Papaleo 2009

Methods	Randomised controlled trial
Participants	Infertile women with PCOS undergoing ovulation induction for ICSI (n = 60) Mean age (years) treatment: 36.2 ± 2.4; non‐treatment 35.4 ± 2.5 Inclusion criteria: women aged < 40 years with PCOS, indicated by oligomenorrhoea (6 or fewer menstrual cycles during a period of 1 year), hyperandrogenism (hirsutism, acne or alopecia) or hyperandrogenaemia (elevated levels of total or free T) and typical features of ovaries on ultrasound scan. All women had been treated at the IVF clinic for > 12 months. Exclusion criteria: other medical conditions causing ovulatory disorders such as hyperinsulinaemia, hyperprolactinaemia, androgen excess such as adrenal hyperplasia or Cushing's syndrome Duration of infertility (months) treatment: 46.1 ± 18.5, non‐treatment: 37.7 ± 9.6
Interventions	1. Myo‐inositol 2 g + folic acid 400 µg (Inofolic®): 2 tablets a day (n = 30) 2. Folic acid 400 µg (n = 30) Duration: for 1 cycle of ICSI. Treatment starting on the day of GnRH administration
Outcomes	Number of mature oocytes retrieved Embryo quality Pregnancy Implantation rates Total number of days of FSH stimulation Total dose of gonadotropin administered Oestrogen levels Fertilisation rate Number of retrieved oocytes Embryo cleavage rate Live births Miscarriage rates Cancellation rate Incidence of moderate or severe ovarian hyperstimulation syndrome
Notes	The Institutional Review Board approved the protocol, and all participants gave written informed consent before entering into the trial Source of funding not stated Power calculation performed Authors contacted. Trial conducted in Italy, start date March 2004 (unknown end date) Authors could not supply live birth data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised according to "computerised allocation". Authors have since confirmed this
Allocation concealment (selection bias)	Unclear risk	"Computerised allocation"
Blinding (performance bias and detection bias) All outcomes	High risk	Authors confirmed in correspondence that participants and investigators were not blinded; however, outcome assessors and clinicians were blinded. Not a placebo control
Incomplete outcome data (attrition bias) All outcomes	Low risk	No withdrawals or dropouts
Selective reporting (reporting bias)	High risk	Data on live birth were not reported in the paper, even though it was listed as an outcome in the abstract of the paper
Other bias	Low risk	No other bias found