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Background/aim: To investigate the optimal protocol for frozen-thawed embryo transfer (FET) cycles in patients who previously had a cycle cancellation due to uterine peristalsis (UP). Materials and methods: Thirty-four patients with previous embryo transfer (ET) cancellation due to UP during artificial cycle (AC) were included retrospectively. In the proceeding cycle, endometrium was prepared with AC (n: 23) in AC-FET group or with stimulated cycle that contains letrozole (L) (n: 11) in L-FET group. Intravenous bolus dose of 6.75 mg atosiban (Tractocile; Ferring Pharmaceuticals, Switzerland) injection was performed to all patients of AC-FET group due to UP = 4/min on the planned ET day of proceeding cycle. Atosiban was not used in L-FET group. Primary outcome was live birth rate (LBR) per ET. Secondary outcomes were clinical pregnancy rate (CPR) per ET, implantation rate (IR), cycle cancellation rate. Results: The baseline characteristics such as age, body mass index, antral follicle count, duration of infertility, and the number of prior in vitro fertilization attempts of each group were similar. The IR, CPR per ET, LBR per ET, CPR per cycle and LBR per cycle were significantly higher; cycle cancellation rates were significantly lower in L-FET group as compared to the AC-FET group. Conclusion: Endometrial preparation with letrozole significantly improves CPR and LBR in FET cycles of patients with previous cycle cancellations due to UP. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to generate baseline evidence regarding the effectiveness of atosiban in delaying delivery by ≥48 hours among pregnant women presenting with threatened preterm labour (TPL). The secondary objective was to assess the relationship between atosiban success and various perinatal factors and neonatal outcomes. Methods: This retrospective study was conducted between June 2008 and May 2018 at the Sultan Qaboos University Hospital, Muscat, Oman. The medical records of all pregnant women who received atosiban between 24–34 gestational weeks for TPL during this period were reviewed. Results: A total of 159 women were included in the study. Atosiban was successful in delaying delivery by ≥48 hours in 130 cases (81.8%). Approximately half of the women (50.9%) achieved uterine quiescence in <12 hours. Failure to delay delivery by ≥48 hours was significantly lower among women with normal versus abnormal cervical findings (11.1% versus 25.6%; P = 0.023). Only 9.4% of women experienced minor side-effects. Mean birth weight (2,724.55 versus 1,707.59 g; P <0.001) and Apgar scores at 5 minutes (9.66 versus 8.28; P <0.001) were significantly higher among neonates delivered at ≥48 versus <48 hours post-atosiban, whereas the rate of neonatal respiratory distress syndrome was significantly lower (18.4% versus 81.6%; P <0.001). Conclusion: Atosiban was highly effective in delaying delivery by ≥48 hours and resulted in few adverse maternal side-effects and neonatal outcomes. To the best of the authors’ knowledge, this is the first study conducted in Oman to evaluate the effectiveness of atosiban in preventing preterm labour. [ABSTRACT FROM AUTHOR]

Introduction: Breech/transverse presentation is responsible for about 30-50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women's health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice.Objective: To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV.Study Design: Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding "atosiban" and "external cephalic version". We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI).Data Collection and Analysis: Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98-1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69-1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99-1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27-4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58-1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47].Conclusion: The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates. [ABSTRACT FROM AUTHOR]

The key intermediate NH2-Ile-Thr(Bzl)-Asn-Cys(Bzl)-Pro-COOH of Atosiban was prepared from N-Boc-S-Bzl-cysteine by the stepwise lengthening of the chain according to the repetitive N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) strategy. This synthetic route required no chromatography purification and can be readily performed, yielding a highly pure pentapeptide compound.

Background and Objectives: The aim of this study was to investigate the contractile effects of oxytocin (OT) in human detrusor muscle in in vitro conditions.Material and Methods: Human detrusor muscle samples were obtained from seven patients that undergone radical cystectomy. Four female Wistar rats' uterine samples were used as control. Contractile responses were tested of carbachol in organ bath. Cumulative concentration response curves were constructed to OT and then the strips were incubated with atosiban (OT antagonist) and a second concentration response curve to OT were constructed.Results: Carbachol, contracted all human strips for the functionality test whereas OT in any concentrations did not produce significant contraction on all human strips. In only one bladder strip and in a very high concentration slight contraction was recorded. Moreover no contractile response was recorded in any OT concentrations in the presence of atosiban. The rat uterine strips responded to OT in a dose dependent manner. Atosiban, the OT receptor antagonist diminished totally those contractile responses.Conclusion: It is been demonstrated here that there is no contractile response to OT in human detrusor muscle. These findings should be supported by further investigations determining the presence of the OT receptor in human detrusor. [ABSTRACT FROM AUTHOR]

Relevance. Toсolytic therapy is the only method that is used in the treatment of pregnant women with preterm labor. However, the effectiveness and safety of this therapy is still a matter of debate. One of the least studied issues of this problem is the safety of therapy, which is primarily manifested by the frequency of side effects. The aim is to carry out a comparative study of the safety of the most common tocolytic agents - atosiban, nifedipine and hexoprenaline sulfate. Material and methods. The study included 173 pregnant women with threatening premature births in a period of 28 to 34 weeks. In 54 cases, tocolysis with nifedipinum, 57 with atosiban, 62 with hexoprenaline was performed. To assess the effectiveness of tocolysis, clinical and instrumental methods of control (ultrasound with cervicometry) were used. The primary outcome points were the frequency of prolongation of pregnancy at 48 h and the incidence of side effects, including those requiring the termination of tocolysis. Results. Prolongation of pregnancy at 48 h was achieved in groups of nifedipine, atosiban and hexoprenaline sulfate, respectively in 46 (85.19%), 55 (96.49%) and 53 (77.40%) pregnant. Atosiban showed significantly higher efficacy. In 8 cases of tocolysis with nifedipine and 3 - hexoprenaline, the tocolysis protocol was not performed due to intolerance of treatment. In these observations, the highest frequency of preterm labor occurred. After excluding these observations from the analysis of differences in the frequency of prolongation of pregnancy was not. The overall frequency of adverse events in the groups was 38.9, 12.3 and 82.3%, and was significantly lower in the atosiban group than nifedipine and hexoprenaline sulfate. Conclusions. The effectiveness of tocolysis is affected by the tolerability of the drugs. Atosiban showed the best of the three drug safety profile. With comparable efficacy, atosiban has proven to be a drug that, to a greater extent than nifedipine and hexoprenaline sulfate, meets the current requirements for tocolytic drugs.

Background: Recent developments in assisted reproductive technology focus on potential advances to improve its success rate. Atosiban, a combined oxytocin/vasopressin V1a receptor antagonist, is a novel class of drug involved in basic priming of the uterus for successful implantation during embryo transfer (ET). Objectives: The objective of this study is to evaluate the efficacy of atosiban (study group) in ET patients in comparison to placebo (control group) regarding implantation rate (IR), clinical pregnancy rate (CPR), and ongoing pregnancy rate and to assess the safety profile of atosiban. Materials and Methods: A total of 320 women undergoing in vitro fertilization-ET at a tertiary care hospital were enrolled in the study. In the study group, atosiban was given as initial intravenous (IV) bolus injection 0.9 ml (6.75 mg), 30 min before ET followed by continuous IV infusion of atosiban. In the control group, placebo (normal saline) was infused at the same rate and dose. Pregnancy was confirmed 14 days after ET by β-human chronic gonadotropin level. IR and CPR were determined by doing transvaginal sonography 3 weeks and 6 weeks postET, respectively. Results: In women with atosiban treatment, the positive pregnancy rate and CPRs were 41.25% and 36.25%, respectively. The IR per embryo transferred was 17.5%. No major side effects of atosiban were noted among enlisted patients. The miscarriage rate and ectopic pregnancy rate were low (12.12% and 4.54%, respectively). Forty-two women had singleton gestation, while twin and triplet pregnancies were encountered in 13 and 3 women, respectively. No congenital anomalies were observed during an antenatal scan at 18–20 weeks in ongoing pregnancies. The positive pregnancy rate, the CPR, and the IR in the control group was 35%, 30%, and 16.5%, respectively, which was significantly lower than the atosiban group. Conclusion: Atosiban reduces uterine contractions and increases endomyometrial perfusion, both of which have potential benefits regarding improved IRs, CPR, and ongoing pregnancy rates. Atosiban has a good embryonic safety profile.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, we discussed recent tocolytic treatments for the prevention of preterm birth with obstetricians from Korea and Taiwan. The rate of preterm birth in our countries has been increasing, and optimal tocolytic treatments are of great concern. Ritodrine hydrochloride was the first available drug for tocolysis in our countries and is often administered for over 48 h, although it is not recommended for maintenance therapy in Western countries. Meanwhile, there are differences in the use of other tocolytic drugs, based on approval of the drugs and the health insurance systems. Nifedipine and atosiban have not been considered first‐line agents in Japan. The long‐term use of unnecessary tocolysis should be avoided, and the introduction of other tocolytic drugs, including nifedipine or atosiban, should be discussed. [ABSTRACT FROM AUTHOR]

Objective: To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years.Design: The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group.Methods: Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health.Main Outcome Measures: The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years.Results: Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects.Conclusion: Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth.Tweetable Abstract: Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour. [ABSTRACT FROM AUTHOR]

Key points: A moderate level of exercise has beneficial effects for the prevention of gastric ulcers.Although regular aerobic exercise was shown to elevate serum oxytocin levels and exogenously administered oxytocin exerts an anti‐ulcer activity, the role of endogenous oxytocin in the gastroprotective effects of exercise has not yet been elucidated.We showed that increased anxiety and oxidative gastric damage induced by gastric ulcers were reversed in pre‐exercised rats, while reduced hypothalamic oxytocin expression and decreased myenteric oxytocin receptor expression due to gastric ulcers were abolished by exercise.We also reported that the blockade of oxytocin receptors exaggerated gastric damage in exercised rats with ulcers.Our data establish that endogenous oxytocin is the key mediator in the beneficial effects of regular physical activity in alleviating gastric injury. Exercise increases serum oxytocin levels and exogenous oxytocin exerts an anti‐ulcer activity; but the role of oxytocin in the protective effects of exercise against gastric ulcers has not yet been evaluated. This study was designed to investigate the impact of regular swimming exercise on oxidative gastric injury, and the role of oxytocin receptor activity in the anxiolytic and anti‐inflammatory actions of exercise. Adult Wistar albino rats of both sexes performed swimming exercise (30 min/day, 5 days) or stayed sedentary. At the end of the 6‐week exercise/sedentary protocol, rats were injected intraperitoneally with atosiban (0.1 mg/kg/day) or saline for 4 days. On the 5th day, under anaesthesia, acetic acid (ulcer) or saline (sham) was applied onto the gastric serosa and the treatments were continued. On the 9th day, anxiety levels were determined; gastric blood flow was measured, and blood, gastric and brain tissues were obtained. Induction of ulcers in sedentary rats increased anxiety and serum corticosterone levels; but reduced gastric blood flow and resulted in apoptosis and oxidative gastric damage with increased cytokine expressions. However, when ulcers were induced in pre‐exercised rats, behavioural and biochemical alterations due to gastric damage were reversed. The inhibition of oxytocin receptors by atosiban exaggerated pro‐inflammatory cytokine expressions and gastric lipid peroxidation in the stomachs of exercised rats with ulcers. When rats had regularly exercised prior to ulcer induction, reductions in the immunolabelling of hypothalamic oxytocin and myenteric oxytocin receptors were abolished, suggesting that exercise‐induced alleviation of gastric injury may involve the reversal of down‐regulated oxytocinergic activity. Key points: A moderate level of exercise has beneficial effects for the prevention of gastric ulcers.Although regular aerobic exercise was shown to elevate serum oxytocin levels and exogenously administered oxytocin exerts an anti‐ulcer activity, the role of endogenous oxytocin in the gastroprotective effects of exercise has not yet been elucidated.We showed that increased anxiety and oxidative gastric damage induced by gastric ulcers were reversed in pre‐exercised rats, while reduced hypothalamic oxytocin expression and decreased myenteric oxytocin receptor expression due to gastric ulcers were abolished by exercise.We also reported that the blockade of oxytocin receptors exaggerated gastric damage in exercised rats with ulcers.Our data establish that endogenous oxytocin is the key mediator in the beneficial effects of regular physical activity in alleviating gastric injury. [ABSTRACT FROM AUTHOR]

We assessed the effect of atosiban on pregnancy outcomes following in vitro fertilization (IVF) treatment among infertile women requiring different numbers of embryo transfer (ET) cycles (i.e., one, two, and more than two ET cycles). A longitudinal cohort study was conducted by utilizing the data from the Assisted Reproductive Technology Center in a university tertiary hospital during 2007–2017. Patients receiving IVF treatment with at least one ET cycle were included. Pregnancy outcomes following IVF treatment, including biochemical, clinical, and ongoing pregnancies, were investigated. The association between atosiban and IVF pregnancy was assessed using logistic generalized estimating equation models, with adjustment for time-varying clinical characteristics (e.g., maternal age) across multiple ET cycles for an individual. 403 women with 838 ET cycles were included, where 165 patients required one ET cycle, 133 patients required two ET cycles (a total of 266 ET cycles), and 105 patients required more than two ET cycles (a total of 407 ET cycles). Atosiban use was not significantly associated with pregnancy outcomes among all study infertile women undergoing IVF treatment. However, the results for women requiring more than two ET cycles showed significantly increased pregnancy rates associated with atosiban use (i.e., odds ratios [95% confidence interval] of 4.40 [1.52, 12.73] and 2.85 [1.45, 5.60] for clinical and ongoing pregnancies, respectively). This association was not observed for the women requiring only one or two ET cycles. Atosiban is a potential treatment for enhancing IVF pregnancy, especially among infertile women requiring more than two ET cycles. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the efficacy and safety of tocolytic agents - atosiban and hexoprenaline.Patients and methods: The study included 119 pregnant women with threatening preterm labour between 28 to 34 weeks of gestation. Sixty two pregnant received 62 tocolysis by hexoprenaline and fifty seven - atosiban. There were no differences in the clinical condition of pregnant women and features of preterm labour among groups before start of the tocolysis.The degree of effectiveness is determined by the duration of the pregnancy prolongation (48 hours, 7 days, more than 14 days).Results: 9 women of 62 that received hexoprenaline tocolysis (22,6%), and 2 – atosiban (3.5%) failed to prolong the pregnancy for more than 48 hours (p < 0,05). Additionally, 5 women of the hexoprenaline group had premature labour within the first week from the treatment start and eight within 7-14 days. In the group of women with an effective atosiban tocolysis all births took place in a range of more than 7 days from the beginning of tocolysis. Four woman in hexoprenaline group received one repeated course of therapy with this drug (without a loading dose) for 24 hours. In atosiban group full repeated course was conducted in the two cases. Full-term gestation births occurred in 14 women (22.6%) after hexoprenaline tocolysis and in 19 (33.3%) – atosiban (p > 0,05%). On average, atosiban tocolysis allowed to prolong pregnancy by 6.5 days longer than hexoprenaline (p < 0,05).Conclusion: The results of study has shown that atosiban is more effective than hexoprenaline in pregnancy prolongation for more than 48 hours in threatening preterm labor.

The purpose of this study was to evaluate the effect of atosiban on the outcomes of infertile women undergoing in vitro fertilization (IVF) with difficult embryo transfers (ETs). This randomized double-blind study enrolled 204 infertile women with difficult ETs during IVF treatment between June 2014 and June 2018. According to a computer-generated randomization list, participants were randomized into placebo (n = 102) and atosiban (n = 102) groups. In atosiban group, atosiban with a total dose of 37.5 mg was administered. All of the patients underwent IVF-ET using cryopreserved embryos. The clinical pregnancy rate per cycle and implantation rate per transfer (45.1% and 26.5%) in atosiban group were significantly higher than those of placebo group (15.6% and 9.7%, respectively; P <.05). This study showed that administration of atosiban during ET was extraordinarily effective for patients with difficult transfers. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the impact of atosiban as a tocolytic agent in patients treated with the fetoscopic endotracheal occlusion (FETO) procedure due to congenital diaphragmatic hernia (CDH). As premature birth after fetoscopy remains a serious concern, an effort to reduce prematurity is required. Methods: A total of 43 patients with severe CDH treated with FETO were enrolled in this study. The study group consisted of 22 patients who received atosiban during the FETO procedure and a control group of 21 patients who did not receive atosiban during the FETO procedure. Demographic data, gestational age (GA) at delivery, cervical length and GA at premature rupture of membranes (PROM) were evaluated. Results: The GA at delivery was significantly different between the two groups studied. The median GA at delivery was 32.6 and 34.5 weeks in the no-atosiban vs. atosiban groups, respectively (P = 0.013). The median cervical length was 29.9 and 31.2 mm for the no-atosiban and atosiban groups, respectively, and was not statistically significant (P = 0.28). There were no significant correlations between groups for the occurrence of PROM, GA at the time of PROM, duration of the procedures, parity, maternal body mass index (BMI) or age. In the univariate linear regression model, the only factor independently associated with GA at delivery was the use of atosiban during FETO procedures (β = 0.375; P < 0.013). Conclusion: In cases of severe CDH treated with FETO, the use of atosiban as a tocolytic agent during the procedure prolonged pregnancy by 2 weeks. Cervical length, duration of FETO or maternal characteristics were not associated with GA at delivery. [ABSTRACT FROM AUTHOR]

With the advancements of high throughput computational screening procedures, drug repurposing became the privileged framework for drug discovery. The structure-based drug discovery is the widely used method of drug repurposing, consisting of computational screening of compounds and testing them in-vitro. This current method of repurposing leaves room for mechanistic insights into how these screened hits interact with and influence their targets. We addressed this gap in the current study by integrating highly sensitive biophysical methods into existing computational repurposing methods. We also corroborated our computational and biophysical findings on H37Rv for the anti-mycobacterial action of selected drugs in-vitro and ex-vivo conditions. Atosiban and Rutin were screened as highly interacting hits against HemD through multi-stage docking and were cross-validated in biophysical studies. The affinity of these drugs (K ~ 106 M−1) was quantified using fluorescence quenching studies. Differential Scanning Fluorimetry (DSF) and urea-based chemical denaturation studies revealed a destabilizing effect of these drugs on target which was further validated using MD simulations. Conformational rearrangements of secondary structures were established using CD spectra and intrinsic fluorescence. Furthermore, Atosiban and Rutin inhibited M.tb growth in-vitro and ex-vivo while remaining non-toxic to mice peritoneal macrophages. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the efficacy of tocolytic agents - hexoprenaline and atosiban taking into account the gestational age.Patients and methods. The study included 147 pregnant women with threatening preterm labour between 28 to 33 weeks of gestation. Seventy-three pregnant received tocolysis by hexoprenaline (36 of them before 28 weeks of gestation and 37 – 32 weeks and more) and 74 – atosiban (39 of them before 28 weeks of gestation and 35–32 weeks and more). There were no differences in the clinical condition of pregnant women and features of preterm labour among groups before start of the tocolysis.The degree of effectiveness is determined by the duration of the pregnancy prolongation (48 hours, 7 days, more than 14 days).Results. Depending on the gestational age women that received hexoprenaline tocolysis prolonged pregnancy for 48 hours in 80,6% and 81,1%, whereas in the treatment with atosiban in 94,9% and 100%. Full-term gestation births occurred in 24,3% after hexoprenaline tocolysis at 32 weeks and more and in 51,4% with – atosiban (p < 0,05%). On average, atosiban tocolysis allowed to prolong pregnancy by 6–10 days longer than hexoprenaline (p < 0,05).Conclusion: The results of study have shown that atosiban was more effective tocolytic than hexoprenaline in the treatment of threatening preterm labor in both 28-32 and 32 or more weeks of gestation. The efficacy of atosiban slightly increased with gestational age from 28 to 33 weeks.

Oxytocin (OXY) has significant effects on mammalian behavior. Next to its role in lactation and social interactions, it is described to support better wound healing as well. However, direct OXY effects on wound healing and the regeneration of the microvascular network are still not clarified. We therefore examined the effects of OXY and an OXY receptor antagonist [atosiban (ATO)] on skin wound healing, focusing on epithelialization and neovascularization.

• EHG parameters reflect myometrial condition and changes provoked by tocolytic drugs. • Different response to drug was shown in women that will deliver at term vs preterm. • EHG high frequency content reduces faster in term women than preterm during therapy. • EHG complexity increased in preterms during therapy but barely changes for terms. • EHG parameters can separate term from preterm labor prior, during and after therapy. Although research studies using electrohysterography on women without tocolytic therapy have shown its potential for preterm birth diagnosis, tocolytics are usually administered in emergency rooms at the first sign of threatened preterm labor (TPL). Information on the uterine response during tocolytic treatment could prove useful for the development of tools able to predict true preterm deliveries under normal clinical conditions. The aim of this study was thus to analyze the effects of Atosiban on Electrohysterogram (EHG) parameters and to compare its effects on women who delivered preterm (WDP) and at term (WDT). Electrohysterograms recorded in different Atosiban therapy stages (before, during and after drug administration) on 40 WDT and 27 WDP were analyzed by computing linear, and non-linear EHG parameters. Results reveal that Atosiban does not greatly affect the EHG signal amplitude, but does modify its spectral content and reduces the energy associated with the fast wave high component in both WDP and WDT, with a faster response in the latter. EHG signal complexity remained constant in WDT, while it increased in WDP until it reached similar values to WDT during Atosiban treatment. The spectral and complexity parameters were able to separate (p < 0.05) WDT and WDP prior to and during tocolytic treatment and before and after treatment, respectively. The results pave the way for developing better and more reliable medical decision support systems based on EHG for preterm delivery prediction in TPL women in clinical scenarios. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth.Design: An economic analysis alongside a randomised clinical trial (the APOSTEL III study).Setting: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium.Population: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban.Methods: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses.Main Outcome Measures: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes.Results: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group.Conclusion: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation.Tweetable Abstract: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban. [ABSTRACT FROM AUTHOR]

Background: Two tocolytic drugs-atosiban and nifedipine-are currently used for first-line treatment of preterm labor (PTL).Objective: To compare the efficacy and safety of atosiban with nifedipine for PTL treatment.Search Strategy: In May 2017, we searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Clinical Trials with search terms including "nifedipine", "atosiban", and "preterm labor".Selection Criteria: Randomized controlled trials of women with PTL.Data Collection and Analysis: Data were extracted for study design, patient characteristics, risk of bias domains, and study outcomes. A random-effects model was used to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs).Results: We included seven studies that enrolled 992 patients. There was no significant difference between atosiban and nifedipine for pregnancy prolongation of 48 hours or more regarding efficacy (RR 1.06, 95% CI 0.92-1.22; P=0.440) or effectiveness (0.93, 0.84-1.03; P=0.177). Pregnancy prolongation for 7 days or more also did not differ between groups for efficacy (RR 1.04, 95% CI 0.89-1.21; P=0.656) or effectiveness (0.91, 0.79-1.05; P=0.177). Atosiban-however-was associated with fewer maternal side-effects than nifedipine.Conclusion: Atosiban resulted in fewer maternal side-effects than nifedipine, with no difference in pregnancy prolongation. PROSPERO registration: CRD42018090223. [ABSTRACT FROM AUTHOR]

Abstract Aims We hypothesized that copulation-induced temporary anti-nociception in female rats is mediated by the activation of central and/or peripheral oxytocin receptors. To test this hypothesis, we assessed the effects of intraperitoneal (ip), intrathecal (it), and intra-cerebroventricular (icv) administration of an oxytocin receptor antagonist (atosiban), on copulation-induced temporary anti-nociception in estrous rats. Main methods The treatment groups were ovariectomized rats pre-treated subcutaneously (sc) with 10 μg of estradiol benzoate (EB) followed 24 h later by an sc injection of 5 μg EB, and 4 h later, by an sc injection of 2 mg progesterone (P4). Rats were then administered saline vehicle (ip, it, or icv: control groups) or atosiban (500 μg/kg ip; 500 ng it; or 500 ng icv: experimental groups). Thirty minutes after drug or saline administration, their sexual behavior was tested by pairing with a sexually-experienced male rat. Brief pulse trains of 50 Hz, 300 ms duration, supra-threshold tail electrical shocks (STS) were delivered before and during copulatory activity i.e., while the female was receiving mounts, intromissions, or ejaculations, and we recorded whether vocalization occurred in response to each STS. Key findings Replicating our previous findings, the vocalization response to STS in control rats was significantly attenuated during intromissions and ejaculations, compared to their baseline (pre-mating) response, indicative of anti-nociception. By contrast, rats pre-treated with atosiban (each route of administration) failed to show an attenuation of the vocalization response to shock. Significance These findings provide evidence that the temporary anti-nociceptive effect of copulation in female rats is mediated by copulation-induced release of endogenous oxytocin in brain, spinal cord and periphery. Highlights • Copulation induces antinociception in female rats. • Copulation-induced antinociception is reduced by atosiban administration. • Hence, oxytocin plays a significant role in mediating copulation-induced antinociception. [ABSTRACT FROM AUTHOR]

The article tells about the results of management of women with cervical incompetence accompanied by fetal bladder prolapse into the cervical canal or the upper third of the vagina at 24-25 weeks of gestation. In consideration of all contraindications, in 14 observed patients tocolysis with atosiban was initiated followed by antibiotic therapy, then surgical treatment of CI by tucking the bladder outside of the internal os. Tocolysis with atosiban continued for 48 hours; respiratory distress syndrome of the fetus was prevented. In 12 of 14 cases (85.7%) pregnancy ended in timely delivery at 37-39 weeks. In 2 cases premature birth took place (at 29 and 34 weeks), the infants underwent a course of treatment and rehabilitation. Atosiban in combination treatment of complicated CI at 24-25 weeks could be used to prevent very early preterm birth.

There is increasing evidence that oxytocin is involved in learning and memory process. This study investigated the effects of blockade of oxytocin receptors using the selective oxytocin receptor antagonist atosiban (ATO) on contextual fear memory consolidation and reconsolidation in male rats. Post-training injections of different doses of ATO (1, 10, 100 or 1000 µg/kg) impaired the 48 h retention performance in a dose-dependent manner. The same doses of ATO following memory reactivation did not impair subsequent expression of contextual fear memories which formed under low or high shock intensities and tested 24 h or one week following memory reactivation. Also, no effect was found when ATO was administrated in the absence of memory reactivation. Our finding is the first report that indicates endogenous oxytocin released during training play an important role in the consolidation, but not reconsolidation of contextual fear memory in rats. [ABSTRACT FROM AUTHOR]

Objective：To obtain the clinical value of atosiban, ritodrine treatment in late abortion and preterm labour of twin pregnancy. Methods：A retrospective analysis was made of 85 women with late abortion and threatened preterm labor who were treated in the Second Affiliated Hospital of Zhengzhou University from January 2015 to January 2017. According to the drug use situation, they were divided into atoxiban group of 20 cases, ritodrine group of 25 cases, and ritodrine combined with atoxiban group of 40 cases (combined medication group). To observe the success rate, prolonged gestation week, neonatal condition, postpartum bleeding rate and adverse drug reaction. Results：The effect time of atociban was short, there was statistically significant difference between the two groups (all P＜0.05). There were no significant difference between the success rate in three groups ( χ2=0.30, P=0.86). There was no significant difference in neonatal birth weight and neonatal asphyxia rate (all P＞0.05). None of the 3 groups had postpartum hemorrhage. High risk of adverse drug reactions of ritodrine happened in patients, who had the albumin level is lower than 30 g/L, HGB≤100 g/L and the basic heart rate ≥100/min. Conclusions： Atociban can be considered as a first-line medicine in the twin pregnacy with effective contraction, with the albumin level ≤30 g/L, HGB≤100 g/L and the basic heart rate ≥100/min. [ABSTRACT FROM AUTHOR]

Introduction: To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair.Material and Methods: A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints.Results: In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban.Discussion: The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery. [ABSTRACT FROM AUTHOR]

Objective: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. Methods: This was a secondary analysis of the APOSTEL‐III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. Results: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29–1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25–1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36–4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42–1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27–1.27). Conclusion: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Recent developments in assisted reproductive technology focus on potential advances to improve its success rate. Atosiban, a combined oxytocin/vasopressin V1a receptor antagonist, is a novel class of drug involved in basic priming of the uterus for successful implantation during embryo transfer (ET). Objectives: The objective of this study is to evaluate the efficacy of atosiban (study group) in ET patients in comparison to placebo (control group) regarding implantation rate (IR), clinical pregnancy rate (CPR), and ongoing pregnancy rate and to assess the safety profile of atosiban. Materials and Methods: A total of 320 women undergoing in vitro fertilization-ET at a tertiary care hospital were enrolled in the study. In the study group, atosiban was given as initial intravenous (IV) bolus injection 0.9 ml (6.75 mg), 30 min before ET followed by continuous IV infusion of atosiban. In the control group, placebo (normal saline) was infused at the same rate and dose. Pregnancy was confirmed 14 days after ET by ß-human chronic gonadotropin level. IR and CPR were determined by doing transvaginal sonography 3 weeks and 6 weeks postET, respectively. Results: In women with atosiban treatment, the positive pregnancy rate and CPRs were 41.25% and 36.25%, respectively. The IR per embryo transferred was 17.5%. No major side effects of atosiban were noted among enlisted patients. The miscarriage rate and ectopic pregnancy rate were low (12.12% and 4.54%, respectively). Forty-two women had singleton gestation, while twin and triplet pregnancies were encountered in 13 and 3 women, respectively. No congenital anomalies were observed during an antenatal scan at 18-20 weeks in ongoing pregnancies. The positive pregnancy rate, the CPR, and the IR in the control group was 35%, 30%, and 16.5%, respectively, which was significantly lower than the atosiban group. Conclusion: Atosiban reduces uterine contractions and increases endomyometrial perfusion, both of which have potential benefits regarding improved IRs, CPR, and ongoing pregnancy rates. Atosiban has a good embryonic safety profile. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study? We hypothesized that potential anti‐tumour effects of exercise training might be mediated by oxytocin and explored the underlying mechanisms in a mouse model of breast cancer. What is the main finding and its importance? Interval exercise training, by inducing oxytocin secretion, may reduce the activity of the PI3K/Akt and ERK pathways, and consequently, results in a smaller tumour volume in a mouse model of breast cancer. Exercise training can affect the growth of breast tumours. We hypothesized that exercise training might reduce breast tumour growth by inducing oxytocin (OT) secretion and its related signalling pathways, such as PI3K/Akt and ERK. Therefore, 56 BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with interval exercise training on mammary tumour growth, as well as tumour‐related signalling pathways, including PI3K/Akt and ERK. Animal weight, OT plasma concentration, tumour weight and volume were measured at the end of the study. PI3K/Akt and ERK were evaluated by Western blot and qPCR assays. The results showed that OT plasma concentration was significantly increased in trained animals. The volume and weight of tumours were decreased significantly after both exercise training and OT administration. The expression of genes involved in tumour cell proliferation, such as PI3KR2, Akt and mTOR, was notably lower in the exercise‐trained and OT‐treated groups. Furthermore, the expression of genes involved in cell apoptosis, such as caspase‐3 and Bax, was significantly increased in the tumour tissues. In addition, Western blot results showed that phosphorylated Akt and ERK were significantly decreased in the exercise training and OT groups compared with the tumour group. Interestingly, atosiban reversed these effects. These results indicated that interval exercise training, acting via OT secretion, may reduce PI3K/Akt and ERK axis activities, and consequently, decrease tumour volume and weight in a mouse model of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Oxytocin is a peptide-based hormone released from the supraoptic nucleus and paraventricular nucleus in the hypothalamus and consisting of nine amino acids. It has been shown that oxytocin may have an effect on opiate receptors. Atosiban is a oxytocin receptor antagonist. Our aim in this study was to investigate the effects of oxytocin and atosiban on nociception and morphine analgesia. Method: In our study, 48 Wistar Albino 230-260 g male rats were used. The animals were divided into eight groups (control, 200 μg/kg oxytocin, 3 mg/kg atosiban, oxytocin+ atosiban, 5 mg/kg morphine, morphine+ oxytocin, morphine+atosiban and morphine+ oxytocin+ atosiban). Serum physiologic to the control group, oxytocin and atosiban were given intraperitoneally (i.p.) at the indicated doses to the other groups. Morphine was administered subcutaneously (s.c.). Analgesic effects were assessed by hot plate and tail flick analgesia tests. The resulting analgesic effect was measured and recorded at the 15th, 30th, 60th, 90th and 120th minutes. Assessment of analgesic effect was formulated as % analgesia (MPE) (% analgesia = 100x [post drug reaction time-pre drug reaction time]/ [cut off time-pre drug reaction time]). Results: Oxytocin showed analgesic activity (p<0,05). Atosiban showed hyperalgesic activity and decreased the analgesic activity of oxytocin when given with oxytocin (p<0,05). Oxytocin increased the analgesic activity of morphine (p<0.05). In addition, although atosiban did not alter the analgesic activity of morphine, morphine analgesia increased by oxytocin was reduced (p<0.05). Conclusions: According to these results, it can be said that although atosiban does not change on the analgesic effect of morphine alone, it blocks the effect of oxytocin on morphine analgesia. [ABSTRACT FROM AUTHOR]

Objectives: Evidence for the efficacy of atosiban in improving pregnancy outcomes among patients undergoing assisted reproductive technology (ART) remains inconsistent.Methods: The PubMed, EMBASE, and CNKI databases were searched using keywords such as 'atosiban', 'infertility', and 'ART'. Studies that explored the efficacy of atosiban in the field of ART for patients with embryo transfer (ET) were included if they evaluated pregnancy outcomes. Combing using subgroups and sensitivity analysis were conducted, and risk ratios (RRs), and 95% confidence intervals (CIs) were calculated.Results: Six studies were included. Atosiban treatment could improve pregnancy outcomes for all patients undergoing ET, especially for the subgroups of patients with repeated implantation failure (RIF) (implantation rate: RR = 1.806, 95% CI = 1.473-2.215; clinical pregnancy rate: RR = 1.725, 95% CI = 1.394-2.135; live birth rate: RR = 2.141, 95% CI = 1.494-3.068), as shown by the comparison with placebo or no-treatment groups. However, no statistical significance was detected in subgroups of patients undergoing their first or second ET cycle. In addition, no significant differences were observed in positive pregnancy tests, miscarriage rates, multiple pregnancy rates, or ectopic pregnancy rates.Conclusions: Supplementation with atosiban has a positive effect on ART and embryo transfer procedure, especially for women undergoing their third or more ET cycle. [ABSTRACT FROM AUTHOR]

Objective: To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor.Methods: A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses.Results: Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01).Conclusions: Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effect of atosiban on in vitro fertilization (IVF) pregnancy outcome among women with both endometriosis and adenomyosis, and compared it to that of patients with endometriosis but without adenomyosis and that of patients with tubal factor only., Materials and Methods: 106 infertile women (176 embryo transfers) from a medical center in Taiwan were included in the analysis, where 34 (54), 34 (66), and 38 (56) cases (embryo transfers) were endometriosis without adenomyosis, endometriosis with adenomyosis, and tubal infertility factor only, respectively. Adenomyosis morphologies were classified using an ultrasound-based classification system. The logistic generalized estimating equation model was used to analyze the association between atosiban use and pregnancy outcomes., Results: The crude pregnancy rates for the endometriosis-only group were significantly higher than those for the endometriosis + adenomyosis group (i.e., biochemical pregnancy: 50.0% versus 29.7%, p = 0.041; ongoing pregnancy: 35.2% versus 16.9%, p = 0.038). Significantly higher chances of biochemical pregnancy and ongoing pregnancy among endometriosis patients without adenomyosis versus those with both endometriosis and adenomyosis were found (odds ratios [95% confidence intervals]: 2.981 [1.307, 6.803]; p = 0.009, 2.694 [1.151, 6.304]; p = 0.022). A significant positive association between atosiban use and biochemical pregnancy existed among endometriosis cases without adenomyosis (a 2.43-fold [1.01, 5.89] increase in successful pregnancy; p<0.05), but not for the other groups., Conclusions: Poor pregnancy outcomes among adenomyosis-affected women were confirmed. The use of atosiban significantly enhanced IVF pregnancy among endometriosis patients without adenomyosis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)