Effectiveness Of Bushen Tongzhi Formula Pretreatment On Pregnancy Outcomes In Infertile Women With Diminished Ovarian Reserve Undergoing In Vitro Fertilization And Embryo Transfer: Study Protocol For A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial (PRIME Study)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 348
- 试验地点
- 1
- 主要终点
- Cumulative clinical pregnancy rate from a single oocyte retrieval cycle
研究概览
简要总结
The goal of this clinical trial is to learn if a traditional Chinese herbal pretreatment can improve pregnancy outcomes in infertile women with diminished ovarian reserve (DOR) who are undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The main question it aims to answer is:
• Does pretreatment with the Bushen Tongzhi Formula increase the cumulative clinical pregnancy rate from a single egg retrieval cycle compared to a placebo?
Researchers will compare the group taking the herbal formula to the group taking a placebo to see if the herbal formula is more effective.
Participants will:
- Take the assigned study medication (herbal formula or placebo) three times daily for 3 months before starting IVF/ICSI.
- Continue taking the medication during their IVF/ICSI treatment cycle, for up to 6 months total.
- Undergo standard IVF/ICSI procedures as planned by their doctor.
- Have their pregnancy outcomes and health monitored through clinic visits and their medical records.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled, superiority clinical trial. The study aims to evaluate the efficacy and safety of a standardized traditional Chinese medicine (TCM) formula, the "Bushen Tongzhi Formula" (also referred to as the "Xiehe DOR Bushen Tongzhi Formula"), as a pretreatment and adjuvant therapy in infertile women with Diminished Ovarian Reserve (DOR) undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
Background DOR, characterized by a reduced quantity and/or quality of oocytes, presents a significant challenge in assisted reproductive technology (ART), often leading to poor ovarian response, fewer retrievable oocytes, and lower pregnancy rates. While controlled ovarian stimulation protocols continue to evolve, there remains a critical need for interventions that can improve ovarian function and oocyte quality prior to ART cycles. TCM, guided by the theory of "the kidney governing reproduction," offers a potential approach by addressing the root pattern of "kidney essence deficiency," which is central to DOR in TCM diagnostics. Preliminary observations of the Bushen Tongzhi Formula have suggested potential benefits, but robust evidence from large-scale, rigorously designed trials is lacking.
Study Population The study will enroll 348 infertile female participants, aged 22 to 39 years, diagnosed with DOR according to standardized criteria (requiring at least two of the following: baseline FSH 10-25 IU/L, AMH <1.1 ng/mL, or antral follicle count <7). All participants must also meet TCM diagnostic criteria for Kidney Deficiency pattern and be planning to undergo a fresh IVF/ICSI cycle. Key exclusions include significant uterine abnormalities, known chromosomal disorders, severe medical or psychiatric conditions, active genital infections, advanced endometriosis, plans for donor egg or PGT cycles, and a history of multiple prior IVF failures.
Interventions Eligible participants will be randomly assigned in a 1:1 ratio via a centralized interactive web response system (IWRS), stratified by study site and age.
Experimental Group: Participants will take the Bushen Tongzhi Formula granules (20g, three times daily) for a 3-month pretreatment phase. Upon starting their standardized IVF/ICSI protocol, they will continue the herbal medication concurrently for up to an additional 3 months, stopping upon confirmation of clinical pregnancy. The maximum total treatment duration is 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The data manager and the statistician performing the interim and primary analyses are also masked to group assignment until after the database is locked for the final analysis. This ensures blinding is maintained throughout the data processing and analysis phases to prevent bias.
入排标准
- 年龄范围
- 22 Years 至 39 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 22 to 39 years (inclusive).
- •Diagnosis of diminished ovarian reserve (DOR), defined by meeting at least two of the following three criteria: 1, Basal follicle-stimulating hormone (FSH) level between 10 and 25 IU/L (measured on menstrual cycle days 2-4); 2, Anti-Müllerian hormone (AMH) level < 1.1 ng/mL; 3, Antral follicle count (AFC) < 7 (total count of follicles 2-10 mm in diameter in both ovaries).
- •Diagnosis of infertility, defined as failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.
- •Diagnosis of Kidney Deficiency pattern according to Traditional Chinese Medicine criteria, as defined in the study protocol.
- •Scheduled to undergo a fresh in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle.
- •Willing and able to provide written informed consent.
排除标准
- •Uterine structural abnormalities likely to impair implantation or pregnancy (e.g., untreated submucosal fibroids, severe intrauterine adhesions, uterine septum).
- •Known abnormal karyotype in either partner.
- •Uncontrolled or severe medical conditions (e.g., hypertension, diabetes, thyroid dysfunction, hepatic/renal insufficiency, symptomatic heart disease).
- •Diagnosed severe psychiatric disorders (e.g., schizophrenia, bipolar disorder).
- •History of prior pelvic radiation or cytotoxic chemotherapy.
- •Active genital tract infection.
- •Diagnosed or suspected severe (ASRM stage III-IV) endometriosis with recurrent symptoms.
- •Planned use of donor oocytes or preimplantation genetic testing (PGT).
- •History of repeated IVF/ICSI failure (≥3 failed egg retrieval cycles or ≥3 failed transfers of high-quality embryos).
- •Known allergy to any component of the investigational herbal formula.
- •Participation in another clinical trial within the past 3 months.
- •Use of medications known to affect ovarian function (e.g., DHEA, growth hormone) within the past month.
- •Current heavy alcohol consumption or smoking.
- •Any other condition deemed by the investigator to make the participant unsuitable for the study.
研究组 & 干预措施
Bushen Tongzhi Formula Pretreatment plus Standard IVF/ICSI
Intervention: Participants in this arm receive the investigational treatment, which consists of oral administration of the Bushen Tongzhi Formula granules combined with a standard IVF/ICSI protocol.
Details:
Medication: "Bushen Tongzhi Formula" herbal granules (20g per dose).
Dosage & Administration: 20g (one sachet), taken orally three times daily after meals.
Treatment Regimen: The intervention includes a 3-month pretreatment phase prior to the start of ovarian stimulation. Participants continue taking the medication concurrently throughout their subsequent IVF/ICSI treatment cycle (including during gonadotropin stimulation and until pregnancy confirmation). The maximum total treatment duration is 6 months, stopping upon confirmation of clinical pregnancy.
Concurrent Procedure: All participants undergo a standard, clinic-determined controlled ovarian stimulation protocol for IVF or ICSI, followed by egg retrieval, embryo culture, and fresh or frozen-thawed embryo transfer.
干预措施: Bushen Tongzhi Formula (Drug)
Placebo Pretreatment plus Standard IVF/ICSI
Intervention: Participants in this arm receive the control treatment, consisting of an oral placebo combined with a standard IVF/ICSI protocol.
Details:
Medication: Matched placebo granules. These contain no active herbal ingredients and are formulated from inert materials (e.g., dextrin, food-grade flavorings/colorants) to precisely mimic the appearance, taste, smell, and packaging of the active Bushen Tongzhi Formula granules.
Dosage & Administration: 20g (one sachet), taken orally three times daily after meals.
Treatment Regimen: The regimen is identical to the experimental arm: a 3-month pretreatment phase, followed by continued placebo intake concurrently throughout the subsequent IVF/ICSI treatment cycle. The maximum total duration is 6 months, with medication stopping upon confirmation of clinical pregnancy.
Concurrent Procedure: Participants undergo the same standard, clinic-directed IVF/ICSI procedures.
干预措施: Placebo Pretreatment plus Standard IVF/ICSI (Drug)
结局指标
主要结局
Cumulative clinical pregnancy rate from a single oocyte retrieval cycle
时间窗: From randomization until 12 months after the oocyte retrieval procedure.
This outcome measures the proportion of participants in each treatment group who achieve a clinical pregnancy resulting from a single oocyte retrieval procedure. A clinical pregnancy is defined as the ultrasound confirmation of an intrauterine gestational sac with cardiac activity. The rate is "cumulative" because it includes pregnancies achieved from both the initial fresh embryo transfer and any subsequent frozen-thawed embryo transfer(s) utilizing all embryos derived from that single retrieval cycle. Data will be collected until no embryos from the index cycle remain for transfer or a clinical pregnancy is confirmed.
次要结局
未报告次要终点