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  • Environnement et Reproduction
  • Radio/Chimo Thérapie, Ploidie Spermatique et Fertilité
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Fertilité et aneuploïdies spermatiques après traitement par radiothérapie et/ou chimiothérapie pour cancer du testicule ou lymphome

Male fertility and chromosome aneuploidy in sperm cells after radiotherapy or chemotherapy in patients with lymphoma or testicular cancer

Andrologie volume 13, pages 403–411 (2003)Cite this article

Resume

La chimiothérapie et la radiothérapie anticancéreuses ont fait des progrès considérables ces dernières années permettant ainsi d’améliorer le pronostic de nombreuses pathologies malignes. Les effets secondaires de ces traitements sur la fonction de reproduction masculine sont importants à considérer pour tout sujet en âge de procréer.

Tout d’abord, ils entraînent une inhibition de la spermatogenèse, transitoire dans la plupart des cas. Certains facteurs, comme la qualité des paramètres de sperme avant traitement ainsi que la nature, la dose totale et le rythme d’administration des thérapeutiques anti-cancéreuses influencent la reprise de la spermatogenèse. Cependant, il est impossible à ce jour de prédire les chances et le délai de récupération au plan individuel, et la cryoconservation de sperme reste la seule méthode éprouvée pour pallier aux effets stérilisants de ces traitements.

Par ailleurs, la chimiothérapie et la radiothérapie sont susceptibles d’altérer le contenu génétique des cellules germinales. Parmi ces altérations génétiques, les anomalies chromosomiques pourraient, si elles persistent après reprise de la spermatogenèse, être responsables de fausses-couches spontanées ou de malformations congénitales dans la descendance. Les effets à court terme (moins de 3 mois) sur le contenu chromosomique des spermatozoïdes sont maintenant assez bien évalués dans la littérature: les cassures de l’ADN et les anomalies de ségrégation des chromosomes au cours de la méiose sont responsables d’anomalies structurales et numériques. En revanche, à plus long terme, les conséquences ne sont pour l’instant pas clairement établies et les résultats des études réalisées sur le sujet sont contradictoires.

Dans le cadre d’une étude rétrospective incluant des sujets traités par radiothérapie et/ou chimiothérapie entre 1995 et 2000 pour cancer du testicule ou pour lymphome, nous avons comparé les taux d’aneuploïdies spermatiques post-thérapeutiques de ces patients avec ceux de sujets fertiles sains. L’analyse par hybridationin situ de sondes marquées en fluorescence (FISH) de la ségrégation des chromosomes X, Y, 18 chez 13 patients a montré pour 4 d’entre eux une augmentation significative des taux d’aneuploïdes (disomies XY et diploïdies essentiellement). Ces anomalies ne semblent pas être corrélées au délai post-thérapeutique, à la numération spermatique ou à la tératozoospermie.

Ainsi, les données de la littérature et les résultats préliminaires de notre étude montrent que les augmentations des taux d’aneuploïdies spermatiques à distance des traitements anticancéreux sont peu fréquentes et que ces taux sont variables d’un patient à l’autre sans que l’on retrouve de corrélation avec des paramètres clinico-biologiques.

Abstract

Improvements in cancer therapy have considerably modified patient survival rates over recent years. However, the side effects of these treatments especially the effects on fertility, must be taken into account. Anticancer therapy can transiently inhibit spermatogenesis. Factors such as pretreatment semen parameters and the type of chemotherapy or radiotherapy may influence recovery of spermatogenesis, but it is still impossible to predict the probability of and time to recovery for each patient. Sperm banking remains the only way to prevent the effects of cancer treatment on male fertility.

Another possible effect of chemotherapy or radiotherapy is genetic damage to germ cells. For instance, chromosomal abnormalities in viable sperm produced by these patients after recovery of spermatogenesis may result in fetal death or congenital abnormalities in their offspring. It has been fairly well documented that, during the first three months after treatment, DNA breaks and abnormal chromosomal segregation induced by chemotherapy/radiotherapy lead to structural and numerical chromosomal abnormalities in spermatozoa, respectively. However, the long-term effects on genetic sperm content have not been clearly established. The results of published studies are contradictory and are based on limited numbers of patients (maximum of 6).

We present the preliminary results of a retrospective study concerning patients treated for testicular cancer or lymphoma between 1995 and 2000. Fluorescence in situ hybridization (FISH) analysis of chromosomes X, Y and 18 was performed on sperm collected one to five years after treatment and compared to the data obtained for non-affected fertile men. For four out of 13 patients, we found a significantly increased frequency of aneuploidy rates (mainly XY disomy and diploidy), and these results did not appear to be correlated with sperm count, sperm morphology or post-treatment duration.

In conclusion, increased sperm aneuploidy rates appear to only concern a small number of patients, to varying degrees and without any predictive factors. According to published data and our preliminary results, we recommend waiting at least two years before starting ART (Assisted Reproduction Therapy) for patients treated for testicular cancer or lymphoma. Moreover, FISH analysis could be helpful to choose between ART with post-treatment sperm or cryopreserved sperm.

References

  1. AISNER J., WIERNIK P.H., PEARL P.: Pregnancy outcome in patients treated for Hogkin’s disease. J. Clin. Oncol., 1993, 11: 507–512.

    PubMed  CAS  Google Scholar 

  2. AUGER J., KUNTSMANN J.M., CZYGLIK F., JOUANNET P.: Prévention des risques d’infertilité liés aux traitements antitumoraux dans le cancer du testicule. Andrologie, 2000, 10: 194–202.

    Article  Google Scholar 

  3. BAJNOCZKY K., KHEZRI S., KAJTAR P., SZUCS R., KOSZTOLANYI G., MEHES K.: No chromosomal instability in offspring of survivors of children malignancy. Cancer Genet. Cytogenet., 1999, 109: 79–80.

    Article  PubMed  CAS  Google Scholar 

  4. BOTCHAN A., HAUSER R., YOGEV L. et al.: Sperm quality in Hodgkin’s disease versus non-Hodgkin’s lymphoma. Hum. Reprod., 1997, 12: 73–76.

    Article  PubMed  CAS  Google Scholar 

  5. BRANDRIFF B.F., MEISTRICH M.L., GORDON L.A., CARRANO A.V., LIANG J.C.: Chromosomal damage in sperm of patients surviving Hodgkin’s disease following MOPP therapy with and without radiotherapy. Hum. Genet., 1994, 93: 295–299.

    Article  PubMed  CAS  Google Scholar 

  6. BRUSALOMINO E., LUNGHI F., ORLANDI E. et al.: Treatment of early-stage Hodgkin’s disease with four cycles of ABVD followed by adjuvant radiotherapy: analysis of efficacy and long-term toxicity. Haematologica, 2000, 85: 1032–1039.

    Google Scholar 

  7. BYRNE J., RASMUSSEN S.A., STEINHORN S.C. et al.: Genetic disease in offspring of long-term survivors of childhood and adolescent cancer. Am. J. Hum. Genet., 1998, 62: 45–52.

    Article  PubMed  CAS  Google Scholar 

  8. DAUDIN M., HUYGHE E., CHEVREAU C., SOULIE M., BUJAN L.: Cancer du testicule: BEP et spermatogenèse. Andrologie, 2002, 12: 277–283.

    Article  Google Scholar 

  9. DE MAS P., DAUDIN M., VINCENT M-C. et al.: Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin. Hum. Reprod., 2001, 16: 1204–1208.

    Article  PubMed  Google Scholar 

  10. FITOUSSI O., EGHBALI H., TCHEN N., BERJON J.P., SOUBEYRAN P., HŒRNI B.: Semen analysis and cryoconservation before treatment in Hodgkin’s disease. Ann. Oncol., 2000, 11: 679–684.

    Article  PubMed  CAS  Google Scholar 

  11. GENESCÀ, A., MIRÓ, R., CABALLÍN, M.R., BENET, J., GERMÀ, J.R., EGOSCUE, J.: Sperm chromosome studies in individuals treated for testicular cancer. Hum. Reprod., 1990, 5: 286–290.

    PubMed  Google Scholar 

  12. GENESCÀ A., CABALLÍN M.R., MIRÓ R., BENET J., BONFILL X., EGOSCUE J.: Human sperm chromosomes. Longterm effect of cancer treatment. Cancer Genet. Cytogenet., 1990, 46: 251–260.

    Article  PubMed  Google Scholar 

  13. GUERIN J.F.: Traitement anti-cancéreux et fertilité, protection de la fonction de reproduction. Réf. Gynécol. Obst., 1999, 6: 91–94.

    Google Scholar 

  14. HAINES G.A., HENDRY J.H., DANIEL P., MORRIS I.: Increased levels of comet-detected spermatozoa DNA damage following in vivo isotopic- or X-irradiation of spermatogonia. Mutat. Res., 2001, 495: 21–32.

    PubMed  CAS  Google Scholar 

  15. HARTMANN J.T., ALBRECHT C., SCHMOLL H.J., KUCZYK M.A., KOLLMANNSBERGER C., BOKEMEYER C.: Longterm effects on sexual function and fertility after treatment of testicular cancer. Br. J. Cancer, 1999, 80: 801–807.

    Article  PubMed  CAS  Google Scholar 

  16. JENDERNY J., JACOBI M.L., RÜGER A., RÖHRBORN G.: Chromosome aberrations in 450 sperm complements from eight controls and lack of increase after chemotherapy in two patients. Hum. Genet., 1992, 90: 151–154.

    PubMed  CAS  Google Scholar 

  17. LASS A., AKAGBOSU F., ABUSHEIKHA N. et al.: A programme of semen cryopreservation for patients with malignant disease in a tertiary infertility centre: lessons from 8 years’ experience. Hum. Reprod., 1998, 13: 3256–3261.

    Article  PubMed  CAS  Google Scholar 

  18. MARTIN R.H., RADEMAKER A.W., LEONARD N.J.: Analysis of chromosomal abnormalities in human sperm after chemotherapy by karyotyping and Fluorescence In Situ Hybridization (FISH). Cancer Genet. Cytogenet., 1995, 80: 29–32.

    Article  PubMed  CAS  Google Scholar 

  19. MARTIN R.H., ERNST S., RADEMAKER A., BARCLAY L., KO E., SUMMERS N.: Chromosomal abnormalities in sperm from testicular cancer patients before and after chemotherapy. Hum. Genet., 1997, 99: 214–218.

    Article  PubMed  CAS  Google Scholar 

  20. MARTIN R.H., ERNST S., RADEMAKER A., BARCLAY L., KO E., SUMMERS N.: Analysis of human sperm karyotypes in testicular cancer patients before and after chemotherapy. Cytogenet. Cell Genet., 1997, 78: 120–123.

    PubMed  CAS  Google Scholar 

  21. MARTIN R.H., ERNST S., RADEMAKER A., BARCLAY L., KO E., SUMMERS N.: Analysis of sperm chromosome complements before, during and after chemotherapy. Cancer Genet. Cytogenet., 1999, 108: 133–136.

    Article  PubMed  CAS  Google Scholar 

  22. MEIROW D., SCHENKEN J.C.: Cancer and male infertility. Hum. Reprod., 1995, 10: 2017–2022.

    PubMed  CAS  Google Scholar 

  23. MONTEIL M., ROUSSEAUX S., CHEVRET E., PELLETIER R., COZZI J., SÈLE B.: Increased aneuploid frequency in spermatozoa from a Hodgkin’s disease patient after chemotherapy and radiotherapy. Cytogenet. Cell. Genet., 1997, 76: 134–138.

    Article  PubMed  CAS  Google Scholar 

  24. NAYSMITH T.E., BLAKE D.A., VERNON J.H., JOHNSON N.P.: Do men undergoing sterilizing cancer treatments have a fertile future? Hum. Reprod., 1998, 13: 3250–3255.

    Article  PubMed  CAS  Google Scholar 

  25. ROBBINS W.A., MEISTRICH M.L., MOORE D. et al.: Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm. Nat. Genet., 1997, 16: 74–78.

    Article  PubMed  CAS  Google Scholar 

  26. ROUSSEAUX S., SÈLE B., COZZI J., CHEVRET E.: Immediate rearrangements of human sperm chromosomes following in vivo irradiation. Hum. Reprod, 1993, 8: 903–907.

    PubMed  CAS  Google Scholar 

  27. SENTURIA Y.D., PECKHAM M.J., PECKHAM M.J.: Children fathered by men treated for testicular cancer. Lancet, 1985, 11: 766–769.

    Article  Google Scholar 

  28. SWERDLOW A.J., JACOBS P.A., MARKS A. et al.: Fertility, reproductive outcomes, and health of offspring, of patients treated for Hodgkin’s disease: an investigation including chromosome examination. Br. J. Cancer, 1996, 74: 291–296.

    PubMed  CAS  Google Scholar 

  29. TAL R., BOTCHAN A., HAUSER R., YOGEV L., PAZ, G., YAVETZ H.: Follow-up of sperm concentration and motility in patients with lymphoma. Hum. Reprod., 2000, 15: 1985–1988.

    Article  PubMed  CAS  Google Scholar 

  30. VIVIANI S., SANTORO A., RAGNI G., BONFANTE V., BESTETTI O., BONADONNA G.: Gonadal toxicity after combination chemotherapy for Hodgkin’s disease. Comparative results of MOPP vs ABVD. Eur. J. Cancer Clin. Oncol., 1985, 21: 601–605.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. INSERM U309, Université Joseph Fourier, Grenoble

    Sophie Rousseaux, Christine De Robertis, Roberte Pelletier, Bernard Sele & Sylvianne Hennebicq

  2. Laboratoire de Biologie de la Reproduction et CECOS, Centre Hospitalo-Universitaire de Grenoble, PB 217, 38043, Grenoble Cedex 09, France

    Claire Thomas, Sophie Rousseaux, Bernard Sele & Sylvianne Hennebicq

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  1. Claire Thomas
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  2. Sophie Rousseaux
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Correspondence to Sylvianne Hennebicq.

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Thomas, C., Rousseaux, S., De Robertis, C. et al. Fertilité et aneuploïdies spermatiques après traitement par radiothérapie et/ou chimiothérapie pour cancer du testicule ou lymphome. Androl. 13, 403–411 (2003). https://doi.org/10.1007/BF03035207

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Basic and Clinical Andrology

ISSN: 2051-4190