Gonadotropin-releasing hormone (GnRH) antibodies formation in hypogonadotropic azoospermic men treated with pulsatile GnRH--diagnosis and possible alternative treatment.

Five hypogonadotropic azoospermic men received pulsatile, intravenous gonadotropin-releasing hormone (GnRH) treatment over prolonged period. In three patients, the spouses were successful in achieving five pregnancies, three of which generated five healthy newborns, one ended in a first-trimester abortion, and one is ongoing. In one patient, anti-GnRH antibodies were detected, secondary to initial response. This was associated with deterioration of gonadotropin levels and diminution in testosterone to pretreatment levels. The cross-reactivity of the antibodies with five GnRH agonistic analogs was examined. Possible treatment with pulsatile GnRH analogs in such patients is discussed. In light of the relatively long period of treatment needed to achieve spermatogenesis and fertility in patients with hypogonadotropic azoospermia, monitoring the appearance of GnRH antibodies seems appropriate to assess whether therapy should be concluded. The superiority of intravenous pulsatile GnRH treatment to subcutaneous GnRH treatment or to human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) treatment is discussed.