Azoospermia and FNA Mapping in Japan

What is FNA Mapping?

Characteristics of FNA Mapping and Microdissection TESE

Please note: FNA Mapping is a completely different technique from conventional FNA (Fine Needle Aspiration). Traditional FNA involves collecting tissue by puncturing a single location or several random locations and is mainly used to confirm obstructive azoospermia in advance. In contrast, FNA Mapping systematically samples both testes thoroughly using a dedicated device, primarily used for non-obstructive azoospermia. Its goals are to avoid the aftereffects of microdissection TESE and to increase the sperm detection rate. Performing FNA Mapping requires three years of training and certification under the guidance of Dr. Paul Turek, former president of the American Society of Andrology and former professor of urology at UCSF.


Overview of FNA Mapping

FNA Mapping is a surgical procedure that identifies the presence and precise location of sperm within the testes without making incisions. Introduced in 1997 by American urologist Dr. Paul Turek, this technique revolutionized the approach to diagnosing male infertility. Prior to FNA Mapping, diagnoses were commonly made using testicular biopsies, which involved collecting tissue samples from a single location. Dr. Turek’s method proved that even if sperm are not produced in most areas of the testes, some patients still produce sperm in localized regions. This groundbreaking discovery inspired the development of microdissection TESE.

Dr. Turek is a distinguished graduate of Yale University and Stanford University School of Medicine. He is a renowned urologist who has served as the chair of the Department of Urology at the University of California, San Francisco, and as the president of the American Society of Andrology. Currently, he operates The Turek Clinic in Fisherman’s Wharf, San Francisco, specializing in male infertility.


Microdissection TESE Explained

Microdissection TESE, widely performed in Japan, is a surgical technique where the testes are incised, and sperm within the testes are extensively examined using a surgical microscope. Announced in 1999 by Dr. Peter Schlegel, a professor of urology at Cornell University in New York, this method was inspired by the data from FNA Mapping. The advantage of microdissection TESE is that sperm can be directly collected if the sperm-producing site is near the incision line and used immediately for Intracytoplasmic Sperm Injection (ICSI). Consequently, it has become popular, especially in IVF facilities where obstetrics and gynecology are predominant.

However, in more than half of the cases where there is no identifiable sperm-producing site, both testes must be incised. To minimize oversight, tissue must be collected from deep areas away from the incision line, involving random exploration and tissue collection. This approach has raised concerns due to significant damage to the testes, reduction in male hormone levels, and irreversible aftereffects (see Figure 1). An international paper published in 2018 highlighted that when the sperm-producing area is far from the incision line or deep within the testes, there is a 29% chance of overlooking sperm even when performing microdissection TESE (see Figure 2).


Limitations of Incision Techniques in Microdissection TESE

In microdissection TESE, the testis can be incised either horizontally or vertically, but neither method allows for a thorough search of the entire testis. Figure 3 illustrates a horizontal incision, where the upper pole (toward the head) and lower pole (toward the feet) of the testis are scarcely accessible. Forcing a search in these areas increases damage to the testis. Similarly, with a vertical incision, the outer and inner regions of the testis are difficult to examine without causing significant harm.


Case Studies Highlighting the Benefits of FNA Mapping

Patient A: Even with vertical or horizontal incisions during microdissection TESE, there is a risk of overlooking sperm. By performing FNA Mapping beforehand, the exact location of sperm can be identified without incision (see Figures 4-1 to 4-4).

Patient B: A vertical incision might reveal a small number of sperm, but a horizontal incision risks missing them entirely. FNA Mapping clarifies the sperm’s location prior to any incision (see Figures 5-1 to 5-4).

For both patients, preoperative FNA Mapping allows for microdissection TESE through a minimal incision tailored to the sperm’s location. This approach enables the recovery of sufficient sperm in a less invasive manner with a higher success rate (see Figure 6).


Advantages of FNA Mapping Over Microdissection TESE

  • Targeted Incisions: For patients with sperm present in only one testicle, the unaffected testicle remains intact. Over half of azoospermia patients with no sperm in either testicle can avoid unnecessary incisions altogether, reducing the risk of postoperative decreases in male hormone levels.
  • Minimized Damage: Knowing the sperm’s location in advance means incisions are made only where necessary, significantly reducing damage to the testicles and the risk of overlooking sperm.
  • Fixed Sperm-Producing Areas: The regions that produce sperm are fixed in three-dimensional coordinates (α, β, γ) within the ellipsoidal sphere of the testicle and remain consistent throughout a patient’s life (see Figure 7).

Procedure and Efficacy of FNA Mapping

FNA Mapping uses a needle thinner than that used for blood sampling to systematically sample the entire testis, detecting the presence and location of sperm with minimal damage. Sperm diffuse from their production sites through the seminiferous tubules in a concentration gradient, allowing for detection by passing the puncture needle nearby (see Figure 8).

The collected specimens become permanent smears, enabling accurate diagnoses over time and the possibility of multiple reviews if necessary. Figure 9 shows a case where sperm were confirmed in only one of 36 FNA Mapping sites from a patient with Sertoli-cell-only syndrome. This patient had previously undergone extensive microdissection TESE at a major facility without sperm detection. After salvage-directed microdissection TESE, motile sperm were collected and frozen within approximately 20 minutes, leading to the freezing of multiple blastocysts from just one thawed sperm sample. The patient successfully achieved pregnancy and childbirth through embryo transfer.

Studies have reported that sperm were overlooked in 29% of cases where FNA Mapping was performed after unsuccessful microdissection TESE. Conversely, there have been no reports of sperm recovery in cases where sperm were not detected via FNA Mapping and subsequent microdissection TESE was performed. Both theoretical and clinical data indicate that FNA Mapping has higher sperm detection sensitivity than microdissection TESE. Moreover, when FNA Mapping is performed alone or followed by microdissection TESE, only minimal incision and tissue collection are required on one testicle. No patients have experienced significant decreases in male hormone levels, highlighting FNA Mapping’s superior safety profile.


Benefits of Performing FNA Mapping Prior to Microdissection TESE

  1. Reduced Testicular Damage and Aftereffects: Minimizes the risk of male menopause and other hormonal issues by limiting unnecessary incisions and preserving testicular tissue.
  2. Lower Risk of Overlooking Sperm: Enhances the probability of detecting sperm by accurately mapping their location before surgery.

Additionally, over half of azoospermia patients may avoid unnecessary microdissection TESE, leading to reduced medical costs and less physical and emotional strain.


Conclusion

FNA Mapping offers a less invasive, more precise method for locating sperm within the testes, providing significant advantages over traditional microdissection TESE. By incorporating FNA Mapping into the diagnostic and treatment process, patients experience fewer risks, reduced aftereffects, and improved chances of successful sperm retrieval.

For a detailed explanation, please watch the explanatory video by Dr. Paul Turek, the founder of FNA Mapping.

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