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

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 1^st 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