Clinical trial NCT03142035: Dienogest Versus GnRH-a Pre-treatment in Women With Endometriosis Undergoing IVF
Official title: Dienogest Versus Gonadotropin Releasing Hormone Agonist Pre-treatment in Women With Endometriosis Undergoing in Vitro Fertilization
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Endometriosis
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2017-05-05
Enrollment: 189
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Ongoing pregnancy rate
timeFrame: 12 weeks of gestation
Secondary outcomes:
measure: Gonadotropin consumption (IU)
timeFrame: 3 months
measure: stimulation (days)
timeFrame: up to 15 days
measure: metaphase II oocytes retrieved
timeFrame: 12 weeks of gestation
measure: Fertilization rate
timeFrame: day 2
measure: Embryo quality.
timeFrame: day 3 or 5
measure: Clinical pregnancy rate
timeFrame: 12 weeks of gestation
measure: Ongoing pregnancy rate -2
timeFrame: 12 weeks of gestation
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American University of Beirut Medical center
Study officials:
affiliation: American University of Beirut Medical Center
name: Dina Chamsi, MD
role: PRINCIPAL_INVESTIGATOR
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