Pacchiarotti 2016

Methods	Randomised controlled double‐blind trial
Participants	Women with PCOS undergoing ICSI aged between 27 ‐ 38 years (n = 569) Inclusion criteria: absence of tubal, uterine, genetics and male causes of infertility; serum levels of FSH on day 3 of the ovarian cycle 512 IU/L; Rotterdam criteria for PCOS; normal uterine cavity; BMI of 20 to 26 kg/m2; first IVF treatment. Only women undergoing 1st‐time ICSI procedure fulfilling inclusion criteria were enrolled in the study in order to limit their heterogeneity
Interventions	1. Myo‐inositol 4000 mg + folic acid 400 mcg (Inofolic®): 1 tablet twice a day and Melatonin 3 mg: 1 tablet twice a day (n = 178) 2. Myo‐inositol 4000 mg + folic acid 400 mcg (Inofolic®): 1 tablet twice a day (n = 180) 3. Folic acid 400 mcg: 1 tablet twice a day (n = 211) Treatment was from the first day of the cycle until 14 days after embryo transfer
Outcomes	Primary end points were: oocyte and embryo quality, clinical pregnancy (identified by the presence of a gestational sac on ultrasonography 5 weeks after oocyte retrieval) and implantation rates. Secondary outcomes were: gonadotropin IU administered, days of stimulation, serum estradiol(E2) levels and endometrial thickness on the day of human chorionic gonadotropin (hCG) administration.
Notes	Conducted in Italy Trial ran from July 2009 to December 2011 43 women dropped out, 16 from the control, 13 from the intervention group A and 14 from group B; reasons provided Clinical Trial registration Number: NCT01540747 (ClinicalTrials.gov registry) Has an author who was an employee of a pharmaceutical company Funding source not reported Emailed Dr Pacchiarotti 18th October 2016 to ask about allocation concealment and live birth data and asked about trial details from included study Valeri 2015. Contact details; arypac@gmail.com. Dr Pacchiarotti replied 20th March 2017 saying that the clinical pregnancy was per woman as they have 80% of the live birth data. We replied asking whether we could include these data. No reply yet. We will need to follow up on this for next review update. Power calculation performed
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed using a computer based random assignment schedule for each patient"
Allocation concealment (selection bias)	Unclear risk	Unknown
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"double‐blinded" but not placebo‐controlled
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropout reasons were described and numbers given for each group
Selective reporting (reporting bias)	Low risk	Outcomes in the Methods were reported as per protocol
Other bias	Low risk	No other bias found