Edmund Y. Ko

Male infertility testing: reactive oxygen species and antioxidant capacity

Reactive oxygen species (ROS) are an integral component of sperm developmental physiology, capacitation, and function. Elevated ROS levels, from processes such as infection or inflammation, can be associated with aberrations of sperm development, function, and fertilizing capacity. We review the impact of ROS on sperm physiology, its place in infertility evaluation, the implications for reproductive outcomes, and antioxidant therapy. Our systematic review of PubMed literature from the last 3 decades focuses on the physiology and etiology of ROS and oxidative stress (OS), evaluation of ROS, and antioxidants. ROS is normally produced physiologically and is used to maintain cellular processes such as sperm maturation, capacitation, and sperm-oocyte interaction. When ROS production exceeds the buffering capacity of antioxidants, OS occurs and can have a negative impact on sperm and fertility. ROS and antioxidant capacity testing can potentially add additional prognostic information to standard laboratory testing for the infertile male, although its role as standard part of an evaluation has yet to be determined. Elevated ROS levels have been implicated with abnormal semen parameters and male infertility, but the impact of ROS on fertilization rates and pregnancy is controversial. This is partly because of the lack of consensus on what type of patients may be suitable for ROS testing and assay standardization. Routine ROS testing for the infertile male is not currently recommended.

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.

The role of nutraceuticals in male fertility.

Nutraceuticals are food products that that can provide medical or health benefits by preventing or treating disease processes. The high costs associated with assisted reproductive techniques for male infertility have led consumers to find less expensive alternatives for potential treatment. Nutraceuticals are widely available and have many antioxidant properties. This articles reviews the current English literature regarding readily available nutraceuticals and their potential effects on male infertility and potential side effects with excess intake.

Diagnosis of clinical and subclinical varicocele: how has it evolved?

In this review, we examine the evolution and application of various diagnostic modalities for varicoceles starting with venography, scintigraphy, and thermography and their role in the evaluation of a varicocele patient. Some of these methods have been supplanted by less invasive and more easily performed diagnostic modalities, especially ultrasound and Doppler examination of the scrotum. Advances in ultrasound and magnetic resonance imaging hold the potential to expand the role of imaging beyond that of visual confirmation and characterization of varicoceles. The ability to identify the early indicators of testicular dysfunction based on imaging findings may have implications for the management of varicoceles in the future.

Controversies in varicocele repair--much ado about nothing?

and couples requiring assisted reproductive techniques (ARTs) as potential beneficiaries of varicocele repair. Esteves and Glina demonstrated the presence of sperm in the ejaculate of 8 out of 17 formerly azoospermic men after subinguinal microsurgical varicocele repair.8 Men who remain azoospermic after varicocele repair may have a higher rate of successful sperm retrieval during subsequent testicular microdissection sperm extraction.9 In a comparison of 80 men with clinically palpable varicoceles who underwent subinguinal microsurgical varicocelectomy versus 162 untreated men, the former group demonstrated higher pregnancy and live birth rates with lower miscarriage rates with the subsequent use of intracytoplasmic sperm injection.10 This evidence demonstrates a possible role for varicocelectomy to “downgrade” the type of ART required by an infertile couple or increase its success rate in a cost-effective manner. The role of varicocele repair may not necessarily be limited to the treatment of male factor infertility, as there is emerging evidence that varicocele repair can be of benefit in hypogonadal men. A series of 272 men with clinically palpable varicoceles undergoing subinguinal microsurgical varicocelectomy demonstrated a statistically significant increase in serum testosterone level for the subset of men with preoperative baseline testosterone ≤400 ng dl−1.11 One prospective study demonstrated an improvement in serum testosterone level for patients with preoperative baseline serum testosterone <300 ng dl−1 who underwent microsurgical varicocelectomy. In this study, the group undergoing microsurgical varicocelectomy also experienced improved erectile function as measured by International Index of Erectile Function-5 questionnaire.12 There remains the need for well-conducted prospective randomized controlled trials in order to provide higher-level evidence to support varicocele repair for the above-mentioned indications. The ideal trial would involve patients with palpable varicoceles and abnormal conventional semen parameters by World Health Organization criteria, well-documented preand post-treatment semen analyses, and preand post-treatment serum hormone profiles. There should be a robust mechanism for patient randomization into treatment and observation arms. Follow-up should occur for an appropriate timeframe with minimal patient attrition. Accruing patients for such studies may be difficult because of the fact that patients may not be willing to be randomized to an observation arm because of the potential delay in treatment. Assisted reproductive technologies as well as crossover to the treatment arm may aid in convincing patients to enroll. Contemporary studies with improved methodology and incorporating microsurgical techniques of varicocele repair have been increasingly optimistic regarding the benefits of varicocele repair in treating male factor infertility and hypogonadism. As prospective studies with improved methodology continue to be published and the body of literature accumulates, it is our opinion that varicocele repair will no longer remain “much ado about nothing.”

Role of reactive oxygen species in male infertility: An updated review of literature

Abstract Objectives To review the literature and provide an updated summary on the role of reactive oxygen species (ROS) in male infertility. Methods A review of PubMed, Cochrane review, and Web of Science databases for full-text English-language articles published between 1943 and 2017 was performed, focusing on the aetiology of ROS, physiological role of ROS on spermatic function, pathological role of ROS in infertility, evaluation of ROS, and role of antioxidants in oxidative stress. Results ROS play a role in spermatic function and fertilisation. The literature describes both a physiological and a pathological role of ROS in fertility. A delicate balance between ROS necessary for physiological activity and antioxidants to protect from cellular oxidative injury is essential for fertility. Conclusion Although elevated levels of ROS are implicated as a cause of infertility, there is no consensus on selecting patients to test for ROS, which test to perform, or if treatment for ROS can have a positive impact on infertility rates and pregnancy.

Food intake diet and sperm characteristics in a blue zone: a Loma Linda Study

OBJECTIVES The study examined the effect the life-long vegetarian diet on male fertility and focused on vegetarians living in the Loma Linda blue zone, a demographic area known for life longevity. The objective was to compare sperm characteristics of vegetarian with non-vegetarian males. STUDY DESIGN The cross-sectional observational study was based on semen analyses of 474 males from 2009 to 2013. Patients categorized themselves as either life-long lacto-ovo vegetarians (N=26; vegetable diet with dairy and egg products), vegans (N=5; strictly vegetables with no animal products) or non-vegetarians (N=443; no diet restrictions). Sperm quality was assessed using a computer-aided sperm analyzer and strict morphology and chromatin integrity were manually evaluated. RESULTS Lacto-ovo vegetarians had lower sperm concentration (50.7±7.4M/mL versus non-vegetarians 69.6±3.2M/mL, mean±S.E.M.). Total motility was lower in the lacto-ovo and vegan groups (33.2±3.8% and 51.8±13.4% respectively) versus non-vegetarians (58.2±1.0%). Vegans had lowest hyperactive motility (0.8±0.7% versus lacto-ovo 5.2±1.2 and non-vegetarians 4.8±0.3%). Sperm strict morphologies were similar for the 3 groups. There were no differences in rapid progression and chromatin integrity. CONCLUSIONS The study showed that the vegetables-based food intake decreased sperm quality. In particular, a reduction in sperm quality in male factor patients would be clinically significant and would require review. Furthermore, inadequate sperm hyperactivation in vegans suggested compromised membrane calcium selective channels. However, the study results are cautiously interpreted and more corroborative studies are needed.

Etiology of Cancer-Induced Male Infertility

Male fertility can be temporarily or permanently affected by cancer in various ways. The disease process as well as treatments of cancer can impair the hypothalamic-pituitary-gonadal axis, the structural and functional integrity of the germinal epithelium, and male sexual function. This chapter discusses how cancer in males of reproductive age can cause or worsen male factor infertility through its pre-testicular, testicular, and post-testicular components.

The Importance of Diet, Vitamins, Malnutrition, and Nutrient Deficiencies in Male Fertility

Male-factor infertility is common and is frequently idiopathic in nature. Numerous studies have identified associations between seminal reactive oxygen species, decreased levels of various endogenous/exogenous antioxidants, obesity, and male sub-/infertility. Given these observations, several investigations have evaluated the efficacy of nutrient supplementation on male fertility. Due to the large amount of data available, the objective of this chapter is to compile and summarize pertinent findings of trials reporting fertility outcomes with nutrient supplementation. A literature search was performed of studies evaluating the efficacy of nutrients on male-factor fertility, with priority given to randomized, controlled trials, where available. Nutrients demonstrating potential benefits with male fertility include alpha-lipoic acid, anthocyanins, l-arginine, astaxanthin, beta-carotene, biotin, l-acetyl carnitine, l-carnitine, cobalamin, co-enzyme Q10, ethylcysteine, folic acid, glutathione, inositol, lycopene, magnesium, N-acetyl cysteine, pentoxifylline, phosphodiesterase 5 inhibitors, polyunsaturated fatty acids, selenium, Vitamins A, C, D, and E, and zinc, among others. Results from available data suggest that nutrient supplementation of infertile males may lead to improved pregnancy and live birth rates, reduced DNA fragmentation, and enhanced sperm motility, without improvement in total sperm count. Insufficient data is available to suggest superiority of any one agent. Similarly, the optimal combination and dosing regimen for nutrient supplementation remain unknown. Despite the limited amount of data, given the potential benefits of supplementation and low rate of adverse effects, the routine use of nutritional supplements in sub-/infertile males undergoing assisted reproductive techniques is reasonable. Further well-designed, placebo-controlled trials reporting outcome measures of pregnancy and live birth are mandated.