- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01487486
Proteomics & Glyco-Proteomic Analysis of Follicular Fluid
Proteomics & Glyco-Proteomic Analysis of Follicular Fluid Derived From Health Patient/Donors and Polycystic Ovary Syndrome Patients
To the best of the investigators knowledge, exhaustive characterization of the low and high abundant proteins and glyco-proteins of the Follicular Fluid (FF) has not yet been achieved. Such an analysis may provide critical molecular data on the role of the FF in oocyte maturation and may identify specific changes in the FF proteome of patients with gynecologic problems, such as Polycystic Ovary Syndrome (PCOS).
Specific Aims
- To perform a comprehensive analysis of normal human FF using sensitive mass spectrometry in combination with conventional approaches for proteomic evaluation and using HPLC and Western blot for glyco-proteomic analysis.
- Characterize differential proteomic and glyco-proteomic patterns of the FF in normal women compared to lean and obese women with PCOS.
- To supplement the differential proteomic and glyco-proteomic analysis with steroid hormone analysis in all FF samples.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In this study, we plan to utilize ultrasensitive mass spectrometry (MS) and other conventional proteomic approaches to identify the low and high abundant proteins present in human FF. Additionally, we plan to use high-performance liquid chromatography (HPLC) and Western blot techniques to evaluate the Neu5Gc and glycan array based ELISA techniques to detect anti-Neu5Gc antibody profile in human FF. This analysis will be performed on FF samples obtained from normal women undergoing In-Vitro Fertilization and Embryo Transfers (IVF-ET) for a male factor alone and oocyte donors from our 3rd Party Reproduction Program and from lean and obese women with PCOS. This study will provide information on protein, glycoprotein, and steroid hormone expression during normal folliculogenesis and during the pathologic condition of PCOS, which should also provide basic scientific information on normal and abnormal oocyte development.
Human FF bathes the developing oocyte. Previous studies indicate that the FF contains cytokines, steroidal and protein hormones, and growth factors. The presence of proteins with such significant biological properties implies a paracrine and autocrine role for the FF in promoting normal oocyte development. Furthermore, the presence of any antigenic sialic acid Neu5Gc and the presence of antibodies targeting these antigenic glycoconjugates (glycolipid and glycoproteins decorated with sialic acid) may interfere with oocyte development, hormonal expression, fertilization, and possibly implantation. Here we hypothesize that an exhaustive proteomic and glyco-proteomic characterization of human FF is essential for a thorough understanding of its biological significance. We also hypothesize that PCOS may have differential expression of the FF protein and glyco-protein milieu, and that the expression may differ further between lean and obese women with PCOS. PCOS represents a heterogeneous disorder. The severity of hyperandrogensim, metabolic and menstrual disturbance, and obesity is variable with up to 40% not clinically expressing signs of classic hyperandrogenism. On the other hand, these atypical, often lean, PCOS women can have impaired glucose tolerance and diabetes. Reports suggest that these lean PCOS women have altered serum IGFBP-1, a characteristic endocrine feature of patients with obese PCOS, and related to hyperinsulinemia and/or obesity. The lean phenotype of PCOS and its significance is unclear but may represent a cryptic or unexpressed form of PCOS or may be a prelude to individuals who will later manifest clinical signs of obese/overweight PCOS. Changes in expression may be expected because of the different amounts of steroidal hormones and inflammatory markers in the FF derived from women with PCOS.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Steven Lindheim, MD, MMM
- Phone Number: 513-585-0063
- Email: steven.lindheim@uc.edu
Study Contact Backup
- Name: Julie Sroga, MD
- Phone Number: 513-585-2355
- Email: julie.sroga@uc.edu
Study Locations
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Ohio
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Cincinnati, Ohio, United States, 45219
- Center for Reproductive Health
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Contact:
- Steven Lindheim, MD, MMM
- Phone Number: 513-585-0063
- Email: steven.lindheim@uc.edu
-
Contact:
- Julie Sroga, MD
- Phone Number: 513-585-2355
- Email: julie.sroga@uc.edu
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Principal Investigator:
- Steven Lindheim, MD,MMM
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Women undergoing In Vitro Fertilization who have:
- male factor only infertility diagnosis or are oocyte donors
- PCOS
Description
Inclusion criteria: Inclusion Criteria All
- Female patients undergoing controlled ovarian hyperstimulation (COH), transvaginal oocyte aspiration (TVA), and Saline Infused Sonography (SIS) with UL collection
- Age <35 y/o at time of in vitro fertilization (IVF) cycle
- Normal ovarian function defined Day 3 Follicular Stimulating Hormone (FSH) <8 pg/ml or Anti-Mullerian Hormone (≥ 1.0 ng/ml)
Inclusion Criteria Controls:
- Female patients undergoing COH and TVA donating her oocytes
- Female patients undergoing COH and TVA for male factor infertility only (i.e. no female causes of infertility)
- Normal menstrual cycles
Inclusion Criteria Lean PCOS:
- Diagnosis of PCOS by Rotterdam Criteria
- BMI ≤ 25 kg/m2 Inclusion Criteria Classic PCOS
1. Diagnosis of PCOS by Rotterdam Criteria 2. BMI > 30 kg/m2
Exclusion criteria:
- Age ≥ 35 y/o
- Female partners with infertility associated diagnosis (i.e. tubal factor, cervical factor, endometriosis)
- Unexplained infertility
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Normal patients
Women with infertility diagnosis of male factor only or women who are oocyte donors
|
|
Polycystic Ovary Syndrome, High BMI
Women with Polycystic Ovary Syndrome with a BMI between 30-35
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Polycystic Ovary Syndrome, Low BMI
Women with Polycustic Ovary Syndrom with a BMI between 20 & 25
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proteomic analysis
Time Frame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
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For proteomic analysis the follicular fluid samples will be either directly analyzed by MS or will be processed to deplete albumin which is likely to be present in very high abundance in the FF.
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Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hormone analysis
Time Frame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
|
An aliquot of FF from each patient will be analyzed for the following steroid hormones: progesterone, 17-alpha-hydroxyprogesterone, androstenedione, testosterone, estradiol, and dihydrotestosterone.
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Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Steven Lindheim, MD, MMM, University of Cincinnati
Publications and helpful links
General Publications
- Polson DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries--a common finding in normal women. Lancet. 1988 Apr 16;1(8590):870-2. doi: 10.1016/s0140-6736(88)91612-1.
- Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT. The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust N Z J Obstet Gynaecol. 1994 Feb;34(1):67-72. doi: 10.1111/j.1479-828x.1994.tb01041.x.
- Carmina E, Lobo RA. Do hyperandrogenic women with normal menses have polycystic ovary syndrome? Fertil Steril. 1999 Feb;71(2):319-22. doi: 10.1016/s0015-0282(98)00455-5.
- Carmina E, Wong L, Chang L, Paulson RJ, Sauer MV, Stanczyk FZ, Lobo RA. Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound. Hum Reprod. 1997 May;12(5):905-9. doi: 10.1093/humrep/12.5.905.
- Clayton RN, Ogden V, Hodgkinson J, Worswick L, Rodin DA, Dyer S, Meade TW. How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol (Oxf). 1992 Aug;37(2):127-34. doi: 10.1111/j.1365-2265.1992.tb02296.x.
- Mendoza C, Ruiz-Requena E, Ortega E, Cremades N, Martinez F, Bernabeu R, Greco E, Tesarik J. Follicular fluid markers of oocyte developmental potential. Hum Reprod. 2002 Apr;17(4):1017-22. doi: 10.1093/humrep/17.4.1017.
- Suikkari AM, Koivisto VA, Rutanen EM, Yki-Jarvinen H, Karonen SL, Seppala M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab. 1988 Feb;66(2):266-72. doi: 10.1210/jcem-66-2-266.
- Conover CA, Lee PD, Kanaley JA, Clarkson JT, Jensen MD. Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans. J Clin Endocrinol Metab. 1992 Jun;74(6):1355-60. doi: 10.1210/jcem.74.6.1375600.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Proteomics of FF in PCOS
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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