For men with obstructive azoospermia, several surgical sperm retrieval techniques can facilitate conception with assisted reproductive technology. The evolution of both percutaneous and open approaches to sperm retrieval has been affected by technological innovations, including the surgical microscope, in vitro fertilization, and intracytoplasmic sperm injection. Further modifications to these procedures are designed to minimize patient morbidity and increase the quality and quantity of sperm samples. Innovative technologies promise to further ameliorate outcomes by selecting the highest quality sperm. Although various approaches to surgical sperm retrieval are now well established, several advancements in sperm selection and optimization are being developed.
Key points
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The evolution of operative techniques for sperm retrieval, coupled with the introduction of in vitro fertilization and intracytoplasmic sperm injection, have afforded previously untreatable men with obstructive azoospermia reliable pathways to conception.
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Percutaneous sperm aspiration techniques have remained highly effective tools with minimal modifications since their introduction.
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Open approaches to sperm extraction continue to shift toward more minimally invasive practices in the hopes of facilitating their use in the clinic setting while minimizing patient morbidity.
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Innovations in sperm selection and purification may offer a means of improving the fertility potential of specimens and address important sperm parameters, including DNA fragmentation.
Introduction
Advancements in operative technology, coupled with the introduction of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have afforded previously untreatable infertile men with reliable pathways to conception. In particular, the introduction of the surgical microscope revolutionized the surgical management of male infertility and sperm retrieval. For men with obstructive azoospermia (OA), sperm can now be extracted from several different sites using a variety of surgical techniques. The obstruction can occur anywhere along the passage of sperm from the efferent ducts within the testis, along the epididymis, through the vas deferens, the ejaculatory ducts, the penile urethra, or even the urethral meatus. Of the 15% of infertile men presenting with azoospermia, approximately 30% to 40% have an obstructive cause. , Because of preserved spermatogenesis, sperm extraction with high-quality samples can be obtained upstream from the site of obstruction or by relieving the obstruction itself. This extraction is accomplished through reconstructive microsurgery, resection of the obstruction, percutaneous aspiration, or open surgical retrieval.
Although the last few decades have produced reliable surgical options for men with OA, further advances show promise in improving outcomes, reducing surgical time, and decreasing procedure-related morbidity. This article traces the evolution of sperm extraction techniques for OA and highlights new developments and innovations in sperm selection and purification.
History and evolution of sperm extraction techniques
The first reported use of aspirated sperm was published by Temple-Smith and colleagues in 1985. The case involved a 42-year-old man with a history of vasectomy and 2 subsequent failed reversals with vasoepididymostomy. Following prolonged epididymal massage and aspiration, a total of 0.2 mL was retrieved with 76% motility and an estimated concentration of 4.28 × 10 6 sperm per milliliter. Successful fertilization and clinical pregnancy was achieved through IVF using this sample. Building on this work, Silber and colleagues published their approach to microsurgical epididymal sperm aspiration (MESA) in 1988. The article outlines a technique for epididymal sperm aspiration under 10 to 40 times magnification that begins in the distal corpus of the epididymis and continues proximally until motile sperm are retrieved. The 2 patients in whom this procedure was initially described both had congenital bilateral absence of the vas deferens (CBAVD). This new technique to be used in conjunction with IVF was well received and offered a path to pregnancy for men with OA. However, early fertilization and pregnancy rates did not produce favorable results. Many centers reported a success rate less than 10%. Poor fertilization and pregnancy rates, coupled with the need for an operative microscope, limited the initial uptake of the MESA approach. The advent of ICSI a few years later led to significant improvements in outcomes with epididymal sperm. With these changes came renewed interest in MESA. More recently, modifications to the MESA technique have been published, including the mini-MESA, obliterative MESA, and minimally invasive epididymal sperm aspiration (MIESA).
Nearly 10 years after Temple-Smith and colleagues published their technique of epididymal sperm aspiration, Craft and colleagues described a percutaneous approach using a 21-gauge needle. This approach formed the basis of what is now considered a conventional percutaneous epididymal sperm aspiration (PESA). The procedure was well received because many surgeons did not have access to an operating microscope to perform MESA. PESA was initially performed with intravenous or general anesthesia but is now commonly done with local anesthesia in the office setting.
The introduction of ICSI in 1992 made it possible to use sperm aspirated from the testes. The first uses of testicular sperm for fertilization were reported in 1993 by Schoysman and colleagues. They describe obtaining samples by testicular biopsy in men who were previously unable to produce an epididymal sperm sample. This technique is now commonly referred to as testicular sperm extraction (TESE). Using ICSI, successful fertilization and pregnancy was achieved. This method overcame initial concerns of the fertilizing potential of less mature testicular sperm. In an attempt to minimize morbidity, percutaneous testicular sperm aspiration (TESA) was explored. Before this, TESA had been described as a diagnostic tool in azoospermic men. The first report of TESA for ICSI was published by Bourne and colleagues in 1995. Their technique used a 20-gauge Menghini biopsy needle under negative pressure in 2 men with OA. High rates of normal fertilization and subsequent pregnancy were achieved using the aspirated sample. TESA was seen as a way to overcome the need for an operative microscope, avoid general anesthesia, and reduce patient morbidity. The procedure has evolved over time to include multiple needle passes with thinner-gauge needles. The most recent development in sperm retrieval from the testis is microdissection testicular sperm extraction as first described by Peter Schlegel in 1999. After observing that seminiferous tubules had different morphologic characteristics under the operating microscope, selective extraction of larger tubules (more likely to contain sperm) was performed. This technique allowed improved identification and retrieval of sperm while removing less tissue from the testis. For men with nonobstructive azoospermia (NOA), the technique has emerged as a more effective and reliable technique than multiple-pass TESE.
Given the success of TESA and PESA percutaneous approaches, Qiu and colleagues explored vasal sperm aspiration as another means of obtaining sperm percutaneously. Their 1997 article discussed percutaneous vasal sperm aspiration (PVSA) in 6 men diagnosed with ejaculatory duct obstruction. Of the 6 men included in the study, adequate sperm for intrauterine insemination (IUI) was obtained in 3 men. Only 1 resulted in a pregnancy. With the vas deferens fixed to the skin by a clip, a 21-gauge needle was advanced into the lumen of the vas deferens followed by a 23-gauge blunt needle. The 23-gauge needle was advanced through the 21-gauge needle in the direction of the epididymis. Aspiration was done using a 5-mL syringe. The evolution of sperm retrieval techniques is shown in Fig. 1 .
Current role of epididymal and testicular sperm retrieval in obstructive azoospermia
Percutaneous Approaches to Sperm Retrieval
Percutaneous methods of sperm retrieval provide several benefits to both patients and surgeons. These procedures are particularly appealing because they can be performed on short notice under local anesthesia in the outpatient setting, have minimal patient downtime, and are highly reproducible. Unlike more invasive methods of sperm retrieval, percutaneous aspiration does not require additional equipment or training in microsurgery. Percutaneous sperm extraction can be targeted at the level of the testis, epididymis, or vas deferens.
Percutaneous Epididymal Sperm Aspiration
Among men with OA, sperm retrieval rates with PESA range from 51% to 100%, irrespective of the cause of their obstruction. Retrieval of motile sperm is high, with reported rates ranging from 62% to 94%. In men with postvasectomy OA who do not desire a reversal, PESA offers an appealing method of sperm extraction. Collins and colleagues reported one of the few comparative studies with PESA as an intervention. They performed MESA and PESA on both testes in men with previously proven fertility seeking vasectomy reversal. There was no difference in the rate of successful sperm retrieval between MESA and PESA. These investigators therefore advocate PESA when possible in men with OA secondary to vasectomy. More recently, Yafi and Zini reported on 255 men with OA undergoing PESA. The study included men with OA of various causes, including vasectomy, vasectomy with prior failed reversal, and CBAVD. Motile sperm was found in 75.3% of men. Younger paternal age and testicular size were predictive of finding motile sperm. For patients with a prior history of PESA, repeat PESA has been reported on the ipsilateral testis with lower rates of sperm retrieval (26.3%). One important consideration with PESA is that up to 25% of patients are unsuccessful in retrieval of sperm on their first attempt. Patients then require a subsequent TESA or TESE. The rate of complications in PESA has been reported at 3.4% and includes pain, hydrocele, infection, and swelling.
Testicular Sperm Aspiration
Retrieval of testicular sperm by percutaneous needle aspiration can be done in the outpatient setting with reliable results. TESA is most commonly performed on the day of egg retrieval because the amount of testicular tissue is minimal and may not be adequate for cryopreservation. However, Garg and colleagues reported TESA outcomes in a retrospective case series of 40 patients from 2003 to 2007 and had adequate sperm retrieved for cryopreservation in 39 of 40 patients (97.5%) with no complications reported. In the modern-day evaluation of OA, TESA has continued utility as a diagnostic procedure. Among men with indeterminate clinical findings for OA versus NOA, it can be used to determine the presence or absence of spermatogenesis. There is also a role for TESA in the setting of a failed PESA. Often now termed a rescue TESA, this approach has been shown to have higher rates of successful sperm retrieval than PESA and represents an alternative backup option when PESA is unsuccessful. The quantity and motility of sperm in these cases tends to be lower than in a successful PESA. Although TESA with proper technique results in rates of sperm recovery sufficient for ICSI in nearly 100% of men with azoospermia, other methods of sperm aspiration may produce superior samples with quantity more sufficient for cryopreservation.
Percutaneous Vasal Sperm Aspiration
Vasal sperm aspiration is an option for men with obstruction at the level of the prostate or distal vas deferens, as well as in men with ejaculatory dysfunction. Reports of PVSA to achieve pregnancy have shown the technique to be highly successful. Qiu and colleagues published their series of 26 patients with anejaculation who underwent sperm retrieval with PVSA followed by IUI. There was a 100% retrieval rate, with a pregnancy rate of 73.1%. Sperm was retrieved in sufficient volume and quality for IUI. Vasal sperm have the benefit of full maturation, making them an excellent sample for subsequent ICSI, IVF, IUI, or cryopreservation. The site of obstruction is an important factor when PVSA is being considered, because healthy sperm in the scrotal vas are only likely to be present in cases of more distal obstruction, such as inguinal or ejaculatory duct obstruction.
Open Surgical Approaches to Sperm Retrieval
Although more invasive than percutaneous approaches, open surgical sperm extraction techniques play an important role in the diagnosis and management of men with OA. Both TESE and MESA reliably produce large numbers of sperm in men with OA.
Testicular Sperm Extraction
In men with OA, there is no consensus with respect to the superiority of sperm retrieved from the epididymis or testis in terms of IVF/ICSI outcomes, assuming sperm are successfully retrieved and readily available for use by the embryologist. Despite promising results of early studies of epididymal sperm, systematic reviews and meta-analyses have failed to find sufficient evidence to recommend one sperm retrieval technique rather than another. Over time, TESE has become the most well-known and ubiquitous sperm retrieval technique, in large part because of the familiarity of urologists with testicular biopsy.
In men with OA, TESE produces a near-100% sperm retrieval rate. TESE has an important diagnostic role in men with normal testicular volume, palpable vasa deferentia, and normal or near-normal serum follicle-stimulating hormone levels. In addition to providing a tissue diagnosis of OA for men with no sperm in their samples, TESE allows extraction of a sufficient volume of sperm for cryopreservation. Any other method of percutaneous or open sperm retrieval that fails to identify sperm may be converted to a TESE with relative ease, and the ability to maneuver the conversion to a TESE should be made feasible within the chosen operative setting.
Microsurgical Epididymal Sperm Aspiration
MESA offers several benefits as a method of sperm retrieval in men with OA. Retrieval rates in appropriately selected men approach 100%. The number of sperm retrieved far exceeds those required for a single ICSI/IVF cycle and the sperm can be cryopreserved in 98% to 100% of cases. On average, MESA yields 15 × 10 6 to 95 × 10 6 total sperm with 15% to 42% total motility. , Combined with ICSI, epididymal sperm obtained by MESA has a clinical pregnancy rate of 42% to 60%. , , Unlike TESE and percutaneous retrieval methods, MESA requires the use of an operative microscope and additional microsurgical training, which may limit its use by practitioners who either do not have access to a microscope or are less familiar with microsurgical techniques.
Minimally Invasive Epididymal Sperm Aspiration
Although MESA has emerged as reliable sperm retrieval procedure for men with OA, advances in technical aspects of the procedure have been designed to reduce the morbidity and complexity of the procedure. The mini-MESA, first described in 1998, decreased the incision size on a traditional MESA in hopes of improving postoperative pain and recovery time. , However, this did not address one of the main factors limiting the clinical use of MESA: the need for an operative microscope. Coward and Mills further simplified the mini-MESA by performing the procedure solely under loupe magnification without compromising sperm yields. This approach is called a MIESA and can be performed either under oral or monitored anesthesia care (MAC) sedation.
A MIESA begins much in the same way as a mini-MESA with a 1-cm transverse upper hemiscrotal incision. The testicle is exposed and an eyelid retractor is positioned within the tunica vaginalis to maintain exposure ( Fig. 2 ). The caput of the epididymis is then rotated into the window opening and a 3-0 traction suture is placed in the upper third of the epididymis ( Fig. 3 ).
