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the question of whether elderly men with compensated hypogonadism might benefit from early testosterone replacement. Future research with randomized clinical trials would be required to address this specific issue. Tomas L. Griebling, MD, MPH
Suggested Reading Makhsida N, Shah J, Yan G et al: Hypogonadism and metabolic syndrome: implications for testosterone therapy. J Urol 2005; 174: 827. Jarow JP, Troiani J, McNellis D et al: Use of biomarkers to assess tissue specific androgen adequacy: defining male hypogonadism. J Urol 2013; 189: 633.
Male Infertility Re: Cancer Risk among Children Born after Assisted Conception C. L. Williams, K. J. Bunch, C. A. Stiller, M. F. Murphy, B. J. Botting, W. H. Wallace, M. Davies and A. G. Sutcliffe Institute of Child Health, University College London and Reproductive Medicine Unit, University College London Hospitals, London, Childhood Cancer Research Group, Department of Paediatrics, University of Oxford, Oxford, and Paediatric Oncology Department, Royal Hospital for Sick Children, University of Edinburgh, Edinburgh, United Kingdom N Engl J Med 2013; 369: 1819e1827.
Abstract available at http://jurology.com/ Editorial Comment: Since the introduction of in vitro fertilization, investigators and clinicians have rightly questioned whether the offspring of this artificial reproductive technology were at increased risk for disease compared to their naturally conceived peers. The risk of cancer has been an area particularly scrutinized. These researchers linked 2 large databases, 1 containing data on all children born in Britain between 1992 and 2008 with assisted conception and without the use of a sperm donor and 1 with data from the United Kingdom National Registry of Childhood Tumours, with an analysis to identify children younger than 15 years old in whom cancer developed. Fortunately they did not observe an increased overall risk of cancer in the children conceived by artificial reproductive technology. There remains some question about hepatoblastoma and rhabdomyosarcoma but the numbers are small enough that a relationship cannot be absolutely confirmed. While molecular events derived from artificial reproductive technology leading to cancers in later life cannot be excluded by this study, these results give some solace to those concerned about oncogenesis and its relationship to in vitro fertilization. Craig Niederberger, MD
Re: Testicular Cell Transplantation into the Human Testes K. Faes, H. Tournaye, L. Goethals, T. Lahoutte, A. Hoorens and E. Goossens Biology of the Testis, Research Laboratory for Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium Fertil Steril 2013; 100: 981e988.
Abstract available at http://jurology.com/ Editorial Comment: If a prepubertal boy requires cytotoxic chemotherapy, currently such lifesaving care often renders fatherhood in later life impossible. Researchers have been investigating ways in which spermatogonial stem cells (SSCs) could be transplanted into the testis, and if feasible in humans, SSCs removed from a boy before chemotherapy could be transplanted back into the testis later, making future fatherhood possible. Such transplantation was shown to be successful in animal
1846
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models, and these investigators take the technique a step further by injecting mouse testicular cells into human cadaveric testes and demonstrating cellular uptake in the seminiferous tubules. We are getting closer to a time when SSC transplantation may preserve fertility even in prepubescent boys undergoing cytotoxic chemotherapy. Craig Niederberger, MD
Re: Impact of Chemotherapy and Radiotherapy for Testicular Germ Cell Tumors on Spermatogenesis and Sperm DNA: A Multicenter Prospective Study from the CECOS Network L. Bujan, M. Walschaerts, N. Moinard, S. Hennebicq, J. Saias, F. Brugnon, J. Auger, I. Berthaut, E. Szerman, M. Daudin and N. Rives de ration Franc¸ aise des Centre d’Etude Fe et de Conservation des Œufs et du Sperme Humains (CECOS), Paris, France Fertil Steril 2013; 100: 673e680.
Abstract available at http://jurology.com/ Editorial Comment: Impaired spermatogenesis as a result of cytotoxic chemotherapy and radiotherapy for testis cancer viewed through the lens of declining bulk seminal parameters is well documented. Results of studies assessing sperm DNA quality after these treatments are mixed, likely indicating that we really do not understand the clinical implications of these laboratory assays that we are currently using to assess sperm DNA integrity. These authors report results of a prospective study tracking bulk seminal parameters and sperm DNA metrics after chemotherapy and radiotherapy for testicular germ cell tumors, observing that radiotherapy or more than 2 bleomycin, etoposide and cisplatin cycles suppressed bulk seminal parameters for at least 1 year. DNA integrity test results were less clear, and we likely will have to await more sophisticated assays that account for local DNA effects before we know the full story regarding the consequences on male reproduction of chemotherapy and radiotherapy for testis cancer. Craig Niederberger, MD
Re: Increased Risk of Cancer among Azoospermic Men M. L. Eisenberg, P. Betts, D. Herder, D. J. Lamb and L. I. Lipshultz Departments of Urology and Obstetrics/Gynecology, Stanford University School of Medicine, Stanford, California Fertil Steril 2013; 100: 681e685.
Abstract available at http://jurology.com/ Editorial Comment: In a large database of more than 22,000 men evaluated for infertility during a 30-year period Walsh et al noted an increased incidence of high grade prostate cancer.1 In the current study Eisenberg et al report findings of an investigation derived from a large state cancer registry relating tumors of any sort to the presence of male infertility. These researchers found that cancer was correlated with male infertility, with nearly all of the association due to whether the infertile man had azoospermia. These findings argue that cancer and azoospermia may derive from a common cause, with perhaps both due to the same dysregulation of genetic events. Craig Niederberger, MD 1. Walsh TJ, Schembri M, Turek PJ et al: Increased risk of high-grade prostate cancer among infertile men. Cancer 2010; 116: 2140.
MALE INFERTILITY
1847
Re: A Novel Cell-Processing Method ‘AgarCytos’ in Conjunction with OCT3/4 and PLAP to Detect Intratubular Germ Cell Neoplasia in Non-Obstructive Azoospermia Using Remnants of Testicular Sperm Extraction Specimens M. Hessel, L. Ramos, A. F. Hulsbergen, K. W. D’Hauwers, D. D. Braat and C. A. Hulsbergen-van de Kaa Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Hum Reprod 2013; 28: 2608e2620.
Abstract available at http://jurology.com/ Editorial Comment: It is common practice to send a biopsy of testis tissue for pathological evaluation when testicular extraction of sperm is performed as a means of assessing the histopathology of spermatogenic dysfunction as well as investigating whether neoplasia is present. These investigators describe a novel method of assessing testis tissue used in extracting sperm to detect the presence of intratubular germ cell neoplasia. Since a larger sampling size for detecting neoplasia would increase its accuracy, this innovative method if validated would provide valuable information without sacrificing additional testis tissue. Craig Niederberger, MD
1845
the question of whether elderly men with compensated hypogonadism might benefit from early testosterone replacement. Future research with randomized clinical trials would be required to address this specific issue. Tomas L. Griebling, MD, MPH
Suggested Reading Makhsida N, Shah J, Yan G et al: Hypogonadism and metabolic syndrome: implications for testosterone therapy. J Urol 2005; 174: 827. Jarow JP, Troiani J, McNellis D et al: Use of biomarkers to assess tissue specific androgen adequacy: defining male hypogonadism. J Urol 2013; 189: 633.
Male Infertility Re: Cancer Risk among Children Born after Assisted Conception C. L. Williams, K. J. Bunch, C. A. Stiller, M. F. Murphy, B. J. Botting, W. H. Wallace, M. Davies and A. G. Sutcliffe Institute of Child Health, University College London and Reproductive Medicine Unit, University College London Hospitals, London, Childhood Cancer Research Group, Department of Paediatrics, University of Oxford, Oxford, and Paediatric Oncology Department, Royal Hospital for Sick Children, University of Edinburgh, Edinburgh, United Kingdom N Engl J Med 2013; 369: 1819e1827.
Abstract available at http://jurology.com/ Editorial Comment: Since the introduction of in vitro fertilization, investigators and clinicians have rightly questioned whether the offspring of this artificial reproductive technology were at increased risk for disease compared to their naturally conceived peers. The risk of cancer has been an area particularly scrutinized. These researchers linked 2 large databases, 1 containing data on all children born in Britain between 1992 and 2008 with assisted conception and without the use of a sperm donor and 1 with data from the United Kingdom National Registry of Childhood Tumours, with an analysis to identify children younger than 15 years old in whom cancer developed. Fortunately they did not observe an increased overall risk of cancer in the children conceived by artificial reproductive technology. There remains some question about hepatoblastoma and rhabdomyosarcoma but the numbers are small enough that a relationship cannot be absolutely confirmed. While molecular events derived from artificial reproductive technology leading to cancers in later life cannot be excluded by this study, these results give some solace to those concerned about oncogenesis and its relationship to in vitro fertilization. Craig Niederberger, MD
Re: Testicular Cell Transplantation into the Human Testes K. Faes, H. Tournaye, L. Goethals, T. Lahoutte, A. Hoorens and E. Goossens Biology of the Testis, Research Laboratory for Embryology and Genetics, Vrije Universiteit Brussel, Brussels, Belgium Fertil Steril 2013; 100: 981e988.
Abstract available at http://jurology.com/ Editorial Comment: If a prepubertal boy requires cytotoxic chemotherapy, currently such lifesaving care often renders fatherhood in later life impossible. Researchers have been investigating ways in which spermatogonial stem cells (SSCs) could be transplanted into the testis, and if feasible in humans, SSCs removed from a boy before chemotherapy could be transplanted back into the testis later, making future fatherhood possible. Such transplantation was shown to be successful in animal
1846
MALE INFERTILITY
models, and these investigators take the technique a step further by injecting mouse testicular cells into human cadaveric testes and demonstrating cellular uptake in the seminiferous tubules. We are getting closer to a time when SSC transplantation may preserve fertility even in prepubescent boys undergoing cytotoxic chemotherapy. Craig Niederberger, MD
Re: Impact of Chemotherapy and Radiotherapy for Testicular Germ Cell Tumors on Spermatogenesis and Sperm DNA: A Multicenter Prospective Study from the CECOS Network L. Bujan, M. Walschaerts, N. Moinard, S. Hennebicq, J. Saias, F. Brugnon, J. Auger, I. Berthaut, E. Szerman, M. Daudin and N. Rives de ration Franc¸ aise des Centre d’Etude Fe et de Conservation des Œufs et du Sperme Humains (CECOS), Paris, France Fertil Steril 2013; 100: 673e680.
Abstract available at http://jurology.com/ Editorial Comment: Impaired spermatogenesis as a result of cytotoxic chemotherapy and radiotherapy for testis cancer viewed through the lens of declining bulk seminal parameters is well documented. Results of studies assessing sperm DNA quality after these treatments are mixed, likely indicating that we really do not understand the clinical implications of these laboratory assays that we are currently using to assess sperm DNA integrity. These authors report results of a prospective study tracking bulk seminal parameters and sperm DNA metrics after chemotherapy and radiotherapy for testicular germ cell tumors, observing that radiotherapy or more than 2 bleomycin, etoposide and cisplatin cycles suppressed bulk seminal parameters for at least 1 year. DNA integrity test results were less clear, and we likely will have to await more sophisticated assays that account for local DNA effects before we know the full story regarding the consequences on male reproduction of chemotherapy and radiotherapy for testis cancer. Craig Niederberger, MD
Re: Increased Risk of Cancer among Azoospermic Men M. L. Eisenberg, P. Betts, D. Herder, D. J. Lamb and L. I. Lipshultz Departments of Urology and Obstetrics/Gynecology, Stanford University School of Medicine, Stanford, California Fertil Steril 2013; 100: 681e685.
Abstract available at http://jurology.com/ Editorial Comment: In a large database of more than 22,000 men evaluated for infertility during a 30-year period Walsh et al noted an increased incidence of high grade prostate cancer.1 In the current study Eisenberg et al report findings of an investigation derived from a large state cancer registry relating tumors of any sort to the presence of male infertility. These researchers found that cancer was correlated with male infertility, with nearly all of the association due to whether the infertile man had azoospermia. These findings argue that cancer and azoospermia may derive from a common cause, with perhaps both due to the same dysregulation of genetic events. Craig Niederberger, MD 1. Walsh TJ, Schembri M, Turek PJ et al: Increased risk of high-grade prostate cancer among infertile men. Cancer 2010; 116: 2140.
MALE INFERTILITY
1847
Re: A Novel Cell-Processing Method ‘AgarCytos’ in Conjunction with OCT3/4 and PLAP to Detect Intratubular Germ Cell Neoplasia in Non-Obstructive Azoospermia Using Remnants of Testicular Sperm Extraction Specimens M. Hessel, L. Ramos, A. F. Hulsbergen, K. W. D’Hauwers, D. D. Braat and C. A. Hulsbergen-van de Kaa Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Hum Reprod 2013; 28: 2608e2620.
Abstract available at http://jurology.com/ Editorial Comment: It is common practice to send a biopsy of testis tissue for pathological evaluation when testicular extraction of sperm is performed as a means of assessing the histopathology of spermatogenic dysfunction as well as investigating whether neoplasia is present. These investigators describe a novel method of assessing testis tissue used in extracting sperm to detect the presence of intratubular germ cell neoplasia. Since a larger sampling size for detecting neoplasia would increase its accuracy, this innovative method if validated would provide valuable information without sacrificing additional testis tissue. Craig Niederberger, MD
