Kidney-Tonifying Chinese Herbal Therapy Before and During Letrozole Ovarian Stimulation for Infertility Associated With Diminished Ovarian Reserve: A Multicenter Randomized Trial Protocol

Background: Diminished ovarian reserve (DOR) is a leading cause of female infertility, with an increasing prevalence and a younger age at onset. Traditional Chinese medicine (TCM), based on the theory that ‘the kidney governs reproduction’, shows potential for improving ovarian function, but evidence remains limited by small sample sizes and inadequate blinding.Methods: This randomized, double-blind, placebo-controlled superiority trial will be conducted at 18 centers in China and will enroll 320 eligible women aged 22–39 years. Participants will be randomized in a 1:1 ratio to receive either Xiehe DOR Kidney-Tonifying Formula granules or matched placebo granules. During the first 3 months, participants will receive only the assigned granules. Participants who remain nonpregnant after the first 3 months will continue to receive the assigned granules and will additionally receive letrozole for three cycles.Results: The primary outcome is the cumulative clinical pregnancy rate within 6 months after randomization, as confirmed by transvaginal ultrasonography. Secondary outcomes include ovulation, biochemical pregnancy, live birth, and miscarriage rates; ovarian reserve markers (anti-Müllerian hormone, follicle-stimulating hormone, and antral follicle count); TCM syndrome and quality-of-life scores; and safety outcomes. The primary analysis will follow the intention-to-treat principle.Conclusions: This trial is expected to provide rigorous evidence on the efficacy and safety of TCM for DOR-associated infertility and to inform the development of an integrative treatment strategy.Clinical Trial Registration: ClinicalTrials.gov (NCT07296614) and the International Traditional Medicine Clinical Trial Registry (ITMCTR2026000661).