N-Acetylcysteine for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Table 1

Characteristics of included studies: study information, treatments, inclusion and exclusion criteria systematic reviews of randomized controlled trials.

Study ID	Study period	Country	Treatment arms	Study duration	Diagnosis criteria	Inclusion criteria	Exclusion criteria
Among women with polycystic ovary syndrome
Salehpour et al. 2009 [17]	Feb 2007–February 2008	Iran	NAC: 1800 mg/day, divided into three daily doses; placebo: ORS, divided into three daily doses	6 months	Rotterdam criteria, ESHRE/ASRM 2003	Presence of PCOS; spontaneous onset of maturation; and normal sexual development	Diabetes mellitus; use of medications affecting glucose metabolism; Use hormonal analogues other than progesterone; Severe hepatic or kidney diseases; active peptic ulcer
Gayatri et al. 2010 [28]	June 2006–December 2007	India	NAC: 1800 mg/day, orally divided in three doses; metformin: 500 mg/day for week 1; 500 mg twice daily for week 2 and 500 mg thrice daily afterwards	3 months	Rotterdam criteria, ESHRE/ASRM 2003	Presence of PCOS	Diabetes mellitus; use of medications affecting glucose metabolism; Use hormonal analogues other than progesterone; Severe hepatic or kidney diseases; active peptic ulcer
Oner and Muderris 2011 [18]	March 2008–April 2009	Turkey	NAC: 1800 mg/day, orally divided in three doses; metformin: 1500 mg/day, orally divided in three doses	6 months	Rotterdam criteria, ESHRE/ASRM 2004	Presence of PCOS	Diabetes mellitus; thyroid disease; Use of any drugs that could interfere with the normal function of the hypothalamic-pituitary-gonadal axis
Salehpour et al. 2012 [19]	Jan 2008–Dec 2009	Iran	NAC: 1200 mg/day, divided into two daily doses; Placebo: ORS, divided into two daily doses	3 months	Rotterdam criteria, ESHRE/ASRM 2004	Presence of PCOS; Age 20–35 years; Infertility duration less than 10 years; BMI <35 kg/m^2; Normal semen analysis	Thyroid dysfunction; History of large ovarian cyst formation (>6 cm); History of visual disturbance caused by CC; History of asthma and or allergy to medications; Use of medications affecting glucose metabolism; Use hormonal analogues other than progesterone;
Among women with clomiphene resistant polycystic ovary syndrome
Rizk et al. 2005 [20]	March 2002–Nov 2003	Egypt	NAC:		Other	Presence of CC resistant PCOS; Age 18–39 years	Thyroid disfunction; Allergy to medications; Use of medications affecting glucose metabolism; Use hormonal analogues other than progesterone;
Elnashar et al. 2007 [14]	Dec 2004–Dec 2005	Egypt	NAC: 1800 mg/day, orally divided in three doses; Metformin: 1500 mg/day, orally divided in three doses	2 months	Rotterdam criteria, ESHRE/ASRM 2003	Presence of CC resistant PCOS; Age 18–39 years; Period of infertility >2 years	History of pelvic surgery or infertility factor other than anovulation; Patients with hyperglycemia (fasting blood sugar of <100 mg/dL)
Hashim et al. 2010 [21]	Jan 2005–June 2009	Egypt	NAC: 1800 mg/day, orally divided in three doses; Metformin: 1500 mg/day, orally divided in three doses	3 Months	Rotterdam criteria, ESHRE/ASRM 2003	Presence of CC resistant PCOS	Diabetes mellitus; Use of medications affecting glucose metabolism; Use hormonal analogues other than progesterone; Smoking & alcohol use; Age more than 40 years
Nasr 2010 [22]	April 2007–June 2009	Egypt	NAC: 1200 mg/day, divided into two daily doses; Placebo: ORS, divided into two daily doses	12 months	Rotterdam criteria, ESHRE/ASRM 2003	Presence of CC resistant PCOS; Age 18–38 years; >2 years with infertility; Patent fallopian tubes & Normal semen analysis	Use hormonal analogues other than progesterone; contraindications to laparoscopy or general anaesthesia

Note: All the studies were carried out in single center within academic medical centers. Rotterdam European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine-sponsored PCOS Consensus Workshop, that is, the presence of at least two of the following three criteria: (1) oligo- or anovulation, (2) clinical and/or chemical signs of hyperandrogenism, and/or (3) polycystic ovaries; and exclusion of other aetiologies such as congenital adrenal hyperplasia, Cushing’s syndrome or androgen-secreting tumours. Clomiphene Citrate (CC) resistant was defined as 100 mg CC daily for 5 days per cycle for at least three cycles for persistent anovulation in Rizk et al. 2005 [20] and 150 mg CC daily for 5 days per cycle for at least three cycles for persistent anovulation in other studies. Gayatri et al. 2010 [28] used 50 mg/day of CC from day 2 to 6 and gradual increment in next cycle by 50 mg/day with maximum up to 150 mg/day. None of the included studies were funded by commercial funding agencies like Pharmaceutical Industries. However, drugs for the studies were provided by the Pharmaceutical Companies. All the women were asked to have normal life-style and eating habit during the study.