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NCMBJ 2026, 16(64): 29-41 |
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Karami Z, Khodarahmi P, Tafvizi F, Ghaffari-Novin M. The Role of Metformin in Modulating IGF1 and IGF2 Protein Expression in Patients with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection. , NCMBJ. 2026; 16 (64) :29-41
URL: http://ncmbjpiau.ir/article-1-1897-en.html
URL: http://ncmbjpiau.ir/article-1-1897-en.html
Department of Biology, Pa. C., Islamic Azad University, Parand, Iran
Abstract: (4 Views)
| Extended Abstract
Background and Aim: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age and is associated with ovulatory dysfunction, infertility, hyperandrogenism, insulin resistance, and metabolic abnormalities. These disturbances may adversely affect follicular development and oocyte maturation. The insulin-like growth factor (IGF) system, particularly IGF-1 and IGF-2, plays an important role in ovarian function, granulosa cell activity, folliculogenesis, and oocyte development. Alterations in IGF signaling may contribute to the abnormal ovarian microenvironment observed in women with PCOS. Metformin, an insulin-sensitizing agent commonly prescribed for PCOS, may influence this system by improving metabolic and endocrine regulation. However, its effects on IGF-1 and IGF-2 protein levels in different biological compartments remain incompletely understood. This study aimed to investigate the association between metformin treatment and IGF-1 and IGF-2 protein levels in serum, follicular fluid (FF), and cumulus cells (CCs) of women with PCOS undergoing intracytoplasmic sperm injection (ICSI).
Materials and Methods: This case–control study included 90 women aged 20–35 years undergoing ICSI at Sarem Hospital, Tehran, Iran. Participants were divided into three groups: healthy controls (n = 30), women with untreated PCOS (n = 30), and women with PCOS receiving metformin treatment (n = 30). Samples were collected between November 2021 and March 2023. Metformin was prescribed by fertility specialists, with the daily dose gradually increased from 500 mg during the first week to 2,000 mg during the fourth week. Serum samples were collected before follicular aspiration. Follicular fluid was obtained during ultrasound-guided oocyte retrieval, and blood-contaminated samples were excluded. Cumulus cells were isolated from cumulus–oocyte complexes using hyaluronidase treatment and mechanical separation. IGF-1 and IGF-2 protein concentrations in serum, FF, and CCs were measured using enzyme-linked immunosorbent assays (ELISA). Statistical analyses were performed using SPSS version 25. One-way analysis of variance followed by Tukey’s post hoc test was used for group comparisons, and p < 0.05 was considered statistically significant.
Results: IGF-1 protein levels showed distinct patterns across biological compartments. In women with untreated PCOS, IGF-1 concentrations were significantly higher in serum and FF but significantly lower in CCs than in controls (p < 0.001). In the metformin-treated group, serum IGF-1 levels were significantly lower than those in untreated PCOS, whereas FF levels remained largely unchanged. Conversely, IGF-1 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.001). IGF-2 concentrations were significantly elevated in serum, FF, and CCs in untreated PCOS compared with controls. Metformin treatment significantly reduced serum IGF-2 levels relative to untreated PCOS. Nevertheless, IGF-2 concentrations in FF and CCs remained significantly higher than those in controls (p < 0.001). Furthermore, IGF-2 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.01). These findings demonstrate that the changes associated with metformin differed between systemic circulation and the local ovarian environment. The findings indicate that PCOS is associated with compartment-specific alterations in IGF-1 and IGF-2 protein levels in serum, follicular fluid, and cumulus cells. Metformin treatment was associated with reduced circulating IGF-1 and IGF-2 levels and altered protein profiles in cumulus cells, while elevated IGF-2 levels persisted in follicular fluid and cumulus cells.
Conclusion: These observations suggest that the systemic and local ovarian components of the IGF system may respond differently to metformin treatment. The findings provide additional insight into the potential relationship between metabolic regulation and ovarian growth-factor signaling in women with PCOS undergoing ICSI. However, because of the observational design and relatively short treatment period, causal effects of metformin cannot be established. Further prospective studies with larger sample sizes, longer treatment periods, and direct assessment of oocyte quality, embryo development, implantation, and pregnancy outcomes are required to clarify the clinical significance of these changes.
Background and Aim: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age and is associated with ovulatory dysfunction, infertility, hyperandrogenism, insulin resistance, and metabolic abnormalities. These disturbances may adversely affect follicular development and oocyte maturation. The insulin-like growth factor (IGF) system, particularly IGF-1 and IGF-2, plays an important role in ovarian function, granulosa cell activity, folliculogenesis, and oocyte development. Alterations in IGF signaling may contribute to the abnormal ovarian microenvironment observed in women with PCOS. Metformin, an insulin-sensitizing agent commonly prescribed for PCOS, may influence this system by improving metabolic and endocrine regulation. However, its effects on IGF-1 and IGF-2 protein levels in different biological compartments remain incompletely understood. This study aimed to investigate the association between metformin treatment and IGF-1 and IGF-2 protein levels in serum, follicular fluid (FF), and cumulus cells (CCs) of women with PCOS undergoing intracytoplasmic sperm injection (ICSI).
Materials and Methods: This case–control study included 90 women aged 20–35 years undergoing ICSI at Sarem Hospital, Tehran, Iran. Participants were divided into three groups: healthy controls (n = 30), women with untreated PCOS (n = 30), and women with PCOS receiving metformin treatment (n = 30). Samples were collected between November 2021 and March 2023. Metformin was prescribed by fertility specialists, with the daily dose gradually increased from 500 mg during the first week to 2,000 mg during the fourth week. Serum samples were collected before follicular aspiration. Follicular fluid was obtained during ultrasound-guided oocyte retrieval, and blood-contaminated samples were excluded. Cumulus cells were isolated from cumulus–oocyte complexes using hyaluronidase treatment and mechanical separation. IGF-1 and IGF-2 protein concentrations in serum, FF, and CCs were measured using enzyme-linked immunosorbent assays (ELISA). Statistical analyses were performed using SPSS version 25. One-way analysis of variance followed by Tukey’s post hoc test was used for group comparisons, and p < 0.05 was considered statistically significant.
Results: IGF-1 protein levels showed distinct patterns across biological compartments. In women with untreated PCOS, IGF-1 concentrations were significantly higher in serum and FF but significantly lower in CCs than in controls (p < 0.001). In the metformin-treated group, serum IGF-1 levels were significantly lower than those in untreated PCOS, whereas FF levels remained largely unchanged. Conversely, IGF-1 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.001). IGF-2 concentrations were significantly elevated in serum, FF, and CCs in untreated PCOS compared with controls. Metformin treatment significantly reduced serum IGF-2 levels relative to untreated PCOS. Nevertheless, IGF-2 concentrations in FF and CCs remained significantly higher than those in controls (p < 0.001). Furthermore, IGF-2 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.01). These findings demonstrate that the changes associated with metformin differed between systemic circulation and the local ovarian environment. The findings indicate that PCOS is associated with compartment-specific alterations in IGF-1 and IGF-2 protein levels in serum, follicular fluid, and cumulus cells. Metformin treatment was associated with reduced circulating IGF-1 and IGF-2 levels and altered protein profiles in cumulus cells, while elevated IGF-2 levels persisted in follicular fluid and cumulus cells.
Conclusion: These observations suggest that the systemic and local ovarian components of the IGF system may respond differently to metformin treatment. The findings provide additional insight into the potential relationship between metabolic regulation and ovarian growth-factor signaling in women with PCOS undergoing ICSI. However, because of the observational design and relatively short treatment period, causal effects of metformin cannot be established. Further prospective studies with larger sample sizes, longer treatment periods, and direct assessment of oocyte quality, embryo development, implantation, and pregnancy outcomes are required to clarify the clinical significance of these changes.
Type of Study: Research Article |
Subject:
Embryology
Received: 2026/11/14 | Accepted: 2026/12/1 | Published: 2026/12/1
Received: 2026/11/14 | Accepted: 2026/12/1 | Published: 2026/12/1
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