Efficacy of varicocele embolization versus ligation of the left internal spermatic vein for improvement of sperm quality

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Inrernational Journal of Andrology, 1992, 15, pages 338-344 Efficacy of varicocele embolization versus ligation of the left internal spermatic vein for improvement of sperm quality H. YAVEZ, R. LEVY, J. PAPO, L. YOGEV, G. PAZ, A. J. JAFFA and Z.. HOMONNAI Institute for the Study of Fertility, Serlin Maternity Hospital, el A viv Sourasky Medical Center, Sackler Faculty of Medicine, el A viv University, POB 7079, el A viv 61 070, Israel Summary Efficacy of surgical varicocelectomy versus embolization of the spermatic vein was studied in 137 men diagnosed as suffering from left varicocele. he men were divided randomly into three groups according to the methods of treatment: A - embolization of the internal spermatic vein (51 men): B - Ivanissevich technique of high ligation of the spermatic veins (43 men); and C - Bernardi technique of high ligation (43 men). he groups were similar in terms of age, duration of infertility and possessed semen characterized as oligoteratoasthenozoospermia. he fertility of the female partners was evaluated carefully and they were found to be potentially fertile. Varicocele was diagnosed by at least two of the following methods: physicaf palpation during valsalva manoeuvre, venography, or scrota1 scanning using the technetium pertechnate radioactive method. Semen quality was assessed before treatment and at 3, 6 and 9 months post-treatment. Fecundity was followedup for 18 months. he major results were: (i) Shrinkage of the varicocele was found in all three groups studied. he same rate of recurrence was recorded in the three groups (249 0, 37% and 35% in groups A, B and C, respectively). (ii) Improvement of sperm quality was significant in groups A and 3, with better results in group B. (iii) he pregnancy rate was significantly higher in group B, compared with A (38.2% vs. 20.6%; P<0.05). hus, high ligation of the internal spermatic vein yields better results than low ligation or embolization as far as semen quality and pregnancy is concerned. Keywords: embolization, fertility, sperm quality, varicocele. Introduction Spermatic vein varicocele is a well-known syndrome which may lead to subfertile sperm quality characterized by oligoteratoasthenozoospermia (OA). It appears as Correspondence: Dr Haim Yavetz, Institute for the study of Fertility, Serlin Maternity Hospital, P.O. Box 7079, el Aviv, Israel 61070. 338

Varicocele treatment-embolization versus ligation 339 if impaired drainage of blood from the testis is associated with increased temperature which causes deleterious changes in spermatogenesis (Zorgniotti & MacLeod, 1973). he aetiology of this syndrome was described in the past, and was shown to be accompanied by changes in blood supply (Shafik et al., 1972; Sayfan et al., 1984), hormones (Hudson et al., 1986; Nagao et al., 1986) and tissue metabolism (Comhaire & Vermeulen, 1974; Ito et al., 1982). he diagnosis is based mainly upon palpation of the veins in the scrotum during valsalva manoeuvre supported by sophisticated diagnostic methods such as doppler scanning, radioactive scanning and thermography of the scrotum. When two methods confirm the existence of a varicocele, it is usually accepted as an aetiology for OA syndrome. Surgical treatment of the syndrome is usually recommended with satisfactory results in terms of improvement in sperm quality and pregnancy rates (Dubin & Amelar, 1975; Homonnai et al., 1980; Segenreich et al., 1986; Pryor & Howards, 1987). Recently, a new non-surgical method of varicocele treatment was introduced based on the selective catheterization of the left internal spermatic vein percutaneously, a procedure which allows the diagnostic procedure of venography, combined with definitive occlusion of the vein. his procedure has several advantages over the standard surgical approach. It can be performed on an outpatient basis with less expense and there is no need for general anaesthesia. It allows precise occlusion of the veins involved in varicocele formation with a low rate of recurrence (Riedl et al., 1981; White et al., 1981; Morag et al., 1984). he purpose of the present study was to evaluate the efficacy of the new embolization method of varicocele repair in terms of sperm quality and fecundity, compared to the conventional surgical methods. Materials and methods Patients One hundred and thirty-seven men underwent left-sided varicocelectomy because of varicocele-associated infertility. Men who had additional pathologies which might have interfered with fertility were not included in this study. One hundred and seven men (78%) suffered from primary infertility and 30 men (22%) from secondary infertility. All the female partners had undergone complete gynaecological evaluation, i.e., hormones, cervical mucus score, basal body temperature and hysterosalpingography. In a few cases, a laparoscopy was performed. Men whose partners were found to have any reproductive pathology were not included in this study. A full medical history was taken from each man and a physical examination was performed. Varicocele diagnosis he diagnosis of varicocele was made by an experienced andrologist. he patient was examined in the upright position. he reflux of blood into the scrotum was determined by manual palpation, while the patient performed the valsalva manoeuvre. his manoeuvre enabled the diagnosis of small varicoceles. he size of the varicocele was classified pre-operatively as large, moderate or small, according to

340 H. Yavetz et al. the definitions introduced by Dubin & Amelar (1975). his was verified using the radioactive technetium pertechnetate (c"") scanning technique (Merimsky et (11.. 1986). Semen analvsis wo semen specimens were obtained from each patient prior to treatment, with an interval of 2 weeks. Semen quality was checked every 3 months following treatment for at least 9 months, and there was 18 months follow-up of fecundity. Semen samples were obtained by masturbation after 3 days of sexual abstinence. he laboratory examination which was performed included semen volume and sperm quality. Sperm motility was assessed microscopically 1 h after ejaculation. A spermcytogram was performed using smeared ejaculate stained with haematoxylin and eosin. he cells were classified according to the World Health Organization definitions (WHO, 1980). Sperm concentration was estimated by counting in a haemocytometer (Paz et al., 1977). Varicocele ligationlsperrnatic vein ernbolization Following two semen examinations, patients with varicocele were assigned to one of three treatment procedures. Spermatic vein embolization (group A - 51 men) (Merimsky et al., 1986), or high ligation of the internal spermatic vein (group B - 43 men) using the techniques introduced by Ivanissevich (196O), or Bernardi (1947) (group C - 43 men). he Ivanissevich technique (I) was performed under general anaesthesia, and the veins were ligated very high, close to the iliac crest. he patients were hospitalized for several days. he Bernardi technique (B) was performed under local anaesthesia. he internal spermatic vein was ligated close to its exit from the inguinal ring. During the operation the patients were asked to perform the valsalva manoeuvre to aid in the detection of the veins. he patients were discharged on the day of operation. he embolization method was performed during a venography procedure using an HL Cerebral Catheter, 6.5 French (Cook Group Company, U.S.A.). he catheter was inserted into the right internal jugular vein and then via the right atrium into the inferior vena cava, and then via the left renal vein into the left spermatic vein. At the desired level in the spermatic vein, where no collateral vein bypassed this spot, 15 ml contrast material was injected during a valsalva manoeuvre to demonstrate the anatomical distribution of the veins and to ascertain the presence of the varicocele and of venous reflux. A single X-ray was taken to document the findings. hen one or two Gianturco coils, 3 or 5 mm wide according to the width of the vein, were inserted through the catheter (Cook's occluding spring embolus). Seririn FSH measurement Serum was prepared at the first interview for follicle stimulating hormone (FSH) determination by radioimmunoassay using commercial kits. Patient follow-up A follow-up of semen quality and varicocele recurrence (reappearance of the varicocele detected by the methods described above) was carried out for 18 months post-treatment.

~~ ~ Varicocele treatment-embolization versus ligation 341 Statistics Statistical analysis was performed by the statistics laboratory of the el Aviv University. Paired t-test was used to analyse the significance of differences for each semen variable during the study period (square-root transformations were used in order to normalize the variance). In order to compare the three treatment groups, analysis of variance was used. Results able 1 and Figure 1 summarize the results for serum FSH levels at admission and sperm analysis performed for each group during the study period. No differences were noted among the FSH levels of the three groups. Pretreatment sperm values are given as absolute values, and the changes from these basic values are depicted after 3, 6 and 9 months following treatment. here was no difference in pretreatment values between the three groups of men, apart from sperm morphology which was significantly better in group C (42 Ifr 19 vs. 27 k 15 and 34 k 20% in groups A and B respectively; P<0.01). During the 9 months of follow-up, a significant increase in sperm concentration and total sperm count was found in groups A and B, with no significant differences between these two groups. Sperm motility also improved in groups A and B, with the highest increase in group B at nine months after operation (P<0.05). Only in group B did sperm morphology improve, with the highest improvement being after 9 months (P<0.005). In group C, despite slight improvement in the total sperm count after 9 months, no further improvement was noted in all the other semen characteristics. Recurrence of varicocele was assessed in all three groups of men for 18 months following treatment (able 2). No significant differences were found among the groups. Minor complications were recorded post-varicocelectomy in seven able 1. Serum FSH levels at admission and sperm quality hefore treatment (P) and at 3. 6 and 9 months following either embolization or surgery by two different techniques (Ivanissevich B, and Bernardi C). Pretreatment values are the absolute numbers, while the change in the variables are given after 3, 6 and 9 months of follow-up. Results are mean f SD Sperm otal Sperm Sperm reatment conccntration sperm count motility morphology FSH group Sperm (10" mi-') (IO") ("/.I (% normal forms) (miu m1-i) A.enibolization P 9 i 10 30 F 41 30 i 15 27 i 1s 6.9 i 3.9 (PI = 51) 3 12 f ly*'<.? 35 i 6.73,' 7 i IS* 4 f 10" 6 9 i 17'.r 46 f 104": 9 f Ih" 2 f 17 9 15 i 1y:~'r' 61 F 11g.r.;::~ Si17 4fl6 B.varicocelectomy P 13 f 18 34 f 46 31 k 17 34 F 20 (n = 43) 3 13 * 2y*p 30 i 69:' 7 f IJ:i-* 4 2 13 7.1 i 4.1 6 9 1 I f 70'- 9 f 18"" 30 i Xi*" 2s f 528 h f 15": 11 * 17'" 10 F 19"'" 13 f 192*:::.? C.varicocelectnmy P 12 f 13 36 i 42 34 f 18 41 f 19 7.2 i 5.6 (n = 43) 3 7 f 26 21 k 70 3 f IS -1 k22 h 3 f 17 10 f 47 3 f I4-1 f 17 9 9 f 30 2' f 55'; 1 k I2-4k 14.'Pt0.05. **P io.005. :'""Pi0.001. compared with pretreatment values.

~ ~ ~ ~ :I p w 342 H. Yavetz et al. Concentration Varicocelectomy 1 Emboliration... 354...r I... Varicocelectomy B r 160 1211 100 c 4 80-60 otal count i.. 10 5 40 M 0 P 3 6 9 ime (months) 0 Motility Morphology I ime (months) P 3 6 9 P 3 6 9 P 3 6 9 ime (manms) Fig. 1. Sperm quality in relation to the method of treatment. P = pretreatment value. he numbers 3. 6 and 9 on the abscissa represent months following treatment. and the values shown are the differences from the pretreatment value. he variables measured are printed on the left upper part of each histogram. Numbers are means k SD. he number of patients in each group is given in able 1. he asterisks depict significant changes from pretreatment values as shown in able 1: ;P<O.OS; **f < O.OO5 ; * * * P < 0.000 1. able 2. Recurrence of varicocele according to the method of treatment Number of men Number of with recurrent Per cent Group reat men t men varicocele recurrence A Embolization 51 B Varicocelectomy 43 C (Ivanissevich) Varicocelectom y 43 (Bernardi) otal 137 12 24 16 37 15 35 43 31 patients. Of three patients in group A one developed an allergic reaction to the contrast media which necessitated antihistamine drug administration, and two other patients complained of left lower abdominal pain which lasted for two months. Wound infection developed in two cases out of 43 patients participating in group B. Among the patients in group C, a scrota1 haematoma developed in one, and in another patient an epididymitis necessitated anti-inflammatory treatment.

Varicocele treatment- embolization versus ligation 343 Fecundity is given in able 3. he couples included in this follow-up were only those who reported pregnancy during 18 months following treatment. A significant difference was found among the groups, with the lowest rate among patients being in group A, who were treated by embolization of the internal spermatic vein (P<0.05, compared with group B). able 3. Pregnancy rate of couples according to the method of treatment of the male partner Number of Number of pregnant Per cent Group reatment men women pregnant A Em bolization 34 B Varicocelectomy 34 C (Ivanissevich) Varicocelectom y 35 (Bernardi) otal 103 'Significantly higher than group A by Chi-squared test (P<O.OS). 7 13 9 29 20.6 38.2' 25.7 28.2 Discussion reating varicocele-associated infertility by embolization has many advantages theoretically. Besides its low cost and risk, it is performed under constant imaging of the veins at an optimal level and beyond the site of collateral veins. hus a low rate of recurrence of varicocele is expected. Indeed, several studies reported good results and low recurrence (White et al., 1981; Morag et al., 1984; Merimsky et al., 1986; Pryor & Howards, 1987). Sperm quality was reported to be improved (Riedl et al., 1981; Marsman, 1985) with a pregnancy rate ranging between 24-51%, (Riedl et al., 1981; Comhaire & Kunnen, 1985; Shuman et al., 1986). hese reports are rather disappointing because if the occlusion of the dilated veins is performed with accuracy at the optimal level, better results would be expected, or at least better than those reported in the literature after surgical management of varicocele. he present study was conducted in order to evaluate whether embolization has advantages over the traditional surgical ligation among our population in terms of sperm quality. recurrence of varicocele and pregnancy rate. he study failed to demonstrate any advantage of the embolization procedure, except for shorter hospitalization and less discomfort, which make this procedure more acceptable. No difference in the rate of recurrence was noted among the groups. While no change in sperm characteristics were noted in group C, in groups A and B sperm quality improved significantly. he highest degree of improvement was recorded in group B, in which all sperm parameters were better than in the other groups. he pregnancy rate in couples studied was significantly lower among the patients undergoing embolization compared to at least one surgical group - group B. hus, although the rate of recurrence was found to be the same. and despite the reduced amount of discomfort with embolization or the Bernardi operation. high ligation of the spermatic vein yields better results as far as sperm quality and pregnancy rates are concerned.

344 H. Yavetz et al. References Bernardi, R. (1947) Varicocele semiologia y cirugia. Editorial Liberia El Ateneo Buenos Aires, pp. 166-186. Comhaire, F. & Vermeulen, A. ( 1974) Varicocele sterility: cortisol and catecholamines. Fertility and Sterility, 25, 88-95. Comhaire, F. & Kunnen, M. (1985) Factors affecting the probability of conception after treatment of subfertile men with varicocele by transcatheter embolization with Bucrylate. Fertility and Sterility, 43, 781-786. Dubin, L. & Amelar, R. D. (1975) Varicocelectomy as a therapy in male infertility: a study of 504 cases. Journal of Urology, 113, 640-641. Homonnai. Z.. Fainman. N., Engelhard. Y.. Rudberg. Z.; David. M. & Paz, G. (1980) Varicocelectomy and male fertility: Comparison of semen quality and recurrence of varicocele following varicocelectomy by two techniques. Ititernalional Journal of Andrology, 3. 3-17-35 I. Hudson. R.. Perez-Marrero. R.. Crawford. V. & McKay. D. (1986) Hormonal paramcters in incidental varicocele and those causing infertility. Fertility und Sterili/v, 45. 691-700. Ito, H.. Fuse. H.. Minagawa. H.. Kawamura. K.. Murakami. M. 81 Shimnzaki, J. (19x2) Internal spermatic vein prostaglandins in varicocele patients. Fertility and S/erility, 37, 218-222. Ivanissevich. 0. (1960) Left varicocele due to reflux. Experience with 4470 operative cases in 42 years. Jo~irtial of Surgery. 34. 732-755. Marsman. J. ( 1985) Clinical versus subclinical varicocele: venographic findings and improvement of fertility after embolization. Radiology, 155. 635-638. Merimsky, E., Papo, J.. Zaltzman. S. & Braf. Z. (1986) High ligation or embolization of varicocele. Israel Journul of Medical Science, 22. 877-879. Morag, B.. Rubinstein, Z. J., Goldwasser. B.. Yerushalmi, A. & Lunenfeld, B. (198-1) Percutaneous venography and occlusion in the management of spermatic varicoceles. American Jotrrncrl of Roentgenology, 143. 635-6411. Nagao, R., Plymate, S., Berger. R.. Perin, E. & Paulsen. C. (1986) Comparison of gonadal function between fertile and infertile men with varicoceles. Fertility and Sterility. 46. 930-933. Paz, G.. Sofer, A.. Homonnai. Z.. & Kraicer, P. F. (1977) Human semen analysis. Seminal plasma and prostatic fluid compositions and their interrelation with sperm quality. Internutional Journal of Ferriliry. 22. 140-147. Pryor. J. & Howards. S. (1987) Varicocele. Urologic Clinics of North Americu, 14, 499-506. Riedl, P., Lunglmayr. G. & Stackl, W. (1981) A new method of transfemoral testicular vein obliteration for varicocele using a balloon catheter. Radiology. 139. 323-325. Sayfan, J.. Halevy. A.. Oland. J. & Nathan. H. (1984) Varicocele and left renal vein compression. Fertility and S/erifi/y, 41. 41 1-417. Segenreich. E.. Shmuely. H.. Singer. R. & Servadio. C. (1986) Andrological parameters in patients with varicocele and fertility disorders treated by high ligation of the left spermatic vein. International Journul of Fertility. 31, 200-203. Shafik. A,, Khalil. A. & Saleh, A. (1972) he fasciomuscular tube of the spermatic cord. Britixh Journul of Urology, 44, 147-151. Shuman, L., White, R.. Mitchell, S.. Kadi. S. L., Kaufman, S. & Change. R. (1986) Right-sided varicocele: technique and clinical results of balloon embolotherapy from the femoral approach. Radiology, 158. 787-791. White. R., Kaufman, S.. Barth. K.. Kadin. S.. Smyth. W. & Walsh. P. (1981) Occlusion of varicocele with detachable balloons. Radiology, 139. 327-335. World Health Organization (1980) Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction (eds Belsey, M. A,, Eliasson, R., Gallegos, A. J., Moghissi, K. S., Paulsen, C. A. and Prasad, M. R.), pp. 9-24. Press Concern, Singapore. Zorgniotti, A. & MacLeod, J. (1973) Studies on temperature, human semen quality, and varicocele. Fertility and Sterility, 24, 854-863, Received 20 June 1991; accepted 16 March 1992