Defective sperm–zona pellucida interaction: a major cause of failure of fertilization in clinical in-vitro fertilization

Abstract

Sperm-zona pellucida binding and penetration were assessed on the oocytes that failed to fertilize from couples with >/=3 oocytes treated by standard in-vitro fertilization (IVF). There were four groups: fertilization rate 0% (n = 369), 1-25% (n = 194), 26-50% (n = 81) and 51-95% (n = 100). Of the couples with zero fertilization rate 70% had </=5 spermatozoa bound per zona pellucida and 42% had no spermatozoa penetrating the zona pellucida of any oocyte. In contrast, in the 51-95% fertilization rate group, only 17% had </= 5 spermatozoa bound per zona pellucida and 6% had no spermatozoa penetrating the zona pellucida. There was a significantly higher frequency of poor sperm morphology (</= 5% normal) in couples with zero fertilization rate (36%) than in the fertilization rate group 51-95% (7%). Incubation of oocytes from 68 couples with zero fertilization rate and low sperm-zonae pellucidae binding with fertile donor spermatozoa resulted in normal sperm-zona pellucida binding and most zonae pellucidae being penetrated. In conclusion, defective sperm-zona pellucida interaction was the major cause for low fertilization rates in standard IVF. This was usually because of defects of the spermatozoa rather than defects of the oocytes. Sperm defects likely to cause failure of fertilization should be diagnosed before commencing IVF and the patients directed to intracytoplasmic sperm injection.

Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility

“…Because UTJ morphology is divergent among species and is a rather simple funnel shape in human females (45), human spermatozoa may no longer need ADAM3 for UTJ migration. However, human spermatozoa are able to bind to cumulus-free ZP and thus ZP-binding ability is well correlated with male fertility (46,47). There are at least 21 ADAM family members found in humans and seven are testis specific, so other ADAM protein(s) may substitute for the ADAM3 function.…”

Effects of pentoxifylline treatment before freezing on motility, viability and acrosome status of poor quality human spermatozoa cryopreserved by the liquid nitrogen vapor method

“…Sperm function tests such as the acrosome reaction are better fertility predictors than traditional semen parameters (21)(22)(23)(24)(25)(26)(27)(28). The mechanism of the acrosome reaction induced by ionophores differs from the physiological acrosome reaction induced by the zona pellucida (22).…”

“…We did not test other physiological agonists on the acrosome reaction, such as progesterone or recombinant zona pellucida. Instead, we elected to use the ionophore-induced acrosome reaction because it has been extensively validated as a sperm function test with excellent predictive values for outcomes in assisted reproduction (23)(24)(25)(26)(27)(28). Using an ARIC cutoff of 10%, the sensitivity of the test in predicting subfertility was 54%, with a positive predictive value of 64% and specificity of 85% (24)(25)(26).…”

Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition

“…Indeed, the World Health Organization (WHO) estimates that 50% of all infertility is due to abnormalities associated with the structure or function of the male gamete (McLachlan and de Kretser, 2001). Of these abnormalities, one of the greatest problems appears to lie in an inability of spermatozoa to recognize and bind to the zona pellucida (ZP), a protective glycoprotein layer that surrounds the oocyte (Liu and Baker, 2000). Nevertheless, despite the importance of sperm -ZP adhesion in the etiology of male infertility, the molecular basis of this process is not well understood.…”