Tocolytic Research Articles

Uterocervical Angle Anterior, Posterior, and Cervical Length Ultrasound as a Predictors for Successful Delay in Labor of Pregnant Women with Threatened Preterm Birth (PTB)

Introduction: To determine whether the examination of the uterocervical angle anterior, posterior, cervical length, and combination can be used as a predictor of successful delay in labor in patients with threatened preterm birth (PTB). Methods: This is a prospective cohort analytical observational study of 44 women admitted to our hospital gestational age 28-36 weeks diagnosed with threatened preterm birth. Cervical length, anterior uterocervical angle, and posterior uterocervical angle examinations were performed. Patient then observed for 2x24 hours whether there was a delay in labor or not. If there is a delay, the patient followed until delivery. Results: CL cut off value > 2.66 cm delaying labor for 2x24 hours and > 2.81 cm delaying labor until term. UCA posterior cut off value < 113.2o delaying labor for 2x24 hours and < 107.8o delaying labor until term. Anterior UCA cut off values < 103.2o delaying labor for 2x24 hours and < 93.1o delaying labor until term. Statistical Analysis showed that CL was significant as a single tool for predictor of delayed labor either 2x24 hours or up to term, while posterior and anterior UCA was not. But if this 3 single tools combinate, CL, anterior UCA, and posterior UCA was statistically significant as a predictor of delay in labor either 2x24 hours or until term, with the best predictive value is a combination of CL and posterior UCA of 25.2% for predicting delay of labor 2x24 hours and the combination of CL, posterior, and anterior UCA was 24.6% for predicting delay labor until term. Conclusion: Cervical length ultrasound examination and the combination of CL, anterior UCA, and posterior UCA can be predictors of delayed labor in patients with threatened preterm birth but not for anterior and posterior uterocervical angle as a single tool.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo.

Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2 -mimetic terbutaline and magnesium sulfate (MgSO4 ) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia-inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. In the isolated organ bath studies, rhythmic contractions of 22-day- pregnant Sprague-Dawley rats were stimulated with KCl, and cumulative dose-response curves were constructed in the presence of MgSO4 or terbutaline. The uterus-relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+ -poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+ -poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia-inducing effect of terbutaline in late pregnant rats. The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia-inducing side effect of terbutaline.

Delegating violence in democracies: embedded developmentalism and persistence of labor repression in South Korea

AbstractWe address how democracy has influenced the ways in which the Korean state has managed the issue of labor-based collective action and suppression thereof. During the authoritarian period, the state, through specialized riot police, frequently, and violently, cracked down on protest movements and other forms of collective action. During democratization and post-democratic consolidation, private specialists in violence, operating with the consent of the state, began to replace public forces on the front lines, while working in concert out of the view of the public. Although such state/non-state collaboration in the market for oftentimes illegal violence has been addressed in scholarship elsewhere, we demonstrate through detailed evaluation that the extant explanations are largely incomplete, as they fail to capture the effects of changing relative levels of state-based autonomy from societal and corporatist influence.

Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants.

Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

Use of Nitroglycerine Patch in the Management of Preterm Labor

Background: Preterm birth is the delivery of the baby before 37 completed weeks of pregnancy. The goal of tocolytic therapy is to reduce neonatal mortality and morbidity by delaying birth, allowing for corticosteroid administration and maternal transfer to the tertiary care center. This study was conducted to observe the tocolytic efficacy of GTN transdermal patches in preterm labor between 28 – 36 weeks of pregnancy. Methods: This cross-sectional study was done in Obstetrics &amp; Gynecology Department at Mufti Mehmood Memorial Hospital, Dera Ismail Khan, from July 2017 to December 2017. Non-probability consecutive samplings of 186 pregnant women with preterm labor were included in the study. Detailed history and examination, routine investigations and ultrasound were performed to confirm viability, gestational age and exclusion of multiple pregnancies, lethal fetal malformation and intrauterine death. Effectiveness of the GTN patch was considered successful if the cessation of uterine contraction occurred within 24 hours of the application of the GTN patch and persisted for 48 hours to achieve the effect of steroids. Results: Tocolytic efficacy of GTN transdermal patch in preterm labor between 28 to 36 weeks of pregnancy was 88.71%. Regarding the parity of the women, 75.8% of women had multipara (parity 2 to 5) and 24.2% had primipara. The average gestational age was 33.15±2.28 weeks. . Two to three uterine contractions per 10 minutes were observed in 75.8% of women while four uterine contractions per 10 minutes were observed in 24.19% of cases. 2cm cervical dilatation was observed in 82 women (44.09%) and 3cm was 75 women (40.32%). Practical implication: The incidence of preterm delivery can be minimized using GTN patch to reduce the uterine contractions and increase the fetal viability inside the womb. Conclusion: There is no better incubator than a mother's womb. The GTN patch appears to be a safe, non-invasive method of suppressing uterine contractions in pre-term labor and also a simple, quicker and cost-effective tocolytic agent. Keywords: Pre-term labor; Tocolytic; Transdermal patch; Uterine contractions.

Investigations on incidence and relevant factors of allergies in 5725 urban pregnant women: a cohort study in China

BackgroundAllergic diseases are highly prevalent in the women of childbearing age. As we know, the immune system could change when pregnancy, which may affect the course of allergic diseases. Meanwhile, they also can affect the course and outcome of pregnancy. The data on incidence of allergies during pregnancy is lacking and conducting clinical trials in pregnant women was limited, therefore, we observed a prebirth cohort to supplement the relevant data and strengthen concerned research conductions.ObjectiveWe aim to obtain the incidence of allergies in urban pregnancy and explore the relevant factors of allergic diseases in urban pregnancy.MethodsWe design a multicenter and prospective cohort in 20 institutions above municipal level which were eligible according to the study design from 14 provinces covering all-side of China. This cohort was conducted from 13+6 weeks of gestation to 12 months postpartum and in our study, we chose the prenatal part to analyze. The outcome was developing allergies during pregnancy, which were diagnosed by clinicians according to the uniform criterion from National Health Commission. All the data was collected by electronic questionnaires through tablet computers.ResultsThe incidence of allergic diseases in urban pregnant women was 21.0% (95%CI 20.0% ~ 22.0%). From social demography data, the history of allergies of pregnant women and their parents had statistical significance(p < 0.01); For exposure to living or working environment, house decoration for less than half a year, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agent and probiotics had statistical significance (all p < 0.05); For psychological status, self-rated depression and anxiety had statistical significance (p = 0.026;p = 0.006).ConclusionThe incidence of allergic diseases in urban pregnant women was similar to the former study and kept a medium–high level. The history of allergies of pregnant women and their parents, house decoration time, exposure to plush toys, disinfectants, insecticides, antihistamines, glucocorticoids, antipyretic analgesics, tocolytic agents, probiotics, self-rated depression, and anxiety were relevant factors of allergic diseases during pregnancy.

Labor Repression, Democracy, and Growth in South Korea: Data Construction and Preliminary Results

Labor Repression, Democracy, and Growth in South Korea: Data Construction and Preliminary Results

ANESTHESIA FOR FETAL SURGERY - PRINCIPLES AND CONSIDERATIONS: A CONCISE REVIEW.

Fetal surgery, an integral part of fetal therapy has undergone evolution since is conception, which was possible due to continuous renements in surgical as well as anesthetic techniques The fetal surgery can be done in various stages of the gestation for corrective treatment. Time tested criteria have been laid down for patient selection which help improve the outcome of the whole exercise. The anesthesia concerns and considerations are unique as are the ethical issues involved in this treatment modality involving two patients with contrasting physiological needs. This article reviews salient aspects of fetal physiology in detail. Anesthesia for the fetal interventions is curated as per the invasive nature of surgical interventions. The type of fetal interventions are classied as minimally invasive procedures, Open mid gestation procedures and Ex-utero intrapartum treatment (EXIT) procedures. Preoperative evaluation is dictated by extent of gestation, and invasiveness of the surgical procedure apart from medical status of mother and fetus. This review also tries to enumerate number of clinically useful pharmacological agents in fetal anesthesia including essential tocolytic agents, in addition to management of common fetal complications with a separate section on fetal bradycardia.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Risk factors contributing to this condition are: advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, hypertension and In patients with gestational hypertension (GH) and other risk factors close monitoring is mandatory during pregnancy as well as in the postpartum period. Case report: A 38 year- old patient previously treated for endometriosis, infertility and GH was transferred from the Clinic of Gynecology due to diagnosed congestive heart failure. Five days prior admission she gave birth to her first child. Prior delivery she was treated with tocolytic therapy. She received methyldopa due to GH, that was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension (PAH) secondary to left ventricular failure. During hospitalization the patient was with signs of volume overload, but with well response on parenteral diuretic therapy. She was additionally treated with guideline recommended heart failure therapy. The controlled echocardiography showed improvement of the left ventricular function with an EF of 42%. Conclusion: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta trigger resolution of symptoms and recovery to the nonpregnant state of various organism, the contrary happens with blood pressure. Its peaking time is three to six days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy are a risk factor for PPCM due to causing decreased baroreflex sensitivity Patients with risk factors should be closely monitored for eventual cardiac complications.

Synthesis of 5- and 7-hydroxy indolizidin-2-one prostaglandin-F2α modulators and activity on myometrial contractility towards development of agents for delaying preterm birth.

In pursuit of more effective-labor delaying tocolytic agents, the prostaglandin F2α (PGF2α) receptor (FP) modulator PDC113.824 [(6S)-2] represents a potent lead for developing therapy to treat preterm birth. Derivatives of FP modulator (6S)-2 were synthesized, possessing respectively 5- and 7-hydroxyl groups on the indolizidin-2-one amino acid (I2 aa) residue. The effects of the alcohol substituents were examined in a PGF2α-induced myometrial contraction assay. Based on knowledge of dihedral angle values of model I2 aa peptides from X-ray analyses, the results of the study indicate respectively encouraging and limited potential for creating improved tocolytic agents by modifications at the 5- and 7-positions.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. The risk factors contributing to this condition are advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, and hypertension. In patients with gestational hypertension (GH) and other risk factors, close monitoring is mandatory during pregnancy as well as in the postpartum period. CASE REPORT: A 38-year-old patient previously treated for endometriosis, infertility, and GH was transferred from the clinic of gynecology due to diagnosed congestive heart failure. 5 days before admission, she gave birth to her first child. Before delivery, she was treated with tocolytic therapy. She received methyldopa due to GH which was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular (LV) systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension secondary to LV failure. During hospitalization, the patient was with signs of volume overload, but with a good response on parenteral diuretic therapy. She was additionally treated with guideline-recommended heart failure therapy. The controlled echocardiography showed improvement of LV function with an EF of 42%. CONCLUSION: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta triggers the resolution of symptoms and recovery to the nonpregnant state of various organisms, the contrary happens with blood pressure. Its peak time is 3–6 days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy is a risk factor for PPCM due to causing decreased baroreflex sensitivity. Patients with risk factors should be closely monitored for eventual cardiac complications.

The expertise effect: the impact of legal specialists’ intervention on the timely delivery of laymen's judgments

France relies exclusively on lay assessors to solve conflicts between entrepreneurs and employees for the longest time compared to any other civil jurisdiction. Given the lack of legal training of labor judges, the paper tests whether an intensification in the offer for legal services, whether coming from professional judges or specialized labor lawyers, induces delays in the procedure. Using a two-stage least squared estimating method and an innovative dataset on French labor courts between 2013 and 2017, the manuscript estimates the effect of an increase in the intervention of legal experts in labor litigation. The analysis showed that referrals to a professional judge delay labor cases’ solutions but refuted the long-standing economic theory that lawyers induce delay to acquire higher fees. This study indicates that the current structure of employment courts, entirely left in the hand of laymen with little knowledge of the ever-changing labor legislation, should be reconsidered to foster collaborative solutions accounting for industrial experience and, at the same time, legal competency.

Arresting the Opposition: Labor Repression and Trade Liberalization in Developing Countries

AbstractAt the turn of the twenty-first century, why did country after country in the developing world open their economies to the global market? This paper argues that increases in democracy were more likely to lead to trade liberalization when governments violated workers’ basic rights to act collectively. Democracy empowered pro-trade domestic groups and therefore had the potential to lead to trade liberalization, but respect for labor rights empowered protectionist labor unions to launch protests and strikes that hampered such reforms. This paper supports these arguments with a multimethod approach that combines quantitative analysis of data from 126 developing countries from 1985 to 2010 with qualitative case studies of Argentina and Mexico. In general, the empirical evidence suggests that democracy and labor repression often worked together to facilitate the process of trade liberalization in developing countries.

Magnesium Sulphate and Nifedipine in Management of Preterm Premature Rupture of Membranes

Premature rupture of membranes (PROM) is defined as rupture before delivery that can occur at any gestational age. If it occurs before 37 weeks of gestation, it’s called Preterm Premature Rupture of Membrane (PPROM). PROM is a condition that still occurs in both developed and developing countries and cause a serious threat to the fetal and maternal well-being if not managed properly. Conservative management is chosen in PPROM until the fetus is viable, consist of hospitalization, assessment of sign of infection, well-being of the fetal and maternal. Spesific treatment includes the administration of corticosteroid, antibiotics, and tocolytics. Tocolytic agents that are widely used as first-line agents are magnesium sulphate (MgSO4) and nifedipine, one of the Calcium Channel Blocker (CCB) groups. MgSO4 and nifedipine both have an effect in reducing myometrial contractility. MgSo4 also has a neuroprotective effect in PPROM less than 31 weeks if there is a threat of delivery within 24 hours. Meta-analysis related to the use of these two agents in PPROM is still subject to differing result. Some studies have shown nifedipine is considered to have milder side effect than MgSO4, more easily tolerated by oral administration, and more affordable. However, some studies have shown that the two agents have the same efficacy. Other studies have shown no significant benefit in administering nifedipine to neonates or prolong pregnancy in women with PPROM without contractions.

Betamethasone use and risk factors for pulmonary edema during the perinatal period: a single-center retrospective cohort study in Japan

BackgroundA few studies have reported that maternal administration of antenatal corticosteroids increased the risk of pulmonary edema (PE). However, despite the increasing usage rate of betamethasone as antenatal corticosteroid, maternal administration of betamethasone as a risk factor for PE has not been well studied. This study aimed to evaluate how maternal backgrounds and complications, tocolytic agents, and betamethasone affect the incidence of PE during the perinatal period and determine the risk factor for PE.MethodsThis was a single-center retrospective cohort study in Kurashiki, Japan. The study subjects were patients who had been admitted to our hospital for perinatal management including pregnancy, delivery and puerperium between 2017 and 2020. The primary outcome measure was defined as the incidence of PE during hospitalization. First, in all study subjects, Cox proportional hazards model was used to determine the risk factor for PE during the perinatal period. Next, using propensity score matching, we divided the patients into the betamethasone and betamethasone-free groups and examined the association between betamethasone use and the incidence of PE with Cox proportional hazards model.ResultsDuring the study period, 4919 cases were hospitalized, and there were 16 PE cases (0.3%). In all analyzed subjects, the occurrence of PE was significantly associated with preeclampsia (hazard ratio 16.8, 95% confidence intervals (CI) 5.39–52.7, P < 0.001) and the combined use of the tocolytic agents such as ritodrine hydrochloride and magnesium sulfate, and betamethasone (hazard ratio 11.3, 95% CI 2.66–48.1, P = 0.001). In contrast, after propensity score matching, no statistically significant difference was found between the betamethasone and betamethasone-free groups in the incidence of PE (hazard ratio 3.19, 95% CI 0.67–15.3, P = 0.145).ConclusionsA combined use of tocolytic agents and antenatal corticosteroids such as betamethasone may be an independent risk factor for PE during the perinatal period. On the other hand, betamethasone use alone may not be associated with the incidence of PE. When tocolytic agents and betamethasone are administrated to pregnant women, it is important to pay attention to the appearance of maternal respiratory symptoms.

Global newborn health research priorities identified in 2014: A review to evaluate the uptake.

SummaryBackgroundIn 2014, World Health Organization published global research priorities for newborn health till 2025. We conducted this review to summarize completed or ongoing research on the twenty priorities.MethodsWe conducted searches for twenty questions on MEDLINE via PubMed, Cochrane CENTRAL, Web of Science, clinical trial registries, and funder websites between July 2014 and May 2022. Studies addressing research questions using adequate design were included. Adequacy of uptake of a priority was assessed based on predefined criteria.FindingsThe uptake of research priorities was high for 8 (40%), moderate for 11 (55%), and one priority, effectiveness of training community health workers (CHWs) to treat neonatal sepsis at home remains unaddressed. Priorities with moderate uptake include effectiveness of simplified neonatal resuscitation programme, simple clinical algorithms for CHWs to neonatal infection, CHWs training in basic neonatal resuscitation, community-initiated kangaroo mother care, perinatal audits, and novel tocolytic agents, scaling-up chlorhexidine cord application, stable surfactant with simpler administration, accurate, affordable methods to diagnose fetal distress, strategies for prevention and treatment of intrauterine growth retardation, and causal pathways for antenatal stillbirths.InterpretationAdequate research was undertaken on pressing global concerns in newborn health. Funders and researchers should reflect on and address less researched areas.FundingNone.

Hexoprenaline Compared with Atosiban as Tocolytic Treatment for Preterm Labor.

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 Pearsonʼs and Fisherʼs 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.

Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis

BackgroundWorldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA).MethodsWe investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks’ gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata.ResultsWe detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47–1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80–5.1).Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69–0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14–0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73–1.4) or 7 days (OR 1.3, 95% CI 0.85–5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60–3.4).ConclusionsIn this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug.Study registrationWe conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.

P-122 Optimising IUI; a systematic review and network meta-analysis

Abstract Study question What is the effectiveness of add-on interventions to the standard intra-uterine insemination (IUI) protocol in improving reproductive outcomes? Summary answer Amongst the add-ons studied only luteal phase support and endometrial scratch were found beneficial for (LBR)/ongoing pregnancy rate (OPR) in IUI cycles. What is known already IUI is a fertility treatment offered to couples and single women for varied indications worldwide. Although cheaper and less invasive than in-vitro fertilization (IVF), it has received less attention and success rates remain low. Various add-ons have been introduced to boost IUI outcomes. However, their use remains largely empirical and is not standardized. Exploring the effectiveness of different protocol add-ons in comparisons with each other and with the standard protocol, could help develop evidence-based recommendations and optimize IUI treatment. Study design, size, duration We conducted a systematic review and meta-analysis aiming to assess the value of various IUI add-ons on clinical outcomes (PROSPERO registration number CRD42022300857). A computerized literature search was performed using EMBASE, MEDLINE, CINAHL and the Cochrane Central from database inception to October 2021. Two authors independently assessed the studies for quality and risk of bias. Studied add-ons included use of hydrotubation, endometrial scratch, trigger, double insemination, ultrasound guidance, bed rest, tocolysis and luteal phase support. Participants/materials, setting, methods Randomized controlled trials (RCTs) were included, reporting on one or more cycles of IUI with any protocol and indication using partner’s or donor sperm. We summarized the LBR or OPR when LBR was not available. We calculated odds ratios with 95% confidence intervals (CI) using random effects meta-analysis after transforming data using Freeman-Tukey double arcsine transformation. Heterogeneity was reported as I2 and Tau2 estimates. Main results and the role of chance Sixty one RCTs were included in the analysis. Amongst the add-ons studied, luteal phase support and endometrial scratch were found to increase chance of LBR/OPR by 1.48 times (CI 1.1243-1.9402, I2= 13.3%, Tau2= 0,0156 p = 0.330) and 1.58 times (CI 1.0992-2.2685, I2= 0.0%,Tau2=0,00 p = 0.510) respectively. No statistically significant difference was found for the use of hydrotubation (pooled OR 1.4192, CI 0.4936 - 4.0804, I2= 67.3%, Tau2=0,57 p = 0.047), trigger (pooled OR 0.6649, CI 0.2422- 1.8257, I2= 74.7%, Tau2=0,3972, p = 0.047), hCG versus agonist trigger (pooled OR 1.1570, CI 0.7501- 1.7847, I2=0.0%, Tau2=0.00, p = 0.502), ultrasound guidance (pooled OR 2.119, CI 0.8289-5.3809, p = 0.437), double IUI (pooled OR 0.9718, CI 0.5721-1.6508, I2=0.0%, Tau2=0.00, p = 0.567), and bed rest (pooled OR 1.1459, CI 0.4789-2.7418, I2=0.0%, Tau2=0.00, p = 0.005). No eligible studies were found on tocolytic agents. Two studies were identified for the use of misoprostol but the authors do not report results on the outcomes of interest. Limitations, reasons for caution The risk of bias was considered as “high”/“some concerns” for all included studies and the overall quality of evidence is low. Included studies randomized both per woman and per cycle and significant differences were noticed in ovarian stimulation protocols. More well-designed RCTs are needed in order to reach sound conclusions. Wider implications of the findings This meta-analysis provides evidence that luteal phase support and endometrial scratch provide clinical benefit for IUI success rates. However, it is possible that different add-ons could benefit specific patient groups. There is place for more research in the field to explore the value of add-ons in relation to subfertility background. Trial registration number n/a