Oxidative Stress In Follicular Fluid Research Articles

Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial

BackgroundThis study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS).MethodsFifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial.ResultsResveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05).ConclusionsThese findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction.Trial registration numberhttp://www.irct.ir; IRCT20221106056417N1; 2023 February 09.

The Impact of Follicular Fluid Oxidative Stress Levels on the Outcomes of Assisted Reproductive Therapy.

Oocyte quality is a pivotal determinant of assisted reproductive outcomes. The quality of oocytes is intricately linked to their developmental microenvironment, particularly the levels of oxidative stress within the follicular fluid. Oxidative stress levels in follicular fluid may have a substantial influence on oocyte health, thereby impacting the outcomes of ART procedures. This review meticulously explores the intricate relationship between oxidative stress in follicular fluid and ART outcomes. Furthermore, it delves into strategies aimed at ameliorating the oxidative stress status of follicular fluid, with the overarching goal of enhancing the overall efficacy of ART. This research endeavors to establish a robust foundation and provide valuable guidance for clinical treatment approaches, particularly in the context of infertile women, including those of advanced maternal age.

Unveiling follicular fluid oxidative stress biomarkers at polycystic ovary syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Oxidative Stress in Follicular Fluid of Low Responder and Hyporesponse Patients Undergoing the IVF Program at Halim Fertility Center, IVF Clinic, Division of Reproductive Endocrinology, Faculty of Medicine, USU Medan

Oxidative Stress in Follicular Fluid of Low Responder and Hyporesponse Patients Undergoing the IVF Program at Halim Fertility Center, IVF Clinic, Division of Reproductive Endocrinology, Faculty of Medicine, USU Medan

Follicular fluid oxidative stress biomarkers and ART outcomes in PCOS women undergoing in vitro fertilization: A cross-sectional study.

BackgroundPolycystic ovarian syndrome (PCOS) is the most common cause of anovulatory infertility. Oxidative stress (OS), which plays an important role in determining the developmental competence of an oocyte, may be involved in understanding infertility and poor outcomes cycles in PCOS women undergoing in vitro fertilization (IVF).Objective To measure OS biomarkers in the follicular fluid of PCOS women undergoing IVF.Materials and Methods In this cross-sectional study, 100 women with PCOS (n = 43) and tubal factor (n = 57) undergoing IVF, who were referred to a tertiary medical center between January 2016 and September 2017 were enrolled. OS markers like reactive oxygen species (ROS), total antioxidant capacity (TAC), and 8-Isoprostane (8-IP) were tested in the follicular fluid and various IVF outcomes in the form of oocytes retrieved, fertilized, cleavage rate, grading of embryos and pregnancy outcomes were compared between the two groups.ResultsThe results indicated that the levels of ROS, TAC, and 8-IP were higher in the PCOS group compared to the tubal group (p = 0.21, p = 0.95, and p 0.05, respectively). Biomarkers based on the number of retrieved oocytes, cleavage rate, and grades of embryos did not differ significantly in the two groups. The median ROS, TAC, and 8-IP were not significantly different in the two groups in relation to the pregnancies, although the 8-IP levels were significantly raised in the PCOS women who had a miscarriage (p = 0.02).ConclusionThis study concluded the possible role of OS in PCOS women with increased higher level of 8-IP biomarker as a potential biomarker that needs further evaluation.

Assessment of oxidative stress in follicular fluid of infertile women undergoing IVF procedure

Oxidative stress (OS) plays an important role in biological processes of reproduction, and yet there is no accurate indicator to measure it. The objective of the study was to correlate the effect of ROS (reactive oxygen species) on embryo quality and pregnancy outcome. This was achieved by measuring levels of ROS present in granulosa cells and follicular fluid (FF) of women undergoing IVF (in vitro fertilization). ROS in FF is measured using thiobarbituric acid reactive substances assay kit (Abcam) and granulosa cells were measured with the help of flow cytometry. The results showed that high levels of FF malondialdehyde were found in nonpregnant women as compared to pregnant group and were found to be significant (P 0.05) but had an impact on the quality of embryos (P

Assessment of oxidative stress in follicular fluid of infertile women undergoing IVF procedure

Assessment of oxidative stress in follicular fluid of infertile women undergoing IVF procedure

Effect of Alpha-Lipoic Acid on Blood Hormonal Parameters and Follicular Fluid Oxidative Stress Factors in Infertile Women with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection

Effect of Alpha-Lipoic Acid on Blood Hormonal Parameters and Follicular Fluid Oxidative Stress Factors in Infertile Women with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection

Association Between Systemic and Local Oxidative Stress of Infertile Women Undergoing Ivf/Icsi

Oxidative stress (OS) may affect in vitro fertilization (IVF) outcomes in infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The aim of this study is to explore the possible relationships between OS parameters in serum and follicular fluid (FF) from infertile women with male cause infertility (n=40), women with polycystic ovary syndrome (PCOS) (n=40), and women with unexplained infertility (UI)(n=45) undergoing IVF/ICSI. The collection of blood and FF samples was done at the day of oocyte aspiration. Total peroxide (TPX) level, total antioxidant capacity (TAC), and malondialdehyde (MDA) level were measured in serum and FF; whereas, glutathione-s-transferase (GST) activity and superoxide dismutase (SOD) activity were measured in FF. Also, oxidative stress index (OSI) that is the percentage ratio of TPX to TAC, was calculated. In the control group, correlation analysis reveals the presence of a significant positive association between FF OSI with serum OSI, FF TPX with FF OSI, and serum TPX with FF GST activity. In the PCOS group, there was a significant negative association between: FF TPX and serum TAC level. However, non-significant relationship was found between serum and FF OS status parameters in the UI group. It’s concluded from the present study that systemic OS may give valuable information about local OS occurrence (blood OS reflects FF OS) only in control group and PCOS group. Such information could be useful for a better understanding of the pathological OS mechanisms involved in IVF failure for patients with different causes of infertility.

Role of oxidative stress in follicular fluid on embryos of patients undergoing assisted reproductive technology treatment.

Oxidative stress (OS) is defined as an imbalance between oxidants and antioxidants in favor of the oxidants, and the disruption of redox signaling leads to molecular damages. This study was conducted to clarify the effect of OS in individual follicular fluid (FF) on oocyte fertilization and embryonic division. A total of 124 patients who underwent assisted reproductive technology treatment in our hospital underwent intracytoplasmic sperm injection and 211 FF were collected. The ova were fertilized, and embryos were individually cultured until cleavage stage or blastocyst stage and classified according to the Veeck classification system or Gardner classification system. The follicular fluid corresponding to the ovum was analyzed by measuring the OS marker, the reactive oxygen metabolites (d-ROM test), and the antioxidant marker (biological antioxidant potential marker [BAP] test), and the relation between these markers and clinical parameters was analyzed. The value of d-ROM was correlated with the proper fertilization status and formation of good quality cleavage embryo, whereas the elevated value of BAP was observed in better embryonic development group. Oxidative stress index, defined as d-ROM/BAP × 100 clearly indicated that lower oxidative stress index was associated with better fertilization status and embryo development. Our results clearly indicate that the balance between OS and antioxidant capacity in FF at the time of oocyte retrieval is possibly important in the processes of fertilization and embryo division; thus, we propose that oxidative status and balance in FF might be used as novel biomarkers in assisted reproductive technology.

The role of stimulation protocol, number of oocytes retrieved with respect to follicular fluid oxidative stress and IVF outcome

The study was conducted on a population of 203 women attending the IVF clinic, Ahmedabad, India, to explore the role of stimulation protocol and the number of oocytes retrieved on oxidative stress in follicular fluid and IVF outcome. Follicular fluid was collected during ovum pick-up to determine the oxidative stress markers: superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), total thiols (TT), l-ascorbic acid (AA), total protein, glutathione S-transferase (GST) and glutathione reductase (GRD). The average number of oocytes retrieved was significantly higher in the women receiving a long GnRH agonist protocol compared to GnRH antagonist protocol while the percentage of women with positive IVF outcome was lower in the long agonist protocol. The level of total thiols was significantly lower in the group of women administered a short agonist protocol. The proportion of ETs carried out and positive IVF outcome were higher following retrieval of an intermediate number of oocytes (6–10 oocytes) compared to a lower (0–5 oocytes) and higher (>10 oocytes) number. Mean glutathione reductase (GRD) activity in follicular fluid was significantly elevated in the intermediate (6–10) and higher (>10) oocyte retrieval groups compared to the lower oocyte retrieval group. Positive IVF outcomes were highest when oocyte retrieval was in the range of 6–10 oocytes, and the level of MDA was lower (1.76 ± 0.13 nmol/ml) as compared to 0–5 and >10 oocytes retrieved groups.

Determination of oxidative stress balance in follicular fluid

AbstractBackground:The role of oxidative stress in female reproduction is an area that needs more investigation. This study aims to assess the oxidative stress levels in follicular fluid (FF) samples of women undergoing in vitro fertilization (IVF) and to relate them to different diagnoses.Methods:A total of 199 woman were enrolled; 37 of them were diagnosed with polycystic ovary syndrome (PCOS), 71 with endometriosis and 41 with tubal factor infertility (TFI) and 50 of the patients were used as a control group. A sample of FF was collected from each patient at an oocyte retrieval day and analyzed for oxidative stress by measuring a class of reactive oxygen metabolites (ROMs) (dROMs test) and also analyzed for the plasma antioxidant test (PAT).Results:The data analyzed in FF were related to different diagnoses. Groups were not significantly different in age and body mass index (BMI), except for the PCOS group. There was a significant difference between dROMs and PAT levels in FF of patients vs. control group. The same finding was seen when the dROM/PAT ratio was used.Conclusions:We conclude that the evaluation of oxidative stress in FF needs more investigation with regard to markers in the follicular microenvironment.

Follicular fluid lipid peroxidation levels in women with endometriosis during controlled ovarian hyperstimulation

This observational study aimed to establishing a relationship between lipid peroxidation and endometriosis in women undergoing controlled ovarian hyperstimulation. A total of 79 women were divided into two groups: (i) controls (tubal or male factor); and (ii) endometriosis (stages III/IV). The endometriosis diagnosis was confirmed by videolaparoscopy and the controlled ovarian stimulation protocol was similar to all patients. Follicular fluid (FF) lipid peroxidation levels were determined through the quantification of malondialdehyde. Statistical analysis was performed using parametric and non-parametric tests, logistic regression was performed to estimate the chance of achieving a pregnancy in each group and a moving average was calculated for the endometriosis group. Peroxidation levels in the endometriosis group were significantly higher when compared to controls. The moving average showed a decrease of MDA levels in the endometriosis group with increasing female age. Moreover, women with endometriosis who were under 33 years of age were 4.3 times more likely to achieve a pregnancy than women above that age. In conclusion, endometriosis is associated with increased FF oxidative stress (OS) in patients undergoing in vitro fertilization (IVF). Also, increasing age is associated with a decrease in severity of the oxidative status, but a decreased chance of pregnancy.

Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF

BackgroundThe status characterized by the imbalance between pro-oxidants and antioxidants molecules, defined as oxidative stress, has been suggested to be involved in the pathogenesis of subfertility in females. This study aims to evaluate the impact of a complete micronutrients supplementation on oxidative stress levels in follicular microenvironment as well as on in vitro fertilization (IVF) outcome.MethodsThis preliminary study was conducted between January 2014 and July 2015 at the Siena University Hospital Infertility Clinic. Serum and follicular fluid were collected from infertile women aged > 39 years who underwent two in vitro fertilization cycles: in the first cycle they were treated with GnRH-antagonist protocol and gonadotropins for controlled ovarian hyperstimulation, whereas in the second cycle ovarian stimulation protocol was associated to micronutrients supplementation, starting three months earlier. Protein oxidation levels and total antioxidant capacity in serum and in follicular fluid were evaluated in IVF cycles with or without micronutrients supplementation. Differences in IVF outcome parameters were statistically evaluated.ResultsTwo-dimensional electrophoresis analyses demonstrated that when patients assumed micronutrients before IVF cycles, follicular fluid and serum proteins were protected from oxidative damage. Comparable results were obtained when total antioxidant capacity was measured. Moreover, the mean number of good quality oocytes retrieved when patients received micronutrients supplementation was significantly increased.ConclusionThe additional treatment with micronutrients, starting three months before IVF cycles, protects the follicular microenvironment from oxidative stress, thus increasing the number of good quality oocytes recovered at the pick up.

Oxidative stress in follicular fluid of young women with low response compared with fertile oocyte donors

The aim of this study was to determine the concentrations of oxidative stress markers, antioxidant enzymes and cytokines in the follicular fluid of young women with low response in ovarian stimulation cycles compared with high responders and fertile oocyte donors of the same age, to assess the impact of oxidative stress on ovarian reserve. The activity of follicular fluid antioxidant enzymes glutathione transferase, glutathione reductase and glutathione peroxidase was significantly lower in young women with reduced ovarian reserve compared with that in high responders and oocyte donors. Follicular fluid concentrations of oxidative stress marker malondialdehyde combined with 4-hydroxyalkenals and nitric oxide were higher in low responders than in high responders and oocyte donors. Significant differences between low responders and donors in concentrations of IL-2, IL-6, IL-8 and vascular endothelial growth factor were observed, with higher concentrations in low responders. However, IL-10 concentration was lower in low responders than in high responders and donors. No significant differences were found in follicular fluid concentrations of tumour necrosis factor alpha between the three groups. These results demonstrate that different concentrations of oxidative stress markers, oxidant enzymes and cytokines in low responders compared with high responders and oocyte donors may negatively impact ovarian response.

A new method to assess oxidative stress in ART cycles

The role of oxidative stress (OS) in female reproduction is an understudied area for investigation. The aim of the study was to assess reactive oxygen species (ROS) levels both in follicular fluid (FF) and in serum samples of women undergoing IVF and to relate them to clinical outcomes. A total of 56 women were enrolled. From each patient a sample of serum and FF were collected at oocyte retrieval day and analyzed for OS, by measuring a class of reactive oxygen metabolites (ROMs) (dROMs test) and for biological anti-oxidant potential levels (BAP test). The data analyzed in serum and in FF were related to pregnancy outcomes. There was no significant relationship between d-ROMs and BAP levels in serum or FF GROUP A and B and the clinical parameters of prognosis of women: age, number of oocytes retrieved number of oocytes methaphase II, FSH, fertilization rate and cleavage rate, number of embryos transferred and embryo score. There was a positive association between systemic levels of OS measured in serum GROUP A and pregnancy outcomes (p = 0.007) suggesting that the evaluation of OS in FF needs more investigation about markers in follicular microenvironment in order to predict IVF success.

Folliküler Sıvı Oksidatif Stresin Oosit Kalitesi ve Embriyo Gelişimi Üzerine Etkisi

Amaç: Oksidatif metabolizmanın in vitro fertilizasyon (IVF) üzerindeki rolü çok iyi araştırılmamıştır. Amacımız oksidatif stres belirteçlerinin müteakip oosit ve embriyo kalitesine etkisini incelemektir. Gereç ve Yöntemler: ICSI uygulanan 67 hastadan elde edilen toplam 214 folliküler sıvı değerlendirildi. Folliküler sıvı oksidatif stres belirteç düzeyleri ile [Malondialdehit (MDA), nitrik oksit (NO) ve protein karbonil] takip eden oosit kalitesi, fertilizasyon ve embriyo morfolojileri arasındaki ilişki araştırıldı. Bulgular: Ortalama MDA seviyeleri fertilize olan oositlerin folliküler sıvılarında anlamlı olarak yüksekti. Ortalama NO seviyeleri yüksek kaliteli embriyo gelişen oositlerin folliküler sıvılarında anlamlı olarak düşükken ortalama protein karbonil düzeyleri anlamlı olarak yüksekti. Sonuç: Folliküler sıvı oksidatif stres, fertilizasyonda ve embriyo morfolojisinde önemli bir rol oynar gibi görünmektedir. Farklı oksidatif stres yolaklarının oosit gelişimi üzerinde farklı etkileri olabilir. Oosit matürasyonu için folliküler sıvıdaki belirli bir düzeyde oksidatif strese ihtiyaç olabilir. Objective: The role of oxidative metabolism on in vitro fertilization (IVF) has not been studied in detail. Our aim was to investigate the impact of oxidative stress markers on subsequent oocyte and embryo quality. Material and Methods: A total of 214 oocytes and their corresponding follicular fluid (FF) samples from 67 women undergoing intracytoplasmic sperm injection (ICSI) were assessed. The relationship between FF levels of oxidative stress markers [malondialdehyde (MDA), nitric oxide (NO) and protein carbonyl] levels and subsequent oocyte quality, fertilization and embryo morphologies were evaluated. Results: The mean MDA levels were significantly higher in FFs of fertilized oocytes. The mean NO levels were significantly lower in FFs of top-quality embryos whereas mean protein carbonyl levels were significantly higher in FFs of top quality embryos. Conclusion: FF oxidative stress seems to play an important role in fertilization and embryo morphology. Different oxidative stres pathways might have different effects on oocyte development, and also particular oxidative stress in FF might be needed for oocyte maturation.

Abdominal obesity can induce both systemic and follicular fluid oxidative stress independent from polycystic ovary syndrome

ObjectiveThe abdominal form of obesity is prevalent in women with polycystic ovary syndrome (PCOS). Visceral fat accumulation seems to play an important role in etiology of PCOS. In this cross-sectional study we evaluated the association of oxidative stress (OS) induced with PCOS and abdominal obesity in serum and follicular fluid (FF) of infertile women. Study designA total of 80 women younger than 37 years old undergoing an IVF program were studied in the same period of time from September 2012 to October 2013. Blood serum and FF obtained from 40 women with PCOS (diagnosed by the Rotterdam 2004 criteria) and 40 women without PCOS undergoing IVF were evaluated for two OS markers: lipid peroxide (LPO) and total antioxidant capacity (TAC), after puncture. The patients were divided into 4 groups on the basis of presence of PCOS and waist-to-hip ratio (WHR) or abdominal obesity (OA). ResultsHealthy and PCOS women with abdominal obesity had significantly higher amounts of LPO in the serum and FF as compared with women without abdominal obesity. LPO concentration in FF was significantly lower than in serum and corroborates the hypothesis that the germinal cells have a potent antioxidant mechanism. We also found that LPO concentration in the PCOS group associated with AO had an increasing trend vs. those AO patients without PCOS but this difference was not significant, so the increase in LPO level was approximately independent of PCOS. Based on our results, the association and interaction between PCOS and AO can lead to TAC concentration reduction in patients. ConclusionsAbdominal obesity can induce local and systemic oxidative stress in PCOS and non-PCOS patients. We suggest that PCOS-induced disorders are likely to be exacerbated in the presence of abdominal obesity.

Obesity and follicular fluid oxidative stress: Relationship to ICSI outcome

Abstract Objective To study the influence of female obesity on follicular fluid oxidative stress and to correlate it to intracytoplasmic sperm injection (ICSI) outcome. Study design Seventy-four normal females below the age of 40 undergoing ICSI for reason of male factor infertility were enrolled in the study. They were divided into 2 groups according to body mass index (BMI); Group I (non-obese) ( n = 24, BMI 2 ) and Group II (obese) ( n = 50, BMI ⩾ 25 Kg/m 2 ). Oxidative stress markers (MDA (malonaldehyde), NO 2 /NO 3 (Nitrite/Nitrate) ratio, GSH (reduced glutathione) and GSH/GSSG (reduced glutathione/oxidized glutathione) ratio) were measured by high performance liquid chromatography (HPLC). Results Obese women had significantly higher mean follicular fluid MDA ( P = 0.006) as well as NO 2 /NO 3 ratio ( P = 0.004). BMI strongly correlated to follicular fluid MDA ( P = 2 /NO 3 ratio ( P = 0.02). GSH and GSH/GSSG ratio showed a non-significant difference between the two groups ( P = 0.14 and 0.67, respectively). Clinical pregnancy rate was significantly higher in the non-obese group (87%) compared to the obese (43%) ( P = P = Conclusion Obesity aggravates follicular fluid oxidative stress with a negative impact on pregnancy outcome of ICSI cycles.

Markers of oxidative stress in follicular fluid of women with endometriosis and tubal infertility undergoing IVF

Oxidative stress and trace elements in the oocytes environment is explored in endometriosis and impact on in vitro fertilization (IVF) outcome assessed. Follicular fluid was aspirated at the time of oocyte retrieval from endometriosis (n=200) and tubal infertility (n=140) and the analytes measured using spectroscopy and HPLC. Increased concentration of reactive oxygen species (ROS), nitric oxide (NO), lipid peroxidation (LPO), iron, lead, cadmium and reduced levels of total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), vitamins A, C, E, copper, zinc and selenium was observed compared to tubal infertility. Increased ROS and NO in endometriosis and tubal infertility associated with poor oocytes and embryo quality. Increased levels of ROS, NO, LPO, cadmium and lead were observed in women who did not become pregnant compared to women who did. Intrafollicular zinc levels were higher in women with endometriosis who subsequently became pregnant following IVF.