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Background: We investigated the impacts of tocolytic agents on maternal and neonatal blood glucose levels in women with gestational diabetes mellitus (GDM) who used tocolytics for preterm labor., Methods: This multi-center, retrospective cohort study included women with GDM who were admitted for preterm labor from twelve hospitals in South Korea. We excluded women with multiple pregnancies, anomalies, overt DM diagnosed before pregnancy or 23 weeks of gestation, and women who received multiple tocolytics. The patients were divided according to the types of tocolytics; atosiban, ritodrine, and nifedipine group. We collected baseline maternal characteristics, pregnancy outcomes, maternal glucose levels during hospitalization, and neonatal glucose levels. We compared the frequency of maternal hyperglycemia and neonatal hypoglycemia among three groups. A multivariate logistic regression analysis was performed to evaluate the contributing factors to the occurrence of maternal hyperglycemia and neonatal hypoglycemia., Results: A total of 128 women were included: 44 (34.4%), 51 (39.8%), and 33 (25.8%) women received atosiban, ritodrine, and nifedipine, respectively. Mean fasting blood glucose (FBG) (112.3, 109.6, and 89.5 mg/dL, P < 0.001) and 2-hour postprandial glucose (PPG2) levels (145.4, 148.3, and 116.5 mg/dL, P = 0.004) were significantly higher in atosiban and ritodrine group than those in nifedipine group. Even after adjusting for covariates including antenatal steroid use, gestational age at admission, and pre-pregnancy body mass index, there was an increased risk of high maternal mean FBG (≥ 95 mg/dL) and PPG2 (≥ 120 mg/dL) levels in the atosiban and ritodrine group than in nifedipine group. The atosiban and ritodrine groups are also at increased risk of neonatal hypoglycemia (< 47 mg/dL) compared to the nifedipine group with the odds ratio of 4.58 and 4.67, respectively ( P < 0.05)., Conclusion: There is an increased risk of maternal hyperglycemia and neonatal hypoglycemia in women with GDM using atosiban and ritodrine tocolytics for preterm labor compared to those using nifedipine., Competing Interests: Hyun Soo Park and Hyun-Joo Seol participated in the Tractocile (atosiban) Advisory Board and received consulting fees from Ferring Pharmaceuticals Korea on October 24, 2023. Other authors have no potential conflicts of interest., (© 2024 The Korean Academy of Medical Sciences.)

Although it is widely used, there is still no valid treatment for ototoxicity caused by the antineoplastic drug cisplatin. In this study, we aimed to investigate the efficacy of intratympanic resveratrol and intratympanic dexamethasone treatment in cisplatin-induced ototoxicity. We also compared intratympanic atosiban (oxytocin antagonist) and oxytocin in cisplatin ototoxicity. In this study, 30 rats (60 ears) were used by separating into 5 groups. Cisplatin, oxytocin, dexamethasone, atosiban and 0.9% NaCl were administered intraperitoneally to all groups separately. Auditory Brainstem Response and Distortion Product Otoacoustic Emission tests were performed on all groups before and 72 h after the procedure. Pre-treatment values were higher than post-treatment values in all groups ( p  < 0.001). There was no significant prolongation of the post-treatment Auditory Brainstem Response I-IV interval in the oxytocin and dexamethasone groups ( p  > 0.05). There was no significant decrease in the frequencies of 2832 and 4004 after treatment in the oxytocin and dexamethasone group compared to pre-treatment in Distortion Product Otoacoustic Emission. As a result, it has been shown that intratympanic oxytocin may be an option that can be used in the treatment, although it is not as effective as dexamethasone in preventing cisplatin ototoxicity., Competing Interests: Conflict of InterestThe authors declared no potential conflicts of interest concerning the research, authorship and/or publication of this article., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Milk ejection disorders were induced by oxytocin receptor blockade. We tested the hypothesis that the degree of udder emptying at incomplete milk ejection can be estimated based on the concentration of various milk constituents in different milk fraction samples. To induce different levels of spontaneous udder emptying (SUE) 10 Holstein dairy cows were milked either with or without i.v. injection of the oxytocin receptor blocking agent atosiban (ATO). In ATOearly, 12 µg/kg BW ATO was injected immediately before and in ATOlate directly after a 1-min manual udder preparation. The normal milking routine served as the control treatment. In all 3 treatments the udder was completely emptied by the i.v. injection of 10 IU oxytocin (OT) at the end of spontaneous milk flow. During all experimental milkings 4 milk samples were taken in all treatments: at the start of udder preparation (foremilk; FM), immediately after cessation of spontaneous milk flow and cluster detachment by hand stripping (strip milk; SM), from spontaneous removed milk in bucket 1 (milk before OT; MBOT) and from the milk obtained after OT injection in bucket 2 (milk after OT; MAOT). Fat, protein, lactose, and electrolytes (Na, Cl, and K) were measured in each milk sample. In addition, electrical conductivity (EC) was determined in parallel to continuous milk flow recording. The treatments induced individual degrees of SUE; therefore, the final evaluations of data were based on SUE classes instead of treatments. The most pronounced differences of milk constituents at different degrees of SUE were found for the milk fat content. The fat content of SM and MBOT remained almost unchanged up to 60% SUE, but was considerably higher if >80% of the milk was spontaneously removed. The concentrations of Na and Cl were highest and of K lowest if less than 20% of milk was received in the different samples. The EC was higher in SM and MBOT if <20% of milk was received. In conclusion, the blockade of the OT effect influences primarily the fat content, which confirmed an OT-induced fat secretion during milking. Similar effects are likely found in situations of disturbed milk ejections, caused by a lack of or reduced release of OT in response to different degrees of tactile udder stimulation. Our results show that the measurement of fat content and the EC in SM samples collected after cluster detachment can be used to estimate the completeness of udder emptying., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Dysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis., Methods: Between January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses., Results: The study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis., Conclusions: Administering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis., (© 2024. The Author(s).)

Objective: To investigate the interaction between atosiban and growth hormone (GH) as adjuvants in frozen-thawed embryo transfer (FET) cycles., Method: A total of 11627 patients who underwent FET at Xiamen University Affiliated Chenggong Hospital between January 2018 to December 2022 were retrospectively analyzed. Among them, 482 patients received atosiban and 275 patients received GH. The interactions were estimated by comparing the odds ratio (OR) for pregnancy comparing patients with or without atosiban adjuvant in cohorts stratified according to the presence of GH use in either the overall cohort or a propensity score (PS) matched cohort. An interaction term (atosiban × GH) was introduced to a multivariate model to calculate the ratio of OR (ORR) adjusted for confounders., Results: For all patients receiving atosiban administration, no obvious effect on pregnancy was observed in comparison with either matched or unmatched controls. However, when the patients were stratified according to GH administration, atosiban showed a significant association with clinical pregnancy in comparison with either matched or unmatched controls among patients with GH treatment with rate ratios (RR) of 1.32 (95%CI: 1.05,1.67) and 1.35 (95%CI: 1,1.82), respectively. On the other hand, however, the association was absent among patients without GH treatment. The adjusted ORRs in both matched and unmatched cohorts were 2.44 (95%CI: 1.07,5.84) and 1.95 (95%CI: 1.05, 3.49) respectively., Conclusion: The combination use of atosiban and GH in FET cycles is potentially beneficial to the pregnancy. However, indications for the use of atosiban and GH may need further assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Cai, Sun, Liu, Liu, Gao, Jiang and Ren.)

Oxytocin is a peptide released into brain regions associated with the processing of aversive memory and threat responses. Given the expression of oxytocin receptors across this vigilance surveillance system of the brain, we investigated whether pharmacological antagonism of the receptor would impact contextual aversive conditioning and memory. Adult male rats were conditioned to form an aversive contextual memory. The effects of peripheral administration of either the competitive antagonist Atosiban or noncompetitive antagonist L-368,899 were compared to saline controls. Oxytocin receptor antagonism treatment did not significantly impact the consolidation of aversive contextual memory in any of the groups. We conclude that peripheral antagonism of oxytocin signalling did not impact the formation of aversive memory., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as β2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair., Methods: Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery., Results: Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL -1 vs. 13.06 ± 6.35 mg.dL -1 , for atosiban, p = 0.001) levels., Conclusions: Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair., Competing Interests: Conflicts of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Purpose: To evaluate the effects of atosiban on clinical outcomes in patients undergoing frozen-thawed embryo transfer., Methods: The clinical data of 1093 infertile patients who underwent frozen-thawed embryo transfer in our center from January 2019 to December 2020 were retrospectively analyzed (control, 418; atosiban, 675). Propensity score matching (PSM) analysis identified 400 matched pairs of patients. The implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate between the two groups were compared., Results: Before PSM, patients differed by infertility factors, number of transferred embryos, and endometrial preparation protocol (P < 0.05). After PSM, characteristics were similar in corresponding patients of the atosiban and control groups. After propensity score matching, we found that there was no significant difference in the implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate in atosiban and control group (P > 0.05)., Conclusion: Atosiban did not improve the clinical outcomes of infertile patients with frozen-thawed embryo transfer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 ~ 10 6  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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.)

Background: Atosiban is commonly used to delay premature labor in pregnant women and is thought to have few side effects., Objectives: To report a case of acute pulmonary edema (APE) following administration of atosiban and conduct a systematic review to identify common characteristics and risk factors of atosiban-associated APE., Methods: Searches were performed in Pubmed, Embase, and Web of Science using the keyword "Atosiban" combined with the terms "Pulmonary edema" or "Dyspnea" or "Hypoxia" on 9th July 2022. Only case reports of atosiban-associated APE were included without language restrictions. Data were extracted from the reports, and median, range, and percentages were calculated as applicable. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist for case reports., Results: Seven cases of atosiban-associated APE were included in the systematic review, including our case. APE occurred at a median gestational age of 32 + 6 weeks. Most patients were nulliparous (6/7, 85.7%) and were in multiple pregnancies (5/7, 71.4%). All patients were prescribed antenatal corticosteroids and tocolytics, with three (42.9%) receiving only atosiban and four (57.1%) receiving atosiban and other tocolytics. The median interval from starting atosiban administration to APE onset was about 40 h, and three patients (42.9%) showed symptoms 2-10 h after the end of atosiban treatment. Radiographic examinations (chest X-ray and/or computer tomography scan) confirmed APE in all patients and pleural effusion in four patients (57.1%). Five patients (71.4%) underwent emergency cesarean section, one patient (14.3%) with twin pregnancy had vaginal delivery with the help of suction cup and forceps, and another patient (14.3%) continued the pregnancy. All patients recovered well after administration of oxygen, diuresis, and other supportive therapy., Conclusion: Atosiban may cause acute pulmonary edema in patients with underlying risk factors. This complication remains rare, but caution during tocolytic treatment using atosiban is recommended., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: 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., Methods: 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., Results: 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, I 2 = 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., Conclusion: 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Huang, Tan and Xia.)

Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP 3 ) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10 -7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10 -9 -10 -5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP 3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca 2+ /calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC β1, which in turn liberates IP 3 , which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction.

Objective: To explore the efficacy of Atosiban combined with Ritodrine treatment on spontaneous threatened preterm birth and its effect on platelet-activating factor (PAF) and fetal fibronectin levels., Methods: Medical records from 120 patients with threatened preterm birth admitted to Baoji Maternal and Child Health Hospital from October 2020 to December 2021 were collected for this retrospective analysis. A total of 56 patients treated with Ritodrine alone were taken as the control group (CG), and the other 64 patients given combined treatment of Atosiban and Ritodrine were seen as the observation group (OG). Indexes of uterine contraction inhibition rate, pregnancy prolongation time, onset time, adverse reactions and pregnancy outcomes were compared between the two groups; in addition, the levels of inflammatory factors as well as PAF and fFN before and after treatment were detected and compared between two groups., Results: Compared with the CG, the uterine contraction inhibition rate as well as the pregnancy prolongation time in the OG were evidently higher (all P<0.05); the time of the disappearance of uterine contraction in the OG was significantly shorter (P<0.05); the rate of full-term delivery and neonatal 1-min Apgar score in the OG were obviously higher (P<0.05); and the incidence of total adverse reactions in the OG was markedly lower (P<0.05). However, there was no significant difference observed in the neonatal asphyxia rate and the number of fetuses between the two groups (P>0.05). After treatment, the OG was observed with markedly lower level of inflammatory factors C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) than the CG (P<0.05); levels of PAF and fFN decreased significantly in both two groups (P<0.05), and the levels in the OG were comparatively lower as compared to the CG (P<0.05). The areas under the ROC curve for PAF and fFN to predict pregnancy outcome were 0.766 and 0.757, respectively., Conclusion: Atosiban combined with Ritodrine evidently improves the therapeutic efficacy in patients with threatened preterm labor, reduces the occurrence of adverse pregnancy outcomes as well as the levels of PAF and fFN., Competing Interests: None., (AJTR Copyright © 2022.)

Objective: This study aimed to evaluate the effectiveness of intrapartum acute tocolysis for nonreassuring fetal heart rate tracing in decreasing the incidence of cesarean delivery. Secondary outcomes included modes of delivery other than cesarean delivery, successful acute tocolysis, time-to-delivery interval, and short-term perinatal outcomes., Data Sources: Searches were performed in MEDLINE/PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from the inception of each database until February 2022., Study Eligibility Criteria: Selection criteria included randomized controlled trials of laboring patients with singleton gestations randomized to receive intrapartum acute tocolysis for nonreassuring fetal heart rate tracing, as defined by the original trial., Methods: All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. A frequentist network-meta-analysis was performed., Results: Four randomized clinical trials were eligible, including 605 patients with nonreassuring fetal heart rate tracing and singleton gestations at gestational ages >32 weeks. The cesarean delivery rate was similar among patients managed with different types of acute tocolysis. Acute tocolysis, compared with emergency delivery, was associated with improved neonatal acid-base status (notably decreasing the prevalence of base deficit >12 mmol/L [beta-2 agonists odds ratio, 0.61; 95% confidence interval, 0.37-0.99] and the rate of neonatal intensive care unit admission [beta-2 agonists odds ratio, 0.42; 95% confidence interval, 0.22-0.78]) and with an increase in the time-to-delivery interval (beta-2 agonists mean difference, 17.62 minutes; 95% confidence interval, 15.66-19.58); there was no reduction of cesarean delivery rate, showing an increased rate with atosiban and beta-2 agonists., Conclusion: The cesarean delivery rate was not reduced by acute tocolysis when used for nonreassuring fetal heart rate tracing during labor. Acute tocolysis is associated with improved short-term fetal outcomes and safely increases the time-to-delivery interval., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: On January 2020, the French College of Gynecologists and Obstetricians (CNGOF) issued new Clinical Practice Guidelines (CPG) "Breech Presentation". Since then, it is recommended to use a tocolytic agent to improve the success rate of External Cephalic Version (ECV). The aim of this study, one year after these CPG, is to compare ECV without (before CPG) and with (after CPG) tocolysis in a type III maternity hospital. We intend to assess its effects on immediate success rate of ECV and obstetrical and neonatal outcomes., Materials and Methods: This is a single-center retrospective study conducted in Nantes University Hospital. We collected patient characteristics, immediate success rate, and maternal and neonatal outcomes at delivery of all ECV over two periods: the first one during 2019 (before CPG) and the second one from June 2020 to June 2021 (after CPG)., Results: We included 253 patients: 126 in the first period and 127 in the second period. Immediate success rate of ECV was significantly higher since the use of tocolysis: 38.6 % (period 2) vs 23.8 % (period 1) (P=0.011). However, there was not significant difference found for cephalic presentation at birth, mode of delivery or obstetrical and neonatal outcomes., Conclusion: The immediate success rate is significantly improved with the widespread use of tocolysis during ECV, with no change in obstetrical and neonatal outcomes., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF., Methods: A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration., Results: There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E 2 ) on the day of hCG above the median level. And, there was no correlation between the serum E 2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth., Conclusions: These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients., Trial Registration: The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722., (© 2022. The Author(s).)

Objective: To investigate the efficacy of atosiban combined with ritodrine in threatened preterm labor (TPL) treatment and analysis of related risk factors of different pregnancy outcomes., Methods: A retrospective study was conducted on the clinical data of 127 patients with TPL who were hospitalized in the Children's Hospital of Shanxi and Women's Health Center of Shanxi from January 2020 to November 2021. There from, 58 patients treated with ritodrine were seen as the control group (CG), and 69 treated with atosiban and ritodrine were regarded as the joint group (JG). The inhibition rate after treatment was compared, and the changes of tissue inhibitor of metalloproteinase-1 (TIMP-1), nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in the amniotic fluid before and after treatment were assessed. The pregnancy outcomes of patients were recorded, and the risk factors of adverse pregnancy outcomes were analyzed. The full-term delivery rate, cesarean section rate and neonatal Apgar score >7 were compared, and their adverse reactions were evaluated., Results: Compared with the JG, the improvement of uterine contraction in the CG was obviously lower, and so was the inhibition rate (P<0.05). The rates of full-term delivery and neonatal Apgar score >7 in the CG were lower than those in the JG, while that of cesarean section was higher (P<0.01). After treatment, the TIMP-1 level in the amniotic fluid in the CG was markedly lower (P<0.001), while the NO, IL-6 and PGE2 levels were higher (P<0.001) as compared with the joint group. The total incidence of adverse reactions in the JG was lower than that in the CG (P<0.05). Logistics regression analysis revealed that age<26 and use of Atosiban combined with Ritodrine are protective factors for pregnancy outcomes, while BMI≥20 before pregnancy is a risk factor for adverse pregnancy., Conclusion: Atosiban combined with ritodrine can improve the condition of TPL patients, enhance the treatment efficacy, and reduce the occurrence of adverse pregnancy outcomes., Competing Interests: None., (AJTR Copyright © 2022.)

Introduction Preterm birth is defined as a live birth before 37 weeks of gestation and is associated with increased neonatal morbidity and mortality. The aim of this study is to compare the efficacy of hexoprenaline and atosiban for short- and long-term tocolysis and their effects on neonatal and maternal outcomes. Methods This retrospective cohort study included women with threatened preterm labor between 24 + 0 and 34 + 0 weeks of gestation without premature rupture of membranes. The tocolytic efficacy of hexoprenaline and atosiban was compared in women receiving one of the two medications for short- and long-term tocolysis. Continuous variables were compared using t-test or Mann-Whitney U test, as appropriate. Comparison of categorical variables between the two groups was done with χ 2 test after Pearson's and Fisher's exact test. Results 761 women were enrolled in this study; 387 women received atosiban and 374 women received hexoprenaline as their primary tocolytic agent. Atosiban showed a higher efficacy as a primary tocolytic agent (p = 0.000) within 48 hours. As regards long-term tocolysis, there were no differences between the treatment groups (p = 0.466). Maternal side effects such as tachycardia (p = 0.018) or palpitations (p = 0.000) occurred more frequently after the administration of hexoprenaline, while there were no differences between the two drugs administered with regard to any other maternal or neonatal outcome parameter. Conclusion Our retrospective study shows a significantly higher efficacy of atosiban in the first 48 hours, especially when administered at an early gestational age. There were no significant differences in terms of neonatal outcome but significantly more maternal adverse effects during the administration of hexoprenaline., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: The physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its physicochemical properties., Study Design: Test admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods., Results: None of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range., Conclusions: Our study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

What Is Known and Objective: Premature birth affects more than 15 million infants, as well as mothers and families around the world. With the relaxation of the two-child policy, the problem of premature birth has become relatively prominent in China. According to statistics, China had a birth population of 15.23 million in 2018, with a considerably large number of premature births. This study aims to evaluate the efficacy and safety of tocolysis in the treatment of preterm delivery, provide clinical evidence for medical staff and promote the self-management of patients with premature births., Methods: Four English databases (PubMed, Embase, Cochrane Library and Web of Science) were retrieved by computer, the retrieval time was from the establishment of each database to November 2021, and the randomized controlled trials for the treatment of preterm delivery were screened according to the pre-set natriuretic exclusion criteria. After literature screening, data selection and risk of bias evaluation were independently conducted by two researchers. R 4.1.1 and Stata 17.0 software were used for statistical analysis., Results and Discussion: A total of 44 RCTs were included, including 6939 patients. The results of network meta-analysis reveal that in terms of effectiveness, indomethacin was the most effective intervention measure, followed by nifedipine, and the difference was statistically significant; regarding safety, nifedipine was the safest intervention measure, followed by indomethacin, and the difference was statistically significant; and in respect of adverse reactions, ritodrine had the highest probability, and the difference was statistically significant., What Is New and Conclusion: Nifedipine may be better for delayed delivery and less likely to produce adverse pregnancy outcomes, followed by indomethacin. Limited by the number and quality of recipient studies, the aforementioned conclusions need to be verified through more high-quality studies. At the same time, the focus should be on patients with twin pregnancy and patients with clinical manifestations of extreme preterm delivery., (© 2022 John Wiley & Sons Ltd.)

Aims: This study verified the action of oxytocin (OT) as a preventive measure to control bone damage during aging in female rats., Main Methods: Wistar rats received saline (0.15 mol/L/IP; Vehicle Group), Atosiban/AT (300 μg/Kg/IP; At Group), OT (134 μg/Kg/IP; Ot Group), or AT+OT (OT injections 5 min after AT; At+Ot Group), at 19 and 20 months of age. A functional test was performed immediately before and 30 days after the injections to analyze the animals' gait., Key Findings: Animals in the At group had higher alkaline phosphatase (ALP) activity, lower cortical and trabecular thickness, fewer trabeculae, higher expression of tartrate-resistant acid phosphatase (TRAP) and lower osteocalcin (OCN), higher cortical porosity, and lower moment of inertia and bone strength at the femoral neck. OT administration increased lipidic peroxidation and plasma superoxide dismutase (SOD), and provided, in the femoral neck, lower expression of TRAP and higher OCN, greater cortical and trabecular thickness, a greater number of trabeculae, bone mineral density (BMD), higher inertia bone strength, and lower cortical porosity. At + Ot group showed great similarity with the vehicle group, higher SOD, and BMD. An increase in stride length and no increase in base width of 21-month-old animals were observed after OT, unlike animal's vehicle or AT., Significance: Endogenous OT plays an important role in the regulation of bone remodeling during periestropause, and exogenous OT stands out as a potential preventive intervention in this period to improve bone quality with functional repercussions, possibly providing better gait activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Clinically, 5-fluorouracil (5-Fu) is a first-line drug for the treatment of patients with colorectal cancer (CRC). However, chemoresistance to 5-Fu-based chemotherapy is a leading obstacle in achieving effective treatment for CRC, especially microsatellite stable (MSS) CRC. Since the cytotoxicity of 5-Fu is negatively correlated with oxytocin receptor (OXTR) expression in MSS CRC cell lines, our current study aimed to investigate the synergistic antitumor activity of 5-Fu combined with atosiban, an antagonist of OXTR. Our results suggested that atosiban remarkably potentiated the inhibitory effect of 5-Fu on the growth of MSS-type CRC cells in vitro and in vivo. Moreover, 5-Fu induced GATA3 in MSS CRC cells and tumors, which were eradicated by atosiban. Further investigation showed that atosiban strengthened the antitumor activity of 5-Fu through eradiation of 5-Fu-induced GATA3 in MSS-type CRC cells. Taken together, our findings suggest that atosiban potentiates the antitumor effect of 5-Fu by abolishing 5-Fu-induced GATA3, which provides a novel therapeutic strategy for MSS-type CRC via the combination of atosiban and 5-Fu., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The key intermediate NH 2 -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.

Introduction: The breech presentation represents 4,7% of deliveries at term. There is a method of external cephalic version (ECV) performed from 36 weeks of gestation. French guidelines for the clinical practice of ECV were published in 2020., Objective: To evaluate the national practices of ECV in French maternity units, especially on the use of tocolysis, 1 year after publication of the French clinical recommendations guidelines by the French national college of obstetricians and gynecologists (CNGOF)., Methods: Data self-reported for this national descriptive study were collected from March to May 2021 by an online questionnaire distributed to all French maternities. The 25 items of the questionnaire collected information of maternity units, the general practice of ECV, use or not of tocolysis for ECV attempt and the relevance of a prospective study., Results: Of the 517 French maternity units, 150 (29%) responded to the online survey.  95,3% systematically performed ECV. A Kleihauer test was routinely performed in 71 units (49.7%). A tocolysis was associated with ECV attempt in 52.4% of cases. The drugs used were intravenous atosiban (30,7%), mainly in levels 2b and 3 maternity units, intravenous salbutamol (24%), other mode of administration of salbutamol (14,7%) and oral nifedipine (22,6%) mainly in levels 1 and 2a maternity units. Adverse effects were described in 20%, mainly with the use of salbutamol (73,3%)., Conclusions: 52.4% of the French maternity units surveyed used tocolysis for the ECV attempt, although it is systematically recommended. The choice of tocolytic drug differed according to the maternity units., Competing Interests: Declaration of Competing Interest Any authors have financial competing interests. Vincent Dochez is a regular reviewer of the editorial board. Norbert Winer and Thibault Thubert are associate editors of this journal. The other authors have no non-financial competing interests., (Copyright © 2021. Published by Elsevier Masson SAS.)

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 (χ 2 ) (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.

A systematic literature review and meta-analysis was conducted to evaluate whether the administration of an oxytocin receptor antagonist (OTR-a) around embryo transfer is associated with live birth and pregnancy achievement in IVF treatment. Multiple databases were searched for randomized controlled trials (RCT) comparing the outcome of IVF treatment with administration of an OTR-a before, during or after embryo transfer versus administration of placebo/nil. The literature search identified 11 eligible RCT. The active compound was intravenous atosiban (n = 7), subcutaneous barusiban (n = 1) and oral nolasiban (n = 3). Clinical pregnancy rate was significantly higher in women receiving an OTR-a around embryo transfer (relative risk [RR] 1.31, 95% confidence interval [CI] 1.13-1.51, P = 0.0002, I 2  = 61%, n = 11 studies, n = 3611); however, live birth rate was not statistically significantly affected (RR 1.09, 95% CI 0.98-1.20, P = 0.11, I 2  = 25%, n = 5 studies, n = 2765). A sensitivity analysis on low risk of bias studies likewise indicates a higher clinical pregnancy chance (RR 1.11, 95% CI 1.01-1.22, P = 0.03, I 2  = 5%, n = 5 RCT, n = 2765). OTR-a administration in IVF treatment has the potential to increase IVF efficacy, although the treatment effects observed so far are small and have not been sufficiently corroborated., (Copyright © 2021. Published by Elsevier Ltd.)

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., (© 2021 Japan Society of Obstetrics and Gynecology.)

Methamphetamine (METH) is a highly neurotoxic psychoactive substance that can directly damage the central nervous system through prolonged use. Oxytocin (OT) has attracted much attention because of its neuroprotective effect. The purpose of this study was to investigate whether OT is neuroprotective against METH-induced damage in rat hippocampal neurons. Our results revealed that pre-incubation with OT significantly prevented the damage of METH to hippocampal neurons, including the decrease of mitochondrial membrane potential and the increase of ROS (reactive oxygen species). OT pre-incubation attenuated the up-regulation of Cleaved-Caspase-3 expression and the down-regulation of Bcl-2/Bax expression induced by METH. Pre-incubation with OT prevented the decrease in oxytocin receptor density and P-CREB (phosphorylation of cAMP-response element binding) expression induced by METH in rat hippocampal neurons. Moreover, Pre-incubation of atosiban (ATO) significantly prevented these changes. In conclusion, our study proved that pre-administration of OT could significantly attenuate hippocampal neuron apoptosis induced by METH. Oxytocin receptor activation is involved in the preventive effect of OT on METH-induced apoptosis in rat hippocampal neurons., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Wang, Wang, Chen, Bai, Ban and Wu.)

Background: Embryo transfer without difficulty in a patient with cervical stenosis can be a great challenge for in vitro fertilization (IVF). We report a successful pregnancy following a frozen thawed embryo transfer after administration of an oxytocin antagonist at the same time as using a Foley catheter with cotton swab in a patient with refractory cervical stenosis., Case Presentation: A 40-year-old woman undergoing IVF. The patient's previous embryo transfers were difficult. For every transfer, uterine manipulation was needed, force was required, and dilatation was necessary. A Foley catheter with a cotton swab was inserted into the cervical canal, atosiban was administered at the same time, and the Foley catheter was removed immediately before embryo transfer. A smooth transfer was performed without bleeding, force, uterine manipulation, or cervical dilator. The patient became pregnant and delivered by cesarean section at term., Conclusion: This method is effective in performing atraumatic embryo transfer in patients with cervical stenosis.

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., Competing Interests: The authors declare that they have no conflicts of interest. No funding support was used for this study., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

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., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest., (© Copyright 2021, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Repeated implantation failures are a constant challenge in reproductive medicine with a significant impact both on health providers and on infertile couples. Several approaches have been proposed so far as effective; however, accumulative data have clarified that most of the treatment options do not have the evidence base for a generalized application to be suggested by the relevant societies. Implantation failures are attributed to either poor quality embryos or to defected endometrial receptivity. The current review aims to summarize in a systematic way all the new trends in managing RIF via interference with endometrial receptivity. The authors focus mainly, but not exclusively, on endometrial injury prior to embryo transfer and endometrial priming with autologous cells or biological agents. To this direction, a systematic search of the Pubmed database has been conducted taking into account the emerged evidence of the last two decades. All the suggested interventions are herein presented and analyzed in terms of reproductive outcomes. It is evident that properly powered and designed randomized trials are needed to support a new standard approach in RIF treatment that will safely be incorporated in national and international guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Makrigiannakis, Makrygiannakis and Vrekoussis.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

Objective: To estimate the effectiveness of Atosiban in improving the outcome after embryo transfer. The effectiveness of embryo transfer per cycle is still relatively low. One possible explanation might be uterine contractility that expels the transferred embryos. Atosiban improved the outcome of embryo transfer by reducing uterine contractility., Methods: Data sources: A systematic review of papers in English using MEDLINE and EMBASE (1990-2019). Search terms included Atosiban, embryo transfer. Study selection: We included studies that compared the outcomes of embryo transfer with Atosiban and a control group. Data Extracting: Independent extraction of papers by two authors, using predefined data fields, including study quality indicators., Results: All pooled analyses were based on a fixed-effect model. Four randomised controlled trials, including 1,025 women, and two non-randomised trials, including 686 patients, met our inclusion criteria. In both studies, the heterogeneity was moderate. Atosiban increased clinical pregnancy rates regardless of the indication for ART or type of embryo transferred. Pooled OR in randomized controlled trials reached 1.47 (1.18-1.82), and in non-randomised controlled trials it reached 1.50 (95% CI 1.10-2.05)., Conclusion: Atosiban appears to increase the clinical pregnancy rates in women undergoing embryo transfer.

Objective: To compare the efficacy of atosiban with conventional treatment of the threatened preterm labor., Materials and Methods: All 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., Results: The 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., Conclusions: Our results support that atosiban would represent an advance over current tocolytic therapy especially for the high gestational ages., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

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., (© 2020 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Social factors have a dual influence on addictive disorders. While social defeat stress in rodents increases the response to drug reward, positive social conditions, such as pair housing, increase stress resilience. The objective of the present study was to confirm whether oxytocin (OT) mediates this social buffering. To this end, male mice were housed in pairs and administered the OT receptor antagonist atosiban prior to each stress episode or for ten days after the stress protocol. The response to cocaine was assessed using a conditioned place preference paradigm. Our results confirmed that OT activity mediates the protective effect of pair housing and highlights its therapeutic potential., Competing Interests: Declaration Of Competing Interest Declarations of interest: none, (Copyright © 2020 Elsevier Inc. All rights reserved.)

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: 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., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

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.

Consulting the national pharmacopoeia, no official quality standard was found for estimation of related substances and assay of atosiban acetate injection, of which main active component is atosiban. To solve this problem, herein, a novel high performance liquid chromatographic (HPLC) method was developed and validated in this study. A chromatographic system comprising an Inertsil ODS-2 analytical column, mobile phase-A of water (pH adjusted to 3.2 with trifluoroacetic acid)-acetonitrile-methanol (77:14:9, v/v/v), mobile phase-B of acetonitrile-methanol (65:35, v/v), a flow rate of 1.0 mL min-1 and a UV detector set at 220 nm with column temperature at 35 °C has shown simple, reproducible and specific determination for atosiban and its five related substances. Also, we combined with mass spectrometry to characterize the molecular weight and tentative structure of the impurities. Using HPLC verified methodology, results of the validation study showed that the precision, specificity and accuracy of the five impurities, good linear equation R squared was greater than 0.9993, and as such, the limit of detection and the limit of quantification have been determined. The proposed method in this study, which, to the best of our knowledge, is the most comprehensive HPLC determination applied to the routine analysis in quality control of this injection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Introduction: Preterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed., Methods and Analysis: We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30-34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective., Ethics and Dissemination: This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC's in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results., Trial Registration Number: Nederlands Trial Register (Trial NL6469)., Competing Interests: Competing interests: JT received a number of lectures and medical advisory fees from Ferring pharmaceuticals between 2000 and 2016., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

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.

Background: The herbal medicine Bryophyllum pinnatum has been used as a tocolytic agent in anthroposophic medicine and, recently, in conventional settings alone or as an add-on medication with tocolytic agents such as atosiban or nifedipine. We wanted to compare the inhibitory effect of atosiban and nifedipine on human myometrial contractility in vitro in the absence and in the presence of B. pinnatum press juice (BPJ)., Methods: Myometrium biopsies were collected during elective Caesarean sections. Myometrial strips were placed under tension into an organ bath and allowed to contract spontaneously. Test substances alone and at concentrations known to moderately affect contractility in this setup, or in combination, were added to the organ bath, and contractility was recorded throughout the experiments. Changes in the strength (measured as area under the curve (AUC) and amplitude) and frequency of contractions after the addition of all test substances were determined. Cell viability assays were performed with the human myometrium hTERT-C3 and PHM1-41 cell lines., Results: BPJ (2.5 μg/mL), atosiban (0.27 μg/mL), and nifedipine (3 ng/mL), moderately reduced the strength of spontaneous myometrium contractions. When BPJ was added together with atosiban or nifedipine, inhibition of contraction strength was significantly higher than with the tocolytics alone (p = 0.03 and p < 0.001, respectively). In the case of AUC, BPJ plus atosiban promoted a decrease to 48.8 ± 6.3% of initial, whereas BPJ and atosiban alone lowered it to 70.9 ± 4.7% and to 80.9 ± 4.1% of initial, respectively. Also in the case of AUC, BPJ plus nifedipine promoted a decrease to 39.9 ± 4.6% of initial, at the same time that BPJ and nifedipine alone lowered it to 78.9 ± 3.8% and 71.0 ± 3.4% of initial. Amplitude data supported those AUC data. The inhibitory effects of BPJ plus atosiban and of BPJ plus nifedipine on contractions strength were concentration-dependent. None of the test substances, alone or in combination, decreased myometrial cell viability., Conclusions: BPJ enhances the inhibitory effect of atosiban and nifedipine on the strength of myometrial contractions, without affecting myometrium tissue or cell viability. The combination treatment of BPJ with atosiban or nifedipine has therapeutic potential.

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., (© 2019 Royal College of Obstetricians and Gynaecologists.)

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., (© 2019 International Federation of Gynecology and Obstetrics.)

We report the case of a pregnant woman, treated by nifedipine and next by atosiban for premature labour, who develop an acute pulmonary edema. The severity of symptoms and hypoxemia lead the patient to a cesarean and next to the intensive care hospitalization. This clinical case allow us to make a review of literature and reminds us the differential diagnosis to look for during an acute dyspnea in a pregnant woman and the treatment of acute pulmonary edema in these circumstances. The pathophysiological mechanisms which are at the origins of this condition and the implication of the tocolytic treatment will also be discussed.