This study is to evaluate the effectiveness and safety of Bushen Culuan Decoction in the treatment of anovulatory infertility, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency and ovarian insufficiency, through a randomised, double-blinded, double-dummy, parallel positive controlled, adaptive multicenter clinical trial.
Anovulation is one of the main causes of female infertility. Anovulatory infertility account for a proportion of 25-30% in whole female infertility. In western medicine, hormone induced ovulation and assisted reproduction technology are two main ways to solve the problem and Clomiphene citrate is the first-line medication in ovulation induction. There are many side effects being reported in the treatment with modern medicine technique such as ovarian hyperstimulation syndrome, complication with uteroscope and puncture egg retrieval, low pregnancy rate with high ovulation rate, potential cancer occuring risk and offspring healthy risk. Bushen Culuan Decoction is a traditional Chinese medicine recipe with 10 Chinese herbs including Tusizi, Yinyanghuo, Xianmao, Xuduan, Gouqizi, Nvzhenzi, Zelan, Shengpuhuang, Xiangfu and Chuanshanlong. Previous laboratory and exploratory clinical researches have proved Bushen Culuan Decoction had an exactly efficacy in treating anovulatory infertility safely. In the first stage, the primary sample size In the study is 528. Half patients will receive Bushen Culuan Decoction and clomiphene citrate placebo, while the other half will receive clomiphene citrate tablets and Bushen Culuan Decoction placebo. When 1/3 of 528 patients complete the treatment, we will analysis the treatment efficacy of 6 diseases separately, and find which of them could be the target diseases of Bushen Culuan Decoction. Then we will modify the sample size depending on the result in first stage, and the research will only be processed in the target diseases being chosen. In the next stage, half patients will receive Bushen Culuan Decoction and clomiphene citrate placebo, while the other half will receive clomiphene citrate tablets and Bushen Culuan Decoction placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
528
the same as group description including dosage, frequency and duration
the same as group description including dosage, frequency and duration
Pregnancy Rate
Time frame: Within 12 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Ovulation Rate
If the patient participate 1 treatment cycle, the ovulation will be measured 3 menstrual cycles, and if the patient participate 2 treatment cycle, the ovulation will be measured 6 menstrual cycles.
Time frame: At every ovulation phase (about day14 in a period cycle) within 3 or 6 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Basal Body Temperature
Time frame: At every morning within 3 or 6 menstrual cycles from the first time that patient taking medicines to the end of the treatment. (Each cycle is 28 days)
Endocrine Hormone
Including Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin (PRL), Estradiol (E2), Progesterone(P), Testosterone (T).
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Inhibin B
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Anti-Mullerian Hormone (AMH)
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Antral Follicle Count
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Volume of Uterus and Bilateral Ovaries at the Early Follicle Phase
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Thickness of Endometrium at the Early Follicle Phase
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Type of Endometrium at the Early Follicle Phase
The type of endometrium is measured by ultrasound. The type of endometrium contains type A, B, and C. Type A means the endometrium thickness is about 4-9mm, and there is a "trilaminar patterns" in the image. Type B means the endometrium thickness is about 9-12mm, the image shows moderate homogeneous echo. Type C means the endometrium thickness is about 10-14mm with a strong homogeneous echo. The type only represents different forms of endometrium, but not represents endometrium level or grade.
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
the Size of Dominant Follicle
Time frame: At every ovulation phase (about day14 in a period cycle) within 3 or 6 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Peak-Systolic Flow Velocity of Uterus and Bilateral Ovaries
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Pulsatility Index of Uterus and Bilateral Ovaries
Pulsatility Index (PI) of Uterus and Bilateral Ovaries is the pulsatility index of uterine arteries and bilateral ovarial arteries. The normal range of uterine PI has no unified standard, but the smaller the index is, the better the endometrial receptivity is. Generally, when uterine PI\<2, the endometrial receptivity will be good enough to get zygote implantation, and when uterine PI\>3, the endometrial receptivity is too improper to get zygote implantation.
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Resistant Index of Uterus and Bilateral Ovaries
Resistant Index (RI) of Uterus and Bilateral Ovaries is the resistant index of uterine arteries and bilateral ovarial arteries. The normal range of uterine RI has no unified standard, but the smaller the index is, the better the endometrial receptivity is.
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Coagulation Indicator
Including prothrombin time, activated partial thromboplastin time, fibrinogen and thrombin time
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Traditional Chinese Medicine Symptom Score
Traditional Chinese Medicine Symptom Score (point) including: amenorrhea (0-3); delayed menstruation (0-3); scant menstruation (0-3); weakness in lower back, waist and knees (0-3); dizziness and tinnitus (0-3); sexual apathy (0-3); fatigue (0-3); colorless transparent urination(0-3); frequent urination at night (0-3); feeling obstruction with menstruation (0-3); profuse menstruation with dark color (0-3); clot in menstruation (0-3); stabbing pain in lower abdomen area, may aggravating with sexual intercourse (0-3); dysmenorrhea (0-3) The total score will be measured by summing the subitems' score above, and the total score range is 0-42. The higher the score is, the worse the situation is.
Time frame: At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.