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The Journal of Obstetrics and... Jul 2023To estimate the incidence and identify risk factors of postpartum hemorrhage (PPH) after vaginal delivery. (Meta-Analysis)
Meta-Analysis Review
AIM
To estimate the incidence and identify risk factors of postpartum hemorrhage (PPH) after vaginal delivery.
METHODS
A systematic review and meta-analysis was conducted. PubMed, Cochrane Library, CINAHL, Web of Science, EMBASE, and ClinicalTrials.gov databases were systematically searched from inception to April 30th, 2022. Cross-sectional, cohort, case-control, and secondary analysis of randomized controlled studies that reported the incidence of PPH and the related risk factors in vaginal delivery were eligible through screening of 2343 articles. The incidence, associated standard error, adjusted odds ratios, relative risks and associated 95% confidence intervals were combined in the meta-analysis.
RESULTS
Thirty-six articles were included in the descriptive review. The incidence of PPH (blood loss ≥500 mL and blood loss ≥1000 mL) was 17% and 6%, respectively. Forty-one identified risk factors were divided into five categories under two criteria: history and demographics; maternal comorbidity; pregnancy-related factors; labor-related factors; delivery-related factors.
CONCLUSIONS
With the increasing incidence of PPH globally, obstetric health care providers need to improve their awareness of these multi-factorial risks to optimize obstetric care and reduce maternal morbidity. This systematic review and meta-analysis have raised important questions about the nature of vaginal delivery, such as the duration of prolonged labor, details on the use of oxytocin, and the presence of genital tract trauma. There should be highlighted by obstetric personnel on these factors during a patients' labor process.
Topics: Pregnancy; Female; Humans; Postpartum Hemorrhage; Oxytocics; Incidence; Cross-Sectional Studies; Delivery, Obstetric; Oxytocin; Risk Factors
PubMed: 37069822
DOI: 10.1111/jog.15654 -
Psychological Bulletin 2023While there has been an increase in studies investigating the relationship between endogenous oxytocin (OXT) concentrations and human social interactions over the past... (Meta-Analysis)
Meta-Analysis
While there has been an increase in studies investigating the relationship between endogenous oxytocin (OXT) concentrations and human social interactions over the past decades, these studies still seem far from converging, both in methodological terms and in terms of their results. This systematic review and meta-analysis were aimed at a comprehensive evaluation and synthesis of empirical evidence on the relationship between endogenous OXT concentrations and human social interactions by reviewing studies published between 1970 and July 2020 and addressing various related methodological and analytical limitations. Sixty-three studies were included in the qualitative synthesis, and results from 51 studies were pooled in a meta-analysis (n = 3,741 participants). The results indicated that social interaction did not lead to an expected hormonal response in causal designs, either in a pre-post design (g = 0.079) or when comparing experimental conditions with and without social interaction (g = 0.256). However, in correlational designs, the overall mean effect size (ES) of the correlations between indicators of social interaction and OXT concentrations was significantly different from zero (z = 0.137). In both designs, subgroup analyses revealed that studies involving either parent-child interactions, or the utilization of the enzyme-linked immunosorbent assay method for OXT analysis, or unrestricted eating, drinking, or exercise before biofluid collection showed significantly higher than zero mean ESs. This review exposes the observed inconsistencies and suggests that standardized, replicable, and reliable approaches to assessing social interaction and measuring OXT concentrations need to be developed to study neurochemical mechanisms of sociality in humans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Oxytocin; Humans; Social Interaction
PubMed: 38713749
DOI: 10.1037/bul0000402 -
Contraception Nov 2023This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion.
STUDY DESIGN
We searched PubMed on December 18, 2022, to find published articles describing the outcomes of treatment with misoprostol-only for abortion of viable intrauterine pregnancy at ≤91 days of gestation. From each article identified, two authors independently abstracted relevant data about each group of patients treated with a distinct regimen. We assessed the risk of bias using four defined indicators. We estimated the proportion of patients with treatment failure using meta-analytic methods as well as the proportion hospitalized or transfused after treatment. We examined associations between treatment failure and selected characteristics of the groups.
RESULTS
We identified 49 papers with 66 groups that collectively included 16,354 evaluable patients, of whom 2960 (meta-analytic estimate 15%, 95% CI 12%, 19%) had treatment failures. Of 9228 patients assessed for ongoing pregnancy after treatment, 521 (meta-analytic estimate 6%, 95% CI 5%, 8%) had that condition. Failure risk was significantly associated with misoprostol dose, the total allowed number of doses, the maximum duration of dosing, and certain indicators of risk of bias. Among 11,007 patients allowed to take at least three misoprostol doses, the first consisting of misoprostol 800 mcg administered vaginally, sublingually, or buccally, the meta-analytic estimate of the failure risk was 11% (95% CI 8%, 14%). At most, 0.2% of 15,679 evaluable patients were hospitalized or received transfusions.
CONCLUSIONS
Although some studies in this updated review were adjudicated to have a high risk of bias, the results continue to support the key conclusion of our 2019 analysis: misoprostol-only is effective and safe for the termination of first-trimester intrauterine pregnancy.
IMPLICATIONS
Misoprostol-only is a safe and effective option for medication abortion in the first trimester if mifepristone is unavailable or inaccessible.
Topics: Pregnancy; Female; Humans; Misoprostol; Abortifacient Agents; Pregnancy Trimester, First; Mifepristone; Abortion, Induced; Abortifacient Agents, Nonsteroidal
PubMed: 37517447
DOI: 10.1016/j.contraception.2023.110132 -
Psychoneuroendocrinology Jul 2021This is a systematic review about the association between empathic behavior and oxytocin (OXT). Searches were conducted in the electronic databases PubMed, Web of... (Review)
Review
This is a systematic review about the association between empathic behavior and oxytocin (OXT). Searches were conducted in the electronic databases PubMed, Web of Science, PsycINFO, SciELO, and LILACS using the search terms "oxytocin", "empathy", and "empathic". Forty-four studies were reviewed. Scarce findings point to a lack of association between baseline endogenous OXT levels and empathy traits, and for a trend towards a direct relationship between oxytocinergic reactivity and empathic functioning. The results showed that variations in empathy were related to polymorphisms in the OXT receptor gene, especially in rs53576, and that this relationship seems to mediated by individual, ethnic, and cultural characteristics. Most studies on the exogenous administration of OXT tested a single dose (24 IU) with positive effects mainly on the affective domain of empathy. At the neural level, findings were inconsistent. Taken together, the results of the studies reviewed support the existence of a relationship between OXT and empathy that is complex and multifaceted. Robust evidence is still needed to elucidate existing links. Future investigations could benefit from methodological improvements aimed at increasing the reproducibility and applicability of findings, as well as the systematic assessment of the effects of exogenous OXT considering dose and frequency of administration, genotyping, and hormonal availability at the peripheral and central levels. This should lead to significant progress in the understanding of the therapeutic possibilities of OXT in the domain of empathic behavior.
Topics: Empathy; Humans; Oxytocin
PubMed: 34023733
DOI: 10.1016/j.psyneuen.2021.105268 -
European Journal of Obstetrics,... Aug 2023A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods... (Review)
Review
Efficacy of pharmacological and mechanical cervical priming methods for induction of labour and their applicability for outpatient management: A systematic review of randomised controlled trials.
BACKGROUND
A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods are available to achieve cervical ripening prior to induction of labour (IOL). In this systematic review, we will report the literature to date, and investigate the efficacy and safety of using the Foley catheter balloon or prostaglandins for cervical ripening, comparing both methods with each other, and discuss the implications of these findings for midwifery led units.
METHODS
English peer-reviewed journals were systematically searched in the databases PubMed, MEDLINE, EMCARE, EMBASE and CINAHL, for studies investigating cervical ripening using the FC or PGs. Additional randomised controlled trials (RCTs) and non-RCTs were identified by a manual search. Search terms included: cervix dilatation effacement, cervix ripening, outpatient, ambulatory care, obstetric patients, pharmacological preparations, and Foley catheter. Only RCTs of FC versus PG or either intervention versus placebo or intervention in the in-patient Vs. outpatient setting were included. 15 RCTs were included.
RESULTS
The results of this review show that both FC and PG analogues are equally effective cervical ripening agents. When compared to FC, PGs lead to a reduced requirement for oxytocin augmentation and a shorter intervention to delivery interval. However, PG use is also associated with an increased risk of hyperstimulation, cardiotocographic monitoring abnormalities and negative neonatal outcomes.
CONCLUSIONS
FC cervical ripening is an effective method of outpatient cervical priming, which is safe, acceptable, and cost-effective and thus has a potential role in both resource-rich and resource-poor countries. With appropriate dosing, some PG analogues also appear to offer similar outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Dinoprostone; Outpatients; Cervix Uteri; Oxytocics; Labor, Induced; Prostaglandins; Abortifacient Agents, Nonsteroidal; Cervical Ripening
PubMed: 37300982
DOI: 10.1016/j.ejogrb.2023.05.037 -
Neuroscience and Biobehavioral Reviews Nov 2022The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their... (Review)
Review
The last couple of decades have witnessed a rapid accumulation of studies implicating oxytocin (OT) in several neurobiological underpinnings of human behaviour and their impairment in psychiatric illness. Specifically, a neuroimaging genetics approach is helping elucidate the impact of variations in OT pathway genes on the human brain. In this review, we provide the first systematic account and discussion of all previous findings arising from human neuroimaging (epi)genetic studies of OT-related genes. To improve our mechanistic interpretation of such findings, we used data from the Genotype-Tissue Expression project to explore the functional impact the genetic variations may have on the human transcriptome. As a result, we provide an up-to-date summary of brain circuits found to be impacted by OT-relevant (epi)genetic variability, map brain pathways linking OT genes to disease, and highlight several (epi)genetic factors that modulate brain responses to intranasal OT. Finally, we provide some suggestions we believe might improve future research in the field.
Topics: Humans; Administration, Intranasal; Brain; Neuroimaging; Oxytocin; Transcriptome
PubMed: 36228928
DOI: 10.1016/j.neubiorev.2022.104912 -
Journal of Neuroendocrinology Jul 2023Pregnancy is associated with prominent structural changes in brain areas involved in Theory of Mind (ToM), pointing to the possibility of modifications in ToM-related... (Review)
Review
Pregnancy is associated with prominent structural changes in brain areas involved in Theory of Mind (ToM), pointing to the possibility of modifications in ToM-related behavior and brain responses in parents. We performed a systematic review screening for studies that examined ToM in pregnant and/or early postpartum parents. The evaluation of the included 12 studies allowed us to construct an overview of ToM changes during pregnancy and postpartum as well as other associated factors, such as oxytocin, mental health, and parental behavior. Four studies examined ToM changes by comparing pregnant/early postpartum parents with nulliparous parents or prepregnancy measures. They reported no differences between groups measured with a self-report questionnaire but found group differences using an experimental approach. The results from the summarized studies further suggest a mediatory role of oxytocin between ToM and certain parental behavior. In addition, while no link between postpartum depression and ToM was observed, findings do point to an association between depressive and remote maternal behavior and anxious attachment style and ToM abilities in pregnant participants. Research findings regarding the interaction of ToM with both parity and maternal attachment to the fetus are ambivalent. Overall, research on this topic is scarce, limiting our ability to draw firm conclusions and stressing the need for further research on this topic. This review presents an overview of research findings on ToM and associated factors in pregnancy and the postpartum period and discusses directions for future research.
Topics: Pregnancy; Female; Humans; Oxytocin; Theory of Mind; Postpartum Period; Maternal Behavior; Depression, Postpartum
PubMed: 37094082
DOI: 10.1111/jne.13266 -
The Cochrane Database of Systematic... May 2023Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breech presentation at term can cause complications during birth and increase the chance of caesarean section. Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) at the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of changing breech presentation to cephalic presentation. This is an update of a review first published in 2005 and last published in 2012.
OBJECTIVES
To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (which includes trials from CENTRAL, MEDLINE, Embase, CINAHL, and conference proceedings), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) (4 November 2021). We also searched MEDLINE, CINAHL, AMED, Embase and MIDIRS (inception to 3 November 2021), and the reference lists of retrieved studies.
SELECTION CRITERIA
The inclusion criteria were published and unpublished randomised or quasi-randomised controlled trials comparing moxibustion either alone or in combination with other techniques (e.g. acupuncture or postural techniques) with a control group (no moxibustion) or other methods (e.g. acupuncture, postural techniques) in women with a singleton breech presentation.
DATA COLLECTION AND ANALYSIS
Two review authors independently determined trial eligibility, assessed trial quality, and extracted data. Outcome measures were baby's presentation at birth, need for ECV, mode of birth, perinatal morbidity and mortality, maternal complications and maternal satisfaction, and adverse events. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: This updated review includes 13 studies (2181 women), of which six trials are new. Most studies used adequate methods for random sequence generation and allocation concealment. Blinding of participants and personnel is challenging with a manual therapy intervention; however, the use of objective outcomes meant that the lack of blinding was unlikely to affect the results. Most studies reported little or no loss to follow-up, and few trial protocols were available. One study that was terminated early was judged as high risk for other sources of bias. Meta-analysis showed that compared to usual care alone, the combination of moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth (7 trials, 1152 women; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.78 to 0.99, I = 38%; moderate-certainty evidence), but the evidence is very uncertain about the effect of moxibustion plus usual care on the need for ECV (4 trials, 692 women; RR 0.62, 95% CI 0.32 to 1.21, I = 78%; low-certainty evidence) because the CIs included both appreciable benefit and moderate harm. Adding moxibustion to usual care probably has little to no effect on the chance of caesarean section (6 trials, 1030 women; RR 0.94, 95% CI 0.83 to 1.05, I = 0%; moderate-certainty evidence). The evidence is very uncertain about the effect of moxibustion plus usual care on the the chance of premature rupture of membranes (3 trials, 402 women; RR 1.31, 95% CI 0.17 to 10.21, I = 59%; low-certainty evidence) because there were very few data. Moxibustion plus usual care probably reduces the use of oxytocin (1 trial, 260 women; RR 0.28, 95% CI 0.13 to 0.60; moderate-certainty evidence). The evidence is very uncertain about the chance of cord blood pH less than 7.1 (1 trial, 212 women; RR 3.00, 95% CI 0.32 to 28.38; low-certainty evidence) because there were very few data. We are very uncertain whether the combination of moxibustion plus usual care increases the chance of adverse events (including nausea, unpleasant odour, abdominal pain and uterine contractions; intervention: 27/65, control: 0/57), as only one study presented data in a way that could be reanalysed (122 women; RR 48.33, 95% CI 3.01 to 774.86; very low-certainty evidence). When moxibustion plus usual care was compared with sham moxibustion plus usual care, we found that moxibustion probably reduces the chance of non-cephalic presentation at birth (1 trial, 272 women; RR 0.74, 95% CI 0.58 to 0.95; moderate-certainty evidence) and probably results in little to no effect on the rate of caesarean section (1 trial, 272 women; RR 0.84, 95% CI 0.68 to 1.04; moderate-certainty evidence). No study that compared moxibustion plus usual care with sham moxibustion plus usual care reported on the clinically important outcomes of need for ECV, premature rupture of membranes, use of oxytocin, and cord blood pH less than 7.1, and one trial that reported adverse events reported data for the whole sample. When moxibustion was combined with acupuncture and usual care, there was very little evidence about the effect of the combination on non-cephalic presentation at birth (1 trial, 226 women; RR 0.73, 95% CI 0.57 to 0.94) and at the end of treatment (2 trials, 254 women; RR 0.73, 95% CI 0.57 to 0.93), and on the need for ECV (1 trial, 14 women; RR 0.45, 95% CI 0.07 to 3.01). There was very little evidence about whether moxibustion plus acupuncture plus usual care reduced the chance of caesarean section (2 trials, 240 women; RR 0.80, 95% CI 0.65 to 0.99) or pre-eclampsia (1 trial, 14 women; RR 5.00, 95% CI 0.24 to 104.15). The certainty of the evidence for this comparison was not assessed.
AUTHORS' CONCLUSIONS
We found moderate-certainty evidence that moxibustion plus usual care probably reduces the chance of non-cephalic presentation at birth, but uncertain evidence about the need for ECV. Moderate-certainty evidence from one study shows that moxibustion plus usual care probably reduces the use of oxytocin before or during labour. However, moxibustion plus usual care probably results in little to no difference in the rate of caesarean section, and we are uncertain about its effects on the chance of premature rupture of membranes and cord blood pH less than 7.1. Adverse events were inadequately reported in most trials.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Breech Presentation; Cesarean Section; Moxibustion; Oxytocin; Parturition; Premature Birth
PubMed: 37158339
DOI: 10.1002/14651858.CD003928.pub4 -
The Cochrane Database of Systematic... May 2022Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently,... (Review)
Review
BACKGROUND
Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes. This is an update of a review last published in 2011.
OBJECTIVES
To compare the effectiveness and side effects of different medical methods for first trimester abortion.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
AUTHORS' CONCLUSIONS
Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Spontaneous; Diarrhea; Drug Therapy, Combination; Estradiol; Female; Humans; Letrozole; Methotrexate; Mifepristone; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, First; Prostaglandins; Tamoxifen
PubMed: 35608608
DOI: 10.1002/14651858.CD002855.pub5 -
The Cochrane Database of Systematic... Sep 2021Embryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative... (Review)
Review
BACKGROUND
Embryo transfer (ET) is a crucial step of in vitro fertilisation (IVF) treatment, and involves placing the embryo(s) in the woman's uterus. There is a negative association between endometrial wave-like activity (contractile activities) at the time of ET and clinical pregnancy, but no specific treatment is currently used in clinical practice to counteract their effects. Oxytocin is a hormone produced by the hypothalamus and released by the posterior pituitary. Its main role involves generating uterine contractions during and after childbirth. Atosiban is the best known oxytocin antagonist (and is also a vasopressin antagonist), and it is commonly used to delay premature labour by halting uterine contractions. Other oxytocin antagonists include barusiban, nolasiban, epelsiban, and retosiban. Administration of oxytocin antagonists around the time of ET has been proposed as a means to reduce uterine contractions that may interfere with embryo implantation. The intervention involves administering the medication before, during, or after the ET (or a combination).
OBJECTIVES
To evaluate the effectiveness and safety of oxytocin antagonists around the time of ET in women undergoing assisted reproduction.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in March 2021; and checked references and contacted study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of the use of oxytocin antagonists for women undergoing ET, compared with the non-use of this intervention, the use of placebo, or the use of another similar drug.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth and miscarriage; secondary outcomes were clinical pregnancy and other adverse events.
MAIN RESULTS
We included nine studies (including one comprising three separate trials, 3733 women analysed in total) investigating the role of three different oxytocin antagonists administered intravenously (atosiban), subcutaneously (barusiban), or orally (nolasiban). We found very low- to high-certainty evidence: the main limitations were serious risk of bias due to poor reporting of study methods, and serious or very serious imprecision. Intravenous atosiban versus normal saline or no intervention We are uncertain of the effect of intravenous atosiban on live birth rate (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.88 to 1.24; 1 RCT, N = 800; low-certainty evidence). In a clinic with a live birth rate of 38% per cycle, the use of intravenous atosiban would be associated with a live birth rate ranging from 33.4% to 47.1%. We are uncertain whether intravenous atosiban influences miscarriage rate (RR 1.08, 95% CI 0.75 to 1.56; 5 RCTs, N = 1424; I² = 0%; very low-certainty evidence). In a clinic with a miscarriage rate of 7.2% per cycle, the use of intravenous atosiban would be associated with a miscarriage rate ranging from 5.4% to 11.2%. Intravenous atosiban may increase clinical pregnancy rate (RR 1.50, 95% CI 1.18 to 1.89; 7 RCTs, N = 1646; I² = 69%; low-certainty evidence), and we are uncertain whether multiple or ectopic pregnancy and other complication rates were influenced by the use of intravenous atosiban (very low-certainty evidence). Subcutaneous barusiban versus placebo One study investigated barusiban, but did not report on live birth or miscarriage. We are uncertain whether subcutaneous barusiban influences clinical pregnancy rate (RR 0.96, 95% CI 0.69 to 1.35; 1 RCT, N = 255; very low-certainty evidence). Trialists reported more mild to moderate injection site reactions with barusiban than with placebo, but there was no difference in severe reactions. They reported no serious drug reactions; and comparable neonatal outcome between groups. Oral nolasiban versus placebo Nolasiban does not increase live birth rate (RR 1.13, 95% CI 0.99 to 1.28; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence). In a clinic with a live birth rate of 33% per cycle, the use of oral nolasiban would be associated with a live birth rate ranging from 32.7% to 42.2%. We are uncertain of the effect of oral nolasiban on miscarriage rate (RR 1.45, 95% CI 0.73 to 2.88; 3 RCTs, N = 1832; I² = 0%; low-certainty evidence). In a clinic with a miscarriage rate of 1.5% per cycle, the use of oral nolasiban would be associated with a miscarriage rate ranging from 1.1% to 4.3%. Oral nolasiban improves clinical pregnancy rate (RR 1.15, 95% CI 1.02 to 1.30; 3 RCTs, N = 1832; I² = 0%; high-certainty evidence), and probably does not increase multiple or ectopic pregnancy, or other complication rates (moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We are uncertain whether intravenous atosiban improves pregnancy outcomes for women undergoing assisted reproductive technology. This conclusion is based on currently available data from seven RCTs, which provided very low- to low-certainty evidence across studies. We could draw no clear conclusions about subcutaneous barusiban, based on limited data from one RCT. Further large well-designed RCTs reporting on live births and adverse clinical outcomes are still required to clarify the exact role of atosiban and barusiban before ET. Oral nolasiban appears to improve clinical pregnancy rate but not live birth rate, with an uncertain effect on miscarriage and adverse events. This conclusion is based on a phased study comprising three trials that provided low- to high-certainty evidence. Further large, well-designed RCTs, reporting on live births and adverse clinical outcomes, should focus on identifying the subgroups of women who are likely to benefit from this intervention.
Topics: Abortion, Spontaneous; Embryo Transfer; Female; Humans; Infant, Newborn; Live Birth; Oxytocin; Pregnancy; Pregnancy Rate
PubMed: 34467530
DOI: 10.1002/14651858.CD012375.pub2