Linggui Yangyuan paste for patients with male infertility: a study protocol for a multicenter, double-blind, double-dummy, randomized controlled trial

Male infertility affects millions of men worldwide and is increasing in prevalence, with asthenozoospermia (AS) and oligoasthenozoospermia (OA) being the most frequent causes, and current treatments are limited. A previous research reported that Linggui Yangyuan paste (LGYY) enhanced sperm viability and motility, but there is a lack of multicenter, rigorous, randomized and controlled studies on its efficacy. Wuzi Yanzong oral solution (WZYZ), a traditional Chinese herbal formula, is one of the most important and first-line drugs for AS and OA in China. We designed a direct comparison of LGYY's effectiveness and safety against WZYZ in treating male infertility, specifically AS and OA. We propose a multicenter, double-blind, double-dummy, randomized controlled trial, which is planned to recruit 162 participants with AS or OA from five centers and will randomize them into two groups, whereby the treatment group will receive intervention with LGYY and WZYZ mimetics, while the control group will receive intervention with WZYZ and LGYY mimetics. The medications will be administered twice daily for 12 weeks, followed by a 12-week follow-up. The primary outcome will be total progressive motile sperm count (TPMSC), and the secondary outcomes will be semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility (PR), PR + nonprogressive motility (NP), Chinese Medicine Symptoms Score (CMSS), spouse pregnancy rate and time to pregnancy. The safety outcomes will be based on the results of routine blood and urine tests, liver and kidney function tests and electrocardiography. Overall, this study aims to provide valuable insights into the potential efficacy and safety of LGYY compared to WZYZ for male infertility (AS or OA), which could guide clinicians to an alternative drug approach to treat patients with AS or OA. This clinical trial is registered at ClinicalTrials.org under the identifier NCT05792813.