Zishen Yutai Pill increased live births in advanced maternal age women: a randomized clinical trial

Advanced maternal age (AMA, ≥35 years) women undergoing assisted reproductive technology (ART) face reduced live birth rates (LBR) and remain a major clinical challenge. In a large randomized trial, Zishen Yutai Pill (ZYP) improved LBR in the general population, and a subsequent post hoc analysis suggested efficacy in AMA women, though it was underpowered to draw firm conclusions. To address the issue, we conducted a multicenter, prospective, double-blind, placebo-controlled, randomized trial (NCT03703700) to evaluate whether ZYP increases LBR in AMA women. Women aged 35-42 years with BMI < 28 kg/m² at 12 tertiary-level hospitals in China were randomly assigned to receive ZYP or placebo orally (5 g once, three times daily) from day 19-23 of the preceding menstrual cycle until 2 weeks after embryo transfer, continuing to 5 weeks post transfer if biochemical pregnancy was confirmed. The primary outcome was fresh-cycle LBR. A total of 1467 participants (734 ZYP, 733 placebo) were enrolled. In the intention-to-treat analysis, live birth occurred in 23.3% (171/734) with ZYP vs. 19.0% (139/733) with placebo (relative ratio 1.23 [95% CI, 1.01-1.50]; absolute difference 4.3% [95% CI, 0.2-8.5]; P = 0.042). This study showed that Zishen Yutai Pill increased live birth rates in women aged 35-42 undergoing IVF, without elevating the risk of maternal or neonatal adverse events. (NCT03703700, https://clinicaltrials.gov/study/NCT03703700 ).