Successful Use of Pulsatile Gonadotropin-Releasing Hormone (GnRH) for Ovulation Induction and Pregnancy in a Patient with GnRH Receptor Mutations 1

Abstract

GnRH receptor mutations have recently been identified in a small number of familial cases of nonanosmic hypogonadotropic hypogonadism. In the present report we studied a kindred in which two sisters with primary amenorrhea were affected with GnRH deficiency due to a compound heterozygote mutation (Gln106Arg, Arg262Gln) and performed extensive phenotyping studies. Baseline patterns of gonadotropin secretion and gonadotropin responsiveness to exogenous pulsatile GnRH were examined in the proband. Low amplitude pulses of both LH and free α-subunit (FAS) were detected during 24 h of every 10 min blood sampling. The proband then received exogenous pulsatile GnRH iv for ovulation induction, and daily blood samples for gonadotropins and sex steroids were monitored. At the conventional GnRH replacement dose for women with hypogonadotropic hypogonadism (75 ng/kg), no follicular development occurred. At a GnRH dose of 100 ng/kg, the level and pattern of gonadotropin secretion more closely mimicked the follicular ph...