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

Conditions

Pregnancy, Polycystic Ovary Syndrome, Infertility

Keywords

Infertility, Polycystic Ovary Syndrome, Clomiphene citrate, Acupuncture

Brief 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).

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

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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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

20 Years to 40 Years

Healthy volunteers

No

Inclusion 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

Design outcomes

Primary

Measure	Time frame
Live birth rate	Up to 3 years

Secondary

Measure	Time frame	Description
Ongoing pregnancy rate	Aprial 2012 to July 2014 (up to 3 years)	Up to 3 years
Multiple pregnancy rate	Up to 2 years	—
Miscarriage rate	Up to 2 years	loss of an intrauterine pregnancy before 20 completed weeks of gestation.
Ovulation rate	Up to 3 years	—
Metabolic profile	Up to 2 years	Metabolic profile includes: Serum glucose concentration, Insulin concentration, cholesterol, Triglycerides (TG), High density lipoprotein cholesterol (HDL-C) and Low density lipoprotein cholesterol (LDL-C)
Side effect profile	Up to 2 years	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.
Hormonal profile	Up to 2 years	Hormonal profile include: Testosterone(T), Sex hormone-binding globulin (SHBG), Follicle stimulating hormone (FSH),Luteinizing hormone(LH),and Dehydroepiandrosterone sulfate (DHEAS).

Countries

China

Outcome results

None listed