Written by Eric K. Seaman M.D., F.A.C.S.
In 1677, Antonie van Leeuwenhoek, used an improvised microscope to observe for the first time that semen contained sperm cells. This discovery became the ancestor of microscopic semen analysis, which has remained the primary method for evaluating male infertility for at least the past 100 years. The modern Andrologist typically attempts to estimate a man’s fertility by interpreting a number of factors including sperm concentration (aka sperm count), motility, semen volume, pH, and sperm shape (aka morphology).
The three most commonly used parameters: count, motility, and morphology, are essentially interpretations of the cells seen through the microscope. Does the sperm count look adequate? Are the sperm moving quickly enough? Is the shape normal? Although these parameters evaluate the appearance of the sperm, they cannot judge the ability of the sperm to fertilize an egg. Appearances can be deceiving.
A History of Sperm Function Testing
There have been a number of attempts to measure aspects of sperm function that are not revealed by the microscope. For instance, the Penetrak assay tested the ability of sperm to move through cervical mucus (using bovine mucus as a substitute for the human variety). The Sperm penetration assay simulated the act of fertilization by providing a specially processed hamster egg as a target. Finally, several assays attempt to measure the integrity of DNA inside the sperm nucleus including the comet assay, and more recently the SCSA (sperm chromatin structural assay) and the TUNEL assay. These assays attempt to use the prevalence of fragmented sperm DNA within a semen as an aid in evaluating a man’s fertility on the premise that sperm function is dependent on DNA integrity. Although these tests held promise for evaluation of male infertility, clinical results have varied and the ASRM recommends these tests be used only for research use.
A new test that assesses the fertilizing ability of a man’s sperm is now available from a company named Androvia. Before fertilization, an individual sperm must complete three preliminary steps: (1) capacitation, (2) hyperactivation, and (3) the acrosome reaction. Androvia uses technology that identifies the ability of sperm to undergo the first step: capacitation.
Capacitation is a series of internal chemical changes that a sperm must undergo prior to fertilizing an egg. These changes are not visible under the microscopes typically used for semen analysis. The next step, hyperactivation, is defined as an increase in motion of the sperm tail resulting in more vigorous sperm motility and may occur simultaneously with capacitation. The final step, the acrosome reaction is the removal (exocytosis) of the acrosome within the head of the sperm in preparation for penetrating an egg. These three stages normally precede the fertilization of an egg.
Developed from research by Dr. Alex Travis, the Androvia Cap-Score™ test uses the location of a sperm membrane component, GM1, on the surface of the sperm head to assess the potential for capacitation. GM1 is an organic lipid-sugar hybrid compound (“ganglioside”) that regulates the opening and closing of calcium ion channels. Gangliosides, such as GM1, are versatile compounds that commonly help cells regulate signals that cross their surface membranes including calcium ions.
Capacitation, hyperactivation and the acrosome reaction each require an influx of calcium ions. By detecting the presence and location of GM1 in the sperm membrane, and measuring the number sperm are undergoing capacitation, a Cap-Score™ can be generated that is predictive of the fertilizing potential of sperm in the ejaculate. Preliminary data from Androvia have confirmed the ability of the test to determine differences between fertile and infertile groups of men.
The Cap Score test is currently available directly from Androvia, and at the office of Dr. Eric Seaman in Millburn, New Jersey. Given this new axis of measurement for male fertility the Cap Score could prove to be a game changer for physicians who treat infertility and for their patients.