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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Male Infertility

Intervention / Treatment
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* Drug: Bravelle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infertility group<br>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 | Drug: Bravelle<br>* 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.<br>|
| No Intervention: Fertily group<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 weeks after treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | First week and end of treatment visit (12 weeks). | 
| 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. | First week and end of treatment visit (12 weeks) | 
| Pregnancy rate. | To analyze the results of assisted reproduction treatments in patients receiving FSH treatment. | 6-7 weeks after transfer of the embryo. |