VEGF Concentration in a Preovulatory Leading Follicle Relates to Ovarian Reserve and Oocyte Maturation during Ovarian Stimulation with GnRH Antagonist Protocol in In Vitro Fertilization Cycle

Wu, Wen‐Bin; Chen, Hsuan‐Ting; Lin, Junjie; Lai, Tsung‐Ching

doi:10.3390/jcm10215032

Cited by 9 publications

(4 citation statements)

References 54 publications

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“…We also found a decrease in the level of PEDF protein in the FF; however, the FF/GC ratio was similar in both age groups, implying that there is no change in the secretion of the protein into the FF. Our finding of an elevated concentration of VEGF protein in the FF of RA patients, in accordance to the literature [ 44 , 45 ], point to a gene-specific mechanism and not a general property of aging. VEGF elevation, along with PEDF reduction, intensified the inverted relationship between PEDF and VEGF, as demonstrated in various models [ 30 , 46 , 47 ].…”

Section: Discussionsupporting

confidence: 92%

The Role of PEDF in Reproductive Aging of the Ovary

Nemerovsky

Bar‐Joseph

Eldar‐Boock

et al. 2022

IJMS

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Reproductive aging is characterized by a decline in ovarian function and in oocytes’ quantity and quality. Pigment epithelium-derived factor (PEDF), a pivotal player in ovarian angiogenic and oxidative balance, was evaluated for its involvement in reproductive aging. Our work examines the initial stage of reproductive aging in women and mice, and the involvement of PEDF in the process. Granulosa cells from reproductively-aged (RA) women and mice (36–44 years old and 9–10 months old, respectively) indicated an increase in the level of PEDF mRNA (qPCR), with yet unchanged levels of AMH and FSHR mRNAs. However, the PEDF protein level in individual women showed an intra-cellular decrease (ELISA), along with a decrease in the corresponding follicular fluid, which reflects the secreted fraction of the protein. The in vitro maturation (IVM) rate in the oocytes of RA mice was lower compared with the oocytes of young mice, demonstrated by a reduced polar body extrusion (PBE) rate. The supplementation of PEDF improved the hampered PBE rate, manifested by a higher number of energetically-competent oocytes (ATP concentration and mtDNA copy number of individual oocytes). Our findings propose PEDF as an early marker of reproductive aging, and a possible therapeutic in vitro agent that could enhance the number of good-quality oocytes in older IVF patients.

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Section: Discussionsupporting

confidence: 92%

The Role of PEDF in Reproductive Aging of the Ovary

Nemerovsky

Bar‐Joseph

Eldar‐Boock

et al. 2022

IJMS

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“…Currently, there are conflicting reports regarding the effect of VEGF and TNF-α on embryogenesis. Increased levels of VEGF in follicular fluid have been associated with the development of ovarian hyperstimulation syndrome, poor fertilization and premature luteinization (Kudsy et al 2016;Wu et al 2021). In other studies (Monteleone et al 2008;Chen et al 2023), on the contrary, high levels of VEGF contributed to a higher fertilization rate, the production of better quality embryos and more frequent pregnancy.…”

Section: Resultsmentioning

confidence: 97%

Assessment of VEGF and TNF-alpha levels in patients with an unexpectedly poor and suboptimal response during the treatment of infertility using ART methods

Perfilova,

Muzyko,

Tikhaeva

et al. 2024

RRP

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Introduction: The problem of infertility treatment currently has medical, socio-demographic and economic significance. Progress in the field of reproductive technologies has improved the situation, but the issue has not yet been completely resolved. Infertility is diagnosed in 8-12% of couples of reproductive age; in Russia this figure exceeds 15%, and, according to WHO, it is a critical level. It is known that immunological factors can disrupt the reproductive process at the stages of folliculogenesis, ovulation, and implantation. These include vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and others. The aim of this study: to assess the levels of VEGF and TNF-α in women with different outcomes of hormonal stimulation of the ovaries during the treatment of infertility using ART methods. Materials and methods: Based on voluntary informed consent, a simple open comparative randomized study was conducted with the participation of 71 women in the Volgograd region undergoing infertility treatment using ART methods. Inclusion criteria were the age up to 42 years inclusive and the anti-Mullerian hormone level over 1.2 ng/mL. Before ovulation stimulation with gonadotropins, data on ovarian reserve parameters were collected. Based on the results of stimulation, women were divided into 3 groups: Group 1 – with high and normal ovarian response – 10 or more oocytes were obtained (control group); Group 2 – with suboptimal ovarian response – 5-9 oocytes received; Group 3 – with a poor response – 4 or less oocytes were received. After venipuncture, which was performed in preparation for standard anesthesia, VEGF and TNF-α were quantitatively determined in the blood plasma using an enzyme-linked immunosorbent assay. Results: The study results showed a statistically significant difference in VEGF levels in follicular fluid and serum between the groups of women with high/normal, suboptimal and poor ovarian response to gonadotropin stimulation. A higher level of this marker was observed in the serum of patients with high/normal and poor response – 48.15±4.23 and 41.29±8.26 pg/mL, respectively, while in women with a suboptimal response a lower VEGF level was determined –29.19±3.41 pg/mL. The levels of VEGF in the follicular fluid of women included in the high/normal, suboptimal and poor response groups were 35.95±3.20; 27.42±2.53 and 41.22±3.23 pg/mL, respectively (Table 1). As for TNF-α, its serum level in women with a high and normal response was lower than in the patients with a suboptimal response. In the follicular fluid of patients of group 3, there was a higher level of TNF-α, compared to groups 1 and 2, where the indicator was almost the same. However, the difference was not statistically significant. Conclusions: Thus, VEGF is directly involved in the mechanisms of regulation of oocyte maturation and can be not only a marker of poor ovarian response, but also a predictor of unsatisfactory results of ovarian stimulation in the treatment of infertility using ART methods. TNF-alpha in follicular fluid does not have a statistically significant effect on follicle development in the treatment of infertility using assisted reproductive technologies.

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“…The FF sample collection was performed as previously described by our laboratory ( 8 ). FF was collected immediately after isolation of the cumulus-oocyte complexes.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, the decrease in vascularization is thought to be a cause or consequence of atresia, perhaps because dying follicles fail to produce angiogenic factors needed to support the vasculature. The levels of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), growth differentiation factor-9 (GDF-9), and insulin-like growth factor (IGF) correlate with folliculogenesis and oocyte maturation ( 6 – 8 ). These factors are either indirectly induced or directly produced by follicular granulosa cells (GCs) and VEGF, FGF-2, and IGF have been shown to associate with angiogenesis among these factors ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential angiogenic biomarkers in human follicular fluid for predicting oocyte maturity

Chen,

Wu,

Lin

et al. 2023

Front. Endocrinol.

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BackgroundAngiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (FF) during folliculogenesis is clinically significant and important for in vitro fertilization. This study aims to identify the key angiogenic factors in FF for predicting oocyte maturity during in vitro fertilization.Materials and methodsForty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, > 18 mm; one mid-antral follicle, < 14 mm) were collected without flushing during oocyte retrieval. In total, 80 FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in FF were analyzed via Luminex high-performance assays. Recorded patient data included antral follicle count, anti-müllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH/LH/E2/P4, trigger day E2/LH/P4, and retrieval day E2/LH/P4 were measured by chemiluminescence assay.ResultsTen angiogenic factors were highly expressed in FF: eotaxin, Gro-α, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-α and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p < 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.ConclusionOur findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro fertilization.

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VEGF Concentration in a Preovulatory Leading Follicle Relates to Ovarian Reserve and Oocyte Maturation during Ovarian Stimulation with GnRH Antagonist Protocol in In Vitro Fertilization Cycle

Cited by 9 publications

References 54 publications

The Role of PEDF in Reproductive Aging of the Ovary

The Role of PEDF in Reproductive Aging of the Ovary

Assessment of VEGF and TNF-alpha levels in patients with an unexpectedly poor and suboptimal response during the treatment of infertility using ART methods

Identification of potential angiogenic biomarkers in human follicular fluid for predicting oocyte maturity

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