Efficacy of Lingji Formula in the Treatment of Male Infertility in Obese Men: Study Protocol for a Randomized Controlled Trial

Hao Wang, Hongyuan Chang, Wenguang Zhou, Yongqing Zhao, Jiwei Zhang, Di Sun Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiwei Zhang, Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China, Email [email protected] Di Sun, Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of China, Email [email protected]: The incidence of male infertility is rising, with obesity being a significant-contributing factor. Studies showed that obese men often have lower sperm concentration and motility. Levocarnitine oral solution has been supported by guidelines and expert consensus in China. However, this treatment has limited efficacy and potential side effects, creating a need for new therapeutic options. Traditional Chinese Medicine (TCM) offers a multi-target approach that may improve both semen quality and obesity. Lingji formula is based on the classical TCM formula named Erjing Pill in Song Dynasty of ancient China. Lingji formula has been developed to treat male infertility in obese men by tonifying the kidney and eliminating dampness from the perspective of TCM. However, there is a lack of clinical trials on TCM interventions in male infertility of obese men.Methods: This study protocol outlines a 1:1 randomized controlled trial that will enroll 78 participants diagnosed with male infertility, oligoasthenozoospermia, and obesity. Participants will be randomly assigned to a treatment group or a control group. The treatment group will receive the Lingji formula, while the control group will receive Levocarnitine oral solution for a duration of 12 weeks. The primary outcome measure is the total progressive motile sperm count at week 12. Secondary outcomes include routine semen indicators, pregnancy rate, Body Mass Index (BMI), waist-to-hip ratio, lipid-related indicators, and Traditional Chinese Medicine symptom scores, which will be assessed at baseline and at weeks 4, 8, and 12.Results: The findings of this trial will fill a research gap in the use of TCM for treating male infertility in obese men and provide important clinical evidence for the application of TCM in managing obesity-related male reproductive disorders.Conclusion: This study aims to provide the first clinical evidence on the efficacy and safety of the Lingji formula for treating obesity-associated male infertility. The research findings will provide significant clinical evidence for the use of TCM in regulating fertility in obese men. The study has been registered with the http://itmctr.ccebtcm.org.cn (ITMCTR number is ITMCTR2025001503). Registration Date: July 28, 2025.Keywords: obese men, Lingji formula, protocol, male infertility, sperm