Surgical Sperm Retrieval in Non-obstructive Azoospermic Men: Microdissection Testicular Sperm Extraction vs. Multiple Needle-pass Percutaneous Testicular Sperm Aspiration

Background Infertility is a significant social- and health problem in the Western World and at the moment in Denmark one in ten babies are born with the help of assisted reproduction. In 50% of infertile couples a male factor can be identified as a contributing cause (1).

Azoospermia is defined as the absence of spermatozoa in the ejaculate and it is a condition affecting 10-15% of infertile men (2, 3). Azoospermia is divided into obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) of which the latter constitutes 60% (2, 3). In NOA the production of spermatozoa in the testis is either absent or markedly decreased.

Since 1999 microdissection testicular sperm extraction (mTESE) has become the preferred treatment option for NOA in many centers worldwide (4). The procedure is performed in general anesthesia using an operating microscope to carefully examine the entire testicular tissue for the presence of spermatozoa which can be used for intracytoplasmic sperm injection (ICSI). The advantages of mTESE include high sperm retrieval rates (SRR), in recent systematic reviews reported around 52% (5-8), and low reported complication rates (9-11). However mTESE is a time-consuming invasive procedure requiring the right expertise, the right equipment and a proper setup of the fertility clinic.

An alternative to mTESE is a percutaneous testicular sperm aspiration (TESA). This procedure is simple to perform using a biopsy needle to aspirate testicular tissue. The aspirated tissue is examined for the presence of spermatozoa and SRR for this procedure is usually reported around 25% (5-8). The lower SRR compared to mTESE is the main limitation of this method, but the procedure is well tolerated by patients and due to its simplicity and short duration it can easily be performed in the out-patient clinic. In collaboration with University of Michigan the TESA technique has been improved by using an 18 gauge needle and performing multiple (50-100) passes throughout the entire testicular tissue while applying a vacuum. In the remainder of this document this multiple needle-pass TESA will be referred to as "TESA". Recently the investigators retrospectively evaluated this approach and found a SRR of 30% using TESA and interestingly the SRR of mTESE following a failed TESA was only 11% (12).

However, there is no robust evidence on the optimal sperm retrieval protocol on men with NOA. This is in part due to the fact that no randomized trials have been performed to compare the two procedures. Often patients from different countries are required to pay the infertility treatment themselves and the cost for a TESA is around $500 while a mTESE is around $8.000. This makes it difficult to perform a randomized trial in most countries but because of the public health systems of Denmark and Sweden there is a unique possibility to be the first in the world to do a randomized trial on this matter.