Brusco 2013

Methods	Open‐label RCT Patients divided, according to a controlled randomized pattern, into two groups
Participants	Women undergoing ICSI (n = 149) Inclusion criteria: Age between 37 ‐ 40 years; "The recruitment criteria include being under 40 years old, at least one previous failed attempt with ICSI with low‐quality oocyte recovery, diagnosis of PCOS (i.e., with oligomenorrhea, hyperandrogenism and pelvic ultrasonographic appearance characterized by multiple anechoic areas) 8, diagnosis of “poor responders” (i.e., with poor ovarian response to hormonal stimulation, an age greater than 37 years and the need for high doses of FSH stimulation in previous cycles). Only ICSI treatments arrived to the transfer of embryos in the uterus (Embryo‐Transfer) and carried out on Day +2/3 are included in the study". Exclusion criteria: "Patients with a partner with a diagnosis of severe male infertility such as cryptozoospermia (i.e., retrieval of sperm in the semen after centrifugation) and azoospermia (i.e., eventual retrieval of sperm from the testicle or epididymis) were excluded from the study."
Interventions	1. Myo‐inositol 2000 mg, D‐chiro‐inositol 400 mg, and folic acid 400 mg: 1 of each tablet a day (n = 58) 2. Folic acid 400 mg: 1 tablet a day (n = 91) Treatment duration 3 months before the ICSI cycle
Outcomes	Oocyte quality Embryo quality Biochemical pregnancy Clinical pregnancy "Each patient was included only once; therefore, the results for each patient refer to a single treatment cycle"
Notes	Conducted in Perugia Italy Trial duration between June 2012 and May 2013 Email sent to author regarding randomised pattern, allocation concealment and whether there were any dropouts; gianfrancesco.brusco@ospedale.perugia.it; no reply. No mention of ethics approval, consent or funding Authors state "no conflicts of interest"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	"According to a randomized pattern, the total number of patients was divided into two groups". "The two groups were homogeneous within the parameters of inclusion adopted for the study". Numbers are very unequal between the groups, with 58 in the intervention group and 91 in control
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment
Blinding (performance bias and detection bias) All outcomes	High risk	"An open study"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No dropouts mentioned and groups are unequal
Selective reporting (reporting bias)	Low risk	All outcomes were reported in the Results
Other bias	Low risk	No other bias found