Linggui Yangyuan Paste for Male Infertility with Shen (Kidney) Deficiency and Blood Stasis Syndrome: A Multicenter,...

To evaluate the efficacy and safety of Linggui Yangyuan Paste (LG) in treating male infertility caused by asthenozoospermia (AZS) and oligoasthenozoospermia (OAZS) associated with the Chinese medicine (CM) pattern of Shen (Kidney) deficiency and blood stasis.

This randomized, double-blind, double-dummy, parallel-group, multicenter clinical trial enrolled 162 male infertility patients at 5 hospitals in China from June 2023 to February 2024. Using block randomization within strata, participants were assigned (1:1) to LG + Wuzi Yanzong Oral Solution (WZ) placebo or WZ + LG placebo for 12 weeks (each LG 1 sachet and WZ 1 vial, twice daily), with a 12-week follow-up. The primary outcome was the change in total progressive motile sperm count (TPMSC) from baseline to week 12. Secondary outcomes included pregnancy rate, CM symptom score (CMSS), and semen parameters including semen volume (SV), sperm concentration (SC), total sperm count (TSC), progressive motility (PR), and PR + non-progressive motility (NP). Prespecified subgroup analyses on cumulative pregnancy rate and semen parameters were performed for participants with AZS and OAZS. Safety was monitored throughout the trial.

Of 162 randomized participants, 145 completed the trial (75 in the LG group and 70 in the WZ group) and were included in the per-protocol analysis. At week 12, the LG group showed significantly greater improvement in TPMSC compared to the WZ group, with an adjusted between-group difference of 8.81 × 10⁶ sperm (P<0.05, 95% confidence interval 2.75-14.87). The cumulative pregnancy rate at week 24 was significantly higher in the LG group than the WZ group [24.0% (18/75) vs. 10.0% (7/70), P<0.05)]. CMSS decreased significantly in both groups, with greater reduction in the LG group (P<0.05). Subgroup analysis showed that cumulative pregnancy rates were higher in the LG group than in the WZ group in the AZS subgroup at both weeks 12 and 24 (both P<0.05). In the AZS subgroup analysis, PR and PR+NP showed significantly greater improvements in the LG group (P<0.05). In the OAZS subgroup, SV, SC, TSC, PR, and PR+NP all showed greater improvements in the LG group (P<0.05). No adverse events or adverse drug reactions were reported in either group.

LG demonstrates significant efficacy and safety in treating male infertility associated with Shen deficiency and blood stasis syndrome, supporting its clinical application as an integrative therapy for male infertility. (Registration No. ITMCTR2023000009).