PTU - Polskie Towarzystwo Urologiczne
list of articles:

Karyotype 46,XX as a cause of male infertility
Article published in Urologia Polska 2008/61/Supl. 1.


Jan Karol Wolski, Alicja Ilnicka, Barbara Pawłowska, Janusz G. Zimowski, Joanna Bogdanowicz, Katarzyna Kozioł, Piotr Lewandowski
Przychodnia „Novum” w Warszawie
Zakład Genetyki, Instytut Psychiatrii i Neurologii w Warszawie



Due to WHO definition, infertility “is an inability of sexually active couple to initiate a pregnancy after one year of unprotected regular intercourse”. This disturbance was stated as a regular disease and was added into International Classification of Diseases ICD-10 (male infertility – N.46, female infertility N.97.0-97.9). According to epidemiological data infertility is a global problem and affects approximately 1/6 of all couples. Responsibility for infertility blames equal men and women. About 20% causes of male infertility have genetic origin. Karyotype 46,XX appears in men with frequency 0.005% (1/20.000) live male births. Characteristic clinical sings
are: male phenotype, adequate size of penis, small testes and azoospermia. Sex identity is male and orientation is heterosexual. The nature of these disturbances is translocation of short arm of Y-chromosome to X-chromosome or, more rare, to one of the autosome during meiosis in paternal gonads. Gene SRY (Sex-determining Region on the Y-chromosome) in the short arm Y-chromosome (Yp) codes protein TDF (Testis Determining Factor) and determines male phenotype in fetus. Because translocation doesn’t contain long arm of the Y-chromosome (Yq) where region AZF is located, no spermatogenesis in carriers of this chromosome’s rearrangement are noticed and azoospermia results. Thus, besides obligatory guidelines in azoospermia, in 46,XX male there is no indication for testicular biopsy, because of expected results of pathologic evaluation – no germinal cells, hyalinization, tubules fibrosis and hyperplasia of Leydig’s cells are reported.


The goal of this work is clinical presentation correlated with genetic evaluations in 4 men with 46,XX karyotype.

Materials and methods.

Among infertile couples admitted to the fertility center, hypogonadal men with azoospermia recorded in two spermiograms were selected. During regular diagnosis according to WHO and EAU guidelines, evaluation of blood hormones (FSH, testosterone) and ultrasound of the gonads were done. For differentiation with other clinical syndromes with hypogonadism and azoospermia and determination for testicular biopsy patients had genetic tests. In 4 men (b. 1971, 1975, 1978, 1980) using GTG procedure karyotype 46,XX was specified and after that FISH (Fluorescence in Situ Hybridization) technique for detection of translocation of SRY gene to X-chromosome was implemented. Using PCR technique (Polymerase Chain Reaction) for size up a fragment of Y-chromosome translocation additional molecular tests for SRY presence and amelogenins genes and regions DYZ1 and DYZ3 were performed.


In each patient clinical examination showed leptosomatic constitution, good size of penis, small testes (mean vol. 3 mL) and hypoandrogenic body features (weak hair growing on patient’s face). Lab tests: semen exams showed azoospermia, FSH levels were elevated in 4 patients while testosterone levels were near low normal range in 3 pts and below normal in 1. Hyperechogenicity (testicular failure) in gonadal ultrasound was noticed in all cases. All patients had male sex identity, heterosexual preference. Moreover, no reduction of libido, no erectile dysfunctions and no problem with ejaculations were reported. In 4 men karyotypes were 46,XX. In 3 of them, FISH
technique confirmed translocation of the fragment of short arm of the Y-chromosome with SRY gene to the short arm of the X-chromosome. In all groups, PCR technique confirmed translocations of SRY gene and didn’t show fragment of the Y-chromosome with amelogenins gene and DYZ1, DYZ3 regions.


1. In each infertile man with hypogonadism and azoospermia genetic evaluations should be done before the testicular biopsy. 2. Genetic diagnostics including determination of the karyotype and tests with FISH and PCR techniques give the possibility for establishment of adequate clinical diagnosis. 3. Nevertheless WHO/ EAU guidelines for azoospermic men, patients with 46,XX karyotype do not have indication for testicular biopsy, because of known result of histopathological exams. 4. Men with 46,XX karyotype are excluded from the active procreation. 5. According to low blood level of testosterone 46,XX male should be subjected to regular control of androgens and are predicted for androgen’s supplementations in the future.