Herbal therapeutics for female infertility: A systematic review and meta-analysis

Infertility is a global public health issue related to gynecological diseases and psychological disorders such as stress, depression, and fatigue. Prescriptions of various herbs in traditional East Asian medicine (TEAM) have recently gained attention among patients as a complementary alternative therapy for female infertility. However, studies on systemic analysis of the use of herbal medicines according to TEAM patterns or the therapeutic effects of herbal medicines on female infertility are limited. We aimed to systematically investigate the single herb and TEAM patterns that are commonly used for treating female infertility using network analysis. Additionally, we performed a meta-analysis to assess the effect of herbal medicine on the pregnancy rate in women with infertility. PubMed, EMBASE, Korean Studies Information Service System, Science ON, Research Information Sharing Service, and Oriental Medicine Advanced Searching Integrated System were searched for randomized controlled trials (RCTs) reporting the pregnancy rate of herbal medicine for infertility until July 2021. Following identifying the top three herbs used in treating female infertility, a network analysis was performed to reveal the TEAM pattern relationships between each herb. A meta-analysis was performed to evaluate the therapeutic effect of herbal medicine on pregnancy rate. Moreover, the methodological quality of RCTs was analyzed using Consolidated Standards of Reporting Trials (CONSORT) extension guidelines and the Risk of bias (RoB) tool. Eighteen RCTs with 2,662 participants were included. Cuscuta chinensis Lam. (Tusizi) is the most commonly used herb for treating female infertility, followed by Angelica gigas Nakai (Danggui) and Cyperus rotundus L. (Xiangfuzi). These herbs were mainly used to treat patients with kidney deficiency or kidney deficiency combined with blood stasis or Phlegm-dampness on the TEAM pattern. The meta-analysis revealed that the effect of herbal medicine led to a significant increase in pregnancy rates compared to the placebo treatment. Adverse events in the included studies were generally mild and infrequent. The methodological quality of RCTs using CONSORT extension was poor, while the RoB of the included RCTs was generally low. The findings of this review suggest that herbal medicine will be beneficial for treating female infertility by improving pregnancy rates. However, more carefully designed studies on herbal medicines are encouraged to improve the quality of herbal medicine research in the future.