IN 1677, Antonie van Leeuwenhoek became the first man to identify sperm within semen under microscopic examination. His discovery laid the foundation for what would become the semen analysis, typically the first step in fertility evaluation for a man.
Semen analysis, in one form or another has remained the initial test of choice for the evaluation of male infertility for well over 100 years. Currently semen analysis attempts to assess a man’s reproductive potential based on characteristics of semen including volume, pH, sperm density (or count), percent motility, quality of motility and the shape (or morphology) of the sperm.
But each of the three major parameters of count, motility and morphology essentially rely on appearances. Does it look like the sperm are moving well? Does it look like the count is high? Does the shape look normal? No parameter actually evaluates sperm’s real function of being able to fertilize an egg.
Previous tests of sperm function have come and gone. Some include the Penetrak assay where the ability of sperm to move through bovine mucus was assessed as a proxy for sperm viability in cervical mucus. The mannose binding assay was used as a proxy for sperm’s ability to bind to an egg. The Sperm penetration assay measure sperm’s ability to fuse to a hamster egg stripped of its zona pellucida as a proxy for sperm’s fertilizing ability. Most recently, several assays were developed to measure DNA fragmentation of sperm including the SCSA (sperm chromatin structural assay), comet assay ,and the TUNEL assay. All attempt to answer the question of whether global quality in DNA across all the sperm in the ejaculate affect a man’s fertility potential. Initially these tests were hailed as a major breakthrough in the evaluation of male infertility; however clinical study results varied and currently the tests are still considered by the ASRM to be research tools only and they remain of limited if any clinical utility.
Coming soon, a company named Androvia will be releasing a new test that assesses the fertilizing ability of a man’s sperm. Prior to fertilization, an individual sperm must complete three tasks: “capacitation”, “hyperactivation” and the “acrosome reaction”. Androvia uses technology that identifies the ability of sperm to undergo capacitation.
Before fertilizing an egg, the sperm must “capacitate” in order to acquire a “hyperactivated” pattern of mobility in the flagellum or tail, and the ability to undergo the ‘acrosome reaction” in the head. Hyperactivation refers to a characteristic increase in motion of the sperm tail. Acrosome reaction refers to removal (exocytosis) of the acrosome within the head of the sperm. Capacitation refers to specific biochemical and physiologic changes the sperm must undergo, changes which are largely invisible by light microscopy.
Based on the work of Dr. Alex Travis, the Androvia Cap-Score™ test relies on the localization of GM1 on the sperm head. GM1 is a sperm membrane component that regulates the opening and closing of specific calcium ion channels on the surface of the sperm head. Specifically, GM1 is a “ganglioside” which is an organic compound comprised of a “ceramide” (lipid molecule) linked on to a sugar chain called an oligosaccharide. Gangliosides are present on different cell membranes in the body and play a role in signal transduction, as their hydrocarbon ceramide component lies within the cell membrane while its oligosaccharide portion extends onto and beyond the cell surface. GM1 or monosialotetrahexosylganglioside is one of sixty or so gangliosides that have been identified.
Capacitation, hyperactivation and the acrosome reaction require an influx of calcium ions. By identifying the presence and location of GM1 in the sperm membrane across a number of sperm, and identifying how many sperm are undergoing capacitation, a “Cap-Score™” can be generated that is predictive of the fertilizing ability of sperm in the ejaculate. Androvia’s preliminary research has already validated the ability of the test to discriminate between fertile and infertile populations of men.
More accurate testing is the first step towards more effective treatment. Looking forward, a new test for male infertility could potentially prove to be a game changer for physicians who treat infertility and for their patients. We are eagerly anticipating the release of this test in the (hopefully near) future.
