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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

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 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

NCT ID

NCT02605070

First Posted

November 9, 2015

Last Updated

March 1, 2018

Sponsor

Instituto de Investigacion Sanitaria La Fe

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

5. Study Description

Brief Summary

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

Arm Title

Fertily group

Arm Type

No Intervention

Arm Description

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

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

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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Results Reference

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PubMed Identifier

11756355

Citation

Dohle GR, Halley DJ, Van Hemel JO, van den Ouwel AM, Pieters MH, Weber RF, Govaerts LC. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia. Hum Reprod. 2002 Jan;17(1):13-6. doi: 10.1093/humrep/17.1.13.

Results Reference

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PubMed Identifier

9091344

Citation

Simoni M, Gromoll J, Dworniczak B, Rolf C, Abshagen K, Kamischke A, Carani C, Meschede D, Behre HM, Horst J, Nieschlag E. Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia. Fertil Steril. 1997 Mar;67(3):542-7. doi: 10.1016/s0015-0282(97)80083-0.

Results Reference

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PubMed Identifier

15465836

Citation

Gianotten J, Lombardi MP, Zwinderman AH, Lilford RJ, van der Veen F. Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short-cut to better understanding. Hum Reprod Update. 2004 Nov-Dec;10(6):533-9. doi: 10.1093/humupd/dmh045. Epub 2004 Oct 1.

Results Reference

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PubMed Identifier

23024648

Citation

Jenkins TG, Carrell DT. Dynamic alterations in the paternal epigenetic landscape following fertilization. Front Genet. 2012 Jul 31;3:143. doi: 10.3389/fgene.2012.00143. eCollection 2012.

Results Reference

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Citation

Kelly TL, Li E, Trasler JM. 5-aza-2'-deoxycytidine induces alterations in murine spermatogenesis and pregnancy outcome. J Androl. 2003 Nov-Dec;24(6):822-30. doi: 10.1002/j.1939-4640.2003.tb03133.x.

Results Reference

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Citation

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Results Reference

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Citation

Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, Sasaki H, Yaegashi N, Arima T. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007 Nov 1;16(21):2542-51. doi: 10.1093/hmg/ddm187. Epub 2007 Jul 17.

Results Reference

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Citation

Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, Guerin JF. Influence of global sperm DNA methylation on IVF results. Hum Reprod. 2005 Mar;20(3):768-73. doi: 10.1093/humrep/deh684. Epub 2005 Jan 7.

Results Reference

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Citation

Reyes-Fuentes A, Chavarria ME, Carrera A, Aguilera G, Rosado A, Samojlik E, Iranmanesh A, Veldhuis JD. Alterations in pulsatile luteinizing hormone and follicle-stimulating hormone secretion in idiopathic oligoasthenospermic men: assessment by deconvolution analysis--a clinical research center study. J Clin Endocrinol Metab. 1996 Feb;81(2):524-9. doi: 10.1210/jcem.81.2.8636262.

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Citation

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Citation

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Results Reference

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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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