Right varicocelectomy in selected infertile patients who have failed to improve after previous left varicocelectomy*

FERTILITY AND STERILITY Copyright L 1987 The American Fertility Society Printed in U.s.A. Right varicocelectomy in selected infertile patients who have failed to improve after previous left varicocelectomy* Richard D. Amelar, M.D.t Lawrence Dubin, M.D. Department of Urology, New York University Medical Center, New York, New York In the past 8 years we found 41 infertile men with poor semen quality in whom an overlooked right varicocele might have been the reason for failure to improve after previous left varicocelectomy. None had ever fathered a child. After we performed sequential right varicocelectomy in these 41 patients, semen quality improved in 23 (56%). Twenty-seven pregnancies have been achieved to date by the wives of 18 (43%) of the patients whose semen improved. No pregnancies were caused by those whose semen failed to improve. Infertile men should be carefully examined for varicoceles on both sides, and bilateral varicocelectomy should be performed when indicated. Selected infertile patients who have failed to improve after left varicocelectomy and are found subsequently to have a right varicocele may yet improve following correction of the right varicocele. Fertil Steril 47:833, 1987 In our urologic practice, which is devoted entirely to male infertility problems, patients are occasionally referred to us after failure of their semen quality to improve following a left varicocelectomy performed elsewhere. Some of these patients who preoperatively had severe oligospermia subsequently improved and fathered children after we treated them empirically with a supplemental course of human chorionic gonadotropin (hcg) injections. 1 2 From 1978 through 1984, we saw 41 patients with normal endocrine studies who had persistent poor semen quality and infertility after an anatomically satisfactory left varicocelectomy in whom we diagnosed the presence of a right varicocele. None of the patients had ever fathered any Received August 14, 1986; revised and accepted January 14, 1987. *Presented at the Forty-Second Annual Meeting of The American Fertility Society and the Eighteenth Annual Meeting of the Canadian Fertility and Andrology Society, September 27 to October 2, 1986, Toronto, Canada. treprint requests: Richard D. Amelar, M.D., 137 East 36th Street, New York, New York 10016. children. Right varicocelectomy was performed as further therapy for their infertility, the reasoning being that this overlooked right varicocele might be the cause of failure of improvement after left varicocelectomy. This article reports our results in the treatment of these 41 patients. MATERIALS AND METHODS A careful history was taken and a complete physical examination performed on each patient, with the techniques and survey summary form we have described. 3 Each patient was examined by both authors and by one of various New York University urology residents assigned on rotation for a 3-month elective in our practice. These selected patients all had testicles that were judged normal in size. The epididymides and vasa deferentia of all patients were normal to palpation bilaterally, except in one patient who had an absent left vas deferens. Patients were examined while standing upright and nude in a warm examining room, with Amelar and Dubin Sequential varicocelectomy 833

and without Valsalva maneuver during palpation for varicoceles on both sides, and the varicoceles were classified as small, moderate, or large in size. 4 Preoperative and postoperative semen analyses were performed at Fertility Laboratory, Inc., New York City, using our modification 5 of the method of MacLeod. 6 We have defined improvement as a significant change for the better in overall semen quality that would be expected by a clinician to result in significantly improved fertility potential for any given patient, all other factors being equal. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were measured by radioimmunoassays. The range of normal laboratory values for the hormonal assays are as follows: FSH, 3 to 18 miu/ml; LH, 3 to 18 miu/ml; and T, 0.25 to 1.0 mg/dl. Right varicocelectomy was performed with our modification of the Ivanissevich procedure for inguinal ligation of the right internal spermatic veins. 7,8 Two or three semen analyses were performed on each patient preoperatively. After the right varicocelectomy those patients with preoperative sperm counts> 10 x 106/ml were requested to have follow-up semen analyses starting 3 months postoperatively and every 3 months thereafter. On the basis of our previously reported experience, l those patients who had preoperative sperm counts averaging < 10 x 106/ml were given a supplemental series of hcg injections, 2000 to 4000 U twice weekly starting 1 week postoperatively for 10 weeks, and semen analyses were requested every 3 months commencing after the hcg injections were completed. Additionally, five of those patients who had preoperative sperm counts> 10 x 106/ml and whose semen quality did not improve significantly within 6 months were also given supplemental hcg injections, 2000 to 4000 U twice weekly for 10 weeks. 2 Each patient was followed for at least 18 months postoperatively. One patient refused to have postoperative semen analyses and was lost to follow-up. Another patient was fitted with a scrotal hypothermia device 6 months postoperatively. RESULTS From 1978 through 1984, we performed right varicocelectomy in 41 selected patients in whom 834 Amelar and Dubin Sequential varicocelectomy we diagnosed a previously overlooked right varicocele and who had failed to improve after a left varicocelectomy that had been performed elsewhere. These patients were all followed for at least 18 months after the right varicocelectomy. The results are presented as of July 1986.* The patients had an average age of 35.3 years when the right varicocele was diagnosed (range, 23 to 48 years). Semen quality improved in 23 (56%), and pregnancies occurred in 18 (43%). Of these, nine patients each caused 2 pregnancies, for a total of 27 pregnancies. So far, there have been 13 sons, 11 daughters, and 3 miscarriages. In those patients in whom semen quality improved, the improvement was usually apparent within 6 months after completion of treatment and was so recorded. The miscarriages all occurred as first pregnancies, and in each case the miscarriage was followed by a full-term pregnancy. The average time after the right varicocelectomy for the conception of the first "good" pregnancy (i.e., one not ending in miscarriage) was 8.4 months (range, 4 to 15 months). Although there was no possible control group for this selected series of 41 patients, it must be mentioned that none of the patients had fathered any children before the sequential right varicocelectomy and that there were no pregnancies caused by any of the 18 men (44%) whose semen quality failed to improve. Twenty-one of the 41 patients received no additional therapy after the right varicocelectomy. In this group, 18 improved and of these, 15 succeeded in becoming fathers. One of the patients refused follow-up semen analyses and has been lost to follow-up. For this study he is considered not to have improved or caused pregnancy. Another patient had a splendid improvement in semen quality after right varicocelectomy but was divorced shortly thereafter, and his new fertility potential has not been realized. Nineteen patients were given supplemental therapy in the form of intramuscular injections with hcg (in doses of 2000 to 4000 U twice weekly for 10 weeks). Thirteen of these patients had preoperative sperm counts averaging < 10 x 10 6 /ml, and 3 of these 13 caused pregnancies re- *Tabular material including details of preoperative and postoperative semen analyses and endocrine tests and results for each of the 41 patients is available from the authors on request. Fertility and Sterility

suiting in the births of four children and one miscarriage. After the fathers had received supplemental hcg therapy, all of the children conceived were female. The sex of the conceptus in the early miscarriage is unknown. There was improvement but no pregnancy in one patient whose wife has endometriosis, and in the patient who incidentally had congenital absence of the left vas and a solitary right kidney.9 Besides the 13 severely oligospermic patients who were given supplemental hcg injections starting immediately postoperatively, an additional 6 patients were given supplemental hcg injections when they exhibited no improvement in their semen quality within 3 to 6 months after the right varicocelectomy, and none of these had any subsequent improvement in their semen quality. One patient whose semen quality failed to improve was subsequently fitted with a scrotal hypothermia device 10 that he wore for 8 months without any benefit. Another patient had received hcg injections and then wore a scrotal hypothermia device without benefit in 1983, following the previous left varicocelectomy. This was followed by striking improvement in his poor semen quality and a pregnancy within 6 months after correction of his previously overlooked right varicocele. One patient had an upper-normal semen volume with severe oligospermia preoperatively and received supplemental hcg injections after his right varicocelectomy (as well as after the previous left varicocelectomy). There was a significant improvement in sperm numbers, motility, and morphology. Split ejaculate studies revealed an excellent first fraction, and a daughter was conceived with the couple using the withdrawal coital technique. ll 12 Pregnancies were also achieved with the withdrawal coital technique in two additional couples. Artificial insemination by husband (AIH) with the good first fraction of split ejaculates has been tried several times in a patient whose wife has endometriosis. The couple is now waiting to be accepted into an in vitro fertilization (lvf) program. Severe endometriosis has also been found to be the factor now preventing pregnancy in the wife of another patient whose semen quality had great improvement. Hamster ova sperm penetration assays have been excellent, but there has been no pregnancy after two cycles of IVF. One patient had marked improvement in his semen quality after right varicocelectomy and a postoperative series of hcg injections, with conception occurring 11 months after surgery. A right hydrocele developed in the patient, and he had a right hydrocelectomy performed 1 year after the birth of his daughter. This right hydrocele was the only complication of right varicocelectomy encountered in this series. The age of the infertile men with varicocele in this series ranged from 23 to 48 years. The oldest patient in our series had an excellent result. He was 48 years old when he was first seen and had a passable sperm count, but poor sperm motility and very poor morphology. He had previously been treated elsewhere with left varicocelectomy, followed by therapy with fiuoxymesterone, then doxycycline (although no infection had been demonstrated), and then a series ofhcg injections, all without benefit. He had significant improvement in his semen quality 3 months after the right varicocelectomy and now has two sons born after our surgery. At the other age extreme in this series, there was no improvement in the very poor semen quality of our 23-year-old patient, whose FSH level was in the upper-normal range. We have reported our experience that the size of a varicocele as judged preoperatively has no relation to the expected results after varicocelectomy.4 In this series of patients, the right varicocele was considered to be moderate in size in 31 (76%) of the 41 patients. Of these, semen quality improved in 18 (58%), and pregnancies occurred in 15 cases (48%). In 10 (24%) of the 41 cases, the right varicocele was judged to be small in size preoperatively. Of these, semen quality improved in 5 (50%), and 4 (40%) achieved pregnancies. There were no large right varicoceles in this series. Looking at the results in relation to size of the right varicocele in these 41 patients from another perspective, of the 23 patients in the series who improved, 18 (78%) had moderate-sized varicocele and 5 (22%) small varicoceles. Of the 18 patients who did not improve after right varicocelectomy, 13 (72%) had moderate-sized varicoceles and 4 (28%) had small varicoceles. Thus the results in relation to varicocele size in this series lend support to our observation that the size of the varicocele as judged preoperatively has no significant relation to the expected results after varicocelectomy. We have also reported our experience that results in a large series of varicocelectomy patients Amelar and Dubin Sequential varicocelectomy 835

were much better when preoperative sperm counts were> 10 x 106/ml than when patients were severely oligospermic with sperm counts < 10 x 106/ml.1 This experience is also reflected in this current series of right varicocelectomies, in which 28 of the 41 patients had preoperative sperm counts> 10 x 106/ml. Of these 19 (68%) had improved semen quality, and 15 (54%) had fathered children. Our results indicate that the supplemental use of hcg in this series has not been helpful when given later to any of the patients who had preoperative sperm counts> 10 x 106/ml and who had failed to improve after right varicocelectomy. HCG injections were not effective as "salvage therapy" in this group. Thirteen of the 41 patients had preoperative sperm counts < 10 x 106/ml, and because of our reported experience,l all of them were given a supplemental series of hcg injections postoperatively. The semen quality of 4 of the 13 patients (31%) improved, and 3 men (23%) fathered children. DISCUSSION Varicocele has been described as occurring predominantly on the left side, and the classic early radiographic studies by Brown et al. 13 and subsequent studies by Riedl14 concentrated on the anatomy of the left internal spermatic vein. Chatel et al. 15 in Paris in 1978 set out to study the right internal spermatic vein as well as the left but occasionally encountered difficulty visualizing the right internal spermatic vein using their transfemoral catheterization approach. They were able to demonstrate right-sided reflux in 60% of 76 men with a clinical left varicocele. To circumvent the difficulty of venographic ally visualizing the right internal spermatic vein imposed by the transfemoral technique, Narayan et al. 16 employed percutaneous transjugular venography of the internal spermatic veins on both sides. They also found right-sided reflux in 60% of 14 men with clinical left varicoceles, and they postulated that the bilateral effects of left-sided clinical varicoceles might not be due to crosscommunication, but to unrecognized bilateral reflux. Subsequently, Gonzalez et al.17 at the same center using transjugular venography reported 836 Amelar and Dubin Sequential varicocelectomy demonstrating a 61% incidence of bilateral reflux in 39 infertile patients. However, transjugular venography of the internal spermatic veins with the catheter traversing the heart is not a procedure to be undertaken lightly and is not recommended for most patients. In 1982, Bigot et al.18 (in an extension of the work reported by Chatel et al. in 197815) using transfemoral venography with Val salva maneuver in supine patients reported that the last 100 varicoceles they had demonstrated by phlebography were as follows: bilateral varicoceles, 53; left unilateral varicoceles, 27; and right unilateral varicoceles, 20. They suggested that an overlooked varicocele on the right side could be the cause of failure to obtain clinical improvement following left varicocelectomy in some patients. The clinical diagnosis of varicocele is not always a simple matter. In our practice we rely on careful palpation. Contact scrotal thermography using the Clark Topical Thermograph (Clark Research and Development, Inc., New Orleans, LA) has been a useful supplemental diagnostic tool,19, 20 but for this study we have relied entirely on our careful palpation for making the decision about whether or not a patient had a varicocele and whether it was small, moderate, or large in size. Patients must be examined in the upright position because all but very large varicoceles will be overlooked because of venous decompression if the patient is supine. Reflux of blood down the internal spermatic veins into the scrotum should be determined by careful palpation of both left and right spermatic cords while the standing patient performs the Valsalva maneuver.21 This maneuver is extremely important because small varicoceles will not be diagnosed without it, and correct bilateral therapy will not be suggested. If by this method of careful palpation we cannot detect a varicocele, we do not diagnose a varicocele in that patient. We have not subscribed to the existence of the so-called subclinical varicocele that cannot be detected by careful palpation with the Valsalva maneuver. With this method of careful palpation for diagnosis, as well as the criteria of characteristic poor semen quality and lack of demonstrable endocrinopathy, we have reported that in the 2-year period from January 1980 through December 1981, we performed 870 varicocelectomy procedures, Fertility and Sterility

and of these 490 cases (56%) were bilateral, while 347 (40%) were on the left side, and 33 (4%) were on the right side. 22 In a~other comtemporary series, Cockett et a1. 23 reported that during the years 1979 to 1983 they performed 130 varicocelectomy procedures, and of these, 81 cases (62%) were bilateral while 49 (38%) were on the left side. We, and others, are certainly giving greater attention now than in the past decades to the examination of the patient for varicocele on the right side as well as on the left side, and it seems likely that many right-sided varicoceles may have been overlooked in the past, when the incidence of right-sided varicocele in infetile men was thought to be no more than about 15%Y Most recently in 1986, McClure and Hricak 24 studied 50 infertile men using scrotal sonography and found that 24 (48%) had bilateral varicoceles as detected with ultrasound (as opposed to an 8% incidence of bilateral varicoceles in fertile controls). Thus, from a large number of studies including our own, it now appears that the incidence of bilateral varicoceles in infertile men with varicocele may be around 50% to 60%. Infertile men should be carefully examined for varicoceles on both sides, and bilateral varicocelectomy should be performed when indicated. Furthermore, we have demonstrated that selected infertile patients who have failed to improve after left varicocelectomy and are found subsequently to have a right varicocele may yet improve after correction of the right varicocele. REFERENCES 1. Dubin L, Amelar RD: 986 cases of varicocelectomy: a 12 year study. Urology 10:446, 1977 2. Samburg I, Zilberman A, SharfM: The value ofhcg after varicocelectomy in severely oligospermic men. In Varicocele and Male Infertility II, Edited by M Glezerman, EW Jecht. Berlin, Springer-Verlag, 1984, p 111 3. Amelar RD, Dubin L: Examining the patient. In Male Infertility, Edited by RD Amelar, L Dubin, PC Walsh. Philadelphia, WB Saunders, 1977, p 141 4. Dubin L, Amelar RD: Varicocele size and results ofvaricocelectomy in selected subfertile men with varicocele. Fertil Steril 21:606, 1970 5. Amelar RD, Dubin L, Schoenfeld C: Semen analysis. Urology 2:605, 1973 6. MacLeod J: The semen examination. Clin Obstet Gynecol 8:115,1965 7. Dubin L, Amelar RD: The varicocele and infertility. In Male Infertility, Edited by RD Amelar, L Dubin, PC Walsh. Philadelphia, WB Saunders, 1977, p 57 8. Stewart BH: The Amelar-Dubin approach to varicocele repair. In Urologic Surgery. Third edition. Edited by JF Glenn. Philadelphia, JB Lippincott, 1983, p 1093 9. Amelar RD, Dubin L: Importance of careful palpation of vas deferens. Urology 4:495, 1974 10. Zorgniotti AW, Cohen MS, Sealfon AT: Chronic scrotal hypothermia: results in 90 infertile couples. J Urol 135: 944, 1986 11. Amelar RD, Hotchkiss RS: The split ejaculate; its use in the management of male infertility. Fertil Steril 16:46, 1965 12. Amelar RD, Dubin L: A new method of promoting fertility. Obstet Gynecol 45:56, 1975 13. Brown JS, Dubin L, Becker M, Hotchkiss RS: Venography in the subfertile man with varicocele. J UroI98:388, 1967 14. Riedl P: Selektive phlebographie und katheterthrombosierung der vena testicularis bei primarer varikocele. Wien Klin Wochenschr (Suppll 91:99, 1979 15. Chatel A, Bigot JM, Helenon CH, Dectot H, Rotman J, Salat-Baroux J: Interet de la phlebographie spermatique dans Ie diagnostic des sterilites d'orgine circulatoire (varicocele). Comparison avec les donnees cliniques thermographieques et anatomiques. Ann Radiol (Paris) 21:565, 1978 16. Narayan P, Amplatz K, Gonzalez R: Varicocele and male subfertility. Fertil Steril 36:92, 1981 17. Gonzalez R, Reddy P, Kaye KW, Narayan P: Comparison of Doppler examination and retrograde spermatic venography in the diagnosis of varicocele. Fertil Steril 40:96, 1983 18. Bigot JM, Barret F, Henelon C: Phlebography ofthe right spermatic vein in varicoceles. In Varicocele and Male Infertility, Edited by EW Jecht, E Zeitler. Berlin, Springer-Verlag, 1982, p 59 19. Comhaire F, Monteyne R, Kunnen M: The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of "subclinical" varicocele. Fertil Steril 27:694, 1976 20. Lewis RW, Harrison RM: Contact scrotal thermography. II. Use in the infertile male. Fertil Steril 34:259, 1980 21. Amelar RD: Infertility in Men. Philadelphia, FA Davis, 1966 22. Amelar RD, Dubin L: Infertility in the male. In Practice of Surgery (Urology), Edited by R Kendall, L Kerafin. Philadelphia, Harper & Row, 1984, vol 2, chap 21, p 43 23. Cockett ATK, Takihara H, Consentino MJ: The varicocele. Fertil Steril 41:5, 1984 24. McClure RD, Hricak H: Scrotal ultrasound in the infertile man: detection of subclinical unilateral and bilateral varicoceles. J Urol 135:711, 1986 Amelar and Dubin Sequential varicocelectomy 837