This research project integrates our clinical and basic science interests and is designed to identify objective biochemical measurements in sperm that affect and predict the fertilizing potential of male factor infertility patients. We demonstrated an inverse correlation between sperm concentrations and per sperm creatine-N-phosphotransferase (CPK) activity in normospermic and oligospermic men. This suggested to us that there are biochemical differences between sperm of these two groups. We tested this hypothesis and found that CPK activities predicted fertilizing potential in fertile and infertile men. We have also discovered a five-fold difference in the relative concentrations of B-type and M-type CPK isoforms in sperm samples with a high correlation between CPK activities and M-CPK concentrations (R=0.70, p<0.001, N=159). In ongoing research, funded by an R01 grant, we pursue clinical studies focusing upon the role of CPK activity and CPK isoform ratios in the prediction of sperm quality and fertilizing potential. We are also looking at the structure, biosynthesis and immunology of sperm CPK, and searching for further biochemical probes that may reflect sperm function. The Fogarty International Research Collaboration Award will extend our clinical studies to the Szent-Gyorgyi Albert Medical School at Szeged, Hungary. We propose to carry out CK- isoform ratio measurements in four patient groups: (a) in a retrospective study of couples treated for male factor infertility; (b) in a prospective study of infertile couples; (c) in couples with suspicion of unexplained male factor infertility and (d) in oligospermic men with varicocele before and after corrective surgery. The last project will tie in with an ongoing WHO study in Szeged. Due to the proposed collaboration, the sperm quality of varicocele patients will be also evaluated with the sperm CK-isoform ratios. The Fogarty Award will enable the collaborative investigators in Szeged to participate in a new research area of basic andrology, and it will provide the infertile couples a diagnostic technology which is presently not available in Hungary.