FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Azienda USL Modena
• Collaborators: Istituto Clinico Humanitas; University of Florence; University of Halle Medical Faculty; University of Padova; University of Roma La Sapienza
• Treatments: Follicle Stimulating Hormone

Criteria

Inclusion Criteria:

• age 20-50 years

• idiopathic male factor infertility for at least one year;

• homozygous FSHR allele at codon 680 (wild type: Asn/Asn or Ser/Ser);

• sperm DFI > 15%;

• normal serum FSH levels (< 8 IU/L)

• normal serum LH, testosterone, prolactin and estradiol levels

• normal ovulatory female partner These men might have impaired ejaculate parameters (decreased sperm count and/or decreased proportion of sperm with progressive motility and/or decreased proportion of sperm with normal morphology) of unknown aetiology.

Exclusion Criteria:

• azoospermia

• all known aetiologies of male infertility (endocrine disorders, genetic disorders, chromosome abnormalities, congenital bilateral absence of the vas deferens, microdeletions within the AZF regions of the Y chromosome, varicocele, cryptorchidism, infections, immunological infertility, and obstructive infertility)

• all known aetiologies of female infertility in the partner (tubal blockage, endocrine abnormalities including anovulation and PCO, anatomical abnormalities, infections)

• heterozygous FSHR allele at codon 680

• drug abuse and major systemic diseases

• testicular insufficiency