Clinical trial NCT02676713: Traditional Chinese Medicine Sequential Treatment for Endometriosis Associated Infertility
Official title: Activating Blood, Dredging Liver and Nourishing Kidney Sequential Treatment for Endometriosis Associated Infertility - a Randomized Double-blind Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Endometriosis
Infertility
Keywords: Traditional Chinese Medicine
Chinese Herbal
Lead sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
name: Beijing Hospital
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
name: The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine
First posted: 2016-02-08
Enrollment: 204
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pregnancy rate
timeFrame: six menstrual cycles（each cycle is 28±7 days）
Secondary outcomes:
measure: Clinical pregnancy rate (with intrauterine pregnancy sac)
timeFrame: at 6～8 weeks of pregnancy
measure: Clinical pregnancy rate (with a heart throb)
timeFrame: at 6～8 weeks of pregnancy
measure: Continued pregnancy rate
timeFrame: at the 12～14 weeks of pregnancy
Other outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: six menstrual cycles（each cycle is 28±7 days）
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine
state: Anhui
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital,Captial Medical University
state: Beijing
city: Beijing
country: China
facility: GAMHospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: Traditional Chinese Medicine Hospital of Guangdong Province
state: Guangdong
city: Beijng
country: China
facility: Beijng Hospital
Study officials:
affiliation: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
name: Ruihua Zhao, Doctor
role: STUDY_CHAIR
References:
citation: Duffy JM, Arambage K, Correa FJ, Olive D, Farquhar C, Garry R, Barlow DH, Jacobson TZ. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2014 Apr 3;(4):CD011031. doi: 10.1002/14651858.CD011031.pub2.
citation: Yap C, Furness S, Farquhar C. Pre and post operative medical therapy for endometriosis surgery. Cochrane Database Syst Rev. 2004;2004(3):CD003678. doi: 10.1002/14651858.CD003678.pub2.
citation: Zhao RH, Hao ZP, Zhang Y, Lian FM, Sun WW, Liu Y, Wang R, Long L, Cheng L, Ding YF, Song DR, Meng QW, Wang AM. Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medicine. Chin J Integr Med. 2013 Nov;19(11):820-5. doi: 10.1007/s11655-012-1247-z. Epub 2012 Dec 22.
citation: Zhao RH, Liu Y, Lu D, Wu Y, Wang XY, Li WL, Zeng C, Meng QW, Lian FM, Zhou J, Shi Y, Sun WW, Han Q, Tang Y, Shi G. Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial. Chin J Integr Med. 2020 Feb;26(2):92-99. doi: 10.1007/s11655-019-3208-2. Epub 2020 Jan 29.