Ignite Creation Date:
2025-12-24 @ 10:37 PM
Ignite Modification Date:
2026-04-02 @ 4:19 PM
Study NCT ID:
NCT03142035
Status:
UNKNOWN
Last Update Posted:
2022-05-23
First Post:
2017-02-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Dienogest Versus GnRH-a Pre-treatment in Women With Endometriosis Undergoing IVF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D004715', 'term': 'Endometriosis'}], 'ancestors': [{'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C023635', 'term': 'dienogest'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 189}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2017-10-22', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-05', 'completionDateStruct': {'date': '2023-02-22', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2022-05-20', 'studyFirstSubmitDate': '2017-02-22', 'studyFirstSubmitQcDate': '2017-05-03', 'lastUpdatePostDateStruct': {'date': '2022-05-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-05-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-02-22', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Ongoing pregnancy rate', 'timeFrame': '12 weeks of gestation', 'description': 'pregnancy positive fetal cardiac activity with beyond 12 weeks of gestation (%)'}], 'secondaryOutcomes': [{'measure': 'Gonadotropin consumption (IU)', 'timeFrame': '3 months', 'description': 'Gonadotropin consumption (IU)'}, {'measure': 'stimulation (days)', 'timeFrame': 'up to 15 days', 'description': 'Duration of stimulation (days)'}, {'measure': 'metaphase II oocytes retrieved', 'timeFrame': '12 weeks of gestation', 'description': 'Number of metaphase II oocytes retrieved at the time of egg collection (n).'}, {'measure': 'Fertilization rate', 'timeFrame': 'day 2', 'description': 'the number of 2PN zygotes divided by the total number of mature metaphase II oocytes retrieved (%).'}, {'measure': 'Embryo quality.', 'timeFrame': 'day 3 or 5', 'description': 'Embryo quality according to embryo grading at day 3 or day5'}, {'measure': 'Clinical pregnancy rate', 'timeFrame': '12 weeks of gestation', 'description': 'the presence of a gestational sac, with or without cardiac activity, on ultrasound assessment (%).'}, {'measure': 'Ongoing pregnancy rate -2', 'timeFrame': '12 weeks of gestation', 'description': 'pregnancy positive fetal cardiac activity with beyond 12 weeks of gestation (%)'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Endometriosis']}, 'referencesModule': {'references': [{'pmid': '15541453', 'type': 'BACKGROUND', 'citation': 'Giudice LC, Kao LC. Endometriosis. Lancet. 2004 Nov 13-19;364(9447):1789-99. doi: 10.1016/S0140-6736(04)17403-5.'}, {'pmid': '6216124', 'type': 'BACKGROUND', 'citation': 'Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982 Dec;38(6):667-72. doi: 10.1016/s0015-0282(16)46691-4.'}, {'pmid': '16437491', 'type': 'BACKGROUND', 'citation': 'Sallam HN, Garcia-Velasco JA, Dias S, Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis. Cochrane Database Syst Rev. 2006 Jan 25;2006(1):CD004635. doi: 10.1002/14651858.CD004635.pub2.'}, {'pmid': '20089522', 'type': 'BACKGROUND', 'citation': 'Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010 Mar;25(3):633-41. doi: 10.1093/humrep/dep469. Epub 2010 Jan 19.'}, {'pmid': '12057720', 'type': 'BACKGROUND', 'citation': 'Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002 Jun;77(6):1148-55. doi: 10.1016/s0015-0282(02)03112-6.'}, {'pmid': '3091408', 'type': 'BACKGROUND', 'citation': 'Matson PL, Yovich JL. The treatment of infertility associated with endometriosis by in vitro fertilization. Fertil Steril. 1986 Sep;46(3):432-4. doi: 10.1016/s0015-0282(16)49581-6.'}, {'pmid': '8046030', 'type': 'BACKGROUND', 'citation': 'Simon C, Gutierrez A, Vidal A, de los Santos MJ, Tarin JJ, Remohi J, Pellicer A. Outcome of patients with endometriosis in assisted reproduction: results from in-vitro fertilization and oocyte donation. Hum Reprod. 1994 Apr;9(4):725-9. doi: 10.1093/oxfordjournals.humrep.a138578.'}, {'pmid': '9447453', 'type': 'BACKGROUND', 'citation': 'Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG. Ovarian dysfunction in endometriosis-associated and unexplained infertility. J Assist Reprod Genet. 1997 Nov;14(10):554-7. doi: 10.1023/a:1022568331845.'}, {'pmid': '11808845', 'type': 'BACKGROUND', 'citation': 'Norenstedt SN, Linderoth-Nagy C, Bergendal A, Sjoblom P, Bergqvist A. Reduced developmental potential in oocytes from women with endometriosis. J Assist Reprod Genet. 2001 Dec;18(12):644-9. doi: 10.1023/a:1013111200251.'}, {'pmid': '9591505', 'type': 'BACKGROUND', 'citation': 'Nakahara K, Saito H, Saito T, Ito M, Ohta N, Takahashi T, Hiroi M. Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies. Fertil Steril. 1998 May;69(5):931-5. doi: 10.1016/s0015-0282(98)00038-7.'}, {'pmid': '9757870', 'type': 'BACKGROUND', 'citation': 'Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril. 1998 Sep;70(3):425-31. doi: 10.1016/s0015-0282(98)00204-0.'}, {'pmid': '10685541', 'type': 'BACKGROUND', 'citation': 'Toya M, Saito H, Ohta N, Saito T, Kaneko T, Hiroi M. Moderate and severe endometriosis is associated with alterations in the cell cycle of granulosa cells in patients undergoing in vitro fertilization and embryo transfer. Fertil Steril. 2000 Feb;73(2):344-50. doi: 10.1016/s0015-0282(99)00507-5.'}, {'pmid': '12372468', 'type': 'BACKGROUND', 'citation': 'Garcia-Velasco JA, Mulayim N, Kayisli UA, Arici A. Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis. Fertil Steril. 2002 Oct;78(4):855-9. doi: 10.1016/s0015-0282(02)03320-4.'}, {'pmid': '18948311', 'type': 'BACKGROUND', 'citation': 'Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod. 2009 Feb;24(2):254-69. doi: 10.1093/humrep/den379. Epub 2008 Oct 23.'}, {'pmid': '12419041', 'type': 'BACKGROUND', 'citation': 'Geber S, Ferreira DP, Spyer Prates LF, Sales L, Sampaio M. Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment. Reprod Biomed Online. 2002 Sep-Oct;5(2):162-6. doi: 10.1016/s1472-6483(10)61619-7.'}, {'pmid': '12592242', 'type': 'BACKGROUND', 'citation': 'Aboulghar MA, Mansour RT, Serour GI, Al-Inany HG, Aboulghar MM. The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study. Am J Obstet Gynecol. 2003 Feb;188(2):371-5. doi: 10.1067/mob.2003.13.'}, {'pmid': '9653702', 'type': 'BACKGROUND', 'citation': 'Tei C, Miyazaki T, Kuji N, Tanaka M, Sueoka K, Yoshimura Y. Effect of danazol on the pregnancy rate in patients with unsuccessful in vitro fertilization-embryo transfer. J Reprod Med. 1998 Jun;43(6):541-6.'}, {'pmid': '8092234', 'type': 'BACKGROUND', 'citation': 'Marcus SF, Edwards RG. High rates of pregnancy after long-term down-regulation of women with severe endometriosis. Am J Obstet Gynecol. 1994 Sep;171(3):812-7. doi: 10.1016/0002-9378(94)90103-1.'}, {'pmid': '8530675', 'type': 'BACKGROUND', 'citation': 'Chedid S, Camus M, Smitz J, Van Steirteghem AC, Devroey P. Comparison among different ovarian stimulation regimens for assisted procreation procedures in patients with endometriosis. Hum Reprod. 1995 Sep;10(9):2406-11. doi: 10.1093/oxfordjournals.humrep.a136308.'}, {'pmid': '9532465', 'type': 'BACKGROUND', 'citation': 'Ruiz-Velasco V, Allende S. Goserelin followed by assisted reproduction: results in infertile women with endometriosis. Int J Fertil Womens Med. 1998 Jan-Feb;43(1):18-23.'}, {'pmid': '25069386', 'type': 'BACKGROUND', 'citation': 'Bizzarri N, Remorgida V, Leone Roberti Maggiore U, Scala C, Tafi E, Ghirardi V, Salvatore S, Candiani M, Venturini PL, Ferrero S. Dienogest in the treatment of endometriosis. Expert Opin Pharmacother. 2014 Sep;15(13):1889-902. doi: 10.1517/14656566.2014.943734. Epub 2014 Jul 29.'}, {'pmid': '22128200', 'type': 'BACKGROUND', 'citation': 'Klipping C, Duijkers I, Remmers A, Faustmann T, Zurth C, Klein S, Schuett B. Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women. J Clin Pharmacol. 2012 Nov;52(11):1704-13. doi: 10.1177/0091270011423664. Epub 2011 Nov 29.'}, {'pmid': '12372443', 'type': 'BACKGROUND', 'citation': 'Surrey ES, Silverberg KM, Surrey MW, Schoolcraft WB. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization-embryo transfer in patients with endometriosis. Fertil Steril. 2002 Oct;78(4):699-704. doi: 10.1016/s0015-0282(02)03373-3.'}]}, 'descriptionModule': {'briefSummary': '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 .\n\nIn 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '38 Years', 'minimumAge': '18 Years', 'genderBased': True, 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Primary or secondary infertility\n* 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)\n* Normal uterine cavity assessed by hysteroscopy or hysterosalpingogram\n* Normal hormonal profile: TSH, prolactin, fasting blood sugar\n* Normal semen analysis and mild/moderate male factor (Total motile sperm count \\> 5 million/ml and/or normal WHO morphology \\>20%)\n* First IVF cycle or history of failed IVF cycles\n* Washout period of ≥6 months after any diagnostic or therapeutic surgery for endometriosis or after any medical treatment with Dienogest or GnRH agonist.\n\nExclusion Criteria:\n\n* • 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.\n\n • Absolute contraindications to dienogest, including:\n* undiagnosed abnormal vaginal bleeding\n* pregnancy and/or lactation\n* active venous thromboembolic disorder\n* history of or current arterial and cardiovascular disease (eg, MI, CVA)\n* diabetes mellitus with vascular involvement\n* history of or current severe hepatic disease where liver function tests remain abnormal\n* history of or current hepatic neoplasia (benign or malignant)\n* known or suspected sex-hormone-dependent malignancy\n* ocular lesions due to ophthalmic vascular disease, such as partial or complete vision loss or defect in visual fields\n* current or history of migraine with focal aura\n* hypersensitivity or poor tolerance to dienogest'}, 'identificationModule': {'nctId': 'NCT03142035', 'briefTitle': 'Dienogest Versus GnRH-a Pre-treatment in Women With Endometriosis Undergoing IVF', 'organization': {'class': 'OTHER', 'fullName': 'American University of Beirut Medical Center'}, 'officialTitle': 'Dienogest Versus Gonadotropin Releasing Hormone Agonist Pre-treatment in Women With Endometriosis Undergoing in Vitro Fertilization', 'orgStudyIdInfo': {'id': 'OGY.DC.03'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dienogest', 'description': 'patients will receive daily dienogest (2mg) for a total of 3 months (84 days)', 'interventionNames': ['Drug: Dienogest 2 MG', 'Procedure: IVF/IVF+ART']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'GnRH agonist', 'description': 'patients will receive a single GnRH-a injection (3.25mg) every 28 days for three months.', 'interventionNames': ['Drug: gonapeptyl', 'Procedure: IVF/IVF+ART']}, {'type': 'OTHER', 'label': 'Control Group', 'description': 'patients will not receive any medical intervention and will proceed with their IFV/ICSI cycles.', 'interventionNames': ['Procedure: IVF/IVF+ART']}], 'interventions': [{'name': 'Dienogest 2 MG', 'type': 'DRUG', 'description': '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', 'armGroupLabels': ['Dienogest']}, {'name': 'gonapeptyl', 'type': 'DRUG', 'description': 'gonadotropic releasing hormone agonist', 'armGroupLabels': ['GnRH agonist']}, {'name': 'IVF/IVF+ART', 'type': 'PROCEDURE', 'description': 'In-vitro fertilization +/- assisted reproductive technology', 'armGroupLabels': ['Control Group', 'Dienogest', 'GnRH agonist']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Beirut', 'status': 'RECRUITING', 'country': 'Lebanon', 'contacts': [{'name': 'Dina Chamsi', 'role': 'CONTACT', 'email': 'dc09@aub.edu.lb', 'phone': '961-1350000', 'phoneExt': '5612'}], 'facility': 'American University of Beirut Medical center', 'geoPoint': {'lat': 33.89332, 'lon': 35.50157}}], 'centralContacts': [{'name': 'Dina Chamsi, MD', 'role': 'CONTACT', 'email': 'dc09@aub.edu.lb', 'phone': '961-01350000', 'phoneExt': '5612'}], 'overallOfficials': [{'name': 'Dina Chamsi, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'American University of Beirut Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'American University of Beirut Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor,Minimally Invasive Gynecologic Surgery', 'investigatorFullName': 'Dina Chamsy', 'investigatorAffiliation': 'American University of Beirut Medical Center'}}}}