Endocrine Abstracts

We present a case of a thirty year old female with a history of primary amenorrhoea due to hypogonadotropic hypogonadism (HH) who was further investigated as family history revealed a brother and sister with normosmic hypogonadotropic hypogonadism due to a homozygous pathogenic variant c.1195T>A in the KISS1 receptor gene. Our patient carried the same homozygous mutation, and both parents (unrelated) were heterozygous carriers. KISS1-receptor mutations are a rare cause of congenital hypogonadotropic hypogonadism, present in 2-4% of cases. Kisspeptin is now known to be a key factor in stimulation of puberty and overall fertility. As part of fertility planning aged 25, an anti-mullerian hormone (AMH) level was found to be very low at 0.3 pmol/l (NR>20 pmol/l for this age) and transvaginal ultrasound showed no antral follicles. Following a lack of response to gonadotropin stimulation in an attempt to preserve oocytes by vitrification, she was referred to a reproductive endocrinology centre. It was hypothesised that the very low AMH level was potentially due to lack of exposure to endogenous GNRH and trial of gonadotropin releasing hormone (GNRH) pump was commenced. This led to regular menstrual cycles and ovulation was confirmed by ultrasound and elevated luteal progesterone. After six months of GnRH pump therapy, AMH increased to 3.98 pmol/l. Subsequently, when the patient was ready to actively try to conceive, and following confirmation of normal fallopian tubes and normal semen analysis, she was restarted on GnRH pump therapy. She conceived without other intervention, on the seventh menstrual cycle. Data surrounding fertility in congenital hypogonadotropic hypogonadism secondary to KISS1R mutations is limited and this case highlights that anti-mullerian hormone may be unreliable in this cohort, and that gonadotropin therapy may not always be successful in HH, likely in this case due to the low AMH and finally that conception is possible with GnRH pump therapy.