Ranjith Ramasamy, MD

Men’s Health Mythbuster is a section on UrologyTimes.com that explores common statements and beliefs about men’s health and evaluates whether these statements are false.

In this article, we strive to discuss the impact smoking and drinking can have on fertility. We provide a summary of recent data on these social behaviors and how they may influence reproductive potential.

While the proportion of smokers has declined, 17.8% of adults in the United States continue to report smoking cigarettes. When looking at gender differences, 20.5% and 15.3% of men and women report smoking, respectively 

 Cigarette smoking can lead to numerous adverse maternal-fetal health consequences. These can range from preterm delivery, intrauterine growth restriction, to even perinatal mortality 

 A survey of female employees at a Connecticut hospital found over 95% of respondents knew about the cardiac and respiratory consequences of smoking, but only 27% and 22% were aware of the risks of ectopic pregnancy and infertility, respectively. Public health campaigns have done well at increasing awareness of the more common adverse health consequences of smoking, but further awareness is required for its effect on fertility 

 Smoking can also lead to significant abnormalities with respect to sperm production and semen parameters. These include a reduction in sperm concentration and motility as well as DNA damage. The exact mechanism that leads to sperm impairment is yet to be fully elucidated, but a potential causative agent may be nicotine, which was found to have a dose-dependent deleterious effect on sperm characteristics in male rats 

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Paternal smoking has also been shown to significantly impact the success of assisted reproductive technology (ART) such as in vitro fertilization and even intracytoplasmic sperm injection. Abnormal DNA may be the cause of the failure in the development of the embryo 

 Not only is there evidence to support the strong association between smoking and abnormal semen parameters, sperm DNA, and failure of ART, but reports suggest abnormal sperm parameters in males who had exposure to cigarette smoke in utero 

 Therefore, it is critical from a public health perspective to increase the awareness of not only the more commonly known consequences of smoking but also the adverse effects to reproduction. E-cigarettes contain nicotine to various concentrations, with a study finding nicotine levels even in products that were labeled nicotine-free, suggesting insufficient manufacturing quality control. Given the use of e-cigarettes is quite prevalent among young adults, it is important to counsel patients on the potential impact it may have on reproduction 

Cannabis has become the most popular illicit drug in the United States. It was estimated by the United Nations Office on Drugs and Crime that cannabis use increased from 37.6 million in 2005 to 49.2 million in 2015. Use of cannabis is most prevalent in those less than 35 years old, an age where reproductive potential is most typically of utmost importance.

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A systematic review published in 2017 found limited published data evaluating cannabis use and the impact on male factor infertility; however, the small data available demonstrated a negative impact on male reproduction 

 Other reviews have reported a decrease in sperm concentration with the use of cannabinoids 

 As an increasing number of states pass legislation to legalize it, more data will be available to evaluate the impact of cannabis on reproduction.

Alcohol use has increased dramatically over the past 2 decades, with excessive intake leading to approximately 88,000 deaths and 2.5 million years of potential life lost each year in the United States from 2006 to 2010 

Given the impact of alcohol on the fetus, it has been recommended that women avoid any alcohol consumption as no safe dose has been identified. With respect to male alcohol consumption, the data are quite varied, with reports having suggested alterations in semen parameters as well as sperm DNA. It is also recommended that males avoid alcohol consumption prior to providing a sample for in-vitro fertilization 

 is a fellow in reproductive urology and 

 is director of male reproductive urology and assistant professor of urology at the University of Miami.

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“There exists compelling evidence to suggest smoking and drinking alcohol can have a dramatic impact on male and female reproductive potential,” write Premal Patel, MD, and Ranjith Ramasamy, MD.

How do smoking and drinking affect fertility?

	Varicocele is a pathologic enlargement of the testicular veins that is associated with impaired spermatogenesis and infertility. In fact, varicocele is the most common correctable cause of male infertility. Varicoceles are found in up to 15% of the adult male population, but fortunately not all men with varicoceles are infertile. However, varicoceles are found in approximately 35% of men with primary infertility and up to 80% of men with secondary infertility (Wein AJ, Kavoussi LR, Partin AW, Peters CP, editors. 

	Varicoceles are diagnosed by physical exam and are graded I-III. Grade I varicocele is palpable only during the Valsalva maneuver; grade II varicocele is palpable in the standing position; and grade III varicocele is visible without palpation. The use of scrotal ultrasound in diagnosis should be restricted to men with a difficult physical exam, such as those with prior surgical history or challenging body habitus. It is important to distinguish a subclinical varicocele-a varicocele that is not visible on exam and detected only with ultrasound-because surgical correction has not been shown to improve semen parameters.

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	This article presents an overview of the pathophysiology of varicoceles and discusses indications for treatment, two primary repair techniques, and treatment outcomes.

	Varicoceles form because of increased hydrostatic pressure in the internal spermatic veins, possibly because of incompetent or absent venous valves. Anatomic differences cause increased hydrostatic pressures, making varicoceles more common on the left 

 Therefore, isolated right-sided varicoceles are rare and, when identified, should prompt a workup for an ipsilateral pathologic retroperitoneal process with imaging.

	Clinical varicoceles can negatively affect sperm concentration, motility, and morphology. The following five mechanisms contribute to the pathogenesis of impaired testicular function: hypoperfusion from retrograde flow leading to hypoxia, heat stress from impaired countercurrent heat exchange, oxidative stress from accumulation of reactive oxygen species, hormonal imbalances from abnormal Leydig cell function and decreased intra testicular testosterone, and accumulation of exogenous toxins. However, no single mechanism accounts for the observed impairment 

 Literature supports that grade of varicocele is associated with degree of spermatogenesis impairment and worse semen parameters.

Not all varicoceles require treatment. The American Society for Reproductive Medicine (ASRM) Practice Committee guideline indicates that treatment of the varicocele should be considered when most or all of following conditions are met: the couple is attempting to conceive; the varicocele is palpable on physical examination; the couple has known infertility; the female partner has normal fertility or a potentially treatable cause of infertility, and time to conception is not a concern; and the male partner has abnormal semen parameters 

 Observation is an acceptable option if the patient does not meet any of the previously mentioned criteria.

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	Varicocele repair for men with severe spermatogenic failure-nonobstructive azoospermia (NOA) and severe oligospermia-remains controversial. A 2016 meta-analysis showed increased pregnancy and live birth rates in men with azoospermia and severe oligospermia who underwent varicocele repair prior to in vitro fertilization (IVF) 

 Additionally, men with persistent azoospermia post varicocele repair had higher rates of sperm retrieval on microsurgical testicular sperm extraction.

	It is possible that some men with NOA can have return of sperm in ejaculate and can avoid undergoing a testis biopsy for sperm retrieval. Also, men with severe oligospermia can have improvements in sperm parameters and would qualify them for intrauterine insemination-a less-expensive and less-invasive treatment option compared to IVF. Despite improvements in sperm parameters, the vast majority of couples with severe sperm production defect will require assisted reproductive techniques to achieve a pregnancy. More research is needed to better evaluate the role of varicocele repair in men with testis failure.

	Varicocele repair in adolescents also remains controversial, as many have not reached sexual maturity or have attempted to conceive a child. As such, most indications for repair from the ASRM do not apply. Many pediatric urologists use testicular size discrepancy and testis pain as indications for varicocele repair. Further complicating the decision to intervene is the paucity of information on normal adolescent semen analysis because the 2010 WHO reference values are based on healthy fertile adult males. More research is needed to address optimal management of the adolescent population.

	Varicoceles are treated with either surgery or embolization. Regardless of technique, the ultimate goal is to occlude all spermatic veins draining the affected testis. Surgical options include both laparoscopic and open approaches 

 Laparoscopy is chosen more often in in the pediatric population because of the smaller size of the vessels in the inguinal canal when compared to adults. Open surgical approaches are either inguinal or subinguinal with or without the assistance of an operating microscope; however, microscope-assisted subinguinal varicocelectomy is the gold standard for varicocele repair (figure), with the lowest incidence of arterial injury, hydrocele, and recurrence 

 The use of intraoperative micro-Doppler aids in the identification of the testicular artery and decreases arterial injury.

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	Percutaneous embolization offers a rapid recovery and can be successfully accomplished in approximately 90% of attempts, with higher failure rates for right-sided varicoceles. Nonetheless, the technique demands interventional radiologic expertise and has potentially serious complications, including vascular perforation, coil migration, and thrombosis of pampiniform plexus. Percutaneous embolization can be a valuable treatment option for recurrences after surgery and for men complaining of scrotal pain (orchialgia) from varicocele because inflammation and scarring from open surgery may contribute to additional pain.

	Evaluation for successful varicocele repair is done at least 3 to 6 months postoperatively because spermatogenesis requires approximately 72 days. Data from multiple studies support that men can expect an average increase in sperm concentration of approximately 10 million/cc, 10% increase in motility, and increased overall pregnancy rates 3 months postoperatively compared to preoperative values

 A prospective, randomized, controlled trial showed a significant increase in spontaneous pregnancy in men post-varicocele repair compared to men electing observation (32.9% vs. 13.9%, respectively) 

	Additionally, varicocele repair has been associated with up to 20% improvements in percent sperm DNA fragmentation in infertile men 

 Overall complications are lowest after microsurgical inguinal and subinguinal varicocelectomy 

 Although men with varicoceles have normal serum testosterone, surgical correction of varicocele can increase serum testosterone by approximately 100 ng/dL in select populations, specifically men with low or borderline low preoperative serum testosterone and the elderly 

 Table 2 summarizes the average improvements seen with varicocele repair in men with oligospermia and infertility.

	Varicoceles, a pathologic enlargement of the testicular veins, are the most common correctable cause of male infertility. Not all men with varicoceles require treatment. The decision to treat a varicocele should be based on goals of the patient (and/or partner). Indications for varicocele repair in adolescents and men with NOA require more study. Regardless of technique, varicocele repair leads to improvement in sperm parameters, pregnancy rates, and serum testosterone.

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This article presents an overview of the pathophysiology of varicoceles and discusses indications for treatment, two primary repair techniques, and treatment outcomes.

Varicocele: Treatment indications and repair techniques

, is a resource for urologists and other clinicians who focus on men’s health. ‘Y’tube covers surgical aspects of a variety of men’s health issues with the ultimate goal of accumulating a library of videos to serve as a reference. In this installment, two expert infertility groups demonstrate approaches for obtaining sperm in men with azoospermia.  

	Male infertility can be secondary to azoospermia (lack of sperm in the ejaculate) secondary to testicular failure. Sperm retrieval in combination with intracytoplasmic sperm injection (ICSI) offers a chance of fathering a biological child. The video reviews microdissection testicular sperm extraction (microTESE) as well as multiphoton microscopy, a novel tool that can aid in identification of sperm within the testis. 

Microsurgical testis sperm extraction is now a leading technique in harvesting sperm and confers many advantages. Challenges remain in improving yields, as a visually identified fat tubule may not necessarily bear sperm. In this video, the investigators demonstrate a promising technique using multiphoton microscopy to find tubules containing sperm during microsurgical testis sperm extraction. Should it be demonstrated safe and effective, it may be a significant step in the hunt to track down the ever-elusive testicular sperm.

 The Weill Cornell team demonstrates a novel approach to optimize chances of obtaining sperm in men with spermatogenic failure through microTESE. Dr. Schlegel, who pioneered this technique in 1999 and has the largest case series of microTESE cases, demonstrates meticulous tissue handling, operating in a bloodless field to optimize visual identification of dilated tubules that are more likely to contain mature sperm. The video then goes on to demonstrate an animal model of spermatogenic failure and the use of multiphoton microscopy to identify tubules containing sperm and, importantly, shows that this technique does not harm the sperm. Improvement of identification of sperm in microTESE would represent a major advancement in this technique and would allow more men with spermatogenic failure to have biologic children. We look forward to further work demonstrating the efficacy of this technique in humans. 

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In this video, the investigators demonstrate a promising technique using multiphoton microscopy to find tubules containing sperm during microsurgical testis sperm extraction.

Ranjith Ramasamy, MD

Articles

How do smoking and drinking affect fertility?

Varicocele: Treatment indications and repair techniques

Sperm extraction: MicroTESE and multiphoton microscopy