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

Male Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02605070
• Other study ID #: FSH_IMEN
• Status: Terminated
• Phase: Phase 3
• First received: November 9, 2015
• Last updated: March 1, 2018
• Start date: November 2015
• Est. completion date: June 13, 2017

Study information

• Verified date: May 2017
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: June 13, 2017
• Est. primary completion date: June 13, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 45 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Infertility
• Infertility, Male
• Male Infertility
• Oligospermia

Intervention

Drug:
• Bravelle
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.

Locations

Country	Name	City	State
Spain	Hospital Universitari i Politècnic La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (12)

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

Boissonnas CC, Jouannet P, Jammes H. Epigenetic disorders and male subfertility. Fertil Steril. 2013 Mar 1;99(3):624-31. doi: 10.1016/j.fertnstert.2013.01.124. Review. — View Citation

Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007 Jun;22(6):1506-12. Epub 2007 Mar 21. Erratum in: Hum Reprod. 2007 — View 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. — View Citation

Fujisawa M, Kanzaki M, Hayashi A, Tanaka H, Okada H, Arakawa S, Kamidono S. Alteration of the hypothalamus-pituitary-testis axis in oligozoospermic men with normal gonadotropin levels. Int J Urol. 1995 Sep;2(4):273-6. — View 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. Epub 2004 Oct 1. Review — View Citation

Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One. 2007 Dec 12;2(12):e1289. — View Citation

Jenkins TG, Carrell DT. Dynamic alterations in the paternal epigenetic landscape following fertilization. Front Genet. 2012 Jul 31;3:143. eCollection 2012. — View 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. — View 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. Epub 2007 Jul 17. — View Citation

Reyes-Fuentes A, Chavarría 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 deconvoluti — View 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 — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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)
Secondary	Pregnancy rate.	To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.	6-7 weeks after transfer of the embryo.