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CompletedNCT01573858PCOSActUpdated Aug 25, 2021

Acupuncture and Clomiphene Citrate on Live Birth in Anovulatory Women With Polycystic Ovary Syndrome

An interventional study of Acupuncture treatment 1 and Acupuncture treatment 2 in Pregnancy, Polycystic Ovary Syndrome and Infertility, sponsored by Heilongjiang University of Chinese Medicine. Completed at 25 sites in China. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2021-08-25.

Sponsored by Heilongjiang University of Chinese Medicine · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
1,000
Allocation
Randomized
Ages
20 Years to 40 Years
Sex
Female
01

Study summary

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).
Read the detailed description

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
02

Conditions studied

  • Pregnancy
  • Polycystic Ovary Syndrome
  • Infertility

Keywords

  • Infertility
  • Polycystic Ovary Syndrome
  • Clomiphene citrate
  • Acupuncture
03

In context

Polycystic Ovary Syndrome

944 studies on the registry are indexed under Polycystic Ovary Syndrome; 174 are open to participants now.

This study's enrollment of 1,000 is above the median of 70 across 685 interventional studies indexed under Polycystic Ovary Syndrome.

Browse Polycystic Ovary Syndrome studies →

Lead sponsor

Heilongjiang University of Chinese Medicine is the lead sponsor of 19 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Eligibility criteria

  1. Inclusion Criteria:

    • Age of women between 20 and 40 years.
    • Confirmed diagnosis of PCOS according to the modified Rotterdam criteria and all subjects must have anovulation plus either polycystic ovaries and/or hyperandro-genism.
    • Patency of at least one tube and a normal uterine cavity shown by hysterosalpingogram, HyCosi or diagnostic laparoscopy.

    • Semen analysis:

      1. a. Sperm concentration ≥15×106/ml and b. total motility (a+b+c) ≥40% or forward motility (a+b) ≥32% in the semen analysis of the husband (based on World Health Organization, 2010).
      2. Total motile sperm count ≥9 million [based on WHO (2010) criteria, volume 1.5 ml; conc 15 million; motility 40%. 1.5 x 15 x 0.04=9 million].

  2. Exclusion Criteria:

    • Exclusion of other endocrine disorders

      • Patients with hyperprolactinemia (defined as two prolactin levels at least one week apart 25 ng/mL or greater or as determined by local normative values). The goal of eliminating patients with documented hyperprolactinemia is to decrease the heterogeneity of the PCOS population. These patients may be candidates for ovulation induction with alternate regimens (dopamine agonists). A normal level within the last year or on treatment is adequate for entry.
      • Patients with FSH levels > 15 mIU/mL. A normal level within the last year is adequate for entry.

    • Patients with uncorrected thyroid disease (defined as TSH \< 0.2 mIU/mL or > 5.5 mIU/mL). A normal level within the last year is adequate for entry.

      • Patients diagnosed with Type I or Type II diabetes who are poorly controlled (defined as a glycohemoglobin level > 7.0%), or patients receiving antidiabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas likely to confound the effects of study medication; patients currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.
      • Patients with suspected Cushing's syndrome.
    • Use of hormonal or other medication including Chinese Herbal prescriptions which may affect the outcome at least in the past 2 months.
    • Pregnancy within the past 6 weeks.
    • Within 6 weeks post-abortion or postpartum.
    • Breastfeeding within the last 6 months.
    • Acupuncture within the last 6 months.
    • Not willing to give written consent to the study.

    • Additional exclusion criteria

      • Patients on oral contraceptives, depot progestins, or hormonal implants (including Implanon). A two month washout period will be required prior to screening for patients on these agents. Longer washouts may be necessary for certain depot contraceptive forms or implants, especially where the implants are still in place. A one-month washout will be required for patients on oral cyclic progestins.
      • Patients with liver disease defined as AST or ALT > 2 times normal or total bilirubin >2.5 mg/dL. Patients with renal disease defined as BUN > 30 mg/dL or serum creatinine> 1.4 mg/dL.
      • Patients with significant anemia (Hemoglobin \< 10 g/dL).
      • Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.
      • Patients with known heart disease that is likely to be exacerbated by pregnancy.
      • Patients with a history of, or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal Pap smear result will be required for women 21 and over.
      • Patients with a current history of alcohol abuse. Alcohol abuse is defined as > 14 drinks/week or binge drinking.
      • Patients enrolled simultaneously into other investigative studies that require medications, proscribe the study medications, limit intercourse, or otherwise prevent compliance with the protocol.
      • Patients who anticipate taking longer than a one month break during the protocol should not be enrolled.
      • Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, GnRH agonists and antagonists, antiandrogens, gonadotropins, anti-obesity drugs, Chinese herbal formula, anti-diabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, ACE inhibitors, and calcium channel blockers. The washout period on all these medications will be two months.
      • Patients with a suspected adrenal or ovarian tumor secreting androgens.
      • Couples with previous sterilization procedures (vasectomy, tubal ligation) which have been reversed. The prior procedure may affect study outcomes, and patients with both a reversed sterilization procedure and PCOS are rare enough that exclusion should not adversely affect recruitment.
      • Subjects who have undergone a bariatric surgery procedure in the recent past (\< 12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon.
      • Patients with untreated poorly controlled hypertension defined as a systolic blood pressure 160 mm Hg or a diastolic 100 mm Hg obtained on two measures obtained at least 60 minutes apart.
      • Patients with known congenital adrenal hyperplasia.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
1,000 participants (actual)

Study arms

  • Experimental
    Acupuncture treatment 1 plus CC

    Other: Acupuncture treatment 1 · Other: CC

  • Active comparator
    Acupuncture treatment 2 plus CC

    Other: Acupuncture treatment 2 · Other: CC

  • Active comparator
    Acupuncture treatment 1 plus CC placebo

    Other: Acupuncture treatment 1 · Other: CC placebo

  • Active comparator
    Acupucture treatment 2 and CC placebo.

    Other: Acupuncture treatment 2 · Other: CC placebo

Interventions

  • OtherAcupuncture treatment 1

    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.

  • OtherAcupuncture treatment 2

    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.

  • OtherCC

    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.

  • OtherCC placebo

    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.

06

What researchers measure

Primary outcomes

  1. Live birth rate

    Time frame: Up to 3 years

Secondary outcomes

  1. Ovulation rate

    Time frame: Up to 3 years

  2. Ongoing pregnancy rate

    Up to 3 years

    Time frame: Aprial 2012 to July 2014 (up to 3 years)

  3. Multiple pregnancy rate

    Time frame: Up to 2 years

  4. Miscarriage rate

    loss of an intrauterine pregnancy before 20 completed weeks of gestation.

    Time frame: Up to 2 years

  5. 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

  6. 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

  7. 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

07

Study locations

25 sites
  • First Affiliated Hospital，Anhui University of Chinese Medicine
    Hefei, Anhui 230031, China
  • First Affiliated Hospital，Guangzhou University of Chinese Medicine
    Guangzhou, Guangdong 510000, China
  • Guangzhou Liwan Chinese Hospital
    Guangzhou, Guangdong 510000, China
  • Guangdong Chinese Hospital
    Guangzhou, Guangdong 510120, China
  • Daqing LongNa Hospital
    Daqing, Heilongjiang 163000, China
  • The Daqing Oilfield General Hospital
    Daqing, Heilongjiang 163000, China
  • Forth Affiliated Hospital of Harbin Medical University
    Harbin, Heilongjiang 150001, China
  • Second Affiliated Hospital，Heilongjiang University of Chinese Medicine
    Harbin, Heilongjiang 150001, China
  • First Affiliated Hospital，Heilongjiang University of Chinese Medicine
    Harbin, Heilongjiang 150040, China
  • Henan Chinese Medicine Hospital
    Zhengzhou, Henan 450002, China
  • Wuhan Tongji Hospital
    Wuhan, Hubei 430000, China
  • Hubei Chinese Medicine Hospital
    Wuhan, Hubei 430060, China
  • First Affiliated Hospital，Hunan University of Chinese Medicine
    Changsha, Hunan 410007, China
  • Maternal and Child Health Hospital of Huaian
    Huaian, Jiangsu 223002, China
  • Suzhou Chinese Medicine Hospital
    Suzhou, Jiangsu 215003, China
  • Maternal and Child Health Hospital of Xuzhou
    Xuzhou, Jiangsu 221000, China
  • Jiangxi University of Chinese Medicine Affiliated Hospital
    Nanchang, Jiangxi 330000, China
  • Dalian maternity hospital
    Dalian, Liaoning 116000, China
  • Liaoning University of Chinese Medicine Affiliated Hospital
    Shenyang, Liaoning 110000, China
  • Shanxi Chinese Medicine Hospital
    Shangxi, Shanxi 030012, China
  • First Affiliated Hospital，Tianjin University of Chinese Medicine
    Tianjin, Tianjin 300193, China
  • Tianjin Tanggu Maternity and Child Care Center
    Tianjin, Tianjin 300451, China
  • Integrated Chinese and Western Medicine Hospital of Zhejiang Province
    Hangzhou, Zhejiang 310000, China
  • Wenzhou Chinese Medicine Hospital
    Wenzhou, Zhejiang 325000, China
  • Hangzhou Chinese Medicine Hospital
    Hangzhou, 310000, China
08

References and documents

Publications

  • Luo X, Yang XM, Cai WY, Chang H, Ma HL, Peng Y, Wu XK. Decreased Sex Hormone-Binding Globulin Indicated Worse Biometric, Lipid, Liver, and Renal Function Parameters in Women with Polycystic Ovary Syndrome. Int J Endocrinol. 2020 Jun 25;2020:7580218. doi: 10.1155/2020/7580218. eCollection 2020. PubMed 33101409 ↗
  • Zhang D, Gao J, Liu X, Qin H, Wu X. Effect of Three Androgen Indexes (FAI, FT, and TT) on Clinical, Biochemical, and Fertility Outcomes in Women with Polycystic Ovary Syndrome. Reprod Sci. 2021 Mar;28(3):775-784. doi: 10.1007/s43032-020-00316-1. Epub 2020 Sep 28. PubMed 32989632 ↗
  • Zhang D, Yang X, Li J, Yu J, Wu X. Effect of hyperinsulinaemia and insulin resistance on endocrine, metabolic and fertility outcomes in women with polycystic ovary syndrome undergoing ovulation induction. Clin Endocrinol (Oxf). 2019 Sep;91(3):440-448. doi: 10.1111/cen.14050. Epub 2019 Jun 28. PubMed 31222771 ↗
  • Ma HL, Xie LZ, Gao JS, Cong J, Deng YY, Ng EHY, Liu JP, Wu XK. Acupuncture and clomiphene for Chinese women with polycystic ovary syndrome (PCOSAct): statistical analysis approach with the revision and explanation. Trials. 2018 Nov 1;19(1):601. doi: 10.1186/s13063-018-2942-7. PubMed 30382872 ↗
  • Li J, Wu Q, Wu XK, Zhou ZM, Fu P, Chen XH, Yan Y, Wang X, Yang ZW, Li WL, Stener-Victorin E, Legro RS, Ng EH, Zhang H, Mol BWJ, Wang CC; for PCOSAct Study Group. Effect of exposure to second-hand smoke from husbands on biochemical hyperandrogenism, metabolic syndrome and conception rates in women with polycystic ovary syndrome undergoing ovulation induction. Hum Reprod. 2018 Apr 1;33(4):617-625. doi: 10.1093/humrep/dey027. PubMed 29471520 ↗
  • Wu XK, Stener-Victorin E, Kuang HY, Ma HL, Gao JS, Xie LZ, Hou LH, Hu ZX, Shao XG, Ge J, Zhang JF, Xue HY, Xu XF, Liang RN, Ma HX, Yang HW, Li WL, Huang DM, Sun Y, Hao CF, Du SM, Yang ZW, Wang X, Yan Y, Chen XH, Fu P, Ding CF, Gao YQ, Zhou ZM, Wang CC, Wu TX, Liu JP, Ng EHY, Legro RS, Zhang H; PCOSAct Study Group. Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial. JAMA. 2017 Jun 27;317(24):2502-2514. doi: 10.1001/jama.2017.7217. PubMed 28655015 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 25, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01573858
Lead sponsor
Heilongjiang University of Chinese Medicine
Collaborators
Yale University, Penn State University, Göteborg University, The University of Hong Kong, Beijing University of Chinese Medicine, Sichuan University, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin Medical University, Daqing Oil Field Hospital, Daqing Longnan Hospital, Liaoning University of Traditional Chinese Medicine, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin Tanggu Maternity and Child Care Center, Wenzhou Chinese Medicine Hospital, Jiangsu Province Hospital of Traditional Chinese Medicine, Hangzhou Chinese Medicine Hospital, Shanxi Chinese Medicine Hospital, Henan Chinese Medicine Hospital, Maternal and Child Health Hospital of Xuzhou, Huaian Maternal and Child Health Care Hospital, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Suzhou Chinese Medicine Hospital, Wuhan TongJi Hospital, Hubei Chinese Medicine Hospital, Jiangxi University of Chinese Medicine Affiliated Hospital, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guangdong Provincial People's Hospital, Guangzhou Liwan Chinese Hospital, Dalian maternity hospital
Responsible party
Xiaoke Wu (Professor and Department Chairman of Obstetrics and Gynecology, Heilongjiang University of Chinese Medicine) — Principal investigator
First posted
Apr 10, 2012
Start date
Jul 6, 2012
Primary completion
Nov 8, 2014
Completion
Oct 7, 2015
Last update
Aug 25, 2021

Study contacts

Xiaoke Wu, M.D., Ph.D.
principal investigator · First Affiliated Hospital of Heilongjiang Chinese Medicine University
Lihui Hou, M.D.
principal investigator · First Affiliated Hospital of Heilongjiang Chinese Medicine University
Richard Legro, MD
study chair · Steering Committee, Pennsylvania State University College of Medicine
Heping Zhang, PHD
study chair · Data and Quality Control, Yale University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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