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

NCT01573858 | Completed DMC

• 1 other identifier: PCOSAct
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 25

Brief Summary

The objectives of the present trial are to test the following three hypotheses in anovulatory women with PCOS:

1. 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. 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. 3.Acupuncture protocol 1 plus placebo (Arm C) is more likely to result in live birth than acupuncture protocol 2 plus placebo (Arm D).

Conditions

Pregnancy; Polycystic Ovary Syndrome; Infertility

Keywords

Infertility; Polycystic Ovary Syndrome; Clomiphene citrate; Acupuncture

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Up to 3 years

Secondary Outcomes (7)

• Ovulation rate

  Up to 3 years

• Ongoing pregnancy rate

  Aprial 2012 to July 2014 (up to 3 years)

• Multiple pregnancy rate

  Up to 2 years

• Miscarriage rate

  Up to 2 years

• Hormonal profile

  Up to 2 years

Study Arms (4)

Acupuncture treatment 1 plus CC

EXPERIMENTAL

Other: Acupuncture treatment 1; Other: CC

Acupuncture treatment 2 plus CC

ACTIVE COMPARATOR

Other: Acupuncture treatment 2; Other: CC

Acupuncture treatment 1 plus CC placebo

ACTIVE COMPARATOR

Other: Acupuncture treatment 1; Other: CC placebo

Acupucture treatment 2 and CC placebo.

ACTIVE COMPARATOR

Other: Acupuncture treatment 2; Other: CC placebo

Interventions

Acupuncture treatment 1 OTHER

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.

Acupuncture treatment 1 plus CC; Acupuncture treatment 1 plus CC placebo

Acupuncture treatment 2 OTHER

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.

Acupucture treatment 2 and CC placebo.; Acupuncture treatment 2 plus CC

CC OTHER

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.

Acupuncture treatment 1 plus CC; Acupuncture treatment 2 plus CC

CC placebo OTHER

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.

Acupucture treatment 2 and CC placebo.; Acupuncture treatment 1 plus CC placebo

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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).
• Total motile sperm count ≥9 million \[based on WHO (2010) criteria, volume 1.5 ml; conc 15 million; motility 40%. 1.5 x 15 x 0.04=9 million\].

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Heilongjiang University of Chinese Medicine: lead
• Yale University: collaborator
• Penn State University: collaborator
• Göteborg University: collaborator
• The University of Hong Kong: collaborator
• Beijing University of Chinese Medicine: collaborator
• Sichuan University: collaborator
• Second Affiliated Hospital of Heilongjiang University of Chinese Medicine: collaborator
• Harbin Medical University: collaborator
• Daqing Oil Field Hospital: collaborator
• Daqing Longnan Hospital: collaborator
• Liaoning University of Traditional Chinese Medicine: collaborator
• The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine: collaborator
• Tianjin Tanggu Maternity and Child Care Center: collaborator
• Wenzhou Chinese Medicine Hospital: collaborator
• Jiangsu Province Hospital of Traditional Chinese Medicine: collaborator
• Hangzhou Chinese Medicine Hospital: collaborator
• Shanxi Chinese Medicine Hospital: collaborator
• Henan Chinese Medicine Hospital: collaborator
• Maternal and Child Health Hospital of Xuzhou: collaborator
• Huaian Maternal and Child Health Care Hospital: collaborator
• The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine: collaborator
• Suzhou Chinese Medicine Hospital: collaborator
• Wuhan TongJi Hospital: collaborator
• Hubei Chinese Medicine Hospital: collaborator
• Jiangxi University of Chinese Medicine Affiliated Hospital: collaborator
• The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine: collaborator
• The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine: collaborator
• Guangdong Provincial People's Hospital: collaborator
• Guangzhou Liwan Chinese Hospital: collaborator
• Dalian maternity hospital: collaborator

Study Sites (25)

First Affiliated Hospital，Anhui University of Chinese Medicine

Hefei, Anhui, 230031, China

Location

First Affiliated Hospital，Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, 510000, China

Location

Guangzhou Liwan Chinese Hospital

Guangzhou, Guangdong, 510000, China

Location

Guangdong Chinese Hospital

Guangzhou, Guangdong, 510120, China

Location

Daqing LongNa Hospital

Daqing, Heilongjiang, 163000, China

Location

The Daqing Oilfield General Hospital

Daqing, Heilongjiang, 163000, China

Location

Forth Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Second Affiliated Hospital，Heilongjiang University of Chinese Medicine

Harbin, Heilongjiang, 150001, China

Location

First Affiliated Hospital，Heilongjiang University of Chinese Medicine

Harbin, Heilongjiang, 150040, China

Location

Henan Chinese Medicine Hospital

Zhengzhou, Henan, 450002, China

Location

Wuhan Tongji Hospital

Wuhan, Hubei, 430000, China

Location

Hubei Chinese Medicine Hospital

Wuhan, Hubei, 430060, China

Location

First Affiliated Hospital，Hunan University of Chinese Medicine

Changsha, Hunan, 410007, China

Location

Maternal and Child Health Hospital of Huaian

Huaian, Jiangsu, 223002, China

Location

Suzhou Chinese Medicine Hospital

Suzhou, Jiangsu, 215003, China

Location

Maternal and Child Health Hospital of Xuzhou

Xuzhou, Jiangsu, 221000, China

Location

Jiangxi University of Chinese Medicine Affiliated Hospital

Nanchang, Jiangxi, 330000, China

Location

Dalian maternity hospital

Dalian, Liaoning, 116000, China

Location

Liaoning University of Chinese Medicine Affiliated Hospital

Shenyang, Liaoning, 110000, China

Location

Shanxi Chinese Medicine Hospital

Shangxi, Shanxi, 030012, China

Location

First Affiliated Hospital，Tianjin University of Chinese Medicine

Tianjin, Tianjin Municipality, 300193, China

Location

Tianjin Tanggu Maternity and Child Care Center

Tianjin, Tianjin Municipality, 300451, China

Location

Integrated Chinese and Western Medicine Hospital of Zhejiang Province

Hangzhou, Zhejiang, 310000, China

Location

Wenzhou Chinese Medicine Hospital

Wenzhou, Zhejiang, 325000, China

Location

Hangzhou Chinese Medicine Hospital

Hangzhou, 310000, China

Location

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• Gong Y, Li J, Ma HL, Jiang T, Qin HC, Li MB, Wu XK. High acupuncture expectancy is associated with shorter time to ovulation and higher chances of ovulation in infertile patients with PCOS receiving acupuncture: a secondary analysis of a randomized controlled trial. Acupunct Med. 2025 Jun;43(3):137-143. doi: 10.1177/09645284251342261. Epub 2025 May 19.

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• Chang H, Shi B, Ge H, Liu C, Wang L, Ma C, Liu L, Zhang W, Zhang D, Wang Y, Wang CC, Wu X. Acupuncture improves the emotion domain and lipid profiles in women with polycystic ovarian syndrome: a secondary analysis of a randomized clinical trial. Front Endocrinol (Lausanne). 2023 Aug 29;14:1237260. doi: 10.3389/fendo.2023.1237260. eCollection 2023.

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• 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.

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• 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.

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MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Xiaoke Wu, M.D., Ph.D.

  First Affiliated Hospital of Heilongjiang Chinese Medicine University

  PRINCIPAL INVESTIGATOR

• Lihui Hou, M.D.

  First Affiliated Hospital of Heilongjiang Chinese Medicine University

  PRINCIPAL INVESTIGATOR

• Richard Legro, MD

  Steering Committee, Pennsylvania State University College of Medicine

  STUDY CHAIR

• Heping Zhang, PHD

  Data and Quality Control, Yale University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Department Chairman of Obstetrics and Gynecology

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 10, 2012
• Study Start: July 6, 2012
• Primary Completion: November 8, 2014
• Study Completion: October 7, 2015
• Last Updated: August 25, 2021

Record last verified: 2021-08

Locations

CN (25)