAL AND METHODS: Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). RESULTS: The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. CONCLUSION: A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

Double vertical compression sutures: A novel conservative approach to managing post-partum haemorrhage due to placenta praevia and atonic bleeding.

Compression has been regarded as the main haemostatic mechanism of compression sutures; however, we suggest that reduced uterine blood flow may be another important action. We suggest that our 'double vertical compression sutures' may have dual actions: haemostatic compression of the bleeding surface and reduced uterine blood flow.

Bilateral uterine and ovarian artery ligation in addition to B-lynch suture may be an alternative to hysterectomy for uterine atonic hemorrhage.

PURPOSE OF INVESTIGATION: To evaluate the effectiveness of bilateral uterine arteries and ovarian artery ligation followed by B-Lynch compression suturing in controlling atonic postpartum hemorrhage. METHODS: In this retrospective study, the data of eight patients that had uterine atony during cesarean section and treated by bilateral uterine and ovarian artery ligation followed by B-Lynch compression suturing during the period from February 2009 to September 2010 were collected and analyzed. RESULTS: Eight cases were treated by the above protocol; the average age of the patients was 25.25 +/- 5.09 years, and the mean gestational age was 35.75 +/- 3.80 weeks. Seven of the patients were primiparous. They were hospitalized on average 5.25 +/- 2.31 days. The mean operation time was 61.25 +/- 24.60 minutes and mean estimated blood loss was 2787.5 +/- 1573.38 ml. Internal iliac artery ligation was necessary in one patient only. Hysterectomy was not performed in any of the patients. Five patients had intraoperative or postoperative blood transfusion. CONCLUSION: The addition of uterine artery and ovarian artery ligation to the B-Lynch suture may be considered as a major hemostatic step before proceeding to hysterectomy in cases of uterine atony bleeding, and all gynecologic surgeons should be familiar with it.

Delayed delivery of a twin pregnancy and uterine atony: morphological and clinical evidence.

This report presents the uncommon case of a 154-day delayed delivery in a spontaneous twin pregnancy associated with uterine atony. After abortion of the first fetus at 16 weeks, a healthy male was born at 38 weeks. Postpartum hemorrhage due to uterine atony, which was successfully treated with prostaglandins, occurred.

Intraluminal pressure readings during the establishment of a positive 'tamponade test' in the management of postpartum haemorrhage.

OBJECTIVE: To investigate the proposed mechanism by which intrauterine balloons achieve their tamponade effect of creating an 'intrauterine pressure that is greater than the systemic arterial pressure'. DESIGN: To determine the intraluminal pressures within a Bakri balloon during the establishment of a positive 'tamponade test' in the management of postpartum haemorrhage. To correlate these intraluminal pressures with contemporaneous readings of blood pressure recordings as documented from the operating theatre anaesthetic charts. SETTING: An obstetric unit (approximately 2400 births) in Wollongong, New South Wales, Australia. SAMPLE: Two women in whom first-line uterotonics were unsuccessful and who required a Bakri balloon to control postpartum haemorrhage secondary to an atonic uterus. METHODS: A DigiMano (Netech Corporation, Farmingdale, NY, USA) pressure recorder was attached via a three-way tap to a Bakri balloon. Anaesthetic charts of the two cases were reviewed retrospectively. MAIN OUTCOME MEASURES: Intraluminal pressure readings were recorded after each 50-ml aliquot of normal saline had been insufflated into the balloon whilst the next aliquot was being prepared. RESULTS: There is a curvilinear relationship between the intraluminal pressure and the balloon volume. The pressure does not exceed the systolic blood pressure of the patient at the time of establishment of a positive tamponade test. CONCLUSIONS: The intraluminal pressure within the tamponade balloon does not exceed the systolic blood pressure of the patient when a positive tamponade test is established.

Five unit bolus oxytocin at cesarean delivery in women at risk of atony: a randomized, double-blind, controlled trial.

BACKGROUND: I.v. bolus oxytocin is used routinely during cesarean delivery to prevent postpartum hemorrhage. Its adverse hemodynamic effects are well known, resulting in a recent change in dose from 10 IU to 5. Whether a 5 IU bolus has any advantages over infusion alone is unclear. We tested the hypothesis that a 5 IU i.v. bolus of oxytocin before the initiation of a continuous infusion decreases the need for additional uterotonic drugs in the first 24 hours after delivery in women with risk factors for uterine atony undergoing cesarean delivery, compared with infusion alone. METHODS: A prospective, randomized, double-blind, controlled trial was conducted in 143 subjects undergoing cesarean delivery with at least 1 risk factor for uterine atony. Subjects received 5 IU bolus of oxytocin or normal saline i.v. over 30 seconds after umbilical cord clamping. All subjects received an infusion of 40 IU oxytocin in 500 mL normal saline over 30 minutes, followed by 20 IU in 1 L over 8 hours. The primary outcome was the need for additional uterotonics in the first 24 hours after delivery. Secondary outcomes included uterine tone as assessed by the surgeon (5-point Likert scale: 0 = "floppy," 4 = "rock hard"), estimated blood loss, side effects of bolus administration, and the oxytocin bolus-placental delivery interval. RESULTS: There was no difference in the need for additional uterotonic drugs in the first 24 hours between groups. There was a significant difference in uterine tone immediately after placental delivery (P < 0.01) (2.8 in the oxytocin group [95% confidence interval 2.6-3.0] vs 2.2 in the saline group [95% confidence interval 1.8-2.5]), which disappeared after 5 minutes. There were no differences in observed or reported side effects between groups. CONCLUSIONS: We found that a 5 IU i.v. bolus of oxytocin added to an infusion did not alter the need for additional uterotonic drugs to prevent or treat postpartum hemorrhage in the first 24 hours in women undergoing cesarean delivery with risk factors for uterine atony, despite causing an initial stronger uterine contraction. Our study was not powered to find a difference in side effects between groups. These results suggest that an oxytocin infusion may be adequate without the need for a bolus, even in high-risk patients.

Management of post-partum haemorrhage.

Management of post-partum haemorrhage (PPH) involves the treatment of uterine atony, evacuation of retained placenta or placental fragments, surgery due to uterine or birth canal trauma, balloon tamponade, effective volume replacement and transfusion therapy, and occasionally, selective arterial embolization. This article aims at introducing pregnancy- and haemorrhage-induced changes in coagulation and fibrinolysis and their relevant compensatory mechanisms, volume replacement therapy, optimal transfusion of blood products, and coagulation factor concentrates, and briefly cell salvage, management of uterine atony, surgical interventions, and selective arterial embolization. Special attention, respective management, and follow-up are required in women with bleeding disorders, such as von Willebrand disease, carriers of haemophilia A or B, and rare coagulation factor deficiencies. We also provide a proposal for practical instructions in the treatment of PPH.

Randomized controlled trial of the effect of bilateral uterine artery ligation during cesarean among women at risk of uterine atony.

OBJECTIVE: To assess the effectiveness of prophylactic bilateral uterine artery ligation (BUAL) in reducing the incidence of postpartum hemorrhage (PPH) during cesarean delivery among women at risk of uterine atony. METHODS: A randomized clinical trial at Cairo University Maternity Hospital, Egypt, from December 2017 to December 2018. Women at risk of uterine atony undergoing scheduled or emergency cesarean were randomized to two groups. In the BUAL group, women underwent BUAL before placental delivery; in the control group, women had cesarean delivery without BUAL. The primary outcome was the estimated blood loss during cesarean. RESULTS: Intraoperative blood loss during cesarean was significantly lower in the BUAL group than in the control group (523.4 ± 41.0 vs 619.6 ± 36.1 mL; P=0.003). Blood loss in the first 6 hours after cesarean was also significantly lower in the BUAL group than in the control group (246.1 ± 21.4 vs 326.1 ± 18.5 mL; P=0.006). There was no difference in operative time between the two groups (52.1 ± 6.1 vs 52.2 ± 6.8, P=0.880). CONCLUSION: BUAL during cesarean was found to be an effective method for decreasing blood loss during and after cesarean delivery among women at risk of uterine atony and subsequent PPH. CLINICALTRIALS.GOV: NCT03591679.

The magnitude and associated factors of postpartum hemorrhage among mothers who delivered at Debre Tabor general hospital 2018.

OBJECTIVE: Since data related to postpartum hemorrhage in Ethiopia is scarce, this study was aimed to assess the magnitude and associated factors of postpartum hemorrhage among mothers who delivered in Debre Tabor general hospital. RESULTS: In this study, one hundred forty-four mothers' charts were reviewed which made the response rate 100%. This study revealed that the magnitude of postpartum hemorrhage was 7.6% (CI 6.2, 9.8). Chi-square test revealed that there was an association between postpartum hemorrhage and gravidity, parity, having antenatal care visit, and the previous history postpartum hemorrhage. This finding confirmed that uterine atony, retained placenta, and genital tract trauma were the most common leading cause of postpartum hemorrhage.

[Post-partum transfusion: The view of the anaesthetist in a delivery room]. / Transfusion en obstétrique : le point de vue de l'anesthésiste en salle de naissance.

Uterine atony is the primary cause of post-partum haemorrhage. Blood loss in a maternity setting is difficult to recognize. Early and empiric use of fixed transfusion red blood cell:plasma:platelet ratios is controversial and may not be justified for all causes of haemorrhage.

Intramuscular oxytocin versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery (LabOR trial): study protocol for a randomised controlled trial.

BACKGROUND: Primary postpartum haemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. The most common cause of primary PPH is uterine atony. Atonic PPH rates are increasing in developed countries despite routine active management of the third stage of labour. In less-developed countries, primary PPH remains the leading cause of maternal death. Although the value of routine oxytocics in the third stage of labour has been well established, there is inconsistent practice in the choice of agent and route of administration. Oxytocin is the preferred agent because it has fewer side effects than other uterotonics with similar efficacy. It can be given intravenously or intramuscularly; however, to date, the most effective route of administering oxytocin has not been established. METHODS/DESIGN: A double-blind randomised controlled trial is planned. The aim of the study is to compare the effects of an intramuscular bolus of oxytocin (10 IU in 1 mL) and placebo intravenous injection (1 mL 0.9% saline given slowly) with an intravenous bolus of oxytocin (10 IU in 1 mL given slowly over 1 min) and placebo intramuscular injection (1 mL 0.9% saline) at vaginal delivery. The study will recruit 1000 women at term (>36 weeks) with singleton pregnancies who are aiming for a vaginal delivery. The primary outcome will be PPH (measured blood loss ≥ 500 mL). A study involving 1000 women will have 80% power at the 5% two-sided alpha level, to detect differences in the proportion of patients with measured blood loss > 500 ml of 10% vs 5%. DISCUSSION: Given the increasing trends of atonic PPH it is both important and timely that we evaluate the most effective route of oxytocin administration for the management of the third stage of labour. To date, there has been limited research comparing the efficacy of intramuscular oxytocin vs intravenous oxytocin for the third stage of labour. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN14718882 . Registered on 4 January 2016. Pilot commenced 12.12.2015; trial commenced 04.01.2016. The protocol (Ref 012012) was approved by the National Maternity Hospital Research Ethics Committee on 10.06.2015 and the Research Ethics Committee of the Coombe Women & Infants University Hospital (Ref 26-2015) on 09.12.2015.

Hormonal, Electrolytic, and Electrocardiographic Evaluations in Bitches With Eutocia and Dystocia.

The objective of the study was to assess clinical alterations, electrocardiographic, hematological, biochemical, hemogasometric, electrolytic, and hormone plasma concentrations in bitches with eutocia and dystocia. Overall, 28 bitches (dystocia, n = 22 and eutocia, n = 6) were assessed. The evaluations were performed at 2 time points, M1 (1 hour prepartum-eutocia group and cesarean or clinical intervention-dystocia group) and M2 (postpartum-eutocia or dystocia group and anesthetic recovery-dystocia group). The main clinical finding was the hypothermia (mean: 36.9°C dystocia vs. 36.8°C eutocia). Sinus arrhythmia and tachycardia were the electrocardiographic parameters predominant in eutocia and sinus rhythm in dystocia group. The P wave amplitude, heart rate, creatinine concentration, hematocrit, and hemoglobin were increased in M1 (P < .05), whereas the concentration of TCO2 was higher in M2. There was an increase in P4 concentration in dystocia and total T3 concentrations were increased in M1 in both groups. Total T4 was higher in dystocia during M1 and in dystocia during M2 in eutocia than in dystocia. We concluded that at 1 hour prepartum or pre-cesarean, there is an increase in heart rate in bitches with eutocia or dystocia, and this finding was correlated to thyroid hormone concentration. P4 concentrations remained high during dystocia, and hematological and biochemical changes returned to normal after parturition. The evaluation of these parameters in pregnancy can be used as tool to prevent dystocia and consequent fetal death.

Peripartum hysterectomy incidence, risk factors and clinical characteristics in Ireland.

BACKGROUND: The incidence of peripartum hysterectomy (PH) shows fifty-fold variation worldwide (0.2-10.5/1000 deliveries) and risk factors include advancing maternal age and parity, previous caesarean section (CS) and abnormal placentation. OBJECTIVES: In this first national study of PH in Ireland, our objectives were threefold: to describe the national trend in PH incidence over 15 years since 1999; to assess risk of PH associated with morbidly adherent placenta (MAP), placenta praevia and postpartum haemorrhage (PPH) during 2005-2013; and to describe the causes, interventions and outcomes of PH cases during 2011-2013. STUDY DESIGN: For the 15-year time-trend analysis, PH cases and denominator data were extracted from Ireland's Hospital In-Patient Enquiry database. Multivariate Poisson regression analysis assessed risk of PH associated with MAP, placenta praevia and PPH. In collaboration with the 20 Irish maternity units we carried out a three-year national clinical audit of severe maternity morbidity. PH was a notifiable morbidity and the audit included detailed review of MOH cases. RESULTS: In 1999-2013 there were 298 PH cases, a rate of 0.32/1000 deliveries. During the period 2005-2013, the PH rate was 50 times higher in deliveries involving PPH, 100 times higher with placenta praevia and 1000 times higher with MAP. During the clinical audit (2011-2013) there were 65 PH cases, a rate of 0.33/1000 deliveries, increasing with advancing age and parity. The reporting of abnormal placentation, primarily the co-occurrence of placenta praevia and MAP, was linked with previous CS. Fifty-six of the 65 cases suffered MOH, most commonly associated with placenta praevia, MAP and uterine atony. Prophylactic and therapeutic uterotonic agents were appropriately used in the majority of cases. CONCLUSIONS: The incidence of PH in Ireland has been consistently low over 15 years, averaging one case every 3000 deliveries. The recognised risk factors of MAP, placenta praevia and PPH were independently associated with PH, with MAP being by far the strongest predictor. The vast majority of PH cases in our clinical audit were associated with MOH. Some deficiencies were noted in antenatal care, in certain elements of treatment and clinical governance protocols but adherence to guidelines was generally high.

Nipple stimulation for labor augmentation.

A randomized, prospective study was undertaken to evaluate the efficacy of nipple stimulation with a breast pump as compared to oxytocin for augmentation of labor. The average and maximal uterine activity achieved was significantly higher in the oxytocin-stimulated group, without significant differences in the length of labor stages, cesarean section rate, Apgar scores or umbilical artery pH. Fifty percent of the patients failed to respond to nipple stimulation after 30 minutes and were switched to oxytocin. These patients experienced a more rapid rate of cervical dilation in the active phase and reached higher maximal uterine activity with oxytocin stimulation; however, the cesarean section rate was highest in this group. Nipple stimulation with a breast pump appears to be a safe and effective alternative to oxytocin for the augmentation of labor.

Early detection of abnormal labor using the Friedman labor graph.

Early recognition and appropriate management of abnormal labor can reduce perinatal mortality and morbidity and lower the cesarean section rate. A simple labor graph devised over 25 years ago and later modified makes labor abnormalities easy to detect; the two main divisions of labor, the latent and active phases, are easily recognized. A prolonged latent phase has no serious effects on mother or fetus, but protraction and arrest disorders of the active phase--eg, protracted cervical dilatation, arrest or failure of descent of the presenting part--may have a deleterious effect. Common causes of a prolonged latent phase include false labor and inappropriate use of analgesia and anesthesia. Fetopelvic disproportion and fetal malposition are common causes of disorders of the active phase.