Asian Journal of Andrology

INVITED REVIEW
Year
: 2016  |  Volume : 18  |  Issue : 2  |  Page : 202--204

Critical appraisal of conventional semen analysis in the context of varicocele


Thinus Kruger 
 Aevitas Clinic, Pinelands and Reproductive Biology Unit, Stellenbosch University/Tygerberg Hospital, South Africa

Correspondence Address:
Dr. Thinus Kruger
Aevitas Clinic, Pinelands and Reproductive Biology Unit, Stellenbosch University/Tygerberg Hospital
South Africa

Abstract

Varicocele is present in approximately 15% of men, and, although it is the most commonly diagnosed cause of male infertility, nearly two-thirds of men with varicoceles remain fertile. It was decided to make use of the current evidence obtained from the previous meta-analyses between 2004 and 2015 as well as available articles covering this field, preferably randomized controlled articles dealing with the topic of semen analysis before and after repair. Two important meta-analyses were discussed as well as other articles dealing with the topic of semen analysis before and after varicocelectomy. The evidence suggests that all semen parameters improve after varicocele repair. Based on the available evidence, it is clear that there is a benefit in treating men with a palpable varicocele. One can expect that all semen parameters will improve within 3 months after repair.



How to cite this article:
Kruger T. Critical appraisal of conventional semen analysis in the context of varicocele.Asian J Androl 2016;18:202-204


How to cite this URL:
Kruger T. Critical appraisal of conventional semen analysis in the context of varicocele. Asian J Androl [serial online] 2016 [cited 2022 Jun 28 ];18:202-204
Available from: https://www.ajandrology.com/text.asp?2016/18/2/202/168691


Full Text

 Introduction



Male infertility compromises about 40% or more of infertile couples. Often male factor infertility is unexplained. Varicocele is dilated tortuous spermatic veins usually palpable around the left testis.

Varicocele presents in approximately 15% of men, and, although it is the most commonly diagnosed cause of male infertility, nearly two-thirds of men with varicoceles remain fertile. [1] The fact that most of the work on varicocele repair is retrospective of the evidence of surgical repair and its value in the improvement of fertility is still debated. Eighty-five percent of patients will have a left varicocele and the balance palpable on the right side or bilateral. 11.7% of infertile men with normal semen analysis and 25.4% of those with abnormal analysis were found to have a clinical varicocele. The reason for this discrepancy that some are fertile but others are not, remains unknown, although it is postulated that the cause of infertility is due to increased temperature [1] affecting the DNA fragmentation ratio and reactive oxygen species. [2],[3],[4]

There are a number of treatments available to handle varicoceles. These treatments can be radiological ablation or surgical of which the microsurgical method gives the best long-term results with less complications. It is the consensus opinion of most that only clinically palpable varicoceles should be operated on. The laparoscopic approach does not seem to be superior to the open microsurgical method and thus lately not the operation of choice. [1]

There are a number of interesting factors to be studied in men with varicocele. The interest of the authors for this article is to evaluate the impact/effect of repair of varicocele on semen parameters. It was decided to make use of the current evidence obtained from the previous meta-analyses between 2004 and 2015 as well as available articles covering this field, preferably randomized controlled articles dealing with the topic of semen analysis before and after repair.

 Threshold Values for Semen Analysis



WHO lower reference limits

The WHO has published revised lower reference limits for semen analyses. [5] The following parameters represent the generally accepted 5 th percentile (lower reference limits and 95% confidence intervals [CIs] in parentheses), derived from a study of over 1900 men whose partners had a time-to-pregnancy of ≤12 months. The suggested lower thresholds (subfertile values) were as follows: volume: 1.5 ml (95% CI: 1.4-1.7), Sperm concentration: <15 million spermatozoa per milliliter (95% CI: 12-16), Total sperm number: <39 million spermatozoa per ejaculate (95% CI: 33-46), Morphology: ≤4% normal forms (95% CI: 3-4), using the "strict" Tygerberg method, [6] Vitality: 58% live (95% CI 55-63), Progressive motility: <32% (95% CI: 31-34), and Total motility (progressive + nonprogressive motility): <40% (95% CI: 38-42). [5],[7],[8]

These values will be looked at when analyzing the reports on semen parameters and varicocele. However, since many articles are dating back to periods even before 2000, other thresholds will also be taken into consideration. The percentage increasing or dropping of the parameters will also be taken into account in interpreting the effect of varicocelectomy as well as the concentration per milliliter.

 Evidence Available on The Value of Varicocelectomy on Semen Analysis or Semen Parameters



Meta-analysis

In an attempt to obtain the best evidence, meta-analyses are very helpful to form opinions on a topic and specifically on this topic. Agarwal et al.[9] reported an important meta-analysis, and I am quoting them directly:

"To determine the efficacy of varicocelectomy in improving semen parameters. A meta-analysis was performed to evaluate both randomized controlled trials and observational studies using a new scoring system. This scoring system was developed to adjust and quantify for various potential sources of bias, including selection bias, follow-up bias, confounding bias, information or detection bias, and other types of bias, such as misclassification. Of 136 studies identified through the electronic and hand search of references, only 17 studies met the inclusion criteria. The study population was infertile men with clinically palpable unilateral or bilateral varicocele and at least one abnormal semen parameter who had undergone surgical varicocelectomy (high ligation or inguinal microsurgery). Only those studies that had at least three semen analyses (i.e., sperm count, motility, and morphology) per patient, before and after surgical varicocelectomy, were included." The following results were reported: "the combined analysis demonstrated that the sperm concentration increased by 9.71 × 10 6 ml−1 (95% CI: 7.34-12.08; P < 0.00001) and motility increased by 9.92% (95% CI: 4.90-14.95; P = 0.0001) after microsurgical varicocelectomy. Similarly, the sperm concentration increased by 12.03 × 10 6 ml−1 (95% CI: 5.71-18.35; P = 0.0002) and motility increased by 11.72% (95% CI: 4.33-19.12; P = 0.002) after high ligation varicocelectomy. The improvement in World Health Organization sperm morphology was 3.16% (95% CI: 0.72-5.60; P = 0.01) after both microsurgery and high ligation varicocelectomy."

They concluded that surgical varicocelectomy significantly improved semen parameters in infertile men with palpable varicocele and abnormal semen parameters.

In a follow-up meta-analysis in 2011, Baazeem et al. [10] reported on the assessment of the effect of varicocelelectomy on male infertility. For the purpose of accuracy, the authors are also quoted verbatim:

"Four randomized controlled trials reporting on pregnancy outcomes after repair of clinical varicoceles in oligozoospermic men were identified. Using the random effect model, the combined odds ratio was 2.23 (95% CI: 0.86-5.78; P = 0.091), indicating that varicocelectomy is moderately superior to observation, but the effect is not statistically significant. They identified 22, 17, and 5 prospective studies reporting on sperm concentration, total motility, and progressive motility, respectively, before and after repair of clinical varicocele. The random effect model combined improvement in sperm concentration was 12.32 × 10 6 ml−1 (95% CI: 9.45-15.19; P < 0.0001). The random effect model combined improvement in sperm total and progressive motility were 10.86% (95% CI: 7.07-14.65; P < 0.0001) and 9.69% (95% CI: 4.86-14.52; P = 0.003), respectively. These results indicate that varicocelectomy is associated with a significant increase in sperm concentration as well as total and progressive motility. They stated that prospective studies also show that varicocelectomy reduces seminal oxidative stress and sperm DNA damage as well as improving sperm ultramorphology."

The report by Baazeem et al. [10] concluded: "although there is no conclusive evidence that a varicocele repair improves spontaneous pregnancy rates, varicocelectomy improves sperm parameters (count and total and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology."

There are few randomized controlled studies dealing with the benefit of varicocelectomy in men with abnormal semen parameters. Abdel-Meguid et al.[11] studied men in this fashion with at least one impaired semen parameter (sperm concentration <20 × 10 6 ml−1 , progressive motility <50%, or normal morphology <30%). One group received treatment (subinguinal microsurgical varicocelectomy) and the control group was observed.

They reported: "in CA (Control arm) within-arm analysis, none of semen parameters revealed significant changes from baseline (sperm concentration [P = 0.18], progressive motility [P = 0.29], and normal morphology [P = 0.05]). Conversely, in TA (treatment arm) within-arm analysis, the mean of all semen parameters improved significantly in follow-up versus baseline (P < 0.0001). In between-arm analysis, all semen parameters improved significantly in the TA versus CA (P < 0.0001)." [11]

 Other Articles Dealing with The Impact of Varicoloelectomy on Semen Parameters



Asthenospermia

According to Will et al. [4] 19% of subfertile men would suffer from asthenozoospermia if diagnosed with varicocele. [4],[12] There is consensus in the literature that motility will improve in patients where a palpable varicocele was treated. [12],[13],[14]

Teratozoospermia

The problem with the literature on sperm morphology is the fact that most articles consist of retrospective data and small studies. Therefore, controlled prospective studies are highly needed in the field.

The following authors observed improvement in sperm morphology after varicocelectomy. [15],[16],[17] Interestingly, the study by Cakan et al.[17] showed no improvement in morphology and semen parameters in the control group with no pregnancies over a 12-month follow-up period. As mentioned before, the meta-analysis by Agarwal et al.[9] also concluded that sperm morphology improved after treatment of the varicocele. In contrast to the above, a number of authors did not see any improvement in sperm morphology after surgical removal. [18],[19]

Oligozoospermia

Studies that examined men with low sperm counts in the less severe range showed greater postoperative improvements. Madgar et al.[20] restricted their prospective study to men with sperm concentration between 5 × 10 6 and 20 × 10 6 ml−1 to limit the number of confounding variables; and they were able to demonstrate a significant improvement in sperm concentration, motility, and morphology (by 6 months postoperatively) and higher pregnancy rates than the control group. As mentioned, Baazeem et al.[10] noted similar improvements in semen parameters in their recent review of 360 patients with sperm concentrations ranging 1 × 10 6 -20 × 10 6 ml−1 .

Severe oligozoospermia/nonobstructive azoospermia

Studies from a number of authors published evidence to support that men with severe oligozoospermia (<5 × 10 6 ml−1 ) are less likely to see improvements in semen parameters. [21],[22],[23] Kamal et al.[21] were also able to display a direct relationship between preoperative sperm count and postoperative pregnancy rates. It was observed that men with severe oligozoospermia had much lower chance of spontaneous pregnancy (8% compared to 61% in those with sperm concentration more than 5 × 10 6 ml−1 ). [21]

Matthews et al.[24] wrote recently: "early reports of varicocele repair demonstrate the potential, in some, to induce spermatogenesis." Matthews et al.[24] as well as Kim et al.[25] showed improvement in semen parameters in patients with oligozoospermia and azoospermia. The Matthews group also observed pregnancies after varicoloelectomy in their study. [24]

The question about who are the best candidates for treatment is asked. A number of researchers showed that those with hypospermatogenesis and maturation arrested at later stages are more likely to see return of motile sperm and even pregnancies postoperatively. [25],[26],[27],[28]

As a general principle, one must do a semen analysis at regular intervals (every 6 weeks) and it is a good strategy to freeze sperm as soon as motile samples are available. [28],[29]

Sperm DNA damage

There is a difference between opinions and conflicting results about DNA damage and varicocele possibly due to the size of varicocele. With the advent of new laboratory assessment tools to aid in selection of higher quality sperm with less DNA fragmentation for use with ICSI, [30],[31],[32] it will be interesting to see if varicocelectomy will be required in the future for specifically selected patients prior to ICSI. [4]

 Time to Improvement



In a retrospective study by Al Bakri et al. [33] they evaluated the time taken to observe improvement in semen parameters. All men had at least two preoperative semen analyses as well as semen testings at 3 and 6 months postoperatively.

The authors concluded that after 3 months the maximum effect and benefit was observed. [33] There was a significant improvement in concentration and motility in the 100 men that met the inclusion criteria after 3 months, but this did not change at 6 months or longer. There were no statistically significant differences in the improvement of semen volume, motility, count, or total motile count among the results at 3, 6 and more than 9 months postoperatively.

 Conclusion



Based on the available evidence, it is clear that there is a benefit in treating men with a palpable varicocele. One can expect that all semen parameters will improve within 3 months after repair. It is thus important to examine all men in a fertility clinic, especially those with abnormal semen parameters to be able to make sound clinical decisions and consider a varicocelectomy.

 Competing Interests



The author declares no competing interests.

 Acknowledgments



Mrs. Erna Brummer for editorial assistance.

References

1Sandlow J. Pathogenesis and treatment of varicoceles. BMJ 2004; 328: 967-8.
2Mostafa T, Anis TH, El-Nashar A, Imam H, Othman IA. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl 2001; 24: 261-5.
3Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ Jr, Agarwal A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril 2004; 82: 1684-6.
4Will MA, Swain J, Fode M, Sonksen J, Christman GM, et al. The great debate: varicocele treatment and impact on fertility. Fertil Steril 2011; 95: 841-52.
5World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. Geneva, Switzerland: WHO; 2010.
6Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, et al. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril 1988; 49: 112-7.
7Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16: 559.
8Van der Merwe FH, Kruger TF, Oehninger SC, Lombard CJ. The use of semen parameters to identify the sub-fertile male in the general population. Gynecol Obstet Invest 2005; 59: 86-91.
9Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, et al. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology 2007; 70: 532-8.
10Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, et al. Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol 2011; 60: 796-808.
11Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur Urol 2011; 59: 455-61.
12Boman JM, Libman J, Zini A. Microsurgical varicocelectomy for isolated asthenospermia. J Urol 2008; 180: 2129-32.
13Schatte EC, Hirshberg SJ, Fallick ML, Lipschultz LI, Kim ED. Varicocelectomy improves sperm strict morphology and motility. J Urol 1998; 160: 1338-40.
14Schlesinger MH, Wilets IF, Nagler HM. Treatment outcome after varicocelectomy. A critical analysis. Urol Clin North Am 1994; 21: 517-29.
15Vazquez-Levin MH, Friedmann P, Goldberg SI, Medley NE, Nagler HM. Response of routine semen analysis and critical assessment of sperm morphology by Kruger classification to therapeutic varicocelectomy. J Urol 1997; 158: 1804-7.
16Kibar Y, Seckin B, Erduran D. The effects of subinguinal varicocelectomy on Kruger morphology and semen parameters. J Urol 2002; 168: 1071-4.
17Cakan M, Bakirtas H, Aldemir M, Demirel F, Altug U. Results of varicocelectomy in patients with isolated teratozoospermia. Urol Int 2008; 80: 172-6.
18Seftel AD, Rutchik SD, Chen H, Stovsky M, Goldfarb J, et al. Effects of sub-inguinal varicocele ligation on sperm concentration, motility and Kruger morphology. J Urol 1997; 158: 1800-3.
19Okeke L, Ikuerowo O, Chiekwe I, Etukakpan B, Shittu O, et al. Is varicocelectomy indicated in subfertile men with clinical varicoceles who have asthenospermia or teratospermia and normal sperm density? Int J Urol 2007; 14: 729-32.
20Madgar I, Weissenberg R, Lunenfeld B, Karasik A, Goldwasser B. Controlled trial of high spermatic vein ligation for varicocele in infertile men. Fertil Steril 1995; 63: 120-4.
21Kamal 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: 1013-6.
22Fujisawa M, Dobashi M, Yamasaki T, Okada H, Arakawa S, et al. Therapeutic strategy after microsurgical varicocelectomy in the modern assisted reproductive technology era. Urol Res 2002; 30: 195-8.
23Matkov TG, Zenni M, Sandlow J, Levine LA. Preoperative semen analysis as a predictor of seminal improvement following varicocelectomy. Fertil Steril 2001; 75: 63-8.
24Matthews GJ, Matthews ED, Goldstein M. Induction of spermatogenesis and achievement of pregnancy after microsurgical varicocelectomy in men with azoospermia and severe oligoasthenospermia. Fertil Steril 1998; 70: 71-5.
25Kim ED, Leibman BB, Grinblat DM, Lipshultz LI. Varicocele repair improves semen parameters in azoospermic men with spermatogenic failure. J Urol 1999; 162: 737-40.
26Kadioglu A, Tefekli A, Cayan S, Kandirali E, Erdemir F, et al. Microsurgical inguinal varicocele repair in azoospermic men. Urology 2001; 57: 328-33.
27Esteves SC, Glina S. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology. Int Braz J Urol 2005; 31: 541-8.
28Lee JS, Park HJ, Seo JT. What is the indication of varicocelectomy in men with nonobstructive azoospermia? Urology 2007; 69: 352-5.
29Pasqualotto FF, Sobreiro BP, Hallak J, Pasqualotto EB, Lucon AM. Induction of spermatogenesis in azoospermic men after varicocelectomy repair: an update. Fertil Steril 2006; 85: 635-9.
30Nasr-Esfahani MH, Razavi S, Vahdati AA, Fathi F, Tavalaee M. Evaluation of sperm selection procedure based on hyaluronic acid binding ability on ICSI outcome. J Assist Reprod Genet 2008; 25: 197-203.
31Yagci A, Murk W, Stronk J, Huszar G. Spermatozoa bound to solid state hyaluronic acid show chromatin. J Androl 2010; 31: 566-72.
32Razavi SH, Nasr-Esfahani MH, Deemeh MR, Shayesteh M, Tavalaee M. Evaluation of zeta and HA-binding methods for selection of spermatozoa with normal morphology, protamine content and DNA integrity. Andrologia 2010; 42: 13-9.
33Al Bakri A, Lo K, Grober E, Cassidy D, Cardoso JP, et al. Time for improvement in semen parameters after varicocelectomy. J Urol 2012; 187: 227-331.