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Licensed Unlicensed Requires Authentication Published by De Gruyter November 19, 2020

N-acetyl-cysteine as adjuvant therapy in female infertility: a systematic review and meta-analysis

Nagita Devi, Chandrasekhar Boya, Manik Chhabra ORCID logo and Dipika Bansal



The objective of this study is to explore the efficacy and safety of N-acetyl-cysteine (NAC) as adjuvant therapy in female infertility.


We performed a systematic literature search of PubMed, Cochrane Library, Embase, and Ovid databases through April 2019 for Randomized Controlled Trials (RCTs) evaluating the effectiveness and safety of NAC as adjuvant therapy in female infertility. The outcomes assessed were rates of ovulation, pregnancy, miscarriage and multiple pregnancy, presented as pooled odds ratio with 95% confidence interval (CI) using the random-effects model. Heterogeneity and inconsistency of the measurements were identified through Cochrane’s Q statistic and I2 statistic. We also performed a sensitivity analysis, publication bias (using funnel plot and Begg’s test), and subgroup analysis.


Fifteen RCTs recruiting 2330 female receiving NAC were included. The pooled estimate showed the statistically insignificant improvement in outcomes; clinical pregnancy rate 1.55 (95% CI 0.98–2.47; I2=68%; p<0.01), ovulation rate 1.77 (95% CI 0.76–4.14; I2=90%; p<0.01), multiple pregnancy rate 0.83 (95% CI 0.34–1.99; I2=10%; p=0.31) and miscarriage rate 0.76 (95% CI= 0.37, 1.53; I2=0%; p=0.69) . NAC was found less efficacious and safe than metformin in all outcomes. Overall, NAC showed statistically insignificant (OR=0.98–2.47).


NAC can be an effective adjuvant in PCOS related and unexplained female infertility. The effect could be more profound in women with high BMI, insulin resistance, and oxidative stress. However, the findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in more extended follow-up periods.

Corresponding author: Dipika Bansal, Pharmacy Practice, National Institute of Pharmaceutical Education and Research, SAS Nagar, India, E-mail:

  1. Research funding: None funded.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2020-05-01
Accepted: 2020-08-22
Published Online: 2020-11-19

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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