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Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia

Primary Purpose

Male Infertility

Status
Terminated
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Bravelle
Sponsored by
Instituto de Investigacion Sanitaria La Fe
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Infertility

Eligibility Criteria

25 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers
  • Inclusion criteria for the infertility treatment group (n=30)

    1. Between 25-45 years of age.
    2. Total sperm concentration (concentration in millions/mL x volume in mL) between 1-10 million (oligozoospermia) in at least 2 spermiograms obtained after a 2-4 day period of sexual abstinence and with a 7-day separation period between tests.
    3. Caucasian.
    4. Inability of the couple to become pregnant after one year of sexual relations without using any type of contraception.
    5. FSH 2-12 IU/mL.
    6. Total testosterone >300 ng/mL and bioavailable testosterone (calculated with the Sexual Hormone Binding Globulin or SHBG albumin) >145 ng/dL.
  • Inclusion criteria for the control group of fertile males (n=15)

    1. Between 25-45 years of age.
    2. Caucasian.
    3. Sperm concentration and motility above the 5th percentile according to the parameters set forth in the 5th edition of the World Health Organization (WHO) guidelines in at least two spermiograms obtained after a 2-4 day period of sexual abstinence and with a 7-day period between tests.
    4. Seminal volume >1 mL.
    5. Estradiol <50 pg/mL
    6. FSH <4.5 IU/L.
    7. Total testosterone >300 ng/dL and bioavailable testosterone >145 ng/dL.
    8. No vasectomy.
    9. Has sired a child within the past 5 years.
  • Exclusion criteria for the infertility treatment group.

    1. Total sperm concentration <1 million.
    2. Sperm motility of 0%.
    3. History of cryptorchidism, malignant or benign tumors, known chromosomal abnormalities, testicular tor- sion, testicular trauma, orchitis.
    4. Drug use in the past 120 days. thyroid dysfunction
    5. Medical history:thyroid dysfunction, blood disease, diabetes.
    6. Use of anabolic steroids in the past 2 years or for more than 2 years.
    7. Body mass index >30 kg/m .
    8. Intake of over 21 units of alcohol/week in the past 120 days.

Sites / Locations

  • Hospital Universitari i Politècnic La Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Infertility group

Fertily group

Arm Description

Patients referred will be evaluated to participate in the study and then asked to take part.In this visit,the normal protocol for infertility patients will be followed and at least 2 spermiograms and a blood test analyzing the following parameters:FSH, LH,Estradiol,Total testosterone,SHBG, Albumin,Calculation of bioavailable testosterone,Prolactin.If these tests have not been performed,a second baseline visit will be scheduled.Should the patient meet all the inclusion criteria and after the patient has signed an informed consent form agreeing to participate in the study,the physician will prescribe the medication and schedule visits.Before initiating the treatment, they will provide a semen sample.This sample will be sent to the Center for Reproductive Biology,where the sample will be subjected to epigenetic analysis.The patient will be given samples of Bravelle.It is administered subcutaneously.The dose will be 150 IU 3times a week for 3months

Patients who volunteer will be informed of the nature of the study and asked to sign the informed consent form. At least two spermiograms will be performed along with a blood test analyzing the following parameters:FSH,LH,Estradiol,Total testosterone,SHBG,Albumin,Estimation of bioavailable testosterone,Prolactin. A second baseline visit will be scheduled to evaluate the test results and to check whether these subjects meet all the inclusion criteria for the control group. Those subjects will provide a semen sample which will be stored at -20º C. Outpatient visit: week twelve: a physical exam will be carried out to identify any adverse reactions. A blood test and a semen sample will also be obtained.

Outcomes

Primary Outcome Measures

Epigenetic modification
To determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH administration on these modifications and on male infertility

Secondary Outcome Measures

To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.
To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.
To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.
To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.
Pregnancy rate.
To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.

Full Information

First Posted
November 9, 2015
Last Updated
March 1, 2018
Sponsor
Instituto de Investigacion Sanitaria La Fe
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1. Study Identification

Unique Protocol Identification Number
NCT02605070
Brief Title
Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
Official Title
Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Why Stopped
UNDER RECRUITMENT
Study Start Date
November 2015 (undefined)
Primary Completion Date
June 13, 2017 (Actual)
Study Completion Date
June 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Investigacion Sanitaria La Fe

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Single center, prospective, open clinical study to determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH ( follicle stimulating hormone) administration on these modifications and on male infertility.
Detailed Description
Single center, prospective, open clinical study to determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH ( follicle stimulating hormone) administration on these modifications and on male infertility. Main objective: To determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH administration on these modifications and on male infertility. Secondary objectives To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment. To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment. To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Male Infertility

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Infertility group
Arm Type
Experimental
Arm Description
Patients referred will be evaluated to participate in the study and then asked to take part.In this visit,the normal protocol for infertility patients will be followed and at least 2 spermiograms and a blood test analyzing the following parameters:FSH, LH,Estradiol,Total testosterone,SHBG, Albumin,Calculation of bioavailable testosterone,Prolactin.If these tests have not been performed,a second baseline visit will be scheduled.Should the patient meet all the inclusion criteria and after the patient has signed an informed consent form agreeing to participate in the study,the physician will prescribe the medication and schedule visits.Before initiating the treatment, they will provide a semen sample.This sample will be sent to the Center for Reproductive Biology,where the sample will be subjected to epigenetic analysis.The patient will be given samples of Bravelle.It is administered subcutaneously.The dose will be 150 IU 3times a week for 3months
Arm Title
Fertily group
Arm Type
No Intervention
Arm Description
Patients who volunteer will be informed of the nature of the study and asked to sign the informed consent form. At least two spermiograms will be performed along with a blood test analyzing the following parameters:FSH,LH,Estradiol,Total testosterone,SHBG,Albumin,Estimation of bioavailable testosterone,Prolactin. A second baseline visit will be scheduled to evaluate the test results and to check whether these subjects meet all the inclusion criteria for the control group. Those subjects will provide a semen sample which will be stored at -20º C. Outpatient visit: week twelve: a physical exam will be carried out to identify any adverse reactions. A blood test and a semen sample will also be obtained.
Intervention Type
Drug
Intervention Name(s)
Bravelle
Intervention Description
Bravelle will be provided to all patients in the treatment group by the principal investigator (PI) or another member of the research team. From week nine on, the patients will undergo a physical examination on three different occasions to assess the appearance of any adverse reactions during treatment. It will be up to the patient to communicate the appearance of signs or symptoms which could be associated with the use of the drug. At week 12 the patient will be scheduled for another visit to perform a semen study and to measure new hormone levels. To this end, a blood test will be carried out (FSH, LH, estradiol, total testosterone, SHBG, and albumin to calculate the amount of bioavailable testosterone). A semen sample will also be obtained to carry out a spermiogram according to WHO guidelines; part of this sample will be used for epigenetic analysis.
Primary Outcome Measure Information:
Title
Epigenetic modification
Description
To determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH administration on these modifications and on male infertility
Time Frame
12 weeks after treatment.
Secondary Outcome Measure Information:
Title
To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.
Description
To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.
Time Frame
First week and end of treatment visit (12 weeks).
Title
To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.
Description
To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.
Time Frame
First week and end of treatment visit (12 weeks)
Title
Pregnancy rate.
Description
To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.
Time Frame
6-7 weeks after transfer of the embryo.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for the infertility treatment group (n=30) Between 25-45 years of age. Total sperm concentration (concentration in millions/mL x volume in mL) between 1-10 million (oligozoospermia) in at least 2 spermiograms obtained after a 2-4 day period of sexual abstinence and with a 7-day separation period between tests. Caucasian. Inability of the couple to become pregnant after one year of sexual relations without using any type of contraception. FSH 2-12 IU/mL. Total testosterone >300 ng/mL and bioavailable testosterone (calculated with the Sexual Hormone Binding Globulin or SHBG albumin) >145 ng/dL. Inclusion criteria for the control group of fertile males (n=15) Between 25-45 years of age. Caucasian. Sperm concentration and motility above the 5th percentile according to the parameters set forth in the 5th edition of the World Health Organization (WHO) guidelines in at least two spermiograms obtained after a 2-4 day period of sexual abstinence and with a 7-day period between tests. Seminal volume >1 mL. Estradiol <50 pg/mL FSH <4.5 IU/L. Total testosterone >300 ng/dL and bioavailable testosterone >145 ng/dL. No vasectomy. Has sired a child within the past 5 years. Exclusion criteria for the infertility treatment group. Total sperm concentration <1 million. Sperm motility of 0%. History of cryptorchidism, malignant or benign tumors, known chromosomal abnormalities, testicular tor- sion, testicular trauma, orchitis. Drug use in the past 120 days. thyroid dysfunction Medical history:thyroid dysfunction, blood disease, diabetes. Use of anabolic steroids in the past 2 years or for more than 2 years. Body mass index >30 kg/m . Intake of over 21 units of alcohol/week in the past 120 days.
Facility Information:
Facility Name
Hospital Universitari i Politècnic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
17376819
Citation
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Citation
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Citation
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Citation
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Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia

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