Proteomics & Glyco-Proteomic Analysis of Follicular Fluid

NCT01487486 | Unknown

• 1 other identifier: Proteomics of FF in PCOS
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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

1. 1.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.
2. 2.Characterize differential proteomic and glyco-proteomic patterns of the FF in normal women compared to lean and obese women with PCOS.
3. 3.To supplement the differential proteomic and glyco-proteomic analysis with steroid hormone analysis in all FF samples.

Conditions

Polycystic Ovary Syndrome; Normal Volunteers

Keywords

Polycystic Ovary Syndrome; PCOS; Follicular Fluid; Proteomics; Glyco-proteomics

Outcome Measures

Primary Outcomes (1)

• 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.

  Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.

Secondary Outcomes (1)

• Hormone analysis

  Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.

Study Arms (3)

Normal patients

Women with infertility diagnosis of male factor only or women who are oocyte donors

Drug: IVF Antagonist Protocol

Polycystic Ovary Syndrome, High BMI

Women with Polycystic Ovary Syndrome with a BMI between 30-35

Drug: IVF Antagonist Protocol

Polycystic Ovary Syndrome, Low BMI

Women with Polycustic Ovary Syndrom with a BMI between 20 \& 25

Drug: IVF Antagonist Protocol

Interventions

IVF Antagonist Protocol DRUG

1. 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.

Normal patients; Polycystic Ovary Syndrome, High BMI; Polycystic Ovary Syndrome, Low BMI

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women undergoing In Vitro Fertilization who have: 1. male factor only infertility diagnosis or are oocyte donors 2. PCOS

You may qualify if:

• 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
• Diagnosis of PCOS by Rotterdam Criteria
• \. Diagnosis of PCOS by Rotterdam Criteria 2. BMI \> 30 kg/m2

You may not qualify if:

• Age ≥ 35 y/o
• Female partners with infertility associated diagnosis (i.e. tubal factor, cervical factor, endometriosis)
• Unexplained infertility

Sponsors & Collaborators

• University of Cincinnati: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Center for Reproductive Health

Cincinnati, Ohio, 45219, United States

Location

Related Publications (8)

• 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.

  PMID: 8053879 BACKGROUND

• 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.

  PMID: 9988405 BACKGROUND

• 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.

  PMID: 9194637 BACKGROUND

• 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.

  PMID: 1395063 BACKGROUND

• 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.

  PMID: 11925399 BACKGROUND

• 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.

  PMID: 2895373 BACKGROUND

• 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.

  PMID: 2448329 BACKGROUND

• 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.

  PMID: 1375600 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Follicular Fluid

MeSH Terms

Conditions

Polycystic Ovary Syndrome

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

Study Officials

• Steven Lindheim, MD, MMM

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven Lindheim, MD, MMM

CONTACT

513-585-0063; steven.lindheim@uc.edu

Julie Sroga, MD

CONTACT

513-585-2355; julie.sroga@uc.edu

Study Design

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

Study Record Dates

• First Submitted: November 16, 2011
• First Posted: December 7, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2014
• Last Updated: December 7, 2011

Record last verified: 2011-12

Locations

US (1)