Publications Validate LDT for Sperm Function, as Measure of Fertility

The Cap-Score Sperm Function Test (Androvia LifeSciences) can accurately assess sperms' capaciatation state, a necessary condition for male fertility, and report the percentage of sperm in a sample that can actually fertilize an egg. The company, which published two papers—clinical and technology validation studies—April 18 in Molecular Reproduction and Development, says the test holds clinical value as a general screening test for men uncertain about their fertility.

Approximately 40 percent of infertility is attributable to male factors. Yet, standard semen analysis, which assesses sperm count, motility, and morphology, yields a diagnosis in less than 50 percent of male infertility cases. The rest of infertility cases are believed to be caused by failings in sperm function, which cannot be measured by traditional semen analysis. Experts say that a test that could measure sperm function—a sperm's ability to fertilize—would have huge clinical importance.

"A simple diagnostic assay would provide a needed functional complement to the descriptive assessments of traditional semen evaluations," writes lead author Melissa Moody, from Androvia LifeSciences (Mountainside, N.J.) in one of the papers. "Identifying sperm with deficiencies in fertilizing ability will allow for a more specific understanding of what is now categorized as 'idiopathic infertility.' Of much greater practical importance, such a physiological assessment would enable a clinician to effectively counsel a couple toward the most appropriate form of assisted reproduction to achieve pregnancy."

The Cap-Score is an in vitro, laboratory-developed test designed to assess sperm function, by measuring capacitation. The test involves incubating sperm in non-capacitating medium, as well as medium containing capacitating stimuli. The score measures response to the capacitation stimuli by measuring monosialotetrahexosylganglioside (GM1) localization patterns, responsible for capacitation. The test result—the Cap-Score—reports the proportion of sperm within a sample that display the localization patterns associated with capacitation, compared to a normal, fertile population.

One of the two published papers validated the accuracy, reproducibility, and precision of the Cap-Score test. The second paper assessed the clinical utility of the Cap-Score assay in two clinical trials. Together, these findings showed that capacitation status strongly correlated with a man's history of fertility.

In the first study involving men with long histories of unexplained infertility pursuing assisted reproduction in a tertiary care fertility clinic, men with high Cap-Scores (above a 39.5 percent threshold) had a 92 percent chance of conceiving by natural conception or within three cycles of intrauterine insemination. In contrast, men with Cap-Scores below the 39.5 percent threshold had only a 21 percent chance of conceiving. In the second trial, the Cap-Scores from a group of 76 men with proven fertility were compared against those of 122 men seeking semen analysis because of difficulty conceiving. A significantly higher percentage of men questioning their fertility (34 percent) had abnormally low Cap-Scores, compared with only 13 percent of the known fertile men.

A previous study by the company suggested that use of the Cap-Score to personalize management of couples with unexplained infertility projected to result in higher clinical pregnancy rates and reduced medical costs (nearly $5,000) in couples with women 35 to 37 years of age, compared to the current standard of care.

Takeaway: Results from clinical and technology validation studies of the Cap-Score Sperm Function Test suggest the utility of the test, in conjunction with standard semen analysis, for screening males with suspected infertility.