Traditional Chinese Medicine Sequential Treatment for Endometriosis Associated Infertility

Phase 2

• Conditions: Endometriosis; Infertility
• Interventions: Drug: pre-ovulation Decoction; Drug: pre-ovulation Decoction(placebo); Drug: post-ovulation Decoction; Drug: post-ovulation Decoction(placebo)

• Registration Number: NCT02676713
• Lead Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Brief Summary

Endometriosis is a common, chronic disease. 30% to 50% of women with endometriosis are infertile. There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis increases live birth or ongoing pregnancy rates. There was no evidence of benefit for post-surgical hormonal suppression of endometriosis compared to surgery alone for the outcomes of pregnancy rates. Past studies have confirmed that Chinese herbal medicine can inhibit post-surgical endometriosis recurrence, increase pregnancy rate.This study evaluates the efficacy and safety of Traditional Chinese Medicine Sequential Treatment of endometriosis-associated infertility. The study objective is to confirm that clinical pregnancy rate of patients with endometriosis-associated infertility post-conservative surgery accepting Chinese medicine activating blood, dredging liver and nourishing kidney sequential treatment is higher than expectant treatment.

Detailed Description

This study is a randomized, double-blind, placebo-controlled, multicenter, prospective clinical study, conducted in China (six research centers).

204 cases of patients with endometriosis-associated infertility confined with Syndrome of qi stagnation blood stasis pattern in TCM after conservative surgery will be recruited. Patients will be randomly divided into two groups: experimental group (TCM Sequential Treatment) and control group (placebo). All the patients are treated for six menstrual cycles, taking pre-ovulation decoction before ovulation and post-ovulation decoction after ovulation. Pre-ovulation decoction of experimental group is HuoXueXiaoYi decoction, and post-ovulation decoction is BuShenZhuYun decoction. The drug of control group is placebo.

Each menstrual cycle, patient is monitored of antral follicle count (AFC), ovulation, endometrial thickness, and endometrial blood flow by ultrasonography, and need fill TCM syndrome rating scale, pictorial blood loss assessment chart (PBAC), and the visual analogue scale(VAS).The 1st, 3rd, 6th menstrual cycle after surgery, the level of serum female hormone (FSH, LH, E2) are detected in menstrual period of 2 to 5 days, and female hormone (E2, P) in the middle of the corpus luteum 6-9 days.

Patient must be security check (blood routine, urine routine, liver and kidney function, electrocardiogram) before and after drug treatment. Such as patients find pregnancy during medication, adopt the security check in finding pregnancy 7 days.

Patients after amenorrhea need to be confirmed pregnancy by serum β-HCG detection. According to the level of serum HCG, E2 and P and clinical symptoms, corresponding tocolytic treatment will be given. At 6～8 weeks of pregnancy, patient need to be confirmed the clinical pregnancy by ultrasonography. If confirmed the clinical pregnancy (at least having one heart throb in intrauterine gestational sac), patient need to be confirmed ongoing pregnancy by ultrasonography at the 12～14 weeks of pregnancy.

In the process of the entire study, adverse events will be closely observed, and the frequency and severity of adverse events will be recorded.

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2015-08-16
• Status Verified: 2016-02
• Study First Submitted QC: 2016-02-05
• Study First Posted: 2016-02-08
• Last Update Submitted: 2016-02-17
• Last Update Posted: 2016-02-19
• Primary Completion: 2017-05
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 204

Inclusion Criteria

1. Clinical diagnosis of endometriosis, infertility, with Syndrome of qi stagnation blood stasis pattern in TCM ;
2. The first time undergoing Laparoscopic or laparoscopy combined surgery , in lined with endometriosis-related infertility, tubal patency or obstruction lightly;
3. EFI score greater than 4 points;
4. Early follicular phase FSH≤10mIU / L;
5. 28 days of the menstrual cycle ± 7 days;
6. Female patients between 20-35 years old;
7. No previous history of severe drug allergies;
8. Past Three-month no taking hormone drugs such as danazol, Gestrinone, GnRHa;
9. No severe primary brain vascular diseases, liver, kidney and hematopoietic systems diseases, no history of mental illness, no drugs, alcohol, tobacco, caffeine dependent history;
10. Have signed informed consent

Exclusion Criteria

1. Associated with uterine fibroids, the diameter greater than 4cm, adenomyosis, pelvic tuberculosis, endometrial tuberculosis, intrauterine adhesions, polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction patients.
2. Serious history of drug allergy.
3. Male factor infertility.
4. The couple separated persons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TCM Sequential Treatment	pre-ovulation Decoction	After conservative surgery, patients start to take pre-ovulation decoction for 14 days. Each menstrual period 2～5 days, patients start to take pre-ovulation decoction. If ultrasonography found ovulation, change to take post-ovulation decoction. If having taken 14 days, ultrasonography found LUFS or no follicle develop maturity, change to take post-ovulation decoction. Taking post-ovulation decoction for 14 days, or continue to next time menstruation. Taking medication for six menstrual cycles. Pre-ovulation decoction is HuoXueXiaoYi decoction, and post-ovulation decoction is BuShenZhuYun decoction. 2 bags each time, 2 times a day, fused with hot water, 1 hour after dinner. All drugs are tcm formula granules, manufactured by Jiangyin Tianjiang Pharmaceutical Co. ltd
TCM Sequential Treatment	post-ovulation Decoction	After conservative surgery, patients start to take pre-ovulation decoction for 14 days. Each menstrual period 2～5 days, patients start to take pre-ovulation decoction. If ultrasonography found ovulation, change to take post-ovulation decoction. If having taken 14 days, ultrasonography found LUFS or no follicle develop maturity, change to take post-ovulation decoction. Taking post-ovulation decoction for 14 days, or continue to next time menstruation. Taking medication for six menstrual cycles. Pre-ovulation decoction is HuoXueXiaoYi decoction, and post-ovulation decoction is BuShenZhuYun decoction. 2 bags each time, 2 times a day, fused with hot water, 1 hour after dinner. All drugs are tcm formula granules, manufactured by Jiangyin Tianjiang Pharmaceutical Co. ltd
Placebo	pre-ovulation Decoction(placebo)	After conservative surgery, patients start to take pre-ovulation decoction(placebo) for 14 days. Each menstrual period 2～5 days, patients start to take pre-ovulation decoction. If ultrasonography found ovulation, change to take post-ovulation decoction. If having taken 14 days, ultrasonography found luteinized unruptured follicle syndrome (LUFS) or no follicle develop maturity, change to take post-ovulation decoction. Taking post-ovulation decoction(placebo) for 14 days, or continue to next time menstruation. Taking medication for six menstrual cycles. 2 bags each time, 2 times a day, fused with hot water, 1 hour after dinner. Pre-ovulation decoction and post-ovulation decoction is placebo, manufactured by Jiangyin Tianjiang Pharmaceutical Co. ltd
Placebo	post-ovulation Decoction(placebo)	After conservative surgery, patients start to take pre-ovulation decoction(placebo) for 14 days. Each menstrual period 2～5 days, patients start to take pre-ovulation decoction. If ultrasonography found ovulation, change to take post-ovulation decoction. If having taken 14 days, ultrasonography found luteinized unruptured follicle syndrome (LUFS) or no follicle develop maturity, change to take post-ovulation decoction. Taking post-ovulation decoction(placebo) for 14 days, or continue to next time menstruation. Taking medication for six menstrual cycles. 2 bags each time, 2 times a day, fused with hot water, 1 hour after dinner. Pre-ovulation decoction and post-ovulation decoction is placebo, manufactured by Jiangyin Tianjiang Pharmaceutical Co. ltd

Primary Outcome Measures

Name	Time	Method
Pregnancy rate	six menstrual cycles（each cycle is 28±7 days）	Pregnancy rate is defined as the proportion of participants finding pregnancy after amenorrhea and confirming serumβ-HCG positive.

Secondary Outcome Measures

Name	Time	Method
Clinical pregnancy rate (with intrauterine pregnancy sac)	at 6～8 weeks of pregnancy	defined as the proportion of participants confirmed there are at least one gestational sac in uterine cavity (No matter whether there is a heart throb) by ultrasonography.
Clinical pregnancy rate (with a heart throb)	at 6～8 weeks of pregnancy	defined as the proportion of participants confirmed at least having one heart throb in intrauterine gestational sac by ultrasonography.
Continued pregnancy rate	at the 12～14 weeks of pregnancy	defined as the proportion of participants confirmed at least one live fetuses by ultrasonography.

Trial Locations

Locations (6)

The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine; 🇨🇳 Guangzhou, Guangdong, China

GAMHospital; 🇨🇳 Beijing, Beijing, China

Traditional Chinese Medicine Hospital of Guangdong Province; 🇨🇳 Guangzhou, Guangdong, China

Beijing Obstetrics and Gynecology Hospital,Captial Medical University; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine; 🇨🇳 Hefei, Anhui, China

Beijng Hospital; 🇨🇳 Beijng, China