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Table 1 Main randomized studies on the impact of Myo-inositol (MI), alone or in combination, for induction, ovarian stimulation, or IVF/ICSI in women with PCOS

From: Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies

Authors Material/Methods Results Conclusions
Induction/Ovarian stimulation    
 Gerli [4] RCT, 92 women: 47 receiving FA 400 µg/day vs 45 receiving MI 4 g/day et FA 400 µg/day – 3 months With MI: ovulation (25 vs 15%; p < 0.01), reduced follicular phase duration (24.5 vs 40.5 j; p < 0.05)
Clinical pregnancy rates no significantly different
Beneficial effect on ovulation
 Raffone [26] RCT, 120 women: 60 receiving MI 4 g/day et FA 400 µg/day vs 60 receiving 1500 mg/day of MET. If no pregnancy was obtained, addition of rFSH (375 UI/day) during 3 cycles With MET: 15% ovulated and 18.3% of spontaneous pregnancies. 42 women received rFSH: 26.1% pregnancy rate (cumulative rate 36.6%)
With MI: 65% ovulated, 30% of spontaneous pregnancies. 38 women received rFSH, 28.9% pregnancy rate (NS) (cumulative rate: 48.4%—NS)
Myo-inositol appears to be more effective than metformin
Bias risks: random sequence generation and incomplete outcome data
 Morgante [27] RCT, 30 women with clomiphene failure, were stimulated with step-down protocol (150 IU FSH – 3 d, then 75 IU/d after): 15 receiving 1.5 g MI (and lactoferrin 100 mg, and bromelain 20 mg)/day vs 15 without MI—1 month before induction With MI, on the day of hCG: total number of follicles > 15 mm (2.1 vs 3.5) and > 18 mm (1.1 vs 2), estradiol levels 441 vs 955 pg/ml) and cancellation rate (0 vs 40%) were significantly lowerThe clinical pregnancy rate was not significantly different (33.3 vs 13.3%) MI supplementation increase clinical results in ovulation induction
 Ozay [28] RCT, 196 women: 98 receiving MI 4 g/day and FA 400 µg/day vs 98 receiving FA 400 µg/day – 3 months before FSH and during FSH stimulation and IUI With MI: 9 spontaneous pregnancies
Decrease in total FSH dose and duration of stimulation (p < 0.05); increase in pregnancy rate (18.6 with MI and FA vs 12.2% with FA alone) in IUI
Myo-inositol increases IUI pregnancy rate, and decreases total FSH dose and duration of stimulation
Bias risks: allocation concealment and incomplete outcome data
 Agrawal [29] RCT, 120 women: 60 receiving MET 1500 mg/day and MI 1.8 g/day vs 60 receiving MET 1500 mg/day – 3 months
If no pregnancy was obtained: FSH and IUI
With MET + MI: improvement in cycle duration
Birth rate: 55% (MET + MI) vs 26.6% with MET only (p: 0.002)
Increase in pregnancy rate with MET + MI
IVF/ICSI    
 Papaleo [11] RCT, 60 women without hyperinsulinism: 30 receiving FA 400 µg/day vs 30 receiving MI 4 g/day and FA 400 µg/day, from the start of agonist treatment (long protocol) With MI: decrease in total dose of rFSH (1958 vs 2383 UI), decrease in stimulation duration (11.4 vs 12.4 j) and decrease in estradiol level on the day of ovulation triggering (2232 vs 2713 pg/ml) (p < 0.05)
No difference in the number of oocytes retrieved, but a significant decrease in immature or degenerative oocytes and a tendency for an increase in metaphase II oocytes
Reduction of immature and degenerative oocytes, decrease in estradiol levels on the day of ovulation triggering, no difference in embryo quality and pregnancy rate
Bias risks: random sequence generation, allocation concealment and incomplete outcome data
 Unfer [6] RCT, 84 women without hyperinsulinism: 43 undergoing MI 4 g/day vs 41 undergoing DCI 1.2 g/day – 2 month prior to FSH treatment With MI: increase significantly in mature oocytes (8.21 vs 7.08), good quality embryos (1.64 vs 0.76) and pregnancy rate (51 vs 24%). No difference in the number of oocytes retrieved Increase in oocyte and embryo quality
Increase in the pregnancy rate
Bias risks: random sequence generation and incomplete outcome data
 Ciotta [30] RCT, 34 women: 17 undergoing MI 4 g/day and FA 400 µg/day vs 17 undergoing FA 400 µg/day – 3 months prior to FSH treatment and during ovarian stimulation With MI: increased (p < 0.05) number of oocytes retrieved (12 vs 8.5) and embryos grade 1 (68.1 vs 29%) Beneficial effect of MI in oocyte maturation
Bias risks: random sequence generation, allocation concealment, binding of participants and personnel and incomplete outcome data
 Colazingari [12] RCT, 100 women without hyperinsulinism: 47 undergoing MI 1.1 g/day and DCI 27.6 mg/day vs 53 undergoing DCI 1 g/day – 3 months prior to FSH treatment With MI + DCI: ≤ 35 years of age: decrease in total FSH dose (1569 vs 1899 IU; p < 0.05) and increase in good quality embryos (0.96 vs 0.73; p < 0.001)
With MI + DCI: > 35 years of age: decreased estradiol level on day of hCG trigger and decreased number of oocytes retrieved (p < 0.05), increased number of good quality embryos (p < 0.05)
MI + DCI increases oocyte and embryo quality
Bias risks: random sequence generation, allocation concealment, binding of participants and personnel and incomplete outcome data
 Pacchiarotti [13] RCT, 331 women: (A) 165 undergoing MI 4 g/day, FA 400 µg/day and melatonin 3 mg/day vs (B) 166 undergoing MI 4 g/day and FA 400 µg/day vs (control) 195 undergoing FA 400 µg/day – From 1st day of ovarian stimulation to14 days after embryo transfer Decrease in total FSH dose (A: 2058 IU; B: 3113 and control: 3657; p < 0.001)
Increase in the number of metaphase II oocytes (A: 48.2%; B: 35 and control: 38.2) and good quality embryos (A: 45.7%; B: 30.4 and control: 25.6)
MI increases egg and embryo quality
Bias risks: random sequence generation and incomplete outcome data
 Lesoine [31] RCT, 29 women: 15 undergoing placebo vs 14 undergoing MI 4 g/day and FA 400 µg/day – 2 months prior to FSH treatment
Antagonist protocol
With MI: decrease in follicle/oocyte ratio (p < 0.05), increase (p < 0.05) in fertilization rate and good quality embryos. Decrease (p < 0.05) in the duration of stimulation Increase in fertilization rate and embryo quality
The decrease of the oocyte retrieved can be reduced the risk of hyperstimulation
Bias risks: random sequence generation, binding of participants and personnel and incomplete outcome data
  1. The randomized studies were evaluated for the risk of bias using the Cochrane risk of bias assessment tool
  2. RCT: randomized controlled trial; FA: folic acid; MI: myo-insotitol; MET: metformin; IUI: intra-uterine insemination; DCI: D-chiro-inositol; NS: not significant