Metformin and fertility
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Metformin and Fertility: A Comprehensive Overview
Metformin and Female Fertility in PCOS
Metformin in IVF and ICSI Treatments
Metformin is widely used in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). It helps reduce hyperinsulinemia and suppresses excessive ovarian androgen production, potentially improving outcomes such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates. However, evidence on its effectiveness in improving live birth rates remains inconclusive. In long gonadotrophin-releasing hormone agonist (GnRH-agonist) protocols, metformin may increase clinical pregnancy rates but does not conclusively improve live birth rates. Conversely, in short GnRH-antagonist protocols, metformin may reduce live birth rates .
Metformin for Ovulation Induction
Metformin is also used for ovulation induction in women with PCOS, often in combination with clomiphene citrate (CC). Studies suggest that metformin may improve live birth rates compared to placebo and increase clinical pregnancy and ovulation rates. However, it is associated with higher gastrointestinal side effects. When combined with CC, metformin may improve ovulation and pregnancy rates, particularly in CC-resistant women, although the evidence is not definitive .
Metformin and Menstrual Regularity
Metformin alone has been shown to restore regular menstrual cycles and spontaneous ovulation in women with PCOS, but there is no strong evidence supporting an improvement in pregnancy rates. The addition of metformin to other ovulation induction methods like CC or gonadotropin injections may enhance outcomes, but more well-designed studies are needed to confirm these findings.
Metformin and Male Fertility
Impact on Male Reproductive Health
Recent studies indicate that metformin can influence male reproductive health. In obese male mice, metformin improved insulin sensitivity but reduced fertility rates, suggesting a complex relationship between insulin sensitivity and reproductive success. Additionally, metformin has been shown to improve testosterone production and spermatogenesis in men with metabolic disorders, potentially enhancing fertility .
In Utero Exposure to Metformin
Exposure to metformin in utero has been linked to reduced fertility in male offspring. Studies in mice have shown that male offspring exposed to metformin during fetal development exhibited lower fertility rates, increased sperm head abnormalities, and greater DNA damage. These findings highlight the need for further research to understand the long-term reproductive effects of prenatal metformin exposure.
Metformin in Fertility Preservation
During Chemotherapy
Metformin has shown promise in preserving ovarian function during cyclophosphamide-based chemotherapy. In mice, concurrent metformin treatment significantly attenuated chemotherapy-induced gonadotoxicity, suggesting its potential as a fertility-preserving agent during cancer treatment.
In Endometrial Hyperplasia and Cancer
Metformin, combined with medroxyprogesterone acetate (MPA), is being investigated for its potential to inhibit disease relapse and improve fertility outcomes in patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). Preliminary studies suggest that metformin may enhance the effectiveness of MPA therapy and reduce relapse rates.
Conclusion
Metformin plays a multifaceted role in fertility, particularly in women with PCOS and men with metabolic disorders. While it shows promise in improving ovulation and pregnancy rates, its impact on live birth rates remains uncertain. Additionally, metformin's potential in preserving fertility during chemotherapy and its effects on male reproductive health warrant further investigation. As research continues, metformin may become a more integral part of fertility treatments and preservation strategies.
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