The objectives of the present trial are to test the following three hypotheses in anovulatory women with PCOS: 1. Acupuncture protocol 1 plus CC (Arm A) is more likely to result in live birth than acupuncture protocol 2 combined with CC (Arm B), 2. Acupuncture protocol 2 plus CC (Arm B) is more likely to result in live birth than acupuncture protocol 1 plus placebo (Arm C), 3. Acupuncture protocol 1 plus placebo (Arm C) is more likely to result in live birth than acupuncture protocol 2 plus placebo (Arm D).
This is a multicenter, randomized, controlled, 2 by 2 factorial clinical trial for Chinese women with PCOS. Primary outcomes: \- Live birth rate Secondary outcomes: * Ovulation rate * Ongoing pregnancy rate * Multiple pregnancy rate * Miscarriage rate * Hormonal profile * Metabolic profile * Side effect profile
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,000
Two sets of acupuncture points will be alternated every second treatment. The first set consists of CV3, CV 6, and ST 29 bilaterally,SP 6 and SP 9 bilaterally. Needles will also be placed in LI bilaterally and GV 20. CV 3, CV 6, ST 29, SP 6, and SP 9 will be connected to and electrical stimulator and stimulated with low-frequency EA of 2Hz, 0.3 ms.
Needles will be inserted to a depth of \<5 mm, one in each shoulder and on in each upper arm at non-acupuncture points. Electrodes will be attached to the needles and the stimulator will be turned on at an intensity of zero (no active current) in order to mimic EA in the acupuncture treatment 1. No manual stimulation of the needles will be performed.
CC 50 mg every day for 5 days (day 3-7 of cycle), for a total of 4 cycles. Non-response will be defined after 4 weeks of CC placebo administration with 3 consecutive weekly negative P4 and hCG levels. Then during the fifth week a higher dose consisting of one more tablet per day (up to 3 tablets per day at third or fourth cycles, if they remain non-responders) will be given 5 days.
CC placebo 50 mg every day for 5 days (day 3-7 of cycle), for a total of 4 cycles. Non-response will be defined after 4 weeks of CC Placebo administration with 3 consecutive weekly negative P4 and hCG levels. Then during the fifth week a higher dose consisting of one more tablet per day (up to 3 tablets per day at third or fourth cycles, if they remain non-responders) will be given 5 days.
First Affiliated Hospital,Anhui University of Chinese Medicine
Hefei, Anhui, China
First Affiliated Hospital,Guangzhou University of Chinese Medicine
Guangzhou, Guangdong, China
Guangzhou Liwan Chinese Hospital
Guangzhou, Guangdong, China
Guangdong Chinese Hospital
Guangzhou, Guangdong, China
Daqing LongNa Hospital
Daqing, Heilongjiang, China
The Daqing Oilfield General Hospital
Daqing, Heilongjiang, China
Forth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, China
Second Affiliated Hospital,Heilongjiang University of Chinese Medicine
Harbin, Heilongjiang, China
First Affiliated Hospital,Heilongjiang University of Chinese Medicine
Harbin, Heilongjiang, China
Henan Chinese Medicine Hospital
Zhengzhou, Henan, China
...and 15 more locations
Live birth rate
Time frame: Up to 3 years
Ovulation rate
Time frame: Up to 3 years
Ongoing pregnancy rate
Up to 3 years
Time frame: Aprial 2012 to July 2014 (up to 3 years)
Multiple pregnancy rate
Time frame: Up to 2 years
Miscarriage rate
loss of an intrauterine pregnancy before 20 completed weeks of gestation.
Time frame: Up to 2 years
Hormonal profile
Hormonal profile include: Testosterone(T), Sex hormone-binding globulin (SHBG), Follicle stimulating hormone (FSH),Luteinizing hormone(LH),and Dehydroepiandrosterone sulfate (DHEAS).
Time frame: Up to 2 years
Metabolic profile
Metabolic profile includes: Serum glucose concentration, Insulin concentration, cholesterol, Triglycerides (TG), High density lipoprotein cholesterol (HDL-C) and Low density lipoprotein cholesterol (LDL-C)
Time frame: Up to 2 years
Side effect profile
Side effects of CC include hot flashes, mood changes, bloating, formation of ovarian cysts, and pain, extremely rare are pituitary apoplexy and deep venous thrombosis. The major side effects of acupuncture are local skin irritation, discomfort, and vasovagal reactions during the procedure. All above mentioned side effects will be recorded weekly.
Time frame: Up to 2 years
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