- Email: [email protected]
Male Infertility
MALE INFERTILITY
755
Robotic Radical Prostatectomy in Patients With Preexisting Inflatable Penile Prosthesis (IPP) J. Rehman, K. Guru, B. Chughtai, R. Shabsigh and D. Samadi Department of Urology, School of Medicine, SUNY–Stony Brook Health Sciences Center, Stony Brook, New York Can J Urol 2008; 15: 4,263– 4,265.
Purpose: We present our initial experience with performing robotic-assisted prostatectomies in men with a 3-piece inflatable penile prosthesis with a pelvic reservoir. Material and Methods: Four patients underwent transperitoneal robotic-assisted radical prostatectomies with a penile prosthetic implant in place. The reservoir was left inflated for easy identification. A flaccid reservoir may be more difficult to identify, and be prone to damage. The reservoir was left attached to the abdominal wall. Dissection was performed outside the fibrous capsule of the reservoir. The tissue around the capsule of the reservoir peeled off without difficulty. Cutting current close to the capsule can be used if needed as per American Medical System with no limit to voltage. The penile prosthesis is then inflated to empty the reservoir creating more prevesical space and preventing the reservoir from obscuring visualization. The remaining portion of the procedure is completed using our standard technique. After completing the urethrovesical anastomosis using the 16 French Foley, the prosthesis is cycled under direct vision and the penile prosthesis is deflated (reservoir full). The prosthesis is not used for 6 weeks to prevent stretching of the urethrovesical anastomosis. Results: All patients (n ⫽ 4) had no reported complications and all prostheses are functioning properly. The margin status was negative postoperatively. Conclusion: Robotic prostatectomy is technically feasible in patients with inflatable penile prostheses by surgeons experienced in robotic surgery. However, the presence of an indwelling penile prosthesis does increase the complexity of surgery. Editorial Comment: This is an interesting surgical nuance for those who perform robotic prostatectomy. The presence of an inflatable penile prosthesis should not preclude the robotic procedure. Allen Seftel, M.D.
Male Infertility Varicocele Repair: Does it Still Have a Role in Infertility Treatment? D. B. French, N. R. Desai and A. Agarwal Reproductive Research Center, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Curr Opin Obstet Gynecol 2008; 20: 269 –274.
Purpose of Review: To review the role of varicocele repair in the treatment of male infertility. Recent Findings: Varicocele is a common finding among men with infertility and its repair has been a mainstay of surgical therapy in these men. Although each year multiple discoveries are made concerning the mechanism of varicocele-induced infertility, the exact pathophysiologic mechanism remains unknown. This study will update significant findings in regard to the pathophysiology of varicocele-induced infertility, such as increased expression of the aquaporin receptor and new findings related to testicular blood flow and vas deferens motility. Recent information concerning the effects of apoptosis and oxidative stress are also reviewed. With regard to the efficacy of varicocele repair, previous meta-analysis of the available data has been misleading due to improper selection criteria. Available clinical data are critically evaluated, with a focus on new meta-analyses that contradict the findings of the Cochrane database review, a study that has been accepted by many as evidence against varicocele repair. Summary: We conclude that varicocele repair not only is an effective treatment for appropriately selected patients but can also be the most cost effective option.
756
MALE INFERTILITY
Editorial Comment: Benjamin Disraeli wrote, “There are three kinds of lies: lies, damned lies and statistics.” The modern version of this quote made popular by Mark Twain must be, “lies, damned lies and meta-analyses.” With the advent of evidence-based medicine meta-analyses have assumed a special place in the medical literary canon. Yet these kinds of reports are not absolute truth, and are subject to the same potential flaws as all studies. Such is the case with the 2004 Cochrane review of varicocele.1 Including subclinical varicoceles, which since the early 1990s have clearly been demonstrated not to warrant varicocelectomy, the 2004 Cochrane review concluded that all varicoceles do not merit treatment. It is as if a meta-analysis on adrenalectomy including small, stable lesions concluded that all adrenal tumors should not be subjected to surgery. French et al do an excellent job of summarizing current concepts in the pathophysiology of varicocele, discrediting the remarkably flawed 2004 Cochrane review, presenting a corrected analysis that demonstrates the usefulness of varicocelectomy and reviewing modern studies that support treatment of varicocele in the right circumstances. Most importantly these authors present their review in a widely read obstetrics and gynecology journal. After all, urologists have generally agreed for decades about the usefulness of varicocelectomy. Our most important audience to educate includes those who serve on the front lines of fertility care. Craig Niederberger, M.D. 1. Evers JL and Collins JA: Surgery or embolisation for varicocele in subfertile men. Cochrane Database Syst Rev 2004; 3: CD000479.
Bilateral but Not Unilateral Testicular Hypotrophy Predicts for Severe Impairment of Semen Quality in Men With Varicocele Undergoing Infertility Evaluation A. K. Wu, T. J. Walsh, S. Phonsombat, M. S. Croughan and P. J. Turek Department of Urology, University of California, San Francisco, School of Medicine, San Francisco, California Urology 2008; 71: 1114 –1118.
Objectives: Varicocele is a common cause of infertility, and varicocele-associated testicular hypotrophy has been described as a potential cause of decreased semen quality. We investigated the relationship between testicular hypotrophy and poor semen quality in infertile men with varicoceles. We hypothesized that bilateral hypotrophy is required before the semen quality is severely impaired. Methods: We retrospectively identified consecutive patients with palpable varicoceles undergoing an infertility evaluation at a single academic center. Each patient was evaluated by the same clinician with history and physical examination. Testicular hypotrophy was defined as a size discrepancy of greater than 3 mL or an absolute size of less than 14 mL. Multivariate logistic regression analysis was used to determine the clinical predictors of total motile sperm count (TMC) of less than 20 million. Results: A total of 245 men with complete data were identified, and 103 men with a TMC of less than 20 million sperm (mean age 36.2 ⫹/⫺ 6.6 years) were compared with 142 men with normal TMCs (mean age 37.1 ⫹/⫺ 6.5 years). On multivariate analysis, men with bilateral hypotrophy were nearly nine times more likely to have a TMC of less than 20 million sperm than were men without hypotrophy (odds ratio 8.8, 95% confidence interval 2.4 to 32.1), and six times more likely than those with unilateral hypotrophy (odds ratio 6.0, 95% confidence interval 1.4 to 26.3). Unilateral hypotrophy alone did not predict for a low TMC. Conclusions: Among men with varicoceles undergoing infertility evaluation, those with bilateral hypotrophy are at the greatest risk of impaired semen quality. Editorial Comment: One source of confusion about the relationship between varicocele and infertility is that many men with varicoceles father children. Thus, it is useful for the urologist to be able to predict whether a man presenting with varicocele is likely to be infertile. Investigators have long observed that men with a unilateral varicocele often are infertile, suggesting a contralateral effect of a unilateral varicocele. Is it worse to have bilateral varicoceles and smaller testes?
MALE INFERTILITY
757
These authors compared semen of men with bilateral varicoceles to those with a unilateral varicocele, and observed that men with bilateral varicoceles and testes 14 ml or smaller as measured by a Prader orchidometer were most likely to have total motility counts less than 20 million per ml. The authors also observed that larger varicoceles are more likely to affect bulk semen parameters adversely. While the question remains open as to whether fixing varicoceles associated with 2 small testes yields small or large results, and whether semen analysis is the perfect assessor of infertility we would prefer it to be, these investigators present compelling data arguing that testis size is a good predictor of subfertility in men with bilateral varicoceles. Craig Niederberger, M.D.
Paternal Age and Adverse Birth Outcomes: Teenager or 40ⴙ, Who is at Risk? X. K. Chen, S. W. Wen, D. Krewski, N. Fleming, Q. Yang and M. C. Walker OMNI Research Group, Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada Hum Reprod 2008; 23: 1290 –1296.
Background: Most previous studies on the effect of paternal age have focused on the association of advanced paternal age with congenital anomalies. The objective of this study was to determine whether paternal age is associated with the risk of adverse birth outcomes, independent of maternal confounders. Methods: We carried out a retrospective cohort study of 2 614 966 live singletons born to married, nulliparous women aged 20 –29 years between 1995 and 2000 in the USA. Multiple logistic regressions were applied to estimate the independent effect of paternal age on adverse birth outcomes. Results: Compared with infants born to fathers aged 20 –29 years, infants fathered by teenagers (⬍20 years old) had an increased risk of preterm birth [odds ratio (OR) ⫽ 1.15, 95% confidence interval (CI): 1.10, 1.20], low birth weight (OR ⫽ 1.13, 95% CI: 1.08, 1.19), small-forgestational-age births (OR ⫽ 1.17, 95% CI: 1.13, 1.22), low Apgar score (OR ⫽ 1.13, 95% CI: 1.01, 1.27), neonatal mortality (OR ⫽ 1.22, 95% CI: 1.01, 1.49) and post-neonatal mortality (OR ⫽ 1.41, 95% CI: 1.09, 1.82). Advanced paternal age (⬎ or ⫽40 years) was not associated with the risk of adverse birth outcomes. Conclusions: Teenage fathers carry an increased risk of adverse birth outcomes that is independent of maternal confounders, whereas advanced paternal age is not an independent risk factor for adverse birth outcomes. Editorial Comment: It is well-known that birth outcomes worsen with increasing maternal age. Women are born with all of their eggs, and those ova are subjected to the toxins of time. But what about paternal age and birth outcomes? We have recently surveyed studies suggesting that sperm DNA integrity degrades as men become older. Might one implication of this change in sperm DNA be an increase in adverse birth outcomes as men age? Chen et al conducted a large retrospective cohort study of more than 2.5 million singleton births to nulliparous married mothers 20 to 29 years old, allowing a focus on paternal age and birth outcomes. Adverse birth outcomes tracked by the study included preterm delivery, low birth weight, low Apgar score, fetal distress, neonatal death and post-neonatal death. After adjusting for possible confounding variables such as paternal ethnicity, maternal age, race, education, tobacco smoking and alcohol consumption during pregnancy, adequacy of prenatal care and infant gender, the investigators observed an increased risk of adverse birth outcomes for teenage but not for older fathers. These findings suggest that the relationship between adverse birth outcomes and paternal age is far more complex than the notion that DNA may degrade as men age. Craig Niederberger, M.D.
758
MALE INFERTILITY
Male Age Negatively Impacts Embryo Development and Reproductive Outcome in Donor Oocyte Assisted Reproductive Technology Cycles J. L. Frattarelli, K. A. Miller, B. T. Miller, K. Elkind-Hirsch and R. T. Scott, Jr. Reproductive Medicine Associates of New Jersey, Morristown, New Jersey Fertil Steril 2008; 90: 97–103.
Objective: To determine whether male age influences embryo development and reproductive potential in assisted reproductive technology cycles. Design: Retrospective cohort analysis. Setting: Private IVF center. Patient(s): One thousand twenty-three male partners participating in anonymous oocyte donation cycles. Intervention(s): Infertile couples undergoing 1,023 anonymous oocyte donation cycles. Main Outcome Measure(s): Live birth rate. Result(s): A significant increase in pregnancy loss, decrease in live birth rate, and decrease in blastocyst formation rate were noted in men ⬎50 years of age. There was no significant difference in implantation rate, pregnancy rate, or early embryo development through the cleavage stage (demonstrated by fertilization rate, embryo cleavage rate, percentage of nonfertilized or polyspermic embryos, rate of embryo arrest, or seven or more cell embryo development on day 3). Men ⬍ or ⫽45 years of age had significantly more semen volume and more motile sperm than men ⬎45 years of age. There was no significant change in sperm morphology or concentration. Conclusion(s): After controlling for female age with use of the donor oocyte model, male age ⬎50 years significantly affected pregnancy outcomes and blastocyst formation rates. Semen volume and total motility decreased with increasing male age. Initial embryo morphology through the cleavage stage was not affected. Editorial Comment: Increasing evidence suggests that as men age, their overall sperm DNA quality declines. However, it is unclear how these laboratory observations affect male reproductive potential. One way to study the effect of male age on sperm is to measure functional aspects such as how the sperm of older men fare in in vitro fertilization. Frattarelli et al studied men from more than 1,000 couples undergoing donor oocyte artificial reproductive techniques, thus minimizing the effect of female factors. The authors observed a statistically significant difference in blastocyst development on day 5 according to male age, with a threshold of greater than 50 years for paternal age. They also noted a significant increase in pregnancy loss rate and a decrease in live birth rates. No significant decrease in implantation or pregnancy rate was observed, although a trend toward lower rates indicated that higher subject numbers may have revealed an effect in these outcomes. Interestingly, men 45 years and younger had greater semen volume and more motile sperm than men older than 45 years, a finding not typically observed in bulk semen parameters in older men. These findings suggest that sperm DNA effects in male aging may exist and manifest as early as the fifth decade, and call for similar studies correlating DNA integrity to functional outcomes such as how sperm do in ova as men age. Craig Niederberger, M.D.
Varicocelectomy for Infertile Couples With Advanced Paternal Age A. Zini, J. Boman, K. Jarvi and A. Baazeem Division of Urology, Department of Surgery, McGill University, Montreal, Quebec, Canada Urology 2008; 72: 109 –113.
Objectives: To evaluate the reproductive outcomes of infertile couples with a clinical varicocele and advanced paternal age. Methods: We reviewed the clinical records of 581 consecutive, non-azoospermic men presenting with a clinical varicocele and infertility. Results: We identified 115 men aged 40 years and older and 466 men younger than 40 years with a clinical varicocele and infertility. The proportion of men with secondary infertility was significantly higher in the group of men aged 40
MALE INFERTILITY
759
years and older compared with the men younger than 40 years (43% [50 of 115] versus 19% [87 of 466], respectively; P ⬍0.001). There were no significant differences in baseline sperm parameters and in spontaneous pregnancy rates after varicocelectomy in couples with advanced paternal age (40 years or older) compared with the younger couples (49% versus 39%, respectively). However, the spontaneous pregnancy rate in couples with advanced paternal age (40 years or older) who underwent varicocelectomy was significantly greater than that of the age-matched control group who did not undergo surgery (49% versus 21%, respectively; P ⬍0.05). Conclusions: The results of this study suggest that paternal age does not adversely influence pregnancy outcome after varicocelectomy. The data support the practice of varicocelectomy for treatment of clinical varicocele and infertility in older men. Editorial Comment: It is well established that testosterone declines as men get older, with bioavailable testosterone declining even more precipitously. We have also surveyed articles in this section during the last 2 years that indicate sperm DNA integrity may decline as men age. However, the nature, degree and severity of the change in DNA is unclear. So a reasonable question to ask is, for a pathological entity such as varicocele, does repair lead to worse outcomes in older men? Excluding subclinical varicoceles, Zini et al compared varicocelectomy outcomes for men younger than 40 years and those 40 years or older, finding that while not statistically significant, the mean increases in sperm concentration, motility and morphology were actually greater in older men, as were the spontaneous and overall pregnancy rates. Interestingly, comparing men 40 years or older who underwent varicocelectomy to those who did not, the spontaneous pregnancy rate was significantly greater for those who had undergone surgery. These results support the value of varicocelectomy even, and especially, in men older than 40 years. Craig Niederberger, M.D.
755
Robotic Radical Prostatectomy in Patients With Preexisting Inflatable Penile Prosthesis (IPP) J. Rehman, K. Guru, B. Chughtai, R. Shabsigh and D. Samadi Department of Urology, School of Medicine, SUNY–Stony Brook Health Sciences Center, Stony Brook, New York Can J Urol 2008; 15: 4,263– 4,265.
Purpose: We present our initial experience with performing robotic-assisted prostatectomies in men with a 3-piece inflatable penile prosthesis with a pelvic reservoir. Material and Methods: Four patients underwent transperitoneal robotic-assisted radical prostatectomies with a penile prosthetic implant in place. The reservoir was left inflated for easy identification. A flaccid reservoir may be more difficult to identify, and be prone to damage. The reservoir was left attached to the abdominal wall. Dissection was performed outside the fibrous capsule of the reservoir. The tissue around the capsule of the reservoir peeled off without difficulty. Cutting current close to the capsule can be used if needed as per American Medical System with no limit to voltage. The penile prosthesis is then inflated to empty the reservoir creating more prevesical space and preventing the reservoir from obscuring visualization. The remaining portion of the procedure is completed using our standard technique. After completing the urethrovesical anastomosis using the 16 French Foley, the prosthesis is cycled under direct vision and the penile prosthesis is deflated (reservoir full). The prosthesis is not used for 6 weeks to prevent stretching of the urethrovesical anastomosis. Results: All patients (n ⫽ 4) had no reported complications and all prostheses are functioning properly. The margin status was negative postoperatively. Conclusion: Robotic prostatectomy is technically feasible in patients with inflatable penile prostheses by surgeons experienced in robotic surgery. However, the presence of an indwelling penile prosthesis does increase the complexity of surgery. Editorial Comment: This is an interesting surgical nuance for those who perform robotic prostatectomy. The presence of an inflatable penile prosthesis should not preclude the robotic procedure. Allen Seftel, M.D.
Male Infertility Varicocele Repair: Does it Still Have a Role in Infertility Treatment? D. B. French, N. R. Desai and A. Agarwal Reproductive Research Center, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Curr Opin Obstet Gynecol 2008; 20: 269 –274.
Purpose of Review: To review the role of varicocele repair in the treatment of male infertility. Recent Findings: Varicocele is a common finding among men with infertility and its repair has been a mainstay of surgical therapy in these men. Although each year multiple discoveries are made concerning the mechanism of varicocele-induced infertility, the exact pathophysiologic mechanism remains unknown. This study will update significant findings in regard to the pathophysiology of varicocele-induced infertility, such as increased expression of the aquaporin receptor and new findings related to testicular blood flow and vas deferens motility. Recent information concerning the effects of apoptosis and oxidative stress are also reviewed. With regard to the efficacy of varicocele repair, previous meta-analysis of the available data has been misleading due to improper selection criteria. Available clinical data are critically evaluated, with a focus on new meta-analyses that contradict the findings of the Cochrane database review, a study that has been accepted by many as evidence against varicocele repair. Summary: We conclude that varicocele repair not only is an effective treatment for appropriately selected patients but can also be the most cost effective option.
756
MALE INFERTILITY
Editorial Comment: Benjamin Disraeli wrote, “There are three kinds of lies: lies, damned lies and statistics.” The modern version of this quote made popular by Mark Twain must be, “lies, damned lies and meta-analyses.” With the advent of evidence-based medicine meta-analyses have assumed a special place in the medical literary canon. Yet these kinds of reports are not absolute truth, and are subject to the same potential flaws as all studies. Such is the case with the 2004 Cochrane review of varicocele.1 Including subclinical varicoceles, which since the early 1990s have clearly been demonstrated not to warrant varicocelectomy, the 2004 Cochrane review concluded that all varicoceles do not merit treatment. It is as if a meta-analysis on adrenalectomy including small, stable lesions concluded that all adrenal tumors should not be subjected to surgery. French et al do an excellent job of summarizing current concepts in the pathophysiology of varicocele, discrediting the remarkably flawed 2004 Cochrane review, presenting a corrected analysis that demonstrates the usefulness of varicocelectomy and reviewing modern studies that support treatment of varicocele in the right circumstances. Most importantly these authors present their review in a widely read obstetrics and gynecology journal. After all, urologists have generally agreed for decades about the usefulness of varicocelectomy. Our most important audience to educate includes those who serve on the front lines of fertility care. Craig Niederberger, M.D. 1. Evers JL and Collins JA: Surgery or embolisation for varicocele in subfertile men. Cochrane Database Syst Rev 2004; 3: CD000479.
Bilateral but Not Unilateral Testicular Hypotrophy Predicts for Severe Impairment of Semen Quality in Men With Varicocele Undergoing Infertility Evaluation A. K. Wu, T. J. Walsh, S. Phonsombat, M. S. Croughan and P. J. Turek Department of Urology, University of California, San Francisco, School of Medicine, San Francisco, California Urology 2008; 71: 1114 –1118.
Objectives: Varicocele is a common cause of infertility, and varicocele-associated testicular hypotrophy has been described as a potential cause of decreased semen quality. We investigated the relationship between testicular hypotrophy and poor semen quality in infertile men with varicoceles. We hypothesized that bilateral hypotrophy is required before the semen quality is severely impaired. Methods: We retrospectively identified consecutive patients with palpable varicoceles undergoing an infertility evaluation at a single academic center. Each patient was evaluated by the same clinician with history and physical examination. Testicular hypotrophy was defined as a size discrepancy of greater than 3 mL or an absolute size of less than 14 mL. Multivariate logistic regression analysis was used to determine the clinical predictors of total motile sperm count (TMC) of less than 20 million. Results: A total of 245 men with complete data were identified, and 103 men with a TMC of less than 20 million sperm (mean age 36.2 ⫹/⫺ 6.6 years) were compared with 142 men with normal TMCs (mean age 37.1 ⫹/⫺ 6.5 years). On multivariate analysis, men with bilateral hypotrophy were nearly nine times more likely to have a TMC of less than 20 million sperm than were men without hypotrophy (odds ratio 8.8, 95% confidence interval 2.4 to 32.1), and six times more likely than those with unilateral hypotrophy (odds ratio 6.0, 95% confidence interval 1.4 to 26.3). Unilateral hypotrophy alone did not predict for a low TMC. Conclusions: Among men with varicoceles undergoing infertility evaluation, those with bilateral hypotrophy are at the greatest risk of impaired semen quality. Editorial Comment: One source of confusion about the relationship between varicocele and infertility is that many men with varicoceles father children. Thus, it is useful for the urologist to be able to predict whether a man presenting with varicocele is likely to be infertile. Investigators have long observed that men with a unilateral varicocele often are infertile, suggesting a contralateral effect of a unilateral varicocele. Is it worse to have bilateral varicoceles and smaller testes?
MALE INFERTILITY
757
These authors compared semen of men with bilateral varicoceles to those with a unilateral varicocele, and observed that men with bilateral varicoceles and testes 14 ml or smaller as measured by a Prader orchidometer were most likely to have total motility counts less than 20 million per ml. The authors also observed that larger varicoceles are more likely to affect bulk semen parameters adversely. While the question remains open as to whether fixing varicoceles associated with 2 small testes yields small or large results, and whether semen analysis is the perfect assessor of infertility we would prefer it to be, these investigators present compelling data arguing that testis size is a good predictor of subfertility in men with bilateral varicoceles. Craig Niederberger, M.D.
Paternal Age and Adverse Birth Outcomes: Teenager or 40ⴙ, Who is at Risk? X. K. Chen, S. W. Wen, D. Krewski, N. Fleming, Q. Yang and M. C. Walker OMNI Research Group, Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada Hum Reprod 2008; 23: 1290 –1296.
Background: Most previous studies on the effect of paternal age have focused on the association of advanced paternal age with congenital anomalies. The objective of this study was to determine whether paternal age is associated with the risk of adverse birth outcomes, independent of maternal confounders. Methods: We carried out a retrospective cohort study of 2 614 966 live singletons born to married, nulliparous women aged 20 –29 years between 1995 and 2000 in the USA. Multiple logistic regressions were applied to estimate the independent effect of paternal age on adverse birth outcomes. Results: Compared with infants born to fathers aged 20 –29 years, infants fathered by teenagers (⬍20 years old) had an increased risk of preterm birth [odds ratio (OR) ⫽ 1.15, 95% confidence interval (CI): 1.10, 1.20], low birth weight (OR ⫽ 1.13, 95% CI: 1.08, 1.19), small-forgestational-age births (OR ⫽ 1.17, 95% CI: 1.13, 1.22), low Apgar score (OR ⫽ 1.13, 95% CI: 1.01, 1.27), neonatal mortality (OR ⫽ 1.22, 95% CI: 1.01, 1.49) and post-neonatal mortality (OR ⫽ 1.41, 95% CI: 1.09, 1.82). Advanced paternal age (⬎ or ⫽40 years) was not associated with the risk of adverse birth outcomes. Conclusions: Teenage fathers carry an increased risk of adverse birth outcomes that is independent of maternal confounders, whereas advanced paternal age is not an independent risk factor for adverse birth outcomes. Editorial Comment: It is well-known that birth outcomes worsen with increasing maternal age. Women are born with all of their eggs, and those ova are subjected to the toxins of time. But what about paternal age and birth outcomes? We have recently surveyed studies suggesting that sperm DNA integrity degrades as men become older. Might one implication of this change in sperm DNA be an increase in adverse birth outcomes as men age? Chen et al conducted a large retrospective cohort study of more than 2.5 million singleton births to nulliparous married mothers 20 to 29 years old, allowing a focus on paternal age and birth outcomes. Adverse birth outcomes tracked by the study included preterm delivery, low birth weight, low Apgar score, fetal distress, neonatal death and post-neonatal death. After adjusting for possible confounding variables such as paternal ethnicity, maternal age, race, education, tobacco smoking and alcohol consumption during pregnancy, adequacy of prenatal care and infant gender, the investigators observed an increased risk of adverse birth outcomes for teenage but not for older fathers. These findings suggest that the relationship between adverse birth outcomes and paternal age is far more complex than the notion that DNA may degrade as men age. Craig Niederberger, M.D.
758
MALE INFERTILITY
Male Age Negatively Impacts Embryo Development and Reproductive Outcome in Donor Oocyte Assisted Reproductive Technology Cycles J. L. Frattarelli, K. A. Miller, B. T. Miller, K. Elkind-Hirsch and R. T. Scott, Jr. Reproductive Medicine Associates of New Jersey, Morristown, New Jersey Fertil Steril 2008; 90: 97–103.
Objective: To determine whether male age influences embryo development and reproductive potential in assisted reproductive technology cycles. Design: Retrospective cohort analysis. Setting: Private IVF center. Patient(s): One thousand twenty-three male partners participating in anonymous oocyte donation cycles. Intervention(s): Infertile couples undergoing 1,023 anonymous oocyte donation cycles. Main Outcome Measure(s): Live birth rate. Result(s): A significant increase in pregnancy loss, decrease in live birth rate, and decrease in blastocyst formation rate were noted in men ⬎50 years of age. There was no significant difference in implantation rate, pregnancy rate, or early embryo development through the cleavage stage (demonstrated by fertilization rate, embryo cleavage rate, percentage of nonfertilized or polyspermic embryos, rate of embryo arrest, or seven or more cell embryo development on day 3). Men ⬍ or ⫽45 years of age had significantly more semen volume and more motile sperm than men ⬎45 years of age. There was no significant change in sperm morphology or concentration. Conclusion(s): After controlling for female age with use of the donor oocyte model, male age ⬎50 years significantly affected pregnancy outcomes and blastocyst formation rates. Semen volume and total motility decreased with increasing male age. Initial embryo morphology through the cleavage stage was not affected. Editorial Comment: Increasing evidence suggests that as men age, their overall sperm DNA quality declines. However, it is unclear how these laboratory observations affect male reproductive potential. One way to study the effect of male age on sperm is to measure functional aspects such as how the sperm of older men fare in in vitro fertilization. Frattarelli et al studied men from more than 1,000 couples undergoing donor oocyte artificial reproductive techniques, thus minimizing the effect of female factors. The authors observed a statistically significant difference in blastocyst development on day 5 according to male age, with a threshold of greater than 50 years for paternal age. They also noted a significant increase in pregnancy loss rate and a decrease in live birth rates. No significant decrease in implantation or pregnancy rate was observed, although a trend toward lower rates indicated that higher subject numbers may have revealed an effect in these outcomes. Interestingly, men 45 years and younger had greater semen volume and more motile sperm than men older than 45 years, a finding not typically observed in bulk semen parameters in older men. These findings suggest that sperm DNA effects in male aging may exist and manifest as early as the fifth decade, and call for similar studies correlating DNA integrity to functional outcomes such as how sperm do in ova as men age. Craig Niederberger, M.D.
Varicocelectomy for Infertile Couples With Advanced Paternal Age A. Zini, J. Boman, K. Jarvi and A. Baazeem Division of Urology, Department of Surgery, McGill University, Montreal, Quebec, Canada Urology 2008; 72: 109 –113.
Objectives: To evaluate the reproductive outcomes of infertile couples with a clinical varicocele and advanced paternal age. Methods: We reviewed the clinical records of 581 consecutive, non-azoospermic men presenting with a clinical varicocele and infertility. Results: We identified 115 men aged 40 years and older and 466 men younger than 40 years with a clinical varicocele and infertility. The proportion of men with secondary infertility was significantly higher in the group of men aged 40
MALE INFERTILITY
759
years and older compared with the men younger than 40 years (43% [50 of 115] versus 19% [87 of 466], respectively; P ⬍0.001). There were no significant differences in baseline sperm parameters and in spontaneous pregnancy rates after varicocelectomy in couples with advanced paternal age (40 years or older) compared with the younger couples (49% versus 39%, respectively). However, the spontaneous pregnancy rate in couples with advanced paternal age (40 years or older) who underwent varicocelectomy was significantly greater than that of the age-matched control group who did not undergo surgery (49% versus 21%, respectively; P ⬍0.05). Conclusions: The results of this study suggest that paternal age does not adversely influence pregnancy outcome after varicocelectomy. The data support the practice of varicocelectomy for treatment of clinical varicocele and infertility in older men. Editorial Comment: It is well established that testosterone declines as men get older, with bioavailable testosterone declining even more precipitously. We have also surveyed articles in this section during the last 2 years that indicate sperm DNA integrity may decline as men age. However, the nature, degree and severity of the change in DNA is unclear. So a reasonable question to ask is, for a pathological entity such as varicocele, does repair lead to worse outcomes in older men? Excluding subclinical varicoceles, Zini et al compared varicocelectomy outcomes for men younger than 40 years and those 40 years or older, finding that while not statistically significant, the mean increases in sperm concentration, motility and morphology were actually greater in older men, as were the spontaneous and overall pregnancy rates. Interestingly, comparing men 40 years or older who underwent varicocelectomy to those who did not, the spontaneous pregnancy rate was significantly greater for those who had undergone surgery. These results support the value of varicocelectomy even, and especially, in men older than 40 years. Craig Niederberger, M.D.