Induction of Spermatogenesis in a Man with Congenital Hypogonadotrophic Hypogonadism.

AN Comninos, CN Jayasena, D Papadopulou, N Hill, E Bagg, GMK Nijher, N Pitteloud & WS Dhillo.

A 35 year old Portuguese man was referred by his GP to the Endocrine Clinic in late 2013 with inability to conceive a child despite regular unprotected intercourse for several years with his wife who had previously conceived.

He reported a lack of pubertal progression, with only minor testicular, penile and pubic hair development in his late teens. He had abdominal operations as a child (for gastroschisis and umbilical hernia). He was able to engage in intercourse and produce a small volume of clear ejaculate. His siblings had conceived several children naturally.

Examination revealed Tanner Stage 3 genitals and pubic hair, with 6ml testicular volume bilaterally. Flaccid penile length was 4cm. There was sparse axillary and no other body hair. In addition he had a high-arched palate with poor dentition. He had mild cerebellar ataxia.

Bloods revealed LH 0.5 IU/l, FSH 2.2 IU/l with normal other basal pituitary hormone levels. Testosterone was 0.6nmol/l (10-30) with SHBG of 37nmol/l (15-55). Karyotype was 46XY. Genetic testing is currently underway for common genetic causes of idiopathic hypogonadotrophic hypogonadism in Professor Pitteloud’s laboratory.

Formal testing revealed anosmia (University of Pennsylvania Smell Identification Test), normal pituitary (on MRI), a mild bilateral sensorineural hearing loss (on audiometry) and osteoporosis (on DEXA scan). Semen analysis did not reveal any sperm in 1.6ml of semen. Administration of an 8 hour kisspeptin infusion (iv) failed to stimulate LH secretion before and after 6 days of pituitary priming with pulsatile GnRH administration (25ng/kg every 2 hour). Standard GnRH testing, however, elicited a peak LH of 6.9 IU/l.

The patient was keen to have a child. Hence cautious treatment with hCG (Pregnyl) 150iu (twice per week) was commenced with gradual escalation to full dose 1500iu (twice per week) by March 2014 (since his baseline testosterone was 0.6nmol/l). Testosterone was maintained >10nmol/l during treatment. Examination in September 2014 (after 6 months of full dose hCG) revealed increase in bilateral testicular size to 9ml as well as generalised increase in body hair (including facial and pubertal). He reported increased strength and libido. Semen analysis now revealed very occasional sperm in 1.9ml of semen. As a result we have added Menopur (with combined LH and FSH activity; 75/75iu) twice weekly to promote further spermatogenesis.

Conclusion: This is a case of Congenital Hypogonadotrophic Hypogonadism with GnRH deficiency causing infertility. Induction of spermatogenesis according to current guidelines is being undertaken in order to achieve fertility with promising results to date.