Table 1

AuthorsStudy designStudy sizePopulation characteristicsType of treatmentMean age (years)Mean BMI (kg/m)Main findings

(Papaleo et al., 2009) [11]Randomized controlled trial60 women with PCOS
Treatment: 30
Placebo: 30
Women with PCOS as defined by oligo/amenorrhea, hyperandrogenism/nemia, and PCO, undergoing ICSI Treatment: 2 g myo-inositol twice a day plus 400 mg folic acid
Placebo: 400 mg folic acid
Treatment: 36.2
Placebo: 35.4
Treatment: 26.7
Placebo: 26.3
Significant reduction in total rFSH units (26 versus 31.7 IU, ), number of days of stimulation (11.4 versus 12.4, ), peak E2 level at hCG administration (2,232 versus 2,713 pg/mL, ), number of germinal vesicles and degenerated oocytes (1.0 ± 0.9 versus 1.6 ± 1.0), and number of cancelled cycles (1 versus 3, ) in treatment group versus placebo; no significant differences in mature oocytes, fertilization rate, cleavage rate, embryo quality, implantation rate, clinical pregnancy, or miscarriage rate

(Ciotta et al., 2011) [41]Randomized controlled trial34 women with PCOS
Group A: 17
Group B: 17
Women with PCOS (Rotterdam criteria) undergoing ICSI or IVF Group A: 2 g of myo-inositol + 200 μg folic acid twice a day × 3 months
Group B: 200 μg folic acid twice a day × 3 months
Age < 40
Mean age: not mentioned
Mean BMI: not mentionedSignificantly reduced total rFSH units, peak E2 level at hCG administration, and cancelled cycles (2 versus 5) in group A versus group B. In group A, higher number of mature oocytes, greater number of oocytes retrieved (12 versus 8.5, ); significantly higher mean number of transferred embryos with greater number of grade I embryos (30 versus 9, ) in group A. No significant differences in number of fertilized oocytes and total number of biochemical pregnancies between the two groups

(Unfer et al., 2011) [70]Randomized trial84 women with PCOS
Group A: 43
Group B: 41
Women with PCOS (Rotterdam criteria) undergoing ICSI Group A: myo-inositol 2 g twice a day for 8 weeks
Group B: D-chiro-inositol (DCI) 0.6 g twice a day for 8 weeks
Group A: 35.5
Group B: 36.5
Group A: 24.6
Group B: 25.3
In group A, significant reduction in total rFSH units (1953.6 versus 2360.5 IU, ), number of stimulation days (11.1 versus 12.7, ), and peak estradiol levels (2261.2 versus 2740.0 pg/mL; ); no cycle cancellation in group A versus 4 in group B (); no difference between the total number of oocytes retrieved between two groups; in group A, significantly greater number of mature oocytes (8.21 versus 7.08, ), number of grade 1 embryos (1.64 versus 0.76, ), number of pregnancies (22 versus 10; ); no significant differences in clinical pregnancies (15 versus 5, = NS) and spontaneous abortions (4 versus 3; = NS) in group A versus group B, respectively

(Isabella and Raffone 2012) [54]Randomized controlled trial54 women with PCOS
Placebo: 11
Group A: 10
Group B: 11
Group C: 10
Group D: 12
Women with PCOS (Rotterdam criteria) undergoing ICSI Placebo group
Group A: DCI 300 mg daily
Group B: DCI 600 mg daily
Group C: DCI 1200 mg daily
Group D: DCI 2400 mg daily
Treatment given for 8 weeks
Placebo: 36.9 ± 1.5
Group A: 36.8 ± 1.6
Group B: 36.9 ± 1.52
Group C: 36.7 ± 1.57
Group D: 37.0 ± 1.25
Placebo: 24.4 ± 2.8
Group A: 25.2 ± 3.5
Group B: 24.7 ± 3.5
Group C: 25.1 ± 3.1
Group D: 25.6 ± 2.9
Significantly increased FSH dose (IU) administered in the two highest DCI dose groups versus placebo (placebo 2239.7 versus group A 2379.1 versus group B 2305.9 versus group C 2368 versus group D 2983.0); number of stimulation days significantly greater in the 3 higher dose DCI groups versus placebo (placebo 11.4 versus group A 12.1 versus group B 12.5 versus group C 12.9 versus group D 13.8); estradiol levels at hCG administration significantly increased in highest dose DCI group versus placebo (placebo group 1429.69 versus group D 1490.24); no significant differences in number of cycles cancelled or total number of oocytes retrieved; significantly lower number of mature (MII) oocytes in group D compared to placebo group (); significantly lower embryo quality in DCI supplemented groups versus placebo ()

(Colazingari et al., 2013) [28]Randomized trial100 women with PCOSPCOS (as per Rotterdam criteria) patients with BMI < 28 and FSH < 10 IU/L undergoing IVF-ETGroup A (): MYO 550 mg and DCI 13.8 mg orally twice a day for 12 weeks
Group B (): DCI 500 mg orally twice a day for 12 weeks
Not mentionedNot mentionedDecreased dose of rFSH (1,569.0 versus 1,899.2 IU; ) and lower E2 levels before hCG administration (2,185.09 versus 2,519.85, ) in the MYO group versus DCI group, respectively; the number of oocytes retrieved was higher in the DCI group (8.35 in the MYO-DCI group versus 10.75 in the DCI group); reduced number of degenerated oocytes in MYO-DCI group (age < 35: 1.04 versus 1.82; age > 35: 1.00 versus 1.45); fertilization rate was higher in MYO-DCI treated group (0.75 versus 0.58 in the DCI treated group; ). Greater number of transferred embryos in group A versus B (2.22 versus 1.67, ); higher embryo quality in MYO-DCI treated group (0.96 versus 0.7, )

Pacchiarotti et al., 2016 [72]Randomized, controlled double-blind trialControl ()
Group A ()
Group B ()
PCOS (Rotterdam criteria), FSH < 12 IU/L, and BMI (20 to 26) undergoing first time ICSIControl (folic acid 400 mcg)
Group A (MYO 4000 mg + folic acid 400 mcg + melatonin 3 mg daily)
Group B (MYO 4000 mg + folic acid 400 mcg); given from cycle day 1 until 14 days after ET
Control: 32 ± 3.6
Group A: 31.2 ± 2.1
Group B: 31.5 ± 2.8
Control: 22.8 ± 1.3
Group A: 22.8 ± 1.3
Group B: 23.1 ± 1.7
Less total gonadotropin dose (IU) administered in group A 2058 versus group B 3113 and versus control group 3657 (); increased number of mature oocytes reaching MII stage in group A (48.2%) versus group B (35.0%) and control group (38.2%); increased percentage of grade I embryos in group A (45.7%) versus 30.4% in group B and only 25.6% in the control group

Rago et al., 2015 [73]Prospective study37 women with PCOSPCOS patients based on 2 of the Rotterdam criteria (PCO morphology and oligomenorrhea) undergoing IVF MYO (2 g) and α-lipoic acid (800 mg) per day for 3 months in previously MYO-treated group 18–42 years<24.9No differences in total dose of FSH administered and duration of stimulation between two groups (1501.9 versus 1498.0 IU; , and 11.6 versus 10.8; , resp.); in MYO and α-lipoic acid group, significant reduction in immature oocytes (0.2 versus 1.0; ), with improvement in mature oocytes (0.87% versus 0.81%, ) and increase in grade 1 embryos (75.7% versus 57.7%, ) in comparison to MYO alone group; no difference in fertilization and cleavage rates between groups; greater number of pregnancies in MYO and α-lipoic acid group in comparison to MYO alone group (52% versus 33.3%, )

ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; ET, embryo transfer; PCOS, polycystic ovary syndrome; PCO, polycystic ovaries; MYO, myo-inositol; DCI, D-chiro-inositol; BMI, body mass index; rFSH, recombinant follicle stimulating hormone; E2, estradiol; hCG, human chorionic gonadotropin; IU, international units; MII, metaphase II.