Varicocele: "The Bag of Worms"

A varicocele (from the Latin word, varix for dilated vein; and the Greek word, kele for tumor) is an enlargement of the veins in the scrotum and is similar to varicose veins that occur in the legs.  In younger men and boys, an abnormal appearing or feeling scrotum is often the reason for coming to a doctor.  In adult men, varicoceles most often present during an evaluation for infertility.  When a couple presents for infertility, a male factor is present in approximately 50% of couples (30% independent male factor infertility, 20% combined male and female factor infertility).  In this group, varicocele is related to semen abnormalities and is the #1 correctable male infertility factor.[1]

Etiologies of Male Infertility [1]

Varicoceles are present in:
- 10-15% of the general population
- 30-40% of men with primary infertility (couples never able to have children)
- 80% of men with secondary infertility (couples who have children, but are having difficulty conceiving now)

The anatomic defect in varicocele is an abnormal enlargement of the pampiniform venous plexus that drains the testicle in the scrotum.  The pampiniform plexus is a collection of veins that helps regulate the temperature of the testicle - as the testicle best makes sperm at temperature two degrees lower than body temperature.  The vast majority (99%) of varicoceles are left-sided and 30% of patients can have a varicocele on both sides.  Right-sided varicoceles are rare and can indicate a malignant process blocking the drainage on the right side of the abdomen.

Varicoceles are graded on a scale from I-III, based on physical examination findings and are often described as appearing "like a bag of worms" in the scrotum.  A Valsalva maneuver is performed by forcefully exhaling against a closed airway (like bearing down to have bowel movement), and helps to distinguish the grades of varicocele.

Grade III Varicocele

Grade I:  Present by palpation only with Valsalva
Grade II: Present by palpation without Valsalva
Grade III: Visible on exam

The work-up for a varicocele usually only involves a semen analysis, fertility labs when applicable, and does not generally involve imaging studies.  Occasionally small, non-palpable varicoceles can be found on scrotal ultrasounds done for other reasons.  These non-palpable varicoceles are not associated with infertility.

There are a number of mechanisms by which varicoceles can cause decreased spermatogenesis (or the creation of sperm).  These mechanisms involve loss of the "heat sink" to the testicle which can cause:

• damage by direct hyperthermic injury to sensitive sperm progenitors via DNA damage or reactive oxygen species (ROS)
• testicular atrophy
• inadvertent delivery of adrenal metabolites to the testicles

There are therefore three scenarios where correction of a varicocele are routinely recommended: [2,3]

1. Adult Man with a palpable or visible varicocele 
• abnormal semen parameters 
• in a couple with known infertility
• normal, corrected or optimized female factor infertility
2. Adult Man with a palpable or visible varicocele 
• abnormal semen parameters 
• not in a relationship but desiring fertility preservation
3. Adolescent Man with a palpable or visible varicocele
• 10-20% reduction of testicular size (i.e. volume) on the same side
• Pain - often dull or throbbing, worse with standing

The options for treatment and outcomes for men undergoing repair of their varicocele will be reviewed in later entries of this blog.  To read more about varicocele and repair options check the Brady Website.

This blog entry was written by Jason Michaud, MD, PhD, Junior Assistant Resident (URO-2) at the Brady Urological Institute at Johns Hopkins.









[1] Sigman M, Lipshultz L.l., Howards S.S. Infertility in the Male, 4th Ed. Chapter 10.
[2] Sharlip I, Jarow J. Report on Varicocele and Infertility. AUA Best Practice Policy and ASRM Practice Committee Report. April 2001.
[3] Guidelines for the investigation and treatment of male inferltility. Eur Urol 2012. Jan;61(1):159-63

AUA Highlights: Infertility, by Dr. Rao

Male infertility was well represented at AUA (American Urological Association) Annual Meeting 2014 in Orlando, Florida. In the plenary session, the risks of increased paternal age were outlined. Notably, children of older fathers are at higher risk of autism, schizophrenia, and achondroplasia (dwarfism). Although the relative increase in incidence of these conditions is alarming, the overall incidence remains low, even in children of older fathers. (Click here to see the video of this Critical Discussion: Advanced Paternal Age - What Are the Real Risks?)

A topic that received continued attention is the increased use of testosterone. This is of particular importance for men with impaired fertility. Use of testosterone replacement therapy causes reversible infertility in most men, however some patients may not recover even after discontinuing the medication. It is critical that men with low testosterone and infertility should not be treated with testosterone replacement therapy, but other alternative medications should be considered instead.

Much research was presented on the outcomes after varicocele. Notably, a meta-analysis of previous studies showed an improvement in pregnancy and life birth rates after varicocele repair in couples using assisted reproductive techniques such as IVF and ICSI. In addition, successful sperm retrieval rates were higher in men who underwent extraction procedures after varicocele repair compared to men with untreated varicoceles. (PD24-01; see below)

In addition, many studies were presented that investigated various genes and DNA modifications that may play a role in infertility. However, none of these will cause immediate change in the treatment of infertile men. Currently, here at the Brady, we are collaborating with many Hopkins scientists to investigate molecular causes for infertility. These studies include finding unidentified genes causing infertility, investigating whether transposons are interrupting critical DNA sequences of sperm production, and identifying other molecules that may play roles and in male infertility treatment for male contraception.

This blog was written by Pravin Rao, M.D., Assistant Professor and Director of Reproductive Medicine and Surgery at the Brady Urological Institute at Johns Hopkins.

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PD24-01: The role of varicocele repair prior to assisted reproductive technology 

Saneal Rajanahally*, Houston, TX, Edgar Kirby, Karen Crowell, Robert Coward, Chapel Hill, NC

Abstract: PD24-01 

Introduction and Objectives 

While it has been established that varicoceles can contribute to infertility, and that varicocele repair (VR) can improve semen parameters such that fertility can be achieved, the relationship between VR and subsequent success with assisted reproductive technologies (ART) has yet to be definitively elucidated. This study is a systematic review the available literature describing the impact of VR on ART outcomes. 

Methods 

A PubMed search from 1/1982-9/2013 was performed to identify prospective, prospective-controlled, and retrospective studies addressing the relationship between VR and ART outcomes in couples with male factor infertility. Studies were excluded if they did not include fertilization, pregnancy, and/or live birth rates. Statistical analysis was performed using Fisher’s exact test. 

Results 

Seven studies were identified (1 prospective, 4 prospective controlled, 2 retrospective). Five of 7 studies utilized intracytoplasmic sperm injection (ICSI), 1 reported in vitro fertilization (IVF) outcomes, and 1 used intrauterine insemination (IUI). There was no difference in fertilization rate between surgical and non-surgical groups (67.8% vs 66.1%). However, 245 of 505 patients (48.5%) who underwent VR achieved pregnancy compared with 199 of 475 (41.9%) with untreated varicocele (p<0.05). Live birth rate was significantly higher after VR (n=314, 46.5%) in comparison to the uncorrected varicocele cohort (n=374, 32.1%, p<0.001). Pregnancy (11.8% vs. 6.3%, p<0.05) and live birth rate (11.8% vs. 2.1%, p<0.05) per IUI cycle were both significantly higher in patients after VR in comparison to those untreated. Individuals with non-obstructive azoospermia (NOA) had a significantly higher sperm retrieval rate after VR (n=140, 57.1%) than those with NOA and untreated varicocele (n=218, 38.9%, p<0.005). 

Conclusions 

Available data in this systematic review demonstrate a higher pregnancy and live birth rate in men after VR compared with those with uncorrected varicoceles, along with increased sperm retrieval rates in men with NOA. The positive impact that VR may have on ART outcomes should be discussed with couples with male factor infertility due to varicocele. 

Date & Time: May 19, 2014 3:30 PM-5:30 PM 

Session Title: Infertility: Therapy 

Sources of Funding: None 

Classic Manuscript in Urology: Schoor et al, Testicular Biopsy & Infertility, 2002

Azoospermia is the condition in which there are no sperm in the semen (ejaculate fluid).
In the past, almost all men with azoospermia underwent a diagnostic testicular biopsy to distinguish obstructive (blockage) from non-obstructive (sperm production) causes; normal sperm production found in the tissue suggests obstructive causes. Previously, most men with non-obstructive azoospermia had no options to father biologically related children. However, with the emergence of assisted reproductive techniques (ART) such as in-vitro fertilization  (IVF) and intracytoplasmic sperm injection (ICSI), a pregnancy could be initiated using very low numbers of sperm.

For men with non-obstructive azoospermia, we typically offer microsurgical-dissection testicular sperm extraction (microTESE), which gives the best chance of finding sperm within the testis that can be used with ART. In contrast, men with obstructive azoospermia can seek reconstruction to relieve the obstruction and attempt natural conception, or they can use surgically retrieved sperm with similar assisted reproductive techniques. To plan for the most appropriate treatment, it is highly valuable to be able to characterize the cause of azoospermia without a diagnostic biopsy.

Schoor RA, Elhanbly S, Niederberger CS, Ross LS.  The Role of Testicular Biopsy in the Modern Management of Male Infertility.  J Urol 2002; 167(1):197-200.

PubMed.
Journal of Urology.

In this study, Dr. Schoor and colleagues retrospectively reviewed the records of 153 azoospermic men.  The authors recognized that classic texts of infertility described men with obstructive azoospermia having “normal” endocrine profiles, testicular volumes and long axis length, while men with nonobstructive azoospermia will have an abnormality in 1 or more of these parameters.  However, the importance of these abnormalities had not been defined in the modern era of infertility.

They investigated a number of parameters including follicle stimulating hormone (FSH), leutenizing hormone (LH), prolactin, and testicular size, were analyzed as predictors for obstructive vs. non-obstructive azoospermia.  FSH and testicular long axis were found to be the best individual diagnostic predictors:

• 96% of men with obstructive azoospermia had:
• FSH <7.6 mIU/mL
• Testicular Long Axis > 4.6cm
• 89% of men with nonobstructive azoospermia had: 
• FSH >7.6 mIU/mL
• Testicular Long Axis < 4.6cm 

Take Home: Not only did this study define clinical parameters to distinguish obstructive and nonobstructive azoospermia, but is also implies that testicular biopsy is generally unnecessary in the initial evaluation of azoospermia.  Avoiding testicular biopsy reduced the cost and risk associated with evaluation of azoospermia for many men.

For the majority of patients with findings suggesting non-obstructive azoospermia, we now proceed directly to microTESE. Diagnostic biopsy is still performed for a small subset of patients whose findings suggest obstructive azoospermia, as a significant fraction of them may still have a sperm production problem within the testis. For more information, see: http://malefertility.jhu.edu/fertility_evaluation.php

This blog entry was written by Pravin Rao, MD, Director of Reproductive Medicine and Surgery at the Brady Urological Institute at Johns Hopkins.

Classic Manuscripts in Urology will be posted on this blog on regular basis.  These articles are meant to highlight the achievements of our predecessors, recognize the work from which we build our careers and stimulate new conversations and discussion on a variety of urological topics.  Please feel free to comment on this manuscript, help point out its strengths and weaknesses, or suggest a new manuscript and topic.