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Dienogest Versus GnRH-a Pre-treatment in Women With Endometriosis Undergoing IVF

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ClinicalTrials.gov Identifier: NCT03142035
Recruitment Status : Unknown
Verified January 2018 by Dina Chamsy, American University of Beirut Medical Center.
Recruitment status was:  Recruiting
First Posted : May 5, 2017
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
Dina Chamsy, American University of Beirut Medical Center

Brief Summary:

Endometriosis is a chronic gynecologic disease that affects approximately 10% of women in the reproductive age group . It is characterized by the presence of endometrial tissue outside the uterus, causing pelvic pain and subfertility. It is estimated that around 40% of infertile women have the diagnosis of endometriosis . Infertility secondary to endometriosis is thought to be multifactorial. Women with endometriosis often require in vitro fertilization (IVF). One medical intervention that has been shown to improve IVF outcomes in women with endometriosis is hormonal suppression with gonadotropic releasing hormone agonist (GnRH-a) for a period of 3 to 6 months .

In recent years, the effectiveness of dienogest, a fourth-generation progestin, for endometriosis treatment has been demonstrated. Dienogest seems to be as effective as GnRH-a in improving endometriosis-related pelvic pain [4]. However, no study has yet assessed whether dienogest has any benefit in treating endometriosis associated infertility.

The aim of our study is to evaluate the efficacy of dienogest versus GnRH-a in improving ongoing pregnancy rates in women undergoing IVF due to endometriosis. We will conduct a non-blinded randomized controlled trial. One group will receive dienogest 2mg daily for a period of 3 months followed by a standard IVF/Intracytoplasmic Sperm Injection (ICSI) cycle. The second group will receive one injection of 3.75mg of GnRH-a every 28 days for three doses followed by a standard IVF/ICSI cycle 3 months later. The third group will not receive any medical interventions before the planned IVF/ICSI cycle. We hypothesize that patients receiving dienogest will have similar ongoing pregnancy rates compared to patients receiving the GnRH-a injection. Secondary outcomes including number of gonadotropins consumed, number of stimulation days, number of metaphase II eggs retrieved, fertilization rate, embryo quality, miscarriage rate, clinical pregnancy rates, live birth rates and potential maternal and obstetrical complications will also be evaluated. We will also compare ongoing pregnancy rates between the groups receiving Dienogest and placebo, and GnRH agonist and placebo.


Condition or disease Intervention/treatment Phase
Endometriosis Drug: Dienogest 2 MG Drug: gonapeptyl Procedure: IVF/IVF+ART Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 189 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dienogest Versus Gonadotropin Releasing Hormone Agonist Pre-treatment in Women With Endometriosis Undergoing in Vitro Fertilization
Actual Study Start Date : October 22, 2017
Estimated Primary Completion Date : February 22, 2020
Estimated Study Completion Date : February 22, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis
Drug Information available for: Dienogest

Arm Intervention/treatment
Experimental: Dienogest
patients will receive daily dienogest (2mg) for a total of 3 months (84 days)
Drug: Dienogest 2 MG
Dienogest is a fourth-generation progestin of 19-nortestosterone derivative, that has been shown to improve endometriosis associated pelvic pain. It is well tolerated with no androgenic, glucocorticoid or mineralocorticoid activity. Dienogest creates a hyperprogestogenic and hypoestrogenic environment that initially induces a secretory state and then a decidualization of the ectopic endometrium and finally its atrophy. It also inhibits aromatase and COX-2 expression as well as prostaglandin E2 production in endometriotic stromal cells. It also normalizes the activity of natural killer cells and decreases the release of interleukin-1b by macrophages. These anti-inflammatory properties further help in reducing the size of endometriotic lesions

Procedure: IVF/IVF+ART
In-vitro fertilization +/- assisted reproductive technology

Active Comparator: GnRH agonist
patients will receive a single GnRH-a injection (3.25mg) every 28 days for three months.
Drug: gonapeptyl
gonadotropic releasing hormone agonist

Procedure: IVF/IVF+ART
In-vitro fertilization +/- assisted reproductive technology

Control Group
patients will not receive any medical intervention and will proceed with their IFV/ICSI cycles.
Procedure: IVF/IVF+ART
In-vitro fertilization +/- assisted reproductive technology




Primary Outcome Measures :
  1. Ongoing pregnancy rate [ Time Frame: 12 weeks of gestation ]
    pregnancy positive fetal cardiac activity with beyond 12 weeks of gestation (%)


Secondary Outcome Measures :
  1. Gonadotropin consumption (IU) [ Time Frame: 3 months ]
    Gonadotropin consumption (IU)

  2. stimulation (days) [ Time Frame: up to 15 days ]
    Duration of stimulation (days)

  3. metaphase II oocytes retrieved [ Time Frame: 12 weeks of gestation ]
    Number of metaphase II oocytes retrieved at the time of egg collection (n).

  4. Fertilization rate [ Time Frame: day 2 ]
    the number of 2PN zygotes divided by the total number of mature metaphase II oocytes retrieved (%).

  5. Embryo quality. [ Time Frame: day 3 or 5 ]
    Embryo quality according to embryo grading at day 3 or day5

  6. Clinical pregnancy rate [ Time Frame: 12 weeks of gestation ]
    the presence of a gestational sac, with or without cardiac activity, on ultrasound assessment (%).

  7. Ongoing pregnancy rate -2 [ Time Frame: 12 weeks of gestation ]
    pregnancy positive fetal cardiac activity with beyond 12 weeks of gestation (%)



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Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary or secondary infertility
  • Endometriosis, stage III - IV, confirmed surgically by laparoscopy or laparotomy and/or radiologically by the presence of endometrioma on pelvic ultrasound or magnetic resonance imaging (MRI)
  • Normal uterine cavity assessed by hysteroscopy or hysterosalpingogram
  • Normal hormonal profile: TSH, prolactin, fasting blood sugar
  • Normal semen analysis and mild/moderate male factor (Total motile sperm count > 5 million/ml and/or normal WHO morphology >20%)
  • First IVF cycle or history of failed IVF cycles
  • Washout period of ≥6 months after any diagnostic or therapeutic surgery for endometriosis or after any medical treatment with Dienogest or GnRH agonist.

Exclusion Criteria:

  • • Low ovarian reserve defined by one of the following: low AMH ≤1.5ng/mL and/or basal day 3 FSH ≥ 10mIU/mL and/or basal day 3 Estradiol ≥ 60ng/mL and/or previous egg collection yield of ≤3 oocytes.

    • Absolute contraindications to dienogest, including:

  • undiagnosed abnormal vaginal bleeding
  • pregnancy and/or lactation
  • active venous thromboembolic disorder
  • history of or current arterial and cardiovascular disease (eg, MI, CVA)
  • diabetes mellitus with vascular involvement
  • history of or current severe hepatic disease where liver function tests remain abnormal
  • history of or current hepatic neoplasia (benign or malignant)
  • known or suspected sex-hormone-dependent malignancy
  • ocular lesions due to ophthalmic vascular disease, such as partial or complete vision loss or defect in visual fields
  • current or history of migraine with focal aura
  • hypersensitivity or poor tolerance to dienogest

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03142035


Contacts
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Contact: Dina Chamsi, MD 961-01350000 ext 5612 dc09@aub.edu.lb

Locations
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Lebanon
American University of Beirut Medical center Recruiting
Beirut, Lebanon
Contact: Dina Chamsi    961-1350000 ext 5612    dc09@aub.edu.lb   
Sponsors and Collaborators
American University of Beirut Medical Center
Investigators
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Principal Investigator: Dina Chamsi, MD American University of Beirut Medical Center
Publications:

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Responsible Party: Dina Chamsy, Assistant Professor,Minimally Invasive Gynecologic Surgery, American University of Beirut Medical Center
ClinicalTrials.gov Identifier: NCT03142035    
Other Study ID Numbers: OGY.DC.03
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: January 11, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endometriosis
Dienogest
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral
Contraceptive Agents, Female
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents