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An Increased CAG Repeat Length in the Androgen Receptor Gene in Azoospermic ICSI Candidates

JOSEP ORIOLA

CARLOS ASCASO

JOSÉ L. BALLESCÀ

From the Departments of ^* Physiology, Human Genetics Research Group, and Public Health, Biostatistics Unit, IDIBAPS, Faculty of Medicine, University of Barcelona; and Hormonal and^|| Genetics Service and Institut Clínic de Ginecologia, Obstetricia i Neonatología, Hospital Clínic i Provincial, Barcelona, Spain.

Correspondence to: Dr Rafael Oliva, Genetics Service, Hospital Clínic i Provincial, Villarroel 170, 08036 Barcelona, Spain.

The androgen receptor gene has a polymorphic trinucleotide repeat that encodes a polyglutamine tract in its N-terminal transactivation domain. We started this study in order to find out whether a correlation existed between the length of this polymorphic tract and the presence of azoospermia in candidates for intracytoplasmic sperm injection (ICSI). The CAG repeat length in exon 1 of the androgen receptor (AR) gene was directly sequenced in 102 patients with azoospermia and in 96 fertile controls. Hormone levels were also measured in patients with azoospermia. The mean AR gene CAG repeat length was significantly larger in azoospermic subjects than it was in control fertile men (23.25 ± 2.7 versus 22.42 ± 2.8; P = .033). A receiver operating characteristic analysis evidenced a cutoff point at 22/23 CAG repeats at which the probability of being azoospermic increased 2.2 times. Subsequent logistic regression analysis of the data showed that the odds for azoospermia increased with the number of CAG repeats. Men with more than 26 CAG repeats have a 4.09 greater risk of being azoospermic. Therefore, in our candidates for ICSI, a direct correlation exists between the CAG repeat length in the exon 1 of the AR gene and the risk of being azoospermic.

     Key words: Assisted reproduction, male infertility, spermatogenesis

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