The Future of Male Infertility Treatment by Peter Schlegel, MD
microTESE, STAR, and Beyond
By Peter N. Schlegel, MD New York Men’s Health Medical, New York, NY
The management of severe male infertility has evolved progressively over the past years.
Non-Obstructive Azoospermia: A Treatable Condition
The first observation of importance was that men with the most severe male infertility — the condition of non-obstructive azoospermia (NOA) — was treatable. NOA reflects a condition where sperm production is so low that no sperm are present in the ejaculate. Most studies suggest that at least one-half of men with NOA will still have sperm in the testis, despite the lack of sperm in the ejaculate. That condition can be treated by surgery to extract the rare sperm from the testes, with the most effective surgical technique being microdissection testicular sperm extraction, also known as microTESE. Unfortunately, effective treatment of NOA is available at only a limited number of centers with extensive experience in the United States, and it has been difficult to expand access to all IVF units. The surgical search for rare sperm is technically challenging, as is the laboratory search for these sperm within testicular tissue.
Extended Sperm Search: Finding What Standard Testing Misses
Although NOA implies that there is no sperm in the ejaculate, standard sperm testing (semen analysis) can sometimes miss very rare sperm in the ejaculate. Almost 10% of men with NOA on a standard semen analysis, who were thought to require surgery, can have rare sperm found with a more detailed evaluation of the semen. This typically involves a detailed, drop-by-drop search of the semen — a tedious multi-hour lab procedure that is available at very few medical centers in the United States. This evaluation is called an extended sperm search because it is a more careful assessment of rare sperm than standard semen analyses.
The STAR System: AI-Powered Sperm Recovery
A recent innovation for identifying rare sperm in the ejaculate is the STAR system (Sperm Tracking and Recovery). This is an artificial intelligence (AI)-driven image detection process for identifying rare sperm in the ejaculate, developed at the Columbia Fertility Center. Briefly, the semen specimen is passed through a very narrow channel that allows millions of images to be taken of the seminal fluid, with the goal of identifying rare sperm in the ejaculate. AI, trained on millions of images evaluating semen, is used to help identify sperm in the fluid. The recovery process with this system is not perfect — it is not able to “capture” or collect all rare sperm in the ejaculate — but it achieves results that are similar to those obtained with the most effective manual sperm searches at the best centers in the US.
The STAR system has the potential to bring this important extended semen search process to clinics and fertility centers around the country, and possibly around the world. This is important for the management of NOA, as it can allow surgery to be avoided for almost 10% of men with this condition. Therefore, STAR complements the treatment of NOA with microTESE. Identified sperm still need IVF with ICSI (single sperm injection into eggs) to effectively use the sperm, whether obtained from surgery, STAR, or manual extended sperm search.
There is also some experience using STAR on testicular tissue retrieved with microTESE. Typically, tissue retrieved during surgery must be processed — mechanically or with enzymes — to identify the rare sperm present in it. STAR has the potential to help identify sperm for an IVF lab, even if the laboratory has relatively limited experience in identifying and using rare sperm in the ejaculate. This can provide results comparable to those achieved at centers of excellence in the treatment of this condition, where an entire team of lab experts is needed to identify the rare sperm present in the testicular tissue of men with NOA.
Looking Ahead: The Future of NOA Treatment
Despite the best treatments for NOA, many men with this condition do not have sperm found or identifiable and able to be used with ICSI. For men with no sperm found with extended sperm search or STAR, and no sperm found with effective microTESE, current options for treatment are limited, as microTESE and IVF are the most effective treatments for NOA. Of note, not all microTESE procedures are done the same way, so some procedures may be more effective than others. Future treatment for these men may include efforts to enhance the development of sperm-making cells, or stem cell-based treatments for men where no sperm-making cells are present in the testis — a condition referred to as Sertoli cell-only pattern. These treatments are not currently available but are being researched in a number of laboratories around the world. There are no viable experimental treatments yet for men where no sperm can be found with a complete microTESE procedure, but many new interventions are being developed.