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Male Infertility and Variation in CAG Repeat Length in the Androgen Receptor Gene: A Meta-analysis

Departments of Preventive Medicine (C.A.D.-D., E.D.T., V.K.C.), Urology (E.D.T.), and Obstetrics, Gynecology, and Medicine (R.Z.S.), Keck School of Medicine of the University of Southern California, Los Angeles, California 90033

Address all correspondence and requests for reprints to: Victoria Cortessis, Ph.D., Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MC-9175, Los Angeles, California 90033. E-mail: cortessi{at}usc.edu.

Context: Many studies have investigated the association between male infertility and trinucleotide repeat polymorphisms in the androgen receptor (AR) gene, but no comprehensive meta-analysis of all published studies has been conducted.

Objective: Our goals were to summarize published data on associations between AR CAG and GGC repeat lengths and male infertility and investigate sources of variation between study results.

Data Sources: We searched for reports published before October 2006 using Medline, PubMed, and Web of Science.

Study Selection: All selected studies included the following: a case group with infertility as measured by semen parameters, a control group of known or presumed fertile men, and measurement of CAG and/or GGC repeat lengths among cases and controls. Thirty-nine reports were selected based on these criteria, and 33 were ultimately included in the meta-analysis.

Data Extraction: One investigator extracted data on sample size, mean and SD of trinucleotide repeat length, and study characteristics.

Data Synthesis: Estimates of the standardized mean difference (95% confidence interval) were 0.19 (0.09–0.29) for the 33 studies and 0.31 (0.14–0.47) for a subset of 13 studies that used more stringent case and control selection criteria. Thus, in both groups, cases had statistically significantly longer CAG repeat length than controls. Publication date appeared to be a significant source of variation between studies.

Conclusions: This meta-analysis provides support for an association between increased androgen receptor CAG length and idiopathic male infertility, suggesting that even subtle disruptions in the androgen axis may compromise male fertility.

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