Microdeletions in the Y chromosome and recurrent reproductive loss.

Abstract

Objective: Investigators have recently linked sperm chromosomal aneuploidy frequency with recurrent miscarriage. A male genetic factor, based on such gross cytogenetic analysis, may imply a need for further investigation on the molecular level. Therefore, a pilot study was undertaken to assess whether a causal link between male gamete genetic abnormalities at the microscopic level and recurrent pregnancy loss could be established.Design: Seven male partners of women with recurrent pregnancy loss were tested for microdeletions in their Y chromosome.Materials/Methods: “Recurrent pregnancy loss” was defined as history of two or more spontaneous abortions. Male gamete genetic abnormalities at the microscopic level were tested in the Y chromosome, flanking the AZF region (“MYC” Test). Patient DNA was extracted via the buccal swab method, and PCR analysis was then performed on eighteen (18) loci (Promega Corporation, Madison, WI). Such a “MYC” Test result was considered positive when at least one such microdeletion in the Y chromosome was identified.Results: Five of the seven patients (71.4%) tested MYC positive. Two patients were teratozoospermic (strict sperm morphology < or = 4% normal). Three patients (60%) were normozoospermic. Of the three MYC positive patients: Their microdeletions ranged in number from 1 to 8. Their microdeletions were all found in the AZFd region, specifically at locus DYS236.Conclusions: Male genetic abnormalities, in the form of microdeletions in the Y chromosome, were found in the partners of women experiencing recurrent reproductive loss. Since this genetically abnormal semen was analyzed and tested as normal, semen analysis alone may prove insufficient for the exclusion of male factor etiology. Consequently, such “MYC” testing may be necessary to accomplish a thorough work-up for poor reproductive history cases. Undoubtedly, greater numbers of such cases should be similarly evaluated to confirm these early findings. Male genetic abnormalities may then prove, in certain cases, the causal factors for recurrent reproductive loss. Objective: Investigators have recently linked sperm chromosomal aneuploidy frequency with recurrent miscarriage. A male genetic factor, based on such gross cytogenetic analysis, may imply a need for further investigation on the molecular level. Therefore, a pilot study was undertaken to assess whether a causal link between male gamete genetic abnormalities at the microscopic level and recurrent pregnancy loss could be established. Design: Seven male partners of women with recurrent pregnancy loss were tested for microdeletions in their Y chromosome. Materials/Methods: “Recurrent pregnancy loss” was defined as history of two or more spontaneous abortions. Male gamete genetic abnormalities at the microscopic level were tested in the Y chromosome, flanking the AZF region (“MYC” Test). Patient DNA was extracted via the buccal swab method, and PCR analysis was then performed on eighteen (18) loci (Promega Corporation, Madison, WI). Such a “MYC” Test result was considered positive when at least one such microdeletion in the Y chromosome was identified. Results: Five of the seven patients (71.4%) tested MYC positive. Two patients were teratozoospermic (strict sperm morphology < or = 4% normal). Three patients (60%) were normozoospermic. Of the three MYC positive patients: Their microdeletions ranged in number from 1 to 8. Their microdeletions were all found in the AZFd region, specifically at locus DYS236. Conclusions: Male genetic abnormalities, in the form of microdeletions in the Y chromosome, were found in the partners of women experiencing recurrent reproductive loss. Since this genetically abnormal semen was analyzed and tested as normal, semen analysis alone may prove insufficient for the exclusion of male factor etiology. Consequently, such “MYC” testing may be necessary to accomplish a thorough work-up for poor reproductive history cases. Undoubtedly, greater numbers of such cases should be similarly evaluated to confirm these early findings. Male genetic abnormalities may then prove, in certain cases, the causal factors for recurrent reproductive loss.