A Trial of Personalized Acupuncture, Fixed Acupuncture, Letrozole and Placebo on Live Birth in Women With PCOS

NCT03625531 | Completed Phase 3 DMC

• 1 other identifier: PPCOSAct
• Study Type: interventional
• Target: 1,103
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized assessor-blind controlled trial. A total of 1,103 women with PCOS will be recruited from 20 hospitals and randomly allocated into four groups: personalized acupuncture, fixed acupuncture, letrozole or placebo letrozole. Patients will receive treatment for 16 weeks and the primary outcome is live birth.

Conditions

Polycystic Ovary Syndrome

Keywords

Acupuncture; Polycystic Ovary Syndrome; Personalized protocol; Fixed protocol; Letrozole

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Live birth rate defined as a delivery after ≥20 weeks gestation.

  Up to 14 months

Secondary Outcomes (20)

• Ovulation rate

  Up to 4 months

• Conception rate

  Up to 4 months

• Pregnancy rate

  Up to 6.5 months

• Pregnancy loss rate

  Up to 9 months

• Follicle stimulating hormone (FSH)

  Up to 4 months

Study Arms (4)

Personalized acupuncture

EXPERIMENTAL

Two sets of acupoints will be selected for the two types. The basic acupoint-prescription includes CV 4, CV 6, CV 12 and SP 6 bilaterally, ST 25 bilaterally, EX-CA 1 bilaterally, ST 40 bilaterally and SP 9 bilaterally. Additional point ST 36 bilaterally and moxibustion as adjuvant therapy will be added for the type of yang deficiency of spleen and kidney, while additional points K 13, LR 3 for the type of yin deficiency of liver and kidney. Besides, flexible modifications of 2-3 acupoints will be performed according to patients special symptoms.

Other: Acupuncture

Fixed acupuncture

EXPERIMENTAL

Two sets of acupuncture points will be alternated every second treatment. The first set consists of CV 3, CV 6, ST 29 bilaterally, SP 6 bilaterally, SP 9 bilaterally, GV 20 and LI 4 bilaterally. The second set consists of 13 needles: ST 25 bilaterally, ST 29 bilaterally, CV 3, CV 6, SP 6 bilaterally, LR 3 bilaterally, PC 6 bilaterally and GV 20. The following points will be connected to an electrical stimulator: ST 25 bilaterally, ST 29 bilaterally, SP 6 bilaterally, LR 3 bilaterally.

Other: Acupuncture

Letrozole

ACTIVE COMPARATOR

Women in the letrozole group will be given letrozole (Femara, Novartis Pharmaceuticals, Basel, Switzerland) from day 3 to day 7 of the spontaneous menstrual cycle or after a withdrawal bleeding following progestin. The maximum daily dose of letrozole will be 7.5 mg (3 pills) daily for five days.

Drug: Letrozole

Placebo letrozole

PLACEBO COMPARATOR

Women will receive placebo letrozole with no acupuncture from day 3 to day 7 of the spontaneous menstrual cycle or after a withdrawal bleeding following progestin. Placebo letrozole will be given in the same way as letrozole.

Drug: Placebo letrozole

Interventions

Letrozole DRUG

Letrozole will be started on day 3 to day 7 of the spontaneous period or a withdrawal bleeding following progestin. If there is response with ovulation, this dose will be maintained. In those with no ovulatory response, letrozole tablets of the next ovulation cycle will be take on the day 28 of the menstrual cycle and the letrozole dose will be increased to 5 mg (2 pills) a day for 5 days. If there is still no response, the dose will be increased to 7.5 mg per day for 5 days in the next cycle. The maximum daily dose of letrozole will be 7.5 mg (3 pills) daily for five days.

Also known as: Femara, Novartis Pharmaceuticals

Letrozole

Placebo letrozole DRUG

Placebo letrozole will be given in the same way as letrozole. Women will receive 1 tablet a day of placebo letrozole from the day 3 to day 7 of the menstrual cycle and placebo letrozole dose will be increased 2 tablets a day in the next cycle if there is no response. The maximum daily dose of placebo letrozole will be 3 tablets daily for five days.

Also known as: Placebo

Placebo letrozole

Acupuncture OTHER

Women in both personalized and fixed acupuncture groups will receive acupuncture treatment three times a week. Acupuncture treatment will start on day 3 after a spontaneous period or after a withdrawal bleeding following progestin. Each treatment session will last for 30-60 minutes, with a maximum of 48 treatment sessions over 16 weeks. If they become pregnant, the acupuncture treatment will be stopped. For personalized and fixed acupuncture group, credibility and expectancy questionnaires will be completed on the third acupuncture treatment and the last acupuncture treatment.

Fixed acupuncture; Personalized acupuncture

Eligibility Criteria

• Age: 20 Years - 40 Years
• Gender Eligibility Details: PCOS is a complex reproductive-metabolic disorder, affects 5-10% of reproductive age women and is the most common cause of anovulatory infertility.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age of women between 20 and 40 years.
• Chronic oligomenorrhea or amenorrhea: oligomenorrhea is defined as an intermenstrual interval \> 35 days or \< 8 menstrual bleedings in the past year. Amenorrhea is defined as an intermenstrual interval \>90 days.
• Hyperandrogenism (either hirsutism or hyperandrogenemia) or polycystic ovaries on ultrasound. Hirsutism is determined by a modified Ferriman-Gallwey Score ≥ 5 at screening examination, and biochemical hyperandrogenism is defined as total testosterone (T) \> 2.6 nmol/L and free testosterone ≥ 6.0 pg/mL. Polycystic ovaries are present when there are ≥ 12 antral follicles (2 - 9 mm) or ovarian volume \> 10 mL on transvaginal scanning.
• At least one patent tube shown by hysterosalpingogram or diagnostic laparoscopy within 3 years if the patient does not have a history of abortion or pelvic operation. If the patient has a history of pregnancy and no history of pelvic operation within the past 5 years, she is not required to undergo a tubal patency test.
• Sperm concentration ⩾ 15 × 106/mL and total motility ⩾ 40% or total motile sperm count ⩾ 9 million in the semen analysis of the husband. Agree to have regular intercourse i.e. 2-3 times per week during the study period.

You may not qualify if:

• Use of other TCM treatments including Chinese herbal prescriptions and acupuncture in the past 3 months.
• Use of other western medications known to affect reproductive function or metabolism in the past 2 months.
• Pregnancy within the past 6 weeks.
• Within 6 weeks postabortion or postpartum.
• Breastfeeding within the last 6 months.
• Not willing to give written consent to the study.
• Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, depot progestins, hormonal implants (including Implanon), GnRH agonists and antagonists, antiandrogens, gonadotropins, antiobesity drugs, antidiabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, angiotensin-converting-enzyme (ACE) inhibitors, and calcium channel blockers. The washout period on these medicationswill be two months, 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 depot 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 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 into other investigative studies that require medications, prescribe 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.

Sponsors & Collaborators

• Hongxia Ma: lead

Study Sites (1)

The first affiliated hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Related Publications (23)

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• Huang S, Hu M, Ng EHY, Stener-Victorin E, Zheng Y, Wen Q, Wang C, Lai M, Li J, Gao X, Wang X, Hu Z, Xia T, Hu R, Liu J, Wen X, Li S, Quan K, Liang X, Shang H, Ma H, Qiao J. A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome. Trials. 2020 Mar 4;21(1):239. doi: 10.1186/s13063-020-4154-1.

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MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Acupuncture Therapy; Letrozole

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

Intervention Hierarchy (Ancestors)

Complementary Therapies; Therapeutics; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Hongxia HX Ma, Dorctor

  The First Affiliated Hospital of Guangzhou Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: July 13, 2018
• First Posted: August 10, 2018
• Study Start: August 13, 2018
• Primary Completion: January 22, 2025
• Study Completion: January 22, 2025
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

CN (1)