EC Gynaecology

Background: PCOS is one of the most common disorders affecting females of reproductive age. Hyperinsulinemia and peripheral insulin resistance feature demonstrated by the ovarian theca and granulosa cells in women with PCOS and insulin sensitivity. Insulin functioning via insulin receptor triggers testosterone generation in theca cells. Therefore, utilizing insulin-sensitizers enhances pe- ripheral insulin sensitivity and thus improves metabolism in PCOS women.

Objectives: Assessing the efficacy of insulin sensitizers on ovulation promotion among PCOS women treated with ART. Selection criteria randomized controlled trials (RCTs) where insulin-sensitizing drugs been used for women with PCOS undergo- ing ART treatment Type of outcome measures: Primary outcomes: (A). Fertilization outcomes (B) Pregnancy outcomes. Secondary outcomes: (C) Treatment-related adverse events

Results: 13 randomized placebo-controlled trials included, encompassing 1251 patients with PCOS undergoing ART cycles. The number of retrieved oocytes, (I2 = 77%, P < 0.001), no statistically significant difference between patients received insulin sensitizers and those received placeboes (MD - 1.15; 95% - 2.60, 0.31; P = 0.12). Fertilization rate, (I2 = 0%, P = 0.5), there was no statistically significant difference between insulin sensitizers and placebo groups (SMD - 0.13; 95% - 0.28, 0.03; P = 0.11). The number of embryos available for transfer, (I2 = 0%, P = 0.75) there was statistically significantly higher number of embryos transferred among patients received insulin sensitizers (MD 0.07; 95% 0.01, 0.12; P = 0.01).

The number of normal oocytes (I2 = 60%, P = 0.11), patients who received insulin sensitizers had statistically significant more mature oocytes than those received placebo (MD 4.24; 95% 1.92, 6.55; P = 0.0003). There was no statistically significant difference between insulin sensitizers and placebo groups regarding the number of normal MII oocytes (MD 1.14; 95% -1.88, 4.16; P = 0.46). Endometrial thickness and implantation rate, no statistically significant difference between insulin sensitizers and placebo groups (MD 0.10; 95% - 0.39, 0.60; P = 0.68). The clinical pregnancy rate (I2 = 41%, P = 0.06), patients who received insulin sensitizers were 1.28 times more likely to experience clinical pregnancy. However, this did not attain a statistically significant level (OR 1.28; 95% 0.92, 1.77; P = 0.14). Biochemical pregnancy no statistically significant difference between both groups (OR 1.18; 95% 0.74, 1.89; P = 0.49). Multiple pregnancy rate (I2 = 0%, P = 0.58), no statistically significant difference between patients subjected to insulin sensitizers and those who received placebo (OR 1.28; 95% 0.57, 2.88; P = 0.56). Miscarriage and abortion rates no statistically significant dif- ference between insulin sensitizers and placebo groups (RR 0.53; 95% 0.24, 1.18; P = 0.12). In this respect, there was no statistically significant difference between both groups regarding the abortion rate (RR 0.43; 95% 0.07, 2.76; P = 0.38). Live birth rate, (I2 = 59%, P = 0.01), patients treated with insulin sensitizers were 1.30 times more susceptible to have a live birth (OR 1.30; 95% 0.81, 2.07; P = 0.28). Ovarian Hyperstimulation Syndrome (OHSS) (I2 = 21%, P = 0.24), the risk of OHSS was significantly low among patients received insulin sensitizers than those subjected to placebo (OR 0.48; 95% 0.30, 0.77; P = 0.002). Total Complications patients who received insulin sensitizers were 3.52 times more vulnerable to experience adverse events (RR 3.52; 95% 2.41, 5.15; P < 0.0001). Gastrointestinal complications Patients who received insulin sensitizers were more susceptible to have nausea (RR 3.40; 95% 1.85, 6.25; P < 0.0001), vomiting (RR 4.68; 95% 1.37, 15.99; P = 0.01), and diarrhea (RR 5.45; 95% 1.91, 15.53; P = 0.001).

Conclusions: Insulin sensitizers increased the number of embryos transferred and mature oocytes. Furthermore, enhanced clinical pregnancy and live birth rates while lowering OHSS risk. Whereas the risk of miscarriage was similar. Patients treated with insulin sensitizers were more prone to treatment-related side effects, particularly gastrointestinal problems.

 Keywords: PCOS; Metformin; Berberine; Thiazolidinedione; Insulin Sensitizing Drugs In PCO; ART; RCT

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