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Some studies suggest metformin improves fertility outcomes in women with PCOS, insulin resistance, and metabolic disorders, while other studies indicate it may not improve live birth rates in IVF or ICSI treatments.
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Metformin, a widely prescribed medication for type II diabetes, has garnered attention for its potential benefits in improving fertility, particularly in individuals with polycystic ovary syndrome (PCOS). This article synthesizes current research on the effects of metformin on fertility outcomes in both women and men, with a focus on its use in assisted reproductive technologies (ART) and ovulation induction.
PCOS is characterized by anovulation, hyperandrogenism, and insulin resistance. Metformin, an insulin-sensitizing agent, has been shown to improve ovulation rates in women with PCOS. Studies indicate that metformin alone can restore regular menstrual cycles and spontaneous ovulation, although its impact on pregnancy rates remains inconclusive . When combined with clomiphene citrate (CC), metformin improves ovulation and pregnancy rates in both CC-resistant and unselected PCOS women .
In the context of ART, metformin has been studied for its potential to enhance outcomes in women with PCOS undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Research suggests that metformin may increase clinical pregnancy rates and reduce the incidence of ovarian hyperstimulation syndrome (OHSS) . However, its effect on live birth rates is less clear, with some studies indicating no significant improvement .
Metformin's benefits extend to male fertility, particularly in men with metabolic syndrome. It has been shown to improve testosterone production and spermatogenesis, thereby enhancing fertility outcomes . However, there are concerns about potential adverse effects, such as an increased risk of genital birth defects in offspring when men use metformin preconceptionally.
Metformin has also been explored as a protective agent against chemotherapy-induced gonadotoxicity. In animal models, metformin has been shown to preserve ovarian function and fertility during cyclophosphamide-based chemotherapy by inhibiting the mTOR pathway and reducing apoptosis in granulosa cells. This suggests a potential role for metformin in fertility preservation during cancer treatment.
Endometriosis, a condition characterized by ectopic endometrial growth, often leads to infertility. Metformin has demonstrated efficacy in reducing the size of endometrial implants and restoring fertility in animal models of endometriosis. This effect is likely due to metformin's ability to down-regulate estrogen secretion, inflammation, and oxidative stress.
Metformin shows promise in improving fertility outcomes in both women and men, particularly those with PCOS and metabolic disorders. While it enhances ovulation and clinical pregnancy rates, its impact on live birth rates remains uncertain. Additionally, metformin may offer protective benefits against chemotherapy-induced gonadotoxicity and endometriosis-associated infertility. Further well-designed studies are needed to fully elucidate its role and optimize its use in fertility treatments.
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