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

Instituto de Investigacion Sanitaria La Fe

Status and phase: Terminated; Phase 3

Conditions: Male Infertility

Treatments: Drug: Bravelle

Study type: Interventional

Funder types: Other

Identifiers

NCT02605070

FSH_IMEN

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: Male

Ages: 25 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Infertility group

Experimental group

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

Treatment:

Drug: Bravelle

Fertily group

No Intervention group

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.