Techniques for surgical retrieval of sperm prior to ICSI for azoospermia

Azoospermia, the absence of sperm in ejaculated semen, is the most severe form of male factor infertility and is present in approximately 5% of all investigated infertile couples. The condition is currently classified as "obstructive" or "non-obstructive", although it is important to also consider the specific aetiology of each individual case. Some cases of obstructive azoospermia are treatable using microsurgical reconstruction of the seminal tract (for example, vasectomy reversal). Unreconstructable obstructive azoospermia and non-obstructive azoospermia have historically been relatively untreatable conditions that required the use of donor spermatozoa for fertilisation. The advent of intra-cytoplasmic sperm injection (ICSI), however, has transformed treatment of this type of severe male factor infertility. Sperm can be retrieved for ICSI from either the epididymis or the testis depending on the type of azoospermia.

To evaluate the efficacy of the various surgical retrieval techniques for men with obstructive or non obstructive azoospermia prior to ICSI.

Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information.

Trials were included if they were randomised and compared the effectiveness of sperm retrieval techniques in men with azoospermia prior to ICSI. Due to the lack of RCTs non-randomised trials, who used the participants as their own control, were also considered in the review but not included in the meta-analysis. Trials of surgically extracted sperm versus ejaculated sperm or of diagnostic biopsies with no sperm parameter information were excluded.

One RCT was included in this systematic review which compared micropuncture with nerve stimulation versus microsurgical epididymal sperm extraction. Pregnancy rate, sperm retrieval adequate for ICSI and fertilisation rate were primary outcomes. Another RCT comparing microsurgical epididymal sperm extraction versus testicular sperm extraction, was excluded from the meta-analysis due to poor randomisation. Seven non-randomised comparative trials were also identified and included. Main outcomes were pregnancy rate, sperm retrieval adequate for ICSI, fertilisation rate and implantation rate. Quality assessment and data extraction were performed independently by two reviewers. Meta-analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis was reported as descriptive data and was also included for discussion.

One small RCT comparing two epididymal techniques gave limited evidence that microsurgical epididymal sperm aspiration (MESA) achieved significantly lower pregnancy (OR 0.19, 95% CI 0.04-0.83) and fertilisation rates (OR 0.16, 95% CI 0.05-0.48) than the micropuncture with perivascular nerve stimulation technique. However the small number of participants included and the questionable methodology of this RCT make it impossible to make a definitive statement about the relative merits of either treatment.

There is insufficient evidence to recommend any specific sperm retrieval technique for azoospermic men undergoing ICSI. Further randomised trials are warranted, preferably multi-centred trials.