Document Type : Original Article
Authors
1 Department of Urology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2 Shahid Beheshti University of Medical Sciences, Faculty of Public Health, Tehran, Iran
3 Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran
Abstract
Keywords
Reproductive health is a global health priority and infertility
is one of its critical components regarded as a
global health concern (
About one-sixth, two-fifths, and four-fifths of general
male population and in men with primary and secondary
infertility are diagnosed with varicocele, respectively
(
In many developing countries, including Iran, it is notpossible for young couples to use the assisted reproductivetechnology (ART) due to its economic burden; therefore,
in these countries, it is required to seek more affordableeffective approaches that are associated with fewer side ef.
fects (
This retrospective study was conducted on infertile men
with confirmed varicocele. These men had multiple abnormal
semen analysis results and a 3-5 year history of
primary infertility even after different medical treatments.
The subjects were selected from individuals who referred
to Hazrat Rasoul-e-Akram medical center in Tehran, Iran
between 2009 and 2015. Cases with a history of previous
scrotal or inguinal operation were excluded from our
study. Using G*Power 3.1.9.2 and considering equal number
in each group and 0.386 for effect size from means of
postoperative sperm concentration (million/mL), 0.05 for
alpha, 0.80 for power, and 3 for number of groups, a total
sample size of 70 patients was calculated (
Convenience sampling was done by an expert clinician. Then, patients’ medical history was recorded and physical examination (mode of presentation laterality and varicocele grade) and semen analysis were done for each subject. The results of the last semen analysis before surgery, were considered as the baseline. The patients were classified into three clinical groups: grade 1 (palpable only with a Valsalva maneuver), grade 2 (non-visible but palpable without a Valsalva maneuver), and grade 3 (palpable and visible).
The status of atrophy in patients before and after surgery
was examined using scrotal Doppler ultrasonography.
Atrophy was defined as a testicular volume of <16
ml. According to WHO definition, normal semen samples
have a volume of =1.5 mL, a sperm concentration of =15
million per mL, motility (movement of the sperm) value
of =32% with forward progression (sum of type A and
type B), total motility (sum of type A, B and C) of =40%
and =4% normal morphology (
The sperm concentration was measured using a haemocytometer
utilizing a neubauer sperm counting chamber
after immobilization of spermatozoa by neutral formalin.
The sperm motility was assessed by scanning a few fields
under high-dry objective, until a total of =200 spermatozoa
was enrolled and the sperm morphology was assessed
on the basis of differential counts of morphologically
normal and abnormal spermatozoa sorts on Pap-stained
slides. Different types of sperm motility were classified
into four groups: Quick dynamic (type A), Slow dynamic
(type B), Non-dynamic (type C), and Immotile (type D).
Based on a previous study, motility was defined as the
average percentage of forward progression (sum of type
A and B) divided by all four types of motility (
Information about time of surgery (since anesthesia time), type of anesthesia, and level of pain after surgery were collected for all the patients. Pain was measured using a visual analogue scale (VAS) ranging from zero (no pain) to 10 (severe pain). Three months after the surgery, semen parameters and surgical complications (atrophy, hematoma, recurrence, hydrocele, pneumoscrotum, significant nausea and vomiting, infection, ileus, next organ damages as well as need for blood transfusion, re-operation, changing the laparoscopic surgery to open, and other conditions) were investigated in all patients via clinical examinations, ultrasound test, and semen analysis. An urologist who was completely blind to the medical history and semen analysis, carried out all physical examinations.
Taking into consideration the clinical indication and patients’ preference, they were allocated to different groups of varicocelectomy. All surgeries were done by a single urologist. To compare the effects of surgery in each group, we used Mann-Whitney, Wilcoxon, and McNemar’s tests. To compare the effects of the type of surgery on semen parameters and to compare their side effects, we used chi- square or Kruskal-Wallis test, as appropriate.
Also, univariate general linear model was utilized to compare the effects of the type of surgery on semen parameters, by considering the baseline values of semen parameters as covariates and controlling the effect of other potential confounders. For sensitivity analysis, an additional univariate general linear model was used by controlling other residual (or potential) confounders that were not different among the three groups.
In order to predict the effect of varicocelectomy on semen parameters, we used linear regression in a stepwise manner. In this study, the level of statistical significance was set as a P value less than 0.05. All analyses were performed using SPSS 20 software (SPSS Inc., Chicago, Illinois, USA). All surgeries performed in this study were in accordance with the institutional ethical standards and the study protocol was confirmed by Ethics Committee of Iran University of Medical Sciences, Tehran, Iran. Written informed consent was signed by all participants.
There were 25, 23 and 22 cases in Palomo, Ivanissevich and laparoscopic groups with the mean age of 25.97 ± 5.7 years old which was not significantly different among the groups (P=0.352). In 76% of subjects, varicocele was in left side with no statistically significant differences among the three groups (P=0.513). Grade 3, 2 and 1 of varicocele were observed in 67, 30 and 3%, respectively. The rate of varicocele grade 3 in the Palomo group was significantly higher than that of laparoscopic (P=0.005) and Ivanissevich (P=0.047) groups. Sperm concentration was abnormal in 30 subjects accounting for 42.85% of patients population; there were no significant differences in this parameter among the three groups (P=0.138).
Moreover, there were no statistically significant differences
in other parameters of semen analyzed before the
surgery, among the three groups. There was no atrophy before
the surgery in 56% of the patients (n=39). Presence of
atrophy significantly varied among different groups (64, 35
and 32% of cases in Palomo, Ivanissevich and laparoscopic
groups, respectively; P=0.046). There was a significant
difference among the three groups in terms of the mean
duration of surgery (longer in laparoscopic type than two
others) and type of anesthesia (general anesthesia in most
cases of laparoscopic type and spinal anesthesia in the other
methods) (P<0.001 for both comparisons) (
The results showed that after surgery, the Palomo technique
was significantly associated with fewer complications
compared to other techniques (12, 55 and 44%
for the Palomo, laparoscopic and Ivanissevich groups,
respectively, P=0.006). In all group, no one had significant
nausea and vomiting, infection, ileus, and next organ
damages specifically intestinal damage as well as need
for blood transfusion, re-operation, and changing the laparoscopic
surgery to open method. In general, the most
common complications were hydrocele in 21.4% (n=15),
recurrence in 10% (n=7), and hematoma and pneumoscrotum
each in 8.60% (n=6) of the patients. Pain after
surgery was similar among all groups (
Post-surgery semen analysis of all 70 subjects showed decreases in sperm concentration, normal motility and normal morphology in 7 (10%), 5 (7.4%) and 4 patients (5.9%), respectively. In these patients with semen parameters worsened after the surgery (n=13), from 5 patients with atrophy at baseline, only one had atrophy after the surgery and recurrence was observed in three of them. Moreover, 30 patients had abnormal sperm concentration and 67 patients had abnormal sperm motility at baseline; following the surgery, sperm concentration and sperm motility were within the normal range in 73.3% (n=22) and 40.2% (n=27) of these individuals, respectively (P<0.001 for both).
Basic characteristics of the patients in different groups of surgical treatment
Item | Group | P value | Power (%) | ||
---|---|---|---|---|---|
Laparoscopyn=22 | Ivanissevichn=23 | Palomon=25 | |||
Age (Y)**, *** | 26.59 ± 6.05 | 26.78 ± 6.01 | 24.68 ± 5.23 | 0.352 | 64.01 |
Sperm concentration (million/mL)**, *** | 13.09 ± 9.88 | 18.26 ± 13.38 | 14.96 ± 12.89 | 0.262 | 67.31 |
Sperm normal motility (%)**, ***, # | 16.86 ± 6.77 | 19.56 ± 8.51 | 18.72 ± 9.90 | 0.639 | 59.32 |
Sperm normal morphology (%)**, *** | 46.59 ± 14 | 48.04 ± 12.13 | 47.17 ± 15.87 | 0.871 | 51.04 |
Atrophy, n(%)& | |||||
Positive | 7(32) | 8(35) | 16 (64) | 0.046 | |
Negative | 15(68) | 15(65) | 9(36) | ||
Mode of presentation laterality, n(%)& | |||||
Left unilateral | 18(82) | 18(78) | 17(68) | 0.513 | 16.31 |
Bilateral | 4(18) | 5(22) | 8(32) | ||
Varicocele grade, n(%)*** | |||||
I | 1(5)a* | 1(4)a | 0(0.00) | 0.020 | |
II | 11(50)a | 7(31)a | 3(12) | ||
III | 10(45)a | 15(65)a | 22(88) | ||
Duration of surgery**, *** | 61.59 ± 9.43 | 49.35 ± 6.08b | 51.60 ± 8.50b | <0.001 | |
Type of anesthesia, n(%)& | |||||
General | 20(91) | 5(22) | 8(32) | <0.001 | |
Spinal | 2(9) | 18(78) | 17(68) | ||
All variables refer to the condition of patients before surgery, **; Values are presented as mean ± SD, ***; The comparisons were made by Kruskal-Wallis test, #; Normal motility is sum of A+B motility type, and &; The comparisons were made by Chi-Square test. The same lowercases showed no significant differences in the post-hoc Mann-Whitney tests.
The occurrence of postoperative complications in different groups
Item | Group Total | P value | Power (%) | |||
---|---|---|---|---|---|---|
Laparoscopyn=22 | Ivanissevichn=23 | Palomon=25 | ||||
Complications* | 12(55) | 10(44) | 3(12) | 25 | 0.006 | |
Hematoma** | 1(4.5) | 4(17) | 1(4) | 6(8.60) | 0.657 | 51.23 |
Recurrence** | 5(23) | 2(9) | 0(0.00) | 7(10) | 0.028 | |
Hydrocele** | 8(36) | 5(22) | 2(8) | 15(21.40) | 0.059 | 48.49 |
Pneumoscrotum** | 6(27) | 0(0.00) | 0(0.00) | 6(8.60) | 0.001 | |
Pain*** | 2.19 ± 1.40 | 2.09 ± 1.64 | 2.71 ± 1.87 | 0.430 | 59.79 | |
Data are presented as mean + SD or n (%). *; The comparisons were made by Chi-Square test. Complication: refers to any adverse effect observed in everybody, **; The comparisons were made by Fisher’s exact test between the laparoscopic and open surgical techniques, and ***; The comparisons were made by Kruskal-Wallis test.
Mean values of semen parameters after surgery indicated
significant improvements in all groups of varicocelectomy.
The results of the univariate general linear model (by considering
the preoperative values of semen parameters as
covariates) revealed that the means of sperm concentration,
normal motility and normal morphology were significantly
different among the three groups after the surgery
(P=0.025, 0.023 and 0.047, respectively). Mean values of
sperm concentration and normal motility in the patients in
Ivanissevich and Palomo groups were better than those of
patients in laparoscopic group; however, Palomo technique
had significantly better effect on normal morphology only
compared to the laparoscopic technique (
Comparing the mean differences of semen parameters
among the three groups of varicocelectomy confirmed the
results of univariate general linear model. We also used a
univariate general linear model for controlling other factors
(i.e. duration of surgery, atrophy before surgery, type
of anesthesia and grade of varicocele) which were different
among the three groups. The results of this analysis
showed a significant difference among the groups just in
terms of sperm concentration (P=0.040). Post-hoc analysis
revealed that this difference was statistically significant
only when comparing Ivanissevich (15.13 ± 8.69
million/mL) and laparoscopic (8.77 ± 8.94 million/mL)
groups (P=0.008) (
Age distribution and mode of presentation laterality was not significantly different in the three groups. Nonetheless, the power of this study to detect differences was low. Thus, we can consider the effect of these variables as residual confounders. Controlling these variables in an additional univariate general linear model showed that there was no significant differences among the three groups in terms of improving all semen parameters.
Comparison of the results of surgery before and after utilization of three varicocelectomy techniques
Item | Group | P value | Power (%) | ||
---|---|---|---|---|---|
Laparoscopyn=22 | Ivanissevichn=23 | Palomon=25 | |||
Sperm concentration, million/mL* | |||||
BS** | 13.09 ± 9.88 | 18.26 ± 13.38 | 14.96 ± 12.89 | ||
AS*** | 21.86 ± 10.28 | 33.39 ± 14.66a | 29 ± 13.69a | 0.0255& | |
P value# | 0.001 | <0.001 | <0.001 | ||
Sperm normal motility (%)*, ^ | |||||
BS | 16.86 ± 6.77 | 19.56 ± 8.51 | 18.72 ± 9.90 | ||
AS | 23.81 ± 9.55 | 31.95 ± 13.12b | 32.80 ± 12.99b | 0.0235& | |
P value# | 0.004 | <0.001 | <0.001 | ||
Sperm normal morphology (%)* | |||||
BS | 46.59 ± 14 | 48.04 ± 12.13 | 43.40 ± 20.03 | ||
AS | 54.55 ± 12.71c | 57.39 ± 10.32cd | 58.40 ± 15.72d | 0.0475& | |
P value# | <0.001 | 0.001 | <0.001 | ||
Atrophy, n(%)£ | 0(0.00) | 3(14.29) | 1(4.55) | 0.294 | 4.26 |
BS; Before surgery, AS; After surgery, *; Values are presented as mean ± SD, **; BS refer to values before surgery, ***; AS refer to values after surgery, #; The comparisons were made by Wilcoxon test, &; The Univariate general linear model was used for comparisons among the three groups, by considering the preoperative values of semen parameters as covariate, ^; Normal motility is sum of (A+B) motility type, £; The comparisons were made by Fisher’s exact test between the Laparoscopic and the open surgical techniques. The same lowercases showed no significant differences in post-hoc tests.
Comparing the mean differences of indices before and after surgery among patients undergoing three different surgical techniques
Item | Group | P value | ||
---|---|---|---|---|
Laparoscopyn=22 | Ivanissevichn=23 | Palomon=25 | ||
Sperm concentration (million/mL)*** | 8.77 ± 8.94a | 15.13 ± 8.69b | 14.04 ± 11.51ab | 0.023 |
Sperm normal motility (%)#, & | 6.95 ± 9.11 | 12.39 ± 9.87c | 14.08 ± 8c | 0.014 |
Sperm normal morphology (%)^ | 7.95 ± 4.27d | 9.34 ± 10.47de | 15 ± 12.4e | 0.019 |
*; All values are presented as mean ± SD. All comparisons were made by Kruskal-Wallis test. ***; Mean count after surgery-mean count before surgery, #; Mean normal motility after surgery-mean normal motility before surgery, and normal motility is sum of (A+B) motility type, ^; Mean normal morphology after surgery-mean normal morphology before surgery. The same lowercases showed no significant differences in post-hoc tests.
Stepwise linear regression model for indices of semen analysis after the surgery
Dependent variable | Independent variable | Unstandardized coefficients | Standardized beta | P value | Model | ||
---|---|---|---|---|---|---|---|
Beta | SE of beta | R square | P value | ||||
Sperm concentration after surgery | Sperm concentration before surgery | 0.761 | 0.105 | 0.678 | <0.001 | 0.531 | <0.001 |
Laparoscopic surgical treatment | -7.587 | 2.917 | -0.243 | 0.012 | |||
Atrophy before surgery | -5.449 | 2.614 | -0.196 | 0.042 | |||
Normal motility of sperm after surgery | Sperm normal motility before surgery | 0.992 | 0.146 | 0.649 | <0.001 | 0.505 | <0.001 |
Laparoscopic surgical treatment | -6.334 | 2.637 | -0.229 | 0.020 | |||
Normal morphology of sperm after surgery | Sperm normal morphology before surgery | 0.535 | 0.070 | 0.629 | <0.001 | 0.608 | <0.001 |
Sperm normal motility before surgery | 0.354 | 0.123 | 0.241 | 0.005 | |||
Palomo surgical treatment | 5.375 | 1.953 | 0.217 | 0.008 | |||
Varicocelectomy helps to improve atrophy (P<0.001). So, at all ages and all surgery groups, among 31 patients who had atrophy at baseline, improvement in this respect was seen in nearly all of them (n=26, 83.9%), except for 2 patients at the age of 24 and 36. Atrophy was unknown for 3 patients. Moreover, except for the patients in Ivanissevich group, this positive effect was confirmed in patients of the other groups (P=0.016 for laparoscopy and P<0.001 for Palomo).
The results of stepwise linear regression showed that
sperm concentration prior to the surgery, laparoscopic
varicocelectomy, and atrophy prior to the surgery were
the prognostic factors that could significantly predict the
sperm concentration after the surgery. Laparoscopic varicocelectomy
and presence of atrophy before the surgery
have a negative impact on sperm concentration after the
surgery. The values of normal motility before surgery and
laparoscopic varicocelectomy were independent factors
for predicting the normal motility after surgery. In addition,
the number of sperms with normal morphology after
the surgery, depends on the values of normal morphology
before surgery and normal motility, as well as the utilization
of Palomo technique. The adjusted R-square of the
models (0.531, 0.505, and 0.608) indicates the higher accuracy
of regression models in predicting the morphology
and concentration, regardless of the number of independent
variables entered the model. In each of the models, higher
standardized beta indicates higher values of a variable in
predicting the dependent variable. The values of each semen
parameter prior to the surgery (e.g. sperm concentration)
had the highest values in prediction of these parameters
(e.g. sperm concentration) after the surgery (
In this study, following the surgery, sperm concentration, normal motility, and normal morphology worsened in 10, 7.4, and 5.9% of patients, respectively. Based on univariate analysis, sperm concentration, normal motility and normal morphology after surgery using Ivanissevich and Palomo techniques, were better than those of laparoscopic group; but after controlling for confounders, a significant difference was seen only between Ivanissevich and laparoscopic techniques.
A similar study on 100 infertile patients who underwent
varicocelectomy, showed a significant difference between
open inguinal or laparoscopy methods in terms of sperm
concentration and motility (
According to other studies that had no controlling for
confounding factors and did not consider the type of
varicocelectomy, varicocelectomy could lead to significant
improvements in sperm concentration, motility, and
morphology. The results of our study are in line with the
mentioned studies and confirm their findings (
The results of this study showed that laparoscopic and Palomo surgery had a positive effect on the improvement of the atrophy. Regarding Ivanissevich technique, at least in short-term follow-up in this study, no improvement in atrophy was seen; however, at least in terms of sperm concentration, changes were in direction to improve.
Nevertheless, to check the efficacy of varicocelectomy,
we need to know post-surgery fertility status which was
not assessed in this study. The best modality for treatment
of varicocele in infertile men is a modality which
highly improves semen and increases pregnancy rates
with minimum complication rates (recurrence, hydrocele,
and atrophy). Thus, an ideal technique not only preserves
the lymph nodes and spermatic vessels, but also closes
all external and internal spermatic veins. Although so
far, no treatment modality has been introduced as a "gold
standard" of varicocele treatment. According to the literature,
compared to other varicocelectomy techniques,
microscopic varicocelectomy (MV), despite its need for
more operative time, surgical skills and experiences, was
accepted as a standard treatment which had the lowest
postoperative recurrence and complication rates (
Overall rate of complications in open varicocelectomy
has been reported to be slightly higher than laparoscopic
varicocelectomy (8 vs. 6%, respectively) but this difference
is not significant. Recurrent symptoms of varicocele
were observed only in five and two patients in laparoscopic
and Ivanissevich group, respectively. Other studies have
also shown that higher grades of preoperative varicocele
lead to increased risk of recurrence that can be secondary
to multiple collateral venous channels (
Hydrocele after the surgery has an incidence rate of
up to 10% of cases regardless of type of varicocelectomy
(
There are some limitations in our study such as the retrospective nature of study, non-random sampling, small sample size, short follow-up period and no hormonal and fertility assessment. Moreover, there is a risk of selection bias. A higher proportion of men who underwent a Palomo repair had bilateral disease. Similarly, those who underwent this procedure had a higher grade of varicocele and higher incidence of atrophy, as defined in the study. This might have an impact on the results. However, we used a general linear model in our analyses to overcome this problem and fix this bias. Performing all surgeries by a single surgeon may cause dependency of the results to the surgeon; although, it removed inter-observer bias. In real scenario, most cases are like our cases with high grade of varicocele. So, our results are relatively generalizable.
Varicocelectomy improves sperm parameters. Palomo, Ivanissevich, and laparoscopy methods were similar in terms of sperm normal motility and morphology. However, Ivanissevich was more effective in improving sperm concentration. Regarding complications, Palomo technique caused the lowest rate of post-surgery complications. It seems necessary to conduct further studies with longer follow-up periods to clarify the effect of different types of varicocelectomy on semen parameters and pregnancy rate in Iran.