Effect of Microsurgical Varicocele Repair on Sperm Capacitation and Probability of Generating a Pregnancy as Measured by Pre and Postoperative Novel Testing With Cap-Score.

Objective: To study whether varicocele repair would improve sperm capacitation and probability of generating a pregnancy.

Methods: Data were collected prospectively from 40 consecutive adult men who presented with infertility confirmed by semen analysis (SA) and found to have a varicocele on exam or ultrasound who underwent unilateral or bilateral subinguinal microscopic varicocelectomy. We recorded pre and postoperative SA, Cap-Score, and probability of generating a pregnancy (PGP) with a 3-month follow-up.

Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

Research Questions: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics?

Design: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men.

Cap-Score™ prospectively predicts probability of pregnancy.

Semen analysis (SA) poorly predicts male fertility, because it does not assess sperm fertilizing ability. The percentage of capacitated sperm determined by G localization ("Cap-Score™"), differs between cohorts of fertile and potentially infertile men, and retrospectively, between men conceiving or failing to conceive by intrauterine insemination (IUI). Here, we prospectively tested whether Cap-Score can predict male fertility with the outcome being clinical pregnancy within ≤3 IUI cycles.

Timing of sperm capacitation varies reproducibly among men.

Sperm must mature functionally in the process of capacitation to become able to fertilize. Capacitation depends on membrane lipid changes, and can be quantitatively assessed by redistribution of the ganglioside G , the basis of the Cap-Score™ sperm function test. Here, differences in Cap-Score were compared among and within men at two time points.

Localization patterns of the ganglioside G in human sperm are indicative of male fertility and independent of traditional semen measures.

Semen analysis lacks a functional component and best identifies extreme cases of infertility. The ganglioside G is known to have functional roles during capacitation and acrosome exocytosis. Here, we assessed whether G localization patterns (Cap-Score™) correspond with male fertility in different settings: Study 1 involved couples pursuing assisted reproduction in a tertiary care fertility clinic, while Study 2 involved men with known fertility versus those questioning their fertility at a local urology center.