Creatine Kinase : A New Marker of Sperm Quality
Ashok Agarwal, Ph.D.

Creatine kinase is an enzyme that is involved in the synthesis and utilization of energy in the sperm. Spermatozoa undergo a remarkable transformation during the final stage or sperm differentiation whereby they loose the cytoplasmic component of the cell during release of the mature spermatid from the Sertoli cell. Following spermiation, any residual cytoplasm that is associated with spermatozoa is retained in the mid-piece region as an irregular cytoplasmic mass. If this mass occupies more than one-third of the sperm head, it is termed a cytoplasmic droplet. Creatine kinase levels indicate sperm maturity, with higher levels being found in immature spermatozoa which retain their cytoplasmic droplets. The high creatine kinase levels, unlike sperm concentration correlate inversely with the fertilizing potential of the spermatozoa and indicate the degree of cellular immaturity.

We studied the differences in sperm creatine kinase levels between normal healthy donors and subfertile patients with various diagnoses and the relationship between sperm creatine kinase levels in subfertile men and their clinical diagnosis. Sixty-one subfertile patients with a clinical diagnosis of idiopathic infertility (n = 34), varicocele (n = 20), post-vasectomy reversal (n = 7) or cancer (n = 22) [testicular cancer (n = 10), nontesticular cancer (n = 12)] who were referred to our laboratory for semen evaluation were selected. Healthy normal donors (n = 15) were selected on the basis of a normal semen analysis. We found that the creatine kinase levels were significantly higher in patients with varicocele compared to normal donors (P = 0.0001), cancer patients (P = 0.0002) and men with idiopathic infertility (P = 0.0009). There was no significant difference in creatine kinase levels between normal donors and patients with cancer or idiopathic infertility. The creatine kinase levels in patients with varicocele and those with post-vasectomy reversal were higher than in patients with other diagnoses and normal donors.



We found that subfertile patients had higher levels of creatine kinase activity than normal donors. In our study, creatine kinase activity was higher in oligospermic patients than in subfertile normospermic patients. The majority of normospermic subfertile patients had normal creatine kinase activity. The creatine kinase levels in men with testicular and nontesticular cancers were similar to those in normal donors. This finding suggests that sperm produced by cancer patients may be biochemically immature and incapable of fertilization.


A clinical diagnosis of varicocele or post-vasectomy reversal in subfertile patients indicates a poor semen quality compared to that in subfertile patients with no known causes of infertility. Patients who have varicocele or post-vasectomy reversal and elevated levels of creatine kinase may need surgical correction before invasive assisted reproductive procedures, such as in vitro fertilization or intracytoplasmic sperm injection, are recommended. The similar levels of creatine kinase in cancer patients and normal donors in our study suggest that the final phase of spermatogenesis may not be altered in cancer patients. Therefore, semen from these patients should be banked before initiating chemotherapy or radiation therapy to ensure future fertility. In conclusion, creatine kinase appears to be a reliable biochemical marker for assessing the quality of semen in subfertile men.


1. Sidhu RS, Sharma RK, and Agarwal A.:
Relationship between creatine kinase activity and semen characteristics in subfertile men.
International Journal of Fertility, 43, 1998.
2. Sidhu RS, Hallak J, Sharma RK, Thomas AJ Jr., and Agarwal A.:
Relationship between creatine kinase levels and clinical diagnosis of infertility.
Journal of Assisted Reproduction and Genetics, 15:188-192, 1998.
3. Sidhu RS, Wang Y, and Agarwal A.:
Creatine kinase level and lipid peroxidation rate in human spermatozoa from patients with cancer.
Journal of Assisted Reproduction and Genetics, 14:538-542,1997.
4. Hallak J, Sharma RK, Thomas AJ Jr., and Agarwal A.:
Creatine kinase levels in oligospermia.
1998 AUA abstract #817.


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