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BMJ Paediatrics Open May 2024There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.
BACKGROUND
There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21 July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
INTERVENTIONS
Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.
MAIN OUTCOME MEASURES
Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).
RESULTS
15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.
CONCLUSIONS
Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
Topics: Humans; Infant, Newborn; Cardiotonic Agents; Vasoconstrictor Agents; Infant, Premature; Network Meta-Analysis; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Dobutamine
PubMed: 38769048
DOI: 10.1136/bmjpo-2024-002500 -
Frontiers in Endocrinology 2024Despite the developments of fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Despite the developments of fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure.
METHODS
We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I index was analyzed.
RESULTS
We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I = 24%], but not on LBR. In addition, >150μg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I = 22%], while ≤150μg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection.
CONCLUSION
G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size. https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.
Topics: Humans; Female; Granulocyte Colony-Stimulating Factor; Embryo Implantation; Pregnancy; Pregnancy Rate; Fertilization in Vitro; Embryo Transfer; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 38694938
DOI: 10.3389/fendo.2024.1370114 -
BMC Pregnancy and Childbirth Apr 2024Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling laser-assisted hatching (D-LAH) and thinning laser-assisted hatching (T-LAH). Presently, both methods have limitations, and their comparative efficacy for embryo implantation and clinical pregnancy remains uncertain.
AIM
Evaluate the impact of D-LAH and T-LAH on clinical pregnancy rates within assisted reproductive technology (ART).
METHODS
We systematically searched electronic databases including PubMed, Web of Science, and Cochrane Library until July 20, 2022. This study encompassed observational studies and randomized controlled trials (RCTs). A 95% confidence interval (CI) was utilized for assessing the risk ratio (RR) of pregnancy outcomes. The level of heterogeneity was measured using I statistics, considering a value exceeding 50% as indicative of substantial heterogeneity.
RESULTS
The meta-analysis scrutinized 9 studies involving 2405 clinical pregnancies from D-LAH and 2239 from T-LAH. Findings suggested no considerable variation in the clinical pregnancy rates between the two techniques (RR = 0.93, 95% CI: 0.79-1.10, I = 71%, P = 0.41). Subgroup analyses also revealed no substantial differences. However, D-LAH exhibited a notably higher occurrence of singleton pregnancies compared to T-LAH (RR = 2.28, 95% CI: 1.08-4.82, I = 89%, P = 0.03). There were no noteworthy distinctions observed in other secondary outcomes encompassing implantation rate, multiple pregnancies, ongoing pregnancy, miscarriage, premature birth, and live birth.
CONCLUSION
Both the primary findings and subgroup analyses showed no marked variance in clinical pregnancy rates between D-LAH and T-LAH. Therefore, patients with varying conditions should select their preferred LAH technique after assessing their individual situation. However, due to the restricted number of studies involved, accurately gauging the influence of these laser techniques on clinical outcomes is challenging, necessitating further RCTs and high-quality studies to enhance the success rate of ART.
TRIAL REGISTRATION
PROSPERO: CRD42022347066.
Topics: Humans; Pregnancy; Female; Reproductive Techniques, Assisted; Pregnancy Rate; Zona Pellucida; Lasers; Embryo Implantation; Randomized Controlled Trials as Topic; Pregnancy Outcome; Embryo Transfer
PubMed: 38649878
DOI: 10.1186/s12884-024-06380-8 -
Frontiers in Endocrinology 2024The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the... (Review)
Review
Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis.
The leading indicator for successful outcomes in fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
Topics: Humans; Male; Female; Cyclooxygenase 2; Cumulus Cells; Semen; Oocytes; Gene Expression; Intercellular Signaling Peptides and Proteins; Hyaluronan Synthases
PubMed: 38524634
DOI: 10.3389/fendo.2024.1274376 -
Fundamental & Clinical Pharmacology Feb 2024While ursodeoxycholic acid is used in treating parenteral nutrition-associated cholestasis (PNAC) in neonates, its role in prevention is unclear. (Review)
Review
BACKGROUND
While ursodeoxycholic acid is used in treating parenteral nutrition-associated cholestasis (PNAC) in neonates, its role in prevention is unclear.
OBJECTIVES
In this systematic review and meta-analysis, we attempted to determine the role of ursodeoxycholic acid in preventing PNAC in neonates.
METHODS
PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases were searched on September 16, 2023, for interventional studies comparing ursodeoxycholic acid with placebo.
RESULTS
Of the 6180 unique records identified, five studies were eligible for inclusion (three randomised and two nonrandomised). Evidence from randomised trials showed that ursodeoxycholic acid prophylaxis did not reduce cholestasis, mortality, sepsis, and necrotising enterocolitis. Ursodeoxycholic acid prophylaxis reduced feed intolerance (RR 0.23 (0.09, 0.64); 1 RCT, 102 neonates), peak conjugated bilirubin levels (MD -0.13 (-0.22, -0.04) mg/dL; 1 RCT, 102 neonates), and time to full enteral feeds (MD -2.7 (-5.09, -0.31) days; 2 RCTs, 76 neonates). There was no decrease in hospital stay and parenteral nutrition duration. Data from nonrandomised studies did not show benefit in any of the outcomes. The certainty of the evidence was low to very low.
CONCLUSION
Because of the very low-quality evidence and lack of evidence on critical outcomes, definitive conclusions could not be made on using ursodeoxycholic acid to prevent parenteral nutrition-associated cholestasis in neonates.
PubMed: 38342497
DOI: 10.1111/fcp.12993 -
International Journal of Molecular... Jan 2024During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a... (Review)
Review
During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction.
Topics: Female; Humans; Male; Pregnancy; Calcium; Oocytes; Phosphoinositide Phospholipase C; Semen; Spermatozoa; Type C Phospholipases
PubMed: 38279344
DOI: 10.3390/ijms25021344 -
Journal of Assisted Reproduction and... Feb 2024Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to... (Review)
Review
PURPOSE
Although significant improvements in assisted reproductive technology (ART) outcomes have been accomplished, a critical question remains: which embryo is most likely to result in a pregnancy? Embryo selection is currently based on morphological and genetic criteria; however, these criteria do not fully predict good-quality embryos and additional objective criteria are needed. The cumulus cells are critical for oocyte and embryo development. This systematic review assessed biomarkers in cumulus-oocyte complexes and their association with successful IVF outcomes.
METHODS
A comprehensive search was conducted using PubMed, Embase, Scopus, and Web of Science from inception until November 2022. Only English-language publications were included. Inclusion criteria consisted of papers that evaluated genetic biomarkers associated with the cumulus cells (CCs) in humans and the following three outcomes of interest: oocyte quality, embryo quality, and clinical outcomes, including fertilization, implantation, pregnancy, and live birth rates.
RESULTS
The search revealed 446 studies of which 42 met eligibility criteria. Nineteen studies correlated genetic and biochemical biomarkers in CCs with oocyte quality. A positive correlation was reported between oocyte quality and increased mRNA expression in CCs of genes encoding for calcium homeostasis (CAMK1D), glucose metabolism (PFKP), extracellular matrix (HAS2, VCAN), TGF-β family (GDF9, BMP15), and prostaglandin synthesis (PTGS2). Nineteen studies correlated genetic and biochemical biomarkers in CCs with embryo quality. A positive correlation was reported between embryo quality and increased mRNA expression in CCs of genes encoding for extracellular matrix (HAS2), prostaglandin synthesis (PTGS2), steroidogenesis (GREM1), and decreased expression of gene encoding for hormone receptor (AMHR2). Twenty-two studies assessed genetic and biochemical biomarkers in CCs with clinical outcomes. Increased expression of genes encoding for extracellular matrix (VCAN), and TGF-β family (GDF9, BMP15) were positively correlated with pregnancy rate.
CONCLUSION
Genetic biomarkers from cumulus cells were associated with oocyte quality (CAMK1D, PFKP, HAS2, VCAN, GDF-9, BMP-15, PTGS2), embryo quality (GREM1, PTGS2, HAS2), and pregnancy rate (GDF9, BMP15, VCAN). These results might help guide future studies directed at tests of cumulus cells to devise objective criteria to predict IVF outcomes.
Topics: Pregnancy; Female; Humans; Cumulus Cells; Cyclooxygenase 2; Oocytes; Fertilization in Vitro; Reproductive Techniques, Assisted; Genetic Markers; RNA, Messenger; Transforming Growth Factor beta; Prostaglandins
PubMed: 37947940
DOI: 10.1007/s10815-023-02984-9 -
Reproductive Biomedicine Online Jan 2024The growing utilization of assisted reproductive technology (ART) by the LGBTQ+ community, especially among lesbian couples, challenges societal norms and promotes... (Review)
Review
The growing utilization of assisted reproductive technology (ART) by the LGBTQ+ community, especially among lesbian couples, challenges societal norms and promotes inclusivity. The reception of oocytes from partner (ROPA) technique enables both female partners to have a biological connection to their child. A systematic review was conducted of the literature on ROPA IVF to provide the latest data and a SWOT analysis was subsequently performed to understand the strengths, weaknesses, opportunities and threats associated with ROPA IVF. Publications from 2000 to 2023 with relevant keywords were reviewed and 16 records were included. Five studies provided clinical information on couples who used ROPA IVF. ROPA IVF provides a unique opportunity for a biological connection between the child and both female partners and addresses concerns related to oocyte donation and anonymity. Weaknesses include limited cost-effectiveness data and unresolved practical implications. Opportunities lie in involving both partners in parenthood, advancing ART success rates and mitigating risks. Threats encompass increased pregnancy complications, ethical concerns, insufficient safety data, legal or cultural barriers, and emotional stress. In conclusion, ROPA IVF offers a promising solution for lesbian couples seeking to create a family in which both partners want to establish a biological connection with their child.
Topics: Pregnancy; Child; Female; Humans; Fertilization in Vitro; Reproductive Techniques, Assisted; Homosexuality, Female; Sexual and Gender Minorities; Oocytes; Pregnancy Rate
PubMed: 37925228
DOI: 10.1016/j.rbmo.2023.103411 -
Reproductive Biomedicine Online Dec 2023The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.
Topics: Humans; Female; Fertility Preservation; Oocyte Retrieval; Cryopreservation; Neoplasms; Oocytes; Gonadotropins; Ovulation Induction; Retrospective Studies
PubMed: 37857156
DOI: 10.1016/j.rbmo.2023.103337 -
Journal of Assisted Reproduction and... Oct 2023The biggest cell in the human body, the oocyte, encloses almost the complete machinery to start life. Despite all the research performed to date, defining oocyte quality... (Review)
Review
The biggest cell in the human body, the oocyte, encloses almost the complete machinery to start life. Despite all the research performed to date, defining oocyte quality is still a major goal of reproductive science. It is the consensus that mature oocytes are transcriptionally silent although, during their growth, the cell goes through stages of active transcription and translation, which will endow the oocyte with the competence to undergo nuclear maturation, and the oocyte and embryo to initiate timely translation before the embryonic genome is fully activated (cytoplasmic maturation). A systematic search was conducted across three electronic databases and the literature was critically appraised using the KMET score system. The aim was to identify quantitative differences in transcriptome of human oocytes that may link to patient demographics that could affect oocyte competence. Data was analysed following the principles of thematic analysis. Differences in the transcriptome were identified with respect to age or pathological conditions and affected chromosome mis segregation, perturbations of the nuclear envelope, premature maturation, and alterations in metabolic pathways-amongst others-in human oocytes.
Topics: Humans; Oocytes; Oogenesis; Transcriptome; Cytoplasm; RNA, Messenger
PubMed: 37558907
DOI: 10.1007/s10815-023-02906-9