Archives of Andrology, 51:431–436, 2005 Copyright # Taylor & Francis Inc. ISSN: 0148-5016 print/1521-0375 online DOI: 10.1080/014850190953294 THE ONLY PRESENCE OF SPERM IN URINE DOES NOT IMPLY RETROGRADE EJACULATION J. I. Ariagno, G. R. Mendeluk, M. N. Pugliese, S. L. M. Sardi, C. Acuña, H. E. H. Repetto, and S. M. Curi & Departamento de Bioquı´mica Clı´nica, Facultad de Farmacia, Bioquı´mica, U.B.A. Proyecto UBACYT, Hospital de Clı´nicas ‘‘Jose´ de San Martı´n,’’ Buenos Aires, Argentina & This is a retrospective study of clinical experience collected at the University Clinical Hospital over a 19-year period. Semen samples were analyzed according to WHO criteria. In the postmasturbatory urine, sperm count was performed. Data were expressed as total sperm number in urine (TSNU) and using a retroejaculation index. Patients were categorized into four groups according to the presence of sperm in the studied samples: a) in semen and urine; b) only in urine; c) only in semen; d) neither in semen nor in urine. A control group included nonretroejaculator patients. Retroejaculator patients are those whose TSNU is superior to 3.8 106 and the RI superior to 2.16%. While diagnosing retroejaculation, the only presence of sperm in the postmasturbatory urine is not adequate. The proposed index added to total sperm number in urine and semen volume may identify true retroejaculator patients. Keywords sperm in urine, retrograde ejaculation, diagnosis, prostatic surgery, diabetic neuropathy INTRODUCTION The most widely accepted theory to explain ejaculation consists of two phases: a) phase of accumulation of the various constituents of semen inside the prostatic urethra and b) phase of expulsion with opening of the striated sphincter, while the smooth sphincter of the bladder neck remains closed. Antegrade ejaculation requires intact anatomy and innervation of the bladder neck. Failure of the normal ejaculatory mechanism may lead to retrograde ejaculation. Retrograde ejaculation is an uncommon cause of infertility and can be defined as the escape of seminal fluid from the Supported by a grant from the University of Buenos Aires, UBACYT (B=037). Address correspondence to Julia Irene Ariagno, Departamento de Bioquı́mica Clı́nica, Facultad de Farmacia, Bioquı́mica, U.B.A. Proyecto UBACYT, Hospital de Clı́nicas ‘‘José de San Martı́n,’’ Melian 3862 1430, Buenos Aires, Argentina. E-mail: [email protected] or [email protected] 432 J. I. Ariagno et al. posterior urethra into the bladder [1]. This occurs most commonly as a result of transurethral prostatectomy, retroperitoneal lymph-node dissection [2] and diabetic neuropathy. Surgical therapy of benign prostatic hyperplasia (open surgery or transurethral prostatic resection) is associated with retrograde ejaculation in nearly 100% of cases [3]. Retrograde ejaculation also can be related to a traumatic injury of the posterior urethra due to the trauma itself or the therapy. Finally, the ejaculation disorder can be produced by several drugs that block, as a main or secondary effect, the alpha-adrenoreceptors or act at the central level. Retroejaculation may be suspected on clinical grounds referred to previously and data from the seminal analysis, the finding of either aspermia or a small volume of semen, which does not contain a normal number of sperm. The diagnosis of the retrograde ejaculation in the infrequent complete form is established through its major sign: the aspermia. Hershlag et al. [4] bases the diagnosis on the absence of sperm in the antegrade ejaculate and the presence of sperm in the postmasturbatory urine. The problem is to diagnose the minor forms where only part of the ejaculate is driven into the bladder resulting in a diminution of sperm volume and in some cases also sperm count. Male infertility due to retroejaculatory problems can be effectively treated and accurate diagnosis is required. This is a retrospective study of clinical experience collected at the University Clinical Hospital ‘‘José de San Martin’’ over a 19-year period (1983–2002). The aim of this work is to determine if the only identification of spermatozoa in the postmasturbatory urine confirms the diagnosis or if a cut-off value should be established. MATERIALS AND METHODS Patients Following Institutional Review Board approval specimens in this study were obtained from 87 men attending the Andrological Laboratory at the University Clinical Hospital of Buenos Aires ‘‘José de San Martı́n.’’ The patients were referred to our clinic for infertility problems associated with retrograde ejaculation on clinical or biochemical grounds. The control group included patients referred to our clinic for infertility problems not associated with retrograde ejaculation, based on clinical grounds and data from the seminal analysis (n ¼ 27). Sample Collection and Analysis Voided urine specimens were collected from the patients following production of the semen specimen (masturbation). Semen analysis was Retrograde Ejaculation Diagnosis 433 performed according to WHO regulations [5]. The post masturbatory urine was observed in the microscope (400). If sperm were found, the count was assessed using an improved Neubauer Chamber, if not it was centrifuged and the sediment observed; in case of finding sperm in the sediment its concentration was referred to the total urine volume. Data Expression The total sperm number was assessed when sperm were found either in semen or in urine. Data were expressed as: total sperm number in urine (TSNU) and retroejaculation index (RI) RI ¼ total sperm number in urine 100 total sperm number in urine + total sperm number in semen Statistical Analysis Due to the skewed variables assessed, nonparametric methods were used. Results are expressed as median; 25th percentile; 75th percentile. Wilcoxon test was used to compare differences among groups while the Kruskal-Wallis test was employed on comparing two particular groups; p < 0.05 was accepted as statistically significant. The Spearman correlation was applied between the studied parameters. RESULTS Men were categorized into four groups as follows. Group A had sperm in semen and urine (n ¼ 47); Group B only in urine (n ¼ 7); Group C only in semen (n ¼ 7); Group D neither in semen nor in urine (n ¼ 26). (Figure 1). The high number of patients in Group A with sperm in semen and urine probably includes the minor form of retroejaculation. The presence of sperm in urine in the control group was 1,118 sperm in total urine (median). The sperm number in urine or the retroejaculation index showed significant difference between Groups A and control (p < 0.0001; Table 1); a good correlation was found between TSNU and RI (r ¼ 0.86, p ¼ 0.00001). The TSNU did not correlate with the sperm number in semen in Group A or in the control group. On comparing semen volume in all the groups, a high statistical difference was found (p < 0.00001). The same difference was found on comparing Group A and the control, while no difference was obtained between Group C 434 J. I. Ariagno et al. FIGURE 1 Sperm distribution in groups. and the control. All patients included in Group B were either aspermic or severely hypospermic (median ¼ 0.00001 ml; 25th percentile ¼ 0; 75th percentile ¼ 0.1). Semen volume did not correlate with TSNU, suggesting that although hypospermia may guide to suspect retroejaculation is not a sufficient tool to arrive to the accurate diagnosis. Group A was divided according to semen volume in hypospermic (< 2.0 mL) and normospermic; the median RI was 17.89% in the former and 0.004% in the latter. According to NCCLS guidelines [6], the 2.5th and the 97.5th percentiles from the control group define the reference limits. Considering the 97.5th percentile, retroejaculators are those patients where the TSNU is superior to 3.8 106 and the IR superior to 2.16%. TABLE 1 Comparison between Groups Total sperm number in semen GROUP B 38.4 106; 6.0 106; 155 106 0 GROUP C GROUP D CONTROL GROUP 156000; 45100; 595000 0 92.4 106; 16.49 106; 357.05 106 GROUP A Semen volume (ml) Total sperm number in urine (TSNU) RI (%) 1.20; 0.60; 1.90 5.6 106; 7400; 39 106 10.64; 0.09; 48.87 0.00001; 0; 0.1 26 106; 8.7 106; 29.8 106 0 0 1118; 133; 7912 100 4.3; 3.5; 5.0 1.35; 0.8; 3.0 2.85; 2.02; 3.80 Data are expressed as: median; 25th percentile; 75th percentile. — — 0.0021; 0.0003; 0.0307 Retrograde Ejaculation Diagnosis 435 DISCUSSION Strategy for male infertility is a compromise between diagnosis methods with their efficacy and complexity and treatment with their own risk, cost, and efficacy. Some situations may benefit from specific therapy such as hypogonadotrophic hypogonadism, anejaculations, or retrograde ejaculation. Retrograde ejaculation causes less than 2% of male infertility but is the leading cause of aspermia. The incidence of retrograde ejaculation is increasing due to aggressiveness of modern urologic cancer surgery and an increase in diabetes mellitus. Generally, the only adverse effect is on fertility. If pharmacological attempts to restore antegrade ejaculation fail, sperm recovery from the urine is indicated. Modern assisted reproduction technology is a powerful treatment option for retrograde ejaculation when combined with a technique to retrieve spermatozoa of good quality from the bladder [7]. The benefit of ICSI in cases of anejaculatory infertility due to retrograde ejaculation who are resistant to medical treatment and whose sperm quality is so low or unpredictable that intrauterine insemination or conventional methods of in vitro fertilization are not possible were reported by Okada et al. [8]. Thus, work is needed to achieve objectivity and standardization of the laboratory diagnosis of retroejaculation that should finally be included in the guidelines of the World Health Organization [5] to select an appropriate clinical management for patients looking for fertility. The main purpose of the evaluation of retroejaculation should be established. It provides basic knowledge on the status of a given patient. The information obtained may help to decide where to retrieve sperm in cases of patients looking for fertility. On the other hand data obtained could have a prognostic value, particularly in cases of Type I diabetes [9]. Further studies should be conducted to evaluate the relation of RI and other biochemical and biophysical markers like glycosilated hemoglobin or blood rheology as well as with clinical data like retinopathy to interpret the evolution of disease. Low volume or absent ejaculate was a characteristic of Groups A and B, with a few exceptions, data that could lead to investigate retroejaculation. We tried to clarify the diagnosis and to establish rules that could help to obtain a better diagnosis of the pathology under study. In a pragmatic way patients were selected according to the presence of sperm either in semen or in urine. Thus Group A is composed of true and nonretroejaculators as well as Group D. All the subjects classified into Group B are true retroejaculators while those classified into Group C are nonretroejaculators belonging to severe oligozoospermic patients. It is important to arrive to an accurate diagnosis in Groups A and D. Focusing in this purpose we 436 J. I. Ariagno et al. established a retroejaculation index, a biochemical analysis should be performed in Group D. It is concluded that while diagnosing retroejaculation, the only presence of sperm in the postmasturbatory urine is not enough, the proposed index added to total sperm number in urine and semen volume may lead to identify true retroejaculator patients. REFERENCES 1. Malossini G, Ficarra V, Caleffi G (1999): Retrograde ejaculation. Arch Ital Urol Androl 71(3): 185–196. 2. Kedia K, Markland C, Fraley E (1975): Sexual function following high retroperitoneal limphadenectomy. J Urol 114:237–241. 3. Terrone C, et al. (2001): Iatrogenic ejaculation disorders and their prevention. Minerva Urol Nefrol 53(1):19–28. 4. Hershlag A, Schiff SF, DeCherney AH (1991): Retrograde ejaculation. Hum Reprod 6(2):255–258. 5. World Health Organization (1999): WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th ed. Cambridge: Cambridge University Press, pp 4–33. 6. National Committee of Clinical Laboratory Standards (1995): How To Define and Determine Reference Intervals in the Clinical Laboratory: Approved Guidelines. NCCLS, Pennsylvania, (Document 28-A). 7. Nikolettos N, Al-Hasani S, Baukloh V, et al. (1999): The outcome of intracytoplasmatic sperm injection in patients with retrograde ejaculation. Hum Reprod 14(9):2293–2296. 8. Okada H, Fujioka H, Tatsumi N, et al.(1998): Treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology. J Urol 159(3):848–850. 9. Greene L, Kelalis P (1968): Retrograde ejaculation of semen due to diabetic neuropathy. J Urol 98:693–697.
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