Sperm function tests and fertility

Abstract

Traditionally, the diagnosis of male infertility has depended upon a descriptive evaluation of human semen with emphasis on the number of spermatozoa that are present in the ejaculate, their motility and their morphology. The fundamental tenet underlying this approach is that male fertility can be defined by reference to a threshold concentration of motile, morphologically normal spermatozoa that must be exceeded in order to achieve conception. Many independent studies have demonstrated that this fundamental concept is flawed and, in reality, it is not so much the absolute number of spermatozoa that determines fertility, but their functional competence. In the light of this conclusion, a range of in vitro tests have been developed to monitor various aspects of sperm function including their potential for movement, cervical mucus penetration, capacitation, zona recognition, the acrosome reaction and sperm-oocyte fusion. Such functional assays have been found to predict the fertilizing capacity of human spermatozoa in vitro and in vivo with some accuracy. Recent developments in this field include the introduction of tests to assess the degree to which human spermatozoa have suffered oxidative stress as well as the integrity of their nuclear and mitochondrial DNA. Such assessments not only yield information on the fertilizing capacity of human spermatozoa but also their ability to support normal embryonic development.

An Assessment of New Sperm Tests for Male Infertility

“…10 Limitations to the clinical utility of the SPA include the use of hamster oocytes, its labor-intensive nature and expense, the fact that it is technically demanding to perform, and that it has significant issues of assay standardization. 1 Hemizona Assay (HZA) The HZA, first described by Burkman et al in 1988, was introduced to examine the binding of sperm to the human-oocyte zona pellucida. 11 Quantification of sperm-zona binding uses salt-stored human hemizonae and is a relatively sophisticated and involved bioassay.…”

“…12 Acrosome Reaction (AR) This acrosome reaction is an exocytic secretory event within the sperm head that releases proteolytic enzymes for zona pellucida penetration and remodels the sperm surface in preparation for oocyte fusion. 1,13 It is triggered by sperm-zona binding. The AR status of sperm is assessed using fluorescent lectins that bind to the acrosomal membrane or to the acrosomal contents.…”

“…One limitation of AR assays is that there is a measurable prevalence of spontaneous AR in human sperm (Ͻ4%), making correlations to pregnancy outcomes difficult. 1 Because of this, AR induction with ionophores has been reported to improve the dynamic range of the assay. Unfortunately, using ionophores is a nonphysiological maneuver and avoids the normal receptor-signal activation system that is important to assess.…”

“…However, the idea that fertility can be defined by threshold values of semen parameters is a concept that is fundamentally flawed. 1 Although not a true measure of fertility, the semen analysis, if abnormal, suggests that the probability of achieving fertility is lower than normal. 2 Because of biological variability, two semen analyses are generally needed, performed with two to three days of sexual abstinence and evaluated in a standardized fashion.…”

“…As examples, within-subject, interejaculate coefficients of variation for sperm concentration and motility are estimated at 44.7% and 15% in one study. 1 Thus, even with excellent quality control, wide biological variation in semen quality profoundly challenges the notion that the conventional semen analysis can accurately assess male fertility.…”