CONDITION: Idiopathic male infertility In men with idiopathic infertility, the sperm DNA fragmentation index (DFI) within 12 weeks of FSH therapy and 12 weeks follow-up improves depending on the FSHR genotype as assessed by the non-synonymous SNP rs6166 (wild type or p.N680S). This is a phase II b, multicenter, prospective, open label, one arm, clinical trial stratified according to the patient's genotype. INTERVENTION: FSH therapy (150 I.U. sc every other day for 12 weeks) in infertile men who are homozygous for the wild-type FSHR or the p.N680S allele of the FSHR. Duration of intervention per patient: 12 weeks Primary efficacy endpoint: Sperm DFI. Number of patients with an improvement in DFI > 60% Key secondary endpoint(s): pregnancy, semen parameters, serum levels of inhibin B and AMH.
Name: follitropin alpha
Description: All subjects included in the study will receive recombinant FSH therapy (follitropin alpha: Gonal-f 150 I.U. s.c. every other day for 12 weeks). Follow up: 12 further weeks after end of treatment. Previous studies included in the Cochrane meta-analysis used: hMG/hCG, 150 IU three times a week for 13 weeks; purified FSH, 150 IU/day for 12 weeks; rec hFSH, 150 IU/day for 12 weeks; rec hFSH, 100 IU on alternate days for 3 months. Therefore any dosage > 100 IU on alternate days is eligible. The duration of treatment is based on the duration of one spermatogenetic cycle.Type: DrugArm 1 Arm 2
Description: Serum dosage
Measure: Inhibin B Time: "baseline"Description: Serum dosage
Measure: Inhibin B Time: "after 12 weeks"Description: Serum dosage
Measure: Inhibin B Time: "after 24 weeks"Description: Serum dosage of Anti-Mullerian Hormone
Measure: Anti-Mullerian Hormone (AMH) Time: "baseline"Description: Serum dosage of Anti-Mullerian Hormone
Measure: AMH Time: "after 12 weeks"Description: Serum dosage of Anti-Mullerian Hormone
Measure: AMH Time: "after 24 weeks"Allocation: Non-Randomized
Parallel Assignment
There is one SNP
FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy CONDITION: Idiopathic male infertility In men with idiopathic infertility, the sperm DNA fragmentation index (DFI) within 12 weeks of FSH therapy and 12 weeks follow-up improves depending on the FSHR genotype as assessed by the non-synonymous SNP rs6166 (wild type or p.N680S).
In women, the response to FSH varies depending on the FSH receptor (FSHR) genotype, as determined by the non-synonymous SNP rs6166, which exchanges the amino acid Asn to Ser in codon 680.
The investigators hypothesize that the variable response to FSH in unselected infertile men is due to a different individual sensitivity to FSH as determined by the common FSHR polymorphism rs6166.