Role of FSHR Polymorphism p.N680S in the Therapy With FSH in Patients Who Underwent Varicocele Surgery

NCT02719093 | Unknown Phase 4

• 1 other identifier: CHIRURGIAANDROLOGICA-1
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Two common SNPs are located in linkage disequilibrium in exon 10 of FSHR. The 2039 A\>G variant is regularly analyzed to characterize the exon 10 haplotype. In the last years, it has been showed an influence of FSHR 2039 A\>G on FSH levels, testicular volume, sperm concentration and the total sperm count. A recent Cochrane review showed a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility. Which FSHR polymorphism can benefit from FSH treatment is clinically very important, in particular for what regards nonidiopathic patients. In many andrological units, patients underwent adiuvant therapy with purified or recombinant FSH after varicocelectomy. FSH treatment in patients after varicocelectomy could improve spermatogenesis, but there aren't multicentric trials that confirm its validity. Usually, in our hospital only patients with a morphologic aspect of hypospermatogenesis underwent therapy with purified or recombinant FSH, because this therapy is not much useful in patient with Partial Sertoli-cell-only syndrome or maturation arrest. The purpose of our study is to correlate "non responder" patients who underwent FSH adiuvant therapy after varicocele surgery with a p.N680S FSHR polymorphism. Moreover the investigators suppose that "non responder" patients can beneficiate from a high-dose therapy with FSH. This is a prospective intervention study in which are recruited males with OligoAstenoTeratozoospermic (OAT) and varicocele. The partecipants will undergo subinguinal microsurgical varicocelectomy (Marmar technique) and needle aspiration testicular cytology (Foresta technique).

Conditions

Infertility, Male; Varicocele

Keywords

Infertility Male; Receptors FSH; Varicocele; FSH therapy

Outcome Measures

Primary Outcomes (5)

• Total sperm count

  Response to therapy indicated by significant increase in sperm count (million/ejaculate) according to WHO Laboratory Manual for the Examination and Processing of Human Semen (5th edn.)

  After subinguinal microsurgical varicocelectomy and therapy with recombinant follitropin alfa 150UI i.m. 3 times/week for three months

• Sperm concentration

  Response to therapy indicated by significant increase in sperm concentration (million/mL) according to WHO Laboratory Manual for the Examination and Processing of Human Semen (5th edn.)

  After subinguinal microsurgical varicocelectomy and therapy with recombinant follitropin alfa 150UI i.m. 3 times/week for three months

• Total motility

  Response to therapy indicated by significant increase in total motility (%) according to WHO Laboratory Manual for the Examination and

  After subinguinal microsurgical varicocelectomy and therapy with recombinant follitropin alfa 150UI i.m. 3 times/week for three months

• Progressive motility

  Response to therapy indicated by significant increase in progressive motility (%) according to WHO Laboratory Manual for the Examination and

  After subinguinal microsurgical varicocelectomy and therapy with recombinant follitropin alfa 150UI i.m. 3 times/week for three months

• Sperm morphology (normal forms)

  Response to therapy indicated by significant increase in sperm morphology (normal forms) (%) according to WHO Laboratory Manual for the Examination and

  After subinguinal microsurgical varicocelectomy and therapy with recombinant follitropin alfa 150UI i.m. 3 times/week for three months

Secondary Outcomes (5)

• Total sperm count

  After a daily dose of rFSH 150 UI for additional three months in "non responders" patients to the first three months of therapy with recombinant follitropin alfa 150UI i.m. 3 times/week

• Sperm concentration

  After a daily dose of rFSH 150 UI for additional three months in "non responders" patients to the first three months of therapy with recombinant follitropin alfa 150UI i.m. 3 times/week

• Total motility

  After a daily dose of rFSH 150 UI for additional three months in "non responders" patients to the first three months of therapy with recombinant follitropin alfa 150UI i.m. 3 times/week

• Progressive motility

  After a daily dose of rFSH 150 UI for additional three months in "non responders" patients to the first three months of therapy with recombinant follitropin alfa 150UI i.m. 3 times/week

• Sperm morphology (normal forms)

  After a daily dose of rFSH 150 UI for additional three months in "non responders" patients to the first three months of therapy with recombinant follitropin alfa 150UI i.m. 3 times/week

Study Arms (1)

recombinant FSH

EXPERIMENTAL

recombinant FSH 150UI daily

Drug: recombinant FSH

Interventions

recombinant FSH DRUG

Subcutaneous injection

Also known as: Puregon, Gonal-F

recombinant FSH

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• OligoAstenoTeratozoospemic patient: Spermatozoa \< 15 x 106/ml, Motility \< 32%, \<4% normal forms

You may not qualify if:

• Medications and psychoactive or anabolic drugs in last six months.
• Alcohol abuse in last three months.
• Systemic disease(liver cirrhosis, renal failure or others).
• Exposure to pelvic radiation, cytotoxic agent or exposure to environmental toxins.
• Testicular dysgenesis, cryptorchidism or genetic abnormalities (karyotype, Y-chromosome deletions)
• No trauma, testicular torsion, previous orchitis, previous testicular tumors, surgery that can compromise vascularisation of the testes and lead to testicular atrophy, cryptorchidism or genitourinary infection in last one year.

Sponsors & Collaborators

• U.O. Chirurgia Andrologica: lead
• Androcenter, Napoli, Italy: collaborator

Related Publications (2)

• Tuttelmann F, Laan M, Grigorova M, Punab M, Sober S, Gromoll J. Combined effects of the variants FSHB -211G>T and FSHR 2039A>G on male reproductive parameters. J Clin Endocrinol Metab. 2012 Oct;97(10):3639-47. doi: 10.1210/jc.2012-1761. Epub 2012 Jul 12.

  PMID: 22791757 RESULT

• Casarini L, Moriondo V, Marino M, Adversi F, Capodanno F, Grisolia C, La Marca A, La Sala GB, Simoni M. FSHR polymorphism p.N680S mediates different responses to FSH in vitro. Mol Cell Endocrinol. 2014 Aug 5;393(1-2):83-91. doi: 10.1016/j.mce.2014.06.013. Epub 2014 Jun 23.

  PMID: 24970684 RESULT

MeSH Terms

Conditions

Infertility, Male; Varicocele

Interventions

follitropin beta; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Maurizio Carrino

  AORN A.CARDARELLI

  STUDY DIRECTOR

Central Study Contacts

Maurizio Carrino

CONTACT

+393347967341; cris63@libero.it

Francesco Chiancone

CONTACT

+393408639711; francescok86@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Director of U.O. Chirurgia Andrologica

Study Record Dates

• First Submitted: December 12, 2015
• First Posted: March 25, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 25, 2016

Record last verified: 2016-03