Comments on “A Meta-Analysis of the Efficacy of L-Carnitine/L-Acetyl-Carnitine or N-Acetyl-Cysteine in Men with Idiopathic Asthenozoospermia”

Dear editor,

We have recently read with great interest the systematic review and meta-analysis by Guangzhu Wei and colleagues (2021) published in the American Journal of Men’s Health which aims to statistically investigate the efficacy of L-carnitine/L-acetyl-carnitine (LC/LAC) and N-acetyl-cysteine (NAC) in men with idiopathic asthenozoospermia. Although there are various studies in the literature regarding the use of dietary supplements in treating male infertility, the recommendation of L-carnitine in ameliorating idiopathic asthenozoospermia remains controversial. However, three methodological points that could cause scientific confusion require cohesive clarifications in the study by Wei and colleagues (2021).

Point 1: There was no clear expression of the type of data used, for example, changes in the mean and/or standard deviation (SD) or final measurements, and how these data were statistically calculated. Each clinical trial included in the meta-analysis was carefully revised to compare its results with the values used in the forest plots. Most of the included studies reported their values (baseline and final measurements) as mean ±SD. For certain studies, Wei and colleagues (2021) analyzed the net change in mean and SD (subtracting the final measurement from the baseline measurement); however, in other studies, only the final measurement of mean was used. Combining both data (mean of net change and mean of final measurement) in one forest plot is correct because an unstandardized mean difference was performed (Higgins et al., 2021). However, using both types of data without justifying the reason may be a source of statistical bias.

Point 2: One of the included trials in the meta-analysis reported its data as the median instead of the mean (Sigman et al., 2006). However, Wei and colleagues (2021) included the median value with the mean values from other studies in the forest plot. The median is not representative of the mean value and is often used in skewed data. Initially, median must be converted to the mean and then included in the forest plot (Higgins et al., 2021).

Point 3: NAC supplementation improved the sperm volume among infertile men after being compared with the pretreatment status within one group (Jannatifar et al., 2019). However, Wei and colleagues (2021) included pretreatment status values as a control group in the meta-analysis study. Using the pre-post standardized mean difference to indicate the effect of treatment within one group in meta-analysis could probably result in biased outcomes due to the influence of natural process and characteristics of the patients and settings (Cuijpers et al., 2017).