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Electroejaculation combined with intracytoplasmic sperm injection in patients with psychogenic anejaculation yields comparable results to patients with spinal cord injuries
Electroejaculation combined with intracytoplasmic sperm injection in patients with psychogenic anejaculation yields comparable results to patients with spinal cord injuries Itai Gat, M.D.,a Ettie Maman, M.D.,a Gil Yerushalmi, M.D., Ph.D.,a Micha Baum, M.D.,a Jehoshua Dor, M.D.,a Gil Raviv, M.D.,b Igal Madjar, M.D.,b and Ariel Hourvitz, M.D.a a
In Vitro Fertilization Unit and b Andrology Unit, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel
Objective: To evaluate sperm quality and fertility potential of men with psychogenic anejaculation treated by electroejaculation (EEJ) and intracytoplasmic sperm injection (ICSI). Treatment results were compared to spinal cord injured (SCI) patients treated similarly. Design: Retrospective clinical study. Setting: Academic tertiary referral fertility center. Patient(s): Couples with isolated psychogenic anejaculation or SCI. Intervention(s): Electroejaculation and ICSI. Main Outcome Measure(s): Semen analysis, fertilization rate, implantation rate, pregnancy rate, delivery rate and safety of the procedure. Result(s): Fifteen patients diagnosed with psychogenic anejaculation underwent 40 EEJ/ICSI cycles. The semen retrieved was characterized by low motility (mean 10.7% 12.3%), normal volume (2.2 1.9 mL) and normal count (25.1 29.9 106/mL), according to World Health Organization criteria. Results of EEJ/ICSI were compared with 22 SCI patients treated by 66 EEJ/ICSI cycles during the same period. Mean female age and the number of oocytes retrieved per cycle were similar between the groups. Similar semen parameters after EEJ were found between psychogenic and SCI patients. Fertilization rate was significantly lower in the psychogenic patients compared to SCI (47.0% and 57.0%, respectively). No significant differences were found regarding pregnancy rates (20% and 22.7%, respectively), implantation rate (10.2% and 11.6%, respectively) or delivery rates (15% and 18.2%, respectively). Conclusion(s): Sperm retrieved by EEJ is characterized by asthenospermia and normal count. In spite of the lower fertilization rate in psychogenic patients, combination of EEJ and ICSI gives adequate results to couples with psychogenic anejaculation similar to the results obtained for SCI patients. Current results give these couples a reasonable chance of pregnancy achievement. (Fertil SterilÒ 2012;97:1056–60. Ó2012 by American Society for Reproductive Medicine.) Key Words: Electroejaculation, psychogenic anejaculation, spinal cord injury, intracytoplasmic sperm injection
T
he process of ejaculation includes well-coordinated contractions of striated and nonstriated muscular contractions that ejaculate the sperm and seminal fluid through the urethra. The neurologic involvement relies
mostly on the sympathetic system as well as efferent and afferent pathways—dorsal nerves of the penis, internal pudendal nerve, anterolateral columns of the spinal cord, sympathetic chain ganglia and hypogastric plexus
Received September 11, 2011; revised January 30, 2012; accepted January 31, 2012; published online February 24, 2012. I.G. has nothing to disclose. E.M. has nothing to disclose. G.Y. has nothing to disclose. M.B. has nothing to disclose. J.D. has nothing to disclose. G.R. has nothing to disclose. I.M. has nothing to disclose. A.H. has nothing to disclose. Reprint requests: Itai Gat, M.D., Tel Hashomer, Ramat Gan, 52621 Israel (E-mail: itaigatmd@gmail. com). Fertility and Sterility® Vol. 97, No. 5, May 2012 0015-0282/$36.00 Copyright ©2012 American Society for Reproductive Medicine, Published by Elsevier Inc. doi:10.1016/j.fertnstert.2012.01.129 1056
anterior to the aorta (1). Neurologic impairment may be followed by ejaculatory dysfunction in different etiologies, such as spinal cord injury (SCI), retroperitoneal lymph node dissection, diabetes, multiple sclerosis, drugs and psychogenic anejaculation (2–5). Anejaculation, as well as delayed ejaculation and inhibited ejaculation, are the least common, least studied and least understood male sexual dysfunctions. Their prevalence is unclear for various reasons such as lack of differentiation between delayed ejaculation and anejaculation in VOL. 97 NO. 5 / MAY 2012
Fertility and Sterility® epidemiological studies (6). Although anejaculation accounts for only 2% of male factor infertility (7), in specific populations such as men with SCI it is the major cause for infertility (5). A significant progression in the treatment of anejaculated men was achieved by the method of electroejaculation (EEJ). During EEJ, a rectal probe transmits electrical stimulation to the short postsynaptic sympathetic fibers in the wall of the ejaculatory organs (1), leading to ejaculation and sperm procurement in 70%–90% of attempts (2, 4, 8, 9). Therefore, in a relatively simple, safe, and inexpensive method the barrier of semen achievement can be overcome (1). Semen collected by EEJ can be used in variety of fertilization methods (1, 3, 8–10). Ohl et al. (5) conducted 653 IUI cycles achieving an 8.7% pregnancy rate per IUI cycle. The relatively low pregnancy rate was attributed to the poor quality of the electroejaculates (2). The electroejaculates demonstrated polyspermia, asthenospermia and teratospermia with decreased ability of cervical mucus penetration and impaired fertilizing capacity (1, 4, 5, 8, 11). Because of the low sperm quality in these patients, combined EEJ, IVF, and intracytoplasmic sperm injection (ICSI) became optional procedures to improve pregnancy and delivery rates. Heruti et al. (8) demonstrated pregnancy rate of 26.4% and delivery rate of 20.5% after 68 EEJ/ICSI cycles in 20 couples suffering from SCI anejaculation. Most of the research on anejaculation was conducted mainly in SCI patients, a prominent etiology for anejaculation (5). One of the less investigated populations is the psychogenic anejaculatory patients. These patients are otherwise healthy and may have erections and nocturnal emission but cannot ejaculate even by masturbation (12, 13). The diagnosis of psychogenic anejaculation is made after iatrogenic and pathophysiological etiologies are excluded (6, 14). Studies conducted on patients with psychogenic anejaculation revealed similar asthenospermia as SCI patients (12). Additional research using EEJ combined with ICSI for couples with male factor infertility due to psychogenic anejaculation demonstrated prominent lack of uniformity with diverse results regarding fertilization, pregnancy and delivery rates (13, 15). Sample sizes were relatively low and no comparison was made between psychogenic anejaculation and other anejaculatory populations. In addition, some of the published series on patients with anejaculation were conducted on diverse male impairments (2–5) or included comparisons to male patients who had the ability to ejaculate and suffered from other infertility impairment (15). Therefore, the aim of the current study was to investigate results of EEJ and ICSI for psychogenic anejaculation and to compare them with other homogeneous group of EEJ/ICSI treated population, the SCI patients.
MATERIALS AND METHODS Patients In this retrospective study we enrolled all couples treated by EEJ and ICSI for isolated male psychogenic anejaculation in our units between 2000 and 2010. All male patients underwent complete evaluation including patient history, physical VOL. 97 NO. 5 / MAY 2012
examination, hormonal profile and ultrasound examination as needed. Diagnosis of psychogenic anejaculation was made after exclusion of organic causes for anejaculation in addition to sexual relationship without ejaculations and orgasm in the presence of nocturnal emissions. Female patients underwent detailed investigation including patient history, physical examination, hormonal profile, ultrasound, and, if needed, hysterosalpingogram. Couples with female factor in addition to male infertility were excluded. Indications for ICSI included recurrent failure in IUI treatments or low ejaculate quality such as total motility <10 106/ml. The research was approved by the Institutional Review Board.
Hormonal Stimulation and Electroejaculation Ovarian stimulation for IVF included accepted IVF protocols. Long agonist, antagonist protocol and short agonist protocol of controlled ovarian hyperstimulation were performed as described elsewhere (16, 17). In both groups, hCG was administered when more than two follicles reached 18 mm, followed by oocyte collection 36 hours later. Oocyte retrieval, fertilization, embryo culture and transfer were carried out as previously described (18). Most of the patients in the study group were Orthodox Jews and manual stimulation of a vibrator is absolutely forbidden for religious reasons. Therefore vibratory stimulation had not been performed in our cohort and EEJ is our firstline of treatment for anejaculation. The EEJ procedures were performed 36–38 hours after hCG injection followed by oocytes retrievals. Before EEJ all patients gave their informed consent with comprehensive understanding of the procedure and its possible complications. Under general anesthesia and blood pressure control with patient placed in a lateral decubitus position, a rectal probe was inserted with its electrodes facing anteriorly to the proximity of the prostate (Seager electrical stimulator model 14). The voltage used was 10–15 V for 4–5 seconds duration with maximal current of 25 mA. In cases of rectal temperature of 39.9 C the electrical current was discontinued automatically to avoid thermal injury. There were some differences regarding the performance of EEJ between psychogenic and SCI patients. First, in SCI patients, general anesthesia was performed only in cases of preserved rectal sensation. Second, due to lack of retrograde ejaculation in psychogenic patients, bladder preparation and electrical stimulation were performed differently. Psychogenic patients were instructed to empty their bladder before the procedure, whereas in SCI patients the bladder was washed by plastic catheter with saline bicarbonate solution and 80 mg of garamycin 10–15 mL were instilled. In psychogenic patients single electrical stimulation was sufficient to retrieve sperm by antegrade ejaculation. On the other hand, in some SCI patients the first stimulation did not result with antegrade ejaculation and a recurrent three short stimulation of 5 V for 1 second each were performed. Then a catheter was inserted to retrieve sperm that was retrograde ejaculated. In cases of recurrent failure three more stimulations were given of 5 V of 1-second duration and a final catheter insertion was performed to retrieve as much spermatozoa as possible. In order to avoid autonomic dysreflexia in SCI patients, vital 1057
ORIGINAL ARTICLE: ANDROLOGY signs were monitored continuously and patients with previous event of autonomic dysreflexia were given a blockers prior to EEJ. Repetitive EEJ procedures were performed with shortest interval of 4 weeks to avoid damage to rectal mucosa and because of the time needed to conduct new cycle of ovarian stimulation. When focusing on spontaneous emissions before EEJ in the psychogenic cohort we speculated that masturbation was not performed due to religious beliefs. Data of nocturnal emissions was not available. The ICSI procedure was performed as described previously (19, 20). Fertilization was confirmed by the presence of two pronuclei (2PN) on the day after ICSI. Embryo transfer (ET) was done on day 2 or 3. The number of embryos and the mode of their transfer were determined by their availability as well as by the patient’s age and her clinical history. A pregnancy test was performed 12 days after ET. Clinical pregnancy was defined as the presence of an intrauterine gestational sac with embryonic pole diagnosed by sonography.
Outcome Measures and Statistical Analysis Sperm concentration and motility were analyzed using a Makler camera according to the World Health Organization guidelines (21). No assays of sperm DNA damage were performed in the current research. Implantation rate was calculated as the ratio between the number of embryonal sacs diagnosed by sonography and the number of embryos transferred into the uterus. Pregnancy rate was expressed as the ratio between the number pregnancies and the total number of cycles. Delivery rate was expressed as the ratio between the number of births and the total number of cycles. The EEJ/ICSI results of psychogenic anejaculation infertility were compared with the results of patients with anejaculation due to SCI. The t-test and Fisher’s exact test were used as appropriate. A P value < .05 was considered as statistically significant.
RESULTS Between 2000 and 2010, 15 male patients with psychogenic anejaculation and their spouses underwent 40 cycles of EEJ/ ICSI at the andrology and IVF units, Sheba medical center, Ramat Gan, Israel. The control group included 22 patients with anejaculation due to SCI and their spouses who underwent 66 cycles of EEJ/ICSI. Table 1 presents the characteristics of the male patients and female spouse. The two groups were similar including mean men’s age, mean women’s age and the mean number of EEJ cycles per patient. Sperm was retrieved in all patients by the EEJ procedure. One patient from the SCI population suffered from autonomic dysreflexia, which was treated by a and calcium channel blockers with good response. Thirty minutes after EEJ his blood pressure returned to normal range. Minor bleeding from external hemorrhoids occurred in three SCI patients because of probe insertion, which resolved spontaneously. There were no complications during EEJ among the psychogenic cohort. Electroejaculate parameters are presented in Table 2. No significant differences were found comparing sperm parameters of psychogenic anejaculation patients 1058
TABLE 1 Patient characteristics.
No. of couples No. of cycles Male agea Female agea Primary infertility (no/%)
Psychogenic anejaculation
SCI anejaculation
P value
15 40 36.8 8.2 31.4 6.3 11 (73%)
22 66 35.4 8.2 31.1 6.1 14 (63%)
NS NS NS
Note: Age was compared by t-test whereas infertility was compared by Fisher’s exact test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
and SCI patients. Recurrent EEJ in the same patient resulted in similar sperm parameters as in previous cycles. Forty ICSI cycles (mean 2.7 cycles per couple) were performed for psychogenic anejaculatory patients. Mean oocytes number per cycle was 11.3 with fertilization rate of 47.0%. Ninety-nine embryos were transferred, achieving eight pregnancies documented by positive serum b-hCG in five couples. Five pregnancies were singleton, two twins, and one triplet with selective reduction to twins at the end of the first trimester. Two pregnancies have ended in spontaneous abortion during the first trimester. Nine babies were born on six deliveries to five couples with delivery rate of 15%. Among SCI group average oocytes per cycle of 11.5 leading to fertilization rate of 57.0% compared with 47.0% in the psychogenic group. This difference was statistically significant (P¼ .01). Fifteen pregnancies were achieved with an implantation rate of 11.6% compared with 10.2% in psychogenic patients, without significant difference. Pregnancy rate and delivery rate were similar between the groups (Table 3).
DISCUSSION The prevalence of psychogenic anejaculation is low and varies between different populations. In addition, data regarding the influence on sperm quality, treatment modalities and success rates are limited and mostly lack acceptable control groups. The aim of the current study was to evaluate the benefits of combined procedure of EEJ/ICSI for this group of patients and to compare them with SCI patients treated in the same way. This study shows that although lower fertilization
TABLE 2 Electroejaculate parameters of psychogenic anejaculation patients compared to SCI patients.a
a
Volume (mL) Count (106/mL)a Motility (%)a
Psychogenic anejaculation
SCI anejaculation
P value
2.2 1.9 25.1 29.9 10.7 12.3
1.7 1.8 19.5 23.6 10.8 16.6
NS NS NS
Note: Comparison was made by t-test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
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TABLE 3 Treatment outcome for psychogenic and SCI anejaculatory patients.
a
No. of oocytes per cycle Fertilization rate (%)a Pregnancy rate (%)a Implantation rate (%)a Delivery rate (%)a
Psychogenic anejaculation
SCI anejaculation
P value
11.3 6.3 47.0 22.1 20.0 40.5 10.2 26.3 15.0 36.2
11.5 5.6 57.0 23.2 22.7 42.2 11.6 19.9 18.2 38.9
NS .01 NS NS NS
Note: Number of retrieved oocytes was compared by t-test, whereas fertilization, pregnancy, implantation, and delivery rates were compared by Fisher’s exact test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
rate was demonstrated in the psychogenic population compared with SCI group, acceptable and similar pregnancy and delivery rates were achieved. In the current study all EEJ resulted in sperm retrieval with low rate of complications. This is another example for the efficacy and safety of EEJ as documented in the past (8, 12). Previous studies on semen analysis in psychogenic anejaculatory patients revealed similar asthenospermia as in SCI patients, although psychogenic patients do not suffer from semen destructing factors as SCI patients do such as recurrent urinary tract infections (resulted as chronic pyospermia) and increased scrotal temperature. A similar picture of asthenospermia was demonstrated in both groups in the current study without any significant difference. This finding may be explained by the stasis of seminal fluid or presence of antisperm antibodies (12). Hovav et al. (12) found similar sperm characteristics in psychogenic and SCI patients in spite of the different pathophysiology, emphasizing the notion that EEJ may be associated with a detrimental effect to sperm motility. Our findings may support this hypothesis. Low sperm quality may alternatively be explained by long periods of abstinence, which are typical in unejaculatory patients. Because psychogenic anejaculation patients usually have regular nocturnal emissions we assume this is not the only explanation for the notable and similar asthenospermia in both groups. In this retrospective study no data regarding the presence of leukocytes in the ejaculate (mostly attributed to recurrent urinary tract infections in SCI patients) were available. However, because sperm characteristics were similar between the cohorts we assume that this parameter did not have a major influence on the study results. Previous studies that focused on EEJ in combination with ICSI for psychogenic anejaculation demonstrated diverse outcomes. Hovav et al. (15) studied seven patients who were treated by 16 cycles achieving 27% fertilization rate with one pregnancy and delivery. Fertilization rate was significantly lower compared with average ICSI fertilization rate during the same period (15). Another study included 29 cycles for 17 couples, reaching fertilization rate of 55% and pregnancy rate of 10% (13). Although these were pioneer studies and shed a light on psychogenic anejaculation, there were some drawbacks. First, comparison between psychogenic anejaculation patients and ‘‘general’’ male factor population may be confusing due to the heterogeneity nature of the genVOL. 97 NO. 5 / MAY 2012
eral male infertility control group. Second, the use of EEJ technique only for psychogenic anejaculatory patients may form a bias between the groups due to the possible effect of the procedure on sperm quality. In comparison, the current study demonstrates adequate fertilization, pregnancy and delivery rates of 47.0%, 20% and 15%, respectively. In addition, pregnancy rate for patients with psychogenic anejaculation using combination of EEJ and ICSI were similar to SCI. In order to investigate the relatively of low pregnancy and delivery rates in our cohorts we compared psychogenic group with other couples with matched women age who were treated in 3,069 IVF-ICSI cycles in our unit due to other male infertility causes during the same period. Interestingly, sperm characteristics in the psychogenic group demonstrated significantly lower motility (10.7% 12.3% vs. 28.8% 21.9%, P< .001) and higher count (25.1 29.9 106/mL vs. 10.4 17.1 106/mL, P< .001) with similar sperm volume (2.2 1.9 mL vs. 2.7 2.1 mL, P>.05) compared with ‘‘general’’ ICSI population, similar to previously described pattern (12, 15). Average pregnancy and delivery rates in the IVF-ICSI were 29.7% and 20.1%, respectively. Although pregnancy and delivery rates in the psychogenic EEJ-ICSI cohort were lower, these differences were not significant. Female age were similar between the groups (31.8 6.3 years in the EEJ-ICSI cohort and 32 5.3 years in the IVF-ICSI group) without statistical difference. We assume that the ICSI procedure may explain the lack of significant differences regarding pregnancy and delivery rates in spite of the major sperm differences between the groups. Interestingly, many studies regarding psychogenic anejaculation were conducted in Israel, where the proportion of Jewish orthodox population is relatively high. All psychogenic patients in the current research were Jewish orthodox who suffered from lifelong anejaculation due to psychological and spiritual beliefs regarding sexual relationships related to cultural taboo dealing with this subject. Masters and Johnson (22) have suggested that orthodoxy of religious beliefs in population may impair ejaculation. The perception toward ‘‘spilling seed’’ may cause guilt and anxiety, leading to anejaculation (6). Therefore, the incidence of psychogenic anejaculation may be higher compared to other countries. We assume that this factor attributes to the notable proportion of Israeli research dealing with that unique and quite rare illness. One of the basic dilemmas in treating couples with male factor infertility, including psychogenic anejaculation, is the need for ovarian stimulation. Ideally, in case of EEJ we would suggest a single EEJ procedure to evaluate sperm quality. However, in our Jewish orthodox religious cohort we had to take into consideration the orthodox perception of ‘‘spilling seed’’ as forbidden. Therefore, we had to use the retrieved sperm from the first EEJ procedure without cryopreservation, mostly by IUI combined with ovarian stimulation. We regarded this protocol as a compromise between IUI without any stimulation and IVF-ICSI. The decision regarding ovarian stimulation in the following cycles was calculated according to sperm quality and first cycle results. This is one of the largest published series of EEJ and ICSI for psychogenic anejaculation. To our knowledge, this is the first comparison of fertilization treatments for psychogenic 1059
ORIGINAL ARTICLE: ANDROLOGY anejaculation and other etiology of anejaculation. The use of SCI patients as control group has advantages. This population was extensively studied and represents the role model of EEJ, therefore it is the ‘‘classic’’ control group for psychogenic population. In the current study we achieved high uniformity between both groups regarding age as well as infertility type, treatment regimens, average cycles per couple and mean retrieved ovum per cycles (representation of ovarian response to induction), which gives a reliable base for comparison. Unlike other studies that included different methods such as IUI, IVF, and ICSI (3, 5, 10, 12, 23, 24), in the current study all couples were treated homogenously by EEJ and ICSI. Couples with female infertility were excluded. In addition, most data regarding fertility treatments for psychogenic anejaculation were published more than 10 years ago. These results give an updated picture of treatments’ outcome, which is critical for patients’ consultation. In conclusion, combination of EEJ and ICSI gives adequate results to couples with psychogenic anejaulation as for SCI patients. Current results are better than previously described (12, 15) and give these couples reasonable chance to conceive.
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In Vitro Fertilization Unit and b Andrology Unit, Sheba Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel
Objective: To evaluate sperm quality and fertility potential of men with psychogenic anejaculation treated by electroejaculation (EEJ) and intracytoplasmic sperm injection (ICSI). Treatment results were compared to spinal cord injured (SCI) patients treated similarly. Design: Retrospective clinical study. Setting: Academic tertiary referral fertility center. Patient(s): Couples with isolated psychogenic anejaculation or SCI. Intervention(s): Electroejaculation and ICSI. Main Outcome Measure(s): Semen analysis, fertilization rate, implantation rate, pregnancy rate, delivery rate and safety of the procedure. Result(s): Fifteen patients diagnosed with psychogenic anejaculation underwent 40 EEJ/ICSI cycles. The semen retrieved was characterized by low motility (mean 10.7% 12.3%), normal volume (2.2 1.9 mL) and normal count (25.1 29.9 106/mL), according to World Health Organization criteria. Results of EEJ/ICSI were compared with 22 SCI patients treated by 66 EEJ/ICSI cycles during the same period. Mean female age and the number of oocytes retrieved per cycle were similar between the groups. Similar semen parameters after EEJ were found between psychogenic and SCI patients. Fertilization rate was significantly lower in the psychogenic patients compared to SCI (47.0% and 57.0%, respectively). No significant differences were found regarding pregnancy rates (20% and 22.7%, respectively), implantation rate (10.2% and 11.6%, respectively) or delivery rates (15% and 18.2%, respectively). Conclusion(s): Sperm retrieved by EEJ is characterized by asthenospermia and normal count. In spite of the lower fertilization rate in psychogenic patients, combination of EEJ and ICSI gives adequate results to couples with psychogenic anejaculation similar to the results obtained for SCI patients. Current results give these couples a reasonable chance of pregnancy achievement. (Fertil SterilÒ 2012;97:1056–60. Ó2012 by American Society for Reproductive Medicine.) Key Words: Electroejaculation, psychogenic anejaculation, spinal cord injury, intracytoplasmic sperm injection
T
he process of ejaculation includes well-coordinated contractions of striated and nonstriated muscular contractions that ejaculate the sperm and seminal fluid through the urethra. The neurologic involvement relies
mostly on the sympathetic system as well as efferent and afferent pathways—dorsal nerves of the penis, internal pudendal nerve, anterolateral columns of the spinal cord, sympathetic chain ganglia and hypogastric plexus
Received September 11, 2011; revised January 30, 2012; accepted January 31, 2012; published online February 24, 2012. I.G. has nothing to disclose. E.M. has nothing to disclose. G.Y. has nothing to disclose. M.B. has nothing to disclose. J.D. has nothing to disclose. G.R. has nothing to disclose. I.M. has nothing to disclose. A.H. has nothing to disclose. Reprint requests: Itai Gat, M.D., Tel Hashomer, Ramat Gan, 52621 Israel (E-mail: itaigatmd@gmail. com). Fertility and Sterility® Vol. 97, No. 5, May 2012 0015-0282/$36.00 Copyright ©2012 American Society for Reproductive Medicine, Published by Elsevier Inc. doi:10.1016/j.fertnstert.2012.01.129 1056
anterior to the aorta (1). Neurologic impairment may be followed by ejaculatory dysfunction in different etiologies, such as spinal cord injury (SCI), retroperitoneal lymph node dissection, diabetes, multiple sclerosis, drugs and psychogenic anejaculation (2–5). Anejaculation, as well as delayed ejaculation and inhibited ejaculation, are the least common, least studied and least understood male sexual dysfunctions. Their prevalence is unclear for various reasons such as lack of differentiation between delayed ejaculation and anejaculation in VOL. 97 NO. 5 / MAY 2012
Fertility and Sterility® epidemiological studies (6). Although anejaculation accounts for only 2% of male factor infertility (7), in specific populations such as men with SCI it is the major cause for infertility (5). A significant progression in the treatment of anejaculated men was achieved by the method of electroejaculation (EEJ). During EEJ, a rectal probe transmits electrical stimulation to the short postsynaptic sympathetic fibers in the wall of the ejaculatory organs (1), leading to ejaculation and sperm procurement in 70%–90% of attempts (2, 4, 8, 9). Therefore, in a relatively simple, safe, and inexpensive method the barrier of semen achievement can be overcome (1). Semen collected by EEJ can be used in variety of fertilization methods (1, 3, 8–10). Ohl et al. (5) conducted 653 IUI cycles achieving an 8.7% pregnancy rate per IUI cycle. The relatively low pregnancy rate was attributed to the poor quality of the electroejaculates (2). The electroejaculates demonstrated polyspermia, asthenospermia and teratospermia with decreased ability of cervical mucus penetration and impaired fertilizing capacity (1, 4, 5, 8, 11). Because of the low sperm quality in these patients, combined EEJ, IVF, and intracytoplasmic sperm injection (ICSI) became optional procedures to improve pregnancy and delivery rates. Heruti et al. (8) demonstrated pregnancy rate of 26.4% and delivery rate of 20.5% after 68 EEJ/ICSI cycles in 20 couples suffering from SCI anejaculation. Most of the research on anejaculation was conducted mainly in SCI patients, a prominent etiology for anejaculation (5). One of the less investigated populations is the psychogenic anejaculatory patients. These patients are otherwise healthy and may have erections and nocturnal emission but cannot ejaculate even by masturbation (12, 13). The diagnosis of psychogenic anejaculation is made after iatrogenic and pathophysiological etiologies are excluded (6, 14). Studies conducted on patients with psychogenic anejaculation revealed similar asthenospermia as SCI patients (12). Additional research using EEJ combined with ICSI for couples with male factor infertility due to psychogenic anejaculation demonstrated prominent lack of uniformity with diverse results regarding fertilization, pregnancy and delivery rates (13, 15). Sample sizes were relatively low and no comparison was made between psychogenic anejaculation and other anejaculatory populations. In addition, some of the published series on patients with anejaculation were conducted on diverse male impairments (2–5) or included comparisons to male patients who had the ability to ejaculate and suffered from other infertility impairment (15). Therefore, the aim of the current study was to investigate results of EEJ and ICSI for psychogenic anejaculation and to compare them with other homogeneous group of EEJ/ICSI treated population, the SCI patients.
MATERIALS AND METHODS Patients In this retrospective study we enrolled all couples treated by EEJ and ICSI for isolated male psychogenic anejaculation in our units between 2000 and 2010. All male patients underwent complete evaluation including patient history, physical VOL. 97 NO. 5 / MAY 2012
examination, hormonal profile and ultrasound examination as needed. Diagnosis of psychogenic anejaculation was made after exclusion of organic causes for anejaculation in addition to sexual relationship without ejaculations and orgasm in the presence of nocturnal emissions. Female patients underwent detailed investigation including patient history, physical examination, hormonal profile, ultrasound, and, if needed, hysterosalpingogram. Couples with female factor in addition to male infertility were excluded. Indications for ICSI included recurrent failure in IUI treatments or low ejaculate quality such as total motility <10 106/ml. The research was approved by the Institutional Review Board.
Hormonal Stimulation and Electroejaculation Ovarian stimulation for IVF included accepted IVF protocols. Long agonist, antagonist protocol and short agonist protocol of controlled ovarian hyperstimulation were performed as described elsewhere (16, 17). In both groups, hCG was administered when more than two follicles reached 18 mm, followed by oocyte collection 36 hours later. Oocyte retrieval, fertilization, embryo culture and transfer were carried out as previously described (18). Most of the patients in the study group were Orthodox Jews and manual stimulation of a vibrator is absolutely forbidden for religious reasons. Therefore vibratory stimulation had not been performed in our cohort and EEJ is our firstline of treatment for anejaculation. The EEJ procedures were performed 36–38 hours after hCG injection followed by oocytes retrievals. Before EEJ all patients gave their informed consent with comprehensive understanding of the procedure and its possible complications. Under general anesthesia and blood pressure control with patient placed in a lateral decubitus position, a rectal probe was inserted with its electrodes facing anteriorly to the proximity of the prostate (Seager electrical stimulator model 14). The voltage used was 10–15 V for 4–5 seconds duration with maximal current of 25 mA. In cases of rectal temperature of 39.9 C the electrical current was discontinued automatically to avoid thermal injury. There were some differences regarding the performance of EEJ between psychogenic and SCI patients. First, in SCI patients, general anesthesia was performed only in cases of preserved rectal sensation. Second, due to lack of retrograde ejaculation in psychogenic patients, bladder preparation and electrical stimulation were performed differently. Psychogenic patients were instructed to empty their bladder before the procedure, whereas in SCI patients the bladder was washed by plastic catheter with saline bicarbonate solution and 80 mg of garamycin 10–15 mL were instilled. In psychogenic patients single electrical stimulation was sufficient to retrieve sperm by antegrade ejaculation. On the other hand, in some SCI patients the first stimulation did not result with antegrade ejaculation and a recurrent three short stimulation of 5 V for 1 second each were performed. Then a catheter was inserted to retrieve sperm that was retrograde ejaculated. In cases of recurrent failure three more stimulations were given of 5 V of 1-second duration and a final catheter insertion was performed to retrieve as much spermatozoa as possible. In order to avoid autonomic dysreflexia in SCI patients, vital 1057
ORIGINAL ARTICLE: ANDROLOGY signs were monitored continuously and patients with previous event of autonomic dysreflexia were given a blockers prior to EEJ. Repetitive EEJ procedures were performed with shortest interval of 4 weeks to avoid damage to rectal mucosa and because of the time needed to conduct new cycle of ovarian stimulation. When focusing on spontaneous emissions before EEJ in the psychogenic cohort we speculated that masturbation was not performed due to religious beliefs. Data of nocturnal emissions was not available. The ICSI procedure was performed as described previously (19, 20). Fertilization was confirmed by the presence of two pronuclei (2PN) on the day after ICSI. Embryo transfer (ET) was done on day 2 or 3. The number of embryos and the mode of their transfer were determined by their availability as well as by the patient’s age and her clinical history. A pregnancy test was performed 12 days after ET. Clinical pregnancy was defined as the presence of an intrauterine gestational sac with embryonic pole diagnosed by sonography.
Outcome Measures and Statistical Analysis Sperm concentration and motility were analyzed using a Makler camera according to the World Health Organization guidelines (21). No assays of sperm DNA damage were performed in the current research. Implantation rate was calculated as the ratio between the number of embryonal sacs diagnosed by sonography and the number of embryos transferred into the uterus. Pregnancy rate was expressed as the ratio between the number pregnancies and the total number of cycles. Delivery rate was expressed as the ratio between the number of births and the total number of cycles. The EEJ/ICSI results of psychogenic anejaculation infertility were compared with the results of patients with anejaculation due to SCI. The t-test and Fisher’s exact test were used as appropriate. A P value < .05 was considered as statistically significant.
RESULTS Between 2000 and 2010, 15 male patients with psychogenic anejaculation and their spouses underwent 40 cycles of EEJ/ ICSI at the andrology and IVF units, Sheba medical center, Ramat Gan, Israel. The control group included 22 patients with anejaculation due to SCI and their spouses who underwent 66 cycles of EEJ/ICSI. Table 1 presents the characteristics of the male patients and female spouse. The two groups were similar including mean men’s age, mean women’s age and the mean number of EEJ cycles per patient. Sperm was retrieved in all patients by the EEJ procedure. One patient from the SCI population suffered from autonomic dysreflexia, which was treated by a and calcium channel blockers with good response. Thirty minutes after EEJ his blood pressure returned to normal range. Minor bleeding from external hemorrhoids occurred in three SCI patients because of probe insertion, which resolved spontaneously. There were no complications during EEJ among the psychogenic cohort. Electroejaculate parameters are presented in Table 2. No significant differences were found comparing sperm parameters of psychogenic anejaculation patients 1058
TABLE 1 Patient characteristics.
No. of couples No. of cycles Male agea Female agea Primary infertility (no/%)
Psychogenic anejaculation
SCI anejaculation
P value
15 40 36.8 8.2 31.4 6.3 11 (73%)
22 66 35.4 8.2 31.1 6.1 14 (63%)
NS NS NS
Note: Age was compared by t-test whereas infertility was compared by Fisher’s exact test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
and SCI patients. Recurrent EEJ in the same patient resulted in similar sperm parameters as in previous cycles. Forty ICSI cycles (mean 2.7 cycles per couple) were performed for psychogenic anejaculatory patients. Mean oocytes number per cycle was 11.3 with fertilization rate of 47.0%. Ninety-nine embryos were transferred, achieving eight pregnancies documented by positive serum b-hCG in five couples. Five pregnancies were singleton, two twins, and one triplet with selective reduction to twins at the end of the first trimester. Two pregnancies have ended in spontaneous abortion during the first trimester. Nine babies were born on six deliveries to five couples with delivery rate of 15%. Among SCI group average oocytes per cycle of 11.5 leading to fertilization rate of 57.0% compared with 47.0% in the psychogenic group. This difference was statistically significant (P¼ .01). Fifteen pregnancies were achieved with an implantation rate of 11.6% compared with 10.2% in psychogenic patients, without significant difference. Pregnancy rate and delivery rate were similar between the groups (Table 3).
DISCUSSION The prevalence of psychogenic anejaculation is low and varies between different populations. In addition, data regarding the influence on sperm quality, treatment modalities and success rates are limited and mostly lack acceptable control groups. The aim of the current study was to evaluate the benefits of combined procedure of EEJ/ICSI for this group of patients and to compare them with SCI patients treated in the same way. This study shows that although lower fertilization
TABLE 2 Electroejaculate parameters of psychogenic anejaculation patients compared to SCI patients.a
a
Volume (mL) Count (106/mL)a Motility (%)a
Psychogenic anejaculation
SCI anejaculation
P value
2.2 1.9 25.1 29.9 10.7 12.3
1.7 1.8 19.5 23.6 10.8 16.6
NS NS NS
Note: Comparison was made by t-test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
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TABLE 3 Treatment outcome for psychogenic and SCI anejaculatory patients.
a
No. of oocytes per cycle Fertilization rate (%)a Pregnancy rate (%)a Implantation rate (%)a Delivery rate (%)a
Psychogenic anejaculation
SCI anejaculation
P value
11.3 6.3 47.0 22.1 20.0 40.5 10.2 26.3 15.0 36.2
11.5 5.6 57.0 23.2 22.7 42.2 11.6 19.9 18.2 38.9
NS .01 NS NS NS
Note: Number of retrieved oocytes was compared by t-test, whereas fertilization, pregnancy, implantation, and delivery rates were compared by Fisher’s exact test. NS ¼ not significant; SCI ¼ spinal cord injury. a Mean SD. Gat. EEJ and ICSI for psychogenic anejaculation. Fertil Steril 2012.
rate was demonstrated in the psychogenic population compared with SCI group, acceptable and similar pregnancy and delivery rates were achieved. In the current study all EEJ resulted in sperm retrieval with low rate of complications. This is another example for the efficacy and safety of EEJ as documented in the past (8, 12). Previous studies on semen analysis in psychogenic anejaculatory patients revealed similar asthenospermia as in SCI patients, although psychogenic patients do not suffer from semen destructing factors as SCI patients do such as recurrent urinary tract infections (resulted as chronic pyospermia) and increased scrotal temperature. A similar picture of asthenospermia was demonstrated in both groups in the current study without any significant difference. This finding may be explained by the stasis of seminal fluid or presence of antisperm antibodies (12). Hovav et al. (12) found similar sperm characteristics in psychogenic and SCI patients in spite of the different pathophysiology, emphasizing the notion that EEJ may be associated with a detrimental effect to sperm motility. Our findings may support this hypothesis. Low sperm quality may alternatively be explained by long periods of abstinence, which are typical in unejaculatory patients. Because psychogenic anejaculation patients usually have regular nocturnal emissions we assume this is not the only explanation for the notable and similar asthenospermia in both groups. In this retrospective study no data regarding the presence of leukocytes in the ejaculate (mostly attributed to recurrent urinary tract infections in SCI patients) were available. However, because sperm characteristics were similar between the cohorts we assume that this parameter did not have a major influence on the study results. Previous studies that focused on EEJ in combination with ICSI for psychogenic anejaculation demonstrated diverse outcomes. Hovav et al. (15) studied seven patients who were treated by 16 cycles achieving 27% fertilization rate with one pregnancy and delivery. Fertilization rate was significantly lower compared with average ICSI fertilization rate during the same period (15). Another study included 29 cycles for 17 couples, reaching fertilization rate of 55% and pregnancy rate of 10% (13). Although these were pioneer studies and shed a light on psychogenic anejaculation, there were some drawbacks. First, comparison between psychogenic anejaculation patients and ‘‘general’’ male factor population may be confusing due to the heterogeneity nature of the genVOL. 97 NO. 5 / MAY 2012
eral male infertility control group. Second, the use of EEJ technique only for psychogenic anejaculatory patients may form a bias between the groups due to the possible effect of the procedure on sperm quality. In comparison, the current study demonstrates adequate fertilization, pregnancy and delivery rates of 47.0%, 20% and 15%, respectively. In addition, pregnancy rate for patients with psychogenic anejaculation using combination of EEJ and ICSI were similar to SCI. In order to investigate the relatively of low pregnancy and delivery rates in our cohorts we compared psychogenic group with other couples with matched women age who were treated in 3,069 IVF-ICSI cycles in our unit due to other male infertility causes during the same period. Interestingly, sperm characteristics in the psychogenic group demonstrated significantly lower motility (10.7% 12.3% vs. 28.8% 21.9%, P< .001) and higher count (25.1 29.9 106/mL vs. 10.4 17.1 106/mL, P< .001) with similar sperm volume (2.2 1.9 mL vs. 2.7 2.1 mL, P>.05) compared with ‘‘general’’ ICSI population, similar to previously described pattern (12, 15). Average pregnancy and delivery rates in the IVF-ICSI were 29.7% and 20.1%, respectively. Although pregnancy and delivery rates in the psychogenic EEJ-ICSI cohort were lower, these differences were not significant. Female age were similar between the groups (31.8 6.3 years in the EEJ-ICSI cohort and 32 5.3 years in the IVF-ICSI group) without statistical difference. We assume that the ICSI procedure may explain the lack of significant differences regarding pregnancy and delivery rates in spite of the major sperm differences between the groups. Interestingly, many studies regarding psychogenic anejaculation were conducted in Israel, where the proportion of Jewish orthodox population is relatively high. All psychogenic patients in the current research were Jewish orthodox who suffered from lifelong anejaculation due to psychological and spiritual beliefs regarding sexual relationships related to cultural taboo dealing with this subject. Masters and Johnson (22) have suggested that orthodoxy of religious beliefs in population may impair ejaculation. The perception toward ‘‘spilling seed’’ may cause guilt and anxiety, leading to anejaculation (6). Therefore, the incidence of psychogenic anejaculation may be higher compared to other countries. We assume that this factor attributes to the notable proportion of Israeli research dealing with that unique and quite rare illness. One of the basic dilemmas in treating couples with male factor infertility, including psychogenic anejaculation, is the need for ovarian stimulation. Ideally, in case of EEJ we would suggest a single EEJ procedure to evaluate sperm quality. However, in our Jewish orthodox religious cohort we had to take into consideration the orthodox perception of ‘‘spilling seed’’ as forbidden. Therefore, we had to use the retrieved sperm from the first EEJ procedure without cryopreservation, mostly by IUI combined with ovarian stimulation. We regarded this protocol as a compromise between IUI without any stimulation and IVF-ICSI. The decision regarding ovarian stimulation in the following cycles was calculated according to sperm quality and first cycle results. This is one of the largest published series of EEJ and ICSI for psychogenic anejaculation. To our knowledge, this is the first comparison of fertilization treatments for psychogenic 1059
ORIGINAL ARTICLE: ANDROLOGY anejaculation and other etiology of anejaculation. The use of SCI patients as control group has advantages. This population was extensively studied and represents the role model of EEJ, therefore it is the ‘‘classic’’ control group for psychogenic population. In the current study we achieved high uniformity between both groups regarding age as well as infertility type, treatment regimens, average cycles per couple and mean retrieved ovum per cycles (representation of ovarian response to induction), which gives a reliable base for comparison. Unlike other studies that included different methods such as IUI, IVF, and ICSI (3, 5, 10, 12, 23, 24), in the current study all couples were treated homogenously by EEJ and ICSI. Couples with female infertility were excluded. In addition, most data regarding fertility treatments for psychogenic anejaculation were published more than 10 years ago. These results give an updated picture of treatments’ outcome, which is critical for patients’ consultation. In conclusion, combination of EEJ and ICSI gives adequate results to couples with psychogenic anejaulation as for SCI patients. Current results are better than previously described (12, 15) and give these couples reasonable chance to conceive.
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