Polycystic Ovary SyndromeNCT01487486
Proteomics & Glyco-Proteomic Analysis of Follicular Fluid
An observational study of Polycystic Ovary Syndrome and Normal Volunteers, run by University of Cincinnati at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Normal Volunteers
- What is being tested?
- IVF Antagonist Protocol
- Type of treatment
- Injection or infusion
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Jan 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Women undergoing In Vitro Fertilization who have: 1. male factor only infertility diagnosis or are oocyte donors 2. PCOS
Who may be able to join
- 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)
- 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
Show all 9Show fewer
- 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
Who cannot join
- Age ≥ 35 y/o
- Female partners with infertility associated diagnosis (i.e. tubal factor, cervical factor, endometriosis)
- Unexplained infertility
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Reproductive Health
Cincinnati, Ohio, 45219
Steven Lindheim, MD, MMM, 513-585-0063, steven.lindheim@uc.edu
Julie Sroga, MD, 513-585-2355, julie.sroga@uc.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Polycystic Ovary Syndrome, Normal Volunteers
- Being tested
- IVF Antagonist Protocol
- Keywords
- Polycystic Ovary Syndrome, PCOS, Follicular Fluid, Proteomics, Glyco-proteomics
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVF Antagonist ProtocolDrug
- Ovulation Induction: Achieved with recombinant FSH (Follistim®) with or without HMG (Menopur®) at total doses of 75-450 IU/day subcutaneous (SC) for 9-14 days.
- Ovulation Suppression: GnRH Antagonist (Ganirelix® - 250microgram 0.5ml) will be initiated following ovulation induction when lead follicle >14mm diameter on ultrasound and continued through the day of hCG (Novirel® or Ovidrel ®) injection
- hCG Injection: Once patient has met criteria for oocyte retrieval, she will inject either Novarel® (5,000-10,000 units Intramuscular) or Ovidrel® (250microgram - 500microgram SC) 35 hours prior to oocyte retrieval.
| Study group | Role | What they receive |
|---|---|---|
| Normal patients | Women with infertility diagnosis of male factor only or women who are oocyte donors Receives: Drug: IVF Antagonist Protocol | |
| Polycystic Ovary Syndrome, High BMI | Women with Polycystic Ovary Syndrome with a BMI between 30-35 Receives: Drug: IVF Antagonist Protocol | |
| Polycystic Ovary Syndrome, Low BMI | Women with Polycustic Ovary Syndrom with a BMI between 20 \& 25 Receives: Drug: IVF Antagonist Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proteomic analysis
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.
Measured: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
Secondary outcomes (1)
Hormone analysis
An aliquot of FF from each patient will be analyzed for the following steroid hormones: progesterone, 17-alpha-hydroxyprogesterone, androstenedione, testosterone, estradiol, and dihydrotestosterone.
Measured: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2013 (estimated)
- Study completionJan 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Steven Lindheim, University of Cincinnati
- Investigators
- Steven Lindheim, MD, MMM, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01487486
- Sponsor's protocol ID
- Proteomics of FF in PCOS
- Status last verified
- Dec 2011
- First submitted
- 16 Nov 2011
- Last updated
- 7 Dec 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 8053879Carmina 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.
PubMed 9988405Carmina 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.
PubMed 9194637Clayton 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.
PubMed 1395063Mendoza 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.
PubMed 11925399Polson 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.
PubMed 2895373Suikkari 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.
PubMed 2448329Conover 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.
PubMed 1375600
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proteomics & Glyco-Proteomic Analysis of Follicular Fluid Derived From Health Patient/Donors and Polycystic Ovary Syndrome Patients
- ClinicalTrials.gov ID
- NCT01487486
- Acronym / sponsor ID
- Proteomics of FF in PCOS
- Conditions
- Polycystic Ovary Syndrome, Normal Volunteers
- Keywords
- Polycystic Ovary Syndrome, PCOS, Follicular Fluid, Proteomics, Glyco-proteomics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Dec 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Jan 2014 (estimated)
- First posted
- 7 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal patients | – | Drug: IVF Antagonist ProtocolWomen with infertility diagnosis of male factor only or women who are oocyte donors |
| Polycystic Ovary Syndrome, High BMI | – | Drug: IVF Antagonist ProtocolWomen with Polycystic Ovary Syndrome with a BMI between 30-35 |
| Polycystic Ovary Syndrome, Low BMI | – | Drug: IVF Antagonist ProtocolWomen with Polycustic Ovary Syndrom with a BMI between 20 \& 25 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Women undergoing In Vitro Fertilization who have: 1. male factor only infertility diagnosis or are oocyte donors 2. PCOS
Key inclusion criteria (9 listed)
- 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)
- 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)
Key exclusion criteria (3 listed)
- Age ≥ 35 y/o
- Female partners with infertility associated diagnosis (i.e. tubal factor, cervical factor, endometriosis)
- Unexplained infertility
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVF Antagonist Protocol1. Ovulation Induction: Achieved with recombinant FSH (Follistim®) with or without HMG (Menopur®) at total doses of 75-450 IU/day subcutaneous (SC) for 9-14 days. 2. Ovulation Suppression: GnRH Antagonist (Ganirelix® - 250microgram 0.5ml) will be initiated following ovulation induction when lead follicle >14mm diameter on ultrasound and continued through the day of hCG (Novirel® or Ovidrel ®) injection 3. hCG Injection: Once patient has met criteria for oocyte retrieval, she will inject either Novarel® (5,000-10,000 units Intramuscular) or Ovidrel® (250microgram - 500microgram SC) 35 hours prior to oocyte retrieval. | Drug | Normal patients, Polycystic Ovary Syndrome, High BMI, Polycystic Ovary Syndrome, Low BMI |
Primary outcome
Proteomic analysis
Time frame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
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.
1 secondary outcome
Hormone analysis
Time frame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2011.
- Background: PubMed 8053879Farquhar 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.
- Background: PubMed 9988405Carmina 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.
- Background: PubMed 9194637Carmina 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.
- Background: PubMed 1395063Clayton 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.
- Background: PubMed 11925399Mendoza 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.
- Background: PubMed 2895373Polson 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.
- Background: PubMed 2448329Suikkari 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.
- Background: PubMed 1375600Conover 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Lindheim, MD, MMM principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Polycystic Ovary Syndrome and Normal Volunteers, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Steven Lindheim, MD, MMM (513-585-0063, steven.lindheim@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proteomic analysis (time frame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01487486, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2011.