Ahmad Majzoub

Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios

Sperm DNA fragmentation (SDF) has been generally acknowledged as a valuable tool for male fertility evaluation. While its detrimental implications on sperm function were extensively investigated, little is known about the actual indications for performing SDF analysis. This review delivers practice based recommendations on commonly encountered scenarios in the clinic. An illustrative description of the different SDF measurement techniques is presented. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. High SDF is also linked with recurrent spontaneous abortion (RSA) and can influence outcomes of different assisted reproductive techniques. Several studies have shown some benefit in using testicular sperm rather than ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with evidence of exposure to pollutants can benefit from sperm DNA testing as it can help reinforce the importance of lifestyle modification (e.g., cessation of cigarette smoking, antioxidant therapy), predict fertility and monitor the patient’s response to intervention.

Bibliometrics: tracking research impact by selecting the appropriate metrics

Traditionally, the success of a researcher is assessed by the number of publications he or she publishes in peer-reviewed, indexed, high impact journals. This essential yardstick, often referred to as the impact of a specific researcher, is assessed through the use of various metrics. While researchers may be acquainted with such matrices, many do not know how to use them to enhance their careers. In addition to these metrics, a number of other factors should be taken into consideration to objectively evaluate a scientist′s profile as a researcher and academician. Moreover, each metric has its own limitations that need to be considered when selecting an appropriate metric for evaluation. This paper provides a broad overview of the wide array of metrics currently in use in academia and research. Popular metrics are discussed and defined, including traditional metrics and article-level metrics, some of which are applied to researchers for a greater understanding of a particular concept, including varicocele that is the thematic area of this Special Issue of Asian Journal of Andrology. We recommend the combined use of quantitative and qualitative evaluation using judiciously selected metrics for a more objective assessment of scholarly output and research impact.

Specialized sperm function tests in varicocele and the future of andrology laboratory.

Varicocele is a common medical condition entangled with many controversies. Though it is highly prevalent in men with infertility, still it marks its presence in males who do have normal fertility. Determining which patients are negatively affected by varicocele would enable clinicians to better select those men who benefitted the most from surgery. Since conventional semen analysis has been limited in its ability to evaluate the negative effects of varicocele on fertility, a multitude of specialized laboratory tests have emerged. In this review, we examine the role and significance of specialized sperm function tests with regards to varicocele. Among the various tests, analysis of sperm DNA fragmentation and measurements of oxidative stress markers provide an independent measure of fertility in men with varicocele. These diagnostic modalities have both diagnostic and prognostic information complementary to, but distinct from conventional sperm parameters. Test results can guide management and aid in monitoring intervention outcomes. Proteomics, metabolomics, and genomics are areas; though still developing, holding promise to revolutionize our understanding of reproductive physiology, including varicocele.

Diagnostic application of oxidation-reduction potential assay for measurement of oxidative stress: clinical utility in male factor infertility

The objectives of this study were to: (i) describe a protocol measuring the oxidation-reduction potential (ORP) by MiOXSYS System as an alternative method of seminal oxidative stress (OS) testing; (ii) establish a reference value for static ORP (sORP) to distinguish between controls and male factor infertility patients; (iii) evaluate intra-observer and inter-observer reliability; and (iv) examine association of sORP with sperm parameters predictive of male factor infertility. Elevated levels of sORP were seen in infertile patients (6.22 ± 1.10 mV/106 sperm/ml) compared with controls (1.59 ± 0.29 mV/106 sperm/ml) (P = 0.004). A sORP cut-off value 1.36 mV/106 sperm/ml identified normal semen and abnormal semen quality with a sensitivity 69.6%, specificity 83.1%, positive predictive value 85.3% and negative predictive value 65.9%. The test demonstrated strong intra-observer (CV 8.39%) and inter-observer reliability (correlations >0.97). Higher sORP levels were associated with poor sperm parameters across the fertility status of subjects. Negative correlations were noted with sperm parameters (concentration, total sperm count, motility and morphology) indicating these male infertility parameters are related to OS. In conclusion, the introduction of ORP as a novel clinical test for assessment of OS will help clinicians to better diagnose and manage male factor infertility patients.

The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility

Sperm DNA fragmentation (SDF) testing has been emerging as a valuable tool for male fertility evaluation. While the essential role of sperm DNA integrity in human reproduction was extensively studied, the clinical indication of SDF testing is less clear. This clinical practice guideline provides recommendations of clinical utility of the test supported by evidence. It is intended to serve as a reference for fertility specialists in identifying the circumstances in which SDF testing should be of greatest clinical value. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. Outcomes of natural pregnancy and assisted reproductive techniques (ART) can be predicted by result of SDF tests. High SDF is also linked with recurrent pregnancy loss (RPL) and failure of ART. Result of SDF testing may change the management decision by selecting the most appropriate ART with the highest success rate for infertile couples. Several studies have demonstrated the benefit in using testicular instead of ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with modifiable lifestyle factor may benefit from SDF testing by reinforcing risk factor modification and monitoring patient’s progress to intervention.

ICSI outcome in patients with high DNA fragmentation: Testicular versus ejaculated spermatozoa

Sperm DNA fragmentation (SDF) has emerged as an important biomarker in the assessment of male fertility potential with contradictory results regarding its effect on ICSI. The aim of this study was to evaluate intracytoplasmic sperm injection (ICSI) outcomes in male patients with high SDF using testicular versus ejaculated spermatozoa. This is a prospective study on 36 men with high‐SDF levels who had a previous ICSI cycle from their ejaculates. A subsequent ICSI cycle was performed using spermatozoa retrieved through testicular sperm aspiration. Results of the prior ejaculate ICSI were compared with those of the TESA‐ICSI. The mean (SD) SDF level was 56.36% (15.3%). Overall, there was no difference in the fertilization rate and embryo grading using ejaculate and testicular spermatozoa (46.4% vs. 47.8%, 50.2% vs. 53.4% respectively). However, clinical pregnancy was significantly higher in TESA group compared to ejaculated group (38.89% [14 of 36] vs. 13.8% [five of 36]). Moreover, 17 live births were documented in TESA group, and only three live births were documented in ejaculate group (p < .0001). We concluded that the use of testicular spermatozoa for ICSI significantly increases clinical pregnancy rate as well as live‐birth rate in patients with high SDF.

Role of Antioxidants in Assisted Reproductive Techniques

Oxidative stress (OS) has been recognized as a significant cause of suboptimal assisted reproductive outcome. Many of the sperm preparation and manipulation procedures that are necessary in the in vitro environment can result in excessive production of reactive oxygen species (ROS) thereby exposing the gametes and growing embryos to significant oxidative damage. Antioxidants have long been utilized in the management of male subfertility as they can counterbalance the elevated levels of ROS inducing a high state of OS. Few studies have looked into the clinical effectiveness of antioxidants in patients undergoing assisted reproduction. While an overall favorable outcome has been perceived, the specific clinical indication and optimal antioxidant regimen remain unknown. The goal of our review is to explore the sources of ROS in the in vitro environment and provide a clinical scenario-based approach to identify the circumstances where antioxidant supplementation is most beneficial to enhance the outcome of assisted reproduction.

Outcome of testicular sperm extraction in nonmosaic Klinefelter syndrome patients: what is the best approach?

Klinefelter syndrome (KS) is the most common chromosomal disorder associated with male hypogonadism and infertility. Parenthood can be achieved in men with KS by intracytoplasmic sperm injection (ICSI) using testicular spermatozoon. The aim of this study was to evaluate surgical sperm retrieval (SSR) rate in patients with KS and to investigate the approach associated with the highest SSR. This is a retrospective study where all medical records of patients with KS who underwent SSR for ICSI, in our centre in the past 14 years, were reviewed. Forty‐three patients were included in this study. Twenty‐three underwent conventional testicular sperm extraction (TESE), while 20 patients underwent microsurgical TESE (Micro‐TESE). The SSR was significantly higher in the Micro‐TESE group when compared with the TESE group (30% versus 0% respectively). In the Micro‐TESE group, hormonal stimulation was given to 16 patients, while no treatment was given to four patients. SSR was only successful in hormonally treated patients (6/16). When the type of hormone stimulation was evaluated, SSR was higher in patients receiving aromatase inhibitors (27.8%). SSR in patients with KS is significantly higher when using hormonal stimulation by aromatase inhibitors followed by microsurgical testicular sperm extraction.

Alteration in the etiology of penile fracture in the Middle East and Central Asia regions in the last decade; a literature review

Penile fracture is a well-recognized, relatively uncommon medical condition and its etiology differs according to geographic area. In this review article, we evaluated literature reported in the past decade, aiming to verify whether there has been any change in the etiology of this condition. A literature review was done for studies published in the past 10 years and focusing on the etiology of penile fracture. Inclusion criteria comprised articles in English language, of sample size more than 10 patients and originating from the Middle East and Central Asia. Data relating to the studied population, etiology of penile fracture, clinical presentation, investigations, management, and outcome was analyzed. One thousand six hundred and twenty-nine patients from 21 original articles were included in the study. The mean age ΁ standard deviation of the patients was 33.3 ΁ 3.23 years. Etiologies of penile fracture were vigorous sexual intercourse, manual bending of erect penis, vigorous masturbation, rolling over in bed and blunt trauma in 41%, 29%, 10%, 14% and 6% patients, respectively. Treatment choices were surgery and conservative, in 1580 (95%), 83 (5%) patients, respectively. A higher incidence of complications was found in conservatively treated patients. As a conclusion, in the last 10 years, vigorous sexual intercourse was the commonest etiology of penile fracture in the Middle East and Central Asia regions. Surgery remains the preferred treatment option for patients diagnosed with penile fracture.

Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate

Abstract Objective: To explore the current evidence concerning the effect of oral antioxidant supplementation on various male fertility outcomes, as antioxidants are widely available compounds that are commonly used for the treatment of male infertility. Materials and methods: PubMed, Medline and Cochrane electronic databases were searched according to a modified Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines looking for studies investigating the effect of antioxidant therapy on infertile men. The studies were explored looking for antioxidants: (i) types and doses; (ii) mechanism of action and rationale for use; and (iii) effect on the different outcome measures reported. Results: In all, 26 studies reported a significant positive effect of antioxidant therapy on basic semen parameters, advanced sperm function, outcomes of assisted reproductive therapy, and live-birth rate. Vitamin E, vitamin C, carnitines, N-acetyl cysteine, co-enzyme Q10, zinc, selenium, folic acid and lycopene were most commonly used. The vitamins’ mechanism of action and reported doses is presented in Tables 1 and 2. Conclusion: Antioxidants generally have a favourable effect on male fertility. Further studies are needed to identify the optimal antioxidant regimen that can be used safely and efficiently in clinical practice.