title: Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism.
abstract: OBJECTIVE
  The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method.
  
  
  METHODS
  This was a randomized, open-label treatment protocol at an academic medical center.
  
  
  METHODS
  GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses.
  
  
  RESULTS
  rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts.
  
  
  CONCLUSIONS
  rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles.
authors.affiliation: MD, Endocrine, Diabetes, and Metabolism Service, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, Lausanne, Switzerland 1011. nelly.pitteloud@chuv.ch.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Dwyer
authors.forename: Gerasimos P
authors.initials: GP
authors.lastname: Sykiotis
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Hayes
authors.forename: Paul A
authors.initials: PA
authors.lastname: Boepple
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Loughlin
authors.forename: Martin
authors.initials: M
authors.lastname: Dym
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sluss
authors.forename: William F
authors.initials: WF
authors.lastname: Crowley
authors.forename: Nelly
authors.initials: N
authors.lastname: Pitteloud
mesh_terms: D000328:Adult; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000172:deficiency; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000378:metabolism; D007248:Infertility, Male / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D007265:Inhibins / Q000097:blood; D008297:Male; D020551:Pulse Therapy, Drug; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood; D013076:Sperm Count; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins
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