Alaa Hamada

Insight into oxidative stress in varicocele-associated male infertility: part 2

Varicocele, the leading cause of male infertility, can impair spermatogenesis through several pathophysiological mechanisms. Of these, current evidence suggests that oxidative stress is the central element contributing to infertility in men with varicocele, to which the testis responds by way of heat stress, ischaemia or production of vasodilators, such as nitric oxide. Surgical varicocele repair (varicocelectomy) is beneficial not only for alleviating oxidative stress-associated infertility, but also for preventing and protecting against the progressive character of varicocele and its consequent upregulations of systemic oxidative stress. However, antioxidant therapy in infertile men with surgically treated and those with untreated varicocele is poorly studied, and well-designed trials are needed.

Unexplained Male infertility: diagnosis and Management

Unexplained male infertility is a diagnosis reserved for men in whom routine semen analyses results are within normal values and physical as well as endocrine abnormalities were ruled out. In addition to erectile problems and coital factors, immunologic causes and sperm dysfunction may contribute to such condition. New etiologies of unexplained male infertility include low level leukocytospermia and mitochondrial DNA polymerase gene polymorphism. Contemporary andrology may reveal cellular and sub-cellular sperm dysfunctions which may explain subfertility in such cases, thus aiding the clinician to direct the further work-up, diagnosis and counseling of the infertile male. The objective of this article is to highlight the concept of unexplained male infertility and focuses on the diagnosis and treatment of this condition in the era of modern andrology and assisted reproductive techniques. Extensive literature review was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus.

Cell phones and male infertility: a review of recent innovations in technology and consequences

Cell phones have become a vital part of everyday life. However, the health risks associated with their usage are often overlooked. Recently, evidence from several studies supports a growing claim that cell phone usage may have a detrimental effect on sperm parameters leading to decreased male fertility. Nonetheless, other studies showed no conclusive link between male infertility and cell phone usage. The ambiguity of such results is attributed to the lack of a centralized assay for measuring inflicted damage caused by cell phones. Study design, ethics, and reproducibility are all aspects which must be standardized before any conclusions can be made.

A comprehensive review of genetics and genetic testing in azoospermia

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients.

Proteomic analysis of human spermatozoa proteins with oxidative stress

BackgroundOxidative stress plays a key role in the etiology of male infertility. Significant alterations in the sperm proteome are associated with poor semen quality. The aim of the present study was to examine if elevated levels of reactive oxygen species cause an alteration in the proteomic profile of spermatozoa.MethodsThis prospective study consisted of 52 subjects: 32 infertile men and 20 normal donors. Seminal ejaculates were classified as ROS+ or ROS- and evaluated for their proteomic profile. Samples were pooled and subjected to LC-MS/MS analysis through in-solution digestion of proteins for peptide characterization. The expression profile of proteins present in human spermatozoa was examined using proteomic and bioinformatic analysis to elucidate the regulatory pathways of oxidative stress.ResultsOf the 74 proteins identified, 10 proteins with a 2-fold difference were overexpressed and 5 were underexpressed in the ROS+ group; energy metabolism and regulation, carbohydrate metabolic processes such as gluconeogenesis and glycolysis, protein modifications and oxidative stress regulation were some of the metabolic processes affected in ROS+ group.ConclusionsWe have identified proteins involved in a variety of functions associated with response and management of oxidative stress. In the present study we focused on proteins that showed a high degree of differential expression and thus, have a greater impact on the fertilizing potential of the spermatozoa. While proteomic analyses identified the potential biomarkers, further studies through Western Blot are necessary to validate the biomarker status of the proteins in pathological conditions.

Sperm freezing in transsexual women.

Gender Identity Disorder (GID) is a condition in which a person experiences discrepancy between the sex assigned atbirth and the gender they identify with. Transsexualism is considered the most extreme form of GID and is characterized by the desire to live and be treated as a member of the opposite gender. The prevalence of male-to-female transsexualism in Belgium is estimated at 1 per 12,900 males (De Cuypere et al., 2007). The treatment consists of cross-sex hormone therapy and sex reassignment surgery in accordance with the Standards of Care of the World Professional Association for Transgender Health (WPATH) (7th Version) (www.wpath.org). At the center in Ghent, male-to-female transsexual persons, denoted as transsexual women, are treated in a multidisciplinary approach, including cross-sex hormone therapy and sex reassignment surgery for most. Hormone therapy with anti-androgens and estrogens is used in the majority of transsexual women. After at least 1 year of hormonal therapy, sex reassignment surgery can be offered, which includes orchidectomy andpenectomy in combinationwith vaginoplasty (Selvaggiet al., 2005).Bothhormonalandsurgical interventionsnegativelyaffect the male reproductive system. Hormonal therapy itself leads to decreased spermatogenesis and eventually to azoospermia (Lubbert, Leo-Rossberg, & Hammerstein, 1992; Schulze, 1988). Currently, it is unknown whether spermatogenesis will restore after prolonged estrogen treatment or not (Hembree et al., 2009). Sex reassignment surgery, on the other hand, results in an irreversible loss of natural reproductive capacity in transsexual women. Current reproductive techniques can offer adult transsexual women the possibility of having genetically related children (De Sutter, 2001). They can store their sperm for long-term cryopreservation before undergoing hormonal therapy for future use in assisted reproductive techniques (ART). Sexual orientation of transsexual women may influence the future plans for using the frozen sperm. If transsexual women have a female partner, they can procure children through intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection, based upon the sperm quality after thawing. Reproductive options for transsexual women with a male partner are more difficult as they need oocyte donation as well as a surrogate mother. Reproductive needs and rights of transsexual persons have already been recognized for over 15 years (Lawrence, Shaffer, Snow, Chase, & Headlam, 1996) and since 2001 the WPATH Standards of Care contains a paragraph that addresses the need to discuss reproductive issues with transsexual persons, prior to starting hormonal treatment (Meyer et al., 2001). Also, the new WPATH Standards of Care (Seventh version) (2011) as well as the Clinical Practice Guidelines of the Endocrine Society (Hembree et al., 2009) clearly state that transsexual persons should be encouraged to consider fertility issues before starting cross-gender hormonal treatment. On the other hand, research on this topic is still scarce. In the past 10 years, only two studies have investigated the opinions of transsexual persons themselves concerning this topic (De Sutter, Kira, Verschoor, & Hotimsky, 2002; Wierckx et al., 2012) and few have addressed reproductive difficulties (e.g., access to ART in transsexual patients) (AlvarezK. Wierckx (&) G. T’Sjoen Department of Endocrinology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium e-mail: Katrien.Wierckx@ugent.be

Male infertility: a critical review of pharmacologic management

Introduction: Male factor infertility contributes partially and solely to the problem of childlessness in around 50% of the cases. Unfortunately, 30 – 50% of the etiologies of male infertility are unknown and therefore, no specific therapy can be instituted. Evidence-based medical therapy for male infertility is an attractive research area where a large number of clinical trials, controlled and uncontrolled, using different types of medications have been conducted yielding variable results and outcomes. Areas covered: In this review, we summarize and evaluate the most important and most recent information pertaining to the use of different medications in male infertility and assign level of evidence to these medications. An extensive literature search was performed using the search engines: Pubmed, Science-direct, Ovid and Scopus. Expert opinion: Male infertility represents a very challenging area of clinical medicine. Many different types of medications have been tried and very few have had satisfactory results. There is a huge need to advance and develop andrologic diagnostic techniques, focusing on the metabolomics and proteomics of the sperm, seminal plasma, and testicular tissue. Clarification of the causes of idiopathic male infertility and the discovery of novel molecular targets will help guide future innovative development of new pharmacologic agents.

Two-dimensional differential in-gel electrophoresis–based proteomics of male gametes in relation to oxidative stress

OBJECTIVE To identify the relative abundance of proteins in pooled reactive oxygen species (ROS)-positive (ROS+) and ROS-negative (ROS-) semen samples with the use of two-dimensional differential in-gel electrophoresis (2D-DIGE). DESIGN Spermatozoa suspensions from ROS+ and ROS- groups by 2D-DIGE analysis. SETTING Tertiary hospital. PATIENT(S) 20 donors and 32 infertile men. INTERVENTION(S) Seminal ejaculates evaluated for semen and proteomic analysis. MAIN OUTCOME MEASURE(S) Semen samples from 20 donors and 32 infertile men were pooled, divided into ROS+ and ROS- groups based on the cutoff value of <20 relative light units/s/10(6) sperm and frozen. From each pooled group, spermatozoa were labeled with Cy3/Cy5 fluorescent dye. Duplicate 2D-DIGE gels were run. Image analysis was performed with the use of Decider software. Protein spots exhibiting ≥1.5-fold difference in intensity were excised from the preparatory gel and identified by liquid chromatography-mass spectrometry. Data were analyzed with the use of Sequest and Blast programs. RESULT(S) A total of 1,343 protein spots in gel 1 (ROS-) and 1,265 spots in gel 2 (ROS+) were detected. The majority of protein spots had similar expression, with 31 spots were differentially expressed. Six spots were significantly decreased and 25 increased in the ROS- sample compared with the ROS+ sample. CONCLUSION(S) Significantly different expression of protective proteins against oxidative stress was found in ROS-compared with ROS+ samples. These differences may explain the role of oxidation species in the pathology of male infertility.

Cell Phones and their Impact on Male Fertility: Fact or Fiction

Today, cell phone technology is an integral part of everyday life and its use is not only restricted to voice conversations but also conveying news, high resolution pictures and internet. However, these advances in technology are accompanied by progressive boost in the intensity and frequency of the emitted electromagnetic waves without consideration of their health consequences. Our bodies act as parasitic antennas that receive these waves and convert them into electric and magnetic fields. While thermal effects at the present level of cell phone radiation are negligible, most of the biological interactions are attributed to non-thermal effects. Male reproductive system is highly compartmentalized and sensitive biological system that requires the integration of intrinsic and extrinsic factors to properly function. The generated electrical currents may alter the hormonal milieu and testicular microenvironment, necessary for sperm production. Additionally, sperm are electrically active cells and their exposure to cell phone electromagnetic waves and currents may affect their motility, morphology and even their count. Leaky plasma membranes, calcium depletion and oxidative stress are the postulated cellular mechanisms mediating the harmful effects of cell phones radiation on sperm and male fertility potentials. Evidences for such impacts come from designed animal and in vitro studies which may be different from in vivo human exposure. Nevertheless, the important advice is to apply strict regulations on further increase in the power density of the emitted cell phone radiation and to conduct in vivo human research to study its negative effects on fertility.

Empirical Treatment of Low-level Leukocytospermia With Doxycycline in Male Infertility Patients

OBJECTIVE To design a retrospective study in which infertile men with a seminal leukocyte count of 0.2-1 × 10(6) white blood cells [WBC]/mL were given doxycycline to examine the potential benefits of the treatment on the improvement of semen parameters and natural pregnancy outcomes. It has been reported that even low-level leukocytospermia (0.2-1.0 × 10(6) WBC/mL) could be harmful to male reproductive function and achievement of pregnancy. METHODS The records of 223 patients were reviewed and 61 patients were identified with a leukocyte count of 0.2-1.0 × 10(6) WBC/mL. Of the 61 patients, 27 presented before 2006 and were not routinely treated for this level of leukocytospermia. These patients were our historic control population. Since 2006, 34 patients met these criteria and received empirical antibiotic therapy (treatment group). RESULTS The treatment of low-level leukocytospermia with doxycycline did not show statistically significant differences in the semen parameters among the treated patients. Although the therapy did not alter the semen parameters, low-level leukocytospermia resolved in 56% of the treatment group, well above the spontaneous resolution rate of 25% observed in historic controls. The natural pregnancy rate among the treatment group (15 of 32 [47%]) was significantly greater than that among the controls (5 of 25 [20%]). The odds ratio for pregnancy outcome was 3.7 (95% confidence interval 1.1-11.7; P = .04). CONCLUSION Low-level leukocytospermia might have deleterious effects on male fertility, and antibiotic therapy for such a condition might improve the natural pregnancy rate among infertile couples.