The association between history of retained placenta and success rate of misoprostol treatment for early pregnancy failure.

BACKGROUND: To date, the association between retained placenta and treatment success rate of misoprostol for early pregnancy failure has yet to be evaluated. The aim of this study was to evaluate this association and further investigated the connection between medical, clinical and sonographic parameters and treatment success. METHODS: We conducted a retrospective cohort study of women with early pregnancy failure treated with misoprostol from 2006 to 2021. The success rate of misoprostol treatment was compared between patients with history of retained placenta including women who underwent manual lysis of the placenta following delivery or patients who were found to have retained products of conception during their post-partum period (study group) and patients without such history (controls). Demographic, clinical, and sonographic characteristics as well as treatment outcomes were compared between the groups. RESULTS: A total of 271 women were included in the study (34 women in the study group compared to 237 women in the control group). Two-hundred and thirty-three women (86.0%) presented with missed abortion, and 38 (14.0%) with blighted ovum. Success rates of misoprostol treatment were 61.8% and 78.5% for the study and control groups, respectively (p = 0.032). Univariate analysis performed comparing successful vs. failed misoprostol treatment showed advanced age, gravidity, parity and gestational sac size (mm) on TVUS were associated with higher misoprostol treatment failure rate. Following a multivariate logistic regression model these variables did not reach statistical significance. CONCLUSION: Women who have an event of retained placenta following childbirth appear to have decreased success rate of treatment with misoprostol for early pregnancy failure. Larger studies are needed to confirm this finding.

Carbetocin for the prevention of post-partum hemorrhage after vaginal birth: a real-world application.

OBJECTIVE: To compare maternal outcomes using Carbetocin versus Oxytocin for the active management of the third stage of labor, given a temporary national shortage of Oxytocin. METHODS: We conducted a retrospective observational study on a cohort of 866 women with vaginal deliveries at our center, >36 weeks of gestation, between November 2018 and March 2019. During the shortage period, each woman received a single slow intravenous injection of Carbetocin 100 µg at delivery of the anterior shoulder, rather than Oxytocin 5 UI, as postpartum hemorrhage prophylaxis. 146 (16.9%) patients received Carbetocin versus 720 (83.1%) receiving Oxytocin. The outcomes were rates of postpartum hemorrhage, severe postpartum hemorrhage, and placental retention. RESULTS: Incidence rates of placental retention and postpartum hemorrhage were 4.9% and 9.4% respectively. Placenta retention was significantly more likely following Carbetocin administration (adjusted odds ratio 2.5; 95% confidence interval 1.2-5.0). Postpartum hemorrhage rates were not significantly different (adjusted odds ratio 1.1; 95% confidence interval 0.6-2.1), as were severe postpartum hemorrhage rates (adjusted odds ratio 0.7; 95% confidence interval 0.2-2.2). CONCLUSION: Carbetocin is as effective as Oxytocin for postpartum hemorrhage prevention. However, we would reserve it for use after placental delivery due to the increased retention rates.

Prevention of retained fetal membranes and improvement in subsequent fertility with oxytocin administration in cows with assisted calving.

In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1-5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.

Increase in white blood cell counts by pegbovigrastim in primiparous and multiparous grazing dairy cows and the interaction with prepartum body condition score and non-esterified fatty acids concentration.

The objective of this study was to determine if parity affected the effect of pegbovigrastim (PEG) treatment on white blood cell (WBC) counts in grazing dairy cows. Additionally, the association of prepartum body condition score (BCS) and non-esterified fatty acid (Pre-NEFA) concentration with WBC counts was investigated. The effect of early-lactation disease was included in the statistical analysis. A randomized controlled trial on four commercial grazing dairy farms was performed. Holstein primiparous (Control = 87, PEG = 89) and multiparous (Control = 181, PEG = 184) cows were randomly assigned to one of two treatments: first PEG dose 8 ± 5 (mean ± SD) days before the expected calving date and a second dose within 24 h after calving (PEG) compared to untreated controls (Control). Treatment effects were evaluated with mixed linear regression models. Treatment with PEG increased WBC, neutrophil, lymphocyte and monocyte counts at 6 ± 1 (mean ± SD) days in milk. Parity, BCS and their interactions with treatment were not associated with WBC counts. In control cows, Pre-NEFA concentration was associated with reduced WBC, neutrophil and lymphocyte counts and tended to be associated with reduced monocyte counts. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts and tended to reverse the negative association of Pre-NEFA concentration with WBC counts. In the PEG treated group, cows diagnosed with retained placenta or metritis showed lower neutrophil counts when compared to PEG treated cows without these clinical diseases. These data confirm that PEG treatment increases WBC, neutrophil, lymphocyte and monocyte counts in grazing dairy cows and that this effect is independent of parity. Pegbovigrastim treatment reversed the negative association of Pre-NEFA concentration with neutrophil and monocyte counts, and tended to reverse the negative association of Pre-NEFA concentration with WBC counts.

Pharmacologic intervention for the management of retained placenta: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Retained placenta affects 2% to 3.3% of all vaginal deliveries and is one of the leading causes of postpartum hemorrhage worldwide. Despite the prevalence of this condition, there is limited guidance on its management. OBJECTIVE: A systematic review and meta-analysis were performed to evaluate the efficacy of pharmacologic interventions for the management of retained placenta. STUDY DESIGN: PubMed, ClinicalTrials.gov, Cochrane Library, Web of Science, and Scopus were searched for full-text publications in English. Search terms included "retained placenta" AND "treatment" OR "therapy" OR "disease management" OR "Pitocin" OR "misoprostol" OR "Cytotec" OR "dinoprostone" OR "nitroglycerin" OR "carbetocin" OR "ergotamine," with no restriction on publication dates. Only randomized controlled trials were included. The primary outcome was the need for manual extraction of the placenta or dilation and curettage. Reviewers evaluated the quality of included articles using the Cochrane Collaboration's tool for assessing the risk of bias. Pooled risk ratios were estimated based on random- and fixed-effects analyses. Interstudy heterogeneity was considered when I2≥50%. RESULTS: The literature search identified 29 randomized controlled trials that met the inclusion criteria (2682 subjects). The most commonly used agent across the studies was oxytocin administered via umbilical vein injection; there was high heterogeneity among these studies (I2=62%). Oxytocin was inferior to carbetocin (risk ratio, 1.61; 95% confidence interval, 1.03-2.52) and prostaglandins (risk ratio, 2.63; 95% confidence interval, 1.18-5.86) for the primary outcome. For oxytocin, prostaglandin agents, and nitroglycerin, there was a trend toward favoring the study drug for the primary outcome compared with control or placebo. Compared with placebo or control, estimated blood loss was lower if pharmacologic interventions were administered, with a mean difference of 121.5 mL (95% confidence interval, -185.7 to -52.3). There was no difference in postpartum hemorrhage or the need for blood transfusion between pharmacologic interventions and placebo or control. CONCLUSION: Pooled estimates for oxytocin via umbilical vein injection, prostaglandin agents, and nitroglycerin performed favorably compared with placebo or control for the management of retained placenta. Carbetocin and prostaglandin agents were superior to oxytocin in reducing the need for manual extraction or dilation and curettage.

Umbilical vein injection of 400 versus 800 µg misoprostol for the treatment of retained placenta: A multicenter, randomized double-blind controlled trial.

AIMS: This trial was conducted to determine the efficacy of umbilical vein injection of 400 versus 800 µg misoprostol to deliver retained placenta and to compare both regimens regarding the time of placental delivery and amount of vaginal blood loss. METHODS: A double-blind, multicenter randomized clinical trial was undertaken in four teaching hospitals in the North of Iraq and Al-Azhar University Hospital in Egypt, from March 2016 to May 2019. Group I (274 women) received 400 µg misoprostol and group II (249 women) received 800 µg misoprostol. Data regarding the time of placental separation and amount of vaginal blood loss were analyzed and proportions were compared between groups using Chi-squared test. Mean values were compared using the Student's t-test. The Mann-Whitney test was used to determine the median of vaginal blood loss. RESULTS: The proportion of placental separation was 84.3% among women in group I and 86.7% of women in group II. The mean time of placental separation was 18.86 ± 234.2 and 17.86 ± 213.09 min in groups I and II, respectively (P < 0.05).The mean hemoglobin levels on admission and 24 h after placental deliveries were significantly higher in group I than group II. CONCLUSIONS: Intra-umbilical injection of 400 and 800 µg misoprostol were both safe and effective methods for delivery of retained placenta.

Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK.

BACKGROUND: Retained placenta following vaginal delivery is a major cause of postpartum haemorrhage. Currently, the only effective treatments for a retained placenta are the surgical procedures of manual removal of placenta (MROP) and uterine curettage, which are not universally available, particularly in low- and middle-income countries. The objective of the trial was to determine whether sublingual nitroglycerin spray was clinically effective and cost-effective for medical treatment of retained placenta following vaginal delivery. METHODS AND FINDINGS: A randomised, placebo-controlled, double-blind trial was undertaken between October 2014 and July 2017 at 29 delivery units in the UK (Edinburgh, Glasgow, Manchester, Newcastle, Preston, Warrington, Chesterfield, Crewe, Durham, West Middlesex, Aylesbury, Furness, Southampton, Bolton, Sunderland, Oxford, Nottingham [2 units], Burnley, Chertsey, Stockton-on-Tees, Middlesborough, Chester, Darlington, York, Reading, Milton Keynes, Telford, Frimley). In total, 1,107 women with retained placenta following vaginal delivery were recruited. The intervention was self-administered 2 puffs of sublingual nitroglycerin (800 µg; intervention, N = 543) or placebo spray (control, N = 564). The primary clinical outcome was the need for MROP, assessed at 15 minutes following administration of the intervention. Analysis was based on the intention-to-treat principle. The primary safety outcome was measured blood loss between study drug administration and transfer to the postnatal ward or other clinical area. The primary patient-sided outcomes were satisfaction with treatment and side-effect profile, assessed by questionnaires pre-discharge and 6 weeks post-delivery. Secondary clinical outcomes were measured at 5 and 15 minutes after study drug administration and prior to hospital discharge. There was no statistically significant or clinically meaningful difference in need for MROP by 15 minutes (primary clinical outcome, 505 [93.3%] for nitroglycerin versus 518 [92.0%] for placebo, odds ratio [OR] 1.01 [95% CI 0.98-1.04], p = 0.393) or blood loss (<500 ml: nitroglycerin, 238 [44.3%], versus placebo, 249 [44.5%]; 500 ml-1,000 ml: nitroglycerin, 180 [33.5%], versus placebo, 224 [40.0%]; >1,000 ml: nitroglycerin, 119 [22.2%], versus placebo, 87 [15.5%]; ordinal OR 1.14 [95% CI 0.88-1.48], p = 0.314) or satisfaction with treatment (nitroglycerin, 288 [75.4%], versus placebo, 303 [78.1%]; OR 0.87 [95% CI 0.62-1.22], p = 0.411) or health service costs (mean difference [£] 55.3 [95% CI -199.20 to 309.79]). Palpitations following drug administration were reported more often in the nitroglycerin group (36 [9.8%] versus 15 [4.0%], OR 2.60 [95% CI 1.40-4.84], p = 0.003). There were 52 serious adverse events during the trial, with no statistically significant difference in likelihood between groups (nitroglycerin, 27 [5.0%], versus placebo, 26 [4.6%]; OR 1.13 [95% CI 0.54-2.38], p = 0.747). The main limitation of our study was the low return rate for the 6-week postnatal questionnaire. There were, however, no differences in questionnaire return rates between study groups or between women who did and did not have MROP, with the patient-reported use of outpatient and primary care services at 6 weeks accounting for only a small proportion (approximately 5%) of overall health service costs. CONCLUSIONS: In this study, we found that nitroglycerin is neither clinically effective nor cost-effective as a medical treatment for retained placenta, and has increased side effects, suggesting it should not be used. Further research is required to identify an effective medical treatment for retained placenta to reduce the morbidity caused by this condition, particularly in low- and middle-income countries where surgical management is not available. TRIAL REGISTRATION: ISRCTN.com ISRCTN88609453 ClinicalTrials.gov NCT02085213.

Intra-umbilical vein injection of carbetocin versus oxytocin in the management of retained placenta.

INTRODUCTION: Retained placenta can be defined as lack of expulsion of the placenta within 30 min of delivery of the infant. It is a significant cause of maternal mortality and morbidity throughout the developing world. AIM OF THE WORK: The aim of this study was to compare the efficacy of intra-umbilical vein injection of carbetocin versus oxytocin in the management of retained placenta. PATIENTS AND METHODS: A total of 200 women were included in this study. They were divided into two groups; each 100 women. The first group received intra-umbilical vein injection of 1 mL carbetocin (containing 100 µg carbetocin) diluted in 20 mL normal saline 0.9% and the second group received intra-umbilical vein injection of 20 IU oxytocin diluted in 20 mL normal saline 0.9%. RESULTS: Total blood loss (ml) and duration of the third stage of labor (minutes) were significantly lower in carbetocin group when compared to oxytocin group. Postoperative Hb concentration (g/dl) was significantly higher in carbetocin group. Also there was a highly significant difference between both groups as regard change in Hb concentration (g/dl) with less change in the carbetocin group. The need for additional uterotonic drugs following placental delivery and the occurrence of postpartum hemorrhage and the need for blood transfusion were significantly lower in the carbetocin group. CONCLUSION: Intra-umbilical carbetocin is more effective than intra-umbilical oytocin as a method for management of retained placenta. Intra-umbilical carbetocin seems to have more acceptable hemodynamic safety profile when compared to intra-umbilical oxytocin in the management of retained placenta.

Antibiotic prophylaxis in ragged placental membranes: a prospective, multicentre, randomized trial.

BACKGROUND: Ragged placental membranes is a distinct entity from retained placenta and not uncommonly reported in midwifery texts. Although the incidence of postpartum endometritis is merely 1-5% after vaginal births, it remains the most common source of puerperal sepsis, contributing up to 15% of maternal mortality in low income countries. Geographically-remote centres in Malaysia prophylactically administer antibiotics for women with ragged placental membranes after vaginal birth, extrapolating evidence from retained placenta. We sought to clarify the rationale in continuing such practices. METHODS: This was an open-label, prospective, multicentre, randomized trial. Three hospitals where the current protocol was to administer prophylactic amoxycillin-clavulanic acid served as the sites of recruitment. Women who delivered vaginally beyond 24+ 0 weeks of gestation with ragged membranes were invited to participate in the trial and randomized into prophylaxis or expectant management with medical advice by blocks of 10, at a 1:1 ratio. A medication adherence diary was provided and patients followed up at 2 weeks and 6 weeks postpartum. RESULTS: A total of 6569 women gave birth vaginally in three centres during the trial period, of which 10.9% had ragged membranes. The incidence of endometritis was not significantly raised in women with or without prophylaxis (0.90% vs 0.29%; p = 0.60). All cases of endometritis presented within the first 2 weeks and preventive use of antibiotics did not ameliorate the severity of endometritis since rates of ICU admission, surgical evacuation and transfusion were comparable. CONCLUSION: Preventive use of antibiotics after vaginal delivery in women with ragged placental membranes did not result in a reduction of endometritis. Educating women on the signs and symptoms of endometritis would suffice. Based on the reported incidence of ragged membranes, a change in practice would result in 1500 less prescriptions of antibiotics per annum in these three centres. TRIAL REGISTRATION: NCT03459599 (Retrospectively registered on 9 March 2018).

Therapy of retained fetal membranes in cattle: Comparison of two treatment protocols.

This prospective study was conducted to compare two treatment protocols for retained foetal membranes (RFM) in cattle. The routine therapy consisting of intrauterine tetracycline boluses was compared with the administration of ozone foam, both intrauterine therapies without attempts to manually remove the placenta. Cows undergoing caesarean section, suffering from uterine torsion or prolapse of the uterus, and other illnesses than RFM on the first day post-partum were excluded. Values for baseline variables as age, breed, yearly milk yield, parity, pregnancy duration, calving season and number of routine intrauterine treatments were not different between the groups. Number of days with rectal temperature >39.7 °C within the first 10 days in milk (DIM) were greater in the ozone group. Number of escape therapies were recorded when there was imposing of this therapy as a result of cows having a fever (based on rectal temperature >39.7 °C) and a significant reduced food intake. Escape therapies consisted of parenteral administration of tetracyclines and NSAIDS during the first 10 DIM. Number of escape therapies, however, was not different between the groups. Results from use of a logistic regression model with fever as a dichotomous variable indicated there was no effect of breed, studbook, type of stall, pasture, business and no effect of age or milk yield. In a second assessment, cows were evaluated until 200 DIM. Results from a survival analysis indicated group (Te/Oz) did not affect rate of culling from the herd.

Glyceryl trinitrate to reduce the need for manual removal of retained placenta following vaginal delivery: the GOT-IT RCT.

BACKGROUND: Retained placenta is associated with postpartum haemorrhage and can lead to significant maternal morbidity if untreated. The only effective treatment is the surgical procedure of manual removal of placenta, which is costly, requires skilled staff, requires an operative environment and is unpleasant for women. Small studies suggest that glyceryl trinitrate may be an effective medical alternative. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of sublingual glyceryl trinitrate spray compared with placebo in reducing the need for manual removal of placenta in women with retained placenta after vaginal delivery following the failure of current management. DESIGN: A group-sequential randomised double-blind placebo-controlled trial with a cost-effectiveness analysis. SETTING: There were 29 obstetric units in the UK involved in the study. PARTICIPANTS: There were 1107 women (glyceryl trinitrate group, n = 543; placebo group, n = 564) randomised between October 2014 and July 2017. INTERVENTIONS: Glyceryl trinitrate spray was administered to 541 women in the intervention group, and a placebo was administered to 563 women in the control group. MAIN OUTCOME MEASURES: Four primary outcomes were defined: (1) clinical - the need for manual removal of placenta, (2) safety - measured blood loss, (3) patient sided - satisfaction with treatment and side effects and (4) economic - cost-effectiveness of both treatments using the UK NHS perspective. Secondary clinical outcomes included a > 15% decrease in haemoglobin level, time from randomisation to delivery of placenta in theatre, the need for earlier manual removal of placenta than planned, increase in heart rate or decrease in blood pressure, requirement for blood transfusion, requirement for general anaesthesia, maternal pyrexia, and sustained uterine relaxation requiring additional uterotonics. RESULTS: No difference was observed between the glyceryl trinitrate group and the control group for the placenta remaining undelivered within 15 minutes of study treatment (93.3% vs. 92%; odds ratio 1.01, 95% confidence interval 0.98 to 1.04; p = 0.393). There was no difference in blood loss of > 1000 ml between the glyceryl trinitrate group and the control group (22.2% vs. 15.5%; odds ratio 1.14, 95% confidence interval 0.88 to 1.48; p = 0.314). Palpitations were more common in the glyceryl trinitrate group than in the control group after taking the study drug (9.8% vs. 4.0%; odds ratio 2.60, 95% confidence interval 1.40 to 4.84; p = 0.003). There was no difference in any other measures of patient satisfaction between the groups. There was no difference in costs to the health service between groups (mean difference £55.30, 95% confidence interval -£199.20 to £309.79). Secondary outcomes revealed that a fall in systolic or diastolic blood pressure, or an increase in heart rate, was more common in the glyceryl trinitrate group than in the control group (odds ratio 4.9, 95% confidence interval 3.7 to 6.4; p < 0.001). The need for a blood transfusion was also more common in the glyceryl trinitrate group than in the control group (odds ratio 1.53, 95% confidence interval 1.04 to 2.25; p = 0.033). CONCLUSIONS: Glyceryl trinitrate spray did not increase the delivery of retained placenta within 15 minutes of administration when compared with the placebo, and was not cost-effective for medical management of retained placenta. More participants reported palpitations and required a blood transfusion in the glyceryl trinitrate group. Further research into alternative methods of medical management of retained placenta is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88609453. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 70. See the NIHR Journals Library website for further project information.

A retained placenta is diagnosed when, following the birth of a baby, the placenta is not delivered. When this situation occurs, women are at risk of bleeding heavily. The only way to treat a retained placenta is for a trained doctor to remove it by an operation in theatre. This procedure can be painful and upsetting. Furthermore, the timing of the operation can interrupt mother­baby bonding immediately after giving birth. The study tested if the use of glyceryl trinitrate spray, given as two puffs under the woman's tongue following the diagnosis of retained placenta, may help the placenta to deliver without an operation. The study also tested if glyceryl trinitrate was safe, assessed what women thought about the treatment and compared the costs of glyceryl trinitrate with those of current operative management. This study included 1107 women diagnosed with retained placenta following the birth of their baby. Half of the women were treated with glyceryl trinitrate spray and the other half were treated with a dummy spray, which looked identical but did not contain the active treatment. If the placenta delivered within 15 minutes of the study treatment being taken, this was considered a success. However, if the placenta did not deliver within 15 minutes and the woman had to have her placenta removed by an operation, then this was viewed as unsuccessful. Neither the woman nor the clinical staff knew if the treatment given was the glyceryl trinitrate spray or the dummy spray. The results indicate that, although women were happy to be involved in the trial and the treatment was safe, the use of glyceryl trinitrate spray did not reduce the need for the placenta to be manually removed by an operation in theatre. Furthermore, glyceryl trinitrate spray was not cost-effective.

Administration of an herbal powder based on traditional Chinese veterinary medicine enhanced the fertility of Holstein dairy cows affected with retained placenta.

Herbal powder consisted of Leonurus artemisia (Laur.) S.Y. Hu F, Angelica sinensis (OLIV.) DIELS (radix), Ligusticum chuanxiong HORT (radix), Sparganium stolonif erum (Graebn.) Buch.-Ham.exJuz (radix), Curcuma zedoaria (Christm.) ROSC (radix), Cyperu srotundus Linn. (radix), and Glycyrrhiza uralensis FISCH (radix) has a high efficacy in facilitating earlier expulsion of the placenta and lowering puerperal metritis risk, and reproductive outcomes might represent the ultimate therapeutic goal of a treatment option for retained placenta in cows. This trial was carried out to further evaluate the effect of the herbal powder on the subsequent fertility of Holstein dairy cows with retained placenta. The animals were treated with herbal powder (n = 85, 0.5 g crude herb/kg bw, p.o.) once daily for 1-3 day(s) or ceftiofur hydrochloride (n = 72, 2.2 mg/kg bw, i.m.) twice daily for 3 consecutive days, and 75 cows with no clinically visible pathological conditions, given without assistance and with no retained placenta diagnosis were included into the control group. Calving-to-first-AI interval (67.2 ±â€¯16.2 vs. 81.9 ±â€¯28.7, p < 0.01), services per conception (1.9 ±â€¯1.2 vs. 2.4 ±â€¯1.7, p < 0.05), and calving-to-conception interval (101.8 ±â€¯47.0 vs. 129.6 ±â€¯56.6, p < 0.01) were lower in the herbal group than in ceftiofur group. Percentage of cows pregnant within 180 days postpartum was the higher in cows from the herbal group compared to cows in ceftiofur group (75.0% vs. 90.6%, p < 0.01). Additionally, the cows in the herbal group had a very similar fertility compared to the healthy controls, including calving-to-first-AI interval (67.2 ±â€¯16.2 vs. 66.3 ±â€¯16.9, p＞0.05), first AI conception proportion (48.2% vs. 50.6%, p＞0.05), services per conception (1.9 ±â€¯1.2 vs. 2.0 ±â€¯1.1, p＞0.05), percentage of cows pregnant within 180 days postpartum (90.6% vs. 93.3%, p＞0.05) and calving-to-conception interval (101.8 ±â€¯47.0 vs. 99.0 ±â€¯44.7, p＞0.05). Herbal powder used in this trial might have a beneficial clinical efficacy, and thus, might represent a potential effective treatment strategy to improve the subsequent fertility of dairy cows with retained placenta.

Systematic review of prostaglandin analogues for retained placenta.

BACKGROUND: Medical management of retained placenta could be a safe alternative to manual removal. OBJECTIVE: To evaluate the efficacy of prostaglandin analogues for retained placenta. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, ICTRP, LILACS, and OpenSIGLE were searched without language restrictions from inception to January 31, 2017, by combining terms for retained placenta and prostaglandin analogues. SELECTION CRITERIA: Randomized controlled trials comparing prostaglandin analogues with any other intervention. DATA COLLECTION AND ANALYSIS: Trials were independently assessed for inclusion, data extraction, and risk of bias. Data were extracted for meta-analyses. GRADE was used to evaluate the quality of data. MAIN RESULTS: Seven randomized controlled trials (851 patients) were included. Prostaglandins did not increase the placenta expulsion rate (relative risk [RR] 1.40, 95% confidence interval [CI] 0.83-2.36) or decrease maternal transfusion (RR 0.72, 95% CI 0.43-1.22). In comparison with oxytocin, prostaglandins did not modify the expulsion rate (RR 1.26, 95% CI 0.90-1.78), maternal transfusion (RR 1.05, 95% CI 0.27-4.09), or time for delivery of placenta (mean difference -1.56 minutes, 95% CI, -9.25-6.13). Three trials comparing prostaglandins with oxytocin agonists, ergometrine, and manual removal reported similar results. CONCLUSIONS: Prostaglandin analogues do not offer an effective alternative for management of retained placenta.

Differential effects of a single dose of oral calcium based on postpartum plasma calcium concentration in Holstein cows.

Our objectives were to determine (1) the effect of a single dose of an oral Ca bolus within 24 h after parturition on plasma Ca concentration, (2) the response of primiparous (PP) and multiparous (MP) cows to this supplementation strategy, and (3) differential responses based on plasma Ca at enrollment. For objective 1, cows from 1 commercial dairy in New York State were enrolled within 19 h after parturition (mean ± standard deviation = 8.3 ± 5.3 h) and randomized within parity group (first, second, and ≥third) to control [CON (n = 25); no placebo] or a single dose bolus treatment [BOL (n = 25); 3 oral Ca boluses supplying 54 to 64 g of Ca]. Plasma Ca was measured repeatedly between 1 and 24 h following treatment. For objectives 2 and 3, cows on 6 commercial farms in New York State were assigned to treatment as for objective 1 (CON, n = 1,973; BOL, n = 1,976). Herd records for health, reproduction, and Dairy Herd Improvement Association test day milk production were collected. Mixed effect multivariable models were developed using repeated measures ANOVA, Poisson regression, or proportional hazard models. Objective 2 analyses considered treatment with periparturient risk factors, whereas objective 3 analyses also considered Ca status. No difference was observed for plasma Ca between 1 and 24 h after treatment. Primiparous cows assigned to BOL calving at >712 d old had decreased risk of one or more health disorders [≤30 d in milk; risk ratio (RR) = 0.65, 95% confidence interval (CI) = 0.51 to 0.84] and those with body condition score >3.5 responded to BOL with increased milk production (CON = 31.7 ± 1.1, BOL = 35.1 ± 1.1 kg/d), as did those with days carried calf >277 (CON = 31.9 ± 1.0, BOL = 34.7 ± 1.0 kg/d). Reduced risk of one or more health disorders was observed in parity ≥3 (RR = 0.85, 95% CI = 0.81 to 0.89) and MP cows with body condition score >3.5 (retained placenta; RR = 0.70, 95% CI = 0.58 to 0.84) or that were lame (displaced abomasum; RR = 0.49, 95% CI = 0.32 to 0.75). Differential responses for PP cows by Ca status were minimal. For MP cows with low plasma Ca, BOL decreased risk of additional Ca treatment (≤1.8 mmol/L; RR = 0.57, 95% CI = 0.40 to 0.80) as well as risk of one or more health disorders (≤2.15 mmol/L; RR = 0.90, 95% CI = 0.85 to 0.95). Supplementation with a single oral dose of Ca could be targeted to periparturient risk groups for improved health. Calcium status did not differentiate responses of PP cows, but MP cows with low Ca at parturition had improved health status when supplemented.

A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol.

INTRODUCTION: A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). METHODS AND ANALYSIS: The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISCRTN88609453; Pre-results.

Different routes and forms of uterotonics for treatment of retained placenta: a randomized clinical trial.

OBJECTIVES: To compare between three different uterotonics (oxytocin, carbetocin and misoprostol) given via three different routes (intraumbilical, intravenous and sublingual, respectively) in reducing the need for manual removal of placenta (MROP). METHODS: A randomized trial for cases with retained placenta 30 min following vaginal delivery. They received intraumbilical oxytocin, intravenous carbetocin or sublingual misoprostol. Main outcome measures were delivery of the placenta within 30 min following drug administration, and need for MROP. Secondary outcome measures were injection to placental delivery time, post-delivery hemoglobin, need for blood transfusion or additional uterotonics. RESULTS: The overall success rate was 66.7% (64/96), 71.3% (67/94) and 63.7% (58/91) for oxytocin, carbetocin and misoprostol groups, respectively (p > 0.05). When time needed to achieve placental delivery considered, a significant difference was observed with the shortest time for carbetocin (16.61 ± 3.76 min), then oxytocin (18.28 ± 3.34 min) and lastly misoprostol (23.00 ± 3.38 min) (p <0.001). Again, carbetocin group needed less additional uterotonics to achieve adequate uterine contractions (p <0.001). CONCLUSIONS: Although we aimed to exploit the advantage of certain drug over another, all seemed to have close efficacy but it would be important that further research should highlight availability, cost, ease of administration and storage requirements to determine which agent would best be used in this clinical scenario.

Uterotonics and tocolytics for anesthesiologists.

PURPOSE OF REVIEW: Obstetric anesthesiologists are supposed to understand the uterotonics and tocolytics used in the perinatal period to provide a better clinical practice. This review describes current consensus of uterotonics and tocolytics used in the perinatal period that an obstetric anesthesiologist should know. RECENT FINDINGS: Rational use of uterotonics for cesarean section has been well studied in the past decades. Oxytocin remained as a first line uterotonics for cesarean section. For continuous infusion, it is reported that ED90 is higher for laboring parturients than for nonlaboring parturients (6.2 vs. 44.2 IU/h) implying that protocol for oxytocin infusion should be different between laboring patients with prior exposure to oxytocin and nonlaboring patients. For bolus administration, 'rule of three' has been proposed and its efficacy has been reported. When oxytocin fails to achieve sufficient uterine contraction, second-line agents must be administered, and it has been reported that methylergonovine is a superior second-line uterotonic to carboprost. On the other hand, the role of tocolytic agents in obstetric anesthesia has not been well studied. SUMMARY: Anesthesiologists involved in obstetric anesthesia should be able to determine the appropriate uterotonic for cesarean section and know the indication of tocolytics in perinatal period.

The effects of sequential use of oxytocin and sublingual nitroglycerin in the cases of retained placenta.

OBJECTIVES: To evaluate the effects of adding sublingual nitroglycerin to oxytocin, for delivery of retained placenta after vaginal delivery. METHOD: The study was performed as a placebo controlled clinical trial on women who did not finish delivering placenta after 30 min of active management of the third stage of labor. In case group, 1 mg nitroglycerin and in the control group, placebo was prescribed sublingually. RESULTS: In total, 80 women finished the study. The number of manual removal of placenta did not show significant difference between the two groups [25 women (62.5%) in the case and 30 women (75%) in the control group, p = 0.335]. There was no significant difference between the two groups according to duration of the third stage of labor, hemoglobin index, decline in HB index >30% and maternal vital signs after treatment. There was no significant difference between the two groups according to adverse effects [eight women (20%) in the case group and four (10%) in the control group (p = 0.348)]. CONCLUSION: The sequential use of oxytocin and sublingual nitroglycerin could not lead to delivery of more placentas and did not reduce the necessity of manual removal of placenta in comparison with placebo.

Nitroglycerin for management of retained placenta.

BACKGROUND: Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. OBJECTIVES: To evaluate the benefits and harms of NTG as a tocolytic, either alone or in addition to uterotonics, in the management of retained placenta. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2015), reference lists of retrieved studies and contacted experts in the field. SELECTION CRITERIA: Any adequately randomised controlled trial (RCT) comparing the use of NTG, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included three randomised controlled trials (RCTs) with 175 women. The three published RCTs compared NTG alone versus placebo. The detachment status of retained placenta was unknown in all three RCTs. Collectively, among the three included trials, two were judged to be at low risk of bias and the third trial was judged to be at high risk of bias for two domains: incomplete outcome data and selective reporting. The three trials reported seven out of 23 of the review's pre-specified outcomes.The primary outcome "manual removal of the placenta" was reported in all three studies. No differences were seen between NTG and placebo for manual removal of the placenta (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 to 1.46; women = 175; I² = 81%). A random-effects model was used because of evidence of substantial heterogeneity in the analysis. There were also no differences between groups for risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62 to 1.39; women = 150; studies = two; I² = 0%). Blood transfusion was only reported in one study (40 women) and again there was no difference between groups (RR 1.00, 95% CI 0.07 to 14.90; women = 40; I² = 0%). Mean blood loss (mL) was reported in the three studies and no differences were observed (mean difference (MD) -115.31, 95% CI -306.25 to 75.63; women = 169; I² = 83%). Nitroglycerin administration was not associated with an increase in headaches (RR 1.09, 95% CI 0.80 to 1.47; women = 174; studies = three; I² = 0%). However, nitroglycerin administration was associated with a significant, though mild, decrease in systolic and diastolic blood pressure and a significant increase in pulse rate (MD -3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per minute) respectively (reported by only one study including 24 participants). Maternal mortality and addition of therapeutic uterotonics were not reported in any study. AUTHORS' CONCLUSIONS: In cases of retained placenta, currently available data showed that the use of NTG alone did not reduce the need for manual removal of placenta. This intervention did not increase the incidence of severe postpartum haemorrhage nor the need for blood transfusion. Haemodynamically, NTG had a significant though mild effect on both pulse rate and blood pressure.