Effect of Acupuncture Pre-treatment Combined With Letrozole on Live Birth in Infertile Women With Polycystic Ovary Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 384
- 试验地点
- 1
- 主要终点
- Live birth rate
研究概览
简要总结
This is a study protocol for a multicenter, randomized, and controlled trial. In this protocol, we present a randomized controlled trial comparing acupuncture pretreatment followed by letrozole vs letrozole alone in polycystic ovary syndrome (PCOS) women with anovulatory infertility. The high prevalence of insulin resistance (IR) in women with PCOS women is considered to be one of the major pathophysiological changes of PCOS, leading to anovulatiory infertility. A study has shown that electro-acupuncture could significantly improve insulin sensitivity. The effect of acupuncture pretreatment on anovulatory PCOS women followed by ovulation induction has not been investigated before. A total of 384 patients enrolled in this study will be randomized into one of two groups. The treatment group: a 16 week acupuncture pretreatment followed by 4 cycles of letrozole and the control group: 4 cycles of letrozole alone. The primary outcome is the live birth rate. We postulate that acupuncture pretreatment followed by letrozole results in a higher live birth rate when compared with letrozole alone.
详细描述
- Study content 1.1 Study design This is a multi-centered, randomized, clinical trial. 1.2 Subject selection and exclusion
Initially, 384 PCOS women anovulatory infertility will be recruited from four hospitals in mainland China: Department of Traditional Chinese Medicine in the first affiliated hospital of Guangzhou Medical University, Department of Gynecology in Xuzhou maternity & child health hospital, Department of Reproduction in Dalian Municipal Women and Children's Medical Center, and Department of Traditional Chinese Medicine in Hexian memorial affiliated hospital of Southern Medical University if they meet the inclusion criteria and do not have the exclusion criteria. Eligible subjects will be approached and sign the consent form after detailed explanation and counseling. Recruited subjects will be randomized to one of two groups:
Treatment group: a 16 week acupuncture pre-treatment followed by LE and Control group: LE alone 1.3 Screening visit 1.3.1 Obtain signed informed consent 1.3.2 Complete physical examination Perform complete physical examination including height, weight, hip and waist measurement. Height and weight will be recorded to the nearest 0.1 cm and 0.1 kg respectively. Waist and hip circumference will be recorded to the nearest 1 cm. And assessment of hirsutism by Ferriamn Gallwey score (FG), acne standard acne lesion counts, and pelvic exam with Pap smear or TCT.
1.3.3 Perform transvaginal ultrasound of the uterus and ovaries
- Uterus, including the uterine dimensions, endometrial thickness and echo type, other uterine abnormalities, presence and size of leiomyoma will be obtained through transvaginal ultrasound.
- Ovaries, including the ovarian size in three dimensions, the size of the largest ovarian follicle/cyst and size of every follicle with a mean diameter greater than 10 mm, and total antral follicle (small follicles with mean diameter < 10 mm) count of each ovary will be obtained through transvaginal ultrasound.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged between 20 and 40 years.
- •Confirmed diagnosis of PCOS according to 2003 modified Rotterdam criteria
- •According to World Health Organization standards (2010), semen analysis of the husband must meet ① or ②. ①sperm concentration ≥15*106/ml and total motility ≥40% . ② Total motile sperm count ≥9 million, i.e. semen volume*sperm density*percentage of motile sperm ≥9 million.
- •At least one patent tube shown by hysterosalpingogram or diagnostic laparoscopy. The results will be valid for 3 years if the patients do not have a history of abortion or pelvic operation.
排除标准
- •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.
- •Patientsdiagnosed with Type I or Type II diabetes who are poorly controlled (defined as a Hb A1c 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 (extended release) for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.
- •⑤Patients with suspected Cushing's syndrome. 2) Use of hormonal or other medication including Chinese Herbal prescriptions which may affect the outcome at least in the past 2 months.
- •Acupuncture the last 2 months. 4) Pregnancy within the past 6 weeks. 5) Within 6 weeks post-abortion or postpartum. 6) Breastfeeding within the last 6 months. 7) Not willing to give written consent to the study. 8) Additional exclusion criteria
- •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.
- •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 totalbilirubin >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 or TCT 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.
研究组 & 干预措施
Pre-treatment acupuncture + letrozole
A 16 week acupuncture pretreatment followed by letrozole(LE). Acupuncture treatment will start on day 3-5 after a spontaneous period or after a withdrawal bleeding following progestin. All subjects will be requested to use contraception during the 16 week acupuncture pretreatment. They will receive acupuncture treatment three times a week. Each treatment session lasts for 30 minutes and can be separated by an interval of 1-3 days, with a maximum of 48 treatment sessions during 16 weeks. After 16 weeks of acupuncture treatment, LE will start on day 2-3 after a spontaneous period or after a withdrawal bleeding after progestin administration. The subjects will be instructed to have intercourse on a regular basis during the cycles.
干预措施: Pre-treatment acupuncture (Other)
Pre-treatment acupuncture + letrozole
A 16 week acupuncture pretreatment followed by letrozole(LE). Acupuncture treatment will start on day 3-5 after a spontaneous period or after a withdrawal bleeding following progestin. All subjects will be requested to use contraception during the 16 week acupuncture pretreatment. They will receive acupuncture treatment three times a week. Each treatment session lasts for 30 minutes and can be separated by an interval of 1-3 days, with a maximum of 48 treatment sessions during 16 weeks. After 16 weeks of acupuncture treatment, LE will start on day 2-3 after a spontaneous period or after a withdrawal bleeding after progestin administration. The subjects will be instructed to have intercourse on a regular basis during the cycles.
干预措施: Letrozole (Drug)
Letrozole
LE alone. LE will be started on day 3-5 after a spontaneous period or a withdrawal bleeding following progestin. The subjects will be instructed to have intercourse on a regular basis during the cycles.
干预措施: Letrozole (Drug)
结局指标
主要结局
Live birth rate
时间窗: Up to 18 months
Live birth rate
次要结局
- Body composition(a composite)(Up to 8 months)
- Questionnaires(a composite)(Up to 8 months)
- Side effect profile(Up to 18 months)
- AUCglu(Up to 8 months)
- AUCins(Up to 8 months)
- Ovulation rate(Up to 8 months)
- Ongoing pregnancy rate(Up to 11 months)
- Multiple pregnancy rates(Up to 18 months)
- Miscarriage rate(Up to 11 months)
- Pregnancy complications rate(Up to 18 months)
- Hormonal profile(Up to 8 months)
- Metabolic profile(Up to 8 months)
- HOMA-IR(Up to 8 months)
研究者
Hongxia Ma
Professor
The First Affiliated Hospital of Guangzhou Medical University