Maged 2015

Methods	Randomised study
Participants	Women with PCOS (based on Rotterdam criteria, ESHRE/ASRM 2004), the diagnosis of PCOS is determined by the presence of 2 of the following conditions: oligo‐ovulation or anovulation, hyperandrogenism and polycystic ovaries detected by ultrasonography with the presence of 12 or more follicles measuring 2 – 9mm in diameter, and/or at least 1 enlarged ovary (410 cm). None of the participants had history of clomiphene citrate resistance (n = 120) Timed intercourse Mean age was 26 years for all 3 groups Exclusion criteria: women with endocrinological abnormalities such as thyroid dysfunction or abnormal prolactin levels, those with hypothalamic or pituitary dysfunctions evaluated by low gonadotropin level, other causes of infertility such as tubal factor evaluated by HSG or laparoscopy, abnormal uterine cavity evaluated by sonohystrography or hysteroscopy and male factor, evaluated by semen analysis. Women with ovarian cysts and those with allergy to the study medications were also excluded from the study. Women who had received any hormonal medications (except progesterone for withdrawal bleeding) within the last 3e months before the study were also excluded
Interventions	1. Clomiphene citrate 100 mg orally in 2 divided doses a day. No treatment (n = 40) 2. NAC 1200 mg in 2 divided doses a day (in the form of powder inserted in small pockets to be diluted into a standard glass of water from day 3 until day 7 of the menstrual cycle) (n = 40) 3. Metformin 500 mg: 1 tablet 3 times a day (n = 40) Treatment period; from day 3 to day 7 of the menstrual cycle, treatment was repeated in non‐pregnant cases for 3 successive cycles
Outcomes	Clinical pregnancy (defined as the presence of gestational sac containing fetal hearts on ultrasound scan) Occurrence and day of ovulation Endometrial thickness and pattern Number and size of follicles
Notes	Conducted in Egypt Trial period; September 2012 to March 2014. Funding source not reported Ahmed Mohamed Maged, Obstetrics and Gynecology Department, Kasr Aini Hospital Cairo University, 135 King Faisal Street Haram Giza, Cairo, Egypt. Tel: 0105227404. Fax:35873103. E‐mail prof.ahmedmaged@gmail.com. Email sent 13th October 2016 regarding live birth and any dropouts. No reply.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised at the beginning of each cycle by sealed opaque envelopes containing randomly generated numbers into 3 groups
Allocation concealment (selection bias)	Low risk	Patients were randomized at the beginning of each cycle by sealed opaque envelopes containing randomly generated numbers into 3 groups
Blinding (performance bias and detection bias) All outcomes	High risk	No blinding
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Numbers analysed in each group are not given
Selective reporting (reporting bias)	Low risk	No known selective reporting
Other bias	Low risk	No other bias found