Polycystic Ovary Syndrome
Conditions
Keywords
Acupuncture, Polycystic Ovary Syndrome, Personalized protocol, Fixed protocol, Letrozole
Brief summary
This study is a randomized assessor-blind controlled trial. A total of 1,100 women with PCOS will be recruited from 28 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.
Detailed description
Traditional Chinese Medicine (TCM) usually involves syndrome and disease differentiation, and for acupuncture selection of appropriate points and skillful needling techniques. Many clinical trials on acupuncture used fixed acupuncture protocols without accounting for individual differences. We here design a multicenter randomized controlled trial to evaluate whether personalized or fixed acupuncture increases the likelihood of live births for infertility in women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesis that letrozole is more effective than personalized acupuncture and that personalized acupuncture is more effective than standardized acupuncture, which is more effective than placebo letrozole.
Interventions
OTHERAcupuncture
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.
DRUGLetrozole
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.
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.
Sponsors
Hongxia Ma
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. Age of women between 20 and 40 years. 2. 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. 3. 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. 4. 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. 5. 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.
Exclusion criteria
1. Exclusion of other endocrine disorders: a. patients with hyperprolactinemia (defined as two prolactin levels at least one week apart ≥ 25 ng/mL); b. Patients with FSH levels \> 15 mIU/mL. A normal level within the last year is adequate for entry; c. 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. d. Patients diagnosed with Type I or Type II diabetes who are poorly controlled (defined as HbA1c level \> 7.0%), or patients receiving antidiabetic medications such as metformin, insulin, thiazolidinediones, acarbose, or sulfonylureas. e. Patients with suspected Cushing's syndrome. 2. Use of other TCM treatments including Chinese herbal prescriptions and acupuncture in the past 3 months. 3. Use of other western medications known to affect reproductive function or metabolism in the past 2 months. 4. Pregnancy within the past 6 weeks. 5. Within 6 weeks postabortion or postpartum. 6. Breastfeeding within the last 6 months. 7. Not willing to give written consent to the study. 8. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rate | Up to 14 months | Live birth rate defined as a delivery after ≥20 weeks gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conception rate | Up to 4 months | Conception defined as positive serum hCG. |
| Pregnancy rate | Up to 6.5 months | Around 8-10 weeks gestation. |
| Pregnancy loss rate | Up to 9 months | Pregnancy loss defined as pregnancy loss occurring from conception to 27 completed weeks of gestational age. |
| Follicle stimulating hormone (FSH) | Up to 4 months | Hormonal profile |
| Luteinizing hormone(LH) | Up to 4 months | Hormonal profile |
| Testosterone(T) | Up to 4 months | Hormonal profile |
| Sex hormone-binding globulin (SHBG) | Up to 4 months | Hormonal profile |
| Serum glucose concentration | Up to 4 months | Metabolic profile |
| Insulin concentration | Up to 4 months | Metabolic profile |
| Ovulation rate | Up to 4 months | Ovulation defined as a serum progesterone level \>3 ng/mL on day 21 or day 28 of the cycle. |
| Triglycerides (TG) | Up to 4 months | Metabolic profile |
| High density lipoprotein cholesterol (HDL-C) | Up to 4 months | Metabolic profile |
| Low density lipoprotein cholesterol (LDL-C) | Up to 4 months | Metabolic profile |
| The scores of short form 36 (SF 36) | Up to 4 months | SF-36 is one of questionnaires for assessments of health-related quality of life. It includes 36 items, the scores for each domain range from 0 to 100, with high scores indicating a better status. |
| The scores of polycystic ovary syndrome questionnaire (PCOSQ) | Up to 4 months | PCOSQ is one of questionnaires for assessments of health-related quality of life. It concludes 26 items. Each question is associated with a 7-point scale in which 7 represents optimal function and 1 represents the poorest function. |
| The scores of Chinese quality of life (ChQOL) questionnaire | Up to 4 months | ChQOL is one of questionnaires for assessments of health-related quality of life. The ChQOL is unique in that it is a health-related quality of life （HRQOL） measure specific to Traditional Chinese Medicine (TCM). ChQOL consists of 50 items ,each item is rated on a five-point Likert scale with higher scores indicating better HRQOL. |
| The scores of Zung Self-Rating Anxiety Scale (SAS) | Up to 4 months | Zung SAS is one of questionnaires for symptoms of anxiety and depression. For the SAS, index score of 50 is a cut-off point for clinically significant anxiety, with higher score suggesting more serious depression. |
| The scores of Zung Self-reported Depression Scale (SDS) | Up to 4 months | Zung SDS is one of questionnaires for symptoms of anxiety and depression. Index scores of 25 to 49 indicate nil depression, 50-59 indicate mild to moderate depression, 60-69 indicate moderate to severe depression, and scores over 70 indicate severe depression. |
| Side effect profile | Up to 14 months | Adverse events will be categorized and percentage of patients experiencing. adverse events and serious adverse events during the treatment period will be documented. |
| Cholesterol | Up to 4 months | Metabolic profile |
Countries
China
Contacts
Primary ContactHongxia Ma, Dorctor
Outcome results
None listed