Letrozole Versus Chinese Herbal Medicine on Polycystic Ovary Syndrome (PCOS)

Study Overview
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Brief Summary
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This is a multicenter double-blind randomized controlled trial. A total of 420 anovulatory Chinese women with PCOS will be recruited, and the randomization will be stratified by each participating site. Participants will be randomized into one of the two treatment arms: letrozole and CHMG or letrozole and CHMG placebo. CHMG or its placebo will be taken twice a day for up to six months. Letrozole (2.5 mg daily) was given on days 3-7 of the menstrual cycle after a spontaneous period or withdrawal bleeding, and the dose will be increased to 5.0 mg daily during the last three months for non-pregnant women in both groups.The aim of the present study is to determine the efficacy of combined treatment with letrozole and CHMG on improving live birth rates in infertile Chinese women with PCOS. Our hypothesis is that the combination of letrozole and CHMG is more likely to increase the ovulation rate and decrease the miscarriage rate and result in a higher live birth rate in PCOS women than letrozole alone.

Official Title
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The Effects of Chinese Herbal Medicine and Letrozole on Live Birth in Infertile Women With Polycystic Ovary Syndrome:A Double-blind Randomized Controlled Trial

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Letrozole
* Drug: Chinese herbal medicine granules or Chinese herbal medicine granules placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Chinese women with PCOS. PCOS must have been diagnosed based on the presence of two of the following three Rotterdam criteria : (1) oligomenorrhea, anovulation; (2) hyperandrogenism; and (3) the observation of polycystic ovaries by sonography. 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. History of at least one year of infertility. Age between 20 and 40 years old. Normal semen analysis based on World Health Organization criteria (2010). The husband did not need to sign the consent form because semen analysis is part of the clinical assessment at the sites. A sperm concentration ≥15 × 106/mL and total motility ≥40% in the semen analysis of the husband was required for the woman to be included. Normal uterine cavity and at least one tube patent upon hysterosalpingography or HyCoSy. Exclusion criteria History of significant system diseases such as heart, lung, or kidney diseases. History of other endocrine disorders. Use of hormonal therapy, including metformin, in the past 3 months. Previous sterilization procedures (vasectomy or tubal ligation) that have been reversed.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole+ Chinese herbal medicine granules<br> | Drug: Letrozole<br>* 2.5 mg letrozole daily from day 5 of the menses for 5 days for month 1 to 3, 5.0 mg letrozole daily from day 5 of the menses for 5 days for month 4 to 6.<br>Drug: Chinese herbal medicine granules or Chinese herbal medicine granules placebo<br>* twice a day for 6 month<br>|
| Placebo Comparator: Letrozole+ Chinese herbal medicine granules placebo<br> | Drug: Letrozole<br>* 2.5 mg letrozole daily from day 5 of the menses for 5 days for month 1 to 3, 5.0 mg letrozole daily from day 5 of the menses for 5 days for month 4 to 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovulation rate |  | Up to 1 year | 
| Miscarriage rate |  | Up to 1 year | 
| Change in hormonal profile | Follicle-stimulating hormone, luteinizing hormone, total testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulphate. | Up to 1 year | 
| Change in metabolic profile | glucose and insulin concentrations, cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. | Up to 1 year | 
| Change in physical measurements | weight, vital signs, and hip and waist measurements. | Up to 1 year | 
| Pregnancy complications | gestational diabetes, pregnancy-induced hypertension, intrauterine growth retardation, ectopic pregnancy, congenital anomaly, preeclampsia, preterm labor, HELLP syndrome, preterm premature rupture of membranes, placental abruption, placenta accreta, placenta previa, postpartum hemorrhage, and others. | Up to 1 year | 
| Birth defects |  | Up to 1 year | 
| Safety parameters | renal and liver function tests and complete blood count. | Up to 1 year | 
| Side effect profile | The major risks to the subject are side effects from letrozole and CHMG and the risks associated with pregnancy. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovary syndrome, Randomized controlled trial, Chinese herbal medicine, Chinese herbal medicine granules, Letrozole, Live birth