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Use of electroejaculation in the treatment of ejaculatory failure secondary to diabetes mellitus
ADULT
UROLOGY
ELSEVIER
USE OF ELECTROEJACULATION IN THE TREATMENT EJACULATORY FAILURE SECONDARY TO DIABETES MELLITUS NEL
E. GERIG,
RANDALL
B. MEACHAM,
AND
DANA
OF
A. OHL
ABSTRACT
To describe the experience of two male fertility programs using electroejaculation (EEJ) in the management of men with ejaculatory failure secondary to diabetes mellitus. Methods. Twenty-nine EEJ procedures were performed in 7 diabetic men with ejaculatory failure. Results were reviewed with attention paid to sperm characteristics in both antegrade and retrograde specimens as well as pregnancy rates. Results. Retrograde semen specimens retrieved from the bladder following EEJ contained a mean of 3444.5 million sperm (range 269.2 to 4996 million). Antegrade specimens contained a mean of 698.8 million sperm (range 226.8 to 1961 million). Mean sperm motility was 4% for retrograde specimens (range 0% to 11%) and 7% for antegrade specimens (1% to 15%). In all but 1 case, semen specimens were used for intrauterine insemination. The total number of motile sperm contained in the processed, inseminated specimens ranged from 1 to 87.2 million. In 1 case, the sperm obtained through EEJ was used in an in vitro fertilization procedure. Conclusions. EEJ can be successfully used to obtain sperm from men with ejaculatory failure due to diabetes mellitus. The procedure requires general anesthesia, and pregnancy rates after intrauterine insemination with the processed sperm are low. Advanced reproductive technologies may offer a feasible alternative, providing higher success rates with fewer procedures. Copyright 1997 by Elsevier Science Inc. UROLOGY 49: 239-242, 1997. Objectives.
ince its adaptation from use in veterinary medelectroejaculation (EEJ) has been used in the treatment of men rendered anejaculatory by a variety of causes. Although EEJ has been used extensively in men who have spinal cord injury,’ this technique of procuring semen has also been used to manage ejaculatory failure due to a variety of other causes, including retroperitoneal lymphadenectomy performed for testicular cancer,’ and idiopathic anejaculation. EEJ has been used to a limited degree in diabetic men who have developed ejaculatory failure as a consequence of diabetic neuropathy. We describe the experience of two male reproductive medicine clinics using EEJ
S icine,
Urology,
From the Department of Surgery, Division of University of Colorado Health Sciences Center, Denver, Colorado; and Section of Urology, Department of Surgery, University of Michigan, Ann Arbor, Michigan Reprint Requests: Randall B. Meacham, M.D., University of Colorado Health Sciences Center, Division of Urology, 4200 East Ninth Avenue, Box C-319, Denver, CO 80262 Submitted: April 24, 1996, accepted (with revisions): August 15, 1996 COPVRIGHT ALL RIGIITS
1997 BY ELSEVIER RESERVED
SCIENCE
INC.
in the treatment of diabetic men. We also report the first three successful pregnancies established by diabetic men treated with this method. MATERIAL
AND
METHODS
Twenty-nine EEJ procedures were performed on 7 diabetic men. All patients reported absence of ejaculation, and retrograde ejaculation was ruled out in all cases by evaluation of postejaculatory urine specimens. Furthermore, all patients had failed to ejaculate in response to treatment with sympathomimetic agents. Because all patients had intact sensation to pain, general anesthesia was required in every case. After anesthetic induction, patients were placed in either the dorsal lithotomy or lateral decubitus position. After the bladder was catheterized and drained, approximately 40 mL of appropriate sperm washing medium was instilled. EEJ was performed with a standard technique as previously described.’ Anoscopy was performed before and after the procedure to document integrity of the rectal mucosa. After completion of the procedure, the bladder was again catheterized and evacuated. Antegrade and retrograde specimens were processed using either a swimup or Percoll gradient technique. After 28 EEJ procedures, the sperm were used for intrauterine insemination (WI). After one procedure, the sperm were used for in vitro fertilization (IVF) by intracytoplasmic sperm injection (ICSI). EEJ pro0090-4295/97/$17.00 PI1 SOO90-4295(96)00444-X
239
cedures were timed to coincide with the partners’ ovulatory cycles. Except for the cycle in which IVF was undertaken, no ovarian hyperstimulation protocols were used.
RESULTS As detailed in Table I, the antegrade semen specimens achieved through EEJ contained an average total sperm count of 698.8 million (range 226.8 to 1961.0 million). Specimens retrieved from the bladder, ie, resulting from retrograde ejaculation, contained an average of 3444.5 million sperm (range 269.2 to 4996.0 million) (Table II). Mean sperm motility for antegrade specimens was 7% (range 1% to 15%); for retrograde specimens, the mean motility was 4% (range 0% to 11%). After processing, the total sperm count ranged from 6.1 to 379.0 million, with a mean value of 107.9 million. In the processed specimens (Table III), the total number of motile sperm averaged 22.5 million, with a range of 1 to 87.2 million motile sperm. Two patients established pregnancies. One patient’s partner became pregnant after IUI and subsequently achieved a second pregnancy after IVF. In the two pregnancies achieved by IUI, the inseminated specimens contained 41.2 and 1.0 million motile sperm, respectively. After the most recent EEJ procedure, the sperm were used in an IVF procedure, during which 14 ova were treated with ICSI. In this technique, one sperm is injected directly into the cytoplasm of each ovum. Ten of the ova thus treated showed normal fertilization, and three were transferred to the uterus. An ongoing singleton pregnancy resulted. The only significant complication was that of an intraoperative cardiac arrest which occurred in 1 man with a history of syncopal episodes. While he was anesthetized, ventricular tachycardia and ultimately ventricular fibrillation developed, requiring cardiopulmonary resuscitation. He recovered without sequelae; a cardiac electrophysiologic evaluation was necessary to delineate a therapy for his arrhythmogenic tendency. His complication was deemed to be a result of anesthetic-induced myocardial irritability in the setting of a preexisting cardiac neuropathy. COMMENT Diabetes mellitus often causes erectile dysfunction, affecting up to 50% of diabetic men. This is believed to be due primarily to neuropathic changes involving the parasympathetic nervous system. Diabetic men may also experience ejaculatory failure.4 Successful ejaculation requires three sympathetically mediated events. Neuroelectrical transmission by thoracolumbar ganglia that continue as hypogastric nerves and terminate 240
TABLE
1. Antegrade Total Sperm (X 106)
Subject 1 2 3 4 5 6 7 Combined
399.1 1086.2 1961.0 293.9 226.8 280.3 698.5 698.8
mean
specimens Motility WI 4 15 10 7 5 10 1 7
Total Motile Sperm (x 106) 16.0 162.9 196.1 20.6 11.3 28.0 7.0 63.1
Characteristics of antegrade specimens. (Because multiple procedures were performed in all patients, all values represent each patient’s or the combined mean values.)
TABLE
I I.
Retrograde
Total Sperm lx 107
Subiect 1 2 3 4 5 6 7 Combined
4996.0 2895.0 269.2 3840.5 1778.5 4405.5 3500.5 3444.5
mean
specimens
Motility [%I 6 1 11 6 3 10 <1 4
Total Motile Sperm Ix 109 299.8 29.0 29.6 230.4 53.4 440.6 0.1 154.7
Characteristics of retrograde specimens. (Because multiple procedures were performed in all patients, all values represent each patient’s or the combined mean values.)
TABLE
Processed specimens
Total Sperm (X 106)
Subject 1 2 3 4 5 6 7* Combined
I I I.
mean
53.8 7.5 63.6 145.4 100.0 379.0 6.1 107.9
Motility WI 15 18 38 16 12 23 16 20
Total Motile Sperm (x 106) 8.1 1.4 24.2 23.3 12.0 87.2 1.0 22.5
Characteristics of processed specimens. (Because multiple procedures were performed in all patients, all values represent mean values.~ * These data are not available for the second procedure in this patient since the specimen was usedfor intracytoplasmic sperm injection and did not undergo row tine processing.
as preganglionic fibers in the area of the prostate, seminal vesicles, and vasa deferentia results in seminal emission. Simultaneously the bladder neck closes as alpha-adrenergic receptors are stimulated. Antegrade ejaculation involves coordinated muscle contraction (of the ischiocavernosus, bulUROLOGY
49 (21, 1997
bocavernosus, and pelvic floor musculature), mediated by sacral parasympathetic and somatic efferent nervous activity.4*5 In some diabetic men, impairment of the sympathetic system results in disorders of ejaculation, typically retrograde ejaculation. 6,7 More extensive neuropathy may render such men incapable of seminal emission.8 Sympathomimetic agents may be useful in the treatment of retrograde ejaculation, acting to stimulate contraction of the bladder neck, prostate, seminal vesicles, and vasa deferentia.5,9 Imipramine, a tricyclic antidepressant that blocks norepinephrine reuptake at nerve terminals, is believed to potentiate peripheral adrenergic activity and may be the best agent to treat retrograde ejaculation in diabetic patients.5’10 Other alpha-adrenergic sympathomimetic medications, such as pseudoephedrine, ephedrine, or phenylpropanolamine, can enhance antegrade ejaculation by the same mechanism.5s8’10 Alpha-adrenergic stimulants have been reported to cause retrograde ejaculation in men with ejaculatory failure who were previously aspermic.5 Transrectal electrostimulation provides pulsed electrical stimuli to the sympathetic postganglionic fibers in the region of the prostate, seminal vesicles, and vasa deferentia.8 Seminal emission will result in the majority of patients who undergo this procedure. Although pulsatile antegrade ejaculation occasionally occurs, a weak ejaculation typically is the result, requiring manual milking of the bulbous urethra. Retrograde ejaculation is even more common, requiring preparation of the bladder before the procedure with a buffered solution and subsequent retrieval of sperm.8,11 Retrograde ejaculation was prevalent in the population of patients we report. The average number of motile sperm obtained from the antegrade specimens was 62.8 million, as compared with 154.7 million obtained from the retrograde specimens. It is noteworthy that only three pregnancies were achieved after 29 EEJ procedures. The couple that achieved pregnancy twice used very advanced reproductive technologies to achieve the second pregnancy. If that pregnancy is not considered in the calculation, only 2 pregnancies occurred in 28 procedures (7.1% pregnancy rate). Such low pregnancy rates raise the question of the basic fertility potential of diabetic men. Even when ejaculation can be achieved through pharmacologic means or electrical stimulation, semen quality may be impaired in such men. Variations in semen quality have been reported in diabetic men who are able to ejaculate, but the variations were not necessarily associated with a compromise in fertility.12~13 Murray et al. reported the pituitary-testicular axis in diabetic men with intact ejaculatory function to be comparable to UROLOGY
49 (21, 1997
that of healthy controls.14 However, diabetic men may have decreased serum testosterone due to impaired Leydig cell function.15 Insulin apparently crosses the blood-testis barrier, but its levels in seminal plasma have not been shown to correlate with semen parameters.16 Abnormal spermatic forms have been associated with increased levels of certain amino acids in the ejaculate of human diabetic men,l’ but overall the etiology of altered spermiogenesis in diabetic men remains poorly elucidated. When advanced reproductive technologies are used in a population in which fertility factors may be genetically mediated, transmission of these disorders must be considered. The risk of insulindependent diabetes mellitus (IDDM) is increased in the offspring of a parent with IDDM, as evidenced by aggregation within families. However, the mechanism remains elusive and there is a low prevalence of direct vertical transmission, generally 5% to 10%.18 The genetic transmission of diabetes mellitus may be permissive rather than causal and does not appear to represent a contraindication to assisted reproduction, although counseling of patients with regard to this risk should be undertaken. After 28 of 29 EEJs in this series, the partners of the patients were treated using IUI. Unfortunately, with IUI, pregnancy rates were low. As with other causes of severe male factor infertility, however, the use of more advanced reproductive technologies such as IVF should offer greater hope for successful conception.‘9-22 The use of ICSI, a procedure in which sperm are inserted directly into ova, appears especially promising in cases of severe male factor infertility.20-22 A typical example of this is the couple in the present series who achieved an ongoing pregnancy using EEJ combined with IVF. During this procedure, four embryos were cryopreserved. These embryos can be used for future embryo transfer, which may result in an additional pregnancy without the need for an additional EEJ procedure. Because most diabetic men have relatively intact pain sensation, general anesthesia is typically required for each performance of EEJ. In view of the expense and potential risk associated with general anesthesia, the combination of EEJ with advanced reproductive technologies will likely assume a more prominent role in the management of this population of patients. CONCLUSIONS EEJ has become an accepted form of therapy for the treatment of men who experience ejaculatory failure secondary to lesions such as spinal cord injury and surgical interruption of retroperitoneal 241
nerve structures. Unfortunately, the management of men who are anejaculatory secondary to diabetes has not met with similar success. We now report the first three pregnancies achieved among the partners of men in this population. These results should provide hope for men with this condition, as well as incentive for further research in the management of this challenging group of patients. REFERENCES 1. Oh1 DA: Electroejaculation. Urol Clin North Am 20: 181- 188, 1993. 2. Bennett C, Robinson M, and Oh1 DA: Electroejaculation: new therapy for neurogenic infertility. Contemp Urol2: 25-28, 1990. 3. Bennett CJ, and Oh1 DA: Electroejaculation after retroperitoneal lymph node dissection. Adv Urol 2: 85-96, 1989. 4. Stewart DE, and Oh1 DA: Idiopathic anejaculation treated by electroejaculation. Intl J Psychiatry Med 19: 263268, 1989. 5. Corson SL, Lipshultz LI, McConnell J, and Benson GS: Current concepts of the mechanisms of ejaculation: normal and abnormal states. J Reprod Med 26: 499-507, 1981. 6. Greene LF, and Kelalis PP: Retrograde ejaculation of semen due to diabetic neuropathy. J Urol 98: 693-696, 1967. 7. Hosking DJ, Bennet T, and Hampton JR: Diabetic autonomic neuropathy. Diabetes 27: 1043-1051, 1978. 8. Murphy JB, and Lipshultz LI: Abnormalities of ejaculation. Urol Clin North Am 14: 583-596, 1987. 9. Narayan P, Lange PH, and Fraley EE: Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J Urol 127: 685-688, 1982. 10. Thomas AJ: Ejaculatory dysfunction. Fertil Steril 39: 445-454, 1983. 11. Bennett CJ, Seager SW, Vasher EA, and McGuire EJ: Sexual dysfunction and electroejaculation in men with spinal cord injury: review. J Urol 139: 453-457, 1988.
242
12. Fairburn CG, McCulloch DK, and Wu FC: The effects of diabetes on male sexual function. Clin Endocrinol Metab 11: 749-765, 1982. 13. Vignon F, LeFaou A, Montagnon D, Pradignac A, Cranz C, Winisdzewsky P, and Pinget M: Comparative study of semen in diabetic and healthy men. Diabetes Metab 17: 350-354,1991. 14. Murray FT, Cameron DF, Vogel RB, Thomas RG, Wyss HU, and Zauner CW: The pituitary-testicular axis at rest and during moderate exercise in males with diabetes mellitus and normal sexual function. J Androl 9: 197-206, 1988. 15. Dinulovic D, and Radonjic G: Diabetes mellitus/male infertility. Arch Androl 25: 277-293, 1990. 16. Garcia-Diez LC, Corrales Hernandez JJ, HernandezDiaz J, Pedraz JM, and Miralles JM: Semen characteristics and diabetes mellitus: significance of insulin in male infertility. Arch Andro126: 1199127, 1991. 17. Kaemmerer H, and Mitzkat HJ: Ion-exchange chromatography of amino acids in ejaculates of diabetics. Andrologia 17: 485-487, 1985. 18. Foster DW: Diabetes mellitus, in Wilson JD (Ed): Harrison’s Principles of Internal Medicine, 12th ed. New York, McGraw-Hill, 1991, pp 1740-1741. 19. Ayers JWT, Moinipanah R, Bennett CJ, Randolph JF, and Peterson EP: Successful combination therapy with electroejaculation and in vitro fertilization-embryo transfer in the treatment of a paraplegic male with severe oligoasthenospermia. Fertil Steri149: 1089-1090, 1988. 20. Sherins RJ, Thorsell LP, Dorfmann A, Dennison-Lagos L, Calvo LP, Krysa L, Coulam CB, and Schulman JD: Intracytoplasmic sperm injection facilitates fertilization even in the most severe forms of male infertility: pregnancy outcome correlates with maternal age and number of eggs available. Fertil Steril 64: 369-375, 1995. 21. Schlegel PN, Palermo GD, Alikani M, Adler A, Reing AM, Cohen J, and Rosenwales Z: Micropuncture retrieval of epididymal sperm with in vitro fertilization: importance of in vitro micromanipulation techniques. Urology 46: 238-241, 1995. 22. Payne D, Flaherty SP, Jeffrey R, Warnes GM, and Matthews CD: Successful treatment of severe male factor infertility in 100 consecutive cycles using intracytoplasmic sperm injection. Hum Reprod 9: 2051-2057, 1994.
UROLOGY
49 (21, 1997
UROLOGY
ELSEVIER
USE OF ELECTROEJACULATION IN THE TREATMENT EJACULATORY FAILURE SECONDARY TO DIABETES MELLITUS NEL
E. GERIG,
RANDALL
B. MEACHAM,
AND
DANA
OF
A. OHL
ABSTRACT
To describe the experience of two male fertility programs using electroejaculation (EEJ) in the management of men with ejaculatory failure secondary to diabetes mellitus. Methods. Twenty-nine EEJ procedures were performed in 7 diabetic men with ejaculatory failure. Results were reviewed with attention paid to sperm characteristics in both antegrade and retrograde specimens as well as pregnancy rates. Results. Retrograde semen specimens retrieved from the bladder following EEJ contained a mean of 3444.5 million sperm (range 269.2 to 4996 million). Antegrade specimens contained a mean of 698.8 million sperm (range 226.8 to 1961 million). Mean sperm motility was 4% for retrograde specimens (range 0% to 11%) and 7% for antegrade specimens (1% to 15%). In all but 1 case, semen specimens were used for intrauterine insemination. The total number of motile sperm contained in the processed, inseminated specimens ranged from 1 to 87.2 million. In 1 case, the sperm obtained through EEJ was used in an in vitro fertilization procedure. Conclusions. EEJ can be successfully used to obtain sperm from men with ejaculatory failure due to diabetes mellitus. The procedure requires general anesthesia, and pregnancy rates after intrauterine insemination with the processed sperm are low. Advanced reproductive technologies may offer a feasible alternative, providing higher success rates with fewer procedures. Copyright 1997 by Elsevier Science Inc. UROLOGY 49: 239-242, 1997. Objectives.
ince its adaptation from use in veterinary medelectroejaculation (EEJ) has been used in the treatment of men rendered anejaculatory by a variety of causes. Although EEJ has been used extensively in men who have spinal cord injury,’ this technique of procuring semen has also been used to manage ejaculatory failure due to a variety of other causes, including retroperitoneal lymphadenectomy performed for testicular cancer,’ and idiopathic anejaculation. EEJ has been used to a limited degree in diabetic men who have developed ejaculatory failure as a consequence of diabetic neuropathy. We describe the experience of two male reproductive medicine clinics using EEJ
S icine,
Urology,
From the Department of Surgery, Division of University of Colorado Health Sciences Center, Denver, Colorado; and Section of Urology, Department of Surgery, University of Michigan, Ann Arbor, Michigan Reprint Requests: Randall B. Meacham, M.D., University of Colorado Health Sciences Center, Division of Urology, 4200 East Ninth Avenue, Box C-319, Denver, CO 80262 Submitted: April 24, 1996, accepted (with revisions): August 15, 1996 COPVRIGHT ALL RIGIITS
1997 BY ELSEVIER RESERVED
SCIENCE
INC.
in the treatment of diabetic men. We also report the first three successful pregnancies established by diabetic men treated with this method. MATERIAL
AND
METHODS
Twenty-nine EEJ procedures were performed on 7 diabetic men. All patients reported absence of ejaculation, and retrograde ejaculation was ruled out in all cases by evaluation of postejaculatory urine specimens. Furthermore, all patients had failed to ejaculate in response to treatment with sympathomimetic agents. Because all patients had intact sensation to pain, general anesthesia was required in every case. After anesthetic induction, patients were placed in either the dorsal lithotomy or lateral decubitus position. After the bladder was catheterized and drained, approximately 40 mL of appropriate sperm washing medium was instilled. EEJ was performed with a standard technique as previously described.’ Anoscopy was performed before and after the procedure to document integrity of the rectal mucosa. After completion of the procedure, the bladder was again catheterized and evacuated. Antegrade and retrograde specimens were processed using either a swimup or Percoll gradient technique. After 28 EEJ procedures, the sperm were used for intrauterine insemination (WI). After one procedure, the sperm were used for in vitro fertilization (IVF) by intracytoplasmic sperm injection (ICSI). EEJ pro0090-4295/97/$17.00 PI1 SOO90-4295(96)00444-X
239
cedures were timed to coincide with the partners’ ovulatory cycles. Except for the cycle in which IVF was undertaken, no ovarian hyperstimulation protocols were used.
RESULTS As detailed in Table I, the antegrade semen specimens achieved through EEJ contained an average total sperm count of 698.8 million (range 226.8 to 1961.0 million). Specimens retrieved from the bladder, ie, resulting from retrograde ejaculation, contained an average of 3444.5 million sperm (range 269.2 to 4996.0 million) (Table II). Mean sperm motility for antegrade specimens was 7% (range 1% to 15%); for retrograde specimens, the mean motility was 4% (range 0% to 11%). After processing, the total sperm count ranged from 6.1 to 379.0 million, with a mean value of 107.9 million. In the processed specimens (Table III), the total number of motile sperm averaged 22.5 million, with a range of 1 to 87.2 million motile sperm. Two patients established pregnancies. One patient’s partner became pregnant after IUI and subsequently achieved a second pregnancy after IVF. In the two pregnancies achieved by IUI, the inseminated specimens contained 41.2 and 1.0 million motile sperm, respectively. After the most recent EEJ procedure, the sperm were used in an IVF procedure, during which 14 ova were treated with ICSI. In this technique, one sperm is injected directly into the cytoplasm of each ovum. Ten of the ova thus treated showed normal fertilization, and three were transferred to the uterus. An ongoing singleton pregnancy resulted. The only significant complication was that of an intraoperative cardiac arrest which occurred in 1 man with a history of syncopal episodes. While he was anesthetized, ventricular tachycardia and ultimately ventricular fibrillation developed, requiring cardiopulmonary resuscitation. He recovered without sequelae; a cardiac electrophysiologic evaluation was necessary to delineate a therapy for his arrhythmogenic tendency. His complication was deemed to be a result of anesthetic-induced myocardial irritability in the setting of a preexisting cardiac neuropathy. COMMENT Diabetes mellitus often causes erectile dysfunction, affecting up to 50% of diabetic men. This is believed to be due primarily to neuropathic changes involving the parasympathetic nervous system. Diabetic men may also experience ejaculatory failure.4 Successful ejaculation requires three sympathetically mediated events. Neuroelectrical transmission by thoracolumbar ganglia that continue as hypogastric nerves and terminate 240
TABLE
1. Antegrade Total Sperm (X 106)
Subject 1 2 3 4 5 6 7 Combined
399.1 1086.2 1961.0 293.9 226.8 280.3 698.5 698.8
mean
specimens Motility WI 4 15 10 7 5 10 1 7
Total Motile Sperm (x 106) 16.0 162.9 196.1 20.6 11.3 28.0 7.0 63.1
Characteristics of antegrade specimens. (Because multiple procedures were performed in all patients, all values represent each patient’s or the combined mean values.)
TABLE
I I.
Retrograde
Total Sperm lx 107
Subiect 1 2 3 4 5 6 7 Combined
4996.0 2895.0 269.2 3840.5 1778.5 4405.5 3500.5 3444.5
mean
specimens
Motility [%I 6 1 11 6 3 10 <1 4
Total Motile Sperm Ix 109 299.8 29.0 29.6 230.4 53.4 440.6 0.1 154.7
Characteristics of retrograde specimens. (Because multiple procedures were performed in all patients, all values represent each patient’s or the combined mean values.)
TABLE
Processed specimens
Total Sperm (X 106)
Subject 1 2 3 4 5 6 7* Combined
I I I.
mean
53.8 7.5 63.6 145.4 100.0 379.0 6.1 107.9
Motility WI 15 18 38 16 12 23 16 20
Total Motile Sperm (x 106) 8.1 1.4 24.2 23.3 12.0 87.2 1.0 22.5
Characteristics of processed specimens. (Because multiple procedures were performed in all patients, all values represent mean values.~ * These data are not available for the second procedure in this patient since the specimen was usedfor intracytoplasmic sperm injection and did not undergo row tine processing.
as preganglionic fibers in the area of the prostate, seminal vesicles, and vasa deferentia results in seminal emission. Simultaneously the bladder neck closes as alpha-adrenergic receptors are stimulated. Antegrade ejaculation involves coordinated muscle contraction (of the ischiocavernosus, bulUROLOGY
49 (21, 1997
bocavernosus, and pelvic floor musculature), mediated by sacral parasympathetic and somatic efferent nervous activity.4*5 In some diabetic men, impairment of the sympathetic system results in disorders of ejaculation, typically retrograde ejaculation. 6,7 More extensive neuropathy may render such men incapable of seminal emission.8 Sympathomimetic agents may be useful in the treatment of retrograde ejaculation, acting to stimulate contraction of the bladder neck, prostate, seminal vesicles, and vasa deferentia.5,9 Imipramine, a tricyclic antidepressant that blocks norepinephrine reuptake at nerve terminals, is believed to potentiate peripheral adrenergic activity and may be the best agent to treat retrograde ejaculation in diabetic patients.5’10 Other alpha-adrenergic sympathomimetic medications, such as pseudoephedrine, ephedrine, or phenylpropanolamine, can enhance antegrade ejaculation by the same mechanism.5s8’10 Alpha-adrenergic stimulants have been reported to cause retrograde ejaculation in men with ejaculatory failure who were previously aspermic.5 Transrectal electrostimulation provides pulsed electrical stimuli to the sympathetic postganglionic fibers in the region of the prostate, seminal vesicles, and vasa deferentia.8 Seminal emission will result in the majority of patients who undergo this procedure. Although pulsatile antegrade ejaculation occasionally occurs, a weak ejaculation typically is the result, requiring manual milking of the bulbous urethra. Retrograde ejaculation is even more common, requiring preparation of the bladder before the procedure with a buffered solution and subsequent retrieval of sperm.8,11 Retrograde ejaculation was prevalent in the population of patients we report. The average number of motile sperm obtained from the antegrade specimens was 62.8 million, as compared with 154.7 million obtained from the retrograde specimens. It is noteworthy that only three pregnancies were achieved after 29 EEJ procedures. The couple that achieved pregnancy twice used very advanced reproductive technologies to achieve the second pregnancy. If that pregnancy is not considered in the calculation, only 2 pregnancies occurred in 28 procedures (7.1% pregnancy rate). Such low pregnancy rates raise the question of the basic fertility potential of diabetic men. Even when ejaculation can be achieved through pharmacologic means or electrical stimulation, semen quality may be impaired in such men. Variations in semen quality have been reported in diabetic men who are able to ejaculate, but the variations were not necessarily associated with a compromise in fertility.12~13 Murray et al. reported the pituitary-testicular axis in diabetic men with intact ejaculatory function to be comparable to UROLOGY
49 (21, 1997
that of healthy controls.14 However, diabetic men may have decreased serum testosterone due to impaired Leydig cell function.15 Insulin apparently crosses the blood-testis barrier, but its levels in seminal plasma have not been shown to correlate with semen parameters.16 Abnormal spermatic forms have been associated with increased levels of certain amino acids in the ejaculate of human diabetic men,l’ but overall the etiology of altered spermiogenesis in diabetic men remains poorly elucidated. When advanced reproductive technologies are used in a population in which fertility factors may be genetically mediated, transmission of these disorders must be considered. The risk of insulindependent diabetes mellitus (IDDM) is increased in the offspring of a parent with IDDM, as evidenced by aggregation within families. However, the mechanism remains elusive and there is a low prevalence of direct vertical transmission, generally 5% to 10%.18 The genetic transmission of diabetes mellitus may be permissive rather than causal and does not appear to represent a contraindication to assisted reproduction, although counseling of patients with regard to this risk should be undertaken. After 28 of 29 EEJs in this series, the partners of the patients were treated using IUI. Unfortunately, with IUI, pregnancy rates were low. As with other causes of severe male factor infertility, however, the use of more advanced reproductive technologies such as IVF should offer greater hope for successful conception.‘9-22 The use of ICSI, a procedure in which sperm are inserted directly into ova, appears especially promising in cases of severe male factor infertility.20-22 A typical example of this is the couple in the present series who achieved an ongoing pregnancy using EEJ combined with IVF. During this procedure, four embryos were cryopreserved. These embryos can be used for future embryo transfer, which may result in an additional pregnancy without the need for an additional EEJ procedure. Because most diabetic men have relatively intact pain sensation, general anesthesia is typically required for each performance of EEJ. In view of the expense and potential risk associated with general anesthesia, the combination of EEJ with advanced reproductive technologies will likely assume a more prominent role in the management of this population of patients. CONCLUSIONS EEJ has become an accepted form of therapy for the treatment of men who experience ejaculatory failure secondary to lesions such as spinal cord injury and surgical interruption of retroperitoneal 241
nerve structures. Unfortunately, the management of men who are anejaculatory secondary to diabetes has not met with similar success. We now report the first three pregnancies achieved among the partners of men in this population. These results should provide hope for men with this condition, as well as incentive for further research in the management of this challenging group of patients. REFERENCES 1. Oh1 DA: Electroejaculation. Urol Clin North Am 20: 181- 188, 1993. 2. Bennett C, Robinson M, and Oh1 DA: Electroejaculation: new therapy for neurogenic infertility. Contemp Urol2: 25-28, 1990. 3. Bennett CJ, and Oh1 DA: Electroejaculation after retroperitoneal lymph node dissection. Adv Urol 2: 85-96, 1989. 4. Stewart DE, and Oh1 DA: Idiopathic anejaculation treated by electroejaculation. Intl J Psychiatry Med 19: 263268, 1989. 5. Corson SL, Lipshultz LI, McConnell J, and Benson GS: Current concepts of the mechanisms of ejaculation: normal and abnormal states. J Reprod Med 26: 499-507, 1981. 6. Greene LF, and Kelalis PP: Retrograde ejaculation of semen due to diabetic neuropathy. J Urol 98: 693-696, 1967. 7. Hosking DJ, Bennet T, and Hampton JR: Diabetic autonomic neuropathy. Diabetes 27: 1043-1051, 1978. 8. Murphy JB, and Lipshultz LI: Abnormalities of ejaculation. Urol Clin North Am 14: 583-596, 1987. 9. Narayan P, Lange PH, and Fraley EE: Ejaculation and fertility after extended retroperitoneal lymph node dissection for testicular cancer. J Urol 127: 685-688, 1982. 10. Thomas AJ: Ejaculatory dysfunction. Fertil Steril 39: 445-454, 1983. 11. Bennett CJ, Seager SW, Vasher EA, and McGuire EJ: Sexual dysfunction and electroejaculation in men with spinal cord injury: review. J Urol 139: 453-457, 1988.
242
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