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Re: Alkaline and Neutral Comet Assay Profiles of Sperm DNA Damage in Clinical Groups
MALE INFERTILITY
1873
Re: Seminal Vesicles Ultrasound Features in a Cohort of Infertility Patients F. Lotti, G. Corona, G. M. Colpi, E. Filimberti, S. D. Innocenti, M. Mancini, E. Baldi, I. Noci, G. Forti and M. Maggi Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy Hum Reprod 2012; 27: 974 –982.
Objectives: Previous studies concerning ultrasound evaluation of the seminal vesicles (SV) were performed on a limited series of subjects, and considered few parameters, often only before ejaculation and without assessing the patients’ sexual abstinence. The aim of this study was to evaluate the volume and the emptying characteristics of the SV and their possible correlations with scrotal and transrectal ultrasound features. Methods: The SV of 368 men seeking medical care for couple infertility were evaluated by ultrasound. All patients underwent, during the same ultrasound session, scrotal and transrectal evaluation, before and after ejaculation, and the ejaculate was subjected to semen analysis. A new parameter, SV ejection fraction, calculated as: [(SV volume before ejaculation ⫺ SV volume after ejaculation)/SV volume before ejaculation] ⫻ 100, was evaluated. Results: After adjusting for sexual abstinence and age, both pre-ejaculatory SV volume and SV ejection fraction were positively associated with ejaculate volume. As assessed by receiver operating characteristic curve, a cut-off for SV ejection fraction of 21.6% discriminates subjects with normal ejaculate volume (ⱖ1.5 ml) and pH (ⱖ7.2 ml) with both sensitivity and specificity equal to 75%. Subjects with SV ejection fraction of ⬍21.6% more often had a higher post-ejaculatory SV volume and ejaculatory duct abnormalities. Furthermore, a higher post-ejaculatory SV volume was associated with a higher prostate volume and SV abnormalities. Higher epididymal and deferential diameters were also detected in subjects with a higher post-ejaculatory SV volume or reduced SV ejection fraction. No association between SV and testis ultrasound features or sperm parameters was observed. Associations with SV ejection fraction were confirmed in nested 1:1 case-control analysis. Conclusions: The SV contribute significantly to the ejaculate volume. A new parameter, SV ejection fraction, could be useful in assessing SV emptying. A SV ejection fraction of ⬍21.6% was associated with prostate-vesicular and epididymal ultrasound abnormalities. Editorial Comment: Much has been written about the seminal vesicles. Investigators have painstakingly detailed their size, stuck needles into them and even devised a Whitaker test of sorts. Yet their role in infertility remains stubbornly difficult to precisely define. These authors modeled seminal vesicle volume before and after ejaculation, and developed a functional measure that they call the seminal vesicle ejection fraction. It remains to be seen whether this metric will improve the diagnosis of conditions such as ejaculatory ductal obstruction, although it appears logical and promising. Craig Niederberger, M.D.
Re: Alkaline and Neutral Comet Assay Profiles of Sperm DNA Damage in Clinical Groups J. Ribas-Maynou, A. García-Peiró, C. Abad, M. J. Amengual, J. Navarro and J. Benet Càtedra de Recerca Eugin-UAB, Universitat Autònoma de Barcelona, Bellaterra, Spain Hum Reprod 2012; 27: 652– 658.
Background: The analysis of sperm DNA fragmentation has become a new marker to predict male infertility, and many techniques have been developed. The sperm Comet assay offers the possibility of differentiating single- and double-stranded DNA (ssDNA and dsDNA) breaks, which could have different effects on fertility. The objective of this study was to perform a descriptive characterization of different groups of patients, such as those with asthenoteratozoospermic (ATZ) with or without varicocele, oligoasthenoteratozoospermic (OATZ) or balanced chromosome rearrangements, as compared with fertile donors. The Comet assay was used to investigate sperm samples for ssDNA and
1874
MALE INFERTILITY
dsDNA breaks. Methods and Results: The analysis of alkaline and neutral Comet assays in different groups of patients showed different sperm DNA damage profiles. Most fertile donors presented low values for ssDNA and dsDNA fragmentation (low-equivalent Comet profile), which would be the best prognosis for achieving a pregnancy. OATZ, ATZ and ATZ with varicocele presented high percentages of ssDNA and dsDNA fragmentation (high-equivalent Comet assay profile), ATZ with varicocele being associated with the worst prognosis, due to higher levels of DNA fragmentation. Rearranged chromosome carriers display a very high variability and, interestingly, two different profiles were seen: a high-equivalent Comet assay profile, which could be compatible with a bad prognosis, and a non-equivalent Comet assay profile, which has also been found in three fertile donors. Conclusions: Comet assay profiles, applied to different clinical groups, may be useful for determining prognosis in cases of male infertility. Editorial Comment: These investigators studied sperm DNA fragmentation in various clinical conditions related to male infertility. Of particular interest is that sperm DNA fragmentation in men with varicocele and oligoasthenoteratozoospermia was greater than in men with oligoasthenoteratozoospermia without varicocele. This observation supports the growing body of evidence suggesting that a varicocele exerts ill effects on sperm by vitiating its genetic cargo. Craig Niederberger, M.D.
Re: Semen Analysis in Adolescent Cancer Patients Prior to Bone Marrow Transplantation: When is it Too Late for Fertility Preservation? L. Nahata, L. E. Cohen, L. E. Lehmann and R. N. Yu Division of Endocrinology, Department of Medicine, Children’s Hospital Boston, Boston, Massachusetts Pediatr Blood Cancer 2012; Epub ahead of print.
Background: Sperm banking is an effective method of fertility preservation in adolescent boys with cancer but is strikingly underutilized, partly due to inconsistencies in fertility counseling and unclear guidelines regarding who should bank sperm. Patients undergoing bone marrow transplantation (BMT) are of particular interest given the high risk of infertility in this population. Procedure: We reviewed the charts of male cancer patients who underwent BMT at age ⱖ13 years at the DanaFarber Cancer Institute (DFCI) from 2003 to 2010 to determine the number of fertility preservation attempts prior to initial treatment and/or BMT, and the outcomes of those sperm banking attempts. Results: Sixty-eight male cancer patients who had a BMT at age ⱖ13 years at the DFCI from 2003 to 2010 were included in the analysis. Six patients had attempted sperm banking prior to initial therapy. Thirty-three patients attempted to bank prior to BMT; of those, 39% were azoospermic and 15% were oligospermic. Nineteen patients did not attempt to bank, and in 13 patients the decision to bank was unclear. Conclusions: A more consistent approach to fertility counseling is essential for adolescent cancer patients. Though first line therapy may be low-risk in terms of long-term impact on fertility, our results demonstrate that transient gonadal dysfunction is common and ongoing chemotherapy may affect spermatogenesis. Should a patient undergo BMT during this period, sperm banking is unlikely to be successful; initial fertility risk assessment should account for this possibility. Editorial Comment: We urologists understand the importance of storing sperm for men, including adolescents, undergoing cytotoxic chemotherapy. However, we are few, and many physicians do not take the time for the simple, unobtrusive steps that could make biological fatherhood possible later in life. It is gratifying, then, to see articles such as this in a pediatric oncologic journal arguing for cryopreservation of sperm in adolescents undergoing therapy that will ablate their germ cells. Craig Niederberger, M.D.
1873
Re: Seminal Vesicles Ultrasound Features in a Cohort of Infertility Patients F. Lotti, G. Corona, G. M. Colpi, E. Filimberti, S. D. Innocenti, M. Mancini, E. Baldi, I. Noci, G. Forti and M. Maggi Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy Hum Reprod 2012; 27: 974 –982.
Objectives: Previous studies concerning ultrasound evaluation of the seminal vesicles (SV) were performed on a limited series of subjects, and considered few parameters, often only before ejaculation and without assessing the patients’ sexual abstinence. The aim of this study was to evaluate the volume and the emptying characteristics of the SV and their possible correlations with scrotal and transrectal ultrasound features. Methods: The SV of 368 men seeking medical care for couple infertility were evaluated by ultrasound. All patients underwent, during the same ultrasound session, scrotal and transrectal evaluation, before and after ejaculation, and the ejaculate was subjected to semen analysis. A new parameter, SV ejection fraction, calculated as: [(SV volume before ejaculation ⫺ SV volume after ejaculation)/SV volume before ejaculation] ⫻ 100, was evaluated. Results: After adjusting for sexual abstinence and age, both pre-ejaculatory SV volume and SV ejection fraction were positively associated with ejaculate volume. As assessed by receiver operating characteristic curve, a cut-off for SV ejection fraction of 21.6% discriminates subjects with normal ejaculate volume (ⱖ1.5 ml) and pH (ⱖ7.2 ml) with both sensitivity and specificity equal to 75%. Subjects with SV ejection fraction of ⬍21.6% more often had a higher post-ejaculatory SV volume and ejaculatory duct abnormalities. Furthermore, a higher post-ejaculatory SV volume was associated with a higher prostate volume and SV abnormalities. Higher epididymal and deferential diameters were also detected in subjects with a higher post-ejaculatory SV volume or reduced SV ejection fraction. No association between SV and testis ultrasound features or sperm parameters was observed. Associations with SV ejection fraction were confirmed in nested 1:1 case-control analysis. Conclusions: The SV contribute significantly to the ejaculate volume. A new parameter, SV ejection fraction, could be useful in assessing SV emptying. A SV ejection fraction of ⬍21.6% was associated with prostate-vesicular and epididymal ultrasound abnormalities. Editorial Comment: Much has been written about the seminal vesicles. Investigators have painstakingly detailed their size, stuck needles into them and even devised a Whitaker test of sorts. Yet their role in infertility remains stubbornly difficult to precisely define. These authors modeled seminal vesicle volume before and after ejaculation, and developed a functional measure that they call the seminal vesicle ejection fraction. It remains to be seen whether this metric will improve the diagnosis of conditions such as ejaculatory ductal obstruction, although it appears logical and promising. Craig Niederberger, M.D.
Re: Alkaline and Neutral Comet Assay Profiles of Sperm DNA Damage in Clinical Groups J. Ribas-Maynou, A. García-Peiró, C. Abad, M. J. Amengual, J. Navarro and J. Benet Càtedra de Recerca Eugin-UAB, Universitat Autònoma de Barcelona, Bellaterra, Spain Hum Reprod 2012; 27: 652– 658.
Background: The analysis of sperm DNA fragmentation has become a new marker to predict male infertility, and many techniques have been developed. The sperm Comet assay offers the possibility of differentiating single- and double-stranded DNA (ssDNA and dsDNA) breaks, which could have different effects on fertility. The objective of this study was to perform a descriptive characterization of different groups of patients, such as those with asthenoteratozoospermic (ATZ) with or without varicocele, oligoasthenoteratozoospermic (OATZ) or balanced chromosome rearrangements, as compared with fertile donors. The Comet assay was used to investigate sperm samples for ssDNA and
1874
MALE INFERTILITY
dsDNA breaks. Methods and Results: The analysis of alkaline and neutral Comet assays in different groups of patients showed different sperm DNA damage profiles. Most fertile donors presented low values for ssDNA and dsDNA fragmentation (low-equivalent Comet profile), which would be the best prognosis for achieving a pregnancy. OATZ, ATZ and ATZ with varicocele presented high percentages of ssDNA and dsDNA fragmentation (high-equivalent Comet assay profile), ATZ with varicocele being associated with the worst prognosis, due to higher levels of DNA fragmentation. Rearranged chromosome carriers display a very high variability and, interestingly, two different profiles were seen: a high-equivalent Comet assay profile, which could be compatible with a bad prognosis, and a non-equivalent Comet assay profile, which has also been found in three fertile donors. Conclusions: Comet assay profiles, applied to different clinical groups, may be useful for determining prognosis in cases of male infertility. Editorial Comment: These investigators studied sperm DNA fragmentation in various clinical conditions related to male infertility. Of particular interest is that sperm DNA fragmentation in men with varicocele and oligoasthenoteratozoospermia was greater than in men with oligoasthenoteratozoospermia without varicocele. This observation supports the growing body of evidence suggesting that a varicocele exerts ill effects on sperm by vitiating its genetic cargo. Craig Niederberger, M.D.
Re: Semen Analysis in Adolescent Cancer Patients Prior to Bone Marrow Transplantation: When is it Too Late for Fertility Preservation? L. Nahata, L. E. Cohen, L. E. Lehmann and R. N. Yu Division of Endocrinology, Department of Medicine, Children’s Hospital Boston, Boston, Massachusetts Pediatr Blood Cancer 2012; Epub ahead of print.
Background: Sperm banking is an effective method of fertility preservation in adolescent boys with cancer but is strikingly underutilized, partly due to inconsistencies in fertility counseling and unclear guidelines regarding who should bank sperm. Patients undergoing bone marrow transplantation (BMT) are of particular interest given the high risk of infertility in this population. Procedure: We reviewed the charts of male cancer patients who underwent BMT at age ⱖ13 years at the DanaFarber Cancer Institute (DFCI) from 2003 to 2010 to determine the number of fertility preservation attempts prior to initial treatment and/or BMT, and the outcomes of those sperm banking attempts. Results: Sixty-eight male cancer patients who had a BMT at age ⱖ13 years at the DFCI from 2003 to 2010 were included in the analysis. Six patients had attempted sperm banking prior to initial therapy. Thirty-three patients attempted to bank prior to BMT; of those, 39% were azoospermic and 15% were oligospermic. Nineteen patients did not attempt to bank, and in 13 patients the decision to bank was unclear. Conclusions: A more consistent approach to fertility counseling is essential for adolescent cancer patients. Though first line therapy may be low-risk in terms of long-term impact on fertility, our results demonstrate that transient gonadal dysfunction is common and ongoing chemotherapy may affect spermatogenesis. Should a patient undergo BMT during this period, sperm banking is unlikely to be successful; initial fertility risk assessment should account for this possibility. Editorial Comment: We urologists understand the importance of storing sperm for men, including adolescents, undergoing cytotoxic chemotherapy. However, we are few, and many physicians do not take the time for the simple, unobtrusive steps that could make biological fatherhood possible later in life. It is gratifying, then, to see articles such as this in a pediatric oncologic journal arguing for cryopreservation of sperm in adolescents undergoing therapy that will ablate their germ cells. Craig Niederberger, M.D.