6 Common Myths About Fertility

There’s a lot of information out there, and we know it can be difficult to sort through it all–especially when it comes to something as important as your family. That’s why we’re here—to be your fertility guide! Let’s clear up some of the common misconceptions we hear about fertility.

If Janet Jackson can have her first child in her late 40s, all women can—right?

FALSE.

Not so much. Yes, Janet Jackson announced her first pregnancy at age 49. Actress Marcia Cross had twins at age 44, as did actress Marcia Gay Harden. Late-in-life celebrity pregnancies are in the news consistently. What doesn’t make the news that often is that there’s a very high likelihood that these pregnancies were assisted by reproductive technology, like in vitro fertilization or working with an egg donor.

Celebrities that decide to become pregnant later in life also have thousands of dollars to dedicate to these fertility treatments, which aren’t always covered by health insurance.

Women have fewer eggs as they get older, and they also experience reduced egg quality. Egg quality refers to the state of an egg as being genetically normal or genetically abnormal, and as a woman ages, a higher percentage of her egg reserve is genetically normal.

In a study of over 1 million pregnancies, it was found that risk of miscarriage for women over 40 42 were over 1 in 2; by age 45, over 90%75% of pregnancies ended in miscarriage. (Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27416/)

So, yes, women can have babies in their late 40s, The chance of a successful pregnancy in women aged 40 years or more is poorbut there is a progressive decrease that begins at the time of “peak” fertility in our teens and early 20s and accelerates in our mid-to-late 30s.

 

To get pregnant, you and your partner just need to relax.

FALSE.

While it’s true relaxing could help with infertility caused by chronic stress, infertility isn’t purely a psychological issue. Infertility is a medical condition. Your physical, reproductive health can’t be fixed by positive thinking, a refreshing vacation, or a new mindset.

 

Fertility is a woman’s issue.

FALSE.

It’s not just women that can be infertile. Men can be infertile too. In fact, men and women are equally likely to have fertility problems. About one-third of infertility cases can be attributed to female infertility while men’s problems account for another third of infertility cases. The remaining third of cases may be caused by a combination of male and female infertility, or they may have no known cause.

(Reference: https://www.womenshealth.gov/a-z-topics/infertility)

For the most part, infertility in men is related to issues with the quantity or quality of sperm:

• effective production of sperm

• sperm count, or the number of sperm

• shape of the sperm

• movement of the sperm, which includes both the wiggling motion of the sperm themselves and the transport of the sperm through the tubes of the male reproductive system

Male infertility can also be attributed to certain medical conditions, medications or drugs:

• retrograde ejaculation

• varicocele, or the swelling of the veins around within the testicles testicles that haven’t descended into the scrotum A varicocele is similar to a varicose vein you might see in your leg.

• having antibodies that attack your sperm and destroy them

• a hormonal imbalance, such as low testosterone production

• chemotherapy or radiation therapy

• sulfasalazine and cimetidine may cause male fertility problem (Azulfidine, Azulfidine EN-Tabs), which is used for rheumatoid arthritis (RA) or ulcerative colitis (UC)

• calcium channel blockers, which are used for high blood pressure

• tricyclic antidepressants

• anabolic steroids, which are used for improved athletic performance or hormonal issues

• recreational drugs such as marijuana and cocaine

• long-term use of high-dosage nonsteroidal anti-inflammatory drugs (NSAIDS) such as aspirin (Bayer) and ibuprofen (Advil, Motrin)

 

There’s not much a doctor can do to help male infertility.

FALSE.

Men should plan to see a doctor after one year of trying to conceive or if any of the following apply:

• erectile dysfunction (ED)

• problems with ejaculation

• low sex drive

• pain or swelling in the genital area

• having undergone a previous surgery in the genital area

Your doctor will first take your medical history. During this time, they’ll ask about your overall health, your sexual history, and factors that could affect your fertility. They’ll also perform a physical examination where they check your genitals for any structural abnormalities or lumps.

A semen analysis will likely then be performed, to see how many sperm are present and whether the sperm are shaped normally and moving properly.

Depending on the results of your initial exam and semen analysis, your doctor may want to perform additional genetic or hormone tests.

 

Male infertility can’t be treated.

FALSE.

Depending on the cause, male infertility can be treated with various options, such as surgery, medications and assisted reproductive technology (ART). For example, surgery can fix obstructions that are preventing sperm from being present in the ejaculate. It can also correct conditions such as varicocele.

 

Male infertility can be detected.

TRUE.

There are common signs of infertility in men. Swelling of the testicles, changes in sexual desire, small and firm testicles, and problems maintaining an erection or ejaculation are all indicators of male infertility.

 

In Summary

Around 15 to 20 percent of couples trying to conceive will have trouble with infertility. Female factor infertility is typically to blame 40 percent of the time, while male factor infertility is the cause of issues 30 to 40 percent of the time. A combination of these factors leads to infertility 20 to 30 percent of the time. (Reference: https://www.cornellurology.com/clinical-conditions/male-infertility/general-information/fertility-evaluation/)

If you’ve been diagnosed with infertility, you may still be able to conceive.  The best move you can make is to see your doctor to get a better understanding of how to cope and improve your chances.

Pain Research and Management

Volume 2017 (2017), Article ID 3829168, 5 pages
https://doi.org/10.1155/2017/3829168
Research Article
Characteristics and Etiologies of Chronic Scrotal Pain: A Common but Poorly Understood Condition
Osamah Aljumaily,1,2 Hind Al-Khazraji,1 Allan Gordon,3 Susan Lau,1,4 and Keith A. Jarvi1,2,4,5
1Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
2Murray Koffler Urologic Wellness Centre, Mount Sinai Hospital, Toronto, ON, Canada
3Wasser Pain Management Centre, Mount Sinai Hospital, Toronto, ON, Canada
4Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
5Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada
Correspondence should be addressed to Keith A. Jarvi
Received 28 November 2016; Revised 23 January 2017; Accepted 13 February 2017; Published 2 March 2017
Academic Editor: Yelena Granovsky
Copyright © 2017 Osamah Aljumaily et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 

Abstract

Chronic scrotal pain (CSP) is a common and debilitating condition, but the underlying characteristics and etiology of CSP are poorly understood. The objective of this study is to identify the characteristic and etiologies of CSP. Men presenting for management of CSP completed a standardized questionnaire and underwent a complete physical examination. From Feb 2014 to Sep 2015, a total of 131 men (mean age 43) with CSP were studied. The CSP was of long duration (mean of years) and dramatically affected men’s lives, with adverse effects on normal activities (71.%), ability to work (51.90%), and sexual functioning (61.8%). 50.4% felt depressed on most days, and 67.17% felt either unhappy or terrible with their present condition. Physical examination revealed that the epididymis was the most common tender area found in 70/131 men (53.43%), though a musculoskeletal source for the pain was found in 9.9%. Neuropathic changes were found in 30%. For close to half of the men (43.5%) we were unable to identify any potential cause for the CSP. This study characterizes the dramatic impact that CSP has on the lives of men, while providing an understanding of the common etiologies.
 
1. Introduction
While chronic scrotal pain (CSP), defined as pain in the scrotum of more than 3-month duration, appears to be a very common condition, there are very few studies on the actual incidence of CSP [1]. Ciftci et al. reported that 4.75% of all men presenting to urology clinics for other reasons had CSP [2]. A similar incidence was found in our centre, where Forbes et al. found that 4.3% of all men presenting to a dedicated male infertility clinic self-identified as having CSP (unpublished data). A lower incidence was reported in Switzerland of 350 to 400 cases of CSP per 100,000 men annually [3]. These estimates were based on survey of urologists’ recollections of the numbers of men with CSP they treated and as such will be an underestimate of the true incidence [3].
For a condition which is this common, there is remarkably little known or published about the causes or the characteristics of CSP [4]. Interestingly, there are no guidelines specifically for the investigation or management of CSP, though the European Urology Association included CSP in the guidelines for the management of pelvic pain, but with a very limited section on the guidelines for management of CSP [5].
We have a number of reports on the different potential causes of CSP but no information of the frequency of each of these potential etiologies [2, 4, 5]. In general, CSP could be due to pain arising from the scrotal contents directly or referred from the abdomen/inguinal region, the retroperitoneum, or the nervous system [6]. While there are several papers listing the causes of CSP, there are no reports on the frequencies of any of the causes of CSP [6]. Often no etiology for the CSP is identified [1, 4, 5].
Diagnosing a potential etiology for CSP is also complicated by neuropathic changes which may occur in patients with chronic pain. While the initiating event may be a vasectomy, infection, or other conditions, nervous system plasticity is thought to result in upregulation of both central and peripheral neuropathic pathways in response to chronic pain, leading to neuropathic components to the chronic pain [7]. These neuropathic changes may remain even if the initiating event has disappeared. The neuropathic changes may also be bilateral. A source of pain on one side may also lead to chronic pain on the contralateral side: nerves from the pelvic plexus cross over to the contralateral pelvic plexus, which may play a role in creating a contralateral effect in the presence of unilateral pathology (e.g., varicocele) [8].
While neuropathic changes associated with CSP are recognized, the frequency of neuropathic changes has not been reported to date.
There is also little published information on the clinical condition of CSP, including the characteristics of the pain, the factors which modify the pain (exacerbating and relieving factors), and the impact of the CSP on men’s quality of life, ability to work, and ability to have normal social lives [5].
With limited published information on the etiology and characteristics of CSP, it is not surprising that the optimum method for the evaluation and treatment of this syndrome remains uncertain. The objective of this study is to survey a patient population with CSP to identify the different types of etiologies of CSP, the frequency of the different etiologies, and the different types of characteristics of the CSP in men.
 
2. Material and Methods
This assessment was performed at the Multidisciplinary Orchialgia Clinic (MOC) located at Mount Sinai Hospital in Toronto, Canada, in which the patient is evaluated simultaneously by both urologists with special expertise in CSP and neurologists specialized in chronic pain conditions.
Mount Sinai Hospital local ethical committee approval was obtained prior to commencement of the study and the patients in this manuscript have given written informed consent to publication of their case details. This is a retrospective review of a prospectively collected database of men presenting to a university program specializing in chronic scrotal pain.
The men completed a standardized questionnaire to elicit information on the pain severity, pain duration, potential etiology, quality, location, progression, previous treatments, and impact of different activities on severity of CSP (see Supplementary Material available online at https://doi.org/10.1155/2017/3829168 for full questionnaire). The information on the questionnaires was retrospectively reviewed.
The severity of patients’ average and most severe episodes of pain was recorded in the questionnaire based on the standardized Numeric Rating Scale (NRS) for pain from 0 to 10. The NRS is well known and widely accepted as a valid measure of pain severity in adults [1]. We also developed internally an additional nonvalidated question to determine the frequency of severe pain experienced by the men.
The impact of CSP on men’s sexual and work activities was graded as none, only a little, some, or a lot using the published questionnaire from Nickel et al. [9].
In addition, we included standardized quality of life and depression questions in the questionnaire [9] and depression score questions [10] as well as standardized questionnaires to identify symptoms of androgen insufficiency (ADAM score) [11].
There were no existing questionnaires that we found on CSP potential etiologies, location, and characteristics or modifying factors so we developed but have not validated this portion of the questionnaire internally. Other parts of the questionnaire included general information on demographics, general health and lifestyle factors, and questions on previous therapies for the CSP.
Physical examination was used to identify any palpable abnormalities of the scrotal contents, inguinal region, or the local musculoskeletal structures (adductor tendons, conjoint tendon, etc.). Tender areas were identified by gentle palpation of the above structures. Often more than one area of tenderness was identified and if so we recorded this information taking care to identify the degree of tenderness in each area (e.g., head of left epididymis is more tender than tail of left epididymis). A focussed neurological examination including sensory testing was performed to identify neuropathic changes in the lower abdomen, groin, and legs.
Imaging was not routinely performed on our patients but was reserved for those we suspected had an abnormality in the testis (scrotal ultrasound) or those who had no tenderness found in the scrotum, inguinal region, or the groin (abdominal imaging to identify a retroperitoneal or renal cause for the CSP).
The results were analyzed with descriptive statistics.
 
3. Results
From Feb 2014 to Sep 2015, a total of 131 men presenting for assessment of CSP completed questionnaires. The mean age of the men was (SD) years with a mean duration of CSP of years.
There were a variety of potential causes for the CSP reported by the patients including the following:(1)Unknown: 43.5% (Table 1)(2)Previous vasectomy: 20.6%(3)Testicular trauma: 12.2%(4)Documented testicular, prostate, or epididymal infection: 11.5%(5)Hernia repair: 4.6%(6)Other reported potential causes (varicocelectomy, TURP, hydrocelectomy, donor nephrectomy, orchidectomy, and knee surgery: each was related definitively to the surgery by the patient)
Table 1: Identified causes of the CSP.
The men often complained of other existing chronic pain conditions such as chronic bowel pain found in 28.24%, migraines in 20%, and fibromyalgia in 6.9%. While the pain was described as being in the testes by most of the patients, the most common area of tenderness identified by careful physical examination was the epididymis in 53.43%. Tenderness was found in the testicle in 25.19%, the site of vasectomy in 11.5%, and the conjoint tendon in 10%.
Neuropathic changes were found in the groin regions in close to 30% of the men: there was evidence of hypersensitivity with increased sensitivity to light touch found in 8.4% while conversely decreased sensation to light touch was noted in 5.34% of men. Hyperalgesia was also noted with increased sensitivity to pin prick found in 11% of patients and decreased in 5.3%.
For most men, the scrotal pain was quite severe, but for almost all men the pain tended to wax and wane with time. On average, severe pain episodes (mean pain severity of on a 10-point numeric pain scale) affected men of the time. The level of pain severity was similar in the groups of men with different etiologies for the scrotal pain. Most men had some constant background pain, which the men rated as a pain level of (Figures 1–3). The quality of the pain was also extremely variable, with the pain described as sharp in 52.7%, dull in 38.2%, burning in 6.9%, and throbbing in 2.3%.
Figure 1: Average pain score in patients with CSP.
Figure 2: Pain levels with episodes of severe exacerbations.
Figure 3: Frequency of severe pain episodes in patients with CSP.
The CSP was exacerbated by a number of factors such as sitting for 59.5% of the men, movement (48.1%), tight clothing (44.3%), ejaculation (36.6%), and sex (35.9%). On the other hand, certain factors improved the pain such as lying down (48.85%), sitting (24.4%), and hot baths (4.6%). Unfortunately, for the vast majority of the men, the pain was either becoming more severe with time (49.6%) or continuing at the same pain level (33.6%).
The impact of the CSP on the lives of men was very significant, with 93/131 (71%) of the men noting that the CSP symptoms prevented them from doing normal social activities, 51.9% found the CSP interfered with their ability to work, and 61.8% noted a negative impact on their sexual function and enjoyment. The severity of the pain and the impact on the men’s lives had an effect on the men’s mood, with 50.4% of the patients who answered the question saying they felt depressed on most days. Many more felt either unhappy or terrible (67.2%) with their present condition.
In general, the men had often tried other therapies to manage their pain. Before presenting to our clinic, they(1)used over the counter medications: 60.30%,(2)had been prescribed antibiotics: 58.8%,(3)used anti-inflammatory medications: 65.6%,(4)had used neuropathic pain medications: 31.3%.
The ongoing use of narcotics to manage the pain was extremely common (35.9%), while 38.2% of the men used antidepressants. Only 2 patients (1.52%) used methadone and another 2 used nabilone. Medical marijuana use was uncommon in this group (2.29%).
3.1. Discussion
CSP remains a challenge to clinicians and patients alike. Clinicians are often faced with a patient with a debilitating, high impact and chronic condition. The pain in our patients was severe, usually progressive, was worsened by even simple daily activity, and limited many of the activities of daily life like work, social activities, and sports. Many of the men were depressed and most felt that their condition was “terrible.” A similar finding was published by Nickel et al. [9].
While chronic pain of any origin may be debilitating, limit activities, and lead to poor quality of life and depression, there are some characteristics that are much more common in men with CSP: sex and ejaculation commonly exacerbate the pain for men with CSP, with the men describing impaired sexual function and enjoyment. In addition, sitting for the majority of men exacerbated the pain, while lying down improved the pain levels.
While there is very little published information on CSP, it appears to be an extremely common condition [12, 13], affecting potentially more than 4% of men [2, 12, 13]. This lack of publications and information on CSP makes the challenge to clinicians even greater as there is a lack of information on the frequency of the different potential causes of CSP, the strategies to investigate and manage men with CSP, and outcomes of therapies.
This study and others have identified multiple potential causes for the CSP, varying from previous surgery (most notably vasectomies), infections, trauma, referred pains, and medications. Possibly not surprisingly, for almost half of the men in this series, no potential cause for the CSP was identified.
The use of the term “potential causes” must be emphasized, since there is often no clear direct link between these “potential causes” and the CSP: for example, men may have had a vasectomy (which is common) and also have CSP (also common).
This study does emphasize the variability of presentation, characteristics, and etiology of CSP. It should also be recognized that scrotal pain is not a synonym for scrotal pathology and other sources of referred pain should be evaluated. Many of our patients presented with what by history was chronic scrotal pain, but the source of the pain was not from the scrotal contents. Musculoskeletal pain was the source of the CSP in close to 10% of the men. In addition, neuropathic changes occur in 30% of men with CSP. What may have begun as nociceptive pain arising from the scrotal contents has developed into neuropathic pain and neuroplasticity modified the central and peripheral nerves leading to hyperalgesia and allodynia.
To further complicate matters, men with CSP have significant limitations on their normal activities and often expressed feelings of depression.
For a condition with this type of variability of presentation, characteristics, and etiology, one would also expect a variability of response to activities and therapies. Most patients reported that lying down helped reduce the scrotal pain, while most found that sex/ejaculation and tight clothing exacerbated the pain. Interesting, again illustrating the variability of CSP, a similar number of men found that sitting improved or exacerbated the pain. Patients had used a variety of different medications (often multiple different medications for the same patient) with different responses. The variability of response to medical therapies should not be surprising given the variety of etiologies of CSP and the very high frequency (43.5%) of an unknown etiology.
Clearly, evaluating patients with chronic scrotal pain should be comprehensive and must include evaluations to rule out medically important and treatable urological causes including tumours, intermittent torsion, infection, and varicocele. It is also important to remember that a significant fraction of the men presenting with CSP symptoms have a musculoskeletal or a neuropathic source for the symptoms.
While the history may help to differentiate chronic scrotal contents (testis, epididymis, and paratesticular structures) pain from musculoskeletal or neuropathic pain, a thorough physical examination is essential, providing information about the source of the pain in most cases [14]. This will help determine if the scrotal contents are tender and are the source of the CSP. We also recommend careful examination of the inguinal canal and the adductor tendon. Quite often (just under 10% in our series) the pain is found to arise from a MSK source (the conjoint tendon or the adductor tendon). Additionally, we suggest a focussed neurological examination of the groin to identify increased or decreased sensation to light touch and pin prick. Close to 30% of the men had a neuropathic component of the pain diagnosed by a focussed neurological examination.
Finally, it is also important to provide a psychosocial evaluation in order to determine whether there is any disability associated with the pain and if there are signs or symptoms of depression. Similar to our study, it has also been reported in the literature that a significant number of patients who suffer from chronic orchialgia express signs of major depression and a significant number of these patients have clinical dependencies [15].
While CSP is a challenging condition to investigate and manage, a thorough history to identify the causes and impact of CSP on the patients coupled with a physical examination of the scrotum and groin often identifies the cause and the origin of the pain. While management is often multidisciplinary (pain medicine specialists, neurologists, psychiatrists/psychologists, physiotherapists, orthopaedics, sports medicine, general surgery, and urologists), an understanding of the cause, characteristics, and origin of the CSP is essential to tailor consultations to the appropriate services.
3.2. Limitations
This is a single centre study so the results may not be generalizable to the types of men with CSP seen at other pain centres. In addition, the men who present for investigation and therapy for the CSP are likely to be more severely affected than a general population of men with CSP, which biases our sample to the more severely affected men with CSP.
4. Conclusion
CSP is an extremely variable condition with a wide variety of etiologies, effects on quality of life, exacerbating factors, and treatment responses. This condition represents a challenge to patients and clinicians. A multidisciplinary approach is needed to optimally manage the patients with CSP.
Competing Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
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The relationship between sperm viability and DNA fragmentation rates

Background:  
In humans, sperm DNA fragmentation rates have been correlated with sperm viability rates. Reduced sperm viability is associated with high sperm DNA fragmentation, while conversely high sperm viability is associated with low rates of sperm DNA fragmentation. Both elevated DNA fragmentation rates and poor viability are correlated with impaired male fertility, with a DNA fragmentation rate of > 30% indicating subfertility. We postulated that in some men, the sperm viability assay could predict the sperm DNA fragmentation rates. This in turn could reduce the need for sperm DNA fragmentation assay testing, simplifying the infertility investigation and saving money for infertile couples.

Methods:
All men having semen analyses with both viability and DNA fragmentation testing were identified via a prospectively collected database. Viability was measured by eosin-nigrosin assay. DNA fragmentation was measured using the sperm chromosome structure assay. The relationship between DNA fragmentation and viability was assessed using Pearson’s correlation coefficient.

Results:
From 2008-2013, 3049 semen analyses had both viability and DNA fragmentation testing. A strong inverse relationship was seen between sperm viability and DNA fragmentation rates, with r = -0.83. If viability was ≤ 50% (n = 301) then DNA fragmentation was ≥ 30% for 95% of the samples. If viability was ≥ 75% (n = 1736), then the DNA fragmentation was ≤ 30% for 95% of the patients. Sperm viability correlates strongly with DNA fragmentation rates.

Conclusions:
In men with high levels of sperm viability ≥ 75%, or low levels of sperm viability ≤ 30%, DFI testing may be not be routinely necessary. Given that DNA fragmentation testing is substantially more expensive than vitality testing, this may represent a valuable cost-saving measure for couples undergoing a fertility evaluation.

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Chlamydial Infection and Its Role in Male Infertility

Introduction:
Chlamydia trachomatis is an established cause of tubal factor infertility; however its role in male fertility is not as clear.We sought to determine the prevalence of Chlamydia in infertile men and evaluate its impact onmale reproductive potential.


Materials and Methods:
We compared the incidence of Chlamydia in our infertile male population with that reported in the literature. We then reviewed the impact of Chlamydia infection on male fertility.


Results:
The incidence of Chlamydia infection in our population of infertile men was 0.3%. There is considerable variability in the reported incidence, likely due to variation in the population studied, and detection technique. The optimal testing method and sample are presently unclear. The effect of Chlamydia on male reproductive function is also variable in the literature, but appears to be relatively minimal and may be related primarily to sperm DNA fragmentation or female partner transmission.


Conclusions:
The prevalence of Chlamydia in the infertile male population is low and routine testing is not supported by the literature. For high-risk infertile men, nucleic acid testing of urine +/− semen is the most sensitive method to detect Chlamydia. A validated testing system for semen needs to be developed, so that a standardized methodology can be recommended. In this way the full implications of Chlamydia on male fertility can be elucidated.


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Effect of different cryoprotectant agents on spermatogenesis efficiency in cryopreserved and grafted neonatal mouse testicular tissue

Overview

Restoration of male fertility associated with use of the cryopreserved testicular tissue would be a significant advance in human and animal assisted reproductive technology. 

The purpose of this study was to test the effects of four different cryoprotectant agents (CPA) on spermatogenesis and steroidogenesis in cryopreserved and allotransplanted neonatal mouse testicular tissue. Hank’s balanced salt solution (HBSS) with 5% fetal bovine serum including either 0.7 M dimethyl sulfoxide (DMSO), 0.7 M propylene glycol (PrOH), 0.7 M ethylene glycol (EG), or glycerol was used as the cryoprotectant solution. Donor testes were collected and dissected from neonatal pups of CD-1 mice (one day old). Freezing and seeding of the testicular whole tissues was performed using an automated controlled-rate freezer. Four fresh (non-frozen) or frozen–thawed pieces of testes were subcutaneously grafted onto the hind flank of each castrated male NCr nude recipient mouse and harvested after 3 months. Fresh neonatal testes grafts recovered from transplant sites had the most advanced rate of spermatogenesis with elongated spermatid and spermatozoa in 46.6% of seminiferous tubules and had higher levels of serum testosterone compared to all other frozen–thawed-graft groups (p < 0.05). 

Fresh grafts and frozen–thawed grafts in the DMSO group had the highest rate of tissue survival compared to PrOH, EG, and glycerol after harvesting (p > 0.05). The most effective CPA for the freezing and thawing of neonatal mouse testes was DMSO in comparison with EG (p < 0.05) in both pre-grafted and post-grafted tissues based on histopathological evaluation. Likewise, the highest level of serum testosterone was obtained from the DMSO CPA group compared to all other cryoprotectants evaluated (p < 0.05). 

The typical damage observed in the frozen–thawed grafts included disruption of the interstitial stroma, intercellular connection ruptures, and detachment of spermatogonia from the basement membrane. These findings indicate that neonatal mouse testes were most effectively preserved when frozen with HBSS medium with DMSO and that the type of CPA is a significant factor to obtain the most advanced stages of spermatogenesis and steroidogenesis after cryopreservation, thawing, and transplantation of neonatal mouse testes.

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Quantitative Proteomics Reveals That Enzymes of the Ketogenic Pathway Are Associated with Prostate Cancer Progression

Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in men. One common treatment is androgen-deprivation therapy, which reduces symptoms in most patients. However, over time, patients develop tumors that are androgen-independent and ultimately fatal. 

The mechanisms that cause this transition remain largely unknown, and as a result, there are no effective treatments against androgen-independent prostate cancer. As a model platform, we used the LNCaP cell line and its androgen-independent derivative, LNCaP-SF. Utilizing stable isotope labeling with amino acids in cell culture coupled to mass spectrometry, we assessed the differential global protein expression of the two cell lines. Our proteomic analysis resulted in the quantification of 3355 proteins. Bioinformatic prioritization resulted in 42 up-regulated and 46 down-regulated proteins in LNCaP-SF cells relative to LNCaP cells. 

Our top candidate, HMGCS2, an enzyme involved in ketogenesis, was found to be 9-fold elevated in LNCaP-SF cells, based on peptide ratios. After analyzing the remaining enzymes of this pathway (ACAT1, BDH1, HMGCL, and OXCT1), we observed increased expression of these proteins in the LNCaP-SF cells, which was further verified using Western blotting. To determine whether these enzymes were up-regulated in clinical samples, we performed quantitative PCR and immunohistochemistry on human prostate cancer tissues, from which we observed significantly increased transcript and protein levels in high-grade cancer (Gleason grade > 8). 

In addition, we observed significant elevation of these enzymes in the LuCaP 96AI castration-resistant xenograft. Further assessment of ACAT1 on human castration-resistant metastatic prostate cancer tissues revealed substantially elevated expression of ACAT1 in these specimens. 

Taken together, our results indicate that enzymes of the ketogenic pathway are up-regulated in high-grade prostate cancer and could serve as potential tissue biomarkers for the diagnosis or prognosis of high-grade disease.


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Proteomic Profiling of Androgen-independent Prostate Cancer Cell Lines Reveals a Role for Protein S during the Development of High Grade and Castration-resistant Prostate Cancer

Background:
The mechanisms that cause castration-resistant prostate cancer remain unknown.


Results:
Using high throughput proteomics and subsequent clinical validation, we identified Protein S as being elevated in high
grade/advanced prostate cancer.


Conclusion:
Protein S is elevated in aggressive prostate cancer.


Significance:
Protein S expression could serve as a biomarker of aggressive prostate cancer.


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Varicocele surgery or embolization: Which is better?

Introduction:
Varicocele remains the most commonly identified correctable cause of male factor infertility. Surgical correction is the most commonly performed technique to treat varicoceles with a technical failure rate of less than 5%. An attractive alternative to surgery is the selective catheterization and embolization of the gonadal vein. This data are limited by small series.


Methods:
We reviewed a total of 158 patients. These patients underwent embolization for clinical varicoceles and male factor infertility between 2004 and 2008. Of these, 56% underwent attempted bilateral embolization, 43% unilateral left-sided embolization and 1.3% unilateral right-sided embolization.


Results:
Of these patients who underwent attempted bilateral embolization, 19.3% did not experience a successful obliteration of the right gonadal vein and 2.3% (2/88) experienced a failure rate in the embolization of the left gonadal vein. Of the 2 attempts at unilateral right-sided embolization, there were no failures. Of the 68 unilateral left-sided embolization attempts, there was a 4.4% failure rate. Of all of the right-sided embolization attempts, 18.9% failed, while 3.2% of the left-sided attempts failed.


Conclusion:
This review represents the largest contemporary series of varicocele embolization outcomes currently in the literature. Our 19.3% technical failure rate for bilateral varicocele embolization is higher than the current published rate of 13% and is largely related to failure to successfully occlude the right gonadal vein. This supports our belief that bilateral varicoceles are best managed with a primary microsurgical approach, where technical failure rates are expected to be less than 5% based on published data. Men with unilateral left-sided varicoceles should be offered both options as they have similar failure rates, but with embolization offering some clear advantages to the patient.


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Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry

Background:
Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis.


Results:
Using mass spectrometry, we identified 1708 proteins in the pooled seminal plasma of 5 prostatitis patients. Comparing this list to a previously published list of seminal plasma proteins in the pooled seminal plasma of 5 healthy, fertile controls yielded 1464 proteins in common, 413 found only in the control group, and 254 found only in the prostatitis group. Applying a set of criteria to this dataset, we generated a high-confidence list of 59 candidate prostatitis biomarkers, 33 of which were significantly increased in prostatitis as compared to control, and 26 of which were decreased. The candidates were analyzed using Gene Ontology and Ingenuity Pathway analysis to delineate their subcellular localizations and functions.


Conclusions:
Thus, in this study, we identified 59 putative biomarkers in seminal plasma that need further validation for diagnosis and monitoring of prostatitis.


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Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Overview

Seminal plasma is a promising biological fluid to use for noninvasive clinical diagnostics of male reproductive system disorders. To verify a list of prospective male infertility biomarkers, we developed a multiplex selected reaction monitoring assay and measured the relative abundance of 31 proteins in 30 seminal plasma samples from normal, nonobstructive azoospermia and post-vasectomy individuals. Median levels of some proteins were decreased by more than 100-fold in nonobstructive azoospermia or post-vasectomy samples, in comparison with normal samples.

To follow up the most promising candidates and measure their concentrations in seminal plasma, heavy isotope-labeled internal standards were synthesized and used to reanalyze 20 proteins in the same set of samples. Concentrations of candidate proteins in normal seminal plasma were found in the range 0.1–1000 g/ml but were significantly decreased in nonobstructive azoospermia and post-vasectomy.

These data allowed us to select, for the first time, biomarkers to discriminate between normal, nonobstructive azoospermia, and post-vasectomy (simulated obstructive azoospermia) seminal plasma samples. Some testis-specific proteins (LDHC, TEX101, and SPAG11B) performed with absolute or nearly absolute specificities and sensitivities. Cell-specific classification of protein expression indicated that Sertoli or germ cell dysfunction, but not Leydig cell dysfunction, was observed in nonobstructive azoospermia seminal plasma.

The proposed panel of biomarkers, pending further validation, could lead to a clinical assay that can eliminate the need for testicular biopsy to diagnose the category of male infertility, thus providing significant benefits to patients as well as decreased costs associated with the differential diagnosis of azoospermia.

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