Abstract
Background/Aim: Doppler ultrasound was successfully implemented as part of the diagnostic plan of medical emergencies in scrotal pathology. This study aimed to investigate whether it could play an important role in managing not only varicocele, but patients with secondary infertility as well.
Patients and Methods: The current study included 135 patients with varicocele and infertility. Surgery was performed in 18 cases with painful varicocele, 15 cases with testicular hypotrophy, and 48 cases with infertility.
Results: Among cases with infertility who underwent surgery, aged between 19 and 36 years old, 80% showed a significant improvement in the spermogram after curing the varicocele. In patients over 36 years of age, only 42% had some improvement in the spermogram after surgery. In addition, after surgery, antispermatic antibodies showed a significant decrease in all patients.
Conclusion: Varicocele and secondary infertility are a well-known pathology. While the role of Doppler ultrasonography is established in varicocele diagnosis, we found an important pool of patients with secondary infertility and asymptomatic varicocele that would not have been diagnosed in the absence of Doppler ultrasound investigations. Since the best results in fertility were observed in patients younger than 36 years of age, we reiterate the importance of Doppler ultrasonography in addressing infertility.
Keywords: Doppler, varicocele, infertility
Nowadays, ultrasonography has become a routine investigation for scrotal pathologies, being the first test after clinical examination in the evaluation protocol of the male genitalia. Along with the classical ultrasonography, the more modern modules, like color Doppler, and Pulsed and Power Angio, add more value in clearly defining the diagnosis. We might say that ultrasonography has an essential place both in determining therapy and monitoring its results.
Doppler ultrasonography is able to clearly identify several situations that are considered medical emergencies in the scrotal pathology, such as torsion of the spermatic funicle, avoiding important diagnostic delays, which could negatively impact the outcome and function of the genital organs. The development of modern Doppler modules, which are more sensitive, led to the possibility of more precise evaluation of scrotal vascularization and a more complete description of varicocele. These elements are of mainstay importance for an accurate diagnosis and follow up after surgical treatment. Varicocele is defined as a dilation of the veins of the pampiniform plexus, inducing a high flow of blood around the testis. It is well known that about 90% of all cases occur on the left side, due to the incompetence of the valvular mechanisms on the left spermatic vein. Varicocele could also occur on the right side, secondary to extrinsic compression of the spermatic vein on this side. Regardless of its localization, varicocele might lead to severe hypotrophy of the testis, inducing a decrease in the production of sperm, thus becoming one of the most important causes of infertility in young patients (1,2). Despite the fact that varicocele is well known to the medical world from the first century AD, when Celsius first described the association between the dilation of the veins and testicular atrophy, the continuous evolution of medical sciences has made the principles of diagnosis and treatment go through several stages and changes (1). The association between varicocele and male infertility was first described by Curling, who, in 1856 described the decrease in the output of the testis in patients with varicocele. The twentieth century brought new evidence of the strong interconnection between male infertility and varicocele. In 1955, the first series of patients with improvement in fertility after surgery for varicocele were reported (3). Today, varicocelectomy is widely used for improving fertility in patients with infertility. Ultrasonography is extremely useful in the examination of patients with varicocele, both for diagnosis and staging of the disease but also for follow up after treatment. The examination should be performed with the patient in both the standing and lying positions, because the varicocele, due to venous reflux, might become asymptomatic when the patient is not standing up. The Valsalva maneuver leads to the distension of the veins of the pampiniform plexus; it is known that in normal people, the maximal diameter of the veins is between 2 and 2.5 mm with the patient standing. After the valsalva maneuver, this diameter should not increase by more than 1 mm, any increase above this limit should be diagnosed as varicocele (3-5). In early stages, the varicocele is visualized as a bunch of tubular, transonic structures, presenting vascular flow during the Doppler exam. This flow increases after the valsalva maneuver. In advanced stages, ultrasonography shows large, serpent shaped images, with very low flow due to stasis. After valsalva, the flow becomes evident (6-8) (Figure 1 and Figure 2).
Figure 1. Left varicocele before valsalva maneuver – color Doppler ultrasound revealing the presence of serpent shaped images, with very low flow due to stasis.
Figure 2. Left varicocele after valsalva maneuver – color Doppler ultrasound revealing the fact that after valsalva, the flow becomes evident.
The severity of the reflux is divided into three degrees according to the number of the veins showing reflux after valsalva: less than one third, less than two thirds, more than two thirds. If the varicocele is due to obstruction, the valsalva maneuver shows no blood flow. There are very rare cases of vascular malformations, contributing to an increased flow varicocele (9-11). Doppler ultrasonography also demonstrates vascular dilations inside the testicle, which are not accessible to clinical examination but have a significant impact on fertility. Intratesticular varicocele and venous reflux after valsalva can be diagnosed only using Doppler ultrasonography (12,13). This study aimed to examine correlations between the clinical stage of varicocele and the grade of reflux measured by ultrasonography, and to identify any relations between these features and infertility.
Patients and Methods
The patients included in this study presented to the doctor either for clinical signs of varicocele or for fertility disorders. Some patients were referred by an endocrinologist, while others came directly to the urology department. The investigation protocol included clinical examination, lab tests including spermogram, and, in selected cases, more in-depth investigations, such as testicular biopsy. In all cases we performed standard and Doppler ultrasonography, with the patient standing and in the supine position. We included 135 patients in which varicocele was diagnosed. Of these, 129 patients had left side varicocele, while the other 6 had bilateral varicocele. We didn’t find any case with the disease confined to the right side. In all cases, a titration of antispermatic antibodies was performed. Varicocele was defined as a dilation of more than 2.5 mm of the veins in the standing position, and an increase by more than 1 mm after valsalva (Figure 3).
Figure 3. Significant vascular dilations diagnosed by Doppler ultrasound; the presence of venous stasis is evident.
According to the grade of dilation of the veins, varicocele was divided into three clinical stages: stage I varicocele: venous dilations of less than half the volume of the testis; stage II varicocele: venous dilations with the volume of the testis; stage III varicocele: venous dilations with a volume superior to the testicular volume. Doppler ultrasonography added a new dimension to the diagnosis by evaluating the grade of the venous reflux after valsalva: grade I reflux: reflux in less than one third of the dilated veins, grade II reflux: reflux in less than two thirds of the dilated veins; grade III reflux: reflux in more than two thirds of the dilated veins (Figure 1).
Results
Out of the 135 patients with clinical varicocele, 36 had stage I varicocele, 54 had stage II varicocele, and 45 had stage III disease. In the group with stage II and III varicocele, 12 cases also presented intratesticular varicocele, and the intratesticular dilated veins could only be diagnosed using Doppler ultrasound.
According to the severity of the venous reflux after valsalva, 30 patients had grade I reflux, 48 patients had grade II, and 57 patients had grade III reflux (Figure 4). No direct correlation was observed between the clinical stage of varicocele and the grade of reflux recorded on Doppler ultrasonography.
Figure 4. Grade of reflux after the Valsalva maneuver: According to the severity of the venous reflux after valsalva, 30 cases had grade I reflux, 48 cases had grade II reflux while the remaining 57 patients had a grade III reflux.

In the stage I varicocele series: 9 patients (25%) presented grade I reflux, 15 patients (41%) presented grade II reflux and 12 patients (34%) presented grade III reflux. In the stage II varicocele series: 12 cases (22%) had grade I reflux, 18 cases (33%) had grade II reflux while the remaining 24 cases (45%) had grade III reflux. In the last series, with stage III varicocele: 9 patients (20%) presented grade I reflux, 15 patients (33%) presented grade II reflux while the remaining 21 patients (47%) presented grade III reflux (Figure 5).
Figure 5. Correlation between clinical stage and reflux grade measured by ultrasonography: Among patients diagnosed with stage 1 varicocele there were nine cases with first degree lesions, 15 cases with second degree lesions and 12 cases with third degree lesions. When it comes to stage 2 varicocele there were 122 cases with first degree lesions, 18 cases with second degree lesions and 24 cases with third degree lesions. The remaining 45 patients were diagnosed with first degree lesions in 9 cases, second degree lesions in 15 cases and third degree lesions in 21 cases.

All the patients with intratesticular varicocele (6 cases were in stage II and other 6 were in stage III) presented grade III reflux. Out of the 135 patients with clinical symptomatic varicocele, 48 (35%) presented infertility. In all of these patients, infertility was associated with several disorders of the spermogram. In 30 patients (62.5%), high values of antispermatic antibodies were identified. In 48 patients with varicocele and infertility, 36 presented grade III reflux (and 12 intratesticular varicocele) and 12 had grade II reflux. Nine patients were in stage I, 15 in stage II and 24 in stage III. The statistical analysis demonstrated that infertility is better correlated with the grade of reflux than with the stage of varicocele (Figure 6, Figure 7 and Figure 8).
Figure 6. The presence of antispermatic antibodies: antispermatic antibodies were found in 62% of cases while in the remaining 38% of cases these antibodies were not found.

Figure 7. Correlation between reflux grade and fertility: 25% of patients with grade I reflux and 75% of patients with grade II reflux presented infertility, demonstrating therefore the strong correlation ship between the two parameters.

Figure 8. Correlation between clinical stage and fertility: Among the 48 cases diagnosed with infertility, there were nine cases diagnosed with first stage varicocele, 15 cases diagnosed with second stage varicocele, and 24 cases with stage 3 varicocele respectively.

Surgery was indicated and performed in the following situations: painful varicocele in 18 cases, testicular hypotrophy in 15 cases and infertility in 48 cases.
Among cases submitted to varicocele surgery for infertility (48 cases), the patients’ age ranged between 19 and 46 years old. Among these cases, 80% showed a significant improvement in the spermogram after curing the varicocele. In patients aged over 36 years old, only 42% had some improvement in the spermogram after surgery. In the series of patients with painful varicocele, a successful surgery led to the complete remission of all symptoms, while in the series with testicular hypotrophy, after surgery, 6 patients showed no improvement in the testicular structure and size after 12 months, whereas in 9 cases the testicle grew to 3-5 mm after 12 months (Figure 9, Figure 10 and Figure 11). After surgery, antispermatic antibodies showed a significant decrease in all patients.
Figure 9. Intratesticular varicocele before valsalva maneuver: Following surgery, significant diminish in the degree of intratesticular varicocele was demonstrated.
Figure 10. Intratesticular varicocele after valsalva maneuver: the venous flow is evident.
Figure 11. Postoperative improvement in the spermogram according to age. A) Among patients younger than 36 years of age, 80% of them reported a significant improvement in spermogram after surgery. B) The influence of the surgical procedure on the spermogram in patients over 36 years of age. Red: patients reporting a significant improvement of spermogram after surgery for varicocele. Blue: cases in which the spermogram did not significantly improve after surgery for varicocele.
Discussion
Data from the literature support the improvement in the spermogram after surgery for varicocele (14). Anyhow, the reported numbers vary greatly from one author to the other, both concerning the improvements in the sperm quality and the number of carriages induced after surgery. A metaanalysis evaluating 2,989 patients showed improvements in sperm quality in 71% cases, but clearly stated that only 37% of the subjects were actually able to father children after surgery (15).
A study dating back in 2001, reports a postoperative rate of induced carriages of 61% for men with at least 5 million spermatocites/ml, compared to only 8% if the number of spermatocites is lower (16). Another metaanalysis on 120 patients with surgery for varicocele and 117 patients in the control group demonstrates a rate of induced carriages of 36.4% after surgery compared to only 20% in the control group (17).
The American Urological Association recommends that surgery for varicocele is to be indicated and performed only if the couple cumulates the following four conditions:female partner with no or curable infertility, complete investigation of couple infertility, symptomatic varicocele or ultrasonographicaly diagnosed or pathological alteration on spermogram (18-22).
Despite the classical concept according to which the test simulating GnRH secretion could be useful in evaluating postoperative success, recent data strongly argue against this principle, making the test more useful for research than for daily practice (23). The identification of such factors that could predict the capacity of inducing pregnancy after surgery might narrow the area of surgical indications for varicocele, avoiding surgeries that have no chance of improving fertility. Marks et al. identified four factors with potential contributions in improving postoperative results: no testicular atrophy, over 50 million sperm cells in the ejaculate, over 60% mobility and an FSH level below 330 ng/ml (15).
The continuous development of micro Doppler devices allowed improvements in the surgical technique by real time monitoring of the blood flow speed in the spermatic veins. With the use of such equipment during micro-surgical intervention for varicocele cure the surgeon is able to ligate a significant number of vessels, while preserving the permeability of the spermatic artery (24). This way, therapeutic efficacy increases, whereas the rate of subsequent complications decreases (25).
Conclusion
Due to the development of microsurgery and Doppler ultrasonography a new era and a new perspective arise in the approach of male patients with varicocele and infertility. Color Doppler ultrasonography is extremely useful in appreciating postoperative success by demonstrating the disparition of the venous reflux after valsalva. If the reflux is still present, it is considered that surgery cannot intercept all the spermatic veins. In this case, a laparoscopic approach becomes the best option, due to the better image of the veins, which might be involved. The level of antispermatic antibodies decreases significantly after the surgical cure of varicocele in most cases. In infertile males with varicocele, the spermogram is improved significantly after surgery in most cases. The diagnosis and surgical treatment of varicocele should take place before 36 years of age in infertile males. The identification of infraclinical varicocele, of intratesticular varicocele and the measuring of reflux after surgery makes doppler ultrasonography an indispensable state of the art tool for the modern urologist.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
Authors’ Contributions
VC, IC, CP – performed the surgical procedures; CS, IB – performed literature review, NB performed data analysis; IC, CP and IB prepared the draft of the manuscript; VC and NB reviewed the final version of the manuscript. All patients read and approved the final version.
References
- 1.Lipshultz LI, Jarow JP. Philadelphia, J.B. Lippincott. 1989. Varicocele and male subfertility. In: Gynecology and obstetrics. Speroff SJ (ed.) p. pp. 1. [Google Scholar]
- 2.Schurich M, Aigner F, Frauscher F, Pallwein L. The role of ultrasound in assessment of male fertility. Eur J Obstet Gynecol Reprod Biol. 2009;144 Suppl 1:S192–S198. doi: 10.1016/j.ejogrb.2009.02.034. [DOI] [PubMed] [Google Scholar]
- 3.Stahl P, Schlegel PN. Standardization and documentation of varicocele evaluation. Curr Opin Urol. 2011;21(6):500–505. doi: 10.1097/MOU.0b013e32834b8698. [DOI] [PubMed] [Google Scholar]
- 4.Bertolotto M, Cantisani V, Drudi FM, Lotti F. Varicocoele. Classification and pitfalls. Andrology. 2021;9(5):1322–1330. doi: 10.1111/andr.13053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Hoekstra T, Witt MA. The correlation of internal spermatic vein palpability with ultrasonographic diameter and reversal of venous flow. J Urol. 1995;153(1):82–84. doi: 10.1097/00005392-199501000-00029. [DOI] [PubMed] [Google Scholar]
- 6.Macchi V, Porzionato A, Iafrate M, Ebugheme E, Paoli A, Vigato E, Parenti A, Ficarra V, Artibani W, De Caro R. Morphological characteristics of the wall of pampiniform plexus veins and modifications in patients with varicocele. Ital J Anat Embryol. 2008;113(1):1–8. [PubMed] [Google Scholar]
- 7.Beck EM, Schlegel PN, Goldstein M. Intraoperative varicocele anatomy: a macroscopic and microscopic study. J Urol. 1992;148(4):1190–1194. doi: 10.1016/s0022-5347(17)36857-x. [DOI] [PubMed] [Google Scholar]
- 8.Kathrins M. Historical investigations into varicocele pathophysiology and sperm migration. Fertil Steril. 2018;109(1):75–76. doi: 10.1016/j.fertnstert.2017.11.007. [DOI] [PubMed] [Google Scholar]
- 9.Cimador M, Castagnetti M, Gattuccio I, Pensabene M, Sergio M, De Grazia E. The hemodynamic approach to evaluating adolescent varicocele. Nat Rev Urol. 2012;9(5):247–257. doi: 10.1038/nrurol.2012.41. [DOI] [PubMed] [Google Scholar]
- 10.Shin JI, Lee JS. Comment on: Anatomic and hemodynamic evaluation of renal venous flow in varicocele formation using color Doppler sonography with emphasis on renal vein entrapment syndrome (Scand J Urol Nephrol 2007; 41(1): 42-6) Scand J Urol Nephrol. 2008;42(2):175. doi: 10.1080/00365590801945394. author reply 176. [DOI] [PubMed] [Google Scholar]
- 11.Bakirtas H, Cakan M, Tuygun C, Soylu SO, Ersoy H. Is there any additional benefit of venous diameter and retrograde flow volume as measured by ultrasonography to the diagnosis of suspected low-grade varicoceles. Urol Int. 2009;82(4):453–458. doi: 10.1159/000218537. [DOI] [PubMed] [Google Scholar]
- 12.Skiadas V, Ladopoulos C, Primetis E, Kalovidouris A, V K, Vlahos L. Ultrasound findings of an intratesticular varicocele. Report of a new case and review of the literature. Int Urol Nephrol. 2006;38(1):115–118. doi: 10.1007/s11255-005-0915-8. [DOI] [PubMed] [Google Scholar]
- 13.Bucci S, Liguori G, Amodeo A, Salamè L, Trombetta C, Belgrano E. Intratesticular varicocele: evaluation using grey scale and color Doppler ultrasound. World J Urol. 2008;26(1):87–89. doi: 10.1007/s00345-007-0216-1. [DOI] [PubMed] [Google Scholar]
- 14.Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelectomy. A critical analysis. Urol Clin North Am. 1994;21(3):517–529. [PubMed] [Google Scholar]
- 15.Marks JL, McMahon R, Lipshultz LI. Predictive parameters of successful varicocele repair. J Urol. 1986;136(3):609–612. doi: 10.1016/s0022-5347(17)44990-1. [DOI] [PubMed] [Google Scholar]
- 16.Kamal KM, Jarvi K, Zini A. Microsurgical varicocelectomy in the era of assisted reproductive technology: influence of initial semen quality on pregnancy rates. Fertil Steril. 2001;75(5):1013–1016. doi: 10.1016/s0015-0282(01)01698-3. [DOI] [PubMed] [Google Scholar]
- 17.Pamplona Casamayor M, Duarte Ojeda JM, Villar Esnal R, Bolea Laguarta MA, de la Cruz Bértolo J, Alvarez González E, Rodríguez Antolin A, Leiva Galvis O. [The treatment of varicocele in the infertile male I: results on semen quality] Arch Esp Urol. 2004;57(9):969–980. [PubMed] [Google Scholar]
- 18.Male Infertility Best Practice Policy Committee of the American Urological Association , Practice Committee of the American Society for Reproductive Medicine Report on varicocele and infertility. Fertil Steril. 2004;82 Suppl 1:S142–S145. doi: 10.1016/j.fertnstert.2004.05.057. [DOI] [PubMed] [Google Scholar]
- 19.Cho CL, Esteves SC, Agarwal A. Indications and outcomes of varicocele repair. Panminerva Med. 2019;61(2):152–163. doi: 10.23736/S0031-0808.18.03528-0. [DOI] [PubMed] [Google Scholar]
- 20.Zampieri N. Varicocele and varicocelectomy: Which news from the past. Arch Ital Urol Androl. 2021;93(4):499–500. doi: 10.4081/aiua.2021.4.499. [DOI] [PubMed] [Google Scholar]
- 21.Pagani RL, Ohlander SJ, Niederberger CS. Microsurgical varicocele ligation: surgical methodology and associated outcomes. Fertil Steril. 2019;111(3):415–419. doi: 10.1016/j.fertnstert.2019.01.002. [DOI] [PubMed] [Google Scholar]
- 22.Punjani N, Wald G, Gaffney CD, Goldstein M, Kashanian JA. Predictors of varicocele-associated pain and its impact on semen parameters following microsurgical repair. Andrologia. 2021;53(8):e14121. doi: 10.1111/and.14121. [DOI] [PubMed] [Google Scholar]
- 23.O’Brien J, Bowles B, Kamal KM, Jarvi K, Zini A. Does the gonadotropin-releasing hormone stimulation test predict clinical outcomes after microsurgical varicocelectomy. Urology. 2004;63(6):1143–1147. doi: 10.1016/j.urology.2004.01.044. [DOI] [PubMed] [Google Scholar]
- 24.Cocuzza M, Pagani R, Coelho R, Srougi M, Hallak J. The systematic use of intraoperative vascular Doppler ultrasound during microsurgical subinguinal varicocelectomy improves precise identification and preservation of testicular blood supply. Fertil Steril. 2010;93(7):2396–2399. doi: 10.1016/j.fertnstert.2009.01.088. [DOI] [PubMed] [Google Scholar]
- 25.Ficarra V, Cerruto MA, Liguori G, Mazzoni G, Minucci S, Tracia A, Gentile V. Treatment of varicocele in subfertile men: The Cochrane Review—a contrary opinion. Eur Urol. 2006;49(2):258–263. doi: 10.1016/j.eururo.2005.11.023. [DOI] [PubMed] [Google Scholar]






