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Re: Soy Protein Isolates of Varying Isoflavone Content do Not Adversely Affect Semen Quality in Healthy Young Men
1840
MALE INFERTILITY
Healthy Overweight Male Partners of Subfertile Couples Should Not Worry About Their Semen Quality F. H. Duits, M. van Wely, F. van der Veen and J. Gianotten Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands Fertil Steril 2010; 94: 1356 –1359.
Objective: To study the effect of body mass index (BMI) on semen quality in a cohort of male partners in subfertile couples. Design: Prospective cohort study. Setting: A fertility center based in an academic hospital. Patient(s): Between January 2000 and January 2007, 1466 men visiting the Centre for Reproductive Medicine as part of a subfertile couple. Intervention(s): None. Main Outcome Measure(s): Semen volume (in mL), semen concentration (in millions per mL), percentage of motile spermatozoa, percentage of spermatozoa with normal forms, total sperm count (in millions), and total motile sperm count (in millions). Result(s): After exclusion of men without data on BMI, the data of 1401 men could be analyzed. The group of men with a BMI lower than 20 kg/m2, with a BMI between 25 and 30 kg/m2, and with a BMI⬎30 kg/m2 had a lower semen volume compared with the group with a BMI between 20 and 25 kg/m2. Other semen parameters were not statistically significantly different. Multivariable analysis (generalized linear model), correcting for confounders, showed no statistically significant association between BMI and semen parameters, including semen volume. Conclusion(s): Semen quality was not statistically significantly affected by BMI in a cohort of male partners in subfertile couples. Editorial Comment: A number of studies have appeared in this section demonstrating relationships between increasing body mass and worsening parameters of male reproductive potential. In this provocatively titled publication the authors seem to state that obesity in men of subfertile couples is not related to the semen analysis. However, a look at the numerical results of the study implies otherwise. For example mean total sperm count was 174.3 million in men with a BMI of 20.1 to 25 kg/m2, 153.0 million at a BMI of 25.1 to 30 kg/m2 and 135.6 million at BMI greater than 30 kg/m2. Those numbers sure look like they are decreasing. The authors fell into the old trap of assuming that because they could not prove a difference with type I hypothesis testing, the numbers are the same. That is wrong. In the statistical paradigm used only interrogating the data with type II hypothesis testing investigates similarity. In other words, just because a difference was not seen with a large number of subjects (more than 1,400), it does not mean one was not there. With data as variable as semen parameters even more subjects may be required to prove that the parameters are worsening with increasing body mass. Craig Niederberger, M.D.
Re: Soy Protein Isolates of Varying Isoflavone Content do Not Adversely Affect Semen Quality in Healthy Young Men L. K. Beaton, B. L. McVeigh, B. L. Dillingham, J. W. Lampe and A. M. Duncan Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada Fertil Steril 2010; 94: 1717–1722.
Objective: To determine the effects of consumption of soy protein of varying isoflavone content on parameters of semen quality in healthy young men. Design: Randomized crossover intervention. Setting: University campus. Patient(s): Healthy adult men (age 27.5 ⫾ 5.67 years, body mass index 25.4 ⫾ 3.14 kg/m2). Intervention(s): Milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 ⫾ 0.19 mg isoflavones/day, expressed as aglycone equivalents), and high-isoflavone soy protein isolate (high-iso SPI; 61.7 ⫾ 7.35 mg isoflavones/day, expressed as aglycone equivalents) for 57 days each separated by 28-day washout periods. Main outcome Measure(s): Urinary isoflavones were measured from 24-hour urine samples collected on days 54 –56 of each treatment period. Semen
MALE INFERTILITY
1841
quality parameters (semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, sperm morphology) were measured from semen samples collected on days 1 and 57 of each treatment period. Result(s): Urinary isoflavones were significantly higher after consumption of high-iso SPI compared with the low-iso SPI and MPI. Semen parameters, including semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, and sperm morphology, were not significantly affected by consumption of either low- or high-iso SPI compared with MPI. Conclusion(s): Consumption of soy protein of low or high isoflavone content does not adversely affect semen quality in a sample of healthy adult men. Editorial Comment: Soy isoflavones are under investigation for prevention and treatment of prostate cancer. If these compounds have an estrogenic effect, it is worth asking if they alter male fertility. These authors compared semen changes during an approximate 2-month interval for subjects ingesting low and high isoflavone soy protein isolate. Commendably they included a control, MPI, and their observations are a nice example of how regression to the mean works when studying the highly variable parameters of semen analysis. However, their statistical analysis appears to be searching for differences at a probability threshold of 0.05 rather than attempting to prove similarity. So when I see that sperm motility in the controls increased from 57.3% to 60.5% during the study interval, but decreased from 62.1% to 55.1% in the group ingesting the low isoflavone supplement and decreased from 63.5% to 55.3% in the group ingesting the high isoflavone supplement, I have to wonder if a larger number of subjects would reveal a statistically significant decrease. As a result, this article does not argue persuasively that isoflavones are safe for sperm. Craig Niederberger, M.D.
Protamine Contents and P1/P2 Ratio in Human Spermatozoa From Smokers and Non-Smokers M. E. Hammadeh, M. F. Hamad, M. Montenarh and C. Fischer-Hammadeh Department of Obstetrics and Gynaecology, IVF and Andrology Laboratory, University of Saarland, Homburg/Saar, Germany Hum Reprod 2010; 25: 2708 –2720.
Background: Protamine content is necessary for proper sperm chromatin condensation and subsequent male fertility. The exact effect of smoking on male fertility remains controversial. The objective of this study was to evaluate the effect of smoking on protamine content of sperm in smoker and non-smoker patients. Methods: Protamines 1 (P1) and 2 (P2) were quantified by gel electrophoresis in the sperm of 53 smokers and 63 non-smokers. Sperm DNA fragmentation was analyzed employing the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay and non-condensed chromatin was evaluated using chromomycin A(3) (CMA(3)). Levels of smoking and oxidative stress markers were determined in seminal plasma using an enzyme linked immunosorbant assay (ELISA) and chemical reactions. Results: Protamine 2 concentrations were significantly lower (P ⬍ 0.050) in smokers than in non-smokers. In contrast P1/P2 ratios were significantly higher (P ⬍ 0.010) in smokers (1.34 ⫾ 0.46 ng/10(6) sperm) than in non-smokers (1.11 ⫾ 0.20 ng/10(6) sperm). The oxidative stress and smoking markers, reactive oxygen species (ROS), malondialdehyde, 8-Hydroxyguanosine (8-OHdG) and cotinine were significantly higher (P ⬍ 0.010) in smokers than in non-smokers, and correlated significantly (P ⬍ 0.050) with P1/P2 ratios. P2 showed significant negative (P ⬍ 0.050) correlations with ROS, 8-OHdG and cotinine. CMA(3) and TUNEL were also significantly higher (P ⬍ 0.010) in smokers (36.4 ⫾ 8.1 and 17.4 ⫾ 5.3%) than in non-smokers (29.8 ⫾ 7.1 and 11.3 ⫾ 4.2%). Conclusions: This is the first study to evaluate the effect of smoking on protamines. Abnormal elevation of the P1/P2 ratio appears to be associated with aberrant P2 expression in smokers. These results suggest that induced oxidative stress by cigarette smoking may have significant inverse effect on the protamination process by disrupting P2.
MALE INFERTILITY
Healthy Overweight Male Partners of Subfertile Couples Should Not Worry About Their Semen Quality F. H. Duits, M. van Wely, F. van der Veen and J. Gianotten Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands Fertil Steril 2010; 94: 1356 –1359.
Objective: To study the effect of body mass index (BMI) on semen quality in a cohort of male partners in subfertile couples. Design: Prospective cohort study. Setting: A fertility center based in an academic hospital. Patient(s): Between January 2000 and January 2007, 1466 men visiting the Centre for Reproductive Medicine as part of a subfertile couple. Intervention(s): None. Main Outcome Measure(s): Semen volume (in mL), semen concentration (in millions per mL), percentage of motile spermatozoa, percentage of spermatozoa with normal forms, total sperm count (in millions), and total motile sperm count (in millions). Result(s): After exclusion of men without data on BMI, the data of 1401 men could be analyzed. The group of men with a BMI lower than 20 kg/m2, with a BMI between 25 and 30 kg/m2, and with a BMI⬎30 kg/m2 had a lower semen volume compared with the group with a BMI between 20 and 25 kg/m2. Other semen parameters were not statistically significantly different. Multivariable analysis (generalized linear model), correcting for confounders, showed no statistically significant association between BMI and semen parameters, including semen volume. Conclusion(s): Semen quality was not statistically significantly affected by BMI in a cohort of male partners in subfertile couples. Editorial Comment: A number of studies have appeared in this section demonstrating relationships between increasing body mass and worsening parameters of male reproductive potential. In this provocatively titled publication the authors seem to state that obesity in men of subfertile couples is not related to the semen analysis. However, a look at the numerical results of the study implies otherwise. For example mean total sperm count was 174.3 million in men with a BMI of 20.1 to 25 kg/m2, 153.0 million at a BMI of 25.1 to 30 kg/m2 and 135.6 million at BMI greater than 30 kg/m2. Those numbers sure look like they are decreasing. The authors fell into the old trap of assuming that because they could not prove a difference with type I hypothesis testing, the numbers are the same. That is wrong. In the statistical paradigm used only interrogating the data with type II hypothesis testing investigates similarity. In other words, just because a difference was not seen with a large number of subjects (more than 1,400), it does not mean one was not there. With data as variable as semen parameters even more subjects may be required to prove that the parameters are worsening with increasing body mass. Craig Niederberger, M.D.
Re: Soy Protein Isolates of Varying Isoflavone Content do Not Adversely Affect Semen Quality in Healthy Young Men L. K. Beaton, B. L. McVeigh, B. L. Dillingham, J. W. Lampe and A. M. Duncan Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada Fertil Steril 2010; 94: 1717–1722.
Objective: To determine the effects of consumption of soy protein of varying isoflavone content on parameters of semen quality in healthy young men. Design: Randomized crossover intervention. Setting: University campus. Patient(s): Healthy adult men (age 27.5 ⫾ 5.67 years, body mass index 25.4 ⫾ 3.14 kg/m2). Intervention(s): Milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 ⫾ 0.19 mg isoflavones/day, expressed as aglycone equivalents), and high-isoflavone soy protein isolate (high-iso SPI; 61.7 ⫾ 7.35 mg isoflavones/day, expressed as aglycone equivalents) for 57 days each separated by 28-day washout periods. Main outcome Measure(s): Urinary isoflavones were measured from 24-hour urine samples collected on days 54 –56 of each treatment period. Semen
MALE INFERTILITY
1841
quality parameters (semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, sperm morphology) were measured from semen samples collected on days 1 and 57 of each treatment period. Result(s): Urinary isoflavones were significantly higher after consumption of high-iso SPI compared with the low-iso SPI and MPI. Semen parameters, including semen volume, sperm concentration, sperm count, sperm percent motility, total motile sperm count, and sperm morphology, were not significantly affected by consumption of either low- or high-iso SPI compared with MPI. Conclusion(s): Consumption of soy protein of low or high isoflavone content does not adversely affect semen quality in a sample of healthy adult men. Editorial Comment: Soy isoflavones are under investigation for prevention and treatment of prostate cancer. If these compounds have an estrogenic effect, it is worth asking if they alter male fertility. These authors compared semen changes during an approximate 2-month interval for subjects ingesting low and high isoflavone soy protein isolate. Commendably they included a control, MPI, and their observations are a nice example of how regression to the mean works when studying the highly variable parameters of semen analysis. However, their statistical analysis appears to be searching for differences at a probability threshold of 0.05 rather than attempting to prove similarity. So when I see that sperm motility in the controls increased from 57.3% to 60.5% during the study interval, but decreased from 62.1% to 55.1% in the group ingesting the low isoflavone supplement and decreased from 63.5% to 55.3% in the group ingesting the high isoflavone supplement, I have to wonder if a larger number of subjects would reveal a statistically significant decrease. As a result, this article does not argue persuasively that isoflavones are safe for sperm. Craig Niederberger, M.D.
Protamine Contents and P1/P2 Ratio in Human Spermatozoa From Smokers and Non-Smokers M. E. Hammadeh, M. F. Hamad, M. Montenarh and C. Fischer-Hammadeh Department of Obstetrics and Gynaecology, IVF and Andrology Laboratory, University of Saarland, Homburg/Saar, Germany Hum Reprod 2010; 25: 2708 –2720.
Background: Protamine content is necessary for proper sperm chromatin condensation and subsequent male fertility. The exact effect of smoking on male fertility remains controversial. The objective of this study was to evaluate the effect of smoking on protamine content of sperm in smoker and non-smoker patients. Methods: Protamines 1 (P1) and 2 (P2) were quantified by gel electrophoresis in the sperm of 53 smokers and 63 non-smokers. Sperm DNA fragmentation was analyzed employing the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) assay and non-condensed chromatin was evaluated using chromomycin A(3) (CMA(3)). Levels of smoking and oxidative stress markers were determined in seminal plasma using an enzyme linked immunosorbant assay (ELISA) and chemical reactions. Results: Protamine 2 concentrations were significantly lower (P ⬍ 0.050) in smokers than in non-smokers. In contrast P1/P2 ratios were significantly higher (P ⬍ 0.010) in smokers (1.34 ⫾ 0.46 ng/10(6) sperm) than in non-smokers (1.11 ⫾ 0.20 ng/10(6) sperm). The oxidative stress and smoking markers, reactive oxygen species (ROS), malondialdehyde, 8-Hydroxyguanosine (8-OHdG) and cotinine were significantly higher (P ⬍ 0.010) in smokers than in non-smokers, and correlated significantly (P ⬍ 0.050) with P1/P2 ratios. P2 showed significant negative (P ⬍ 0.050) correlations with ROS, 8-OHdG and cotinine. CMA(3) and TUNEL were also significantly higher (P ⬍ 0.010) in smokers (36.4 ⫾ 8.1 and 17.4 ⫾ 5.3%) than in non-smokers (29.8 ⫾ 7.1 and 11.3 ⫾ 4.2%). Conclusions: This is the first study to evaluate the effect of smoking on protamines. Abnormal elevation of the P1/P2 ratio appears to be associated with aberrant P2 expression in smokers. These results suggest that induced oxidative stress by cigarette smoking may have significant inverse effect on the protamination process by disrupting P2.