Ignite Creation Date:
2024-05-06 @ 8:20 AM
Last Modification Date:
2024-10-26 @ 11:59 AM
Study NCT ID:
NCT02719093
Status:
UNKNOWN
Last Update Posted:
2016-03-25
First Post:
2015-12-12
Brief Title:
Role of FSHR Polymorphism pN680S in the Therapy With FSH in Patients Who Underwent Varicocele Surgery
Sponsor:
UO Chirurgia Andrologica
Organization:
UO Chirurgia Andrologica
Study Overview
Official Title:
Role of FSHR Polymorphism pN680S in the Therapy With FSH in Patients Who Underwent Varicocele Surgery
Status:
UNKNOWN
Status Verified Date:
2016-03
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Two common SNPs are located in linkage disequilibrium in exon 10 of FSHR The 2039 AG variant is regularly analyzed to characterize the exon 10 haplotype In the last years it has been showed an influence of FSHR 2039 AG 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 arent 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 pN680S 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
Detailed Description:
Two common SNPs c919 AG pT307A rs 6165 and c2039 AG pN680S rs6166 are located in linkage disequilibrium in exon 10 of FSHR The 2039 AG variant is regularly analyzed to characterize the exon 10 haplotype
It is well known that follice-stimulating hormone FSH receptor FSHR polymorphism pN680S mediates different responses to FSH in vitro and this polymorphism is associated with the ovarian response in controlled ovarian hyperstimulation In the last years FSHR gene polymorphisms have been studied as potential risk factors for spermatogenetic failure It is shown an influence of FSHR 2039 AG on FSH levels and testicular volume Trends of higher FSH and lower testicular volume were observed in G-allele carriers Ala307Ser680 Men homozygous for Thr307Asn680 had a lower mean serum FSH concentration compared with men with other genotypes In addition sperm concentrations and the total sperm counts were higher and their testes volumes were larger Another clinical study showed that the patients with heterozygous ThrAla AsnSer combined genotype were 265 times more susceptible to infertility than the control group It is also shown the higher sensitivity of the receptor in FSHR 2039 AG AA homozygotes1-2 A recent Cochrane review showed a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility These study suggest that the analysis of this gene represents a valid pharmacogenetic approach to the treatment of male infertility confirming also the importance of strict criteria for the selection of patients to be treated with FSH Which FSHR polymorphism can benefit from FSH treatment is clinically very important in particular for what regards nonidiopathic patients It is also relevant from a pharmacoeconomic point of view 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 arent 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 pN680S 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 One-hundred patients with a morphologic aspect of hypospermatogenesis at testicular cytology will take recombinant follitropin alfa 150UI im 3 timesweek for at least three month At 3th month the partecipants will have a semen analyses without interrupting the treatment and the FSHR gene polymorphism pN680S characterization with PCR in high resolution melting HRM from DNA extracted by a simple blood sample Patients who will have a significative increase in at least two parameters of semen will be considered responders while patients in which semen parameters will not improve or worsen will be considered non responders Responders patients will interrupt their therapy and will have a new semen analyses at six month to verify the maintenance of their semen parameters after only three months of therapy Non responders patients will take a daily dose of rFSH 150 UI for additional three months because the investigators suppose that men with specific polymorphisms who dont response to therapy need an higher dose to stimulate spermatogenesis and to have a spontaneous pregnancy At 6th month also these patients will have a new semen analyses in order to verify if there are some improvements in their spermatogenesis
It is well known that follice-stimulating hormone FSH receptor FSHR polymorphism pN680S mediates different responses to FSH in vitro and this polymorphism is associated with the ovarian response in controlled ovarian hyperstimulation In the last years FSHR gene polymorphisms have been studied as potential risk factors for spermatogenetic failure It is shown an influence of FSHR 2039 AG on FSH levels and testicular volume Trends of higher FSH and lower testicular volume were observed in G-allele carriers Ala307Ser680 Men homozygous for Thr307Asn680 had a lower mean serum FSH concentration compared with men with other genotypes In addition sperm concentrations and the total sperm counts were higher and their testes volumes were larger Another clinical study showed that the patients with heterozygous ThrAla AsnSer combined genotype were 265 times more susceptible to infertility than the control group It is also shown the higher sensitivity of the receptor in FSHR 2039 AG AA homozygotes1-2 A recent Cochrane review showed a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility These study suggest that the analysis of this gene represents a valid pharmacogenetic approach to the treatment of male infertility confirming also the importance of strict criteria for the selection of patients to be treated with FSH Which FSHR polymorphism can benefit from FSH treatment is clinically very important in particular for what regards nonidiopathic patients It is also relevant from a pharmacoeconomic point of view 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 arent 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 pN680S 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 One-hundred patients with a morphologic aspect of hypospermatogenesis at testicular cytology will take recombinant follitropin alfa 150UI im 3 timesweek for at least three month At 3th month the partecipants will have a semen analyses without interrupting the treatment and the FSHR gene polymorphism pN680S characterization with PCR in high resolution melting HRM from DNA extracted by a simple blood sample Patients who will have a significative increase in at least two parameters of semen will be considered responders while patients in which semen parameters will not improve or worsen will be considered non responders Responders patients will interrupt their therapy and will have a new semen analyses at six month to verify the maintenance of their semen parameters after only three months of therapy Non responders patients will take a daily dose of rFSH 150 UI for additional three months because the investigators suppose that men with specific polymorphisms who dont response to therapy need an higher dose to stimulate spermatogenesis and to have a spontaneous pregnancy At 6th month also these patients will have a new semen analyses in order to verify if there are some improvements in their spermatogenesis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None