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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The availability of piperidine, which is widely used for deblocking α-amine groups in solid-phase peptide synthesis using Fmoc methodology, is now significantly limited because this reagent is classified as a controlled substance. Therefore, a search for other available reagents capable of removing Fmoc-protection seems relevant. The suitability of three deblocking reagents based on secondary amines (4-methylpiperidine, pyrrolidine, and piperazine) for the solid-phase synthesis of peptides of various structures, i.e., atosiban (an analog of the neurohypophysial hormone oxytocin), metilin [an agonist of the apelin receptor (APJ)], and a fragment of the 11-19 amino-acid segment of the regulatory myosin light chain was comparatively assessed. These reagents were shown to be suitable alternatives to piperidine for the preparation of the physiologically active peptides being studied. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Evaluation & Analysis of Drug-Use in Hospitals of China is the property of Evaluation & Analysis of Drug-Use in Hospitals of China Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 (IVFET) 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, 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. 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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of International Reproductive Health/Family Planning is the property of Editorial Board of the Journal of International Reproductive Health/Family Planning and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 (IP3) 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 IP3 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 Ca2+/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 IP3, which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction. [ABSTRACT FROM AUTHOR]

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 (E2) on the day of hCG above the median level. And, there was no correlation between the serum E2 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

This work is devoted to the large-scale solid-phase synthesis (SPS) of Atosiban, Mpa1-D-Tyr(OEt)-Ile-Thr-Asn-Cys6-Pro-Orn-Gly-NH2 cyclic 1,6 disulfide, the only clinically used oxytocin receptor antagonist. The conditions have been selected for the closure of the disulfide bond (S–S) in the Atosiban molecule both in the solution and solid phase with the minimal formation of by-products. A comparative assessment of the formation of the S–S bond was carried out under various conditions. The formation of by-products during the closure of the disulfide bond has been studied both in solution and on the polymer support. The developed technique allows for the synthesis of Atosiban on an enlarged scale (10–20 mmol) involving the cyclization of a protected intermediate with the formation of the S–S bond during solid-phase synthesis with the minimal formation of by-products. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Xi'an Jiaotong University (Medical Sciences) is the property of Xian Jiaotong University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Objective  The aim of this study is to assess the efficacy and safety of retosiban in spontaneous preterm labor (sPTL). Study Design  Two multicenter, randomized, and double-blind trials compared retosiban with placebo and retosiban with atosiban in women with a singleton pregnancy and intact membranes in sPTL at 24 to 33 6/7 weeks' gestation. Coprimary endpoints in the placebo-controlled trial were time to delivery (TTD) or treatment failure (whichever occurred first) and neonatal composite morbidity and mortality. The primary endpoint of the atosiban comparator trial was TTD. Results  The trials were terminated early because of slow recruitment. The placebo-controlled trial enrolled 23 participants (February 2016–July 2017; 2.6% of target);the atosiban-comparator trial enrolled 97 (March 2015–August 2017; 29% of target). Baseline participant characteristics were similar between treatments. In the placebo-controlled trial, mean gestational ages at randomization were 30.8 (retosiban, n  = 10) and 30.5 weeks (placebo, n  = 13), and mean times to delivery/treatment failure were 18.9 days (retosiban) and 11.1 days (placebo). Two and four neonates in the retosiban and placebo groups, respectively, had ≥1 component of the neonatal composite endpoint. In the atosiban-comparator trial, mean gestational age at randomization was 31.5 weeks (for both retosiban, n  = 47, and atosiban, n  = 50), and adjusted mean TTDs were 32.51 days (retosiban) and 33.71 days (atosiban; p  > 0.05). Adverse events were no more common with retosiban than placebo or atosiban. Conclusion  Despite considerable efforts to conduct two adequate and well-controlled studies in patients with sPTL, both studies were unable to recruit effectively and consequently terminated prematurely. Key factors negatively affecting participation were patient and physician resistance to use of a placebo comparator, lack of investigator consensus on diagnostic criteria and acceptance of protocol procedures, and ethics committee decisions. Meaningful cooperation between pharmaceutical companies, regulatory authorities, and the obstetric community is essential for future development of drugs to treat sPTL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

Copyright of Magyar Nőorvosok Lapja is the property of Hungarian Society of Obsterics & Gynaecology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

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

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

Copyright of Journal of International Obstetrics & Gynecology is the property of TianJin Medical Information Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

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

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

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

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

Copyright of Cumhuriyet Medical Journal is the property of Cumhuriyet Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

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

Objective: Uterine contraction induced by the embryo transfer (ET) process has an adverse effect on embryo implantation. The aim of this study was to determine the effect of oxytocin antagonist supplementation on the day of ET on in vitro fertilization outcomes via a meta-analysis. Methods: We performed a meta-analysis of randomized controlled trials (RCTs). Four online databases (Embase, Medline, PubMed, and Cochrane Library) were searched through May 2015 for RCTs that investigated oxytocin antagonist supplementation on the day of ET. Studies were selected according to predefined inclusion criteria and meta-analyzed using RevMan 5.3. Only RCTs were included in this study. The main outcome measures were the clinical pregnancy rate, the implantation rate, and the miscarriage rate. Results: A total of 123 studies were reviewed and assessed for eligibility. Three RCTs, which included 1,020 patients, met the selection criteria. The implantation rate was significantly better in patients who underwent oxytocin antagonist infusion (19.8%) than in the control group (11.3%) (n=681; odds ratio [OR], 1.92; 95% confidence interval [CI], 1.25-2.96). No significant difference was found between the two groups in the clinical pregnancy rate (n=1,020; OR, 1.57; 95% CI, 0.92-2.67) or the miscarriage rate (n=456; OR, 0.76; 95% CI, 0.44-1.33). Conclusion: The results of this meta-analysis of the currently available literature suggest that the administration of an oxytocin antagonist on the day of ET improves the implantation rate but not the clinical pregnancy rate or miscarriage rate. Additional, large-scale, prospective, randomized studies are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

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Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Objective: The aim of the present study was to understand the role played by Atosiban, an oxytocin receptor antagonist, on trophoblastic human cells, and the molecular bases of its efficacy and safety in the treatment of preterm labor. NO, peroxinitrite production and NOS expression have been evaluated on placenta obtained from term and preterm labors. Patients and methods: We studied trophoblast cells isolated from selected placental tissue from 20 controls and 20 preterm patients after cesarean sections. Each sample was studied at basal state and after 2 hours incubation with oxytocin and Atosiban. Results: Significant variations of NO levels, peroxynitrite production and iNOS and eNOS expression both in the preterm, term samples and in each of the considered groups were observed. In the control group Atosiban re-established NO levels that were reduced after incubation with oxytocin, while in preterm samples NO levels were not only re-established but, after incubation with Atosiban, significantly increased compared to basal levels. Conclusions: This confirms the beneficial role of Atosiban in prolonging the pregnancy of spontaneous labor at very early gestational periods. In conclusion, Atosiban might be an effective drug to prevent preterm labor, in the therapeutic approach to this pathology. [ABSTRACT FROM AUTHOR]

The central rationale of tocolysis for preterm labor (PTL) is to delay delivery for at least 48 h to allow for transfer of the mother to a tertiary facility and for corticosteroids to induce surfactant production in fetal lungs. Beta-mimetics decrease the number of women in preterm labor giving birth within 48 h without reducing adverse neonatal outcomes. Calcium channel blockers inclusive of nifedipine decrease the adverse neonatal outcomes by significantly delaying delivery. Atosiban has the best maternal and fetal safety profile but does not seem to reduce neonatal complications. Magnesium sulfate is controversial as a tocolytic, but is valuable as a neuroprotective agent and for treatment of eclamptic seizures. Indomethacin may be a reasonable first choice for acute tocolytsis in gestational ages less than 32 weeks' gestation. Prolonged use (>48 h) should be avoided. Transdermal nitroglycerin can reduce neonatal morbidity and mortality as a result of decreased risk of birth before 28 weeks' gestation. Nifedipine may be a reasonable first choice because it is easy to administer and also of limited side effects relative to β2-mimetics. Tocolysis does not appear to significantly lengthen the gestational age beyond seven days. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does atosiban (oxytocin/vasopressin V1A receptor antagonist), given around embryo transfer improve the live birth rate of women undergoing IVF treatment? SUMMARY ANSWER The use of atosiban around embryo transfer did not improve the live birth rate in a general population of IVF patients. WHAT IS KNOWN ALREADY Uterine contractions in IVF cycles were significantly increased following ovarian stimulation and women with frequent uterine contractions had a lower pregnancy rates. A few observational studies suggested that the use of atosiban around embryo transfer resulted in higher pregnancy rates in women with repeated implantation failure (RIF). A non-randomized trial of IVF patients also reported higher implantation and clinical pregnancy rates after the use of atosiban. STUDY DESIGN, SIZE, DURATION This multi-centre randomized double blind study recruited 800 general subfertile women undergoing IVF treatment between November 2011 and March 2013. Subjects were randomized into the atosiban (n = 400) and placebo (n = 400) groups according to a computer-generated randomization list. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects were recruited and randomized in the three IVF units in Guangzhou, Hong Kong and Ho Chi Minh City. Women in the atosiban group received i.v. atosiban 30 min before embryo transfer with a bolus dose of 6.75 mg, and the infusion was continued at 18 mg/h for ∼1 h. The dose of atosiban was then reduced to 6 mg/h continued for another 2 h. Those in the placebo group received i.v. normal saline only. The primary outcome measure was the live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in the live birth rate between the atosiban and placebo groups (39.8 versus 38.0%, P = 0.612, rate ratio 1.051, 95% confidence interval: 0.884–1.251). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy rates and implantation rate per woman. Similar results were found between the groups at different IVF centres, with a repeated cycle, presence of uterine fibroids or a serum estradiol level on the day of hCG above the median level. LIMITATIONS, REASONS FOR CAUTION Limitations include the transfer of early cleavage embryos, no measurement of uterine contractions, no documentation of adenomyosis and incomplete tracking of congenital abnormalities in newborns. WIDER IMPLICATIONS OF THE FINDINGS This randomized double blind study demonstrated that the use of atosiban given around embryo transfer did not improve the live birth rate in a general population of IVF patients; therefore atosiban should be given only in the context of clinical research. STUDY FUNDING/COMPETING INTEREST(S) Centres in Hong Kong and Vietnam received research funding from Ferring, which was not involved in study design, execution, data analysis and manuscript preparation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT01501214. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects. Methods/Design: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of = 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, ß 0.2 at alpha 0.05). Discussion: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour. [ABSTRACT FROM AUTHOR]

Aim of the present study was to evaluate effects of ligands of oxytocin receptors on gene expression of neurofilament proteins (nestin and microtubule-associated protein 2 (MAP2)) associated with neuronal differentiation and growth factors (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) related to neuronal growth. Fluorescent staining of F-actin was used to observe morphology of cells. Co-treatment with oxytocin and oxytocin receptor antagonist-atosiban-resulted in significant increase of MAP2 gene expression in SK-N-SH cells. There was no effect of oxytocin on gene expression of growth factors BDNF and NGF. Surprisingly, oxytocin with atosiban significantly increased mRNA levels for both BDNF and NGF. Gene expression of vasopressin receptor (V1aR) significantly decreased in response to vasopressin. Atosiban decreased mRNA levels for oxytocin receptor (OXTR) and V1aR. Oxytocin significantly decreased OXTR and nestin mRNA levels and increased mRNA levels for BDNF and NGF in U-87 MG cells. The densest recruitment of F-actin filaments was observed in apical parts of filopodia in SK-N-SH cells incubated in oxytocin presence. Present data demonstrate complex role of ligands of oxytocin receptors in regulation of gene expression of intermediate filaments and thus, oxytocin might be considered as a growth factor in neuronal type of cells. [ABSTRACT FROM AUTHOR]

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Purpose: The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model. Methods: Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group ( n = 8), a daily dose of 0.2 ml 0.9 % NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups ( n = 8 and n = 8), 0.5 mg/kg/day i.p. atosiban and 1 mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups. Results: After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group. Conclusions: In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency. [ABSTRACT FROM AUTHOR]