Atosiban Group Research Articles

Investigation of effect peripheral kisspeptin treatment on hypothalamo-pituitary-gonadal axis and hypothalamo-pituitary-adrenal axis in male rats.

Kisspeptin is an endogenous peptide hormone that is the most potent stimulator of the hypothalamo-pituitary-gonadal (HPG) axis. The HPG axis can be suppressed by the activation of the hypothalamo-pituitary-adrenal (HPA) axis. The physiological role of kisspeptin in the interaction of the HPG axis and the HPA axis is not fully understood yet. The purpose of the current study was to investigate the possible effects of peripheral injection (intraperitoneally) of kisspeptin on HPG axis and HPA axis activity as well. Adult male Wistar rats were randomly divided into seven groups as sham (control), kisspeptin(10nmol), p234 (10nmol), kisspeptin + p234, kisspeptin + antalarmin (10mg/kg), kisspeptin + astressin2b (100μg/kg), and kisspeptin + atosiban (0.250mg/kg) (n = 10 each group). At the end of the experiment, the hypothalamus, pituitary gland, and serum samples of the rats were collected. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin and kisspeptin + astressin2b groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin, kisspeptin + antalarmin, kisspeptin + astressin2b, and kisspeptin + atosiban groups that compared to the control group. There was no a significant difference in corticotropic releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone and corticosterone concentrations among all groups. Moreover, no significant difference was found in the concentration of pituitary oxytocin. Our results suggest that peripheral kisspeptin injection induces an activation in the HPG axis, but not in the HPA axis in male rats.

O-029 Atosiban in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer: a placebo-controlled randomized trial

Abstract Study question Does the administration of Atosiban before frozen-thawed blastocyst transfer improve the live birth rate in women with a history of a single implantation failure? Summary answer In women with a single implantation failure undergoing frozen-thawed blastocyst transfer, Atosiban did not improve the ongoing pregnancy rate. What is known already Uterine peristalsis preceding embryo transfer is believed to adversely impact the success rates of IVF. Atosiban can reduce uterine peristalsis and act as a role of oxytocin antagonist. The effectiveness of Atosiban in the general population of IVF patients has not been conclusively shown by randomised clinical trials or meta-analyses. It has been suggested that women with previous implantation failure may potentially benefit from the use of Atosiban, particularly in the presence of uterine peristalsis. We aim to evaluate if Atosiban before embryo transfer increases live birth rate in women undergoing frozen-thawed blastocyst transfer? Study design, size, duration We conducted a single-centre, double-blind placebo randomised controlled trial (RCT) in women with previous single implantation failure undergoing frozen-thawed blastocyst transfer. Between July 2019 and June 2023, we randomised 1,100 participants to either Atosiban or placebo. The primary outcome was live birth (≥20 weeks of gestation) in the first FET after randomization. In this abstract, we present results on ongoing pregnancy. Data on live birth will be available at the conference. Participants/materials, setting, methods We randomised women with a history of one failed fresh or frozen blastocyst, with at least one cryopreserved blastocyst into two groups on the day of transfer. In the Atosiban group, women were administered 37.5mg of Atosiban intravenously 30-min prior to FET. In the placebo group, women received a saline infusion for the same duration. Uterine peristalsis was measured using transvaginal ultrasound prior to administration of study drugs. The analysis was done based on intention-to-treat. Main results and the role of chance The ongoing pregnancy rates were 50.46% (277/549) and 46.82% (258/551) in the Atosiban and control groups, respectively (RR 1.08, 95% CI 0.95 to 1.22, P = .23). Uterine peristalsis was measured in 720 (65%) of all participants. Within this cohort, of the 163 (22%) women with abnormal contractions, the ongoing pregnancy rates were 51.9% and 41.7%, respectively (RR 1.25, 95% CI 0.90 to 1.73, P = .19). Among 208 women (29%) with peristalsis but without abnormal contraction waves, ongoing pregnancy rates were 50.9% and 48.0% (RR 1.06, 95% CI 0.81 to 1.40, P = .67). In 349 women (48%) without peristalsis, the ongoing pregnancy rates were 48.6% in the Atosiban group versus 50.6% in the control group (RR 0.96, 95% CI 0.78 to 1.19, P = .71). Limitations, reasons for caution Our study only included women with previous blastocyst implantation failure. Uterine peristalsis was not initially assessed, resulting in only 65% (720/1,100) of the participants having peristalsis measured. In this abstract, we only report on the ongoing pregnancy rate. We will present data on live birth at the congress. Wider implications of the findings In unselected women undergoing frozen-thawed blastocyst transfer with previous single implantation failure, Atosiban does not enhance the ongoing pregnancy rate. Future research regarding Atosiban in IVF should assess uterine peristalsis and focus on women with abnormal contractions. Trial registration number ChiCTR1900022333

Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 μg), kisspeptin + astressin 2B (1 μg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

Efficacy of atosiban for repeated implantation failure in frozen embryo transfer cycles

Atosiban was commonly added to improve pregnancy outcomes of patients with repeated embryo implantation failure (RIF). In this study, we aimed to investigate the effect of atosiban before transferring the frozen-thawed embryo to RIF patients. This retrospective study was conducted in the Hospital for Reproductive Medicine affiliated to Shandong University from August 2017 to June 2021. A total of 1774 women with a history of RIF undergoing frozen embryo transfer (FET) were included in this study. All the participants were classified into atosiban or control group: Group A included 677 patients who were administered atosiban intravenously 30 min prior to FET with a dose of 37.5 mg; Group B included 1097 patients who received no atosiban before the transfer. There were no significant differences observed in the live birth rate (LBR) (39.73% vs. 39.02%, P = 0.928) between the two groups. Other secondary outcomes including biochemical pregnancy rate, clinical pregnancy rate, implantation rate, clinical miscarriage rate and preterm birth rate were similar between the two groups (all P > 0.05). However, subgroup analysis demonstrated significantly higher preterm birth rates in the control group compared with the atosiban group (0 versus 3.0%, P = 0.024) in the natural FET cycles. Atosiban may not improve pregnancy outcomes of RIF patients in FET cycles. However, the effects of Atosiban on pregnancy outcomes should be assessed in clinical trials with larger sample sizes.

Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis.

Repeated embryo implantation failure (RIF) posed a significant challenge in assisted reproduction. Evidence of its therapeutic effectiveness including atosiban used around embryo transfer to improve pregnancy outcomes in RIF patients undergoing in vitro fertilization-embryo transfer (IVF-ET) remained inconsistent. This study aimed to explore the efficacy of atosiban on pregnancy outcomes of patients with RIF who received IVF-ET. The research was designed using the PICOS format. A systematic search of four English databases, PubMed, EMBASE, Web of Science, Cochrane Library, and one Chinse database, China National Knowledge Infrastructure (CNKI) was conducted. The time range was from inception to December 10, 2022. Then trials comparing the efficacy of atosiban and control group on pregnancy outcomes in RIF patients who receive IVF-ET were included. Subgroup analysis and sensitivity analysis were performed to reduce the influence of heterogeneity between included studies. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The main outcome measure was clinical pregnancy rate (CPR). For the analyses, StataMP 17.0 (Stata Corporation, USA) was used. Two prospective randomized controlled trials (RCTs), one prospective cohort study and four retrospective cohort studies were included. Our results showed that atosiban was associated with higher clinical pregnancy rate (RR=1.54, 95% CI: 1.365-1.735, P < 0.001, I2 = 0.0%). The results of subgroup analysis based on study types (prospective randomized controlled clinical trial, retrospective cohort study and prospective cohort study) showed that in all types of studies, CPR of atosiban group was significantly higher than controlled group. The results of subgroup analysis based upon the diagnostic criteria of number of previous embryo transfer failures showed that the intervention of atosiban improved the CPR whether in participants with 2 previous ET failures or in participants with 3 previous ET failures. Nevertheless, the incidence of ectopic pregnancy, multiple pregnancy, and miscarriages were not significantly different between the case and control groups. For women who are undergoing IVF-ET and have experienced repeated embryo implantation failure, atosiban may be an important factor in enhancing pregnancy outcomes. To confirm this conclusion, more thorough, prospective randomized controlled studies of sizable sample sizes with well design are required.

Effect of administration of atosiban at day of embryo transfer on in-vitro fertilization out come

Background: The most crucial step of assisted reproduction is embryo implantation, which is impacted by a variety of factors, including the patient's age, embryo quality, and endometrial receptivity. The embryo transfer (ET) procedure, which induces uterine contractions, may hinder embryo implantation. Objectives: On the day of embryo transfer, examine the effects of Atosiban administration on implantation, clinical pregnancy, miscarriage, and live birth rates. Material and Methods: The study included 60 individuals with a diagnosis of primary or secondary infertility due to male or female factor, tubal factors, moderate endometriosis, or other unknown reasons. Two groups of patients were selected at random. The first group received 6.75 milligrammes of atosiban intravenously 30 minutes before ET, whereas the second group received no medication. Pregnancy outcomes in both groups were compared. Results: Significantly higher clinical pregnancy and implantation rates were observed (60% versus 30%) and (37.8% versus 17.8%) respectively, with non-significantly higher live birth rates (94.4% versus 66.7%), while the miscarriage rate was lower in the Atosiban group but not significantly (5.6% versus 33.3%). Conclusion: These findings imply that atosiban therapy prior to embryo transfer improves embryo implantation.

Effects of atosiban on uterine peristalsis following frozen embryo transfer: A randomized controlled trial

ObjectivesTo compare the effects of atosiban (oxytocin antagonist) on uterine peristalsis and pregnancy outcomes in the frozen embryo transfer (FET) cycle. SettingSrinagarind Hospital, a university hospital, Khon Kaen, Thailand. DesignA randomized, double-blinded, controlled trial. MethodsFifty infertile women were randomized into the atosiban (n = 25) and placebo group (n = 25). Women in the study group received intravenous atosiban 6.75 mg, 30 min before embryo transfer, and continued infusion at 18 mg/h for 1 h. The dose was reduced to 6 mg/h for another 2 h. Saline solution was applied in the placebo group. The uterine peristalsis frequency was measured by transvaginal ultrasound 30 min before and 3 h after the embryo transfer. ResultsThe respective mean baseline uterine peristalsis frequency (time) in the atosiban and placebo group was 10.3 ± 2.4 and 9.2 ± 3.4. The respective duration of uterine peristalsis in the atosiban and placebo group after receiving the intervention was reduced to 7.9 ± 2.1 and 6.9 ± 2.7. The implantation rate and clinical pregnancy rate were not statistically significant different between atosiban group and placebo group (37.5% versus 31.0%, RR 1.21, 95%CI: 0.60–2.44 and 44% versus 36%, RR 1.22, 95%CI: 0.62–2.42, respectively). Subgroup analysis indicated that the clinical pregnancy rate in those >35 years of age was not significantly different between both groups (31.6% and 18.8 %, RR 1.68, 95%CI: 0.50–5.68). ConclusionAdding atosiban in FET did not reduce uterine peristalsis but may benefit the advanced age group.

Effectiveness and safety of atosiban versus conventional treatment in the management of preterm labor

ObjectiveTo compare the efficacy of atosiban with conventional treatment of the threatened preterm labor. Materials and methodsAll the data of pregnant women with threatened preterm labor from January 1 to December 31, 2017, who received atosiban were collected. Pregnant women with conventional treatment (including β-agonists, indomethacin, magnesium sulphate and calcium channel blockers, alone or in combination) were used as control. ResultsThe proportion of women not requiring an alternative tocolytic treatment within 48 h and remaining undelivered was significantly higher in atosiban treatment group (89.3%; n = 25/28) compared with conventional treatment (24.2%; n = 8/33) (P < 0.0001). For therapy efficacy, there was also no significant difference between atosiban groups and conventional treatment groups in the low gestational ages. However, for the high gestational ages, atosiban treatment group showed higher efficacy (84%; n = 21/25 vs. 37.5%; n = 3/8) (P < 0.05). Moreover, a significantly higher proportion of women in the atosiban treated group (89.3%; n = 25/28) was observed compared with the conventional treatment groups (51.5%; n = 17/33) who did not receive an alternative tocolytic within 48 h (P < 0.01). Maternal and fetal safety was significantly superior with atosiban treatment. ConclusionsOur results support that atosiban would represent an advance over current tocolytic therapy especially for the high gestational ages.

Atosiban versus ritodrine as tocolytics in external cephalic version

Objective To assess the efficacy of atosiban versus ritodrine as tocolytics in external cephalic version (ECV). Materials and methods A prospective comparative trial was carried out in a tertiary hospital. 430 women with singleton breech pregnancies ≥36 weeks were recruited for ECV, 215 with ritodrine and 215 with atosiban as tocolytic agents. The efficacy, complications and perinatal outcomes were compared between both groups. The associations between variables were analyzed using the chi-square test (χ2) (qualitative), Student’s t test (quantitative, parametric) or Mann-Whitney test (nonparametric). Statistical significance was established as p < .05. Results The overall ECV success rate was 47.9% (206/430), 46.0% in the atosiban group (99/215) and 49.8% in the ritodrine group (107/215). This difference showed no statistical significance (p = .440). A higher rate of uterine contractions after the maneuver was observed in the atosiban group (34.4 versus 22.8%; p = .008), but without clinical relevance. Perinatal outcomes were similar in both groups, with no significant differences. Conclusion Atosiban and ritodrine showed similar efficacy as tocolytic agents in ECV, with no differences in complications and perinatal outcomes between these two agents.

The Effect of Atosiban on Patients With Difficult Embryo Transfers Undergoing In Vitro Fertilization-Embryo Transfer.

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.

The use of atosiban prolongs pregnancy in patients treated with fetoscopic endotracheal occlusion (FETO).

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.

Oxytocin Blocks Tachycardic Responses in the Restraint Stress Model Acting on the Oxytocin Receptor Coupled to Gq Protein

IntroductionStress is common in modern life and demands physiological, endocrine and behavioral responses to cope. In acute restraint stress model (ARS), increased OXY is found in plasma whereas no changes are seen in novelty stress (NS). OXT acts on G‐protein receptor (OXTR) recruiting coupled to Gq, Gi and Gs. Atosiban (ATO) was initially categorized as an OXTR antagonist, but was reclassified as an OXTR biased agonist favoring Gi/o over Gq.AimThis study aimed to evaluate the selective functional effects of oxytocin on ARS after treatment with Atosiban.MethodsAll experimental procedures were approved by the University of São Paulo Ethical Committee (number 079/2017). Male Wistar rats, 250g, were used. Pulsatile arterial pressure (PAP) was recorded. Some animals were subjected to hypophysectomy (HYP) or sinoaortic denervation (SAD). Animals were divided into: vehicle, Atosiban (0.3, 1 and 3 μg/kg), dTyr AVP (V1a antagonist receptor, 30 μg/kg), homatropine (M2 antagonist receptor, 200 μg/kg) and exposed to ARS. One vehicle and one Atosiban (1μg/kg) group were exposed to NS. From PAP were calculated: mean arterial pressure (MAP) and heart rate (HR) for time curve analysis, and systolic arterial pressure (SAP) and cardiac interval (CI) for heart rate variability (HRV) and spontaneously baroreflex sensitivity (SBS).ResultsARS increased MAP and HR, due to increased autonomic activity. ATO inhibited ARS‐evoked tachycardia (F3,19=4.074; P&lt;0.05), without effecting MAP increase (F3,19=0.1664, P&gt;0.05). Pretreatment with dTYR AVP did not affect the ATO blockade of tachycardia. HRV analysis of PAS and CI showed a tendency for Atosiban to reduce the low frequency band (P=0.08) and increase the high frequency band (P=0.053) under ARS. The tendency to increase parasympathetic activity was evidenced by parasympathetic blockade with HOM, that reversed ATO effect (HR ‐ ATO vs. HOM+ATO; P&lt;0.05) to that of vehicle group (HR ‐ Vehicle vs. HOM+ATO; P&gt;0.05). SBS analysis of baroreflex effectiveness index (BEI) showed a significant difference in time and treatment for the BEI UP (BEI UP – Time: F8, 32 = 2,702; P&lt;0.05; Treatment: F1, 8 = 6,277; P&lt;0.05). BEI UP tended to increase after ATO on the first hour of restraint (P=0.08). Gain mean analysis showed results similar to BEI; GAIN UP was significantly different after ATO (P&lt;0.05). No differences were observed after ATO in the SAD vs vehicle group. To test if ATO effect depends on oxytocin, HYP animals either ATO or vehicle were subjected to ARS. No differences were observed between ATO and vehicle. Animals were treated with ATO or vehicle were also subjected to NS, an oxytocin secretion‐free stress model, and no differences were observed.ConclusionOur results suggest that OXY secreted to periphery attenuates tachycardic responses evoked by ARS, possibly by a parasympathetic activity facilitation. Atosiban acts on OXTR coupled to Gi/o and OXY secreted is dislocated to OXTR coupled to Gq to promote effects on cardiac frequency during ARS.Support or Funding InformationCAPES, CNPq, FAEPA‐HCFMRP and FAPESP [2016/25502‐7]. Oxytocin mechanism in restraint stress after Atosiban treatmentimageOxytocin mechanism in restraint stress after Atosiban treatmentThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute tocolysis for uterine tachysystole or suspected fetal distress

Acute tocolysis for uterine tachysystole or suspected fetal distress

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

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. 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. 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). 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.

Modern tocolysis and adverse effects of tocolytics

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.

Oxytocin Receptor Antagonist (Atosiban) in the Threat of Preterm Birth: Does It Have Any Effect on Breastfeeding in the Term Newborn?

Oxytocin is a hormone involved in the mechanism of breastfeeding, uterine contractions, and social relationships. Atosiban (competitive oxytocin antagonist) is one of the most commonly used tocolytics for the threat of preterm labor in Europe. The aim of this study is to determinate if the administration of atosiban has any influence in the type of feeding in the term newborn at discharge. The secondary objective is to verify its effectiveness for the prevention of preterm delivery and in the possibility of applying treatment to complete lung maturation. Retrospective cohort study carried out in a tertiary University Hospital distinguished by WHO-UNICEF as a Baby-Friendly Hospital Initiative. The analysis included 264 women exposed to atosiban during a period of 4 years. One hundred met inclusion criteria. Unexposed infants born right after and before the exposed ones were selected as the not exposed subgroup (n = 200). Among women treated with atosiban, 82% maintained exclusively breastfed (EBF), 8% had mixed breastfeeding, and 10% had formula feeding at discharge. In the nonexposed group, 82% maintained EBF, 9.5% had mixed breastfeeding, and 8.5% had formula feeding at discharge (p = 0.84). 97.5% of pregnant women treated with atosiban received corticosteroid for lung maturation, and 49.5% completed gestation with term newborns. There were no significant differences in the type of feeding at discharge between the atosiban group and the nonexposed group. In most cases, the administration of tocolytic therapy allowed to complete lung maturation.

СРАВНЕНИЕ ТОКОЛИЗА ГЕКСОПРЕНАЛИНОМ И АТОЗИБАНОМ

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 &lt; 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 &gt; 0,05%). On average, atosiban tocolysis allowed to prolong pregnancy by 6.5 days longer than hexoprenaline (p &lt; 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.

Effectiveness and safety of the oxytocin antagonist( atosiban) versus beta-adrenergic agonists (salbutamol) in the treatment of preterm labor

Background and Objectives: preterm labor complicates 5-10% of pregnancies and is a leading cause of neonatal morbidity and mortality worldwide and 70-80% of perinatal deaths occur in preterm infants. The aim of this study is to compare the effectiveness, safety and adverse effects of the oxytocin antagonist medication(atosiban) with those of beta-adrenergic agonist (salbutamol) in the treatment of patients with preterm labor.Patients and Methods: one hundred pregnant women with preterm labor were enrolled in this study from the period of( January 2014 – January 2015) at Al-Diwaniya Maternity and Pediatrics Teaching Hospital-Iraq with a gestational age of 24-34 weeks, they were randomly assigned to receive tocolytics either salbutamol (n=50) or atosiban (n=50).Salbutamol was given by(intravenous infusion 10-50 microgram)for up to 48 hour. Atosiban was given by (intravenous bolus dose of 6.75 mg then 300microgram/minute for 3 hour and 100microgram/minute for up to 48hour). Retreatment with the study drugs or alternative tocolytic agents was allowed. Main outcome measures included were tocolytic effectiveness, which was assessed in terms of number of women undelivered after 48hour and 7 days. Tocolytic safety was assessed in terms of maternal and fetal side effects and neonatal morbidity.Results: there were no significant differences between the salbutamol and the atosiban group in prolongation of pregnancy for 48 hour (44% versus 46%;p=0841)and 7 days(20% versus 32%;p=0.171) ,respectively. Maternal adverse events , including tachycardia occurred more frequently in the salbutamol group(22% versus 8%;p=0.050).Neonatal outcomes and complications were comparable between the two study groups(42% versus 32%;p=0.30).Conclusions: the oxytocin antagonist (atosiban) was as effective as beta-agonist(salbutamol) in delaying threatened preterm birth , and found to be better tolerated by both the mother and fetus than salbutamol , with a comparable neonatal safety profil.This study supports the clinical use of atosiban as a first line tocolytic in the treatment of preterm labor.

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial

Objective To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation.Design Multicentre,...

Nifedipine Versus Atosiban for Threatened Preterm Birth (APOSTEL III)

Preterm birth is estimated to affect between 5% and 13% of all pregnancies and is the reason for more than 50% of neonatal morbidity and 50% and 75% of neonatal mortality cases worldwide. It causes long-term physical and developmental impairment, thus having a substantial burden on families and health care costs. A delay of delivery by 48 hours in cases with threatened preterm birth allows for the administration of antenatal corticosteroids, which improves neonatal outcomes. Therefore, treatment with tocolytics for 48 hours may prolong pregnancy long enough to optimize the beneficial effects of steroid administration. However, there is no consensus about which drug is most effective at improving neonatal outcomes while minimizing maternal risks. The aim of this study was to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. The APOSTEL III, multicenter randomized controlled trial was conducted in 10 tertiary and 9 teaching hospitals in the Netherlands and Belgium. Participants included women with threatened preterm birth (gestational age, 25–34 weeks). In this study, 254 women, from 2011 to 2014, were randomly assigned (1:1) to oral nifedipine and 256 to intravenous atosiban for 48 hours. The primary outcome included a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis. Data were analyzed in all women and babies, including during follow-up. The study revealed that the primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk, 0.91; 95% confidence interval, 0.61–1.37). A total of 16 babies (5%) died in the nifedipine group and 7 babies (2%) died in the atosiban group (relative risk, 2.20; 95% confidence interval, 0.91–5.33); all deaths were deemed unlikely to be related to the study drug. It is to be noted that maternal adverse events did not differ between the groups. The study concluded that in women with threatened preterm birth, 48 hours of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. It proposed that future clinical research must focus on large placebo-controlled trials powered for perinatal outcomes.