Ovarian Reserve and Matrix Metalloproteinases

NCT ID: NCT05443282

Last Updated: 2022-07-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

133 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-08-10

Study Completion Date

2022-03-07

Brief Summary

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Primary Ovarian Insufficiency (POI) is dysfunction of ovaries before 40 years of age. It has been reported that genetic factors, endocrine disorders, previous pelvic surgeries, chemotherapy and radiotherapy, and autoimmune mechanisms play a role in 10%, however the etiology has not been clarified in 90% of the cases. Oxidative stress and autoimmunity has been shown to be responsible in the etiopathogenesis of POI. Prolidase is an imidodipeptidase. Prolidase was shown to be related with oxidative stress and autoimmune diseases in previous studies. In addition, it is thought that the level of prolidase plays a role both in the etiopathogenesis and progression of diseases. This study aims to investigate the level of prolidase enzyme in women with POI.

Detailed Description

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Primary Ovarian Insufficiency (POI) is dysfunction of ovaries before 40 years of age. It has been reported that genetic factors, endocrine disorders, previous pelvic surgeries, chemotherapy and radiotherapy, and autoimmune mechanisms play a role in 10%, however the etiology has not been clarified in 90% of the cases that are diagnosed as idiopathic POI. Recent studies concentrated on the role of immune mechanisms in idiopathic POI. Prolidase is a matrix metalloproteinase that plays a role in various metabolic processes and is responsible for the destruction of dipeptides containing proline and hydroxyproline. The prolidase has been shown to be related with oxidative stress and autoimmune diseases in previous studies. Prolidase was shown to be a diagnostic and prognostic value in a number of diseases. Proline and hydroxyproline are metabolites produced through the prolidase activity. Proline itself is also considered as a kind of metabolic stress indicator. On the other hand, free proline in the medium is known to inhibit the prolidase enzyme activity. Therefore, simultaneous measurement of proline and hydroxyproline levels in the medium enables to more accurately calculate the prolidase activity. This study aim to analyze the prolidase level in POI patients compared to healthy menstruating women. Besides the prolidase activity, we also aim to measure proline and hydroxyproline levels in order to provide the calibration for accurate results in terms of prolidase activity.

Conditions

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Oxidative Stress Ovarian Insufficiency, Primary Ovarian Failure, Premature

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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POI group (Study group)

* The study group included 68 women with POI.
* The POI cases had been diagnosed as idiopathic POI.
* The POI diagnosis was based on the presence of amenorrhea before the age of 40, increased serum FSH level higher than 40 mIU/ml, and decreased estradiol levels lesser than 50 pg/mL.

Prolidase Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of prolidase enzyme level by ELISA method.

Follicle Stimulating Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of follicle stimulating hormone level.

Estradiol Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of estradiol hormone level.

Proline Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of proline level.

Hydroxyproline Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of hydroxyproline level.

Anti-mullerian Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of anti-mullerian hormone level.

Antral Follicle Count

Intervention Type DIAGNOSTIC_TEST

Ultrasonographic evaluation of antral follicle count to determine ovarian reserve.

Prolactine Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum prolactine hormone level.

Thyroid Stimulating Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum thyroid stimulating hormone level.

Normally menstruating women (Control group)

* Control group consisted of 65 healthy, regularly menstruating women.
* The women were at the age of lesser than 40 years old.
* The women were recruited consecutively from those that applied to outpatient clinics to get counselling for family planning.

Prolidase Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of prolidase enzyme level by ELISA method.

Follicle Stimulating Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of follicle stimulating hormone level.

Estradiol Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of estradiol hormone level.

Proline Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of proline level.

Hydroxyproline Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of hydroxyproline level.

Anti-mullerian Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum level of anti-mullerian hormone level.

Antral Follicle Count

Intervention Type DIAGNOSTIC_TEST

Ultrasonographic evaluation of antral follicle count to determine ovarian reserve.

Prolactine Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum prolactine hormone level.

Thyroid Stimulating Hormone Level

Intervention Type DIAGNOSTIC_TEST

Measurement of venous blood serum thyroid stimulating hormone level.

Interventions

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Prolidase Level

Measurement of venous blood serum level of prolidase enzyme level by ELISA method.

Intervention Type DIAGNOSTIC_TEST

Follicle Stimulating Hormone Level

Measurement of venous blood serum level of follicle stimulating hormone level.

Intervention Type DIAGNOSTIC_TEST

Estradiol Level

Measurement of venous blood serum level of estradiol hormone level.

Intervention Type DIAGNOSTIC_TEST

Proline Level

Measurement of venous blood serum level of proline level.

Intervention Type DIAGNOSTIC_TEST

Hydroxyproline Level

Measurement of venous blood serum level of hydroxyproline level.

Intervention Type DIAGNOSTIC_TEST

Anti-mullerian Hormone Level

Measurement of venous blood serum level of anti-mullerian hormone level.

Intervention Type DIAGNOSTIC_TEST

Antral Follicle Count

Ultrasonographic evaluation of antral follicle count to determine ovarian reserve.

Intervention Type DIAGNOSTIC_TEST

Prolactine Level

Measurement of venous blood serum prolactine hormone level.

Intervention Type DIAGNOSTIC_TEST

Thyroid Stimulating Hormone Level

Measurement of venous blood serum thyroid stimulating hormone level.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of POI for study group
* Regularly menstruating women for control group
* Normally developed secondary sexual characteristics

Exclusion Criteria

* Cardiovascular diseases including hypertension
* Type 1 or type 2 diabetes mellitus
* Morbid obesity
* Primary adrenal insufficiency
* Uterine fibroids
* Thyroid dysfunctions including Hashimoto thyroiditis and Grave's disease
* Hepatic dysfunctions
* Renal insufficiency
* Genetic disorders in chromosome constitution or karyotype analysis including monosomy X, trisomy X and gene mutations as BMP15, FMR I, POFIB, and GDF9
* Neurologic diseases
* Psychiatric disorders
* Autoimmune diseases or syndromes including Addison's disease, autoimmune syndromes, scleroderma, Sjogren's syndrome, myasthenia gravis, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and familial Mediterranean fever
* History of any malignancy
* History of exposure to chemotherapeutic agents or radiotherapy
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Ankara City Hospital Bilkent

OTHER

Sponsor Role lead

Responsible Party

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Esin Merve Erol Koç

Medical Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Esin Merve Erol Koç, MD

Role: PRINCIPAL_INVESTIGATOR

Ankara City Hospital Bilkent

Locations

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Ankara City Hospital

Ankara, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol. 2014 Jul;124(1):193-197. doi: 10.1097/01.AOG.0000451757.51964.98.

Reference Type RESULT
PMID: 24945456 (View on PubMed)

Szeliga A, Calik-Ksepka A, Maciejewska-Jeske M, Grymowicz M, Smolarczyk K, Kostrzak A, Smolarczyk R, Rudnicka E, Meczekalski B. Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge. Int J Mol Sci. 2021 Mar 5;22(5):2594. doi: 10.3390/ijms22052594.

Reference Type RESULT
PMID: 33807517 (View on PubMed)

Rafique S, Sterling EW, Nelson LM. A new approach to primary ovarian insufficiency. Obstet Gynecol Clin North Am. 2012 Dec;39(4):567-86. doi: 10.1016/j.ogc.2012.09.007.

Reference Type RESULT
PMID: 23182561 (View on PubMed)

Namiduru ES. Prolidase. Bratisl Lek Listy. 2016;117(8):480-5. doi: 10.4149/bll_2016_093.

Reference Type RESULT
PMID: 27546702 (View on PubMed)

Zhou F, Shi LB, Zhang SY. Ovarian Fibrosis: A Phenomenon of Concern. Chin Med J (Engl). 2017 Feb 5;130(3):365-371. doi: 10.4103/0366-6999.198931.

Reference Type RESULT
PMID: 28139522 (View on PubMed)

Hart RJ. Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics. Physiol Rev. 2016 Jul;96(3):873-909. doi: 10.1152/physrev.00023.2015.

Reference Type RESULT
PMID: 27252278 (View on PubMed)

Kitchener RL, Grunden AM. Prolidase function in proline metabolism and its medical and biotechnological applications. J Appl Microbiol. 2012 Aug;113(2):233-47. doi: 10.1111/j.1365-2672.2012.05310.x. Epub 2012 May 10.

Reference Type RESULT
PMID: 22512465 (View on PubMed)

Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2015 Mar;103(3):e9-e17. doi: 10.1016/j.fertnstert.2014.12.093. Epub 2015 Jan 10.

Reference Type RESULT
PMID: 25585505 (View on PubMed)

Myara I, Charpentier C, Lemonnier A. Optimal conditions for prolidase assay by proline colorimetric determination: application to iminodipeptiduria. Clin Chim Acta. 1982 Oct 27;125(2):193-205. doi: 10.1016/0009-8981(82)90196-6.

Reference Type RESULT
PMID: 7139961 (View on PubMed)

Huang Y, Hu C, Ye H, Luo R, Fu X, Li X, Huang J, Chen W, Zheng Y. Inflamm-Aging: A New Mechanism Affecting Premature Ovarian Insufficiency. J Immunol Res. 2019 Jan 2;2019:8069898. doi: 10.1155/2019/8069898. eCollection 2019.

Reference Type RESULT
PMID: 30719458 (View on PubMed)

Bakalov VK, Anasti JN, Calis KA, Vanderhoof VH, Premkumar A, Chen S, Furmaniak J, Smith BR, Merino MJ, Nelson LM. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Fertil Steril. 2005 Oct;84(4):958-65. doi: 10.1016/j.fertnstert.2005.04.060.

Reference Type RESULT
PMID: 16213850 (View on PubMed)

Luborsky J. Ovarian autoimmune disease and ovarian autoantibodies. J Womens Health Gend Based Med. 2002 Sep;11(7):585-99. doi: 10.1089/152460902760360540.

Reference Type RESULT
PMID: 12396892 (View on PubMed)

Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005 Jul-Aug;11(4):391-410. doi: 10.1093/humupd/dmi012. Epub 2005 May 26.

Reference Type RESULT
PMID: 15919682 (View on PubMed)

Carp HJ, Selmi C, Shoenfeld Y. The autoimmune bases of infertility and pregnancy loss. J Autoimmun. 2012 May;38(2-3):J266-74. doi: 10.1016/j.jaut.2011.11.016. Epub 2012 Jan 27.

Reference Type RESULT
PMID: 22284905 (View on PubMed)

La Marca A, Broekmans FJ, Volpe A, Fauser BC, Macklon NS; ESHRE Special Interest Group for Reproductive Endocrinology--AMH Round Table. Anti-Mullerian hormone (AMH): what do we still need to know? Hum Reprod. 2009 Sep;24(9):2264-75. doi: 10.1093/humrep/dep210. Epub 2009 Jun 11.

Reference Type RESULT
PMID: 19520713 (View on PubMed)

Other Identifiers

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E1-20-1189

Identifier Type: -

Identifier Source: org_study_id

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