Ignite Creation Date:
2024-05-06 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 1:53 PM
Study NCT ID:
NCT04704141
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-04-20
First Post:
2021-01-07
Brief Title:
Relationship of the Microenvironment and Male Fertility
Sponsor:
University of Illinois at Chicago
Organization:
University of Illinois at Chicago
Study Overview
Official Title:
Relationship of the Gut and Genitourinary Tract Microenvironment and Male Fertility
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 WHOs cutoff for pyospermia 1 millionmL 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 02 mL is typically used for the semen analysis If over 1 millionmL 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 ie 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
The investigators hypothesize that 1 there are significant populations of seminal microorganisms associated with seminal leukocyte counts well below the WHOs cutoff for pyospermia 1 millionmL 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 02 mL is typically used for the semen analysis If over 1 millionmL 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 ie 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
Detailed Description:
Objectives
1 Characterize the microbiota of the genitourinary tract and testicular microenvironment in infertile men with leukocytes in the semen by using 16S rRNA sequencing to analyze the microbiome of de-identified semen samples and compare the results of semen with normal parameters to the results of semen with leukocytes
2 Evaluate the influence of the gut microbiome on hormone replacement therapy in hypogonadal infertile men who are being treated with hormone replacement therapy by analyzing multiple de-identified blood samples and rectal swabs collected both before and over the course of standard hypogonadism treatment The investigators will use 16S rRNA sequencing on the rectal swabs and hormone level analysis of the blood samples
Identification and Enrollment Participants who meet inclusion criteria will be identified in UIC Urology fertility clinics by attending physician co-investigators during routine chart review for standard patient care The participant will then be approached regarding the study and discuss the following informed consent and information within it basic information about the human microenvironments and significance in laymans terms and reinforce that participation in the study will have no impact on the participants care Consent to participate will be obtained if the participant elects to proceed The participant will receive oral and written information about the study The written information includes understandable information about the study with extensive information on the study and include a copy of the consent form
These participants medical records will be reviewed for basic data listed below and if hypogonadal also periodically after routine blood draws see Venipuncture below
Participant information management Participants names MRN and DOB will be stored in a UIC REDCap database Each participant will also be assigned a study identification number generated by a random number generator This ID number will be used to label the respective participants biospecimen
Semen collection and storage As part of standard infertility workup of men a semen sample will be requested after the diagnosis of infertility is made Semen will be prospectively collected by the UIC Andrology Laboratory 820 S Wood St Room 132 Chicago IL 60612
Participants will be instructed on the following for sample collection adapted from Hou et al
1 Present for sample provision after 3-7 days of abstinence
2 Wash hands 2-3 times with soap and water prior to masturbation
3 Wash penis with a focus on glans and coronal sulcus with soap and water followed by 75 alcohol 2-3 times
4 Avoid contact of specimen with inside side wall of sample container
5 01 mL or less of freshly collected semen will be used for standard semen analysis
6 If semen is identified to have any number of round cells then a leukocyte count will be determined by Papanicolaou staining
7 The remainder of semen will be transferred into microcentrifuge tubes with up to 1 mL each tube and stored in a -80C freezer within 2 hours of collection The -80C freezer is in a locked room of the UIC Andrology Laboratory accessible to authorized personnel only7
Venipuncture Participants will have their blood drawn during standard initial evaluation of infertility This will be performed either by UIC phlebotomy services 1801 W Taylor St Room 4B Chicago IL 60612 or any other phlebotomy site and laboratory based on participant preference The endocrine profile will be determined by testing total testosterone estradiol sex hormone binding globulin SHBG luteinizing hormone LH follicle-stimulating hormone FSH and albumin levels A total of 49 mL venous blood is required for these tests and thus a total of 3 gold-topped vials would be drawn from a vein Men determined to be hypogonadal total testosterone 300 ngdL or bioavailable testosterone 150 ngdL will be requested to provide a rectal swab as well see below As part of standard treatment of their condition these participants will be started on medications to increase endogenous testosterone ie clomiphene citrate anastrozole human chorionic gonadotropin etc Additionally as part of standard care these participants will be requested to return for regular assessment of medication side effects and efficacy with laboratory monitoring of their endocrine profile This is carried out in intervals of 3-4 months at the attending physicians discretion The laboratory data of participants meeting inclusion criteria will be recorded in a de-identified REDCap database identified by the study ID number
Rectal swab collection After review of laboratory results with the participant at the first follow-up appointment if the participant is diagnosed with infertility secondary to hypogonadism with no other identifiable causes he will be requested to provide rectal swabs for analysis of the gut microbiome A rectal swab kit will be provided to the participant After a bowel movement the participant will be asked to use the swab to collect sample from the anus and return the sample in the provided sterile plastic bag This will be stored in a secure locked cabinet A rectal swab will then be requested at the same time intervals as follow-up bloodwork collected and stored in the same manner
Microbiota profile characterization Microbiota analysis will be performed by the Igenomix laboratory in Valencia Spain Ronda Narciso Monturiol 11 B Parque Tecnológico Paterna 46980 - Paterna - Valencia Spain Once the investigators have prospectively collected participant samples semen andor rectal swabs the investigators will periodically send samples to Igenomix for processing as logistically feasible The investigators will send 1 sample of each type of specimen per participant as applicable ie if a participant gave enough semen for 3 additional vials in our storage freezer then 1 vial would be sent to Igenomix if the participant is also hypogonadal then a rectal swab is sent if it is indicated and collected as described above Each of these samples will be identified only by study ID number and will have no PHI Only the study ID number associated with each vial and no other identifying information will be sent with the samples ensuring that no PHI will ever be shared with Igenomix Igenomix laboratory will perform microbiota profiling using 16S rRNA gene sequencing in each specimen There will be no stored samples after the analysis as all the material will be used for DNA extraction and subsequent sequencing All acquired data will be uploaded into a separate UIC REDCap database with each samples dataset identified again only by study ID number
Data analysis Data analysis will be performed by Dr Pagani and UIC co-investigators to analyze the data using de-identified data sets from participant chart review and those provided by the Igenomix laboratory
Cursory analysis of microbiota data sets will determine the exact statistical analyses applicable to address our study objectives and hypotheses The investigators will assess bacterial microbiome composition and abundance using statistics computational programs such as the R package R Foundation for Statistical Computing Vienna Austria The investigators will further characterize the bacterial communities by creating hierarchical clustering based on published methods such as described by Hou et al PMID 23993888 Based on the resulting data the investigators will choose the appropriate statistical procedure to test our 2 hypotheses
Study completion Participants will be followed for 12 months allowing for 4 follow-up appointments and sample collections At the conclusion of our study the investigators will destroy any remaining biospecimen All identifiable data will be purged from the REDCap database
1 Characterize the microbiota of the genitourinary tract and testicular microenvironment in infertile men with leukocytes in the semen by using 16S rRNA sequencing to analyze the microbiome of de-identified semen samples and compare the results of semen with normal parameters to the results of semen with leukocytes
2 Evaluate the influence of the gut microbiome on hormone replacement therapy in hypogonadal infertile men who are being treated with hormone replacement therapy by analyzing multiple de-identified blood samples and rectal swabs collected both before and over the course of standard hypogonadism treatment The investigators will use 16S rRNA sequencing on the rectal swabs and hormone level analysis of the blood samples
Identification and Enrollment Participants who meet inclusion criteria will be identified in UIC Urology fertility clinics by attending physician co-investigators during routine chart review for standard patient care The participant will then be approached regarding the study and discuss the following informed consent and information within it basic information about the human microenvironments and significance in laymans terms and reinforce that participation in the study will have no impact on the participants care Consent to participate will be obtained if the participant elects to proceed The participant will receive oral and written information about the study The written information includes understandable information about the study with extensive information on the study and include a copy of the consent form
These participants medical records will be reviewed for basic data listed below and if hypogonadal also periodically after routine blood draws see Venipuncture below
Participant information management Participants names MRN and DOB will be stored in a UIC REDCap database Each participant will also be assigned a study identification number generated by a random number generator This ID number will be used to label the respective participants biospecimen
Semen collection and storage As part of standard infertility workup of men a semen sample will be requested after the diagnosis of infertility is made Semen will be prospectively collected by the UIC Andrology Laboratory 820 S Wood St Room 132 Chicago IL 60612
Participants will be instructed on the following for sample collection adapted from Hou et al
1 Present for sample provision after 3-7 days of abstinence
2 Wash hands 2-3 times with soap and water prior to masturbation
3 Wash penis with a focus on glans and coronal sulcus with soap and water followed by 75 alcohol 2-3 times
4 Avoid contact of specimen with inside side wall of sample container
5 01 mL or less of freshly collected semen will be used for standard semen analysis
6 If semen is identified to have any number of round cells then a leukocyte count will be determined by Papanicolaou staining
7 The remainder of semen will be transferred into microcentrifuge tubes with up to 1 mL each tube and stored in a -80C freezer within 2 hours of collection The -80C freezer is in a locked room of the UIC Andrology Laboratory accessible to authorized personnel only7
Venipuncture Participants will have their blood drawn during standard initial evaluation of infertility This will be performed either by UIC phlebotomy services 1801 W Taylor St Room 4B Chicago IL 60612 or any other phlebotomy site and laboratory based on participant preference The endocrine profile will be determined by testing total testosterone estradiol sex hormone binding globulin SHBG luteinizing hormone LH follicle-stimulating hormone FSH and albumin levels A total of 49 mL venous blood is required for these tests and thus a total of 3 gold-topped vials would be drawn from a vein Men determined to be hypogonadal total testosterone 300 ngdL or bioavailable testosterone 150 ngdL will be requested to provide a rectal swab as well see below As part of standard treatment of their condition these participants will be started on medications to increase endogenous testosterone ie clomiphene citrate anastrozole human chorionic gonadotropin etc Additionally as part of standard care these participants will be requested to return for regular assessment of medication side effects and efficacy with laboratory monitoring of their endocrine profile This is carried out in intervals of 3-4 months at the attending physicians discretion The laboratory data of participants meeting inclusion criteria will be recorded in a de-identified REDCap database identified by the study ID number
Rectal swab collection After review of laboratory results with the participant at the first follow-up appointment if the participant is diagnosed with infertility secondary to hypogonadism with no other identifiable causes he will be requested to provide rectal swabs for analysis of the gut microbiome A rectal swab kit will be provided to the participant After a bowel movement the participant will be asked to use the swab to collect sample from the anus and return the sample in the provided sterile plastic bag This will be stored in a secure locked cabinet A rectal swab will then be requested at the same time intervals as follow-up bloodwork collected and stored in the same manner
Microbiota profile characterization Microbiota analysis will be performed by the Igenomix laboratory in Valencia Spain Ronda Narciso Monturiol 11 B Parque Tecnológico Paterna 46980 - Paterna - Valencia Spain Once the investigators have prospectively collected participant samples semen andor rectal swabs the investigators will periodically send samples to Igenomix for processing as logistically feasible The investigators will send 1 sample of each type of specimen per participant as applicable ie if a participant gave enough semen for 3 additional vials in our storage freezer then 1 vial would be sent to Igenomix if the participant is also hypogonadal then a rectal swab is sent if it is indicated and collected as described above Each of these samples will be identified only by study ID number and will have no PHI Only the study ID number associated with each vial and no other identifying information will be sent with the samples ensuring that no PHI will ever be shared with Igenomix Igenomix laboratory will perform microbiota profiling using 16S rRNA gene sequencing in each specimen There will be no stored samples after the analysis as all the material will be used for DNA extraction and subsequent sequencing All acquired data will be uploaded into a separate UIC REDCap database with each samples dataset identified again only by study ID number
Data analysis Data analysis will be performed by Dr Pagani and UIC co-investigators to analyze the data using de-identified data sets from participant chart review and those provided by the Igenomix laboratory
Cursory analysis of microbiota data sets will determine the exact statistical analyses applicable to address our study objectives and hypotheses The investigators will assess bacterial microbiome composition and abundance using statistics computational programs such as the R package R Foundation for Statistical Computing Vienna Austria The investigators will further characterize the bacterial communities by creating hierarchical clustering based on published methods such as described by Hou et al PMID 23993888 Based on the resulting data the investigators will choose the appropriate statistical procedure to test our 2 hypotheses
Study completion Participants will be followed for 12 months allowing for 4 follow-up appointments and sample collections At the conclusion of our study the investigators will destroy any remaining biospecimen All identifiable data will be purged from the REDCap database
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None