Congenital anomaly and perinatal outcome following blastocyst- vs cleavage-stage embryo transfer: systematic review and network meta-analysis.

OBJECTIVES: To compare the reported rate of any congenital anomaly and perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer using a pairwise meta-analysis and to evaluate the same outcomes following fresh-blastocyst, frozen-blastocyst, fresh-cleavage or frozen-cleavage embryo transfer using a network meta-analysis. METHODS: A literature search was performed in PubMed, Scopus and CENTRAL and registers for ongoing studies, from inception to February 2022, for randomized controlled trials (RCTs) with any sample size and observational studies including at least 100 live births per group, comparing the rates of any congenital anomaly and perinatal outcome of pregnancy following fresh/frozen embryo transfer at cleavage (day 2-3) vs blastocyst (day 5-7) stage. Risk ratios (RRs) along with their 95% CIs were pooled via a random-effects model meta-analysis. Within a frequentist network meta-analysis framework, outcomes of all four treatment modalities (i.e. fresh-blastocyst, fresh-cleavage, frozen-blastocyst, frozen-cleavage) were compared further. Any congenital anomaly constituted the primary outcome, whereas preterm delivery (delivery < 37 weeks), low birth weight (LBW; < 2500 g), gender of the neonate (male), perinatal death and healthy neonate (defined as liveborn neonate, delivered at term, weighing ≥ 2500 g, surviving for at least 28 days postbirth and without any congenital anomaly) were considered as secondary outcomes. Subgroup analyses by plurality (liveborn singleton vs multiple pregnancy) were conducted in the pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for non-randomized studies. Certainty of evidence was assessed using GRADE. RESULTS: Through the literature search, 550 studies were retrieved and 33 were included in the systematic review. We found no significant difference in the risk for any congenital anomaly between blastocyst- and cleavage-stage transfer (RR, 0.80 (95% CI, 0.63-1.03); 10 studies; n = 192 442; I2 = 85.5%). An increased probability of a male neonate was observed following blastocyst- vs cleavage-stage transfer (RR, 1.07 (95% CI, 1.06-1.09); 18 studies; n = 227 530; I2 = 32.7%). No significant differences in other secondary outcomes or significant subgroup differences between liveborn singletons and multiple pregnancies were observed. The network meta-analysis showed a significantly lower risk for LBW following frozen-blastocyst vs fresh-blastocyst (RR, 0.76 (95% CI, 0.60-0.95)) or fresh-cleavage (RR, 0.74 (95% CI, 0.59-0.93)) transfer. Frozen-blastocyst transfer was associated with an increased risk for perinatal death compared with the fresh-cleavage method (RR, 2.06 (95% CI, 1.10-3.88)). The higher probability of a male neonate following blastocyst transfer remained evident in the network comparisons. All outcomes were assessed to be of very-low certainty of evidence. CONCLUSIONS: Current very-low certainty of evidence shows that there may be little-to-no difference in the risk for congenital anomaly or adverse perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer, although there was a slightly increased probability of a male neonate following blastocyst transfer. When considering cryopreservation, frozen-blastocyst transfer was associated with a reduction in the risk for LBW compared with both fresh-transfer modalities, and fresh-cleavage transfer may be associated with a reduction in the risk for perinatal death compared with frozen-blastocyst transfer. High-quality RCTs with separate data on fresh and frozen cycles and consistent reporting of culture conditions and freezing methods are mandatory. Individual participant data meta-analyses are required to address the substantial inconsistency resulting from current aggregate data approaches. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Could FiLaC™ be effective in the treatment of anal fistulas? A systematic review of observational studies and proportional meta-analysis.

AIM: Fistula Laser Closure (FiLaC™) is a novel sphincter-preserving technique that is based on new technologies and shows promising results in repairing anal fistulas whilst maintaining external sphincter function. The aim of the present meta-analysis is to present the efficacy and the safety of FiLaC™ in the management of anal fistula disease. METHOD: The present proportional meta-analysis was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, clinicaltrials.gov, Embase, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases from inception until November 2019. RESULTS: Overall, eight studies were included that recruited 476 patients. The pooled success rate of the technique was 63% (95% CI 50%-75%). The pooled complication rate was 8% (95% CI 1%-18%). Sixty-six per cent of patients had a transsphincteric fistula and 60% had undergone a previous surgical intervention, mainly the insertion of a seton (54%). The majority had a cryptoglandular fistula. Operation time and follow-up period were described for each study. CONCLUSION: FiLaC™ seems to be an efficient therapeutic option for perianal fistula disease with an adequate level of safety that preserves quality of life. Nevertheless, randomized trials need to be designed to compare FiLaC™ with other procedures for the management of anal fistulas such as ligation of intersphincteric fistula tract, anal advancement flaps, fibrin glue, collagen paste, autologous adipose tissue, fistula plug and video-assisted anal fistula treatment.

Acute kidney injury following the concurrent administration of antipseudomonal ß-lactams and vancomycin: a network meta-analysis.

BACKGROUND: Acute kidney injury is a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. OBJECTIVES: This meta-analysis aims to comparatively assess the nephrotoxicity of antipseudomonal ß-lactams when combined with vancomycin. DATA SOURCES: Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. STUDY ELIGIBILITY CRITERIA: Studies evaluating acute kidney injury risk following the concurrent use of antipseudomonal ß-lactams and vancomycin were selected. PARTICIPANTS: Adult and paediatric patients treated in hospital or intensive care unit. INTERVENTIONS: Administration of vancomycin combined with any antipseudomonal ß-lactam. METHODS: Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. RESULTS: Forty-seven cohort studies were included, with a total of 56 984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates than vancomycin monotherapy (odds ratio (OR) 2.05, 95% confidence intervals (CI) 1.17-3.46) and its concurrent use with meropenem (OR 1.84, 95% CI 1.02-3.10) or cefepime (OR 1.80, 95% CI 1.13-2.77). In paediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR 4.18, 95% CI 1.01-17.29) or vancomycin plus cefepime OR 3.71, 95% CI 1.08-11.24). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. CONCLUSIONS: The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.

Safety of non-steroidal anti-inflammatory drugs in postpartum period in women with hypertensive disorders of pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure when administered for postpartum analgesia in women with hypertensive disorders of pregnancy. METHODS: MEDLINE, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were searched systematically from inception to 5 December 2019 for studies evaluating the safety of postpartum NSAIDs in women with any gestational hypertensive disorder. Randomized controlled trials (RCTs) and cohort studies were eligible for inclusion. Case-control studies, case series and case reports were excluded. The primary outcomes of interest were the incidence of severe hypertension and systolic, diastolic and mean arterial blood pressure. Pooled estimates were obtained by fitting a random-effects statistical model. The quality of evidence was assessed according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: Ten studies were included, comprising five RCTs and five retrospective cohort studies and involving a total of 1647 women. All studies were evaluated qualitatively and eight of them were included in the quantitative meta-analysis. Administration of NSAIDs was not associated with a significantly higher risk of severe postpartum hypertension (odds ratio, 1.52 (95% CI, 0.77-3.01)). Similarly, no significant differences were found in postpartum systolic blood pressure (mean difference (MD), -3.03 mmHg (95% CI, -6.21 to 0.15 mmHg)) and mean arterial pressure (MD, -0.38 mmHg (95% CI, -1.88 to 1.11 mmHg)) between women who received NSAIDs and those who did not, whereas postpartum diastolic blood pressure was marginally lower in women treated with NSAIDs (MD, -2.28 mmHg (95% CI, -4.44 to -0.13 mmHg)). The same effects were observed when studies with a large sample size, RCTs, women with severe pre-eclampsia and studies using ibuprofen as the study drug and acetaminophen as the control treatment were examined separately. The credibility of evidence was judged to be very low according to GRADE, owing to concerns about study limitations, inconsistency and imprecision. CONCLUSIONS: This meta-analysis suggests that postpartum administration of NSAIDs is not associated with elevated blood pressure in women with hypertensive disorders of pregnancy. However, the existing evidence is of very low quality, thus future large-scale RCTs are warranted to verify the safety of postpartum NSAIDs in this population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Serum levels of adipokines in gestational diabetes: a systematic review.

OBJECTIVE: To determine the difference of serum levels of 10 adipokines (apelin, chemerin, fatty acid-binding protein-4, fibroblast growth factor-21, monocyte chemoattractant protein-1, nesfatin-1, omentin-1, resistin, vaspin, and visfatin) among women with gestational diabetes and healthy pregnant controls. MATERIALS AND METHODS: Literature search was conducted using the Medline (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2018), Clinicaltrials.gov (2008-2018) and Google Scholar (2004-2018) databases, along with the reference list of the included studies. RESULTS: Ninety-one studies were included in the present review, with a total number of 11,074 pregnant women. A meta-analysis was not conducted due to the high inter-study heterogeneity. Current evidence suggests that fatty acid-binding protein-4 levels are significantly increased in pregnancies complicated with gestational diabetes, while no association of serum apelin and monocyte chemoattractant protein-1 with the disease can be supported. Data regarding the rest adipokines are conflicting, since the available studies did not unanimously indicate a significant change of their levels in gestational diabetes. CONCLUSIONS: The findings of the present systematic review suggest the promising role of fatty acid-binding protein-4 in the prediction of gestational diabetes, while inconsistent evidence exists regarding the rest novel adipokines. Future cohorts are needed to assess their predictive efficacy and fully elucidate their contribution in the disease.