Endometrial Heparin-binding Epidermal Growth Factor Expression

NCT04175002 | Unknown

• 1 other identifier: UKM PPI.800-1/1/5/JEP-2019-367
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gene Abnormality

Keywords

heparin-binding epidermal growth factor; polycystic ovarian syndrome; implantation window; obese

Outcome Measures

Primary Outcomes (2)

• Endometrial Heparin-binding Epidermal Growth Factor Expression

  For obese and normal BMI PCOS window of implantation based on Noyes criteria

  After 10 days of oral uterogeston 20mg daily

• Endometrial Heparin-binding Epidermal Growth Factor Expression

  For obese and normal BMI normal fertile women window of implantation based on Noyes criteria

  After 5 days of positive urinary LH

Secondary Outcomes (1)

• Hormonal assay

  During day 2-6 of menstrual cycle

Study Arms (4)

Anovulatory PCOS women with a BMI greater than 27

Drug: utrogestan

Anovulatory PCOS women with a BMI lower than 25

Drug: utrogestan

Healthy fertile women with a BMI greater than 27

Healthy fertile women with a BMI lower than 25

Interventions

utrogestan DRUG

oral uterogeston 200mg daily to achieve window of implantation from previous study

Anovulatory PCOS women with a BMI greater than 27; Anovulatory PCOS women with a BMI lower than 25

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

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. Patients 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

You may qualify if:

• All patients between the aged of 18 to 40 years.
• Women diagnosed with polycystic ovarian syndrome fulfilling two out of three Rotterdam criteria (ie, oligo- or anovulation, hyperandrogenism, and polycystic ovaries on ultrasound).
• 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)

You may not qualify if:

• Smoking
• any hormonal treatment or other drugs to treat anovulation for at least 3 months before the study
• Pregnancy or lactation during the preceding 12 months
• Systemic disease such as endocrine or eating disorders besides PCOS
• Diagnosed with a uterine or ovarian disease.
• Any regular medication such as hormones, herbal substance, statins or corticoids for at least 3 months before the study.
• History of intrauterine device placement.
• All patients between the aged of 18 to 40 years.
• 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).
• Smoking
• any hormonal treatment or other drugs to treat anovulation for at least 3 months before the study
• Pregnancy or lactation during the preceding 12 months
• Systemic disease such as endocrine or eating disorders besides PCOS
• Diagnosed with a uterine or ovarian disease.
• Any regular medication such as hormones, herbal substance, statins or corticoids for at least 3 months before the study.

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

Medically Assisted clinic in Obstetrics & Gynaecology department, UKM Medical Centre

Cheras, Kuala Lumpur, 56000, Malaysia

RECRUITING

Related Publications (15)

• 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.

  BACKGROUND

• 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: 22153789 RESULT

• 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: 24549213 RESULT

• 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: 21481376 RESULT

• 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: 25488942 RESULT

• 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: 19733847 RESULT

• 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: 27156350 RESULT

• 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: 24945252 RESULT

• 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: 18708050 RESULT

• 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: 19565643 RESULT

• 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: 23907942 RESULT

• 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: 17341565 RESULT

• 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: 26649621 RESULT

• 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: 11804942 RESULT

• 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.

  PMID: 41195204 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

endometrial tissue, blood

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Obesity

Interventions

Utrogestan

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Muhammad azrai abu, Medical degree

CONTACT

60196410944; azraiabu1983@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 22, 2019
• Study Start: August 1, 2019
• Primary Completion: May 31, 2020
• Study Completion: July 31, 2020
• Last Updated: November 22, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)