Article
Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience

https://doi.org/10.1016/S1472-6483(10)60588-3Get rights and content

Abstract

A total of 3179 patients were screened for Y-chromosome microdeletions and 821 patients for partial AZFc deletions. Thirty-nine Y-chromosomal microdeletions were found (2.4% of men with <1 × 106/ml spermatozoa): two AZFa, two AZFb, one AZFbc, one partial AZFb, one partial AZFb+c and 32 AZFc (b2/b4). Partial AZFc deletions were found in 45 patients (5.5%), mostly gr/gr deletions (n = 28). In patients with AZFc deletion, azoospermia was found in 53.1% and sperm concentrations of mostly <0.1 × 106/ml were found in 46.9%. Semen analyses and FSH measurements showed no trend over time. Elongated spermatids were seen in 6/15 AZFc patients and bilateral Sertoli cell-only was found in 4/15. Testicular sperm extraction (TESE) was attempted in 10 patients and spermatozoa were found in six. Compared with infertile men matched by sperm concentration, no differences in hormonal and seminal parameters could be found in patients with AZFc or gr/gr deletions. It is concluded that: (i) frequency of AZF deletions in Germany is much lower than in other countries; (ii) AZFc deletions are associated with severe disturbances of spermatogenesis and TESE is not possible in half of these patients; (iii) AZFc and gr/gr deletions are not associated with any clinical diagnostic parameter; (iv) and no trend is apparent over time.

Section snippets

Manuela Simoni obtained her MD in 1982, followed by a specialisation in Endocrinology and Metabolism in 1985, from the University of Modena, Italy. In 1991 she completed a PhD in Endocrinology and Metabolism. Since 1990 she has been working at the Institute of Reproductive Medicine of the University of Münster, Germany, where she holds a Professorship for Endocrinology and Molecular Biology of Reproduction. Her research interests are gonadotropin and androgen action, testicular function,

References (126)

  • GB Rucker et al.

    Preoperative screening for genetic abnormalities in men with nonobstructive azoospermia before testicular sperm extraction

    Journal of Urology

    (1998)
  • CF Sargin et al.

    AZF microdeletions on the Y chromosome of infertile men from turkey

    Annales de Génétique

    (2004)
  • H Sawai et al.

    Molecular analysis of the Y chromosome AZFc region in Japanese infertile males with spermatogenic defects

    Journal of Reproductive Immunology

    (2002)
  • M Simoni et al.

    Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia

    Fertility and Sterility

    (1997)
  • NB Abdelmoula et al.

    Evaluation of DAZ microdeletions in 34 infertile men

    Archives of Andrology

    (2006)
  • M Aho et al.

    Y-chromosomal microdeletions among infertile Finnish men

    Acta Obstetricia et Gynecologica Scandinavica

    (2001)
  • R Ambasudhan et al.

    Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion

    Journal of Biosciences

    (2003)
  • B Arredi et al.

    Y-chromosome haplogroups and susceptibility to azoospermia factor c microdeletion in an Italian population

    Journal of Medical Genetics

    (2007)
  • SR Babu et al.

    PCR analysis of Yq microdeletions in infertile males, a study from south India

    Asian Journal of Andrology

    (2002)
  • HM Behre et al.

    Diagnosis of male infertility and hypogonadism

  • P Bor et al.

    Y-chromosome microdeletions and cytogenetic findings in unselected ICSI candidates at a Danish fertility clinic

    Journal of Assisted Reproduction and Genetics

    (2002)
  • ZM Cai et al.

    A genetic study on microdeletion of azoospermia factor region on Y chromosome of azoospermia and oligozoospermia patients

    Chinese Journal of Medical Genetics

    (2005)
  • IE Calleja Macías et al.

    Y chromosome micro–deletion identification in infertile males

    Ginecologia y obstetricia de México

    (2003)
  • SU Chen et al.

    Genetic screening of karyotypes and azoospermic factors for infertile men who are candidates for ICSI

    Archives of Andrology

    (2003)
  • VB Chernykh et al.

    Types of Y chromosome deletions and their frequency in infertile men

    Genetika

    (2006)
  • TG Cooper et al.

    Semen analysis and external quality control schemes for semen analysis need global standardization

    International Journal of Andrology

    (2002)
  • DG Cruger et al.

    Genetic analysis of males from intracytoplasmic sperm injection couples

    Clinical Genetics

    (2003)
  • XF Cui et al.

    Analysis of Yq microdeletions in idiopathic infertile males with azoospermia and oligospermia in Shaanxi province

    National Journal of Andrology

    (2005)
  • R Dada et al.

    Cytogenetic and molecular analysis of male infertility: Y chromosome deletion during nonobstructive azoospermia and severe oligozoospermia

    Cell Biochemistry and Biophysics

    (2006)
  • R Dada et al.

    Yq microdeletions – azoospermia factor candidate genes and spermatogenic arrest

    Journal of Biomolecular Techniques

    (2004)
  • R Dada et al.

    Molecular screening for Yq microdeletion in men with idiopathic oligozoospermia and azoospermia

    Journal of Biosciences

    (2003)
  • R Dada et al.

    AZF microdeletions associated with idiopathic and non-idiopathic cases with cryptorchidism and varicocele

    Asian Journal of Andrology

    (2002)
  • GR Dohle et al.

    Genetic risk factors in infertile men with severe oligozoospermia and azoospermia

    Human Reproduction

    (2002)
  • MK El Awady et al.

    Molecular study on Y chromosome microdeletions in Egyptian males with idiopathic infertility

    Asian Journal of Andrology

    (2004)
  • European Molecular Genetics Quality Network 2007 http://www.emqn.org [accessed 28 November...
  • A Ferlin et al.

    Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy

    Journal of Clinical Endocrinology and Metabolism

    (2007)
  • E Fernandez-Salgado et al.

    Molecular analysis of microdeletions of the Y chromosome in Venezuelan males with idiopathic infertility

    Investigacion Clinica

    (2006)
  • L Fernando et al.

    Y-chromosomal microdeletions and partial deletions of the azoospermia factor c (AZFc) region in normozoospermic, severe oligozoospermic and azoospermic men in Sri Lanka

    Asian Journal of Andrology

    (2006)
  • C Foresta et al.

    Sertoli cell function in infertile patients with and without microdeletions of the azoospermia factors on the Y chromosome long arm

    Journal of Clinical Endocrinology and Metabolism

    (2001)
  • C Foresta et al.

    Y chromosome microdeletions and alterations of spermatogenesis

    Endocrine Reviews

    (2001)
  • A Friel et al.

    Molecular detection of Y chromosome microdeletions: An Irish study

    International Journal of Andrology

    (2001)
  • J Fu et al.

    Relationship between microdeletion on Y chromosome and patients with idiopathic azoospermia and severe oligozoospermia in the Chinese

    Chinese Medical Journal

    (2002)
  • C Giannouli et al.

    Idiopathic non-obstructive azoospermia or severe oligozoospermia: a cross–sectional study in 61 Greek men

    International Journal of Andrology

    (2004)
  • P Grimaldi et al.

    Analysis of Yq microdeletions in infertile males by PCR and DNA hybridization techniques

    Molecular Human Reproduction

    (1998)
  • CJ Gruber et al.

    Absence of microdeletions in the azoospermia-factor region of the Y-chromosome in Viennese men seeking assisted reproduction

    Wiener klinische Wochenschrift

    (2003)
  • L Hadj-Kacem et al.

    Screening of Y chromosome microdeletions in Tunisian infertile men

    Archives of Andrology

    (2006)
  • A Hellani et al.

    Y chromosome microdeletions in infertile men with idiopathic oligo- or azoospermia

    Journal of Experimental and Clinical Assisted Reproduction

    (2006)
  • CV Hopps et al.

    Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions

    Human Reproduction

    (2003)
  • K Hucklenbroich et al.

    Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis

    Human Reproduction

    (2005)
  • A Ioulianos et al.

    A nation-based population screening for azoospermia factor deletions in Greek–Cypriot patients with severe spermatogenic failure and normal fertile controls, using a specific study and experimental design

    International Journal of Andrology

    (2002)
  • Cited by (0)

    Manuela Simoni obtained her MD in 1982, followed by a specialisation in Endocrinology and Metabolism in 1985, from the University of Modena, Italy. In 1991 she completed a PhD in Endocrinology and Metabolism. Since 1990 she has been working at the Institute of Reproductive Medicine of the University of Münster, Germany, where she holds a Professorship for Endocrinology and Molecular Biology of Reproduction. Her research interests are gonadotropin and androgen action, testicular function, genetics of male infertility, endocrinology and pathophysiology of reproduction. She is a member of several international societies and serves on the editorial board of several journals in the fields of endocrinology and reproduction.

    View full text