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Inflammation & Allergy Drug Targets 2015Uranium is the heaviest metal known as nuclear fuel, and employed in the production of glass tinting compounds, ceramic glazes, gyroscope wheels, chemical catalysts and... (Review)
Review
Uranium is the heaviest metal known as nuclear fuel, and employed in the production of glass tinting compounds, ceramic glazes, gyroscope wheels, chemical catalysts and X-ray tube targets. Inhalation and ingestion are two of the most usual ways of exposure. Uranium may be released into drinking water through the mining leading to contamination. Uranium is able to damage the DNA by generation of free radicals and acting as a catalyst in the Fenton reactions causing oxidative stress. In fact, reproductive system contains high amount of polyunsaturated fatty acids, and therefore it is highly vulnerable to reactive oxygen species (ROS) and sensitive to uranium toxicity. Toxic effects of uranium are generally reported through different mechanisms of action including inflammation, degeneration of testis, vacuolization of Leydig cells, spermatocytes necrosis, and oocyte dysmorphism. The present article provides a comprehensive review of the recent findings mostly about the molecular and biochemical toxicity of uranium on the reproductive system.
Topics: Animals; DNA Damage; Female; Heavy Metal Poisoning; Humans; Leydig Cells; Male; Metals, Heavy; Oocytes; Oxidative Stress; Poisoning; Radiation Injuries; Reproduction; Risk Assessment; Risk Factors; Uranium
PubMed: 26728775
DOI: 10.2174/1871528114666160105112441 -
Human Reproduction (Oxford, England) Jun 2022Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Does the addition of hyaluronic acid (HA) to embryo transfer medium improve pregnancy outcomes in both autologous and oocyte donation IVF cycles?
SUMMARY ANSWER
The best available evidence indicates that the addition of HA to embryo transfer medium is clinically beneficial in cycles with autologous oocytes.
WHAT IS KNOWN ALREADY
There is a known clinical benefit of HA addition to embryo transfer media but it is not known if HA affects donor and autologous oocyte cycles differently.
STUDY DESIGN, SIZE, DURATION
A systematic review with meta-analysis was performed. The Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL via Cochrane Register of Studies Online (CRSO), MEDLINE, Embase and PsycINFO electronic databases (until 8 January 2020) were searched for randomized controlled trials (RCTs) examining the effect of HA in embryo transfer medium on pregnancy outcomes.
PARTICIPANTS/MATERIALS, SETTING, METHODS
RCTs with separate donor and autologous oocyte data that compared embryo transfer medium with functional HA concentrations (0.5 mg/ml) to those containing no or low HA concentrations (0.125 mg/ml) were included. Two review authors independently selected trials for inclusion, extracted data and assessed the included studies using the Cochrane risk of bias assessment tool. Pooled risk ratios and 95% CIs were calculated. A summary of findings table was generated using Grading of Recommendations, Assessment, Development and Evaluation criteria. Judgements about evidence quality were justified and incorporated into the reported results for each outcome.
MAIN RESULTS AND THE ROLE OF CHANCE
Fifteen studies, totalling 4686 participants, were analysed. In autologous oocyte cycles, live birth increased from 32% to 39% when embryo transfer media contained functional HA concentrations (risk ratio (RR) 1.22, 95% CI 1.11-1.34; nine studies, 3215 participants, I2 = 39%, moderate-quality evidence (number needed to treat (NNT) 14). HA-enriched media increased clinical pregnancy and multiple pregnancy rates by 5% and 8%, respectively (RR 1.11, 95% CI 1.04-1.18; 13 studies, 4014 participants, I2 = 0%, moderate-quality evidence, NNT 21) and (RR 1.49, 95% CI 1.27-1.76; 5 studies, 2400 participants, I2 = 21%, moderate-quality evidence, number needed to harm 13). Conversely, in donor oocyte cycles, HA addition showed little effect on live birth and clinical pregnancy (RR 1.12 95% CI 0.86-1.44; two studies, 317 participants, I2 = 50%, low-quality evidence) and (RR 1.06, 95% CI 0.97-1.28; three studies, 351 participants, I2 = 23%, low-quality evidence). There was insufficient available information on multiple pregnancy in donor oocyte cycles and on total adverse effects in both groups to draw conclusions.
LIMITATIONS, REASONS FOR CAUTION
There were limited studies with separate data on donor oocyte cycles and limited information on oocyte quality. Additionally, one-third of the included studies did not include the main outcome, live birth rate.
WIDER IMPLICATIONS OF THE FINDINGS
There is a moderate level of evidence to suggest that functional HA concentration in embryo transfer medium increases clinical pregnancy, live birth and multiple pregnancy rates in IVF cycles using autologous oocytes. This effect was not seen in donor oocyte cycles, indicating either intrinsic differences between donor and autologous oocytes or lack of statistical power. The combination of HA addition to transfer media in cycles using autologous oocytes and a single embryo transfer policy might yield the best combination, with higher clinical pregnancy and live birth rates without increasing the chance of multiple pregnancies.
STUDY FUNDING/COMPETING INTEREST(S)
No financial assistance was received. The authors have no competing interests.
REGISTRATION NUMBER
N/A.
Topics: Embryo Transfer; Female; Fertilization in Vitro; Humans; Hyaluronic Acid; Live Birth; Oocytes; Pregnancy; Pregnancy Rate
PubMed: 35595183
DOI: 10.1093/humrep/deac097 -
Reproductive Biology and Endocrinology... Sep 2021Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes...
BACKGROUND
Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.
METHODS
A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.
RESULTS
Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26-1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17-2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20-1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.
CONCLUSION
The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
Topics: Blastocyst; Cleavage Stage, Ovum; Embryo Transfer; Embryo, Mammalian; Female; Fertilization in Vitro; Humans; Infertility; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Treatment Outcome
PubMed: 34521412
DOI: 10.1186/s12958-021-00824-y -
BJOG : An International Journal of... May 2021Advances in vitrification techniques have enabled planned oocyte cryopreservation ('Planned OC'). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Advances in vitrification techniques have enabled planned oocyte cryopreservation ('Planned OC').
OBJECTIVES
To explore the cost-efficiency and utilisation of planned OC, as well as patients' perspectives on the process.
SEARCH STRATEGY
A systematic search in PubMed/MEDLINE, Embase, Cochrane Database and PsychINFO, for all relevant studies published between January 2007 and December 2019.
SELECTION CRITERIA
The protocol followed PRISMA guidelines in PECO format, and was registered with PROSPERO.
DATA COLLECTION AND ANALYSIS
Two independent reviewers evaluated all manuscripts for inclusion eligibility. Authors were contacted for missing data. Included studies were assessed for risk of bias and for heterogeneity. Weighted effects were measured and plotted.
MAIN RESULTS
The search yielded 12 545 records, of which 43 were included. Planned OC is cost-efficient at 35, assuming 60% utilisation; and at 37 assuming utilising donor sperm when necessary. At 38 it is cost-efficient to defer planned OC in favour of undergoing 2 IVF cycles. Currently, utilisation of banked-oocytes within 22-58 months, is up to 15%. Nine percent of warmed banked oocytes result in life births. Online resources and treating physicians are equally important sources of information regarding planned OC. Most patients think planned OC is ideal before age 35 and are not fully aware of what the process entails and tend to overestimate the success rates. The main barrier to wider endorsement of planned OC is being wary of potential health implications or of limited success.
CONCLUSION
Planned OC is an adequate method for preserving fertility. However, knowledge gaps result in under-utilisation leading to reduced cost-efficiency.
TWEETABLE ABSTRACT
Identifying facilitators and barriers for wider adoption of banking oocytes can enhance the cost-efficiency of this modality.
Topics: Cost-Benefit Analysis; Cryopreservation; Fertility Preservation; Humans; Oocytes; Procedures and Techniques Utilization; Vitrification
PubMed: 33021076
DOI: 10.1111/1471-0528.16555 -
Human Reproduction Update Apr 2021Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and... (Meta-Analysis)
Meta-Analysis
Is there an association between paternal age and aneuploidy? Evidence from young donor oocyte-derived embryos: a systematic review and individual patient data meta-analysis.
BACKGROUND
Delayed parenthood, by both women and men, has become more common in developed countries. The adverse effect of advanced maternal age on embryo aneuploidy and reproductive outcomes is well known. However, whether there is an association between paternal age (PA) and embryonic chromosomal aberrations remains controversial. Oocyte donation (OD) is often utilized to minimize maternal age effects on oocyte and embryo aneuploidy, thus providing an optimal model to assess the effect of PA. Several studies have revealed a higher than expected rate of aneuploidy in embryos derived from young oocyte donors, which warrants examination as to whether this may be attributed to advanced PA (APA).
OBJECTIVE AND RATIONALE
The objective of this systematic review and individual patient data (IPD) meta-analysis is to evaluate existing evidence regarding an association between PA and chromosomal aberrations in an OD model.
SEARCH METHODS
This review was conducted according to PRISMA guidelines for systematic reviews and meta-analyses. Medline, Embase and Cochrane databases were searched from inception through March 2020 using the (MeSH) terms: chromosome aberrations, preimplantation genetic screening and IVF. Original research articles, reporting on the types and/or frequency of chromosomal aberrations in embryos derived from donor oocytes, including data regarding PA, were included. Studies reporting results of IVF cycles using only autologous oocytes were excluded. Quality appraisal of included studies was conducted independently by two reviewers using a modified Newcastle-Ottawa Assessment Scale. A one-stage IPD meta-analysis was performed to evaluate whether an association exists between PA and aneuploidy. Meta-analysis was performed using a generalized linear mixed model to account for clustering of embryos within patients and clustering of patients within studies.
OUTCOMES
The search identified 13 032 references, independently screened by 2 reviewers, yielding 6 studies encompassing a total of 2637 IVF-OD cycles (n = 20 024 embryos). Two 'low' quality studies using FISH to screen 12 chromosomes on Day 3 embryos (n = 649) reported higher total aneuploidy rates and specifically higher rates of trisomy 21, 18 and 13 in men ≥50 years. One 'moderate' and three 'high' quality studies, which used 24-chromosome screening, found no association between PA and aneuploidy in Day 5/6 embryos (n = 12 559). The IPD meta-analysis, which included three 'high' quality studies (n = 10 830 Day 5/6 embryos), found no significant effect of PA on the rate of aneuploidy (odds ratio (OR) 0.97 per decade of age, 95% CI 0.91-1.03), which was robust to sensitivity analyses. There was no association between PA and individual chromosome aneuploidy or segmental aberrations, including for chromosomes X and Y (OR 1.06 per decade of age, 95% CI 0.92-1.21). Monosomy was most frequent for chromosome 16 (217/10802, 2.01%, 95% CI 1.76-2.29%) and trisomy was also most frequent for chromosome 16 (194/10802, 1.80%, 95% CI 1.56-2.06%).
WIDER IMPLICATIONS
We conclude, based on the available evidence, that APA is not associated with higher rates of aneuploidy in embryos derived from OD. These results will help fertility practitioners when providing preconception counselling, particularly to older men who desire to have a child.
Topics: Aged; Aneuploidy; Female; Fertilization in Vitro; Humans; Male; Oocyte Donation; Oocytes; Paternal Age; Pregnancy; Preimplantation Diagnosis
PubMed: 33355342
DOI: 10.1093/humupd/dmaa052 -
JBRA Assisted Reproduction Mar 2023The aim of this study is to analyze the efficacy of the dual trigger (human chorionic gonadotropin (hCG) + GnRH agonists) compared to the conventional trigger (hCG) in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study is to analyze the efficacy of the dual trigger (human chorionic gonadotropin (hCG) + GnRH agonists) compared to the conventional trigger (hCG) in terms of oocyte retrieval (number and oocyte maturity), fertilization rate or number of embryos with two pronuclei, number of high-quality embryos, number of transferred embryos, number of cryopreserved embryos, implantation rate, positive β-hCG rate, ongoing pregnancy rate, abortion rate, and live birth rate.
METHODS
This search performed in this systematic review included all literature published in the PubMed database of studies on controlled ovarian stimulation with dual trigger compared with conventional trigger. The meta-analysis included clinical trials and prospective cohort studies.
RESULTS
Statistically significant differences between groups (dual trigger vs. hCG trigger) in terms of number of oocytes retrieved and live birth rate favored the dual trigger protocol. No statistically significant differences were found in the other studied variables. A tend favoring the dual trigger protocol was observed in all studied parameters.
CONCLUSIONS
Dual trigger seems to be more effective in GnRH antagonist cycles in terms of embryo and pregnancy outcome.
Topics: Female; Pregnancy; Humans; Sperm Injections, Intracytoplasmic; Prospective Studies; Ovulation Induction; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Oocytes; Chorionic Gonadotropin; Retrospective Studies
PubMed: 36356171
DOI: 10.5935/1518-0557.20220035 -
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 -
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 -
Human Reproduction Update 2015Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling... (Review)
Review
BACKGROUND
Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health.
METHODS
No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles.
RESULTS AND CONCLUSIONS
Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth. CX40, which characterizes the extravillous trophoblast (EVT), supports proliferation of the proximal EVTs while preventing them from differentiating into the invasive pathway. Furthermore, women with recurrent early pregnancy loss as well as those with endometriosis exhibit reduced levels of CX43 in their decidua. The antimalaria drug mefloquine, which blocks gap junction function, is responsible for increased risk of early pregnancy loss and stillbirth, probably due to inhibition of intercellular communication in the decidua or between trophoblast layers followed by an impairment of placental growth. Gap junctions also play a critical role in regulating uterine blood flow, contributing to the adaptive response to pregnancy. Given that reproductive impairment can result from connexin mutations in mice, it is advised that women suffering from somatic disease symptoms associated with connexin gene mutations be additionally tested for impacts on reproductive function. Better knowledge of these essential connexin functions in human female reproductive organs is important for safeguarding women's reproductive health.
Topics: Animals; Cell Communication; Connexin 26; Connexin 43; Connexins; Cumulus Cells; Embryo Implantation; Embryo Loss; Female; Fertility; Gap Junctions; Humans; Ion Channels; Mefloquine; Mice; Oocytes; Oogenesis; Placenta; Pregnancy; Pregnancy Outcome; RNA, Messenger; Reproductive Health; Trophoblasts
PubMed: 25667189
DOI: 10.1093/humupd/dmv007 -
Journal of Assisted Reproduction and... Jul 2016The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF).
METHODS
A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome).
RESULTS
Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08; p = 0.19) nor patient age (estimate = -2.29; p = 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p = 0.237), suggesting absence of heterogeneity between the studies.
CONCLUSIONS
Pregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly.
Topics: Female; Fertilization in Vitro; Humans; Oocyte Donation; Oocytes; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Retrospective Studies; Risk Factors
PubMed: 27007875
DOI: 10.1007/s10815-016-0701-9