Ignite Creation Date:
2025-12-25 @ 4:02 AM
Ignite Modification Date:
2026-03-02 @ 11:04 PM
Study NCT ID:
NCT04175002
Status:
UNKNOWN
Last Update Posted:
2019-11-22
First Post:
2019-11-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Endometrial Heparin-binding Epidermal Growth Factor Expression
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011085', 'term': 'Polycystic Ovary Syndrome'}, {'id': 'D009765', 'term': 'Obesity'}], 'ancestors': [{'id': 'D010048', 'term': 'Ovarian Cysts'}, {'id': 'D003560', 'term': 'Cysts'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'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'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000624167', 'term': 'Utrogestan'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'endometrial tissue, blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-08-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-11', 'completionDateStruct': {'date': '2020-07-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-11-20', 'studyFirstSubmitDate': '2019-11-18', 'studyFirstSubmitQcDate': '2019-11-20', 'lastUpdatePostDateStruct': {'date': '2019-11-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-11-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-05-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Endometrial Heparin-binding Epidermal Growth Factor Expression', 'timeFrame': 'After 10 days of oral uterogeston 20mg daily', 'description': 'For obese and normal BMI PCOS window of implantation based on Noyes criteria'}, {'measure': 'Endometrial Heparin-binding Epidermal Growth Factor Expression', 'timeFrame': 'After 5 days of positive urinary LH', 'description': 'For obese and normal BMI normal fertile women window of implantation based on Noyes criteria'}], 'secondaryOutcomes': [{'measure': 'Hormonal assay', 'timeFrame': 'During day 2-6 of menstrual cycle'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['heparin-binding epidermal growth factor', 'polycystic ovarian syndrome', 'implantation window', 'obese'], 'conditions': ['Gene Abnormality']}, 'referencesModule': {'references': [{'type': 'BACKGROUND', 'citation': 'Mengling S, Xian X, Yongli L, et al. Expression of heparin-binding epidermal growth factor in the endometrium is positively correlated with IVF-ET pregnancy outcome. Int J Clin Exp Pathol 2016;9(8):8280-8285.'}, {'pmid': '22153789', 'type': 'RESULT', 'citation': "Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012 Jan;97(1):28-38.e25. doi: 10.1016/j.fertnstert.2011.09.024. Epub 2011 Dec 6."}, {'pmid': '24549213', 'type': 'RESULT', 'citation': "Joham AE, Boyle JA, Ranasinha S, Zoungas S, Teede HJ. Contraception use and pregnancy outcomes in women with polycystic ovary syndrome: data from the Australian Longitudinal Study on Women's Health. Hum Reprod. 2014 Apr;29(4):802-8. doi: 10.1093/humrep/deu020. Epub 2014 Feb 18."}, {'pmid': '21481376', 'type': 'RESULT', 'citation': 'Bellver J, Martinez-Conejero JA, Labarta E, Alama P, Melo MA, Remohi J, Pellicer A, Horcajadas JA. Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertil Steril. 2011 Jun;95(7):2335-41, 2341.e1-8. doi: 10.1016/j.fertnstert.2011.03.021. Epub 2011 Apr 9.'}, {'pmid': '25488942', 'type': 'RESULT', 'citation': 'Schulte MM, Tsai JH, Moley KH. Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reprod Sci. 2015 Jan;22(1):6-14. doi: 10.1177/1933719114561552. Epub 2014 Dec 7.'}, {'pmid': '19733847', 'type': 'RESULT', 'citation': 'DeUgarte DA, DeUgarte CM, Sahakian V. Surrogate obesity negatively impacts pregnancy rates in third-party reproduction. Fertil Steril. 2010 Feb;93(3):1008-10. doi: 10.1016/j.fertnstert.2009.07.1005. Epub 2009 Sep 5.'}, {'pmid': '27156350', 'type': 'RESULT', 'citation': 'Piltonen TT. Polycystic ovary syndrome: Endometrial markers. Best Pract Res Clin Obstet Gynaecol. 2016 Nov;37:66-79. doi: 10.1016/j.bpobgyn.2016.03.008. Epub 2016 Apr 1.'}, {'pmid': '24945252', 'type': 'RESULT', 'citation': 'Large MJ, Wetendorf M, Lanz RB, Hartig SM, Creighton CJ, Mancini MA, Kovanci E, Lee KF, Threadgill DW, Lydon JP, Jeong JW, DeMayo FJ. The epidermal growth factor receptor critically regulates endometrial function during early pregnancy. PLoS Genet. 2014 Jun 19;10(6):e1004451. doi: 10.1371/journal.pgen.1004451. eCollection 2014 Jun.'}, {'pmid': '18708050', 'type': 'RESULT', 'citation': 'Lim HJ, Dey SK. HB-EGF: a unique mediator of embryo-uterine interactions during implantation. Exp Cell Res. 2009 Feb 15;315(4):619-26. doi: 10.1016/j.yexcr.2008.07.025. Epub 2008 Aug 3.'}, {'pmid': '19565643', 'type': 'RESULT', 'citation': 'Jessmon P, Leach RE, Armant DR. Diverse functions of HBEGF during pregnancy. Mol Reprod Dev. 2009 Dec;76(12):1116-27. doi: 10.1002/mrd.21066.'}, {'pmid': '23907942', 'type': 'RESULT', 'citation': 'Wirstlein PK, Mikolajczyk M, Skrzypczak J. Correlation of the expression of heparanase and heparin-binding EGF-like growth factor in the implantation window of nonconceptual cycle endometrium. Folia Histochem Cytobiol. 2013;51(2):127-34. doi: 10.5603/FHC.2013.0020.'}, {'pmid': '17341565', 'type': 'RESULT', 'citation': 'Zang H, Sahlin L, Masironi B, Eriksson E, Linden Hirschberg A. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. J Clin Endocrinol Metab. 2007 Jun;92(6):2169-75. doi: 10.1210/jc.2006-2171. Epub 2007 Mar 6.'}, {'pmid': '26649621', 'type': 'RESULT', 'citation': 'Hulchiy M, Nybacka A, Sahlin L, Hirschberg AL. Endometrial Expression of Estrogen Receptors and the Androgen Receptor in Women With Polycystic Ovary Syndrome: A Lifestyle Intervention Study. J Clin Endocrinol Metab. 2016 Feb;101(2):561-71. doi: 10.1210/jc.2015-3803. Epub 2015 Dec 9.'}, {'pmid': '11804942', 'type': 'RESULT', 'citation': 'Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002 Feb;66(2):297-304. doi: 10.1095/biolreprod66.2.297.'}, {'pmid': '41195204', 'type': 'DERIVED', 'citation': 'Hamid FA, Mokhtar MH, Abdul Karim AK, Ahmad MF, Abd Aziz NH, Abdul Wahab AY, Abu MA. Obesity results in lower integrin expression in women with polycystic ovarian syndrome during the window of implantation. Front Endocrinol (Lausanne). 2025 Oct 21;16:1590716. doi: 10.3389/fendo.2025.1590716. eCollection 2025.'}]}, 'descriptionModule': {'briefSummary': "Women with PCOS comprise a majority of fertility clinic attendees. Unfortunately, a high failure rate following fertility treatment was observed especially in obese women due to implantation failure. The local study on PCOS women has shown significant changes in an endometrial tumor - regulatory genes but not focusing on the endometrial implantation failure. Many previous attempts using human chorionic gonadotrophin (HCG) infused embryo, gonadotrophin agonist therapy or progesterone support aiming to improve implantation failure in the assisted reproductive technique still unable to enhance pregnancy rate beyond 40% despite a higher' fertilization rate up to 95%. There is still a research gap on what makes obese PCOS women prone to coincides with implantation failure. Endometrial component related to the expression of growth factors play an integral role in establishing cellular context necessary for successful pregnancy. Thus, a new fundamental knowledge on endometrial specific heparin-binding epidermal growth factor expression in the obese PCOS women is vitally important, not only to predict implantation failure but a potential therapy to improve pregnancy outcome.", 'detailedDescription': "This prospective study is going to be performed at UKM Medical Centre for a duration of 1 year. The PCOS and control women will be recruited from the Medically Assisted clinic in Obstetrics \\& Gynaecology department.\n\nThe sample size of this study is calculated using Power and Sample Size Calculator by Dupont \\& Plummer 1998 for paired t-test response version 3.1.2; using the endpoint of mean of Hb-EGF expression during window of implantation in predicting successful pregnancy following in vitro fertilization (IVF) rate by Mengling et al. 2016 (11) as one of its specific outcome. The auto-generated sample size using this programme is 8 subjects. Considering the dropout rate of the sample is 30%, the total sample size required in this study is 10 subjects each arm, making a total sample size 40.\n\nThe participants are divided into four groups according to PCOS diagnosis and Asian adult population body mass index (BMI):\n\n1. Anovulatory PCOS women with a BMI greater than 27 (OB-PCOS)\n2. Anovulatory PCOS women with a BMI lower than 25 (NW-PCOS)\n3. Healthy fertile women with a BMI greater than 27 (OB-C)\n4. Healthy fertile women with a BMI lower than 25 (NW-C)\n\nIn the PCOS group, generally anovulatory cycle hence the implantation window during mid-secretory endometrium can be exhibit following a daily oral micronized progesterone (Utrogestan 200mg) for 10 days based on previously published methods.\n\nVolunteers in the control group with a normal regular menses will be counseled regarding the procedure and monitored for ovulation. The endometrial biopsy will be acquired during implantation window (mid-secretory endometrium), which occurred 7-9 days after the ultrasound and urinary LH confirmed ovulation.\n\nEndometrial samples are obtained using the Pipelle de Cornier catheter for all participants. The endometrium sample that is taken is divided into two portions; a portion for histopathological examination (HPE) for endometrial dating and a portion frozen in liquid nitrogen at -80 degrees Celsius for real-time PCR analysis.\n\nFor endometrial dating, all samples were analyzed by classical histological analysis according to the criteria of Noyes.\n\nA total amount of RNA was isolated from the endometrial tissue using RNA easy kit by following manufacturer's instruction. Pellet will be suspended in 30ul of RNAase-DNAse free water. Finally, nanodrop will be used to determine the concentration and quality of RNA. By following manufacture's instruction, total RNA will be reversed transcribed to cDNA. The target for cDNA is primers for heparin binding epidermal growth factor. QRT-PCR will be performed using Sybergreen Master Mix and detected using QRT-PCR detector machine in accordance with manufacturer's protocols. The reaction was running in real-time PCR machine with 40 cycles and cycling temperature as follows: 95 ºC for 10 minutes and 15 seconds, 56 ºC for 30 seconds and final dissociation stage: 94 ºC for 15 seconds, 56 ºC for 15 seconds and last 95 ºC for 15 seconds. Relative quantification will be calculated by normalizing against any housekeeping genes available. Positive controls and negative controls will be included in each analysis run."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'This prospective study is going to be performed at UKM Medical Centre for a duration of 1 years. The PCOS and control women will be recruited from the Medically Assisted clinic in Obstetrics \\& Gynaecology department.\n\nPatients will be recruited following written consent. Background information such as age, race, parity, menstrual pattern, associated symptoms will be taken. Clinical assessment which includes height, weight, body mass index and hirsutism (determined by a modified Ferriman and Gallwey score) will be performed. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), cortisol, prolactin (PRL), dehydroepiandrosterone sulfate (DHEAS), and β-human chorionic gonadotropin (β-hCG) are measured for all participants. A transvaginal ultrasound scan of the ovaries will be obtained. Endometrial samples are obtained using the Pipelle de Cornier catheter for all participant', 'healthyVolunteers': True, 'eligibilityCriteria': 'The inclusion criteria for the study group are:\n\n1. All patients between the aged of 18 to 40 years.\n2. Women diagnosed with polycystic ovarian syndrome fulfilling two out of three Rotterdam criteria (ie, oligo- or anovulation, hyperandrogenism, and polycystic ovaries on ultrasound).\n3. Healthy volunteer with confirmed fertility (having at least one child previously), with a normal level of basic reproductive hormones and regular interval of the menstrual cycle (26 to 32 days). (Control group)\n\nThe exclusion criteria are:\n\n1. Smoking\n2. any hormonal treatment or other drugs to treat anovulation for at least 3 months before the study\n3. Pregnancy or lactation during the preceding 12 months\n4. Systemic disease such as endocrine or eating disorders besides PCOS\n5. Diagnosed with a uterine or ovarian disease.\n6. Any regular medication such as hormones, herbal substance, statins or corticoids for at least 3 months before the study.\n7. History of intrauterine device placement.\n\nThe inclusion criteria for the control group are:\n\n1. All patients between the aged of 18 to 40 years.\n2. Healthy volunteer with confirmed fertility (having at least one child previously), with a normal level of basic reproductive hormones and regular interval of the menstrual cycle (26 to 32 days).\n\nThe exclusion criteria are:\n\n1. Smoking\n2. any hormonal treatment or other drugs to treat anovulation for at least 3 months before the study\n3. Pregnancy or lactation during the preceding 12 months\n4. Systemic disease such as endocrine or eating disorders besides PCOS\n5. Diagnosed with a uterine or ovarian disease.\n6. Any regular medication such as hormones, herbal substance, statins or corticoids for at least 3 months before the study.\n7. History of intrauterine device placement.'}, 'identificationModule': {'nctId': 'NCT04175002', 'briefTitle': 'Endometrial Heparin-binding Epidermal Growth Factor Expression', 'organization': {'class': 'OTHER', 'fullName': 'National University of Malaysia'}, 'officialTitle': 'Endometrial Heparin-binding Epidermal Growth Factor Expression in Implantation Window of Obese Women With Polycystic Ovarian Syndrome(PCOS)', 'orgStudyIdInfo': {'id': 'UKM PPI.800-1/1/5/JEP-2019-367'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Anovulatory PCOS women with a BMI greater than 27', 'interventionNames': ['Drug: utrogestan']}, {'label': 'Anovulatory PCOS women with a BMI lower than 25', 'interventionNames': ['Drug: utrogestan']}, {'label': 'Healthy fertile women with a BMI greater than 27'}, {'label': 'Healthy fertile women with a BMI lower than 25'}], 'interventions': [{'name': 'utrogestan', 'type': 'DRUG', 'description': 'oral uterogeston 200mg daily to achieve window of implantation from previous study', 'armGroupLabels': ['Anovulatory PCOS women with a BMI greater than 27', 'Anovulatory PCOS women with a BMI lower than 25']}]}, 'contactsLocationsModule': {'locations': [{'zip': '56000', 'city': 'Cheras', 'state': 'Kuala Lumpur', 'status': 'RECRUITING', 'country': 'Malaysia', 'contacts': [{'name': 'Muhammad azrai abu, Medical degree', 'role': 'CONTACT', 'email': 'azraiabu1983@gmail.com', 'phone': '60196410944'}], 'facility': 'Medically Assisted clinic in Obstetrics & Gynaecology department, UKM Medical Centre'}], 'centralContacts': [{'name': 'Muhammad azrai abu, Medical degree', 'role': 'CONTACT', 'email': 'azraiabu1983@gmail.com', 'phone': '60196410944'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National University of Malaysia', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Azrai Abu', 'investigatorAffiliation': 'National University of Malaysia'}}}}