Clinical trial NCT01487486: Proteomics & Glyco-Proteomic Analysis of Follicular Fluid
Official title: Proteomics & Glyco-Proteomic Analysis of Follicular Fluid Derived From Health Patient/Donors and Polycystic Ovary Syndrome Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Polycystic Ovary Syndrome
Normal Volunteers
Keywords: Polycystic Ovary Syndrome
PCOS
Follicular Fluid
Proteomics
Glyco-proteomics
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-12-07
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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. 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. Characterize differential proteomic and glyco-proteomic patterns of the FF in normal women compared to lean and obese women with PCOS.
3. 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.

Eligibility criteria: Inclusion criteria: Inclusion Criteria All

1. Female patients undergoing controlled ovarian hyperstimulation (COH), transvaginal oocyte aspiration (TVA), and Saline Infused Sonography (SIS) with UL collection
2. Age \<35 y/o at time of in vitro fertilization (IVF) cycle
3. Normal ovarian function defined Day 3 Follicular Stimulating Hormone (FSH) \<8 pg/ml or Anti-Mullerian Hormone (≥ 1.0 ng/ml)

Inclusion Criteria Controls:

1. Female patients undergoing COH and TVA donating her oocytes
2. Female patients undergoing COH and TVA for male factor infertility only (i.e. no female causes of infertility)
3. Normal menstrual cycles

Inclusion Criteria Lean PCOS:

1. Diagnosis of PCOS by Rotterdam Criteria
2. BMI ≤ 25 kg/m2 Inclusion Criteria Classic PCOS

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

Exclusion criteria:

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

Primary outcomes:
measure: Proteomic analysis
timeFrame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
Secondary outcomes:
measure: Hormone analysis
timeFrame: Participants will be followed for one IVF cycle including pregnancy outcomes, on average this will be 6-8 weeks.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Center for Reproductive Health
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Steven Lindheim, MD, MMM
role: PRINCIPAL_INVESTIGATOR
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