Relationship of the Microenvironment and Male Fertility

NCT04704141 | Not Yet Recruiting

• 1 other identifier: 2020-1586
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Although much is known about the microenvironment of the gut and the vagina, very little has been published on the microenvironment of the seminal plasma. The seminal plasma is the support fluid for sperm, providing nutrients, facilitating sperm transit to the uterus, and promoting fertilization. It is a rich area of research for markers of fertility and treatment targets. The investigators hypothesize that (1) there are significant populations of seminal microorganisms associated with seminal leukocyte counts well below the WHO's cutoff for pyospermia (1 million/mL) that were not previously detected by traditional culturing methods, and (2) there are pathologic populations of bacteria within the gut and semen microbiome which negatively impact overall fertility, by directly or indirectly impairing hormone status. Participants will be recruited from the Male Fertility practice at the University of Illinois-Chicago (UIC). All participants will have infertility, diagnosed as an inability to conceive pregnancy after 12 months of unprotected intercourse. The normal evaluation of these participants is to obtain at least one semen analysis and bloodwork investigating their endocrine profile: total testosterone, estradiol, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and albumin. Semen volume is typically \>1 mL, and \<0.2 mL is typically used for the semen analysis. If over 1 million/mL round cells are identified, then a Papanicolaou stain would be performed to identify leukocytes. In this study, any semen demonstrated to have round cells would undergo Papanicolaou staining. A portion of the remaining semen, which would typically be discarded, will be sent for microbiome analysis. Secondly, as part of routine care, fertility patients may be started on medications to increase endogenous testosterone (i.e.: clomiphene citrate, anastrozole, etc). Participants started on medications will also be asked to submit a rectal swab for gut microbiome analysis. Routine care is to monitor the hormonal and testicular response with periodic endocrine blood panels and semen analyses; rectal swabs will be requested at these follow-up intervals also. The control group for both hypotheses will be men with clinical infertility with normal semen analyses and hormone profiles.

Conditions

Male Infertility; Male Hypogonadism

Keywords

Infertility; Microenvironment; Microbiome; Seminal Fluid

Outcome Measures

Primary Outcomes (1)

• Characterization of the Microbiota

  16S rRNA sequencing of bacterial DNA found in semen and rectal swab samples will be completed on all samples obtained from participants. This will characterize the microbiota profile of each sample.

  12 months

Study Arms (3)

Infertile men with leukocytes in semen and eugonadal

Standard fertility evaluation and treatments

Infertile men without leukocytes in semen and eugonadal

Standard fertility evaluation and treatments

Infertile men with hypogonadism

Standard fertility evaluation and treatments, including hormone replacement therapy such as with clomiphene citrate

Drug: Hormone replacement therapy

Interventions

Hormone replacement therapy DRUG

A hormone replacement regimen using any medication of a number of standard treatment options

Infertile men with hypogonadism

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Males referred to University of Illinois Hospital Fertility Services

You may qualify if:

• Men diagnosed with infertility who consent to participate in the study

You may not qualify if:

• Prior hormone replacement therapy
• Antibiotic use in past 6 months
• Inability to consent for self, due to age or mental capacity
• Infertility attributable to identifiable causes other than hypogonadism

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Hospital

Chicago, Illinois, 60612, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be collected for hormone analysis using standard analysis methods. Semen and rectal swabs will be collected and microbiome will be analyzed. All samples will be destroyed after study.

MeSH Terms

Conditions

Infertility, Male; Eunuchism; Infertility

Interventions

Hormone Replacement Therapy

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Hypogonadism; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Samuel Ohlander, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel Ohlander, MD

CONTACT

312-996-9330; sohlande@uic.edu

Study Design

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

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: June 1, 2023
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)