Publication:

Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial

Background Polycystic ovarian disease (PCOD), a common endocrine disorder with multisystem affection, is the most common cause of anovulatory infertility. Our objective is to evaluate the effect of using clomiphene citrate (CC) plus N-acetyl cysteine (NAC) versus letrozole in ovulation induction in infertile patients with PCOD.

Methods Reproductive-aged infertile women either primary or secondary diagnosed as PCOD according to Rotterdam criteria, 2003 were considered for enrollment. Eligible women for were recruited and randomized (1:1) to receive either CC 100 mg plus NAC 600 mg (CC+NAC arm) or letrozole 5 mg (NCT03241472, clinicaltrials.gov). All medications were started from day 3 of the menstrual cycle for 5 days. The primary outcome was the ovulation rate in both groups. Secondary outcomes included the mid-cyclic endometrial thickness, ovarian hyperstimulation, and clinical pregnancy and miscarriage rates.

Results One hundred ten patients were enrolled and randomized to CC+NAC arm (n=55) or letrozole (n=55). The ovulation rate in patients in letrozole arm was significantly higher than CC+NAC arm (71.8% versus 53.2%, p=0.01). Additionally, endometrial thickness was higher in letrozole arm (mean±SD: 11.46±1.61 versus 9.0±1.13, p=0.031). However, no statistical significant difference with regarding the ovarian hyperstimulation rate (1.8% versus 3.6%, p=0.157), clinical pregnancy rate [3/19 patients (27.3%) versus 19/55 (34.5%), p=0.409] and miscarriage rate [4/15 patients (26.7%) versus 19/55 (15.8%), p=0.317] in CC+NAC versus letrozole groups respectively.

Conclusions Addition of NAC to CC in ovulation induction leads to comparable pregnancy rate as letrozole. However, letrozole produces high ovulation rate and the better mid-cyclic endometrial thickness.