Human Reproduction, Vol. 15, No. 7, 1431-1434,
July 2000
© 2000 European Society of Human Reproduction and Embryology
Prognostic value of Y deletion analysis
What is the clinical prognostic value of Y chromosome microdeletion analysis?
1 Immunogénétique Humaine, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France and 2 Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence, Italy
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Abstract |
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In many centres, Y chromosome deletion analysis is still not performed routinely and if so, the results are used for genetic counselling but are not considered as having a useful prognostic value. The type of deletion (AZFa, b or c) has been proposed as a potential prognostic factor for sperm retrieval in men undergoing TESE. AZFc deletions and partial AZFb deletions are associated with sperm retrieval in ~50% of cases while in the case of a patient with complete AZFb deletion the probability of finding mature spermatozoa is virtually nil. Therefore the extent and position of a Y microdeletion is important (complete or partial). The prognostic value of Y chromosome deletion analysis in cases of oligozoospermia is important when one considers the progressive decrease of sperm number over time in men with AZFc deletions. Cryo-conservation of spermatozoa in these cases could avoid invasive techniques, such as TESE/ICSI, in the future. Male offspring that are conceived by ICSI or IVF techniques from father with oligozoospermia or azoospermia would also benefit from knowledge of their Y status, since the identification of the genetic defect will render future medical or surgical therapies unnecessary. Y microdeletion screening is therefore important, not only to define the aetiology of spermatogenic failure, but also because it gives precious information for a more appropriate clinical management of both the infertile male and his future male child.
Key words: AZF deletions/azoospermia/genetic counselling/oligozoospermia/Y chromosome deletion
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Introduction |
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TopAbstractIntroductionReferences |
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Over the last few years, considerable technical advances in the treatment of male factor infertility, have been achieved. This has lead to the opinion that any kind of obstructive and non-obstructive azoospermia or oligozoospermia is suitable for therapy. Unfortunately, the omnipotence of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) procedures has apparently reduced the need for prognostic tests and many clinical practitioners in the field advise either TESE/ICSI or ICSI alone without a complete diagnostic work-up. Considering that TESE/ICSI procedures are highly invasive, with possible adverse effects (Manning et al., 1998
) on the male, with an overall sperm recovery rate of 50% in case of non-obstructive azoospermia (Silber et al., 1995), we would emphasize that data from basic research must be integrated into clinical practice and in the longer term may result in a more appropriate knowledge-based therapy of the infertile male.
Y chromosome microdeletions are a common cause of spermatogenic failure (McElreavey et al., 1999). The incidence of Y microdeletions is 15–20% in men with idiopathic azoospermia, falling to 7–10% in men with idiopathic severe oligozoospermia. Recurrent Y chromosome microdeletions define three non-overlapping regions of Yq, termed AZoospermia Factor (AZF) AZFa, AZFb and AZFc, that have been proposed to be associated with Sertoli cell-only syndrome, spermatogenic arrest and a variable phenotype (severe oligozoospermia or azoospermia) respectively (Vogt et al., 1996). Although genotype/phenotype correlations have been difficult to establish, a number of studies support these general trends (Krausz and McElreavey, 1999).
The type of deletion (AZFa, b or c) has been proposed as a potential prognostic factor for sperm retrieval in men undergoing TESE. Deletions including and extending beyond the AZFc region (AZFb+c and AZFa+b+c) are associated with a total absence of testicular spermatozoa (Silber et al., 1998; Table I) and the presence of an AZFb deletion is a significantly adverse prognostic finding for TESE (Brandell et al., 1998; Table I). In contrast, in ~50% of azoospermic patients with AZFc deletions, mature spermatozoa have been found (Mulhall et al., 1997).
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In many centres, Y chromosome deletion analysis is still not performed as a routine measure and if so, the results are used for genetic counselling but are not considered as having a prognostic value. However, we believe that this position needs to be reconsidered. We recently described an azoospermic man, who was examined at an infertility clinic (unpublished data). Medical examination, hormone profile and karyotype were normal. Neither a diagnostic testicular biopsy nor Y chromosome screening were proposed, but TESE/ICSI was recommended. On the day of TESE, his wife was induced for multiple follicular growth. 24 bilateral testicular biopsies were performed and no spermatozoa was found. Histology of one of the biopsies indicated spermatogenic arrest at spermatocyte stage I. This individual sought a Y chromosome microdeletion screen at the Pasteur Institute in Paris on the basis of information he obtained using the Internet. The analysis of his DNA indicated a de-novo deletion of the entire AZFb region.
This case raises several questions regarding the correct management of couples where the male partner is affected by non-obstructive azoospermia. First, is it necessary to induce multiple follicular growth and carry out the retrieval of oocytes in the female partner considering that the general success rate of sperm retrieval by TESE is only 50%? Cryo-TESE is a good alternative to TESE/ICSI in azoospermic men and avoids unnecessary hormonal stimulation in the female partner. However, cryo-TESE is still a highly invasive technique which consists of multiple testis biopsies with possible adverse effect on the male (Manning et al., 1998), therefore, the need for a predictive diagnostic test before commencing cryo-TESE or TESE/ICSI procedures is clear. Only a few studies have attempted to develop a predictive diagnostic test pre-TESE/ICSI. Prior diagnostic testis biopsy analysed quantitatively (for the presence of mature spermatids) has been reported to be of value in the prediction of subsequent sperm retrieval (Silber et al., 1997). Y chromosome screening (including the AZFb region) has also been reported as a potential prognostic test (Brandell et al., 1998). The deletion of the patient mentioned above is consistent with previous reports of spermatogenic arrest either just prior to, or during meiosis, associated with an AZFb deletion (Vogt et al., 1996; Girardi et al., 1997; Brandell et al., 1998; Kleiman et al., 1999). To date, more than 30 studies have been published on Y chromosome screens of infertile men for microdeletions (for review, see Krausz and McElreavey, 1999). Unfortunately many of these studies did not report the extent of the deletions, testis histology was only available in a minority of cases and no matched phenotype was reported for the different type of AZFb deletions (Kent-First et al., 1999). However, a careful analysis of the literature and of our own cases shows that different subtypes of AZFb deletions do exist (Tables I and II
). Deletions which remove the whole region (complete AZFb deletions (sY113-sY143), as described in the original article of Vogt et al. (1996) are associated with spermatogenic arrest at the spermatocyte (patient 1, 2, 3, 13, 15 in Table II) or spermatid stage (patient 14 in Table II). Deletions which remove the whole AZFb deletions + AZFa and/or AZFc are associated with Sertoli cell-only syndrome (patients 4, 16,17, 20, 26 in Table II) or with spermatogenic arrest (patient 27 in Table II). In contrast, deletions which remove only a part of the region or only a single marker (partial AZFb deletions) are associated with a more heterogeneous phenotype including oligozoospermia (patient 18, 22, 24, 40, 41, 47 in Table II). Unless these atypical deletions are confirmed by Southern blotting their significance is uncertain. Some microdeletions may also represent irrelevant polymorphisms (patient 21 Table II) (Kostiner et al., 1998).
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We believe that the correct management of azoospermic men who are candidates for cryo-TESE or TESE/ICSI procedures should include a Yq microdeletion screen, with markers from both the proximal and distal part of the AZFb region. A precise knowledge of the extent and position of Y deletions is important to define the subtype of AZFb deletion (complete or partial). The probability of finding mature spermatozoa in case of a patient with complete AZFb deletion is virtually nil. Although round spermatids may be found at the diagnostic biopsy (patient 14 in Table I
) or through TESE (Brandell et al., 1998), Round Spermatid Injection (ROSI) is performed with success only in a few infertility centres. Therefore, we suggest that patients with complete AZFb deletion should undergo a diagnostic biopsy rather than the more invasive cryo-TESE. If the biopsy confirms the suspected spermatocytic arrest, cryo-TESE or TESE/ICSI should not be advised.
Azoospermia has also been found in men with AZFa and AZFc deletions. AZFa deletions are exceedingly rare and are associated with Sertoli cell-only syndrome type I (Krausz and McElreavey, 1999).
The situation is different regarding azoospermic patients with deletions of the AZFc region. Deletions of the AZFc region are usually associated with hypospermatogenesis or Sertoli cell-only syndrome type II. It is known that hidden islands of normal spermatogenesis in Sertoli cell-only syndrome type II can be found if multiple biopsies are perfomed (Mulhall et al., 1997; Brandell et al., 1998). Therefore in these cases cryo-TESE (but not TESE/ICSI) seems to be a correct approach.
The prognostic value of Y chromosome deletion analysis in cases of oligozoospermia is not at first apparent but it could have a clinical importance. Partial AZFb and complete AZFc deletions can be associated with oligozoospermia. On the basis of sperm number different types of assisted reproductive technique can be used since Y microdeletion does not preclude the normal fertilizing ability of the spermatozoa (Mulhall et al., 1997; Rossato et al., 1998; Page et al., 1999). However, a progressive decrease of sperm number over several months has been described in some men with AZFc deletions (Girardi et al., 1997; Simoni et al., 1997). Further follow-up studies on this group of men are urgently required to determine both quantative and qualitative changes in sperm production over time. Cryo-conservation of spermatozoa in these cases will avoid invasive techniques, e.g. TESE/ICSI, in the future.
Male offspring that are conceived by ICSI or IVF techniques from father with oligozoospermia or azoospermia would also benefit from knowledge of their Y status. Since AZFc deletions may be associated with a decline in sperm production over time, cryo-conservation of semen in early adulthood should be considered. Moreover, the identification of the genetic defect will render future medical or surgical therapies unnecessary.
In summary, Y microdeletion screening is important not only to define the aetiology of spermatogenic failure but also because it gives precious information for a more appropriate clinical management of both the infertile male and his future male child.
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Acknowledgments |
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The authors are grateful for the financial support of the Italian Telethon (grant n: 281/b), of the l'Association pour la Recherche sur le Cancer (ARC) and Fondation pour la Recherche Médicale (FRM).
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Notes |
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3 To whom correspondence should be addressed at: Immunogénétique Humaine, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. E-mail: ckrausz{at}pasteur.fr or c.krausz{at}dfc.unifi.it
This debate was previously published on Webtrack, May 19, 2000
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References |
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TopAbstractIntroductionReferences |
|---|
Brandell, R.A., Mielnik, A., Liotta, D. et al. (1998) AZFb deletions predict the absence of spermatozoa with testicular sperm extraction:preliminary report of a prognostic genetic test. Hum. Reprod., 13, 2812–2815.
Girardi, S.K., Mielnik, A. and Schlegel, P.N. (1997) Submicroscopic deletions in the Y chromosome of infertile men. Hum. Reprod., 12, 1635–1641.
Kent-First, M., Muallem, A. and Shultz, J. (1999) Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection. Mol. Reprod. Dev., 53, 27–41.[ISI][Medline]
Krausz, C. and McElreavey, K. (1999) Y chromosome and male infertility. Front. Biosci., 15, 1–8.
Krausz, C., Bussani-Mastellone, C., Granchi, S. et al. (1999a) Screening for microdeletions of Y chromosome genes in patients undergoing ICSI procedure. Hum. Reprod., 14, 1717–1721.
Krausz, C., Quintana-Murci, L., Barbaux, S. et al. (1999b) A high frequency of Y chromosome deletions in males with non-idiopathic infertility. J. Clin. Endocrinol. Metab., 84, 3606–3612.
Kleiman, S.E., Yogev, L., Gamzu, R. et al. (1999) Genetic evaluation of infertile men. Hum. Reprod., 14, 33–38.
Kostiner, D.R., Turek, P.J. and Reijo, R.A. (1998) Male infertility: analysis of the markers and genes on the human Y chromosome. Hum. Reprod., 13, 3032–3038.
McElreavey, K., Krausz, C. and Bishop, C.E. (1999) The human Y chromosome and male infertility. In McElreavey, K. (eds), The Genetic Basis of Male Infertility. Springer, Heidelberg, Germany, 211 pp.
Manning, M., Junemann, K.P. and Alken, P. (1998) Decrease in testosterone blood concentrations after testicular sperm extraction for intracytoplasmic sperm injection in azoospermic men. Lancet, 352, 37.[ISI][Medline]
Mulhall, J.P., Reijo, R., Alagappan, R. et al. (1997) Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection. Hum. Reprod., 12, 503–508.
Najmabadi, H., Huang, V., Yen, P. et al. (1996) Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligospermia detected using a sequence tagged site based mapping strategy. J. Clin. Endcrinol. Metab., 81, 1347–1352.[Abstract]
Oliva, R., Margarit, E., Ballesc, J.P. et al. (1998) Prevalence of Y chromosome microdeletions in oligospermic and azoospermic candidates for intracytoplasmic sperm injection. Fertil. Steril., 70, 506–510.[ISI][Medline]
Page, D.C., Silber, S. and Brown L.G. (1999) Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum. Reprod., 14, 1722–1726.
Pryor, J.L., Kent-First, M., Muallem, A. et al. (1997) Microdeletions in the Y chromosome of infertile men. New Engl. J. Med., 336, 534–539.
Reijo, R., Lee, T.Y., Salo, P. et al. (1995) Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genet., 10, 383–393.[ISI][Medline]
Reijo, R., Alagappan, R.K., Patrizio, P. and Page, D.C. (1996) Severe oligospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet, 347, 1290–1293.[ISI][Medline]
Rossato, M., Ferlin, A., Garolla, A. et al. (1998) High fertilization rate in conventional in-vitro fertilization utilizing spermatozoa from an oligozoospermic subject presenting microdeletions of the Y chromosome long arm. Mol. Hum. Reprod., 4, 473–476.
Silber, S.J., Van Steirteghem, A.C. and Devroey, P. (1995) Sertoli cell only revisited. Hum. Reprod., 10, 1031–1032.
Silber, S.J., Nagy, Z., Devroey, P. et al. (1997) Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure. Hum. Reprod., 12, 2422–2428.
Silber, S.J., Alagappan, R., Brown, L.G. and Page, D.C. (1998) Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum. Reprod., 13, 3332–3337.
Simoni, M., Gromoll, J., Dworniczak, B. et al. (1997) Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia. Fertil. Steril., 67, 542–547.[ISI][Medline]
Van der Ven, K., Montag, M., Peshka, B. et al. (1997) Combined cytogenetic and Y chromosome microdeletion sceening in males undergoing intracytoplasmic sperm injection. Mol. Hum. Reprod., 3, 699–704.
Vogt, P.H., Edelmann, A., Kirsch, S. et al. (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum. Mol. Genet., 7, 933–943.
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