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.
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).
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).
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.
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).
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).
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.
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.
Footnotes
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.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this study.
- Received February 25, 2022.
- Revision received May 27, 2022.
- Accepted June 14, 2022.
- Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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