UMIN-CTR Clinical Trial

Recruitment status Completed
Unique ID issued by UMIN UMIN000005234
Receipt No. R000006125
Scientific Title Prospective randomized study of IVF-ET with GnRHa long protocol or Dienogest treatment before GnRHa long protocol in patients with endometriosis
Date of disclosure of the study information 2011/03/10
Last modified on 2020/05/07 (Ver. 9)

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Basic information
Public title Prospective randomized study of IVF-ET with GnRHa long protocol or Dienogest treatment before GnRHa long protocol in patients with endometriosis
Acronym The effectiveness of Dienogest treatment before IVF-ET in infertile patients with endometriosis.
Scientific Title Prospective randomized study of IVF-ET with GnRHa long protocol or Dienogest treatment before GnRHa long protocol in patients with endometriosis
Scientific Title:Acronym The effectiveness of Dienogest treatment before IVF-ET in infertile patients with endometriosis.
Region
Japan

Condition
Condition infertile women, endometriosis
Classification by specialty
Obsterics and gynecology
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 Endometriosis is understood to be the most intractable cause of female infertility. It has been reported that poor oocyte quality, low fertilization rates, poor embryo quality and impaired implantation of endometriosis patients relate to their poor pregnancy outcomes. This study was undertaken to evaluate the effectiveness of Dienogest (a selective progestin that has been used for the treatment of endometriosis) treatment immediately before in vitro fertilization and embryo transfer (IVF-ET) in infertile patients with endometriosis.
Basic objectives2 Safety,Efficacy
Basic objectives -Others
Trial characteristics_1 Exploratory
Trial characteristics_2 Explanatory
Developmental phase Phase IV

Assessment
Primary outcomes pregnancy rate
Key secondary outcomes 1) total amount of FSH/HMG
2) number of growing follicle (<15mm) and mature follicle (<18mm), number of oocyte retrieved
3) fertilization rate, implantation rate
4) serum concentration of estradiol and progesterone (on the day hCG injection)
5) intrafollicular concentration of cytokines (interleukin-6, tumor necrosis factor alpha), oxidative stress markers (8-htdroxy-2'-deoxyguanosine, hexanoyl-lysine), Cu,Zn-superoxide dismutase
6) serum concentration of CA125
7) concentration of interleukin-6 and tumor necrosis factor alpha in peritoneal fluids

Base
Study type Interventional

Study design
Basic design Parallel
Randomization Randomized
Randomization unit Individual
Blinding Open -no one is blinded
Control Active
Stratification NO
Dynamic allocation NO
Institution consideration Institution is not considered as adjustment factor.
Blocking NO
Concealment Numbered container method

Intervention
No. of arms 2
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 L group: Long protocol group (control group: without DNG)
Gonadotropin-releasing hormone agonist (GnRHa, 900 micro g/day) is given from the mid-luteal phase in the previous cycle to the ovulation induction by HCG. Ovarian stimulation is initiated from 2nd day of the IVF-ET cycle, 225 IU follicle stimulating hormone (FSH) for 3days, and thereafter 150 IU human menopausal gonadotropin (HMG). Oocyte retrieval is carried out 35 h after HCG injection. Each mature follicle (more than 18 mm in diameter) is aspirated separately and the follicular fluid containing the oocyte was collected. Immediately after removal of the oocyte, each follicular fluid is centrifuged to remove cellular components, and the supernatant is obtained.
Interventions/Control_2 D group: Dienogest (DNG) group
Dienogest (2mg/day 1mg tablet 2 times/day) is administered orally for three months until the mid-luteal phase in the previous cycle, and followed by GnRHa for standardized IVF-ET long protocol. Ovarian stimulation and oocyte retrieval are same as L group.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit
20 years-old <=
Age-upper limit
40 years-old >=
Gender Female
Key inclusion criteria Endometriosis-associated infertile women who undergo IVF-ET program.
1) woman who has endometrioid cyst (chocolate cyst) (cyst diameter < 4cm) diagnosed by imaging.
2) woman who give written informed consent before entry into this study.
Key exclusion criteria 1) patients who had GnRHa ultra long protocol last 6th month
2) patients who had DNG and/or EP treatment or GnRHa treatment ( > 3 month)for endometriosis
3) patients who has undiagnostic genital bleeding
4) a pregnant woman
5) patients who has estrogen dependence tumor (breast cancer, endometrial cancer)
6) patients who has history of breast cancer
7) patients who has Thrombophlebitis and/or Pulmonary thrombosis, or history of these disease.
8) patients who has the thromboembolism disease of the artery (coronary heart disease, Cerebral apoplexy) or history of these disease
9) patients who has liver dysfunction, or liver disease
10) patients who has Hypersensitivity to DNG, GnRHa, EP, FSH, HMG, HCG
11) patients who is judged to be inappropriate for this study by the doctor
Target sample size 40

Research contact person
Name of lead principal investigator
1st name Norihiro
Middle name
Last name Sugino
Organization Yamaguchi University Graduate School of Medicine
Division name Obstetrics&Gynecology
Zip code 755-8505
Address Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan
TEL +81-836-22-2289
Email sugino@yamaguchi-u.ac.jp

Public contact
Name of contact person
1st name Hiroshi
Middle name
Last name Tamura
Organization Yamaguchi University Graduate School of Medicine
Division name Obstetrics&Gynecology
Zip code 755-8505
Address Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan
TEL +81-836-22-2289
Homepage URL
Email hitamura@yamaguchi-u.ac.jp

Sponsor
Institute Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine
Institute
Department

Funding Source
Organization Mochida Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization Profit organization
Nationality of Funding Organization Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization Ethics Committee/Institutional Review Board of Yamaguchi University School of Medicine
Address Minamikogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan
Tel 0836-22-2428
Email me223@yamaguchi-u.ac.jp

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions 済生会下関総合病院　Saiseikai Shimonoseki General Hospital
吉田レディースクリニック　Yoshida Lady's Clinic

Other administrative information
Date of disclosure of the study information
2011 Year 03 Month 10 Day

Related information
URL releasing protocol https://doi.org/10.1186/s13048-019-0597-y
Publication of results Published

Result
URL related to results and publications https://doi.org/10.1186/s13048-019-0597-y
Number of participants that the trial has enrolled 68
Results 
The numbers of growing follicles, retrieved oocytes, fertilized oocytes, and blastocysts were significantly lower in the DNG group than in the control group. The fertilization and blastocyst rates were also lower in the DNG group than in the control group. Although there was no significant difference in the implantation rate between the groups, the cumulative pregnancy rate and live birth rate were lower in the DNG group than in the control group.
Results date posted
2020 Year 05 Month 05 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
2019 Year 12 Month 12 Day
Baseline Characteristics 
The study inclusion criteria were as follows: infertile women 20 to 40 years of age with endometrial ovarian cysts (<4 cm) diagnosed by ultrasonography or MRI or laparoscopy. The stage of endometriosis (stage III or IV) was defined by the revised American Society for Reproduction Medicine (rASRM) classification via laparoscopy. Women using hormonal contraceptives or other hormonal therapies or who had a disease condition that might interfere with the conduct of the study were excluded. A total of 68 women were therefore included in this study.
Participant flow 
The subjects were randomized to either the DNG group or control group using the envelope method with envelopes distributed by the Department of Obstetrics and Gynecology at Yamaguchi University School of Medicine to each facility (DNG group: 33 cases, control group: 35 cases).
Adverse events 
none
Outcome measures 
Age, stage of endometriosis (rASRM), serum CA125, total amount of FSH (HMG), The numbers of mature follicles, retrieved oocytes, and fertilized oocytes as well as the fertilization rates, implantation rates, and clinical pregnancy rates.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Completed
Date of protocol fixation
2011 Year 02 Month 01 Day
Date of IRB
2011 Year 01 Month 26 Day
Anticipated trial start date
2011 Year 02 Month 01 Day
Last follow-up date
2012 Year 04 Month 01 Day
Date of closure to data entry
2017 Year 01 Month 27 Day
Date trial data considered complete
2017 Year 01 Month 27 Day
Date analysis concluded
2019 Year 12 Month 12 Day

Other
Other related information

Management information
Registered date
2011 Year 03 Month 10 Day
Last modified on
2020 Year 05 Month 07 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000006125