Male Infertility and Assisted Reproduction (#14)
Male infertility is the sole or contributory cause of infertility in half of couples. Clinical evaluation may identify reversible or treatable conditions (e.g. gonadotrophin deficiency) and prevalent co-morbidities (e.g. testosterone deficiency). Assisted reproductive treatments (ART), particularly intracytoplasmic sperm injection (ICSI), allow fertility in many otherwise untreatable male factor couples.
Primary spermatogenic failure is the most common diagnosis encompassing diverse pathogenic processes resulting in reduced sperm number, motility and/or function. A cause may be evident but most are unexplained (idiopathic). Karyotypic anomalies and Y chromosomal microdeletions are prevalent and assessed prior to ART: no single gene defect worthy of routine testing has emerged. Obstruction due to congenital absence of the vasa is associated with cystic fibrosis gene mutations.
Medical interventions for idiopathic infertility lack an evidence base; properly designed studies of therapies to increase natural or ART outcomes are needed such as for clomiphene, aromatase inhibitors, FSH in men with variants of the FSH promoter, and antioxidants.
ICSI is widely applicable and offers excellent fertility prospects with poor quality ejaculated or testicular/epididymal sperm. In azoospermic men with severe spermatogenic failure, testicular biopsy allows sperm isolation in 30-60%; even post chemotherapy or in Klinefelter’s syndrome (wherein the most sperm are euploid). Microsurgical dissection of individual tubules may improve recovery rates. In obstruction, the choice of surgery versus sperm retrieval/ICSI is dictated by the anatomy, surgical skill and female co-factors.
Current areas of interest include assessment of sperm function or DNA integrity that meaningfully impacts treatment, and methods of selecting sperm with optimal fertility potential for ICSI e.g. electrophoresis or morphology on high magnification. Modestly increased rate of congenital malformations and karyotypic anomalies in IVF/ICSI offspring are recognised; the fertility of ICSI-conceived young men is being assessed.