Dataset Information

The role of oxidative stress in patients with recurrent pregnancy loss: a review.

ABSTRACT:

Background

Recurrent pregnancy loss (RPL) presents one of the main problems in the field of reproductive medicine, due to the unknown etiology in 50% of cases, as well as limited evidence-based diagnostic and therapeutic modalities. Recent studies indicate that systemic and placental oxidative stress (OS) represents an essential factor in the etiopathogenesis of RPL. This article is a comprehensive narrative synthesis of previously published studies concerning the role of oxidative stress in the etiology of recurrent pregnancy loss.

Methods

We conducted literature search of published studies in the English language focusing on oxidative stress and its association with recurrent pregnancy loss (RPL) utilizing the Medline and Cochrane databases from 2000 through January 2021. The keywords used were "recurrent pregnancy loss" "oxidative stress and recurrent pregnancy loss" and "oxidative stress biomarkers and recurrent pregnancy loss".

Results

The search yielded 1116 publications, of which 92 were included in the final analysis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) at basal levels have various physiological functions whereas deviation from redox window is associated with different pathologies including early pregnancy loss. The currently available studies support the concept that increased oxidative stress (OS) and deficient antioxidant protection is implicated in the etiology of recurrent pregnancy loss (RPL) but underlying mechanisms through which OS affects pregnancy outcome remains largely indefinable.

Conclusions

Future research in this field can provide new insights regarding the OS-mediated damage in recurrent pregnancy loss as well as potential applications of antioxidant therapy in this group of patients.

SUBMITTER: Zejnullahu VA

PROVIDER: S-EPMC8520213 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

The role of oxidative stress in patients with recurrent pregnancy loss: a review.

Zejnullahu Vjosa A VA Zejnullahu Valon A VA Kosumi Ernad E

Reproductive health 20211016 1

<h4>Background</h4>Recurrent pregnancy loss (RPL) presents one of the main problems in the field of reproductive medicine, due to the unknown etiology in 50% of cases, as well as limited evidence-based diagnostic and therapeutic modalities. Recent studies indicate that systemic and placental oxidative stress (OS) represents an essential factor in the etiopathogenesis of RPL. This article is a comprehensive narrative synthesis of previously published studies concerning the role of oxidative stres ...[more]

PMID: 34656123

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Project description:ObjectiveOxidative stress biomarkers (OSBs) may be strongly associated with disease progression and recurrent pregnancy loss (RPL). However, the research on associations of most OSBs (e.g., 8-nitroguanine [8-NO2Gua] and 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA]) with RPL is limited. Therefore, we aimed to investigate the effect of OSBs exposure on RPL risk by performing a case-control study.Material and methodsWe use our established dataset, Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES), which included 514 Taiwanese reproductive age women (aged 20-50 years; 397 cases and 117 controls) from National Cheng Kung University Hospital. RPL is clinically defined by a history of two or more consecutive miscarriages, where a miscarriage is defined as the termination of pregnancy before 20 weeks of gestation. The urinary levels of several OSBs (e.g., 8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-NO2Gua, 8-isoprostaglandin F2α [8-isoPGF2α], and HNE-MA) and malondialdehyde (MDA) were measured using isotope dilution liquid chromatography-tandem mass spectrometry and thiobarbituric acid reactive substances, respectively.ResultsThe median levels of 8-NO2Gua (6.15 vs. 3.76 ng/mL) and HNE-MA (30.12 and 21.54 ng/mL) were significantly higher in the RPL group than in the control group. By categorizing the OSBs data into tertiles, after we adjusted for age and urine creatinine levels discovered that the RPL risk associated with 8-NO2Gua and HNE-MA levels in the third tertile were approximately 2 times higher than those in the first tertile (8-NO2Gua, adjusted OR = 3.27, 95 % CI = 1.66-6.43; HNE-MA, adjusted OR = 1.96, 95 % CI = 1.05-3.64; p < 0.05). These findings suggest that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA are risk factors for RPL.ConclusionOur findings indicate that specific OSBs are associated with an increased RPL risk, suggesting that reducing OSB levels can improve RPL risk. Nevertheless, more studies on preventive medicine are required to understand the exposure sources and adverse outcome pathways of OSBs associated with RPL.

Project description:BackgroundPregnancy is a complicated physiological process. The multifaceted regulation of maternal-fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion. However, no significant breakthrough has been made. Therefore, it is important to understand the molecular mechanisms of recurrent pregnancy loss (RPL) to identify potential therapeutic strategies. The aim of this study was to investigate the pathogenesis of RPL.MethodsIn this study, Relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify differentially expressed proteins in decidual from RPL patients and matched normal controls. Further, Molecules NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (ndufb3) and cyclooxygenase-2 (COX-2) were validated by immunohistochemistry (IHC), Western blotting, CCK8 and mitochondrial red fluorescent probe (Mito-Tracker Red CMXRos).ResultsA total of 456 proteins reached the threshold of a 1.5-fold change were identified for further bioinformatics analysis. Upon mapping the differentially expressed proteins using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways database, iTRAQ results were confirmed by assessing NDUFB3 and COX-2 protein levels in specimens of decidual tissue by Western blotting. Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL.ConclusionsThis comprehensive analysis of RPL proteomics reveals novel candidate: NDUFB3, which could be further investigated for explanation of the pathological mechanism of RPL.

Project description:Study questionWhat is the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature?Summary answerThe guideline development group formulated 77 recommendations answering 18 key questions on investigations and treatments for RPL, and on how care should be organized.What is known alreadyA previous guideline for the investigation and medical treatment of recurrent miscarriage was published in 2006 and is in need of an update.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 31 March 2017 and written in English were included. Cumulative live birth rate, live birth rate and pregnancy loss rate (or miscarriage rate) were considered the critical outcomes.Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.Main results and the role of chanceThe guideline provides 38 recommendations on risk factors, prevention and investigations in couples with RPL, and 39 recommendations on treatments. These include 60 evidence-based recommendations - of which 31 were formulated as strong recommendations and 29 as conditional - and 17 good practice points. The evidence supporting investigations and treatment of couples with RPL is limited and of moderate quality. Of the evidence-based recommendations, only 10 (16.3%) were supported by moderate quality evidence. The remaining recommendations were supported by low (35 recommendations: 57.4%), or very low quality evidence (16 recommendations: 26.2%). There were no recommendations based on high quality evidence. Owing to the lack of evidence-based investigations and treatments in RPL care, the guideline also clearly mentions investigations and treatments that should not be used for couples with RPL.Limitations reasons for cautionSeveral investigations and treatments are offered to couples with RPL, but most of them are not well studied. For most of these investigations and treatments, a recommendation against the intervention or treatment was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.Wider implications of the findingsThe guideline provides clinicians with clear advice on best practice in RPL, based on the best evidence available. In addition, a list of research recommendations is provided to stimulate further studies in RPL. One of the most important consequences of the limited evidence is the absence of evidence for a definition of RPL.Study funding/competing interestsThe guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. J.E. reports position funding from CARE Fertility. S.L. reports position funding from SpermComet Ltd. S.M. reports research grants, consulting and speaker's fees from GSK, BMS/Pfizer, Sanquin, Aspen, Bayer and Daiichi Sankyo. S.Q. reports speaker's fees from Ferring. The other authors report no conflicts of interest.ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

Dataset Information

The role of oxidative stress in patients with recurrent pregnancy loss: a review.

Background

Methods

Results

Conclusions

Publications

The role of oxidative stress in patients with recurrent pregnancy loss: a review.

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