Is addition of N-Acetyl Cysteine to Clomiphene Citrate Beneficial for Ovulation Induction in Anovulatory Infertility?

Abstract

Background: Anovulation is the major cause of infertility; seen in around 15% of infertile couples and in 40% of women with infertility. Clomiphene citrate has been the gold standard drug for ovulation induction in anovulatory infertility. However, as a singular drug it is not equally effective in all situations. The introduction of an anti-oxidant, N- acetyl cysteine to ovarian stimulation has proven to have many benefits. Objective: To compare the efficacy of combination of clomiphene citrate with N-acetyl cysteine vs clomiphene citrate alone for augmenting ovulation in anovulatory infertility cases. Materials and Method: 117 cases of primary and secondary infertility with anovulation were taken after ruling out other causes of infertility. Patency of bilateral fallopian tubes were confirmed by hysterosalphingography or laparoscopic chromopertubation or sonosalphingography. Their male partners were confirmed to have adequate seminal parameters according to WHO guidelines. Cases were randomized into two groups. Starting on day 3 of menstrual cycle, group CC-NAC (56 patients) were given tablet clomiphene citrate 100mg/day and tablet N-acetyl cysteine 1200mg/day orally and group CC (61patients) were given tablet clomiphene citrate alone 100mg/day for 5 days. Transvaginal ultrasound on day 14th- 16th of the cycle were done for follow up. Advice for timed intercourse daily around the time of ovulation was given. Main outcomes like number and size of growing follicles, endometrial thickness, ovulation rate and pregnancy rate were compared. Results: Ovulation and conception rate were higher in CC-NAC group (96.42%;72.22%) than with CC group (90.16%; 34.54%); (p=0.23; p<0.01 respectively). Endometrial thickness was found to be higher in CC-NAC group (12.19 ± 1.36mm) as compared to CC group (10.17 ± 1.01mm). Clinical pregnancy rate was 94.87% in the combination group which was statistically higher than in CC group (78.94%); p< <0.001. with addition of NAC, lesser cases of multiple pregnancy and miscarriage rates (12.82%; 5.12%) than in CC group (31.57%; 21.05%); = 0.06. However, our study was limited to 3 treatment cycles. No cases of ovarian hyperstimulation were reported. Conclusion: N-acetyl cysteine may be a novel adjuvant to clomiphene citrate, more effective than clomiphene citrate alone in inducing and augmenting ovulation. It could be used as an alternative to other insulin sensitizing agents like metformin. The Spearman’s Rank correlation analysis were done which show highly positive correlation (ρ=0.8) between clomiphene citrate – N-acetyl cysteine and number of pregnancies and weak correlation (ρ<0.1) between clomiphene citrate and number of pregnancies in our study. The outcome in terms of number of pregnancies