A DOUBLE-BLIND, PROSPECTIVE TEST DEMONSTRATES AN ASSOCIATION BETWEEN CAPACITATION STATUS AND PREGNANCY

Abstract

Semen Analysis (SA) often fails to predict fertility, apart from extreme cases, highlighting the need for advanced sperm testing. Cap-Score™ is a validated test that uses changes in GM1 localization patterns to identify sperm that can and cannot capacitate. Since capacitation is requisite for fertilization, men must produce sufficient sperm with this ability for pregnancy generation. The purpose of this study was to use a double-blind prospective analysis to evaluate how predictive a previously defined Cap-Score reference range (Cardona, et al. 2017) was, of male fertility. Cap-Score and SA were performed (n=107) with clinical Intrauterine Insemination (IUI) outcomes available for 24 at the time of analysis. The chance of pregnancy outcome was predicted as either low (n=9) or normal (n=15), based solely on the previously defined reference range. IUI was done blinded to Cap-Score evaluation. Absolute and cumulative pregnancy rates were compared over 1-3 rounds of IUI using a Kaplan-Meier survival analysis. Semen analysis measures were compared between pregnant (n=8) and not-pregnant (n=16) groups using weighted t-tests, with the weights assigned by the number of IUI rounds. Men having low Cap-Scores showed reduced absolute and cumulative pregnancy outcomes (absolute: predicted low [0%] vs. predicted normal [53%; p=0.001]; cumulative predicted low vs normal: 0 vs 33, 0 vs 58, and 0 vs 58% for cycles 1, 2, and 3 [n=24, 11, and 4 rounds of IUI; p=0.025]). Only Cap-Score (35.4±1.7 vs 31.3±2.2; p=0.04) and motility (81.1±2.2 vs 73.9±3.5; p=0.02), differed between the pregnancy groups. No differences were detected between these groups in semen volume (p=0.47), sperm concentration (p=0.83), total motile sperm (p=0.84), or in male (p=0.07) and female age (p=0.06). Cap-Score was associated with a man’s chance of generating a pregnancy, substantiating previous work (Schinfeld, et al. 2018). While motility differed between the pregnancy groups, all men were above the 40% WHO cut-off. All pregnancies occurred within the first two rounds of IUI within the normal Cap-Score group. Quickly identifying men with reduced fertility, rather than after multiple failed IUI attempts, was modeled to improve outcome and save money (Babigumira, et al 2018). Several studies support the improvement of capacitation through lifestyle changes and(or) surgical intervention. Thus, depending on time, resource and treatment goals, multiple options are available for men with reduced Cap-Scores beyond intracytoplasmic sperm injection.